Search Results (94)

Donepezil (DPZ) is an Alzheimer’s disease (AD) drug that promotes cholinergic neurotransmission and exhibits excellent acetylcholinesterase (AChE) selectivity. The current oral formulations of DPZ demonstrate decreased bioavailability, attributed to limited drug permeability across the blood–brain barrier (BBB). In order to overcome these limitations, various dosage forms aimed at delivering DPZ have been explored. This discussion will focus on the nose-to-brain (N2B) delivery system, which represents the most promising approach for brain drug delivery. Intranasal (IN) drug delivery is a suitable system for directly delivering drugs to the brain, as it bypasses the BBB and avoids the first-pass effect, thereby targeting the central nervous system (CNS). Currently developed formulations include lipid-based, solid particle-based, solution-based, gel-based, and film-based types, and a systematic review of the N2B research related to these formulations has been conducted. According to the in vivo results, the brain drug concentration 15 min after IN administration was more than twice as high those from other routes of administration, and the direct delivery ratio of the N2B system improved to 80.32%. The research findings collectively suggest low toxicity and high therapeutic efficacy for AD. This review examines drug formulations and delivery methods optimized for the N2B delivery of DPZ, focusing on technologies that enhance mucosal residence time and bioavailability while discussing recent advancements in the field. Full article

Background and Objectives: Medication overuse headache (MOH) presents unique clinical challenges in older adults due to age-related changes and comorbidities. However, data on MOH characteristics and treatment responses in this population remain limited. This study investigated the clinical features, treatment patterns, and short-term outcomes of MOH in older patients. Methods: We analyzed data from the RELEASE registry, a nationwide, multicenter prospective cohort of MOH patients in South Korea. Participants were stratified into older (≥65 years) and younger (<65 years) groups. We compared clinical features, treatment patterns, and 3-month outcomes, and identified factors associated with treatment response in the older group. Results: Among 791 patients, 72 (9.1%) were older. Compared to younger patients, older patients reported more monthly headache days (30.0 vs. 27.0, p = 0.012), more days using acute medication (30.0 vs. 20.0, p < 0.001), and fewer headache-free days (0.0 vs. 3.0, p = 0.012). They also experienced more severe headache days (12.5 vs. 10.0, p = 0.056). Despite this, older patients showed lower disability, with significantly lower Migraine Disability Assessment scores (30.0 vs. 46.0, p < 0.001) and a trend toward lower Headache Impact Test-6 scores (64.5 vs. 66.0, p = 0.065). In multivariable analysis, poor adherence to preventive treatment (≤24%) was significantly associated with non-response (OR 0.13, 95% CI: 0.02–0.96, p = 0.045) at 3 months. Conclusions: Older patients with MOH showed distinct clinical features, including higher headache frequency and severity but relatively lower disability. Improving adherence to preventive treatment may enhance treatment response. Age-specific management strategies are needed. Full article

Background: With an aging population, dementia prevalence is increasing in Korea. Vascular dementia (VaD), often caused by cerebrovascular disease (CVD), is more common in Korea compared to Western countries. Hwanhon decoction, a traditional medicine containing Ephedrae Herba, Armeniacae Semen, and Glycyrrhizae Radix et Rhizoma, is traditionally used for CVD-related loss of consciousness. This study aimed to assess the cognitive improvement and anti-inflammatory effects of Hwanhon decoction extract (HHex) in a mouse model of VaD caused by chronic cerebral hypoperfusion (CCH). Methods: Key pharmacologically active ingredients of Hwanhon decoction were identified using network pharmacology analysis. VaD was induced in C57Bl/6 male mice through bilateral common carotid artery stenosis (BCAS). Mice were divided into sham surgery, BCAS control, low-dose HHex (L-HHex), and high-dose HHex (H-HHex) groups (n = 5/group). After CCH induction, L-HHex or H-HHex was administered thrice weekly for six weeks. Cognitive function, inflammatory markers, and RNA sequencing data were analyzed. Results: HHex administration reduced cognitive impairment and mitigated CCH-induced astrocyte activation. Inflammatory responses mediated by reactive astrocytes were suppressed, and network pharmacology predicted central proteins influencing HHex’s activity. Conclusions: HHex alleviated cognitive dysfunction and reduced inflammation in a VaD mouse model, suggesting its potential as a therapeutic agent for vascular dementia associated with impaired cerebral blood flow. Full article

