Search Results (444)

Hearing loss (HL) affects more than 1.5 billion people worldwide and remains a leading cause of disability across the lifespan. While genetic predispositions, otitis media (OM), and cholesteatoma are well-recognized contributors, Eustachian tube dysfunction (ETD) is an underappreciated but pivotal determinant of auditory morbidity. By impairing middle ear pressure (MEP) regulation, ETD drives conductive hearing loss (CHL) through stiffness and mass-loading effects, contributes to sensorineural hearing loss (SNHL) via altered window mechanics and vascular stress, and produces mixed hearing loss (MHL) when these pathways converge. A characteristic clinical trajectory emerges in which conductive deficits often resolve quickly with restored ventilation, whereas sensorineural impairment requires prolonged, physiology-restoring intervention, resulting in transient or persistent MHL. This review integrates mechanistic insights with clinical manifestations, diagnostic approaches, and therapeutic options. Diagnostic frameworks that combine patient-reported outcomes with objective biomarkers such as wideband absorbance, tympanometry, and advanced imaging enable reproducible identification of ETD-related morbidity. Conventional treatments, including tympanostomy tubes and balloon dilation, offer short-term benefit but rarely normalize tubal physiology. In contrast, Eustachian tube catheterization (ETC) has emerged as a promising, mechanism-based intervention capable of reestablishing dynamic tubal opening and MEP regulation. Looking forward, integration of physiology-based frameworks with personalized diagnostics and advanced tools such as artificial intelligence (AI) may help prevent progression from reversible conductive deficits to irreversible SNHL or MHL. Full article

Background: Pre-existing atrial fibrillation (AF) is common among patients undergoing transcatheter aortic valve replacement (TAVR). However, evidence regarding its impact on the risk of permanent pacemaker (PPM) implantation and other conduction disturbances (CDs) after TAVR remains inconsistent. The aim of this study was to assess the effect of baseline heart rhythm on the risk of conduction abnormalities following TAVR. Methods: This study included patients with severe AS who underwent TAVR using either balloon-expandable (BEVs) or self-expanding valves (SEVs). The primary endpoint was the incidence of PPM implantation and new or worsening left bundle branch block (LBBB) after TAVR according to baseline rhythm (sinus rhythm vs. AF). Secondary endpoints were predictors of PPM implantation, LBBB, the occurrence of periprocedural stroke, and in-hospital mortality. Results: A total of 5195 TAVR patients were included: 3560 with baseline sinus rhythm and 1635 with baseline AF. PPM implantation was more frequent in patients with AF than in those with sinus rhythm (17% vs. 15%, p = 0.033), whereas new or worsening LBBB was less common (11% vs. 14%, p = 0.026). After adjustment with multivariable logistic regression, these associations were no longer statistically significant (PPM implantation: OR 1.156, 95% CI 0.969–1.379, p = 0.108; new or worsening LBBB: OR 0.826, 95% CI 0.676–1.010, p = 0.062). Independent peri-procedural predictors of PPM implantation included baseline first-degree AV block, pre-procedural RBBB, the use of self-expandable valves, implantation of larger valve sizes (≥23 mm), and the need for valve repositioning. Conclusions: In this large cohort, baseline AF was not associated with an increased risk of PPM implantation or new onset LBBB compared with sinus rhythm. These findings suggest that baseline rhythm alone should not be considered an independent predictor of PPM implantation or CDs following TAVR. Full article

