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Abstract The study investigated PM2.5 and heavy metal pollutant concentrations in Seoul and Wonju, South Korea, emphasizing the importance of considering PM2.5 chemical constituents for health impact assessments. While PM2.5 concentrations were similar between the two cities with slight variations, heavy metal concentrations differed significantly. Regional sources, PM2.5 composition, and meteorological conditions influenced these variations. Exposure to Fe was highest in all areas, with some heavy metals exceeding permissible levels, stressing the need to consider regional characteristics in assessments. Different heavy metals influence health risks differently in each city. When examining the HI (the summation of the hazard quotient for heavy metals), Seoul remained below an HI value of 1, while Wonju exceeded this threshold when exposed to CTE concentrations. In Seoul, As had a significant health impact of PM2.5, while in Wonju, Mn was more influential. Source apportionment confirmed different pollution sources in Seoul and Wonju, affecting the distribution of PM2.5 constituents in the atmosphere. Effective PM2.5 management requires a comprehensive approach considering chemical constituents and health impacts not just mass-based PM2.5 management, emphasizing regional-specific assessments and policy considerations to mitigate health risks. Therefore, tailored management strategies based on regional characteristics are necessary. Graphical Abstract

This study aimed to address a unique case of external nasal valve insufficiency characterized by subjective symptoms of excessive air entry into the nose and throat discomfort despite the absence of apparent anatomical abnormalities or underlying diseases. We focused on devising a novel surgical approach to alleviate patient symptoms and highlighted the importance of considering the structural and functional aspects of nasal airflow in diagnosis and treatment. Paranasal sinus computed tomography and acoustic rhinometry were used to evaluate the anatomical and functional abnormalities. The nose scale was used to assess the subjective symptoms. The patient experienced significant improvement in breathing comfort following surgical intervention. Imaging revealed a widened columella, and the subjective symptoms were alleviated. Acoustic rhinometry measurements within the nasal cavity showed no substantial changes, likely due to the surgical focus on the external nasal valve. This case highlights the complexity of diagnosing and treating external nasal valve insufficiency without traditional anatomical abnormalities. Successful symptomatic management using this novel surgical technique highlights the need to consider structural and functional factors in nasal airway assessments. Further research is encouraged to refine the diagnostic tools and validate the effectiveness of innovative interventions for external nasal valve insufficiency in larger cohorts.

Abstract Atopic dermatitis is a chronic complex inflammatory skin disorder that requires sustainable treatment methods due to the limited efficacy of conventional therapies. Sargassum serratifolium, an algal species with diverse bioactive substances, is investigated in this study for its potential benefits as a therapeutic agent for atopic dermatitis. RNA sequencing of LPS-stimulated macrophages treated with ethanolic extract of Sargassum serratifolium (ESS) revealed its ability to inhibit a broad range of inflammation-related signaling, which was proven in RAW 264.7 and HaCaT cells. In DNCB-induced BALB/c or HR-1 mice, ESS treatment improved symptoms of atopic dermatitis within the skin, along with histological improvements such as reduced epidermal thickness and infiltration of mast cells. ESS showed a tendency to improve serum IgE levels and inflammation-related cytokine changes, while also improving the mRNA expression levels of Chi3l3, Ccr1, and Fcεr1a genes in the skin. Additionally, ESS compounds (sargachromanol (SCM), sargaquinoic acid (SQA), and sargahydroquinoic acid (SHQA)) mitigated inflammatory responses in LPS-treated RAW264.7 macrophages. In summary, ESS has an anti-inflammatory effect and improves atopic dermatitis, ESS may be applied as a therapeutics for atopic dermatitis.

Abstract The glycerol 3-phosphate shuttle (GPS) is composed of two different enzymes: cytosolic NAD+-linked glycerol 3-phosphate dehydrogenase 1 (GPD1) and mitochondrial FAD-linked glycerol 3-phosphate dehydrogenase 2 (GPD2). These two enzymes work together to act as an NADH shuttle for mitochondrial bioenergetics and function as an important bridge between glucose and lipid metabolism. Since these genes were discovered in the 1960s, their abnormal expression has been described in various metabolic diseases and tumors. Nevertheless, it took a long time until scientists could investigate the causal relationship of these enzymes in those pathophysiological conditions. To date, numerous studies have explored the involvement and mechanisms of GPD1 and GPD2 in cancer and other diseases, encompassing reports of controversial and non-conventional mechanisms. In this review, we summarize and update current knowledge regarding the functions and effects of GPS to provide an overview of how the enzymes influence disease conditions. The potential and challenges of developing therapeutic strategies targeting these enzymes are also discussed.