Background/Objectives: Colorectal cancer (CRC) is a major health concern in Korea, with its increasing incidence emphasizing the urgent need to identify risk factors. Recent studies suggest that heme iron elevates CRC risk, but evidence remains conflicting. This study examined the associations between total, heme, and non-heme iron intake and the incidence of colorectal, colon, and rectal cancer in Koreans. Methods: Using the Korean Genome and Epidemiology Study Health Examinee (KoGES HEXA) cohort, a large community-based cohort of healthy Koreans, we constructed a database of iron content for foods listed in a validated food frequency questionnaire (FFQ) and assessed dietary iron intake for each participant. Colorectal, colon, and rectal cancer cases were identified via the national cancer registry up to 2018. The association between iron consumption and cancers was evaluated with hazard ratios (HRs) and 95% confidence intervals (95%CIs) using multivariable-adjusted Cox regression. Results: During the 9.1-year median follow-up of 109,908 participants (37,697 men and 71,401 women, median age: 53.8 years), 608 new CRC cases were identified. Moderate total iron consumption in the second quintile (5.00–6.27 mg/day) decreased CRC (HR: 0.75; 95%CI: 0.58–0.97) and colon cancer (HR: 0.71; 95%CI: 0.51–1.00) risk compared to the lowest consumption quintile (1.09–4.99 mg/day), as did non-heme iron intake in the second quintile (4.98–6.24 mg/day) compared to its lowest quintile (1.09–4.97 mg/day) (CRC HR: 0.75; 95%CI: 0.58–0.98; colon cancer HR: 0.70; 95%CI: 0.49–0.98). Conclusions: Moderate total and non-heme iron intake reduced colorectal and colon cancer risk in Koreans, possibly via the displacement of carcinogens and the increased intake of protective micronutrients from plant-based foods. Larger-scale studies may be instrumental in substantiating these results. Full article

Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic has significantly affected global health, economies, and societies, necessitating a deeper understanding of the factors influencing its spread and severity. Methods: This study employed text network analysis to examine relationships among various risk factors associated with severe COVID-19. Analyzing a dataset of published studies from January 2020 to December 2021, this study identifies key determinants, including age, hypertension, and pre-existing health conditions, while uncovering their interconnections. Results: The analysis reveals five thematic clusters: biomedical, occupational, demographic, behavioral, and complication-related factors. Temporal trend analysis reveals distinct shifts in research focus over time. In early 2020, studies primarily addressed immediate clinical characteristics and acute complications of COVID-19. By mid-2021, research increasingly emphasized long COVID, highlighting its prolonged symptoms and impact on quality of life. Concurrently, vaccine efficacy became a dominant topic, with studies assessing protection rates against emerging viral variants, such as Alpha, Delta, and Omicron. This evolving landscape underscores the dynamic nature of COVID-19 research and the adaptation of public health strategies accordingly. Conclusions: These findings offer valuable insights for targeted public health interventions, emphasizing the need for tailored strategies to mitigate severe outcomes in high-risk groups. This study demonstrates the potential of text network analysis as a robust tool for synthesizing complex datasets and informing evidence-based decision-making in pandemic preparedness and response. Full article

Background/Objectives: During gastroscopy, accurately identifying the anatomical locations of the gastrointestinal tract is crucial for developing diagnostic aids, such as lesion localization and blind spot alerts. Methods: This study utilized a dataset of 31,403 still images from 1000 patients with normal findings to annotate the anatomical locations within the images and develop a classification model. The model was then applied to videos of 20 esophagogastroduodenoscopy procedures, where it was validated for real-time location prediction. To address instability of predictions caused by independent frame-by-frame assessment, we implemented a hard-voting-based post-processing algorithm that aggregates results from seven consecutive frames, improving the overall accuracy. Results: Among the tested models, InceptionV3 demonstrated superior performance for still images, achieving an F1 score of 79.79%, precision of 80.57%, and recall of 80.08%. For video data, the InceptionResNetV2 model performed best, achieving an F1 score of 61.37%, precision of 73.08%, and recall of 57.21%. These results indicate that the deep learning models not only achieved high accuracy in position recognition for still images but also performed well on video data. Additionally, the post-processing algorithm effectively stabilized the predictions, highlighting its potential for real-time endoscopic applications. Conclusions: This study demonstrates the feasibility of predicting the gastrointestinal tract locations during gastroscopy and suggests a promising path for the development of advanced diagnostic aids to assist clinicians. Furthermore, the location information generated by this model can be leveraged in future technologies, such as automated report generation and supporting follow-up examinations for patients. Full article

