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Abstract Health implications of indoor air quality (IAQ) have drawn more attention since the COVID epidemic. There are many different kinds of studies done on how IAQ affects people’s well-being. There hasn’t been much research that looks at the microbiological composition of the aerosol in subway transit systems. In this work, for the first time, we examined the aerosol bacterial abundance, diversity, and composition in the microbiome of the Seoul subway and train stations using DNA isolated from the PM10 samples from each station (three subway and two KTX stations). The average PM10 mass concentration collected on the respective platform was 41.862 µg/m3, with the highest average value of 45.95 µg/m3 and the lowest of 39.25 µg/m3. The bacterial microbiomes mainly constituted bacterial species of soil and environmental origin (e.g., Acinetobacter, Brevundimonas, Lysinibacillus, Clostridiodes) with fewer from human sources (Flaviflexus, Staphylococcus). This study highlights the relationship between microbiome diversity and PM10 mass concentration contributed by outdoor air and commuters in South Korea’s subway and train stations. This study gives insights into the microbiome diversity, the source, and the susceptibility of public transports in disease spreading.

Abstract Backgrounds Remdesivir (RDV) is an antiviral agent approved for the treatment of coronavirus disease 2019 (COVID-19); however, is not recommended for patients with renal impairment. Due to limitations associated with prospective clinical trials, real-world data on the safety and efficacy of RDV in patients with renal impairment are necessary. Methods Propensity score-matched (PSM) retrospective analysis was conducted between March 2020 and September 2022 in COVID-19 patients with an eGFR

Background:Citrus reticulata Blanco essential oil (CBEO) has attracted increasing attention as a potential treatment for depression and anxiety in recent years. However, there is limited evidence regarding the active compounds responsible for its therapeutic effects. In addition, substantial amounts of CBEO and prolonged therapy are often required. This study aims to investigate the rapid acting antidepressant and anxiolytic effects of CBEO, identify the underlying composition as well as optimize its dosage and duration.Methods:CBEO composition was determined using gas chromatography–mass spectrometry (GC–MS), and the corresponding targets were obtained from the SwissTargetPrediction database. Depression-related targets were collected from DisGeNET, GeneCards, Therapeutic Target Database, and Online Mendelian Inheritance in Man. Subsequently, the overlap between CBEO and depression targets was utilized to build a network diagram depicting the relationship between the active ingredients and targets using Cytoscape software. The STRING database facilitated the construction of a protein–protein interaction network, and the Ma’ayan Laboratory Enrichment tool was employed for Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Wiki pathway analyses. Molecular docking was conducted using AutoDock Vina and Discovery Studio Visualizer. Topological analysis predicted the main antidepressant active ingredients in CBEO. A mixture of these compounds was prepared based on their relative GC–MS ratios. Tail suspension test, elevated plus maze, corticosterone-induced PC12 cells, and lipopolysaccharide (LPS)-induced BV2 cells were used to validate the antidepressant and anxiolytic potential of CBEO and CBEO’s main bioactive constituents.Results:CBEO contains 18 components that target 121 proteins. We identified 595 targets associated with depression; among them, 29 targets were located between essential oils and depression. Topological results revealed that linalool, p-cymene, α-terpinene, terpinen-4-ol, and α-terpineol were the major active compounds of CBEO in the management of depression. GO analysis identified G protein-coupled opioid receptor activity, phospholipase C-activating G protein-coupled receptor, and neuron projections that were mostly related to molecular functions, cellular components, and biological processes. Neuroactive ligand-receptor interactions, chemical carcinogenesis, and calcium signaling pathways were the major pathways identified in KEGG analysis. Molecular docking showed that the main bioactive ingredients of CBEO had favorable binding affinities for Protein-Protein Interaction’s hub proteins, including OPRM1, PTGS2, ESR1, SLC6A4, DRD2, and NR3C1. These five compounds were then mixed at 0.8:5:0.6:2:1 (w/w) ratio to form a CBEO antidepressant active compound mixture. An acute intranasal treatment of CBEO (25 mg/kg) only demonstrated an antidepressant effect, whereas the main bioactive compounds combination (12.5 mg/kg) illustrated both antidepressant and anxiolytic effects in mice. Linalool, p-cymene, and terpinene-4-ol exhibited neuroprotective and anti-neuroinflammation in the in vitro study, while these effects were not observed for α-terpinene and α-terpineol.Conclusion:Linalool, p-cymene, α-terpinene, terpinen-4-ol, and α-terpineol cymene might be mainly contributing to CBEO’s antidepressant effect by regulating neuroactive ligand-receptor interaction, neuron projection, and receptor signaling pathway. A mixture of these compounds showed rapid antidepressant potential via intranasal administration, which was comparable to that of CBEO. The mixture also exhibited an anxiolytic effect while not seen in CBEO.

