Intervention fidelity specifies core components and measures adherence. Thrive, an evidence-based transitional care program providing 30-day post-discharge support to Medicaid-insured individuals, was evaluated for intervention fidelity. To (1) evaluate the coverage, content, dose, and overall adherence to Thrive, and (2) examine associations between fidelity and 30-day post-discharge utilization. We evaluated Thrive's intervention fidelity from 2023 to 2025 within four hospitals in an urban health system. Fidelity measures developed using expert consensus included content (9 components), dose (up to 4 weeks), overall adherence, and coverage. High fidelity was defined as receiving ≥80% of all components. Logistic regression models adjusted for patient characteristics and hospital examined fidelity and 30-day post-discharge utilization (primary care, specialty care, readmissions, emergency department (ED) visits). Of 1,301 referred patients, 709 received Thrive services (55% coverage); 75.9% achieved high fidelity. Average content score was 7.6, and 78.8% received 4 weeks of Thrive. In adjusted models, higher content was associated with higher odds of primary care (odds ratio [OR] = 1.30; 95% confidence interval [CI]: 1.10-1.54; p < .01) and lower odds of ED visits (OR = 0.80; 95% CI: 0.64-0.99; p < .05). Receiving 4 weeks of Thrive was associated with higher odds of primary care (OR = 1.79; 95% CI: 1.21-2.65; p < .01), specialty care (OR = 1.56; 95% CI: 1.06-2.31; p < .05), and lower odds of readmissions (OR = 0.53; 95% CI: 0.33-0.86; p < .05). Thrive achieved high intervention fidelity. Patients receiving all 4 weeks of Thrive experienced increased primary and specialty care engagement and fewer readmissions. Routine intervention fidelity assessments of complex, multi-component interventions can reinforce protocols, promoting equitable participation and outcomes. ClinicalTrials.gov NCT05714605; https://clinicaltrials.gov/ct2/show/NCT05714605 and ClinicalTrials.gov NCT06203509; https://clinicaltrials.gov/ct2/show/NCT06203509.
Background: The Veggie Van (VV) model is a mobile produce market intervention previously shown to increase fruit and vegetable (F&V) consumption among lower-income individuals. Although the model was recently evaluated in a multi-state effectiveness trial, preliminary findings suggested challenges to implementing the model with fidelity. This study examined whether variation in implementation fidelity was associated with participant-level dietary, food security, and market utilization outcomes. Methods: This study involved a secondary analysis of participant outcome data from a longitudinal RCT conducted with 9 implementing organizations operating 17 mobile market sites (n=699 participants). Previously collected participant data included baseline and 12-month measures of F&V consumption from 24-hour dietary recalls and self-reported surveys, as well as food security assessed using the USDA 10-item Adult Food Security Survey Module. Participant outcome data were aggregated at the site level and linked with organizational implementation data collected throughout the intervention period. Implementing organizations completed monthly process measures surveys assessing adherence to core VV model components; responses were scored and aggregated into site-level implementation fidelity scores. Correlational analyses and generalized linear models examined associations between implementation fidelity and changes in F&V consumption, food security, and market utilization outcomes over 12 months. Results: The mean implementation fidelity score across sites was 40.6 out of 55 possible points. Higher overall fidelity was positively associated with greater increases in mean F&V consumption over 12 months (Pearson correlation coefficient [PCC]=0.56, p=0.02). Fidelity to the nutrition education component demonstrated a particularly strong association with change in F&V consumption (PCC=0.81, p<0.0001). These associations remained significant in regression analyses. In addition, sites operating markets for ≥10 months annually had 76% greater odds of participants shopping at the mobile market at least once during the intervention period (p=0.04). No significant associations were observed between implementation fidelity and changes in food security. Conclusions: Greater fidelity to the VV model, particularly implementation of nutrition education components, was associated with improved dietary outcomes in this secondary analysis of participant-level RCT data. Findings highlight the importance of evaluating implementation alongside effectiveness outcomes in community-based nutrition interventions and suggest that tailored implementation support strategies may strengthen delivery of intervention components most strongly associated with dietary change. Trial registration: The larger randomized controlled trial, the Veggie Van study, was registered at https://clinicaltrials.gov/ on January 29, 2020 (NCT04246593).