Integrated permitting systems are being progressively implemented by governments worldwide owing to their beneficial effects on site-level environmental management. However, different countries have implemented different systems that reflect their own national conditions, resulting in varying efficacy. Based on experience from Korea, here, we propose an e-permit system that implements (i) package management of industries related to or within the value chain of permitted industries, (ii) site-specific best available techniques (BATs), (iii) automatic calculations of BAT-associated emission levels (BAT-AELs), and (iv) code-based management of environmental factors using a ReGreen-BAT (RG-BAT) diagram. The e-permit system improves permitting process efficiency and reduces the review period from 35 days to 2–23 days depending on the industry sector. Additionally, by leveraging big data collected through the Integrated Environmental Permitting System for post-permit management, administrative efficiency could be further improved. Integrating industries related to or within the value chain of the target industries in the Integrated Environmental Management System (IEMS) can reduce pollution, improve resource circulation, and promote energy efficiency and cost savings. When selecting BATs, the balloon effect and internal site-specific factors should be evaluated to realize more tailored and acceptable BAT selection. Automation of BAT-AEL calculations using Python considerably reduces the processing time to 2–3 weeks. The RG-BAT diagram helps visualize BAT effectiveness and allows businesses to easily identify suitable BATs. The insights gained herein indicate that countries implementing IEMS can benefit from sharing implementation experiences and should collaborate on the development of advanced systems. Full article

Background: Orthostatic hypotension (OH) is identified by a significant decrease in blood pressure upon standing from a seated or supine position. A reduction in systolic blood pressure of 20 mmHg within three minutes of standing meets the criteria for clinical diagnosis. We hypothesized that venous outflow obstruction from jugular valvular dysfunction or extrinsic compression of the left brachiocephalic vein may cause OH. Improving venous return and reducing venous congestion of the autonomic pathways through endovascular intervention could alleviate symptoms. Methods: This retrospective review included six male patients (aged 63–87) with medically refractory OH who underwent venograms revealing jugular, brachiocephalic, or subclavian vein stenosis. Patients were treated with balloon angioplasty and/or stenting. Blood pressure was measured in supine, seated, and standing positions before and immediately after the procedure, with multiple readings per position (total n = 117 for supine-standing comparisons). Statistical analysis used Welch’s t-test to compare pre- and post-procedural systolic blood pressure disparities. Results: The patients showed improved post-procedural blood pressure and reduced OH symptoms. The average supine-standing systolic disparity decreased from 38.68 mmHg preoperatively to 24.61 mmHg postoperatively (p = 0.024). The seated-standing disparity was insignificant, possibly due to autonomic compensation. Patients also reported relief from associated symptoms like headaches, tinnitus, and vertigo. Conclusions: These findings suggest venous outflow obstruction may contribute to OH, and venoplasty/stenting can mitigate symptoms, potentially reducing reliance on medications with adverse effects. Further studies should explore the role of Venous Outflow Obstruction Disorders in neurological conditions. Full article

Aortic stenosis (AS) is a common degenerative valvular disease in elderly patients, causing obstruction of left ventricular outflow and presenting with symptoms such as angina, syncope, and heart failure. Although surgical aortic valve replacement (SAVR) remains the gold standard, its high perioperative risk in frail patients has led to the adoption of transcatheter aortic valve implantation (TAVI) as a less invasive and effective alternative. The transfemoral (TF) access route is generally preferred, but severe peripheral arterial disease may limit its feasibility. We report the case of a 71-year-old woman with critical AS complicated by multiple comorbidities, including extensive vascular calcifications, a porcelain aorta, and significant subrenal abdominal aortic stenosis. Multimodal imaging, including computed tomography, was essential for procedural planning, revealing complex iliofemoral anatomy unsuitable for conventional device passage without intervention. Intravascular lithotripsy (IVL) was used to disrupt calcific plaques and facilitate safe vascular access. The TAVI procedure was successfully performed under local anesthesia via TF access using a 65 cm GORE® DRYSEAL Flex Introducer Sheath (W. L. Gore & Associates, Flagstaff, AZ, USA) (18-Fr). After balloon valvuloplasty performed over a SAFARI2™ Pre-Shaped TAVI Guidewire, Extra Small (Boston Scientific, Marlborough, MA, USA) Curve in the left ventricle, a self-expanding Medtronic Evolut™ FX 26 (Medtronic, Minneapolis, MN, USA)mm transcatheter valve was implanted. Postoperative imaging confirmed optimal valve function and vascular integrity without complications. This case highlights the role of IVL as an innovative adjunctive technique enabling TF-TAVI in patients with challenging vascular anatomy, thereby expanding treatment options for high-risk individuals with severe AS. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as the leading cause of chronic liver disease, closely tied to rising global obesity rates. Endoscopic bariatric therapies (EBTs), including endoscopic sleeve gastroplasty (ESG), intragastric balloons (IGB), duodenal-jejunal bypass liners (DJBL), and duodenal mucosal resurfacing (DMR), offer minimally invasive interventions that target metabolic dysfunction and weight loss. This review synthesizes current evidence on the mechanisms and hepatic outcomes of EBTs in MASLD, highlighting improvements in hepatic steatosis, liver stiffness, and fibrosis biomarkers across multiple modalities. ESG is consistently associated with reductions in hepatic steatosis and fibrosis scores across multiple studies. IGB therapy improves liver stiffness and reduces hepatic fat as assessed by imaging modalities such as MRI- Proton Density Fat Fraction and ultrasound. DJBL lowers liver enzymes and improves non-invasive markers of steatohepatitis like the Fibroscan-AST score, although its effect on fibrosis appears limited. DMR demonstrates reductions in liver fat, particularly in patients with type 2 diabetes, but evidence for histological improvement in MASLD remains inconsistent. Despite their promise, most EBT studies remain limited by small sample sizes and short follow-up. Further randomized trials are needed to validate long-term efficacy and position EBTs alongside or as alternatives to surgical interventions for MASLD. Full article