[This corrects the article DOI: 10.1371/journal.pone.0300306.].

Abstract Impacted mandibular third molars (M3M) are associated with the occurrence of distal caries on the adjacent mandibular second molars (DCM2M). In this study, we aimed to develop and validate five machine learning (ML) models designed to predict the occurrence of DCM2Ms due to the proximity with M3Ms and determine the relative importance of predictive variables for DCM2Ms that are important for clinical decision making. A total of 2642 mandibular second molars adjacent to M3Ms were analyzed and DCM2Ms were identified in 322 cases (12.2%). The models were trained using logistic regression, random forest, support vector machine, artificial neural network, and extreme gradient boosting ML methods and were subsequently validated using testing datasets. The performance of the ML models was significantly superior to that of single predictors. The area under the receiver operating characteristic curve of the machine learning models ranged from 0.88 to 0.89. Six features (sex, age, contact point at the cementoenamel junction, angulation of M3Ms, Winter's classification, and Pell and Gregory classification) were identified as relevant predictors. These prediction models could be used to detect patients at a high risk of developing DCM2M and ultimately contribute to caries prevention and treatment decision-making for impacted M3Ms.

Abstract. Background:. Neck pain and functional impairment are common complications of traffic accidents (TAs); however, the effects of manual therapy on these symptoms have rarely been studied in the literature. Thus, this randomized controlled trial aims to assess the effectiveness and safety of non-resistance manual therapy (NRT)—a treatment combining mobilization and pressure release techniques—on acute neck pain caused by TA. Method:. This study will use a two-armed, parallel, assessor-blinded randomized controlled trial design and will be conducted in the Daejeon Jaseng Hospital of Korean Medicine in South Korea. One hundred twenty patients will be recruited and randomized into an integrative Korean medicine treatment (IMKT) + NRT group and IMKT group in a 1:1 ratio. The primary outcome is a change in the numeric rating scale for neck pain immediately after treatment on hospital day 5 compared to those at baseline. The secondary outcomes are numeric rating scale for radiating arm pain, visual analogue scale for neck pain and radiating arm pain, cervical active range of motion, neck disability index, Patient Global Impression of Change, Short Form-12 Health Survey, and Posttraumatic Stress Disorder Checklist for DSM-5. Discussion:. The findings of this study on the effectiveness and safety of NRT will be helpful for patients with TA-induced neck pain in clinical practice and will provide evidence for developing relevant healthcare-related policies. Trial registration:. This protocol has been registered at Clinicaltrials.gov (NCT04660175).

Background The aim of this study was to evaluate the efficacy of Korean medicine combination treatment on recurrent neck pain after medical procedures. Methods This retrospective study included 158 inpatients of the Daejeon Jaseng Hospital of Korean Medicine who were diagnosed with “Cervical disc disorder with radiculopathy (M50.1)” between December 14th, 2017 and May 29th, 2019. The patients were assigned to 1 of 2 groups based on whether they received medical procedures on the cervical spine at least once. Korean medicine combination treatment was evaluated using EuroQol-5 dimensions index (EQ-5D), numeric rating scale (NRS), and neck disability index (NDI) scores. Results Before and after treatment, the patients who received medical procedures on the cervical spine at least once before admission (Group A) showed a statistically significant difference in the NDI and NRS scores but not in the EQ-5D scores. This was similar to the patients who had not received medical procedures on the cervical spine before admission (Group B) they showed a statistically significant difference in the NDI and NRS scores but not in the EQ-5D scores. When comparing the results of Group A and Group B before and after treatment, no statistically significant differences were observed in the EQ-5D, NDI, and NRS scores. Conclusion Korean medicine combination treatment improves the neck functional disability of patients who suffer from recurrent neck pain despite patients having undergone medical procedures.