Purpose Postural tachycardia syndrome (POTS) is a chronic autonomic disorder characterized by orthostatic intolerance and frequently accompanied by a broad constellation of debilitating symptoms. Emerging evidence suggests that dysregulation within central-autonomic regulatory networks may contribute to symptom persistence. We developed POts Reprocessing Therapy (PORT), a neuroplasticity-informed behavioral intervention adapted from Pain Reprocessing Therapy. This pilot study evaluated the feasibility, acceptability, and preliminary clinical outcomes of PORT for individuals with POTS. Methods We conducted a non-randomized, two-arm, open-label pilot feasibility trial. Adults with clinically significant POTS symptoms (Malmö POTS Symptom Score ≥ 42) received eight weekly PORT sessions ( n  = 14). A comparison group of adults with POTS receiving community care while awaiting entry to an autonomic clinic served as controls ( n  = 15). Self-report measures were collected at baseline and 8-week follow-up, including POTS symptom severity (Malmö), symptom catastrophizing, anxiety, depression, pain, fatigue, and quality of life. Feasibility and acceptability were assessed via recruitment, retention, and treatment satisfaction. Results PORT demonstrated strong feasibility and acceptability, with 83% retention and strong satisfaction ratings among completers. Participants receiving PORT reported greater symptom improvement compared with community care controls. Mixed ANOVA analyses revealed significant group × time interactions for POTS symptoms (ηp² = 0.283), anxiety (ηp² = 0.363), symptom catastrophizing (ηp² = 0.193), and depression (ηp² = 0.186), reflecting moderate-to-large effect sizes. Conclusion This pilot study suggests that PORT is a feasible and acceptable intervention and may be associated with improvements in POTS symptom burden and related psychological processes. Findings provide preliminary support for targeting central-autonomic processes through neuroplasticity-based interventions and warrant larger randomized controlled trials to evaluate efficacy and underlying mechanisms.
A suboptimal diet is a major health risk, yet adopting and maintaining healthy eating habits remains challenging. Just-in-Time (JIT) digital support may help, however, little is known about when and where users are most receptive to such support. This study aimed to evaluate receptivity to a researcher-developed JIT-based app that prompts healthy food choices near food outlets and at preset times. The primary outcome was receptivity to JIT prompts, defined as users' willingness and ability to receive, process, and act upon prompts in daily life. Exploratory outcomes included usability, perceived privacy and perceived effectiveness. In a single-arm mixed-methods study, 14 adults (M = 27 y) used the app for 1 wk after selecting a nutritional health goal. Data were collected via poststudy questionnaires, in-app feedback, and interviews with 8 participants. Receptivity was assessed based on participants' willingness and ability to engage with prompts in real-world contexts. Quantitative data were analyzed descriptively and using exploratory statistical tests; qualitative data were analyzed thematically. Receptivity to JIT prompts was highest when prompts were delivered at meaningful times and locations, particularly at home and in supermarkets, and appeared higher during more positive and calmer emotional states. Exploratory feasibility findings indicated that usability was affected by technical issues and battery drain. Participants generally expressed willingness to share personal data when used transparently for personalization. Users reported improvements in self-rated diet quality and goal-related dietary behavior, and emotional states were associated with perceived momentary effectiveness. Lower-educated participants reported more installation difficulties, less favorable perceptions of prompt tone, and smaller improvements in food choices. Our findings provide initial insight into when and where individuals are most receptive to JIT support for healthy eating, informing the design of future adaptive dietary interventions tailored to users' contexts and momentary states.This trial was registered at clinicaltrials.gov as NCT05773625 (https://clinicaltrials.gov/ct2/show/NCT05773625).