Background and Objectives: While the connection between decreased kidney function and diabetes mellitus (DM) is commonly acknowledged, there is insufficient research examining the relationship between higher-than-normal estimated glomerular filtration rate (eGFR) and the incidence risk of new-onset DM. Our research aimed to explore the relationship between an eGFR and the incidence risk of new-onset DM in the Korean general population through a nationwide longitudinal study. Methods: This research employed the cohort records of the National Health Insurance Service in Korea, analyzing records from 2,294,358 individuals between the ages of 20 and 79 who underwent health check-ups between 2010 and 2011. The eGFR levels from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation were used to assess the renal function. New-onset DM was defined as two or more claims with the International Classification of Diseases-10 classification codes E10 to E14, being prescribed any medication for lowering blood glucose, or having a record of fasting plasma glucose levels of ≥126 mg/dL from a health examination after the index date. Results: The mean age of subjects was 47.34 ± 13.76 years. The 150,813 (6.57%) new-onset DM cases were identified over a median follow-up of 9.63 years. In the multivariable Cox regression analysis, in comparison with the 5th decile, the 10th (≥114.12 mL/min/1.73 m²) (hazard ratio (HR): 0.52, 95% confidence interval (CI) (0.50–0.54), p < 0.001) eGFR decile was significantly associated with a decreased incidence of new-onset DM. Moreover, eGFR >120 mL/min/1.73 m² was associated with a reduced risk of new-onset DM (HR: 0.40, 95% CI (0.39–0.42), p < 0.001). These results were consistent regardless of the presence of impaired glucose tolerance, age, or obesity. Conclusion: Our study showed higher-than-normal eGFR levels were associated with a lower risk of incidence for new-onset DM regardless of the presence of impaired glucose tolerance, age, or obesity. In general population, higher-than-normal eGFR may be associated with a lower risk of incidence of new-onset DM. Full article

Background and Objectives: Owing to the recent reports regarding the efficacy of rhythm step training (RST) in lower limb muscle development and motor skill enhancement, this study aimed to evaluate the effects of RST on foot and lower limb balance in children and adolescents diagnosed with flat feet using radiographic analysis. Materials and Methods: A total of 160 children and adolescents diagnosed with flat feet from a hospital in Seoul were randomly assigned to the general flat feet training (GFFT) (n = 80) or RST (n = 80) group. Patients in both groups exercised for 50 min once a week for 12 weeks. Key variables, such as quadriceps angle (Q-angle), calcaneal pitch angle (CPA), calcaneal–first metatarsal angle (CFMA), and navicular–cuboid overlap ratio (OR) were measured before and after the intervention. Results: Significant improvements in Q-angle (p < 0.001), CPA (p < 0.001), CFMA (p < 0.001), and navicular–cuboid OR (p < 0.001) were observed in the RST group compared to the GFFT group. RST was found to be more effective in normalizing the biomechanical function of the calcaneus and improving lower limb function. Conclusions: RST significantly enhances foot and lower limb balance in children and adolescents with flat feet, suggesting its potential use as an effective intervention for this population. The study did not specifically analyze the effects of various components of rhythm training, such as music, exercise intensity, and frequency, on the outcomes. Further research is needed to determine how each of these elements individually influences the results. Full article

