Search Results (58,066)

Hibiscus syriacus L. (HS), native to Eastern and Southern Asia, has been traditionally used in Asian herbal medicine for its anticancer, antimicrobial, and anti-inflammatory properties. Despite these recognized bioactivities, its potential cardioprotective effects, particularly in the setting of heart failure (HF), remain largely unexplored. This study aimed to investigate the effects of HS extracts and its bioactive constituents on angiotensin II (Ang II)-induced cardiac injury using an in vitro model with H9c2 rat cardiomyocytes. Cells exposed to Ang II were pretreated with HS extracts, and assays were performed to assess cell viability, reactive oxygen species (ROS) generation, protein synthesis, and secretion of inflammatory mediators, including tumor necrosis factor-alpha, interleukin 1β (IL-1β), and interleukin 6 (IL-6), as well as chemokine (CCL20) and HF-related biomarkers, such as brain natriuretic peptide (BNP) and endothelin-1. The results demonstrated that HS extracts significantly and dose-dependently attenuated Ang II-induced ROS accumulation and suppressed the secretion of pro-inflammatory cytokines, chemokines, BNP, and endothelin-1. Additionally, HS and its purified components inhibited Ang II-induced protein synthesis, indicating anti-hypertrophic effects. Collectively, these findings highlight the antioxidative, anti-inflammatory, and antihypertrophic properties of HS in the context of Ang II-induced cardiac injury, suggesting that HS may represent a promising adjunctive therapeutic candidate for HF management. Further in vivo studies and mechanistic investigations are warranted to validate its clinical potential. Full article

The cornea, the transparent anterior window of the eye, critically refracts light and protects intraocular structures. Corneal pathologies, including trauma, infection, chemical injury, metabolic diseases, genetic conditions, and age-related degeneration, can lead to significant visual impairment. While penetrating keratoplasty or full-thickness corneal transplantation remains a standard and effective intervention for severe corneal dysfunction, limitations in donor tissue availability and the risk of immunogenic graft rejection necessitate alternative therapeutic strategies. Furthermore, for cases of isolated epithelial disfunction, a full-thickness cornea graft may not be required or effective. This review examines the potential of corneal epithelial constructs derived from autologous stem cells with functional barrier properties for corneal reconstruction and in vitro pharmacotoxicity testing. In this review, we delineate the current limitations of corneal transplantation, the advantages of stem cell-based approaches, and recent advances in generating engineered corneal epithelium. Finally, we address remaining technical challenges and propose future research directions aimed at clinical translation. Full article

Monitoring position and movements of preterm infants is important to ensure their well-being and optimal development. This study evaluates the feasibility of a pressure-sensitive fiber-optic mattress (FM), made entirely of plastic, for two-dimensional analysis of preterm infant movements and positioning. Before clinical use, we developed a simple, replicable, and cost-effective test protocol to simulate infant movements and positions, enabling early identification of technical limitations. Using data from 20 preterm infants, we assessed the FM’s potential to monitor posture and limb motion. FM-derived pressure patterns were compared with camera-based manual annotations to distinguish between different positions and out-of-bed moments, as well as limb-specific movements. Bench-test results demonstrated the FM’s sensitivity to motion and pressure changes, supporting its use in preclinical validation. Clinical data confirmed the FM’s reliability in identifying infant positions and movement patterns, showing an accuracy comparable to camera annotations. However, limitations such as calibration, sensitivity to ambient light, and edge-related artifacts were noted, indicating areas for improvement. In conclusion, the test protocol proved effective for early-stage evaluation of smart mattress technologies. The FM showed promising clinical feasibility for non-obtrusive monitoring of preterm infants, though further optimization is needed for robust performance in neonatal care. Full article