Spontaneous hemorrhage from meningiomas causing intracranial hematomas is rare (1%-2% of cases), and concurrent acute subdural hematoma (ASDH) is even rarer, which is easily misdiagnosed and may lead to inadequate preoperative planning. Combined endovascular-craniotomy hybrid surgery enables precise diagnosis and treatment, serving as an effective approach for complex intracranial lesions. A 34-year-old married female was admitted with a 4-day history of sudden headache. Cranial CT showed left temporal lobe hemorrhage and left frontoparietotemporal-occipital ASDH; CTA indicated a left temporal mass, subdural hematoma, sigmoid sinus compression, cerebral edema, and tortuous superficial vessels. Emergency hybrid surgery was conducted. Digital subtraction angiography (DSA) first ruled out intracranial vascular malformations and confirmed that the left temporal lesion was supplied by the temporal branch of the left middle meningeal artery (ball-holding sign). Given the tumor's location at the cerebral convexity with a relatively superficial distribution, combined with the potential risk of ischemic complications and aggravated cerebral edema secondary to preoperative endovascular embolization, preoperative embolization of tumor-feeding arteries was therefore omitted. Direct craniotomy was subsequently adopted as the definitive surgical approach. A left subtemporal craniotomy was subsequently performed, achieving gross total resection of the tumor (2 × 3 × 4 cm) and complete evacuation of the hematoma. Postoperative pathology confirmed angiomatous meningioma (WHO Grade Ⅰ) with hemorrhage. The patient recovered well without complications or neurological deficits, and no recurrence was noted at 1-year follow-up. Combined endovascular-craniotomy hybrid surgery achieves integrated diagnosis and treatment through simultaneous endovascular evaluation and craniotomy, improving the efficiency and accuracy in the management of meningioma-related stroke complicated with ASDH. Preoperative endovascular embolization may be added for large, hypervascular tumors to reduce bleeding, but clinicians should remain vigilant for ischemic risks. Rational application of this hybrid surgery effectively improves patient prognosis.
A longitudinal controlled intervention study aimed to assess the impact of a nutrition education program on Lebanese athletes' nutritional knowledge, eating habits, body composition and performance. A sample of 198 athletes was divided into an intervention group (IG) and a control group (CG). The intervention group followed a 4-month intensive nutrition education program set to ensure sufficient time for meaningful learning and behavior change, while remaining short enough to maintain participant engagement and minimize dropout. The athletes' nutritional status and performance were assessed before and after the intervention using a validated food frequency questionnaire, knowledge and eating habits questionnaires, four 24-h recalls, a beep test to estimate VO2 max and one-repetition maximum tests to measure muscle strength. Paired-sample t-tests, McNemar's test and Mixed Factorial Anova test were conducted to examine the effects of the nutritional education program on nutrition knowledge, hydration status, eating habits and performance within both groups. The nutritional knowledge score increased in both groups after the intervention, with a significantly greater improvement of 23% observed in the IG (from 62.6% to 77.1%; p < 0.001). The IG also demonstrated a notable improvement in eating habits compared to the CG (p < 0.001). Following the intervention, body fat percentage decreased from 21.3% ± 6.0% to 18.8% ± 6.0% (p < 0.001), and waist circumference significantly decreased in the IG (p < 0.001). The IG increased their consumption of vegetables (p < 0.001) and yogurt (p = 0.002) and decreased their intake of sugars (p < 0.001) and sunflower oil (p = 0.002). Improvements in both aerobic and strength performance were observed in the IG (p < 0.001). The nutrition education program led to significant improvements in athletes' nutritional knowledge and eating habits, which consequently resulted in enhanced performance.
