Search Results (89)

Background: The occlusal angle (OA), influenced by pillow height, may affect muscle tension in the head and neck. However, its optimal range for minimizing muscle activation has not been clearly defined. Objective: This study aimed to investigate the effects of OA on the resting muscle activity of masticatory and cervical muscles and to identify an optimal OA range using cluster analysis and linear mixed-effects modeling. Methods: The resting muscle activities of the masseter (MAS), temporalis (TEM), sternocleidomastoid (SCM), and posterior vertebral muscles (PVM) were measured at OA conditions modulated by pillow heights of 0, 5, and 10 cm at 0, 1, and 5 min in the supine position. Intraclass correlation coefficients (ICCs) assessed measurement reliability. Statistical analyses included ANOVA, ROC curve analysis, k-means clustering, and linear mixed-effects models. Results: MAS and TEM resting muscle activity ratio (RMR) significantly increased with larger OA values (p < 0.001), while SCM showed decreased activation (p = 0.001). An OA range of 105°–111° was identified as the center of a low-activity cluster, and an upper cut-off of 138° was associated with potential muscular overload. ICC values for MAS and SCM ranged from 0.82 to 0.89, indicating excellent test–retest reliability. Conclusions: OA modulated by pillow height is a modifiable factor that influences muscle activity. An OA of 105°–111° may serve as a practical comfort zone, especially for individuals at risk of TMDs. Full article

Background: Reversible cerebral vasoconstriction syndrome (RCVS) is an uncommon and often underrecognized neurovascular disorder. We aimed to investigate the clinical presentations associated with extracerebral vasoconstriction in patients diagnosed with RCVS. Methods: In this cross-sectional study, we analyzed data from a single-center cohort of patients with RCVS in Korea. Extracerebral vasoconstriction in individuals diagnosed with RCVS was defined by the following criteria: (1) the presence of sudden and severe pain in extracerebral regions (primarily the chest or abdomen) coinciding with the onset of RCVS, (2) resolution of the pain following the administration of vasodilators, and (3) confirmation of vasoconstriction through imaging studies or, at a minimum, the exclusion of other potential causes associated with the pain. Results: Among the 80 eligible patients (median age, 53 years; female sex, 82.5%), 8 patients (10%) experienced extracerebral vasoconstriction. Regarding pain location, four patients reported chest pain, two reported abdominal pain, and two reported pains in both the chest and abdomen. When comparing visit route, the patients were associated with emergency department (odds ratio [OR]: 6; 95% confidence interval [CI]: 1.1–33; reference: outpatient) and inpatient consultation (OR: 25; 95% CI: 1.1–560) compared to those without extracerebral vasoconstriction. Patients with extracerebral vasoconstriction had no prior history of precipitating conditions or medication use before the onset of RCVS. The treatment response to vasodilators was excellent in all patients, and none reported neurovascular or extracerebral complications during the bout of RCVS. Conclusions: A co-occurrence of extracerebral vasoconstriction was not exceptionally uncommon among patients with RCVS. Our findings suggest that extracerebral vasoconstriction may be underrecognized in individuals with RCVS. Full article

Background: Fexofenadine hydrochloride (FEX) is widely used to treat allergic rhinitis. However, poor solubility, high cohesiveness, and risk of polymorphic transformation present significant formulation challenges. Conventional FEX tablet formulations are large and may pose swallowing difficulties for patients with dysphagia. Therefore, a miniaturized FEX tablet that maintained bioequivalence with the marketed product was developed. Methods: An organic solvent-based binder and porous carrier enhanced solubility, flowability, and process efficiency. The formulation was optimized using a design of experiments approach to assess the effects of tablet size and porous carrier incorporation on dissolution and residual solvent content. Scale-up feasibility was evaluated using Froude number-based process optimization, and stability studies were conducted under accelerated conditions (40 °C and 75% relative humidity) to ensure long-term formulation robustness. Results: The miniaturized tablet exhibited dissolution at pH 4.0 and pH 6.8 equivalent to that of the reference product, whereas a faster dissolution rate was observed at pH 1.2. No significant changes were observed in the dissolution rate, crystalline structure, or impurity levels over six months. An in vivo bioequivalence study demonstrated that the test formulation met the bioequivalence criteria, with 90% confidence intervals for the area under the curve and the C_max falling within the regulatory acceptance range. Conclusions: A miniaturized and commercially viable fexofenadine hydrochloride tablet was developed (44% weight reduction and 50% volume reduction compared to the marketed product). The organic solvent-based binder and porous carrier system improved manufacturing efficiency, stability, and solubility, thereby ensuring compliance with regulatory standards. These findings provide valuable insights into size reduction, solubility enhancement, and large-scale production strategies for the development of future pharmaceutical formulations. Full article

