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We hypothesized that an electronic health record (EHR) alert grounded in behavioral science could reduce new antipsychotic medication prescriptions for older adults with dementia. We conducted a pragmatic clinical trial at a large academic health system, randomizing providers to receive the alert (intervention) or not (control) when prescribing new antipsychotic medications to outpatients with dementia. Eligible providers were those who previously signed a new antipsychotic prescription (n&#x2009;=&#x2009;150). The EHR alert contained: (1) text stating that antipsychotic medications increase mortality risk; (2) a link to an after-visit summary handout describing non-pharmaceutical approaches; (3) a default to a lower dose and pill-days. The primary outcome was mean total pill-days over 19&#x2009;months. We used provider-level linear regression, controlling for provider characteristics including prior prescribing behavior. Secondary outcomes included order cancellations and exploratory analyses of treatment effects among providers with above-average baseline prescribing patterns. Between 9/15/2021 and 4/11/2023, 28 providers in the intervention and 21 in the control arm initiated prescriptions to eligible patients, resulting in 139 enrolled patients; mean patient age was 83 (SD 9.7); 67% female. After 19&#x2009;months, raw mean (SD) pill-days were 126 (228) for the intervention and 225 (601) for the control group. Intervention assignment was not significantly associated with total pill-days among enrolled patients (primary outcome, mean difference -113 [95% CI: -256, +30], p&#x2009;=&#x2009;0.12). Orders were canceled in 12/58 (21%) of intervention encounters. The intervention was estimated to reduce pill-days for providers with average baseline prescribing behavior (-126, 95% CI: -3, -248; p&#x2009;=&#x2009;0.04); for each additional 10 baseline pill-days, this reduction effect increased by -8.8 pill-days (95% CI: -3.9, -13.6; p&#x2009;<&#x2009;0.001). This EHR alert did not reduce the primary outcome of antipsychotic pill-days. However, the nonsignificant effect size was substantial, and exploratory analyses revealed that the intervention significantly reduced pill-days for providers with average baseline prescribing. Future alerts should test targeting high prescribers.

Accurate estimation of lesion-specific effective half-life (Teff) is essential for patient-specific dosimetry in radioiodine (I-131) therapy for differentiated thyroid cancer (DTC). Although conventional multi-timepoint imaging provides detailed kinetic information, it is often impractical for routine clinical implementation. This study prospectively evaluated a simplified dual-timepoint planar imaging protocol aimed at balancing quantitative reliability with clinical feasibility. Fifty patients with DTC undergoing I-131 therapy were prospectively analyzed. Whole-body planar images were acquired twice after administration: an early scan at 1.98-3.25 days (mean, 2.71 days) and a delayed scan at 8.97-17.16 days (interval between the two scans ranged from 6.18 to 14.28 days [mean, 12.35 days]). Lesion-specific Teff values were calculated assuming mono-exponential clearance between the two scans using a log-linear approximation of measured activity counts. Quantitative reproducibility was assessed by comparing activity-count calibration slopes derived from an internal reference I-131 capsule between independent imaging sessions. The mean Teff was 2.16&#x2009;&#xb1;&#x2009;0.56 days and 3.11&#x2009;&#xb1;&#x2009;0.74 days for thyroid bed (n&#x2009;=&#x2009;35) and metastatic (n&#x2009;=&#x2009;19; p&#x2009;<&#x2009;0.001) lesions, respectively. Among metastatic sites, bone and lung metastases showed numerically similar Teff values (3.22&#x2009;&#xb1;&#x2009;0.76 and 3.36&#x2009;&#xb1;&#x2009;0.80 days, respectively); however, this subgroup comparison was limited by the small sample size. Calibration slopes derived from the internal reference capsule demonstrated only 5.0% inter-session variability, indicating high quantitative reproducibility. Dual-timepoint planar imaging incorporating internal capsule calibration enables reproducible estimation of lesion-specific Teff in patients undergoing I-131 therapy for DTC. This approach achieves a practical balance between quantitative accuracy and clinical feasibility, enabling reliable characterization of iodine kinetics with minimal imaging burden and supporting individualized dosimetry in routine clinical practice.