Abstract Insulin resistance is associated with the occurrence of stroke and atherosclerotic disease. However, the relationship between insulin resistance and the prognosis of acute ischemic stroke in non-diabetic patients is unclear. We hypothesized that insulin resistance might affect short-term functional recovery after acute ischemic stroke in non-diabetic patients. Between May 2014 and December 2016, 1377 consecutive patients with acute ischemic stroke were enrolled from a prospectively maintained stroke registry. After excluding patients with transient ischemic attacks (TIA), pre-stroke disabilities, diabetes mellitus, and patients with incomplete evaluations, 517 patients were included in the study. The homeostasis model assessment of insulin resistance (HOMA-IR) score was used to evaluate the degree of insulin resistance. The patients with the highest quartile of log HOMA-IR index scores were younger and had higher fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein, and HbA1c levels. Multivariable logistic regression analysis revealed that log HOMA-IR scores were independently associated with poor prognosis after adjusting for age and sex and p

To investigate the morphological characteristics and genetic relationships among isolate of the artificially cultivated mushroom Hypsizygus marmoreus, 111 isolates were collected from Korea and other countries. Random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) and ITS rDNA sequencing were used to confirm the genetic relationships among the collected H. marmoreus isolates. As a result of RAPD analysis using universal rice primer (URP)-PCR, all isolates of H. marmoreus clustered into three groups, which showed high sequence similarity (>90%). In addition, isolates with morphological and geographical differences formed independent clusters. However, it was impossible to distinguish between brown and white strains. Sixteen strains showing morphological and geographic differences were selected, and their ITS region sequences (640 bp) were aligned and compared. The ITS region sequences belonging to these isolates showed 94.8–99.1% similarities to those of publicly available H. marmoreus strains in GenBank. In conclusion, there were differences among isolates in terms of morphology and the area from which they were collected, but all the isolates used in the experiment were classified as H. marmoreus.

Background The purpose of this study was to investigate the clinical efficacy of Korean medicine combination treatments for recurring back pain after medical procedures. Methods This was a retrospective study performed on 311 patients admitted to Daejoen Jaseng hospital who were diagnosed with lumbar spine herniated intervertebral discs. The patients were divided into 2 groups according to whether or not they had undergone at least one medical procedure on the lumbar spine. They were assessed with Numeric Rating Scale (NRS), Oswestry Disability Index (ODI) and EuroQol-5 Dimensions Index (EQ-5D) before and after treatment. Results Patients who experienced a medical procedure on the lumbar spine in the prehospital phase (Group A), statistically significantly improved EQ-5D and ODI scores. The NRS scores also decreased however it was not statistically significant. Patients who had not undergone a medical procedure on the lumbar spine in the prehospital phase (Group B) had statistically significantly improved ODI and NRS scores. The average EQ-5D score decreased however, there was no statistically significant difference before and after scores in Group B. There was no statistically significant difference in variation in EQ-5D, ODI, and NRS scores before and after treatment between the groups. Conclusions The results of this study indicated that even after a bilateral procedure and surgery, when pain in patients with lumbar spine herniated intervertebral disc did not decrease, (as in failed back surgery syndrome), Korean medicine combination treatment of postoperative pain was helpful and there was improvement in daily life.

The frequency and clinical manifestation of lung fibrosis accompanied by coronavirus disease (COVID-19) are not well-established. We aimed to identify the factors attributed to post-COVID-19 fibrosis. This single-center prospective study included patients diagnosed with COVID-19 pneumonia from 12 April to 22 October 2021 in the Republic of Korea. The primary outcome was the presence of pulmonary fibrosis on a CT scan 3 months after discharge; the fibrosis risk was estimated by a multiple logistic regression. The mean patient age was 55.03 ± 12.32 (range 27–85) years; 65 (66.3%) were men and 33 (33.7%) were women. The age, Charlson Comorbidity Index, lactate dehydrogenase level, aspartate aminotransferase level, and Krebs von den Lungen-6 level were significantly higher and the albumin level and the saturation of the peripheral oxygen/fraction of inspired oxygen (SpO2/FiO2) ratio were significantly lower in the fibrosis group than in the non-fibrosis group; the need for initial oxygen support was also greater in the fibrosis group. An older age (adjusted odds ratio (AOR) 1.12; 95% confidence interval (CI) 1.03–1.21) and a lower initial SpO2/FiO2 ratio (AOR 7.17; 95% CI 1.72–29.91) were significant independent risk factors for pulmonary fibrosis after COVID-19 pneumonia. An older age and a low initial SpO2/FiO2 ratio were crucial in predicting pulmonary fibrosis after COVID-19 pneumonia.