Abstract Oregano (Origanum vulgare) seed is used as spices and is known to have anti‐inflammatory, antibacterial, and antioxidant effects. The anti‐fatty liver effects of oregano seed ethyl acetate (OSEA) were evaluated in high‐fat diet (HFD)‐induced obese mice. OSEA was orally administered with HFD for 10 weeks. The body weight, aspartate aminotransferase, alanine aminotransferase, cholesterol, triglyceride, and low‐density lipoprotein levels in the HFD with 100 mg/kg of OSEA significantly decreased by approximately 1.21‐, 1.44‐, 2.12‐, 1.12‐, 1.05, and 1.59 times, respectively, while high‐density lipoprotein levels increased by approximately 1.05 times compared to those in the HFD group (p

Traumatic pseudoaneurysms are uncommon vascular lesions that can result from traumatic injuries to the nasal and facial areas. They pose a significant clinical challenge due to their potential to cause recurrent and life-threatening epistaxis. Understanding the underlying vascular anatomy, causes, and treatment options is essential for optimizing patient outcomes. In this case report, we present a 55-year-old man who developed a traumatic pseudoaneurysm of the sphenoid sinus, arising from the cavernous segment of the internal carotid artery following a traumatic incident. This case was successfully managed with stent-assisted coil embolization.

Abstract The high risk of neurological disorders in postmenopausal women is an emerging medical issue. Based on the hypothesis of altered estrogen receptors (ERα and β) after the decline of estrogen production, we investigated the changes in ERs expressions across brain regions and depressive/amnesic behaviors. C57BL/6J female mice were ovariectomized (OVX) to establish a menopausal condition. Along with behavior tests (anxiety, depression, and memory), the expression of ERs, microglial activity, and neuronal activity was measured in six brain regions (hippocampus, prefrontal cortex, striatum, raphe nucleus, amygdala, and hypothalamus) from 4 to 12 weeks after OVX. Mice exhibited anxiety- and depressive-like behaviors, as well as memory impairment. These behavioral alterations have been linked to a suppression in the expression of ERβ. The decreased ERβ expression coincided with microglial-derived neuroinflammation, as indicated by notable activations of Ionized calcium-binding adapter molecule 1 and Interleukin-1beta. Additionally, the activity of brain-derived neurotrophic factor (BDNF), particularly in the hippocampus, decreased in a time-dependent manner from 4 to 12 weeks post-OVX. Our study provides evidence shedding light on the susceptibility to memory impairment and depression in women after menopause. This susceptibility is associated with the suppression of ERβ and alteration of ERα in six brain regions.

Abstract Semi-infinite single-atom-thick graphene is an ideal reinforcing material that can simultaneously improve the mechanical, electrical, and thermal properties of matrix. Here, we present a float-stacking strategy to accurately align the monolayer graphene reinforcement in polymer matrix. We float graphene-poly(methylmethacrylate) (PMMA) membrane (GPM) at the water–air interface, and wind-up layer-by-layer by roller. During the stacking process, the inherent water meniscus continuously induces web tension of the GPM, suppressing wrinkle and folding generation. Moreover, rolling-up and hot-rolling mill process above the glass transition temperature of PMMA induces conformal contact between each layer. This allows for pre-tension of the composite, maximizing its reinforcing efficiency. The number and spacing of the embedded graphene fillers are precisely controlled. Notably, we accurately align 100 layers of monolayer graphene in a PMMA matrix with the same intervals to achieve a specific strength of about 118.5 MPa g−1 cm3, which is higher than that of lightweight Al alloy, and a thermal conductivity of about 4.00 W m−1 K−1, which is increased by about 2,000 %, compared to the PMMA film.