The purpose of this study is to determine the prevalence of arthrogenic muscle inhibition (AMI) after total knee arthroplasty (TKA) and to identify independent risk factors associated with its persistence during the early post-operative period. This retrospective monocentric study included 229 consecutive patients undergoing primary TKA between January 2024 and May 2025. AMI was assessed pre-operatively and post-operatively at 30 and 60 days using the Sonnery-Cottet (SANTI) clinical classification by trained rehabilitation physicians. Although not specifically validated in TKA patients, this classification was used due to the absence of a validated alternative. Multivariate logistic regression analyses were performed to identify factors associated with AMI. 51.1% were male with a mean age at surgery of 70.7&#x2009;&#xb1;&#x2009;9.6. Pre-operatively, 9.2% of patients showed signs of AMI. The post-operative prevalence was 44.5% at 30 days and decreased to 19.2% at 60 days. Independent risk factors for AMI at 30 days were body mass index&#x2009;&#x2265;&#x2009;30&#x2009;kg/m2 (odds ratio [OR] 1.97; p&#x2009;=&#x2009;0.04), symptom duration&#x2009;&#x2265;&#x2009;4 years (OR 2.60; p&#x2009;=&#x2009;0.003), pre-operative AMI (OR 6.08; p&#x2009;=&#x2009;0.003), post-operative morphine use (OR 2.15; p&#x2009;=&#x2009;0.01) and pre-operative neutral limb alignment (hip-knee-ankle 175&#xb0;-185&#xb0;) (OR 0.38; p&#x2009;=&#x2009;0.006). At 60 days, AMI persistence was associated with age&#x2009;&#x2265;&#x2009;70 years (OR 3.67; p&#x2009;=&#x2009;0.004), pre-operative AMI (OR 4.41; p&#x2009;=&#x2009;0.022), Visual Analogue Scale&#x2009;&#x2265;&#x2009;7 at Day 7 (OR 3.37; p&#x2009;=&#x2009;0.044) and AMI at 30 days (OR 15.6; p&#x2009;<&#x2009;0.001). AMI is a frequent issue after TKA, affecting 45% of patients at 1 month and 20% at 2 months. Its occurrence is associated with pre-operative inhibition, obesity, chronic symptoms, post-operative pain and age. Level III, retrospective cohort study.

Venous thromboembolism (VTE) is a frequent complication following femoral fracture surgery. While intermittent pneumatic compression (IPC) devices serve as an effective mechanical prophylaxis, patient compliance is often suboptimal. This study aimed to investigate the effectiveness of IPC in preventing VTE after femoral fracture surgery and to analyse the key factors influencing patient compliance. This retrospective study included 213 patients with femoral fractures who underwent surgical treatment at Ningbo No.6 Hospital between December 2021 and December 2024. Based on postoperative IPC device usage records from medical charts, patients were divided into a good compliance group (n = 51) and a compliance barrier group (n = 162). Postoperative coagulation parameters [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), and D-dimer (D-D)], VTE incidence at 5 days postoperatively, and the length of hospital stay were systematically collected and compared between the two groups. A self-designed questionnaire was used to assess factors influencing IPC compliance barriers. Among the 213 included patients who underwent femoral fracture surgery, the incidence of postoperative IPC device compliance barriers was 76.06% (162/213). At 5 days postoperatively, significant differences were observed in all coagulation parameters between the two groups. Specifically, the good compliance group had significantly higher PT, APTT, and TT levels compared with the compliance barrier group (all p < 0.05). In contrast, FIB and D-D levels were significantly lower in the good compliance group (all p < 0.05). Regarding clinical outcomes, the incidence of VTE in the good compliance group was 19.61%, significantly lower than the 38.27% in the compliance barrier group (p = 0.014). Furthermore, the median length of hospital stay in the good compliance group [8.00 (8.00, 17.00) days] was significantly shorter than that in the compliance barrier group [12.00 (9.00, 17.00) days] (p = 0.009). The survey results of 162 patients in the compliance barrier group showed that the main obstacles affecting IPC device application compliance were concentrated at the level of patient cognition, experience, and perception. A smaller proportion of patients had concerns about out-of-pocket costs. Healthcare-related factors and device-related factors had a relatively lower impact. The use of IPC after femoral fracture surgery can effectively improve the hypercoagulable state, reduce the incidence of VTE, and shorten hospitalization. However, patient compliance is generally low, primarily influenced by insufficient cognition, poor user experience, and low perceived value of treatment. It is recommended to improve compliance through systematic health education, optimizing comfort and convenience of use, strengthening healthcare follow-up and feedback, and ensuring device maintenance and configuration.