Art therapy serves as a crucial intervention modality for children with autism spectrum disorder (ASD), demonstrating unique value in emotional expression, sensory integration, and social communication. However, current practice presents critical challenges, including the disconnect between design expertise and clinical needs, unclear mechanisms of environmental factors’ impact on therapeutic outcomes, and insufficient evidence-based support for technology integration. Purpose: This study aimed to construct an evidence-based theoretical framework for art therapy environment design for children with autism, clarifying the relationship between environmental design elements and therapeutic effectiveness. Methodology: Based on the Web of Science database, this study employed a dual-track approach comprising bibliometric analysis and micro-qualitative content analysis to systematically examine the knowledge structure and developmental trends. Research hotspots were identified through keyword co-occurrence network analysis using CiteSpace, while 24 representative design cases were analyzed to gain insights into design concepts, emerging technologies, and implementation principles. Key Findings: Through keyword network visualization analysis, this study identified ten primary research clusters that were systematically categorized into four core design elements: sensory feedback design, behavioral guidance design, emotional resonance design, and therapeutic support design. A responsive therapeutic environment conceptual framework was proposed, encompassing four interconnected components based on the ABC model from positive psychology: emotional, sensory, environmental, and behavioral dimensions. Evidence-based design principles were established emphasizing child-centeredness, the promotion of multisensory expression, the achievement of dynamic feedback, and appropriate technology integration. Research Contribution: This research establishes theoretical connections between environmental design elements and art therapy effectiveness, providing a systematic design guidance framework for interdisciplinary teams, including environmental designers, clinical practitioners, technology developers, and healthcare administrators. The framework positions technology as a therapeutic mediator rather than a driver, ensuring technological integration supports rather than interferes with children’s natural creative impulses. This contributes to creating more effective environmental spaces for art therapy activities for children with autism while aligning with SDG3 goals for promoting mental health and reducing inequalities in therapeutic access. Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic immune-mediated neurological disorder that primarily affects young adults and is frequently accompanied by psychiatric comorbidities such as depression and anxiety, both of which significantly diminish patients’ quality of life (QoL). This study investigated the effect of two oral disease-modifying therapies (DMTs), fingolimod and cladribine, on mental health and QoL in patients with relapsing-remitting MS (RRMS). The aim of the study was to compare levels of depression, anxiety, and health-related quality of life (HRQoL) in RRMS patients treated with fingolimod or cladribine, and to evaluate their associations with clinical and radiological parameters. Materials and Methods: Eighty RRMS patients aged 18 to 50 years with Expanded Disability Status Scale (EDSS) scores of 3.0 or less, no recent disease relapse, and no history of antidepressant use were enrolled. Forty patients were treated with fingolimod and forty with cladribine. Depression and anxiety were assessed using the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). QoL was evaluated using the Multiple Sclerosis QoL-54 (MSQOL-54) instrument. Additional clinical data, including MRI-based lesion burden, EDSS scores, age, disease duration, and occupational status, were collected. Results: No statistically significant differences were observed between the two groups regarding HDRS and HARS scores (p > 0.05). However, patients treated with fingolimod had significantly higher scores in the Energy/Fatigue subdomain (7.55 ± 2.02 vs. 6.56 ± 2.57, p = 0.046) and Composite Mental Health (CMH) score (64.73 ± 15.01 vs. 56.00 ± 18.93, p = 0.029) compared to those treated with cladribine. No significant differences were found in the independent items of the MSQOL-54. A negative correlation was identified between total lesion load and QoL scores. Conclusions: Although fingolimod and cladribine exert comparable effects on depression and anxiety levels, fingolimod may be associated with better mental health outcomes and reduced fatigue in RRMS patients. Furthermore, lesion burden and clinical parameters such as age and EDSS score may independently influence QoL, regardless of the DMT used. Full article