Abstract Super Typhoon Mangkhut, which traversed the North Equatorial Current (NEC; 8–17 °N) in the western North Pacific in 2018, was the most intense Category-5 tropical cyclone (TC) with the longest duration in history—3.5 days. Here we show that the combination of two factors—high ocean heat content (OHC) and increased stratification — makes the NEC region the most favored area for a rapid intensification (RI) of super typhoons, instead of the Eddy Rich Zone (17–25 °N), which was considered the most relevant for RI occurrence. The high OHC results from a northward deepening thermocline in geostrophic balance with the westward-flowing NEC. The stratification is derived from precipitation associated with the Inter-Tropical Convergence Zone in the summer peak typhoon season. These factors, which are increasingly significant over the past four decades, impede the TC-induced sea surface cooling, thus enhancing RI of TCs and simultaneously maintaining super typhoons over the NEC region.

Antioxidant activities of an aqueous extract of sesame meal (SM-HW) and an ultrasonicated sesame meal (SSM-HW) were evaluated and anti-obesity activity of SSM-HW was determined using in vitro assays. In addition, metabolite analyses were conducted using GC/MS to determine major non-volatile compounds in SM-HW and SSM-HW. Antioxidant activities of SSM-HW were significantly higher than those of SM-HW. SSM-HW had higher concentrations of some organic acids and amino acids than SM-HW. Differentiation of 3T3-L1 adipocytes was decreased by 20 % after treatment with 10 μg/mL SSM-HW compared to control. Expression levels of several adipocyte marker genes and proteins were significantly decreased compared to control (p

Abstract Developing a deep-learning-based diagnostic model demands extensive labor for medical image labeling. Attempts to reduce the labor often lead to incomplete or inaccurate labeling, limiting the diagnostic performance of models. This paper (i) constructs an attention-guiding framework that enhances the diagnostic performance of jaw bone pathology by utilizing attention information with partially labeled data; (ii) introduces an additional loss to minimize the discrepancy between network attention and its label; (iii) introduces a trapezoid augmentation method to maximize the utility of minimally labeled data. The dataset includes 716 panoramic radiograph data for jaw bone lesions and normal cases collected and labeled by two radiologists from January 2019 to February 2021. Experiments show that guiding network attention with even 5% of attention-labeled data can enhance the diagnostic accuracy for pathology from 92.41 to 96.57%. Furthermore, ablation studies reveal that the proposed augmentation methods outperform prior preprocessing and augmentation combinations, achieving an accuracy of 99.17%. The results affirm the capability of the proposed framework in fine-grained diagnosis using minimally labeled data, offering a practical solution to the challenges of medical image analysis.

Background: To study the effects of the Reflect, Inspire, Strengthen, and Empower (RISE) 2.0 Program designed for professional development of women staff. Topics included emotional intelligence, appreciative coaching, resilience, and strategic career development. Methods: The RISE 2.0 program was held between September 2020 and February 2021. After each session, program satisfaction surveys were sent to evaluate whether session objectives were met. Professional network, professional mentor, and professional goals were surveyed at the introductory session and at 1 month after the program ended. Survey data about leadership self-efficacy, motivation to lead, and well-being were collected at the introductory session (baseline) and at months 1 and 3 to evaluate the sustainability of program outcomes. Results: Of the 71 notified, 41 (58%) committed to the program. Results increased for having a robust professional network from baseline to month 1 for very good (7.3% to 13.3%) and excellent (19.5% to 40%). Those who responded favorably to setting and attaining ambitious goals increased from 78.1% to 93.3%. For leadership self-efficacy, all except 2 respondents reported an increase in ratings from baseline to month 3. Motivation to lead changed only slightly. Well-being scores fluctuated as affected by daily needs and fulfillment. For 10 of 15 respondents, well-being increased overall from baseline to month 1 or 3, from month 1 to 3. Conclusions: Based on participant evaluations and feedback, the RISE 2.0 program received positive responses overall in achieving its learning goals. The program exhibited promise in fostering career advancement and leadership development, particularly when assessed using indicators predictive of successful leadership, such as self-efficacy, motivation to lead, and overall wellbeing.