In this study, we investigated the association between time spent in Type 1 emergency departments (EDs) (consultant led 24-hour service with full resuscitation facilities) and all-cause mortality 30 days after leaving the department alive (either discharged home or admitted to inpatient care). This was a cross-sectional, retrospective, observational study using national linked data. We included individuals who visited a Type 1 ED between 21st March 2021 and 31st March 2022, under a nonimmediate acuity who survived to discharge or admission to inpatient care. Fitting a logistic regression model, we assessed the association between time spent in the ED and the risk of all-cause, 30-day death following departure. Of 6,721,179 individuals (mean age 41.3 years; 52.6% women, 81.4% White), 1.3% died within 30 days of visit. After controlling for confounders, compared with patients who spent 2 hours in the ED, the adjusted odds of postdischarge death were: 1.1 times higher (1.07 to 1.14) for 3 hours; 1.6 times (1.48 to 1.68) for 6 hours; 1.9 times (1.80 to 2.03) for 9 hours; and 2.1 times (2.02 to 2.28) for 12 hours. Longer time spent in the ED for nonimmediate care is associated with increased risk of all-cause mortality within 30 days of discharge or admission. However, the reasons for this association are uncertain and may reflect residual confounding, rather than a direct causal effect of time spent in the ED. Therefore, further research is needed to understand causal drivers of postdischarge mortality.

Early recurrence of atrial tachyarrhythmia (ERAT) after catheter ablation for atrial fibrillation (AF) is common, yet its prognostic significance and implications for the duration of the blanking period remain uncertain. We aimed to evaluate the association between ERAT and post-ablation clinical outcomes, late arrhythmia recurrence, and AF burden, and to explore the optimal duration of the blanking period. This post hoc analysis included 811 patients from the CABANA trial who underwent catheter ablation and had trial-specific electrocardiographic monitoring data available. ERAT was defined as any episode of AF, atrial flutter, or atrial tachycardia lasting >30&#x2005;seconds within the 90-day blanking period. The primary outcome was a composite of all-cause mortality, disabling stroke, serious bleeding, or cardiac arrest. Secondary outcomes included cardiovascular hospitalisation and late atrial tachyarrhythmia recurrence. During a median 4 years (IQR 2.5-5.2) follow-up, ERAT occurred in 567 patients (69.9%). Patients with ERAT had higher risks of cardiovascular hospitalisation [adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) 1.07-1.71] and of the composite outcome of all-cause mortality or cardiovascular hospitalisation (aHR 1.33, 95% CI 1.07-1.66), but no increased risk of the primary composite outcome. ERAT was independently associated with late atrial tachyarrhythmia recurrence (aHR 1.35, 95% CI 1.07-1.71). Prognostic relevance varied by timing, with the strongest association observed for ERAT occurring between 60 and 90 days after ablation (aHR 1.80, 95% CI 1.16-2.79).Receiver operating characteristic analysis identified 58 days as the optimal threshold for predicting late arrhythmia recurrence (AUC 0.727). ERAT was associated with higher risks of cardiovascular hospitalisation and late atrial tachyarrhythmia recurrence in a time-dependent manner, supporting a shorter blanking period to better identify patients at risk of adverse rhythm outcomes.

Children with sickle cell disease (SCD) remain at risk for invasive pneumococcal disease (IPD) because of impaired splenic function and increased susceptibility to encapsulated bacteria. Data describing IPD after allogeneic hematopoietic cell transplantation (HCT) for SCD are limited. We conducted a multicenter retrospective cohort study of children and young adults with SCD undergoing first allogeneic HCT at two participating Sickle Cell Transplant Advocacy and Research (STAR) centers. IPD occurring within 365 days after HCT was identified through registry data, microbiologic culture review, and supplemental chart review. Among 182 patients undergoing HCT, three developed IPD within the first year after transplant. All cases presented with sepsis and bacteremia; one patient also developed meningitis and died of septic shock. IPD occurred between 7 and 365 days after HCT. None of the patients had received post-transplant pneumococcal vaccination before IPD diagnosis. Serotype data were unavailable for all cases. In this multicenter cohort of patients with SCD undergoing allogeneic HCT, IPD was uncommon but clinically severe, including late infections occurring nearly one year after transplantation. Prospective studies evaluating immune recovery, splenic function, pneumococcal vaccination practices, and long-term infectious outcomes are needed to better define persistent susceptibility to invasive pneumococcal disease after HCT in patients with SCD.