Intratumoral injections of macromolecules, such as biologics and immunotherapeutics, show promise in overcoming dose-limiting side effects associated with systemic injections and improve treatment efficacy. However, the retention of injectates in the tumor microenvironment is a major underappreciated challenge. High interstitial pressures and dense tumor architectures create shear forces that rapidly expel low-viscosity solutions post-injection. Injectable hydrogels may address these concerns by providing a viscoelastic delivery vehicle that shields loaded therapies from rapid expulsion from the tumor. A chitosan–glycerol hydrogel was thus developed and characterized with the goal of improving the injection retention of loaded therapeutics. The gelation parameters and mechanical properties of the hydrogel were explored to reveal a shear-thinning gel that is injectable through a 27-gauge needle. Biocompatibility studies demonstrated that the chitosan–glycerol hydrogel was nontoxic. Retention studies revealed significant improvements in the retention of model therapeutics when formulated with the chitosan–glycerol hydrogel compared to less-viscous solutions. Finally, release studies showed that there was a sustained release of model therapeutics of various molecular sizes from the hydrogel. Overall, the chitosan–glycerol hydrogel demonstrated injectability, enhanced retention, biocompatibility, and sustained release of macromolecules, indicating its potential for future clinical use in intratumoral macromolecule delivery. Full article

Background: Breast cancer is the most common neoplasm in women. Despite effective treatments, sequelae such as decreased muscle strength, upper limb dysfunction, and tissue changes are common, highlighting the need for functional assessments during rehabilitation. This study analysed the morphofunctional profile of the upper limbs in breast cancer survivors, comparing muscle strength and ultrasound findings between groups with and without lymphoedema, as well as between ipsilateral and contralateral limbs. Methods: This cross-sectional study included female breast cancer survivors treated at an oncology physical therapy clinic. Muscle strength was measured using dynamometry (handgrip and arm flexor strength), and ultrasound assessed the thickness of the dermal–epidermal complex (DEC), subcutaneous tissue (SUB), and muscle (MT). Results: The upper limbs of 41 women were evaluated. No significant differences were observed between those with and without breast cancer-related lymphoedema (BCRL). When comparing the ipsilateral and contralateral limbs, significant reductions were observed in arm flexor strength (p < 0.001; 95% CI: −9.77 to −2.50), handgrip strength (p < 0.001; 95% CI: −4.10 to −1.22), and tissue thickness, with increased DEC thickness on the forearm (0.20 mm; p = 0.022) and arm flexors (0.25 mm; p < 0.001) of the ipsilateral limb. Conclusion: Significant differences in muscle strength and tissue structure between ipsilateral and contralateral limbs may reflect surgical and local pathophysiological effects. A trend toward reduced values for these parameters was also noted in limbs with BCRL, reinforcing the importance of future research to elucidate underlying mechanisms and guide more effective therapeutic strategies. Full article

Background and aim: Advanced Therapy Medicinal Products (ATMPs) are innovative drugs based on genes, tissues, or cells that target rare and severe diseases. ATMPs have shown promising clinical outcomes but are associated with high costs, raising questions about cost-effectiveness. Hence, this systematic review aims to analyze the cost-effectiveness and cost-utility profiles of the European Medicines Agency-authorized ATMPs for treating rare diseases. Methods: A systematic review was conducted following PRISMA guidelines. Studies were identified by searching PubMed, Embase, Web of Science, and ProQuest scientific databases. Economic evaluations reporting incremental cost-effectiveness/utility ratios (ICERs/ICURs) for ATMPs were included. Costs were standardized to 2023 Euros, and a cost-effectiveness plane was constructed to evaluate the results against willingness-to-pay (WTP) thresholds of EUR 50,000, EUR 100,000, and EUR 150,000 per QALY, as part of a sensitivity analysis. Results: A total of 61 studies met the inclusion criteria. ATMPs for rare blood diseases, such as tisagenlecleucel and axicabtagene ciloleucel, were found to be cost-effective in a majority of studies, with incremental QALYs ranging from 1.5 to 10 per patient over lifetime horizon. Tisagenlecleucel demonstrated a positive cost-effectiveness profile in the treatment of acute lymphoblastic leukemia (58%), while axicabtagene ciloleucel showed a positive profile in the treatment of diffuse large B-cell lymphoma (85%). Onasemnogene abeparvovec for spinal muscular atrophy (SMA) showed uncertain cost-effectiveness results, and voretigene neparvovec for retinal diseases was not cost-effective in 40% of studies, with incremental QALYs around 1.3 and high costs exceeding the WTP threshold set. Conclusions: ATMPs in treating rare diseases show promising economic potential, but cost-effectiveness varies across indications. Policymakers must balance innovation with system sustainability, using refined models and the long-term impact on patient outcomes. Full article