Parents of children with developmental challenges often face constraints that reduce engagement in meaningful activities (MAs). This study evaluated the measurement properties of the Spanish version of the Engagement in Meaningful Activities Survey (EMAS) in this population. A convenience sample of 688 Spanish parents (468 mothers and 220 fathers) of children with developmental challenges completed the Spanish EMAS, the Occupational Balance Questionnaire (OBQ), the Parental Stress Scale (PSS; Baby's Rewards [PSS-BR] and Stressors [PSS-S]), the Hospital Anxiety and Depression Scale (HADS-A and HADS-D), and the Psychological Well-Being Scale (PWBS). Internal consistency, test-retest reliability, structural validity, and construct validity were examined. There was no consumer or community involvement in this study. EMAS scores averaged 31.1 (standard deviation [SD] = 7.1) for mothers and 33.4 (SD = 6.4) for fathers, with no floor or ceiling effects. Internal consistency was high (α = 0.88 for mothers; α = 0.86 for fathers). Test-retest reliability in mothers (n = 75) was moderate (intra-class correlation coefficient [ICC] = 0.59, 95% confidence interval [CI]: 0.42, 0.72; rs = 0.62). A two-factor structure showed acceptable fit. Construct validity was supported through correlations with OBQ (rsm [mothers] = 0.61; rsf [fathers] = 0.63), HADS-A (rsm = -0.41; rsf = -0.36), HADS-D (rsm = -0.50; rsf = -0.47), PSS-BR (rsm = 0.37; rsf = 0.31), PSS-S (rsm = -0.25; rsf = -0.26), and PWBS (rsm = 0.46; rsf = 0.52). The Spanish EMAS shows robust measurement properties for assessing engagement in MAs among parents of children with developmental challenges. Its use may support family-centred interventions and research. This study evaluated how well the Spanish version of the Engagement in Meaningful Activities Survey (EMAS) works for parents of children with developmental challenges. The EMAS assesses how much people feel that their everyday activities are purposeful, satisfying, and aligned with their values. A total of 688 parents whose children attend early intervention centres in Spain completed the EMAS along with other measures of occupational balance, stress, anxiety, depression, and psychological wellbeing. The results showed that the EMAS is a reliable and valid tool for this population. Parents who reported higher engagement in MAs tended to have better occupational balance and psychological wellbeing and lower stress, anxiety, and depressive symptoms. These findings suggest that the EMAS can help occupational therapists understand how parents participate in activities that matter to them and support the design of interventions aimed at enhancing their wellbeing.
Xie, Weiwei, Xianli Wu, Yiding Li, Qing Xiang, Na Wu, Haolun Sun, Bianba Duojie, Hongda Zhao, Jun Liang, and Ye Fan. Erythrocytapheresis Improves Health-Related Quality of Life in High-Altitude Migrans with Chronic Mountain Sickness: A Single-Arm Before-After Trial at 4,000-4,500 m. High Alt Med Biol. 00:00-00, 2026.Chronic mountain sickness (CMS) arises from maladaptive responses to prolonged residence at altitudes exceeding 2,500 m. Despite the known efficacy of erythrocytapheresis on CMS, the impact of this intervention on health-related quality of life for individuals diagnosed with CMS remains poorly understood. We conducted a single-arm before-after trial using erythrocytapheresis on a total of 22 male migrants with CMS who had resided at high altitudes (4,000-4,500 m) for 6.5 (3.8, 9.3) years. Participants underwent between 1 and 4 erythrocytapheresis sessions, with 1-2 days between each one. The participants exhibited significant improvements following the intervention: health-related quality of life score increased from 85.0 (80.0, 85.3) to 90.0 (90.0, 94.3) (p < 0.001, d = 0.57); CMS score decreased from 7.0 (6.0, 8.0) to 3.0 (2.8, 4.0) (p < 0.0001, d = 0.62); the distance in the 6-Minute Walk Test improved from 612.5 (598.8, 623.0) meters to 654.0 (636.3, 676.3) meters (p < 0.0001, d = 0.62); and SpO2 levels rose from 87.5 (85.8, 90.0) to 90.0 (87.0, 92.5) (p = 0.012, d = 0.38). Erythrocytapheresis proves to be an effective intervention for enhancing health-related quality of life and reducing the severity of CMS in migrant populations.