Hereditary angioedema (HAE) is a rare autosomal dominant disorder resulting from SERPING1-related C1-inhibitor deficiency. Surgical stress and airway manipulation may precipitate life-threatening attacks. Experience with kidney transplantation in patients with HAE remains extremely limited. We describe a 19-year-old male with end-stage kidney disease secondary to congenital obstructive uropathy and nephrolithiasis, who underwent successful living-donor kidney transplantation from his mother, also diagnosed with HAE type I. Because danazol is unavailable in Argentina, both donor and recipient received compounded stanozolol 2&#x2009;mg daily, starting 5&#x2009;days preoperatively and continuing for 5&#x2009;days postoperatively. Fresh frozen plasma (FFP, 10&#x2009;mL/kg) was administered before extubation to raise C1-inhibitor levels, and icatibant was kept on standby for rescue. Neither donor nor recipient experienced perioperative angioedema. Both had uneventful recoveries, with the recipient maintaining stable graft function over 10&#x2009;months of follow-up (latest serum creatinine 1.4&#x2009;mg/dL). This report demonstrates that living-donor kidney transplantation between two individuals affected by HAE can be performed safely with individualized prophylaxis and multidisciplinary coordination.

The standard one-injection start (OIS) regimen of aripiprazole once-monthly (AOM) requires a 14-day oral overlap, which may present practical challenges in routine care. This study evaluated whether the accelerated two-injection start (TIS) strategy, which eliminates oral overlap, affects 1-year real-world outcomes in patients with bipolar disorder (BD). This retrospective observational study included 132 inpatients with Bipolar I disorder hospitalized for an acute manic episode (OIS: n&#x2009;=&#x2009;88; TIS: n&#x2009;=&#x2009;44) initiated on AOM between January and December 2024. Primary outcomes were 1-year rehospitalization and emergency room (ER) visits. Exploratory analyses examined relapse-related outcomes, timing of initiation, and baseline illness severity. Baseline and acute-phase characteristics were comparable between groups. Multivariable models confirmed the TIS regimen did not significantly increase the hazard of 1-year rehospitalization (aHR: 0.71, p&#x2009;=&#x2009;0.435) or ER visits (aHR: 0.76, p&#x2009;=&#x2009;0.378) compared to OIS. Among patients who relapsed, TIS was associated with fewer recurrent ER visits (p&#x2009;=&#x2009;0.031) and a longer time to first ER visit (93.5 vs. 40.0&#x2009;days). Exploratory analyses showed numerically lower ER utilization rates for the TIS regimen when initiated early (&#x2264;7&#x2009;days) and among patients with higher baseline illness severity. The TIS regimen appears to be a feasible and safe alternative to OIS in BD, without compromising 1-year clinical outcomes or increasing adjunctive medication use. Exploratory findings suggested a potential trend toward a less intensive relapse course and delayed acute psychiatric service utilization among patients receiving TIS. Given the exploratory nature of these analyses, these observations require confirmation in larger prospective studies.