Abstract Objectives Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a significant medical challenge, with no indisputable pathophysiological mechanism identified to date. Methods Based on clinical clues, we hypothesized that 5-hydroxytryptamine (5-HT) hyperactivation is implicated in the pathogenic causes of ME/CFS and the associated symptoms. We experimentally evaluated this hypothesis in a series of mouse models. Results High-dose selective serotonin reuptake inhibitor (SSRI) treatment induced intra- and extracellular serotonin spillover in the dorsal raphe nuclei of mice. This condition resulted in severe fatigue (rota-rod, fatigue rotating wheel and home-cage activity tests) and ME/CFS-associated symptoms (nest building, plantar and open field test), along with dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis response to exercise challenge. These ME/CFS-like features induced by excess serotonin were additionally verified using both a 5-HT synthesis inhibitor and viral vector for Htr1a (5-HT1A receptor) gene knockdown. Conclusions Our findings support the involvement of 5-HTergic hyperactivity in the pathophysiology of ME/CFS. This ME/CFS-mimicking animal model would be useful for understanding ME/CFS biology and its therapeutic approaches.

As coronavirus disease-2019 (COVID-19) becomes an endemic disease, the virus continues to evolve and become immunologically distinct from previous strains. Immune imprinting has raised concerns about bivalent mRNA vaccines containing both ancestral virus and Omicron variant. To increase efficacy against the predominant strains as of the second half of 2023, the updated vaccine formulation contained only the mRNA of XBB.1.5 sublineage. We conducted a multicenter, test-negative, case-control study to estimate XBB.1.5 monovalent vaccine effectiveness (VE) and present the results of an interim analysis with data collected in November 2023. Patients who underwent COVID-19 testing at eight university hospitals were included and matched based on age (19-49, 50-64, and ≥65 years) and sex in a 1:1 ratio. VE was calculated using the adjusted odds ratio derived from multivariable logistic regression. Of the 992 patients included, 49 (5.3%) received the XBB.1.5 monovalent vaccine at least 7 days before COVID-19 testing. Patients with COVID-19 (cases) were less likely to have received the XBB.1.5 monovalent vaccine (case 3.5% vs. control 7.2%, p=0.019) and to have a history of COVID-19 within 6 months (2.2% vs. 4.6%, p=0.068). In contrast, patients with COVID-19 were more likely to be healthcare workers (8.2% vs. 3.0%, p=0.001) and to have chronic neurological diseases (16.7% vs. 11.9%, p=0.048). The adjusted VE of the XBB.1.5 monovalent mRNA vaccine was 56.8% (95% confidence interval: 18.7-77.9%). XBB.1.5 monovalent mRNA vaccine provided significant protection against COVID-19 in the first one to two months after vaccination.

BackgroundThe assessment of long-term humoral and cellular immunity post-vaccination is crucial for establishing an optimal vaccination strategy.MethodsThis prospective cohort study evaluated adults (≥18 years) who received a BA.4/5 bivalent vaccine. We measured the anti-receptor binding domain immunoglobulin G antibody and neutralizing antibodies (NAb) against wild-type and Omicron subvariants (BA.5, BQ.1.1, BN.1, XBB.1 and EG.5) up to 9 months post-vaccination. T-cell immune responses were measured before and 4 weeks after vaccination.ResultsA total of 108 (28 SARS-CoV-2-naïve and 80 previously infected) participants were enrolled. Anti-receptor binding domain immunoglobulin G (U/mL) levels were higher at 9 months post-vaccination than baseline in SAR-CoV-2-naïve individuals (8,339 vs. 1,834, p

Background: Data on the durability of booster dose immunity of COVID-19 vaccines are relatively limited. Methods: Immunogenicity was evaluated for up to 9–12 months after the third dose of vaccination in 94 healthy adults. Results: Following the third dose, the anti-spike immunoglobulin G (IgG) antibody response against the wild-type was boosted markedly, which decreased gradually over time. However, even 9–12 months after the booster dose, both the median and geometric mean of anti-spike IgG antibody levels were higher than those measured 4 weeks after the second dose. Breakthrough infection during the Omicron-dominant period boosted neutralizing antibody titers against Omicron sublineages (BA.1 and BA.5) and the ancestral strain. T-cell immune response was efficiently induced and maintained during the study period. Conclusions: mRNA vaccine booster dose elicited durable humoral immunity for up to 1 year after the third dose and T-cell immunity was sustained during the study period, supporting an annual COVID-19 vaccination strategy.