Background/Objectives: Mechanical circulatory support (MCS) is increasingly utilized for the management of acute decompensated heart failure (HF) and cardiogenic shock (CS). The primary goals of MCS are to restore systemic perfusion, reduce cardiac workload, and support end-organ function. A thorough understanding of cardiovascular physiology in patients supported by MCS is essential for clinical decision-making. This review summarizes current evidence on the physiological effects of various MCS devices, key monitoring techniques, patient management, and explores the emerging role of artificial intelligence (AI) in this field. Main Text: Short-term MCS devices include intra-aortic balloon pumps (IABP), percutaneous left-sided devices such as Impella (Abiomed, Danvers, MA, USA) and TandemHeart (LivaNova, London, UK), percutaneous right-sided support devices like Protek Duo (LivaNova, London, UK) and Impella RP Flex (Abiomed, Danvers, MA, USA), and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Long-term support is mainly provided by left ventricular assist devices (LVADs), including the HeartMate 3 (Abbott Laboratories, Chicago, IL, USA). Optimal MCS application requires an understanding of device-specific cardiovascular interactions and expertise in appropriate monitoring tools to assess device performance and patient response. The choice of device, timing of initiation, and patient selection must be individualized, with careful consideration of ethical implications. The integration of AI offers significant potential to advance clinical care by improving complication prediction, enabling real-time optimization of device settings, and refining patient selection criteria. Conclusions: MCS is a rapidly evolving field that requires a comprehensive understanding of cardiovascular interactions, careful selection of monitoring strategies, and individualized clinical management. Future research should address current device limitations, clarify device-specific clinical applications, and assess the validity of AI-driven technologies. Full article

Nuclear fuel cladding serves as the primary barrier to the release of radioactive fission products and is subjected to high-temperature and high-pressure environments during both normal reactor operation and accident scenarios such as loss of coolant accidents (LOCAs). Predicting the burst behavior of cladding is essential for ensuring structural integrity, especially under varying heating rates—an aspect inadequately addressed in existing empirical models. In this study, a finite element-based damage model is developed to simulate the ballooning and burst behavior of Zircaloy-4 cladding. The model incorporates creep deformation, stress triaxiality, and time-dependent damage accumulation. Material behavior is characterized using experimentally determined creep constants and the model is calibrated against burst test data from the literature. A new heating-rate-dependent burst correlation is proposed based on model outputs. The results indicate that increasing the heating rate raises the burst temperature due to reduced exposure time in the temperature regime where creep damage accumulates significantly. The model accurately reproduces burst behavior across a wide range of internal pressures (1–10 MPa) and heating rates (5–100 °C/s). The newly developed correlation improves predictive capability in accident analysis tools and can be directly implemented into safety analysis codes for Indian pressurized heavy water reactors (PHWRs), contributing to enhanced reactor safety evaluations. Full article