Osteoporotic vertebral compression fractures (OVCF) are common and disabling. Augmentation techniques differ by access (uni vs. bi), trajectory (curved vs. straight), and implant platform, but direct head-to-head evidence is limited.&#xa0;We conducted a frequentist random-effects network meta-analysis (NMA) of randomized controlled trials (RCTs) with method-specific nodes (unipedicular percutaneous vertebroplasty (UPVP), bipedicular percutaneous vertebroplasty (BPVP), unipedicular percutaneous kyphoplasty (UPKP), bipedicular percutaneous kyphoplasty (BPKP), percutaneous curved vertebroplasty (PCVP), percutaneous curved kyphoplasty (PCKP), deflectable percutaneous kyphoplasty (DPKP), dual-plane UPVP, KIVA, TIVAD, and conservative care). Risk of bias was assessed using the Cochrane risk-of-bias tool. Outcomes were Visual Analog Scale score (VAS) (&#x2264;&#x2009;14 days, 1-3 months, >&#x2009;6 months), the Oswestry Disability Index (ODI) (post-operative, long-term) (measured at the earliest post-procedural assessment and at long-term follow-up >&#x2009;6 months), vertebral height restoration (%), local kyphotic angle (LKA) at last follow-up, bone-cement leakage, secondary vertebral fractures, and operative time.&#xa0;Twenty-eight RCTs (n&#x2009;=&#x2009;3,049) were included. By P-scores, DPKP and dual-plane UPVP ranked highest for VAS&#x2009;&#x2264;&#x2009;14 days (conservative ranked last), PCVP and UPKP ranked highest at 1-3 months, and dual-plane UPVP and PCVP ranked highest at >&#x2009;6 months. For disability, PCKP and UPKP ranked best post-operatively, and dual-plane UPVP and PCKP ranked best at long-term follow-up. Radiographically, BPKP and KIVA ranked highest for vertebral height restoration, while PCKP and UPKP yielded the lowest LKA at last follow-up. Leakage was lowest with the Shield kyphoplasty system (Soteira), PCVP and PCKP, secondary fractures were lowest with TIVAD and KIVA, and operative time was shortest with UPKP and PCVP.&#xa0;In an RCT-based NMA of OVCF treatments, augmentation generally ranked above conservative care for pain, but no single technique dominated all endpoints. Procedure selection should be tailored to the clinical goal - pain control, height/alignment, safety, or efficiency - while considering patient factors.

CAR-T cell therapy is a cellular cancer immunotherapy that has impressively improved outcomes in hematological malignancies compared to conventional treatments. Yet, many patients do not respond permanently. Nonlinear mixed-effects modeling can support a better understanding of the unique and not fully understood dose-exposure and exposure-response relationships for CAR-T cell therapy by integrating available knowledge into a quantitative, physiology-motivated framework. However, to unfold its full potential, it requires informative and efficient study designs for clinical data collection. We aimed to develop an optimal experimental design framework informing a robust and feasible clinical CAR-T cell study design based on a published mechanistic model of CAR-T cell kinetics and tumor dynamics. By considering variability between study populations and parameter uncertainty, we (1) identified the minimal population size required to inform model parameters, (2) assessed different sampling strategies, and (3) informed flexible sampling windows instead of fixed sampling timepoints. The optimized study design consisted of 60 patients, three fixed assessments of tumor burden (days 0, 30 and 90), and three feasible CAR-T cell sampling windows (days 2-4, 12-18 and 32-47 after infusion). In stochastic simulation and estimation, the optimized design with sampling windows showed better performance in informing model parameters, including those characterizing heterogeneous outcomes, than designs with fixed sampling timepoints, confirming its efficiency and robustness. This framework shall facilitate future feasible and resource-efficient CAR-T cell clinical data collection, thus showcasing the potential of optimal experimental design to advance the development and optimization of complex cancer immunotherapies in clinical trials and clinical practice.

Effective neuroprotective therapies for acute ischemic stroke (AIS) remain limited due to the complex interplay between neuroinflammation and apoptosis. Sinomenine (Sino), a bioactive alkaloid derived from Sinomenium acutum, exhibits anti-inflammatory and anti-apoptotic activities; however, its molecular targets and mechanisms in AIS remain unclear. This study aimed to identify potential targets and key pathways of Sino and validate its neuroprotective effects in AIS. A combined approach integrating network pharmacology, Mendelian randomization (MR), molecular docking, and in vivo validation was adopted. Potential targets of Sino and ischemic stroke were identified using public databases. Overlapping targets were analyzed through protein-protein interaction network construction and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Sprague-Dawley rats were randomly assigned to four groups, and a middle cerebral artery occlusion/reperfusion (MCAO/R) model was established (n = 12 per group): Sham, MCAO/R, Sino (20 mg/kg), and Sino +LY294002 (LY, 10 mg/kg). Sino and Sino + LY were administered intraperitoneally within 6 h after surgery and once daily thereafter for three days. Sham and MCAO groups were given the same amount of physiological saline undergoing the same procedures. Sino was administered intraperitoneally within 6 h after surgery and once daily thereafter for three days. Neurological deficits, infarct volume, neuronal injury, apoptosis, activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway, and inflammatory responses were assessed using behavioral tests, 2,3,5-Triphenyltetrazolium chloride (TTC)/Nissl/Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) staining, Western blotting, immunofluorescence, enzyme-linked immunosorbent assay (ELISA). Twelve overlapping targets between Sino and ischemic stroke were identified, with Akt1 recognized as a central hub. Enrichment analysis highlighted the PI3K/Akt pathway as a critical signaling axis, while MR analysis indicated a nominal association between Akt1 and ischemic stroke. Molecular docking predicted stable binding between Sino and Akt1. In MCAO/R rats, Sino significantly improved neurological function, reduced infarct volumes, attenuated neuronal apoptosis, and increased neuronal survival. Mechanistically, Sino increased the p-PI3K/PI3K and p-Akt/Akt ratios, upregulated Bcl-2 expression, and decreased the expression of Bax, cleaved caspase-3, ionized calcium-binding adapter molecule 1 (Iba1), inducible nitric oxide synthase (iNOS), interleukin-1&#x3b2; (IL-1&#x3b2;), interleukin-6 (IL-6), and tumor necrosis factor-&#x3b1; (TNF-&#x3b1;). These beneficial effects were notably attenuated by LY. This study establishes PI3K/Akt as a functionally necessary mediator of Sino's neuroprotection against cerebral ischemia/reperfusion injury. The incomplete LY reversal indicates multi-target activity, supporting Sino's development as an adjunctive therapeutic candidate for ischemic stroke.