In South Korea, because of manpower and budgetary limitations, antimicrobial stewardship programs have relied on preauthorization. This study analyzed the impact of a prospective audit and feedback (PAF) program targeting inpatients undergoing intermittent hemodialysis or continuous renal replacement therapy, which was implemented at two community-based university hospitals. During three years of PAF, 27,906 antimicrobial prescriptions were reviewed, with 622 (2.2%) interventions. The mean incidence density per 1000 patient days of multidrug-resistant organisms, except for carbapenem-resistant Acinetobacter baumannii, decreased in the study population, whereas it increased among inpatients. Multivariable Poisson regression analysis revealed that after PAF, the incidences of vancomycin-resistant Enterococcus and mortality decreased (incidence risk ratio, 95% confidence interval: 0.53, 0.31–0.93 and 0.70, 0.55–0.90, respectively). Notably, after PAF, incorrect antimicrobial dosing rates significantly decreased (tau −0.244; p = 0.02). However, the incidences of other multidrug-resistant organisms, Clostridioides difficile, length of stay, and readmission did not significantly change. This study shows that in patients undergoing intermittent hemodialysis or continuous renal replacement, targeted PAF can significantly reduce multidrug-resistant organism rates and all-cause hospital mortality, despite limited resources. Furthermore, it can improve antimicrobial dosage accuracy.

Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins interact with toll-like receptors (TLR), causing an increased inflammatory response and altered cholesterol homeostasis. We aimed to determine the effects of TLR antagonists on cholesterol efflux and foam cell formation in human macrophages. Stimulated monocytes were treated with TLR antagonists (MIP2), and the cholesterol efflux transporter expression and foam cell formation were analyzed. The administration of MIP2 attenuated the foam cell formation induced by lipopolysaccharides (LPS) and oxidized low-density lipoproteins (ox-LDL) in stimulated THP-1 cells (p < 0.001). The expression of ATP-binding cassette transporters A (ABCA)-1, ABCG-1, scavenger receptor (SR)-B1, liver X receptor (LXR)-α, and peroxisome proliferator-activated receptor (PPAR)-γ mRNA and proteins were increased (p < 0.001) following MIP2 administration. A concentration-dependent decrease in the phosphorylation of p65, p38, and JNK was also observed following MIP2 administration. Moreover, an inhibition of p65 phosphorylation enhanced the expression of ABCA1, ABCG1, SR-B1, and LXR-α. TLR inhibition promoted the cholesterol efflux pathway by increasing the expression of ABCA-1, ABCG-1, and SR-B1, thereby reducing foam cell formation. Our results suggest a potential role of the p65/NF-kB/LXR-α/ABCA1 axis in TLR-mediated cholesterol homeostasis.

Recently, respiratory syncytial virus (RSV) vaccines based on the prefusion F (pre-F) antigen were approved in the United States. We aimed to develop an enzyme-linked immunosorbent assay (ELISA)-based protocol for the practical and large-scale evaluation of RSV vaccines. Two modified pre-F proteins (DS-Cav1 and SC-TM) were produced by genetic recombination and replication using an adenoviral vector. The protocol was established by optimizing the concentrations of the coating antigen (pre-F proteins), secondary antibodies, and blocking buffer. To validate the protocol, we examined its accuracy, precision, and specificity using serum samples from 150 participants across various age groups and the standard serum provided by the National Institute of Health. In the linear correlation analysis, coating concentrations of 5 and 2.5 μg/mL of DS-Cav1 and SC-TM showed high coefficients of determination (r > 0.90), respectively. Concentrations of secondary antibodies (alkaline phosphatase-conjugated anti-human immunoglobulin G, diluted 1:2000) and blocking reagents (5% skim milk/PBS-T) were optimized to minimize non-specific reactions. High accuracy was observed for DS-Cav1 (r = 0.90) and SC-TM (r = 0.86). Further, both antigens showed high precision (coefficient of variation < 15%). Inhibition ELISA revealed cross-reactivity of antibodies against DS-Cav1 and SC-TM, but not with the attachment (G) protein.