Background: Accurate and timely prediction of mortality in intensive care unit (ICU) patients, particularly those with COVID-19, remains clinically challenging due to complex immune responses. Proteomic cytokine profiling holds promise for refining mortality risk assessment. Methods: Serum samples from 89 ICU patients (55 discharged, 34 deceased) were analyzed using a multiplex 21-cytokine panel. Samples were stratified into three groups based on time from collection to outcome: ≤48 h (Group 1: Early), >48 h to ≤7 days (Group 2: Intermediate), and >7 days to ≤14 days (Group 3: Late). Cytokine levels, simple cytokine ratios, and previously unexplored complex ratios between pro- and anti-inflammatory cytokines were evaluated. Machine learning-based feature selection identified the most predictive ratios, with performance evaluated by area under the curve (AUC), sensitivity, and specificity. Results: Complex cytokine ratios demonstrated superior predictive accuracy compared to traditional severity markers (APACHE II, SAPS II, SOFA), individual cytokines, and simple ratios, effectively distinguishing discharged from deceased patients across all groups (AUC: 0.918–1.000; sensitivity: 0.826–1.000; specificity: 0.775–0.900). Conclusions: Multiplex cytokine profiling enhanced by computationally derived complex ratios may offer robust predictive capabilities for ICU mortality risk stratification, serving as a valuable tool for personalized prognosis in critical care. Full article

Congenital cataracts (CCs) are a leading cause of preventable childhood blindness, with genetic factors playing a crucial role in their etiology. Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder associated with CCs but is often underdiagnosed due to variable expressivity, particularly in female carriers. Objective: This study aimed to explore the genetic landscape of CCs in a Swiss cohort, focusing on two novel NHS and one novel GJA8 variants and their phenotypic presentation. Methods: Whole-exome sequencing (WES) was conducted on 20 unrelated Swiss families diagnosed with CCs. Variants were analyzed for pathogenicity using genetic databases, and segregation analysis was performed. Clinical data, including cataract phenotype and associated systemic anomalies, were assessed to establish genotype–phenotype correlations. Results: Potentially pathogenic DNA sequence variants were identified in 10 families, including three novel variants, one in GJA8 (c.584T>C) and two NHS variants (c.250_252insA and c.484del). Additional previously reported variants were detected in CRYBA1, CRYGC, CRYAA, MIP, EPHA2, and MAF, reflecting genetic heterogeneity in the cohort. Notably, NHS variants displayed significant phenotypic variability, suggesting dose-dependent effects and X-chromosome inactivation in female carriers. Conclusions: NHS remains underdiagnosed due to its variable expressivity and the late manifestation of systemic features, often leading to misclassification as isolated CC. This study highlights the importance of genetic testing in unexplained CC cases to improve early detection of syndromic forms. The identification of novel NHS and GJA8 variants provides new insights into the genetic complexity of CCs, emphasizing the need for further research on genotype–phenotype correlations. Full article