Newborn screening (NBS) for inborn errors of immunity increasingly uses T-cell receptor excision circles (TREC) and, in some programs, Kappa-deleting recombination excision circles (KREC) to detect early T- and B-cell lymphopenia. While TREC-based screening is well established, the significance and management of isolated low KREC remain unclear. To evaluate the implications of two different regional post-screening algorithms for isolated low KREC and to characterize the clinical course, immunological profile, and follow-up of term newborns with transient B-cell lymphopenia. We performed a retrospective multicenter study of term newborns with isolated low KREC identified through NBS, confirmed B-cell lymphopenia, and subsequent normalization during follow-up. KREC levels, B-cell counts, and serum immunoglobulins were assessed longitudinally by RT-PCR and flow cytometry. Eighteen newborns were enrolled. At the first evaluation (V1; mean age 13.5&#x2009;days), all had marked peripheral B-cell lymphopenia (CD19+&#x2009;&#x2264;&#x2009;2%; mean 54 cells/&#x3bc;L), although repeat dried blood spot (DBS) testing already showed KREC values above the diagnostic cutoff in 78%. By the second visit (V2; mean age 50&#x2009;days), B-cell percentages and absolute counts normalized in all infants, with emerging IgA and IgM production, and normal KREC on whole blood. No infectious or immunological complications were recorded over 39.5 person-years of follow-up (mean 2.3&#x2009;&#xb1;&#x2009;1.7&#x2009;years). Isolated low KREC at birth may identify newborns with transient B-cell lymphopenia that resolves during early infancy. Repeat KREC testing on a second DBS before referral may represent a pragmatic triage step to reduce unnecessary immunological evaluations, while preserving early assessment for newborns with persistent abnormalities. Prospective studies are needed to refine post-screening strategies.

To compare short-term corneal epithelial thickness changes measured by optical coherence tomography (OCT) in eyes fitted with two different silicone hydrogel bandage contact lenses (BCL) following trans-epithelial photorefractive keratectomy (t-PRK). In this prospective contralateral-eye study, 60 eyes of 30 patients with myopia without astigmatism underwent t-PRK using WaveLight EX500 excimer laser. Balafilcon A was applied to one eye and senofilcon A to the fellow eye in a randomized manner. All BCLs were removed on postoperative day 5. Corneal epithelial thickness was assessed preoperatively and on postoperative days 5, 15, and 30 using spectral-domain optical coherence tomography (REVO FC). Measurements were obtained centrally and across eight mid-peripheral quadrants. Epithelial thickness and spherical equivalent (SE) were compared. The mean age of the participants was 27.11&#x2009;&#xb1;&#x2009;6.80&#xa0;years. Preoperatively, no significant differences were observed between the groups in SE (-&#x2009;2.93&#x2009;&#xb1;&#x2009;1.11 D vs.&#x2009;-&#x2009;2.71&#x2009;&#xb1;&#x2009;1.44 D; p&#x2009;=&#x2009;0.353), ablation depth, central corneal thickness, or epithelial thickness. On postoperative day 5, slightly higher epithelial thickness values were observed in the nasal, temporal, and superotemporal quadrants in the balafilcon A group in unadjusted analyses; however, these differences did not remain statistically significant after false discovery rate correction. No significant differences were observed between the other regions. By postoperative days 15 and 30, epithelial thickness was comparable across all quadrants. At 1&#xa0;month, the SE values were similar (p&#x2009;=&#x2009;0.302), although balafilcon A showed a trend toward values closer to emmetropia. Both bandage contact lens materials demonstrated broadly comparable short-term postoperative epithelial remodeling patterns and refractive outcomes after t-PRK. Minor early regional differences observed on OCT should be interpreted cautiously.