As the legislative pressure to reduce energy consumption is increasing, data analysis of power consumption is critical in the production planning of manufacturing facilities. In legacy studies, a machine conducting a single continuous operation has been mainly observed for power estimation. However, the production machine of a modularized line, which conducts complex discrete operations, is more like the actual factory system than an identical simple machine. During the information collection of this kind of production line, it is important to interpret mixed signals from multiple machines to ensure that there is no reduction in the information quality due to noise and signal fusion and discrete events. A data pipeline—from data collection (from different sources) to preprocessing, data conversion, synchronization, and deep learning classification—to estimate the total power use of the future process plan, is proposed herein. The pipeline also establishes an auto-labeled data set of individual operations that contributes to building an power estimation model without manual data preprocessing. The proposed system is applied to a modular factory, connected with machine controllers, using standardized protocols individually and linked to a centralized power monitoring system. Specifically, a robot arm cell was investigated to evaluate the pipeline, with the result of the power profile being synchronized with the robot program.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Much progress has been made regarding the understanding of hepatocarcinogenesis, yet the long-term survival rate of HCC patients remains poor. Recent efforts have shown parafibromin has a pathologic role in many human cancers, but little is known about the effects of parafibromin in HCC. This study aimed to investigate the pattern of parafibromin expression and its clinicopathologic significance in human HCC. Immunohistochemical analysis of HCC and matched non-tumor liver tissues from 50 HCC patients showed that the nuclear expression of parafibromin was higher in HCC tissues (50/50 cases) than in non-tumor liver tissues (17/50 cases). Moreover, elevated parafibromin expression was found to be significantly correlated with the presence of microvascular invasion (p = 0.017), hepatitis virus infection-induced occurrence (p = 0.005), and poorer tumor differentiation (Edmondson–Steiner grade; p = 0.000). Kaplan–Meier analysis showed that HCC patients with elevated parafibromin expression had poorer recurrence-free (p = 0.014, log-rank test = 6.079) and overall survival (p = 0.036, log-rank test = 4.414). These findings indicate parafibromin may be related to the pathogenesis of HCC and a potential prognostic marker for HCC patients after hepatectomy.

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.

Abstract Bone homeostasis is maintained by an intricate balance between osteoclasts and osteoblasts, which becomes disturbed in osteoporosis. Metallothioneins (MTs) are major contributors in cellular zinc regulation. However, the role of MTs in bone cell regulation has remained unexplored. Single-cell RNA sequencing analysis discovered that, unlike the expression of other MT members, the expression of MT3 was unique to osteoclasts among various macrophage populations and was highly upregulated during osteoclast differentiation. This unique MT3 upregulation was validated experimentally and supported by ATAC sequencing data analyses. Downregulation of MT3 by gene knockdown or knockout resulted in excessive osteoclastogenesis and exacerbated bone loss in ovariectomy-induced osteoporosis. Transcriptome sequencing of MT3 knockdown osteoclasts and gene set enrichment analysis indicated that the oxidative stress and redox pathways were enriched, which was verified by MT3-dependent regulation of reactive oxygen species (ROS). In addition, MT3 deficiency increased the transcriptional activity of SP1 in a manner dependent on intracellular zinc levels. This MT3-zinc-SP1 axis was crucial for the control of osteoclasts, as zinc chelation and SP1 knockdown abrogated the promotion of SP1 activity and osteoclastogenesis by MT3 deletion. Moreover, SP1 bound to the NFATc1 promoter, and overexpression of an inactive SP1 mutant negated the effects of MT3 deletion on NFATc1 and osteoclastogenesis. In conclusion, MT3 plays a pivotal role in controlling osteoclastogenesis and bone metabolism via dual axes involving ROS and SP1. The present study demonstrated that MT3 elevation is a potential therapeutic strategy for osteolytic bone disorders, and it established for the first time that MT3 is a crucial bone mass regulator.