Despite the established health benefits of vegetables, most children do not consume enough to meet dietary recommendations. Early childhood is a critical period for shaping lifelong eating habits, and social eating experiences play an important role in this learning. This review synthesises evidence on how positive social influences support children's vegetable intake. Findings across shared eating occasions, positive eating atmosphere, modelling, and social facilitation, demonstrate that social experiences shape healthy dietary behaviour, including vegetable intake. The review also highlights the importance of individual differences, including children's eating behaviours and household characteristics such as socioeconomic status, food insecurity, and household chaos, which may influence both the feasibility and effectiveness of creating positive social eating environments. In addition, the review identifies key opportunities for intervention and emphasises the need for more longitudinal research to understand how social eating processes evolve across development. Together, the evidence underscores the potential of positive social influences to enhance children's vegetable consumption and supports the development of tailored, socially grounded nutrition interventions.
Artificial intelligence (AI) is transforming neurovascular surgery by improving diagnostic accuracy, risk prediction, treatment planning, and patient outcomes. This narrative review examines AI across the continuum of cerebrovascular care, from initial diagnosis through intervention and long-term prognostication. We discuss how machine learning, deep learning, computer vision, and natural language processing are applied to diverse data sources including neuroimaging, electronic health records, and intraoperative inputs. AI algorithms augment clinical expertise in diagnosis by delivering high speed and precision for tasks such as detecting large vessel occlusions, characterizing aneurysm morphology, and differentiating hemorrhage subtypes. Beyond detection, AI models are increasingly used for risk stratification-predicting aneurysm rupture, functional recovery after stroke, and post-intervention complications. AI also shows promise in therapeutic decision-making through pre-operative simulation, robotic-assisted microsurgery, and intraoperative guidance systems, with preliminary evidence suggesting potential improvements in procedural safety and efficacy (though most intraoperative AI studies remain at the proof-of-concept or single-center retrospective stage). Despite these developments, challenges remain, including algorithmic bias, limited generalizability, lack of interpretability, data privacy concerns, and regulatory barriers. Successful deployment requires seamless workflow integration and a clear understanding that AI assists, not replaces, the neurosurgeon. The convergence of AI with precision medicine holds promise for personalized, data-driven care through synergistic human-AI collaboration.
The oral‑gut axis is an interorgan regulatory network connecting the two core microbial niches in the human body. It sustains systemic homeostasis through bidirectional microbial translocation, metabolite signaling and immune crosstalk. The present review presented a novel barrier‑metabolism‑immunity three‑dimensional regulatory framework that clarifies the core mechanisms of oral‑gut axis dysregulation: Bidirectional translocation of oral and gut microbiota disrupts microbial homeostasis; key metabolites, including short‑chain fatty acids and trimethylamine N‑oxide, mediate interorgan signaling; immune cell migration and barrier damage collectively constitute the pathological basis, which drives multisystem disorders through secondary axes. The present study classified oral‑gut axis imbalance into three quantifiable subtypes: Barrier‑dominant, metabolism‑dominant and immunity‑dominant, each linked to distinct diseases such as inflammatory bowel disease, type 2 diabetes mellitus and rheumatoid arthritis. Accordingly, a stratified, personalized intervention strategy was proposed. Current challenges include difficulties in causal verification, substantial interindividual variability in intervention efficacy and limited tools for real‑time interorgan tracking. Future research will benefit from microbiota gene editing, multi‑omics integration and in vivo imaging to advance mechanistic understanding and clinical translation. This three‑dimensional model provides a standardized theoretical foundation and practical guidance for the diagnosis and treatment of oral‑gut axis‑related diseases.