The mammary gland has a remarkable ability to renew and repair itself, making mammary epithelial stem cells (MESCs) critical targets for understanding lactation biology and developing therapeutic interventions for intramammary infections. The objective of this study was to isolate, culture, and characterize goat mammary epithelial stem cells (GMESCs) from Beetal goats to optimize growth conditions and establish a foundation for future biomedical research. Mammary tissues were harvested from Beetal goats and subjected to enzymatic digestion to isolate GMESCs. To identify the optimal culture environment, the cells were screened across multiple growth and differentiation media containing varying growth factors. Optimization was performed based on proliferation index and population doubling time. Purification of isolated cells was performed using the EasySep&#x2122; PE positive selection kit targeting the CD24 luminal marker. Characterization of stem cells, milk secretion, and proliferation markers was performed using phase-contrast microscopy, colony-forming unit (CFU) assays, qualitative real-time-polymerase chain reaction (qRT-PCR), and immune cytochemistry. The optimal basal growth medium was Dulbecco modified eagle medium (DMEM)/F12 fortified with 10% fetal bovine serum (FBS), three essential growth factors (epidermal growth factor [EGF], basic fibroblast growth factor [bFGF], and insulin), and 1% antibiotics. Under these conditions, the GMESCs exhibited a characteristic cobblestone morphology and successfully differentiated into functional units, including domes, alveoli-like structures, and interconnecting tubules. Although CFU assays revealed relatively low colony-forming efficiency in these epithelial cells, the identity of GMESCs was validated by the presence of specific markers, including endogenous stem cell markers and milk-secreting proteins. Purified CD24+ luminal cells maintained stable morphological characteristics after 10 days of culture. This study successfully established a robust protocol for the isolation and expansion of GMESCs from Beetal goats. By defining the specific markers and media requirements of these cells, this study provides a valuable model for mammary tissue repair and broader applications in veterinary regenerative medicine and sustainable production.

Asciminib (ASC) is a novel BCR::ABL1 tyrosine kinase inhibitor that binds to the ABL myristoyl pocket. Although dose adjustments for renal impairment are generally considered unnecessary, pharmacokinetic data for patients with end-stage renal disease or those on dialysis are limited. A 72-year-old man with chronic phase chronic myeloid leukemia undergoing maintenance hemodialysis for chronic renal failure was treated with ASC. Owing to cardiovascular risk, treatment was initiated at a reduced dose of 40&#xa0;mg once daily. A major molecular response was achieved within 3 months without adverse events. Pharmacokinetic analysis revealed a delayed apparent Tmax (>&#x2009;4&#xa0;h), suggesting prolonged absorption. ASC concentrations did not decrease during dialysis sessions compared with non-dialysis days. The median trough concentration was 89.0 ng/mL, with a coefficient of variation of 30.9%. ASC demonstrated negligible dialyzability, likely because of its high plasma protein binding (97.3%). However, the study revealed a significantly delayed apparent Tmax and high intra-individual variability in plasma concentrations. These findings suggest that clinicians should prioritize monitoring for delayed gastrointestinal absorption and potentially reduced bioavailability in patients undergoing maintenance hemodialysis, rather than focusing on drug removal by dialysis.