Background/Objectives: The management of primary central nervous system lymphoma (PCNSL) has traditionally prioritized diagnostic biopsy, with surgical resection often considered secondary due to risks and potential bias in previous studies, which included patients with deep or multiple tumors. This study aims to evaluate the impact of surgical resection on survival in patients with solitary, resectable PCNSL. Methods: We conducted a retrospective analysis of PCNSL patients treated via brain biopsy or surgical resection at our institution between January 2010 and December 2022. Cases with deep-located tumors (corpus callosum, basal ganglia, thalamus, and brainstem) or multiple lesions were excluded. Survival and clinical outcomes were compared between the two groups. Results: A total of 79 patients (30 resection and 49 biopsy) were included. No significant differences were observed between groups regarding demographics, comorbidities, tumor characteristics, or International Extranodal Lymphoma Study Group scores. Preoperative midline shifting (p = 0.048) and steroid use (p < 0.001) were higher in the resection group, which also demonstrated greater symptom improvement (p < 0.001). The complication rates were comparable between groups. The 5-year overall survival (OS) was 81.3% (resection) vs. 80.1% (biopsy), and the 5-year progression-free survival (PFS) was 53.6% (resection) vs. 60.3% (biopsy), with no significant differences in OS or PFS by Cox regression analysis. Conclusions: Surgical resection does not improve OS or PFS in solitary, resectable PCNSL, though it may provide symptomatic relief in select cases. Further prospective studies are needed to define its role in PCNSL management. Full article

Introduction: This study assessed the therapeutic effectiveness of a single-pill combination (SPC) of olmesartan/amlodipine plus rosuvastatin for blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) in patients with hypertension and dyslipidemia. Methods: Adult patients with hypertension and dyslipidemia who were decided to be treated with the study drug were eligible. The primary endpoint was the proportion of patients who achieved BP, LDL-C and both BP and LDL-C treatment goals at weeks 24–48. Secondary endpoints were assessed at weeks 24–48 and included changes in BP and LDL-C levels from baseline; the proportion of patients who achieved treatment goals who were initially classified as uncontrolled at baseline; changes and percent changes in lipid parameters; changes in both BP and LDL-C levels among patients who reached treatment goals who were followed for more than 24 weeks; and the overall safety profile. Results: A total of 5476 patients were enrolled, and 4411 patients comprised the effectiveness evaluation set. The proportions of patients who reached the treatment goals for BP, LDL-C levels, and both BP and LDL-C levels were 67.93% [95% confidence interval (CI) 66.52–69.32], 80.19% [95% CI 78.85–81.49], and 58.07% [95% CI 56.43–59.7], respectively. Secondary endpoints showed statistically significant changes. Overall, the treatment was well tolerated. Conclusions: The treatment of patients with hypertension and dyslipidemia with the olmesartan/amlodipine plus rosuvastatin SPC was associated with significant decreases in SBP/DBP and LDL-C levels, and a high proportion of patients achieved the BP and LDL-C treatment goals. The finding of this study is worthwhile in that this study evaluated the effectiveness and safety in a broad patient population representative of those seen in everyday clinical practice. Full article