Semen Strychni (family Loganiaceae) has a long‑standing history of cultivation in South Asia. The medicinal value of Semen Strychni has attracted extensive attention due to its potential efficacy in the intervention of nervous system diseases, anti‑arrhythmia, analgesia, anti‑inflammation and antitumor fields. However, research on its pharmacological effects are predominantly limited to in vitro experiments, and a systematic pharmacological exploration of different extracts and monomer compounds from Semen Strychni is lacking. Additionally, notable safety risks exist both before and after the processing of Semen Strychni, thus its clinical application and toxicity mechanisms require further in‑depth analysis. The present review comprehensively evaluated the latest research progress on the traditional medicinal history, chemical composition analysis and pharmacological activity of Semen Strychni, and aimed to provide a systematic theoretical reference for the follow‑up basic research of Semen Strychni and its industrial application in the pharmaceutical field.
Retinopathy of prematurity (ROP) remains a leading cause of childhood blindness. Although current therapies effectively suppress pathological neovascularization, many patients continue to exhibit persistent visual dysfunction despite regression of active disease, highlighting an unmet need for neuroprotective interventions. Sigma 1 receptor (Sig1R), an endoplasmic reticulum-mitochondrial chaperone and regulator of cellular stress responses, has emerged as a promising therapeutic target in neurodegenerative and retinal diseases. Here, we investigated whether Sig1R activation confers sustained neuroprotection following neonatal ischemic retinal injury. Wild-type and Sig1R knockout mice were subjected to oxygen-induced retinopathy (OIR) and treated systemically with the high-affinity Sig1R agonist (+)-pentazocine [(+)-PTZ]. Retinal structure and visual function were assessed longitudinally through 20 weeks of age using visual acuity, contrast sensitivity, electroretinography (ERG), pattern ERG (PERG), spectral-domain optical coherence tomography (SD-OCT), and histological analyses. Chronic Sig1R activation significantly preserved visual acuity, contrast sensitivity, rod- and ganglion cell-mediated retinal function, retinal ganglion cell survival, and inner retinal architecture in OIR mice. These protective effects were abolished in Sig1R-deficient mice, demonstrating a requirement for Sig1R in mediating neuroprotection. Mechanistically, Sig1R activation reduced apoptotic signaling, attenuated oxidative and nitrosative stress, improved mitochondrial respiratory function, and enhanced endogenous antioxidant pathways. Collectively, these findings demonstrate that Sig1R activation provides durable, receptor-dependent neuroprotection following neonatal ischemic retinal injury by coordinating redox, mitochondrial, and cell-survival pathways. These results identify Sig1R as a promising therapeutic target for preserving retinal neuronal integrity and long-term visual function in retinopathy of prematurity.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid‑β deposition, tau pathology, synaptic dysfunction, neuronal loss and neuroinflammation. Regular physical activity is a key non‑pharmacological strategy that can ameliorate cognitive impairment and multiple AD‑related pathological features across experimental models by improving mitochondrial function and quality control, strengthening antioxidant defenses, suppressing neuroinflammation and supporting synaptic plasticity. These effects are closely linked to enhanced neurotrophic signaling and cerebrovascular regulation, both of which contribute to resilience against AD‑associated cognitive decline. Fluoxetine, a selective serotonin reuptake inhibitor widely prescribed for depression, has also shown potential benefits in AD models, including modulation of mitochondrial and redox homeostasis, inflammatory signaling and neuroplasticity. The present review integrates evidence on the convergent and divergent molecular targets of exercise and fluoxetine within core AD pathways, highlighting scenarios in which combined interventions may produce synergistic effects, as well as conditions that could lead to antagonistic effects. By mapping shared nodes and potential points of interference, the present review aims to clarify mechanistic hypotheses and inform the design of optimized, clinically translatable strategies that integrate lifestyle and pharmacological approaches for AD.
To illustrate the potential risks of overlooking WILD (i.e., Worldwide, Insitu, Local and Diverse) approaches in developmental psychology, we examined possible cultural biases in child protection interventions across WEIRD (i.e., Western, Educated, Industrialized, Rich and Democratic) countries. Analyses of national statistics revealed that children from minority cultural backgrounds are consistently overrepresented in care systems. We argue that equitable policies must adopt WILD-informed frameworks that respect cultural diversity while ensuring children's safety and well-being.