Dental bleaching is a widely used esthetic procedure often associated with oral hygiene products such as mouth rinses. However, the effects of different mouth rinse formulations on enamel during bleaching remain unclear. This study evaluated in vitro the properties of dental enamel exposed to mouth rinses with different active ingredients during at-home bleaching with 10% carbamide peroxide. Bovine enamel-dentin discs were randomly assigned to four groups (n=12): distilled water (DW, control), Listerine Cool Mint Zero Alcohol (CMZ, essential oils), Listerine Cool Mint (CM, essential oils + alcohol), and Listerine Whitening Extreme (WE, essential oils + alcohol + hydrogen peroxide). Bleaching was performed for 4 h/day for 14 days, and mouth rinses were applied twice daily. Color parameters (&#x394;L* ,&#x394;a*, &#x394;b*, &#x394;E, &#x394;E), surface roughness (Ra), and microhardness (KHN) were evaluated at baseline and after treatment. Surface morphology was analyzed by scanning electron microscopy (SEM). Data were analyzed using linear mixed models, generalized linear mixed models, and Kruskal-Wallis tests (&#x3b1;=0.05). No significant differences among groups were observed for color change or surface roughness (p&#x203a;0.05). All groups showed a significant reduction in microhardness over time (p&#x2039;0.05). CMZ and CM exhibited the greatest decrease in microhardness at the final evaluation, differing significantly from the other groups (p&#x2039;0.05). SEM images revealed similar surface alterations in all groups, including porosity and depressions. Mouth rinses did not affect bleaching effi cacy or enamel color. Although enamel microhardness, roughness, and morphology changed after bleaching, only microhardness and morphological alterations were influenced by the active ingredients of the mouth rinses. CLINICAL RELEVANCE: The use of mouth rinses during at-home bleaching with carbamide peroxide does not compromise the bleaching efficacy. However, it may adversely affect the properties of dental enamel.

Probiotics have gained increasing attention due to their potential health benefits, antimicrobial properties, and role in promoting overall well-being. In this context, the identification of novel bacterial strains with relevant functional properties and high stability under food processing conditions is essential. This study aimed to identify an isolate from Brazilian semi-hard cheese and assess the presence of virulence genes and genes involved in biogenic amine production, as well as to evaluate bacteriocin production and the in vitro probiotic potential of the strain. Additionally, the strain was microencapsulated by spray-drying to enhance its resistance under gastrointestinal and storage conditions. The isolate was identified as Enterococcus faecium EM03 through 16&#xa0;S rDNA gene sequencing. In vitro safety testing showed susceptibility to most antibiotics tested, with resistance only to ciprofloxacin and gentamicin. Molecular analyses confirmed the absence of genes associated with biogenic amine synthesis and key virulence factors typically considered in Enterococcus safety assessments (ace, asa1, cylA, efaA, esp, and gelE). Conversely, genes associated with bacteriocin production (entB, entP, L50AB, IanM, and IanC) were detected, supporting the results showing inhibition of Listeria monocytogenes and E. faecalis by proteinaceous compounds. Additionally, the strain showed high resistance under simulated gastrointestinal conditions, and microencapsulation by spray-drying further enhanced its stability, allowing probiotic survival for up to 60 days and maintaining good resistance to simulated gastrointestinal conditions while keeping the microparticle properties consistent. Overall, E. feacium EM03 showed strong probiotic potential, combining safety, antimicrobial properties, and technological stability, supporting its use in the development of functional foods.

This study aimed to evaluate the efficacy and safety of the surgical adhesion barrier Medicurtain&#xae; in patients undergoing laparoscopic hysterectomy. The study was a multi-center, non-controlled, evaluator-blinded, randomized clinical trial. A total of 91 participants from 3 study sites were randomly assigned to the hyaluronic acid (HA)- hydroxyethyl starch (HES) barrier agent treatment test group (n=49) or the non-treatment control group (n=42). At Visit 3 (8 weeks&#xb1;5 days), adhesion formation rates and grades were assessed via second-look laparoscopy, and adverse events (AEs) were evaluated. An independent investigator conducted all assessments. At Visit 3, adhesion rates differed significantly between the 2 groups: 73.47% in the test group and 95.24% in the control group (p=0.005). In the intention-to-treat analysis, adhesion grades at Visit 3 were 1.10&#xb1;0.87 in the treatment group and 1.45&#xb1;0.74 in the control group, showing a statistically significant difference (p=0.045). Safety analysis revealed no adverse device effects during the follow-up period in either group and no dropouts due to AEs. Additionally, the test and control groups demonstrated no significant differences in other safety parameters, including vital signs, laboratory tests, physical examinations, and electrocardiogram findings. HA-HES barrier agent appears to be a potentially effective and safe adhesion barrier for laparoscopic procedures. ClinicalTrials.gov Identifier: NCT04672421.