OBJECTIVES:Debates whether metabolically healthy obesity (MHO) increases the cardiovascular risk might be due to the metabolic instability of MHO or the absence of a perfect definition of MHO. Therefore, we aimed to investigate the influence of the MHO phenotype on the coronary artery calcium score (CACS) progression according to definition of MHO. METHODS:We analyzed a retrospective cohort with a CACS of 0 at baseline and available serial CACS measurements taken ≥ 12 months apart (n = 1,218). Obesity was defined as BMI ≥ 25 kg/m2, and MHO was defined as obesity accompanied by ≤ 1 (MHO class I) or 0 (MHO class II) components of metabolic syndrome (MetS). RESULTS:During a median follow-up of 45 months, 32.2% of MHO class I and 10.2% of MHO class II subjects developed MetS. Compared to non-obese/metabolically healthy subjects (reference group), hazard ratios (HR) for development of MetS were 2.174 (95% confidence interval [CI]: 1.513-3.124) and 1.166 (95% CI: 0.434-3.129) for MHO class I and II subjects, respectively. The MHO class I subjects showed a significantly increased risk of CACS progression as compared to the reference group (HR: 1.653; 95% CI: 1.144-2.390), whereas MHO class II subjects did not (HR: 1.195; 95% CI: 0.514-2.778). Among subjects with MHO class I, no significant CACS progression was observed in the subjects who maintained metabolic health during follow-up (HR: 1.448; 95% CI: 0.921-2.278). CONCLUSIONS:The risks of metabolic deterioration and CACS progression were significant in subjects with MHO class I, but not in those with MHO class II.

Hepatic fibrosis is the wound-healing process of chronic hepatic disease that leads to the end-stage of hepatocellular carcinoma and demolition of hepatic structures. Epithelial–mesenchymal transition (EMT) has been identified to phenotypic conversion of the epithelium to mesenchymal phenotype that occurred during fibrosis. Smad decoy oligodeoxynucleotide (ODN) is a synthetic DNA fragment containing a complementary sequence of Smad transcription factor. Thus, this study evaluated the antifibrotic effects of Smad decoy ODN on carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. As shown in histological results, CCl4 treatment triggered hepatic fibrosis and increased Smad expression. On the contrary, Smad decoy ODN administration suppressed fibrogenesis and EMT process. The expression of Smad signaling and EMT-associated protein was markedly decreased in Smad decoy ODN-treated mice compared with CCl4-injured mice. In conclusion, these data indicate the practicability of Smad decoy ODN administration for preventing hepatic fibrosis and EMT processes.

Periodontitis is a chronic inflammatory disease that contributes to the destruction of the gingiva. Porphyromonas gingivalis (P. gingivalis) can cause periodontitis via its pathogenic lipopolysaccharides (LPS). Melittin, a major component of bee venom, is known to have anti-inflammatory and antibacterial effects. However, the role of melittin in the inflammatory response has not been elucidated in periodontitis-like human keratinocytes. Therefore, we investigated the anti-inflammatory effects of melittin on a P. gingivalis LPS (PgLPS)-treated HaCaT human keratinocyte cell line. The cytotoxicity of melittin was measured using a human keratinocyte cell line, HaCaT, and a Cell Counting Kit-8. The effect of melittin on PgLPS-induced inflammation was determined with Western blot, real-time quantitative PCT, and immunofluorescence. PgLPS increased the expression of toll-like receptor (TLR) 4 and proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and interferon-γ (IFN-γ). Moreover, PgLPS induced activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), extracellular signal-regulated kinase (ERK), and protein kinase B/Akt. Melittin also inhibited the expression of proinflammatory cytokines by suppressing the activation of the NF-κB signaling pathway, ERK, and Akt. Melittin attenuates the PgLPS-induced inflammatory response and could therefore be applied in the treatment of periodontitis for anti-inflammatory effects.

A novel polyene compound NPP identified in a rare actinomycetes, Pseudonocardia autotrophica KCTC9441, was shown to contain an aglycone identical to nystatin but to harbor a unique di-sugar moiety, mycosaminyl-(α1-4)-N-acetyl-glucosamine, which led to higher solubility and reduced hemolytic activity. Although the nppDI was proved to be responsible for the transfer of first polyene sugar, mycosamine in NPP biosynthesis, the gene responsible for the second sugar extending glycosyltransferase (GT) as well as NPP post-PKS tailoring mechanism remained unknown. Here, we identified a NPP-specific second sugar extending GT gene named nppY, located at the edge of the NPP biosynthetic gene cluster. Targeted nppY gene deletion and its complementation proved that nppY is indeed responsible for the transfer of second sugar, N-acetyl-glucosamine in NPP biosynthesis. Site-directed mutagenesis on nppY also revealed several amino acid residues critical for NppY GT function. Moreover, a combination of deletions and complementations of two GT genes (nppDI and nppY) and one P450 hydroxylase gene (nppL) involved in the NPP post-PKS biosynthesis revealed that NPP aglycone is sequentially modified by the two different GTs encoded by nppDI and nppY, respectively, followed by the nppL-driven regio-specific hydroxylation at the NPP C10 position. These results set the stage for the biotechnological application of sugar diversification for the biosynthesis of novel polyene compounds in actinomycetes.