Intrathoracic gauze packing is an established damage control technique for life-threatening thoracic hemorrhage in trauma settings. However, its role in nontraumatic coagulopathic bleeding remains unclear, and the mechanisms underlying packing failure have not been well characterized. We report a case in which intrathoracic packing failed due to an unrecognized diaphragmatic injury, highlighting an important limitation of this strategy. An 82-year-old man with chronic kidney disease, diabetes mellitus, and hypoalbuminemia underwent emergency video-assisted thoracoscopic decortication for organized empyema. During surgery, he developed severe intraoperative coagulopathic bleeding in the setting of sepsis. Although the thoracic cavity was temporarily closed, persistent hemorrhage necessitated re-exploration, and intrathoracic gauze packing was undertaken as a damage control strategy. Postoperative imaging suggested adequate filling of the pleural cavity; however, hemodynamic instability persisted. Exploratory laparotomy revealed a previously unrecognized laceration of the left diaphragm, through which the intrathoracic packing gauze had prolapsed into the abdominal cavity. The diaphragmatic injury was repaired, hemostasis was achieved, and the patient subsequently recovered with intensive care support. Intrathoracic gauze packing may serve as a valuable temporizing measure for severe coagulopathic intrathoracic bleeding, even in nontraumatic settings, provided that diaphragmatic integrity is preserved. When adequate tamponade cannot be achieved, an occult diaphragmatic injury should be actively suspected. Because such injuries are often difficult to diagnose radiologically in the absence of herniation, early surgical exploration may be warranted. Awareness of this potential mechanism of packing failure may facilitate timely intervention and improve outcomes in critically unstable patients.
To examine foot care behaviors, perceived benefits and barriers to exercise, and the relationships between these factors among diabetic patients undergoing hemodialysis. This study included 151 adults with type 2 diabetes receiving hemodialysis in Istanbul. Data were collected using the Foot Care Behavior Scale, the Diabetic Foot Care Self-Efficacy Scale, and the Exercise Benefits/Barriers Scale for Dialysis Patients. Descriptive statistics, t-tests, ANOVA, correlation analyses, and linear regression were conducted. Higher education and health literacy were associated with improved foot care behaviors and greater perceived benefits of exercise. Fatigue, comorbidities, and lack of knowledge were identified as major barriers to exercise. Regression analysis showed that gender, age, albumin level, and exercise status significantly influenced perceived benefits and barriers. Nursing interventions should focus on patient education, strengthening self-efficacy, and providing individualized exercise guidance to improve outcomes among diabetic hemodialysis patients. These findings highlight the critical role of nurses in promoting self-care behaviors and physical activity among diabetic hemodialysis patients.
The optimal first-line pharmacological therapy for newly diagnosed type 2 diabetes mellitus (T2DM) remains uncertain. This trial compared the vascular and molecular effects of dapagliflozin monotherapy, metformin monotherapy, and their combination in this population. Sixty participants were randomised 1:1:1 to metformin 500 mg twice daily (n = 19), dapagliflozin 10 mg once daily (n = 20), or dapagliflozin-metformin combination (n = 21) for 12 weeks. The primary endpoint was change in reactive hyperaemia index (RHI) from baseline. Secondary endpoints were pulse wave velocity (PWV) and carotid intima-media thickness (CIMT), analysed by ANCOVA. Exploratory sphingolipid and proteomics profiling was performed using partial least squares discriminant analysis and ROC curve analysis. RHI did not differ significantly between groups (primary endpoint). Dapagliflozin produced significantly greater CIMT reduction versus metformin as a secondary endpoint (-0.058 mm; 95% CI -0.106 to -0.010; p = 0.018). PWV changes were non-significant between groups. Sphingolipid profiling identified dapagliflozin-specific downregulation of pro-inflammatory lactosylceramide species, particularly LacCer(d18:0) (AUC 0.814). Proteomics revealed upregulation of EpCAM and downregulation of endothelial adhesion molecules (JAM-A, PECAM-1, vWF) and tissue plasminogen activator with dapagliflozin compared with metformin. In treatment-naïve newly diagnosed T2DM, dapagliflozin produced significantly greater CIMT reduction versus metformin, accompanied by distinct sphingolipid and proteomic signatures suggesting pleiotropic cardioprotective mechanisms. These hypothesis-generating findings warrant validation in larger adequately powered trials. ClinicalTrials.gov identifier: NCT05440591.