Introduction: Oxidative stress is a key factor in the pathogenesis of many chronic diseases, especially in postmenopausal women. Xylitol, a sugar alcohol with potential antioxidant properties, may affect oxidative balance when used as a sugar substitute. Aim: This pilot study aimed to assess the effect of replacing sucrose with xylitol on serum antioxidant capacity in postmenopausal women. Methods: This study included 34 women aged 50 to 65 years who successively consumed 5 g/d, 10 g/d, and 15 g/d of xylitol. The dietary intervention lasted a total of 6 weeks, with each phase covering a 2-week period. Diet was assessed twice based on a 7-day dietary interview (Diet 6.0, NIZP–PZH, Warsaw). The material for this study was venous blood. Antioxidant capacity was determined using the DPPH radical scavenging method and the ABTS cation radical scavenging method. Results: In both methods, a significant increase in serum antioxidant potential was observed after replacing sugar with xylitol (p < 0.0001). An increase in the ability to neutralize free radicals was observed in almost all women studied. Additional analysis of the effect of selected nutrients on the obtained effects of the nutritional intervention showed that the most significant effect could potentially be exerted by manganese, maltose, sucrose, and mercury, and the strongest positive correlation was exerted by vitamin A, retinol, and vitamin E. Although the values obtained in the constructed models were not statistically significant, the large effect indicates potentially significant relationships that could have a significant impact on serum antioxidant potential in the studied group of women. Conclusions: The results suggest a potential role of xylitol in enhancing antioxidant defense mechanisms in menopausal women. Although the sample size was relatively small, this study was powered at approximately 80% to detect large effects, supporting the reliability of the observed results. Nevertheless, given the pilot nature of this study, further research with larger cohorts is warranted to confirm these preliminary observations and to clarify the clinical significance of xylitol supplementation in populations exposed to oxidative stress. Full article

Background: Cardiac implantable electronic device (CIED) infections necessitate extraction and subsequent pacing interventions. Conventional methods after removing the infected CIED system involve temporary or semi-permanent pacing followed by delayed permanent pacemaker (PPM) implantation. Leadless pacemakers (LPs) may offer an alternative, allowing immediate PPM implantation without increasing infection risks. Our objective is to evaluate the safety and cost-effectiveness of LP implantation during the same procedure of CIED extraction, compared to conventional two-stage approaches. Methods: Pacemaker-dependent patients with systemic or pocket infection undergoing device extraction and LP implantation during the same procedure at Sheba Medical Center, Israel, were compared to a historical group of patients undergoing a semi-permanent (SP) pacemaker implantation during the procedure, followed by a permanent pacemaker implantation. Results: The cohort included 87 patients, 45 undergoing LP implantation and 42 SP implantation during the extraction procedure. The LP group demonstrated shorter intensive care unit stay (1 ± 3 days vs. 7 ± 12 days, p < 0.001) and overall hospital days (11 ± 24 days vs. 17 ± 17 days, p < 0.001). Rates of infection relapse and one-year mortality were comparable between groups. Economic analysis revealed comparable total costs, despite the higher initial expense of LPs. Conclusions: LP implantation during CIED extraction offers significant clinical and logistical advantages, including reduced hospital stays and streamlined treatment, with comparable safety and cost-effectiveness to conventional approaches. Full article

Background: Acute mountain sickness (AMS) is a prevalent and potentially life-threatening condition caused by rapid exposure to high-altitude hypoxia, affecting pulmonary and neurological functions. Tongqiao Jiuxin Oil (TQ), a traditional Chinese medicine formula composed of aromatic and resinous ingredients such as sandalwood, agarwood, frankincense, borneol, and musk, has been widely used in the treatment of cardiovascular and cerebrovascular disorders. Clinical observations suggest its potential efficacy against AMS, yet its pharmacological mechanisms remain poorly understood. Methods: The chemical profile of TQ was characterized using UHPLC-Q-Exactive Orbitrap HRMS. Network pharmacology was applied to predict the potential targets and pathways involved in AMS. A rat model of AMS was established by exposing animals to hypobaric hypoxia (~10% oxygen), simulating an altitude of approximately 5500 m. TQ was administered at varying doses. Physiological indices, oxidative stress markers (MDA, SOD, GSH), histopathological changes, and the expression of hypoxia- and apoptosis-related proteins (HIF-1α, VEGFA, EPO, Bax, Bcl-2, Caspase-3) in lung and brain tissues were assessed. Results: A total of 774 chemical constituents were identified from TQ. Network pharmacology predicted the involvement of multiple targets and pathways. TQ significantly improved arterial oxygenation and reduced histopathological damage in both lung and brain tissues. It enhanced antioxidant activity by elevating SOD and GSH levels and reducing MDA content. Mechanistically, TQ downregulated the expression of HIF-1α, VEGFA, EPO, and pro-apoptotic markers (Bax/Bcl-2 ratio, Caspase-3), while upregulated Bcl-2, the anti-apoptotic protein expression. Conclusions: TQ exerts protective effects against AMS-induced tissue injury by improving oxygen homeostasis, alleviating oxidative stress, and modulating hypoxia-related and apoptotic signaling pathways. This study provides pharmacological evidence supporting the potential of TQ as a promising candidate for AMS intervention, as well as the modern research method for multi-component traditional Chinese medicine. Full article