Purpose: This study was conducted to develop a cultural competence scale for nurses regarding the lesbian, gay, bisexual, and transgender (LGBT) community and to test its validity and reliability. Methods: The study adhered to the 8-step process outlined by DeVellis, with an initial set of 25 items derived through a literature review and individual interviews. Following an expert validity assessment, 24 items were validated. Subsequently, a preliminary survey was conducted among 23 nurses with experience caring for LGBT patients. Data were then collected from a final sample of 322 nurses using the 24 items. Item analysis, item-total score correlation, examination of construct and convergent validity, and reliability testing were performed. Results: The item-level content validity index exceeded .80, and the explanatory power of the construct validity was 63.63%. The factor loadings varied between 0.57 and 0.80. The scale comprised five factors: cultural skills, with seven items; cultural awareness, with five items; cultural encounters, with three items; cultural pursuit, with three items; and cultural knowledge, with three items; totaling 21 items. Convergent validity demonstrated a high correlation, affirming the scale's validity. Internal consistency analysis yielded an overall reliability coefficient of 0.97, signifying very high reliability. Each item is scored from 1 to 6 (total score range, 21-126), with higher scores reflecting greater cultural competence in LGBT care. Conclusion: This scale facilitates the measurement of LGBT cultural competence among nurses. Therefore, its use should provide foundational data to support LGBT-focused nursing education programs. [ABSTRACT FROM AUTHOR]

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) is dominating coronavirus disease 2019 (COVID-19) worldwide. The waning protective effect of available vaccines against the Omicron variant is a critical public health issue. This study aimed to assess the impact of the third COVID-19 vaccination on immunity against the SARS-CoV-2 Omicron BA.1 strain in older individuals. Materials and Methods: Adults aged ≥60 years who had completed two doses of the homologous COVID-19 vaccine with either BNT162b2 (Pfizer/BioNTech, New York, NY, USA, BNT) or ChAdOx1 nCoV (SK bioscience, Andong-si, Gyeongsangbuk-do, Korea, ChAd) were registered to receive the third vaccination. Participants chose either BNT or mRNA-1273 (Moderna, Norwood, MA, USA, m1273) mRNA vaccine for the third dose and were categorized into four groups: ChAd/ChAd/BNT, ChAd/ChAd/m1273, BNT/BNT/BNT, and BNT/BNT/m1273. Four serum specimens were obtained from each participant at 0, 4, 12, and 24 weeks after the third dose (V1, V2, V3, and V4, respectively). Serum-neutralizing antibody (NAb) activity against BetaCoV/Korea/KCDC03/2020 (NCCP43326, ancestral strain) and B.1.1.529 (NCCP43411, Omicron BA.1 variant) was measured using plaque reduction neutralization tests. A 50% neutralizing dilution (ND50) >10 was considered indicative of protective NAb titers. Results: In total, 186 participants were enrolled between November 24, 2021, and June 30, 2022. The respective groups received the third dose at a median (interquartile range [IQR]) of 132 (125 - 191), 123 (122 - 126), 186 (166 - 193), and 182 (175 - 198) days after the second dose. Overall, ND50 was lower at V1 against Omicron BA.1 than against the ancestral strain. NAb titers against the ancestral strain and Omicron BA.1 variant at V2 were increased at least 30-fold (median [IQR], 1235.35 [1021.45 - 2374.65)] and 129.8 [65.3 - 250.7], respectively). ND50 titers against the ancestral strain and Omicron variant did not differ significantly among the four groups (P = 0.57). NAb titers were significantly lower against the Omicron variant than against the ancestral strain at V3 (median [IQR], 36.4 (17.55 - 75.09) vs. 325.9 [276.07 - 686.97]; P = 0.012). NAb titers against Omicron at V4 were 16 times lower than that at V3. Most sera exhibited a protective level (ND50 >10) at V4 (75.0% [24/32], 73.0% [27/37], 73.3% [22/30], and 70.6% [12/17] in the ChAd/ChAd/BNT, ChAd/ChAd/m1273, BNT/BNT/BNT, and BNT/BNT/m1273 groups, respectively), with no significant differences among groups (P = 0.99). Conclusion: A third COVID-19 mRNA vaccine dose restored waning NAb titers against Omicron BA.1. Our findings support a third-dose vaccination program to prevent the waning of humoral immunity to SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background. Quinoline-3-carboxamides have been used to treat autoimmune/inflammatory diseases in humans because they inhibit the functions of S100 calcium-binding protein A9 (S100A9), which participates in the development of neutrophilic inflammation in asthmatics and in an animal model of neutrophilic asthma. However, the therapeutic effects of these chemicals have not been evaluated in asthma. The purpose of this study was to evaluate the effect of paquinimod, one of the quinoline-3-carboxamides, on a murine model of neutrophilic asthma. Methods. Paquinimod was orally administered to 6-week-old C57BL/6 mice sensitized and challenged with ovalbumin (OVA)/complete Freund’s adjuvant (CFA) and OVA. Lung inflammation and remodeling were evaluated using bronchoalveolar lavage (BAL) and histologic findings including goblet cell count. S100A9, caspase-1, IL-1β, MPO, IL-17, IFN-γ, and TNF-α were measured in lung lysates using western blotting. Results. Paquinimod restored the enhancement of airway resistance and the increases in numbers of neutrophils and macrophages of BAL fluids and those of goblet cells in OVA/CFA mice toward the levels of sham-treated mice in a dose-dependent manner (0.1, 1, 10, and 25 mg/kg/day, p.o.). Concomitantly, p20 activated caspase-1, IL-1β, IL-17, TNF-α, and IFN-γ levels were markedly attenuated. Conclusion. These data indicate that paquinimod effectively inhibits neutrophilic inflammation and remodeling in the murine model of neutrophilic asthma, possibly via downregulation of IL-17, IFN-γ, and IL-1β.