Background/Objectives: Proteinuria is documented as a risk factor for atrial fibrillation (AF) and can manifest in either reversible or continued forms. Our objective was to examine the relationship between the change in status for proteinuria and the risk of AF in a longitudinal cohort study on the general population nationwide. Methods: We included participants (n = 1,708,103) who underwent repetitive health examinations. The presence of proteinuria was determined by dipstick urinalysis results. The outcome was the occurrence of AF (International Classification of Diseases-10 code: I48). Results: All included participants, 1,666,111 (97.5%), 17,659 (1.0%), 19,696 (1.2%), and 4637 (0.3%), were categorized into groups of proteinuria-free, improved, progressed, and persistent, respectively. During a median follow-up of 14.5 years, 41,190 (2.4%) cases of AF occurred. In the multivariable analysis, the risk of AF was increased as the initial severity was more severe in the proteinuria-improved and proteinuria-persistent groups (p for trend < 0.001). In a further pairwise comparison, the proteinuria-improved group had a relatively lower risk of AF compared to the proteinuria-persistent group (HR: 0.751, 95% CI: 0.652–0.865, p < 0.001). Conclusions: Our study showed that the risk of AF can change according to alterations in proteinuria status. Notably, recovering from proteinuria can also be considered a modifiable risk factor for AF. Full article

Malaria is one of the most prevalent diseases worldwide with high incidence and mortality. Among the five species that can infect humans, Plasmodium ovale morphologically resembles Plasmodium vivax, resulting in misidentification and confusion in diagnosis, and is responsible for malarial disease relapse due to the formation of hypnozoites. P. ovale receives relatively less attention compared to other major parasites, such as P. falciparum and P. vivax, primarily due to its lower pathogenicity, mortality rates, and prevalence rates. To efficiently produce lactate dehydrogenase (LDH), a major target for diagnosing malaria, this study used three Escherichia coli strains, BL21(DE3), BL21(DE3)pLysS, and Rosetta(DE3), commonly used for recombinant protein production. These strains were characterized to select the optimal strain for P. ovale LDH (PoLDH) production. Gene cloning for recombinant PoLDH production and transformation of the three strains for protein expression were performed. The optimal PoLDH overexpression and washing buffer conditions in nickel-based affinity chromatography were established to ensure high-purity PoLDH. The yields of PoLDH expressed by the three strains were as follows: BL21(DE3), 7.6 mg/L; BL21(DE3)pLysS, 7.4 mg/L; and Rosetta(DE3), 9.5 mg/L. These findings are expected to be highly useful for PoLDH-specific diagnosis and development of antimalarial therapeutics. Full article

Obesity is one of the major risk factors for metabolic diseases worldwide. This study examined the effects of YC-1102, an extract derived from the roots of Rosa multiflora, on 3T3-L1 preadipocytes and high-fat diet (HFD)-induced obese mice. In vivo experiments involved the oral administration of YC-1102 (100, 150, and 200 mg/kg body weight) daily to mice for eight weeks. YC-1102 was found to downregulate the expressions of PPARγ and C/EBPα during adipogenesis, inhibiting adipocyte differentiation and upregulating the expression of PGC-1α for energy metabolism to enhance mitochondrial biogenesis and fatty acid oxidation. It has been shown that daily administration of YC-1102 to mice receiving a HFD prevented an increase in body weight and the accumulation of body fat. YC-1102 administration also reduced TG, TC, and LDL cholesterol levels, as well as glucose and leptin levels, and increased adiponectin levels, thus effectively inhibiting the metabolism of lipids. YC-1102-treated mice showed significant reductions in the mRNA expression of PPARγ and C/EBPα. The levels of PGC-1α involved in energy metabolism increased significantly in the YC-1102-treated mice when compared to the HFD-treated mice. According to the findings of this study, YC-1102 has a dual mechanism that reduces transcription factors that promote the differentiation of adipocytes and increases transcription factors that promote energy consumption. Full article