Lipid nanoparticles (LNPs) have emerged as a prominent delivery vehicle for therapeutics such as mRNA vaccines and genetic medicines. However, current manufacturing technologies struggle to balance precision, scalability, and cost-effectiveness. While microfluidic mixing offers excellent particle control, it often faces operational challenges, including channel fouling and a reliance on costly single-use chips that create bottlenecks for reproducible and scalable production of LNPs. Conversely, bulk methods lack uniformity, and conventional extrusion remains a labor-intensive batch process. Here, we report a hybrid continuous synthesis platform that integrates a reusable 3D-printed milli-fluidic mixer with inline membrane extrusion. By engineering a robust 3D internal architecture at the milli-scale, this system achieves rapid mixing while mitigating clogging risks associated with micro-channels. Our platform also offers a durable, easy-to-clean alternative that enhances process reproducibility while the integrated design enables single-pass refinement of LNPs, streamlining the production workflow to achieve high-quality, uniform LNPs at flow rates of up to 20 mL min-1. Overall, our study provides a scalable, cost-effective, and contamination-resistant pathway for industrial LNP manufacturing, overcoming the limitations of existing disposable cartridge-based systems.
Benzylpenicillin has long been included in treatment protocols for amatoxin poisoning based on experimental evidence suggesting inhibition of hepatocellular amatoxin uptake via OATP1B3. However, no human pharmacokinetic data have confirmed whether therapeutic regimens achieve serum concentrations sufficient to inhibit this transporter in vivo. We retrospectively analyzed serum benzylpenicillin concentrations in 16 patients with confirmed amatoxin poisoning treated at the Florence Poison Control Center between 2020 and 2024. All patients received continuous intravenous benzylpenicillin infusion (500,000 IU/kg/day for 48 h, followed by 250,000 IU/kg/day for 48 h) as part of a standardized multimodal protocol. Serum samples (n = 44) were collected during routine care and analyzed using LC-MS/MS. Concentrations were expressed in micromolar (µM) and compared with the reported OATP1B3 inhibitory concentration (IC50 = 25 µM). During the first 48h, all serum samples exceeded the IC50 threshold, with mean concentrations of 265 ± 87 µM at 24 h and 241 ± 74 µM at 48 h. Across all samples, the median concentration was 176 µM (range 45-430 µM), and 93% exceeded 25 µM. Following dose reduction, mean concentrations declined but remained above the IC50 in 66% of samples. No adverse events attributable to benzylpenicillin were observed, and all patients survived to discharge without liver transplantation. Although benzylpenicillin's clinical efficacy has yielded conflicting results across retrospective series, variability in dosing regimens and timing likely accounts for much of this inconsistency. The present findings demonstrate that continuous infusion maintains pharmacologically relevant exposure throughout the critical window of amatoxin hepatocellular uptake, supporting target engagement in vivo. The reduced-dose regimen sustained inhibitory concentrations in most samples, suggesting dose optimization is feasible without compromising pharmacological activity. Continuous intravenous infusion of benzylpenicillin achieves serum concentrations exceeding the in vitro OATP1B3 inhibitory threshold in patients with amatoxin poisoning, providing human pharmacokinetic support for its proposed antidotal mechanism and its continued inclusion in multimodal treatment protocols.