We set up this study to understand the underlying mechanisms of reduced ceramides on immune cells in acute rejection (AR). The concentrations of ceramides and sphingomyelins were measured in the sera from hepatic transplant patients, skin graft mice and hepatocyte transplant mice by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Serum concentrations of C24 ceramide, C24:1 ceramide, C16:0 sphingomyelin, and C18:1 sphingomyelin were lower in liver transplantation (LT) recipients with than without AR. Comparisons with the results of LT patients with infection and cardiac transplant patients with cardiac allograft vasculopathy in humans and in mouse skin graft and hepatocyte transplant models suggested that the reduced C24 and C24:1 ceramides were specifically involved in AR. A ceramide synthase inhibitor, fumonisin B1 exacerbated allogeneic immune responses in vitro and in vivo, and reduced tolerogenic dendritic cells (tDCs), while increased P3-like plasmacytoid DCs (pDCs) in the draining lymph nodes from allogeneic skin graft mice. The results of mixed lymphocyte reactions with ceranib-2, an inhibitor of ceramidase, and C24 ceramide also support that increasing ceramide concentrations could benefit transplant recipients with AR. The results suggest increasing ceramides as novel therapeutic target for AR, where reduced ceramides were associated with the changes in DC subsets, in particular tDCs. [ABSTRACT FROM AUTHOR]

Background/Aims Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disorder that typically requires long-term maintenance therapy. However, little is known about patient preferences and satisfaction and real-world prescription patterns regarding maintenance therapy for GERD. Methods This observational, cross-sectional, multicenter study involved patients from 18 referral hospitals in Korea. We surveyed patients who had been prescribed proton pump inhibitors (PPIs) for GERD for at least 90 days with a minimum follow-up duration of 1 year. The main outcome was overall patient satisfaction with different maintenance therapy modalities. Results A total of 197 patients were enrolled. Overall patient satisfaction, patient preferences, and GERD health-related quality of life scores did not significantly differ among the maintenance therapy modality groups. However, the on-demand therapy group experienced a significantly longer disease duration than the continuous therapy group. The continuous therapy group demonstrated a lower level of awareness of potential adverse effects associated with PPIs than the on-demand therapy group but received higher doses of PPIs than the on-demand therapy group. The prescribed doses of PPIs also varied based on the phenotype of GERD, with higher doses prescribed for non-erosive reflux disease than erosive reflux disease. Conclusion Although overall patient satisfaction did not significantly differ among the different PPI maintenance therapy modality groups, awareness of potential adverse effects was significantly different between the on-demand and continuous therapy groups. [ABSTRACT FROM AUTHOR]