Lymphovascular invasion (LVI) is one of the most important prognostic factors in gastric cancer as it indicates a higher likelihood of lymph node metastasis and poorer overall outcome for the patient. Despite its importance, the detection of LVI(+) in histopathology specimens of gastric cancer can be a challenging task for pathologists as invasion can be subtle and difficult to discern. Herein, we propose a deep learning-based LVI(+) detection method using H&E-stained whole-slide images. The ConViT model showed the best performance in terms of both AUROC and AURPC among the classification models (AUROC: 0.9796; AUPRC: 0.9648). The AUROC and AUPRC of YOLOX computed based on the augmented patch-level confidence score were slightly lower (AUROC: −0.0094; AUPRC: −0.0225) than those of the ConViT classification model. With weighted averaging of the patch-level confidence scores, the ensemble model exhibited the best AUROC, AUPRC, and F1 scores of 0.9880, 0.9769, and 0.9280, respectively. The proposed model is expected to contribute to precision medicine by potentially saving examination-related time and labor and reducing disagreements among pathologists. Full article

Autonomic dysfunction is a common complication of acute stroke, which impairs functional outcomes and increases mortality. There is a lack of well-established knowledge regarding the influence of autonomic dysfunction in patients with acute stroke. This study aims to investigate the impact of the severity of autonomic dysfunction on functional outcomes in patients with acute stroke. A retrospective analysis was conducted at a single center, involving 22 patients diagnosed with acute stroke. The severity of autonomic dysfunction was evaluated based on the Composite Autonomic Scoring Scale (CASS). The modified Barthel Index, Berg Balance Scale, Functional Ambulatory Category, and modified Rankin Scale were designated as functional outcome measures. The impact of the severity of autonomic dysfunction on functional outcomes was analyzed using one-way analysis of covariance (ANCOVA). A statistically significant difference was observed between the initial and follow-up functional outcomes based on the severity of autonomic dysfunction. This study presents evidence that the severity of autonomic dysfunction influences functional prognosis in patients with acute stroke. The findings will serve as additional considerations for the rehabilitation of patients with acute stroke. Full article

Although proteinuria is a risk factor for heart failure (HF), proteinuria can be reversible or persistent. Our objective was to explore the link between changes in the proteinuria status and the risk of HF. We included participants from a Korean national health screening cohort who underwent health examinations in 2003–2004 and 2005–2006 and had no history of HF. Participants were categorized into four groups: proteinuria-free, proteinuria-resolved, proteinuria-developed, and proteinuria-persistent. The outcome of interest was the occurrence of HF. The study included 1,703,651 participants, among whom 17,543 (1.03%) were in the proteinuria-resolved group and 4585 (0.27%) were in the proteinuria-persistent group. After a median follow-up period of 14.04 years (interquartile range 14.19–15.07), HF occurred in 75,064 (4.41%) participants. A multivariable Cox proportional hazards regression analysis indicated that the proteinuria-persistent group had a higher risk of HF compared with the proteinuria-free group (hazard ratio (HR): 2.19, 95% confidence interval (CI): 2.03–2.36, p < 0.001). In a further pairwise comparison analysis, participants in the proteinuria-resolved group had a relatively low risk of HF compared with those in the proteinuria-persistent group (HR: 0.64, 95% CI: 0.58–0.70, p < 0.001). In conclusion, the risk of HF can change with alterations in the proteinuria status. Full article

Fluorosilicone rubber, essential in automotive and aerospace owing to its excellent chemical resistance, plays a pivotal role in sealing technology, addressing the industry’s evolving demands. This study explores the preparation and properties of fibrillated cellulose-reinforced fluorosilicone rubber composites to enhance their stiffness and oil resistance. Fibrillated cellulose sourced as a wet cake and subjected to processing and modification is incorporated into a fluorosilicone rubber matrix. The resulting composites are analysed by tensile and compression tests, along with compressive stress-relaxation testing in air and in an oil-immersed environment. The findings demonstrate significant improvements in the mechanical properties, including an increased Young’s modulus and elongation at break, whereas the tensile strength remained uncompromised throughout the testing procedures. Morphological analysis of the fracture surfaces revealed a remarkable interfacial affinity between the fibrillated cellulose and rubber matrix, which was attributed in part to the modified fatty acids and inorganic nanoparticles. The presence of fibrillated cellulose enhanced the stress-relaxation characteristics under oil-immersion conditions. These results contribute to the domain of advanced elastomer materials, with potential for applications requiring enhanced mechanical properties and superior oil resistance. Full article