Background/Objectives: Exogenous ketone supplements elevate circulating ketones without carbohydrate restriction, but their long-term hepatic safety remains unclear. This study evaluated the formulation-dependent impact of chronic ketone supplementation on liver histopathology, inflammatory signaling, and systemic biomarkers in rats. Methods: Male Sprague-Dawley rats were orally administered 1,3-butanediol (BD), medium-chain triglycerides (MCTs), ketone ester (KE), ketone electrolytes/salts (KSs), or a ketone salt–MCT combination (KSMCT) for 4 weeks. In a separate arm, animals received standard diet (SD), or SD supplemented with low-dose KE (LKE) or high-dose KE (HKE), for 83 days. Liver structure was assessed by hematoxylin and eosin staining with quantification of red blood cell density and lipid accumulation. Inflammatory and metabolic responses were evaluated by TNF-α and arginase immunohistochemistry. Serum biochemistry included glucose, proteins, electrolytes, and liver and kidney function markers. Results: BD and KE induced macrovesicular steatosis, vascular congestion, and elevated TNF-α and arginase expression, consistent with hepatic stress. MCT caused moderate hepatocellular ballooning and lipid deposition, whereas KS preserved near-normal hepatic morphology. KSMCT produced intermediate effects, reducing lipid accumulation and TNF-α compared with MCT or KE alone. KE supplementation caused dose-dependent reductions in globulin and elevations in creatinine, while HKE reduced sodium and glucose levels. Conclusions: Chronic hepatic responses to exogenous ketones are highly formulation dependent. KS demonstrated the most favorable safety profile under the tested conditions, maintaining normal hepatic structure, while BD and KE elicited adverse changes. Formulation choice is critical for the safe long-term use of exogenous ketones. Full article

The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are a primary cause of cardiovascular diseases such as atherosclerosis and restenosis after angioplasty. Pinocembrin (5,7-dihydroxyflavanone, PCB), a natural flavonoid compound found abundantly in propolis, has been reported to have antibacterial, anti-inflammatory, antioxidant, and anticancer effects, and cardiac function improvement in ischemic heart disease. In this study, the protective effects of PCB against the migration and proliferation of VSMCs were investigated. MTT and BrdU assays were performed to estimate the cytotoxicity and cell proliferative activity of PCB, respectively. Rat aortic VSMC migrations and neointima formation were evaluated using wound healing, boyden chamber assays, and in balloon-injured (BI) rat, respectively. PCB suppressed the phosphorylated levels of p38 in PDGF-BB-induced VSMCs followed by reducing the expression of MMP2 and 9. PCB downregulated the expression levels of cell cycle regulatory proteins such as PCNA, CDK2, CDK4, and Cyclin D1. Furthermore, the phosphorylated levels of FAK at Y397 and Y925 sites and the expression levels of FAK-related proteins such as Integrin β1, Paxillin, Talin, and Vinculin were significantly reduced by PCB in PDGF-BB-induced VSMCs. The neointima formation was markedly decreased by PCB administration in the carotid artery of a balloon-injured rat. In conclusion, PCB inhibits the proliferation and migration of VSMCs by stimulation of PDGF-BB through the regulation of the p38 and FAK signaling pathway. Therefore, PCB may be a promising therapeutic candidate for preventing and treating cardiovascular diseases such as atherosclerosis and restenosis. Full article

This study investigates multi-level coupled dynamic issues in near-space balloon-borne astronomical observation platforms subjected to multi-source disturbances, proposing an integrated azimuth pointing control scheme combining unified modeling with composite control strategies. A nonlinear dynamic model is established to characterize inertial coupling effects between the gondola system and secondary gimbal platform. The velocity-loop feedback mechanism utilizing fiber-optic gyroscopes achieves base disturbance decoupling, while an adaptive fuzzy PID controller enhances position-loop disturbance rejection capabilities. A gain adaptation strategy coordinates hierarchical control dynamics, complemented by anti-windup constraints safeguarding actuator operational boundaries. Simulation verifications confirm the exceptional high-precision pointing capability and robust stability under representative wind disturbances and sensor noise conditions. The system maintains a superior control performance across parameter perturbation scenarios, demonstrating consistent operational reliability. This study provides an innovative technical paradigm for precision observation missions in near space. Full article