Background: This study aims to explore the protective role of JB-V-60—a novel synthetic derivative of decur-sin—against lipopolysaccharide (LPS)-induced inflammation. Methods: We examined the effects of JB-V-60 on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human pulmonary artery endothelial cells (HPAECs). Additionally, we assessed its effects on iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in LPS-exposed mice. Results: JB-V-60 enhanced HO-1 levels, inhibited NF-κB activation, reduced COX-2/PGE2 and iNOS/NO concentra-tions, and lowered phosphorylation of signal transducer and activator of transcription 1. It also promoted the translocation of Nrf2 into the nucleus, allowing its binding to antioxidant response elements and resulting in reduced IL-1β in LPS-stimulated HPAECs. The reduction in iNOS/NO levels by JB-V-60 was reversed when HO-1 was inhibited via RNAi. In the animal model, JB-V-60 sig-nificantly decreased iNOS expression in lung tissues and TNF-α levels in bronchoalveolar lavage fluid. Conclusions: These findings highlight the anti-inflammatory effects of JB-V-60 and its potential as a treat-ment for inflammatory disorders. Full article

Alcohol-associated liver disease (ALD) is a major cause of chronic liver disease, with few effective treatments besides alcohol abstinence. Angelicae Gigantis Radix (AG), Glycyrrhizae Radix et Rhizoma (GR), Paeoniae Radix (PR), and Zizyphi Fructus (ZF) are traditional herbs used to treat various ailments, including liver diseases. While several studies have reported the beneficial effects of GR on ALD, the effects of AG, PR, and ZF remain underexplored. Therefore, their efficacy and mechanisms against ALD were investigated using an alcohol-related liver injury model. The model was induced by ethanol gavage in C57BL/6J mice for 14 days, followed by oral administration of AG, GR, PR, and ZF one hour post-induction. The administration of these herbs reduced liver weight, and improved serum biomarkers of liver injury (ALT, AST, albumin). The herbs enhanced hepatic antioxidant capacity (GSH, SOD, catalase) and suppressed the production of proinflammatory cytokines (TNF-α, IL-1β) and apoptotic changes (caspase-3). The mechanisms of action involved lipid-lowering gene modulation through regulation of the cytochrome P450 2E1/Sirtuin 1/Nrf2 pathways. Histopathological and immunohistochemical analyses revealed that these herbs attenuated hepatocyte damage and steatosis via antioxidant, anti-inflammatory, and antiapoptotic effects. These findings suggest that traditional herbs, particularly AG, could be promising alternative therapies for treating ALD. Full article

The clinical consequences of perioperative albumin extravasation accompanying major abdominal surgery remain underexplored. We retrospectively reviewed the data of patients who underwent cytoreductive surgery (CRS) and hyperthermic intraoperative peritoneal chemotherapy (HIPEC). Parameters of albumin kinetics, including serum albumin concentration decrease (∆Alb) and extravasated albumin level (Alb_shift), were assessed from surgery until postoperative day (POD) 3. Logistic regression analysis identified factors associated with major complications. The association of albumin kinetics with major complications was evaluated using receiver operating characteristic (ROC) curve analysis. Serum albumin levels decreased during surgery and subsequently increased. Of the 121 analyzed patients, 25 (21%) developed major complications. The ∆Alb and Alb_shift during surgery and on POD 3 were greater in patients who developed major complications than in those who did not (12 ± 12 vs. 6 ± 14, p = 0.032, and 127.5 (71.9) vs. 48.5 (44.9), p < 0.001, respectively). Perioperative ∆Alb and Alb_shift were associated with major complications. The areas under the ROC curve of Alb_shift during the 3 days post-surgery and Alb_shift on POD 3 were 0.843 and 0.910, respectively. Alb_shift during the 3 days post-surgery and Alb_shift on POD 3 were correlated with complications (p < 0.05). In conclusion, perioperative albumin loss was associated with major complications in patients undergoing CRS and HIPEC. Alb_shift was associated with serious complications. Full article