Background: Aortic stenosis (AS) is the most common valvular heart disease, associated with poor outcomes if left untreated. Current guidelines recommend that transcatheter aortic valve implantation (TAVI) procedures be performed in hospitals with an on-site cardiac surgery unit due to potential complications requiring surgical intervention. Objective: Based on our experience, we evaluated the feasibility and outcomes of implementing a TAVI program in a cardiology department without an on-site cardiac surgery unit, in collaboration with a remote hospital for surgical backup. Methods: The TAVI program involved pre- and post-procedural evaluations conducted at Meir Medical Center (Kfar Saba, Israel) with a remote surgical team available. The study population included 149 consecutive patients with severe aortic stenosis treated at the Meir valve clinic between November 2019 and December 2023. Procedures were performed by the center’s interventional cardiology team. Results: The mean age of the 149 patients was 80 ± 6 years, and 75 (50%) were female. The average STS score was 4.3, and the EuroSCORE II was 3.1. Among the patients, 68 (45%) were classified as New York Heart Association (NYHA) class III-IV. The valve types used included ACURATE neo2 (57 patients, 38%), Edwards SAPIEN 3 (43 patients, 28%), Evolut-PRO (41 patients, 27%), and Navitor (7 patients, 4%). There were no cases of moderate to severe paravalvular leak and no elevated post-implantation gradients, and there was no need for urgent cardiac surgery. One case of valve embolization was successfully managed percutaneously during the procedure. In-hospital follow-up revealed no deaths and only one major vascular complication. At one-year follow-up, six patients had died, with only one death attributed to cardiac causes. Conclusions: Our findings support the safe and effective performance of transfemoral TAVI in cardiology departments without on-site cardiac surgery, in collaboration with a remote surgical team. Further prospective, multicenter studies are warranted to confirm these results and guide broader clinical implementation of this practice. Full article

Background/Objectives: Pneumatic dilation (PD) is a widely used treatment modality in the management of achalasia. It is particularly relevant in regions where many centers lack access to advanced therapeutic modalities. Therefore, we aimed to assess the effectiveness and safety of PD in our local region. Methods: This study retrospectively analyzed patients with achalasia that underwent PD from 1/2013 to 12/2019. The diagnosis of achalasia was established on the grounds of clinical symptoms, radiological and endoscopic findings, and esophageal manometry. Data on patient’s clinical characteristics, dilation technique and postprocedural follow-up were collected and statistically analyzed. Procedure effectiveness was defined as the postprocedural Eckardt score ≤ 3. Results: PD significantly reduced frequency of dysphagia, regurgitation, and retrosternal pain (p < 0.001). Body-weight increased significantly one month and one year after the procedure (p < 0.001). The procedural success rate was 100%. No severe complications were reported. Conclusions: PD is an effective and safe treatment modality in the management of achalasia. The study limitations include a single center design with the small number of participants, not all of whom underwent manometry, gender disproportion, absence of non-responders, and a short follow-up. Full article