Introduction: Isolated true subclavian artery aneurysm (SAA) is a rare form of peripheral arterial aneurysm that poses significant anatomical challenges to endovascular repair, especially in cases requiring planned vertebral artery (VA) sacrifice. The Balloon Occlusion Test (BOT) is a critical preoperative tool for evaluating collateral circulation before VA embolization. Case Report: A 74-year-old male was admitted with a pulsatile mass in the left supraclavicular fossa, and a 65 mm aneurysm of the intrathoracic segment of the left subclavian artery (LSA) involving critical arterial branches was diagnosed by computed tomography angiography. Due to his comorbidities, the patient was judged unfit for an open surgical repair of the aneurysm, and a two-stage endovascular subclavian aneurysm repair (EVSAR) was planned. The first step included embolization of the internal mammary artery and thyrocervical trunk, followed by BOT of the left VA, which confirmed an adequate perfusion of the posterior cerebral and cerebellar circulation that allowed safe VA embolization. The second step included zone 2 thoracic endograft placement (TEVAR) with LSA coverage and vascular plug occlusion of the proximal segment of the LSA and the axillary artery. Postoperative monitoring revealed no neurological deficit, and the patient was discharged home without complications. Follow-up imaging up to 24 months confirmed complete aneurysm exclusion and significant sac shrinkage. Conclusions: EVSAR with thoracic endograft and VA sacrifice, preceded by BOT, may be a safe and effective minimally invasive approach for the treatment of intrathoracic SAA. Full article

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has become a worldwide health concern. Soy protein isolate (SPI) is a plant-derived protein with high nutritional value and has shown promising effects in regulating lipid metabolism and inflammation. Objectives: This study aimed to investigate the effects of an α-subunit-deficient SPI (α-lack-SPI) on MASLD and the underlying molecular mechanisms. Methods: Rats were fed with a high-fat, high-cholesterol diet (HFD) to induce MASLD. Results: The results showed that α-lack-SPI significantly reduced the levels of hepatic TG and TC, serum ALT, AST, TC, and LDL-C, and increased serum HDL-C in rats with HFD-induced MASLD. α-lack-SPI significantly attenuated hepatic steatosis and hepatocyte ballooning revealed by histopathological analysis. Meanwhile, α-lack-SPI markedly downregulated the mRNA expressions of Srebf1, Acaca, Fasn, Pcsk9, and Hmgcr, while significantly upregulating Pparα. Additionally, α-lack-SPI treatment significantly reduced the mRNA expressions of hepatic pro-inflammatory cytokines (Tnf-α, Il-1β, Il6), chemokine (Ccl2), and inflammasome component (Nlrp3), as well as the protein expression of COX-2. Conclusions: In conclusion, α-lack-SPI alleviated MASLD in HFD-fed rats probably via improving hepatic lipid metabolism and mitigating hepatic inflammation. These findings indicate that α-lack-SPI may serve as a promising nutritional intervention for MASLD management. Full article