Background/Objectives: Self-recognition of recurrent myocardial infarction (re-MI) may be essential for reducing prehospital time contrast to awareness of re-MI symptoms. However, data on the current status and clinical impact of self-recognition of re-MI are limited in the contemporary period. Thus, this study aimed to increase this body of knowledge. Methods: We enrolled 1018 patients with re-MI using data from the Korean Registry of Acute Myocardial Infarction for Regional Cardiocerebrovascular Centres. The patients were classified into self-recognised MI and unrecognised MI groups, and the differences between them were compared. Results: The rate of self-recognition among the patients with previous experience of MI was only 52.4%. Among the patients with re-MI, factors associated with self-recognition included recent first MI within 3 years, prior dyslipidaemia, two or more MI symptoms, and the male gender (p < 0.05). Factors associated with a lack of recognition were older age (≥70 years), prior stroke, and cancer history (p < 0.05). The proportion of symptoms-to-emergency room arrival time within 90 min among the patients with ST-elevation MI was significantly higher in the self-recognised group than in the unrecognised group (52.6% vs. 31.6%, p < 0.001). The self-recognised group showed a lower in-hospital mortality rate (1.5% vs. 6.2%, p < 0.001), and this benefit was maintained even after 1 year (hazard ratio: 0.53; p < 0.001). Conclusions: Only half of the patients who previously experienced a MI recognised a re-MI when it occurred. This recognition reduced prehospital delay and led to higher survival rates, which highlights the importance of patient education as well as objective monitoring devices, irrespective of individual recognition ability for immediate response. Full article

This study investigated the therapeutic effects of exosomes derived from human-induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs) on corneal epithelial wound healing. Exosomes were isolated from the culture medium of the hiPSC-derived ROs (Exo-ROs) using ultracentrifugation, and then they were characterized by a nanoparticle tracking analysis and transmission electron microscopy. In a murine model of corneal epithelial wounds, these exosomes were topically applied to evaluate their healing efficacy. The results demonstrated that the exosome-treated eyes showed significantly enhanced wound closures compared with the controls at 24 h post-injury. The 5-ethyl-2′-deoxyuridine assay and quantitative reverse transcription polymerase chain reaction revealed a substantial increase in cell proliferation and a decrease in inflammatory marker contents in the exosome-treated group. The RNA sequencing and exosomal microRNA analysis revealed that the Exo-RO treatment targeted various pathways related to inflammation and cell proliferation, including the PI3K-Akt, TNF, MAPK, and IL-17 signaling pathways. Moreover, the upregulation of genes related to retinoic acid and eicosanoid metabolism may have enhanced corneal epithelial healing in the eyes treated with the Exo-ROs. These findings suggest that hiPSC-derived RO exosomes could be novel therapeutic agents for promoting corneal epithelial wound healing. Full article

X-linked juvenile retinoschisis (XLRS) is a hereditary retinal degeneration affecting young males caused by mutations in the retinoschisin (RS1) gene. We generated human induced pluripotent stem cells (hiPSCs) from XLRS patients and established three-dimensional retinal organoids (ROs) for disease investigation. This disease model recapitulates the characteristics of XLRS, exhibiting defects in RS1 protein production and photoreceptor cell development. XLRS ROs also revealed dysregulation of Na/K-ATPase due to RS1 deficiency and increased ERK signaling pathway activity. Transcriptomic analyses of XLRS ROs showed decreased expression of retinal cells, particularly photoreceptor cells. Furthermore, relevant recovery of the XLRS phenotype was observed when co-cultured with control ROs derived from healthy subject during the early stages of differentiation. In conclusion, our in vitro XLRS RO model presents a valuable tool for elucidating the pathophysiological mechanisms underlying XLRS, offering insights into disease progression. Additionally, this model serves as a robust platform for the development and optimization of targeted therapeutic strategies, potentially improving treatment outcomes for patients with XLRS. Full article

Human retinal organoids (ROs) have emerged as valuable tools for studying retinal development, modeling human retinal diseases, and screening drugs. However, their application is limited primarily due to time-intensive generation, high costs, and low reproducibility. Quality assessment of RO differentiation is crucial for their application in research. However, traditional methods such as morphological evaluation and immunohistochemical analysis have limitations due to their lack of precision and invasiveness, respectively. This study aims to identify non-invasive biomarkers for RO differentiation quality using exosomal microRNAs (miRNAs), which are known to reflect cell-specific functions and development in the retina. We differentiated ROs from human induced pluripotent stem cells (hiPSCs) and classified them into ‘superior’ and ‘inferior’ groups based on morphological and immunohistochemical criteria. Exosomes from the conditioned media were isolated and analyzed for miRNA content. Our findings revealed distinct miRNA profiles between superior and inferior ROs, with superior ROs exhibiting higher miRNA diversity and specifically up- or down-regulated miRNAs. Gene ontology and pathway enrichment analyses indicated that the target genes of these miRNAs are involved in neuron proliferation and differentiation. The study suggests the potential of exosomal hsa-miR-654-3p and hsa-miR-451a as non-invasive biomarkers for real-time monitoring of RO quality, facilitating the development of standardized, efficient, and cost-effective culture methods. Full article

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca²⁺) and other metal ions, such as zinc (Zn²⁺) and magnesium (Mg²⁺), into the cytosol. This Ca²⁺ influx at the presynaptic terminal triggers the release of Zn²⁺ and glutamate to the postsynaptic terminal. Zn²⁺ is then transported to the postsynaptic neuron via LTCCs. The resulting Zn²⁺ accumulation in neurons significantly increases the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, contributing to reactive oxygen species (ROS) generation and neuronal death. Amlodipine (AML), typically used for hypertension and coronary artery disease, works by inhibiting LTCCs. We explored whether AML could mitigate Zn²⁺ translocation and accumulation in neurons, potentially offering protection against seizure-induced hippocampal neuronal death. We tested this by establishing a rat epilepsy model with pilocarpine and administering AML (10 mg/kg, orally, daily for 7 days) post-epilepsy onset. We assessed cognitive function through behavioral tests and conducted histological analyses for Zn²⁺ accumulation, oxidative stress, and neuronal death. Our findings show that AML’s LTCC inhibition decreased excessive Zn²⁺ accumulation, reactive oxygen species (ROS) production, and hippocampal neuronal death following seizures. These results suggest amlodipine’s potential as a therapeutic agent in seizure management and mitigating seizures’ detrimental effects. Full article

With the development of cloud computing, interest in database outsourcing has recently increased. However, when the database is outsourced, there is a problem in that the information of the data owner is exposed to internal and external attackers. Therefore, in this paper, we propose decimal-based encryption operation protocols that support privacy preservation. The proposed protocols improve the operational efficiency compared with binary-based encryption operation protocols by eliminating the need for repetitive operations based on bit length. In addition, we propose a privacy-preserving k-means clustering algorithm using decimal-based encryption operation protocols. The proposed k-means clustering algorithm utilizes efficient decimal-based protocols that enhance the efficiency of the encryption operations. To provide high query processing performance, we also propose a parallel k-means clustering algorithm that supports thread-based parallel processing by using a random value pool. Meanwhile, a security analysis of both the proposed k-means clustering algorithm and the proposed parallel algorithm was performed to prove their data protection, query protection, and access pattern protection capabilities. Through our performance analysis, the proposed k-means clustering algorithm shows about 10~13 times better performance compared with the existing algorithms. Full article

The lithium-air battery is a new type of secondary battery technology that is currently receiving a lot of attention in the field of power storage technology. These batteries are known to offer high energy densities and potentially longer driving ranges. In this study, NiCo₂O₄ and CNTs were used to create a composite for use as the cathode of a Li-air battery. Improving the 3D needl-like structure that provides extensive transport channels for electrolyte infiltration and numerous sites facilitated charge transfer reactions and the synergistic effect of highly electrocatalytic NiCo₂O₄ with pronounced activity and high conductive CNTs, with the synthesized NiCo₂O₄@CNTs composites exhibiting active catalytic performance for both OER and ORR reactions. It also showed improved cycle performance at high current densities. NiCo₂O₄@CNTs composites were successfully fabricated using a hydrothermal method together with a sequential annealing treatment. The components of the completed composite were confirmed using TGA, XRD, and SEM, and the specific surface area was analyzed using BET. The composite was performed for over 120 cycles at a current density of 200 mA∙g⁻¹, and 500 mA∙g⁻¹ was achieved under the capacity limiting condition of 500 mAh∙g⁻¹. The charging/discharging characteristics were compared under various current densities, exhibiting stable cyclability. The high catalytic activity of NiCo₂O₄ oxide supports its potential use as a cathode in Li-air batteries. Full article