Background and Objectives: Congenital thrombophilias are biologically plausible contributors to chronic thromboembolic pulmonary hypertension (CTEPH), yet their frequency and clinical impact remain uncertain. We undertook a systematic review to (i) estimate the pooled prevalence of specific hereditary defects among adults with CTEPH, (ii) characterise associated demographic and haemodynamic phenotypes, and (iii) summarise peri-operative and survival outcomes after pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) in genetically defined subgroups. Methods: A protocol compliant with PRISMA-2020 was registered prospectively on the Open Science Framework (OSF). PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to 1 June 2025 using validated, PRESS-reviewed strings combining CTEPH and thrombophilia terms. Observational cohorts, case–control studies and trials reporting laboratory-confirmed congenital thrombophilias in adults with right-heart-catheter-defined CTEPH were eligible. Results: Eight studies encompassing 677 unique CTEPH patients met the inclusion criteria. Among the 400 individuals screened for deficiencies of the natural anticoagulant pathways, 56 possessed a defect: protein S deficiency 5.3% (21/400; 95% CI 3.3–8.0), protein C deficiency 4.3% (17/400; 2.5–6.8), and antithrombin deficiency 1.5% (6/400; 0.6–3.3). In 520 genotyped patients, factor V Leiden and prothrombin G20210A were infrequent (1.3% and 1.0%, respectively) and confined to European/North American cohorts. Baseline haemodynamics were uniformly severe (mean mPAP 46.7 mm Hg; pulmonary vascular resistance ≈ 9 WU). Definitive reperfusion therapy was common (PEA 63%; BPA 18%), reducing mPAP to 20.5 mm Hg and yielding a weighted one-year survival of 96.2%. No study demonstrated a thrombophilia-specific effect on surgical candidacy or early survival. Conclusions: Approximately one in seven patients with CTEPH harbours a congenital thrombophilia, most often protein S or protein C deficiency, whereas classic venous-thrombo-embolism mutations are rare and ethnically restricted. Current evidence indicates that genetic status does not materially influence haemodynamic severity, uptake of PEA/BPA, or short-term survival, supporting guideline recommendations for universal referral to specialist reperfusion centres. Future multicentre registries integrating systematic genotyping and long-term outcome capture are needed to clarify genotype-specific prognostic and therapeutic implications. Full article

Introduction: Takotsubo cardiomyopathy (TCM), also known as stress cardiomyopathy or Broken Heart Syndrome, is a reversible, transient state of myocardial dyskinesis and apical ballooning. Infrequently, TCM may progress to severe life-threatening complications such as cardiogenic shock. Early mechanical circulatory support (MCS) is crucial to myocardial recovery in these cases. We present one of the first cases of TCM successfully treated with the advanced micro-axial minimally invasive Impella 5.5 with SmartAssist MCS device. Case Presentation: A female in her late 70s with a history of hypothyroidism, atrial fibrillation post-ablation, and cholelithiasis was referred to our facility for an elective cholecystectomy. Post-anesthesia induction with propofol 2.1 mg/kg (140 mg bolus), she became bradycardic and hypotensive, eventually leading to asystole, requiring CPR and termination of the procedure. Echocardiography revealed a left ventricular ejection fraction (LVEF) of 24% with mid-ventricular akinesis and apical ballooning with mild mitral regurgitation, suggesting the diagnosis of TCM. Cardiac catheterization showed RA 20 and mean PA 42 mmHg. Lactate was 18.7 mmol/L and LDH 1776 U/L, suggesting progressive shock. Continuous epinephrine 0.1 mcg/kg/min and norepinephrine 0.06 mcg/kg/min were titrated for BP 97/58, and she was initially supported with the Impella CP device. Despite aggressive efforts, rising LDH levels and increased vasopressor needs indicated inadequate organ perfusion, requiring an upgrade to Impella 5.5. Impella 5.5 support for 11 days led to impressive myocardial recovery, leading to reductions, and eventual discontinuation, of inotropes and vasopressors. Post-Impella 5.5 explantation, her LVEF was 59–65% and she was discharged with Mobile Cardiac Outpatient Telemetry (MCOT) monitoring for her arrhythmias and reinitiation of guideline-directed medical therapies (GDMTs) for her comorbidities. Her 2-month follow-up shows sustained LVEF greater than 45% with functional improvements. Conclusions: Early escalation within 24 h of Impella CP to Impella 5.5 provided stabilization of cardiometabolic shock, preventing end-organ damage, allowing recovery of native heart function while maintaining ambulatory status, and allowing for optimizing medical therapy. It presents a safe, minimally invasive, and cost-effective intervention in TCM cases refractory to GDMT or when additional time is needed for decision-making in cases presenting with CS. Full article