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Abstract Background Prophylactic parenteral administration of antibiotics is strongly recommended to prevent surgical site infection (SSI). Cefoxitin is mainly administered intravenously in colorectal surgery. The current standard method for administering prophylactic antibiotics in adults is to administer a fixed dose quickly before skin incision. The percentage of time that the unbound concentration is maintained above the minimum inhibitory concentration (fT > MIC) during surgery is used as a surrogate measure for the effectiveness of prophylactic antibiotics. Target-controlled infusion (TCI) is a method of administration that changes the infusion rate to maintain a constant target concentration set by the user in consideration of the patient’s physical characteristics. When cefoxitin is administered using the TCI method, it is possible that fT > MIC can be well maintained while reflecting the patient’s physical characteristics compared to the standard method. Methods This prospective, single-centre, parallel-arm, single-blinded, randomised controlled trial with a 1:1 allocation was designed to compare the effectiveness of the TCI method with that of the standard cefoxitin administration method. We shall enrol 2494 patients scheduled to undergo colon or rectal surgery. Prior to the procedure, we shall randomise each patient to the control group (standard administration method) or study group (TCI method). In the control group, 2 g of cefoxitin was dissolved in 100 ml of normal saline and administered for approximately 10 min. Redosing was performed every 2 h from the start of the first dose of cefoxitin. In the study group, 2 g of cefoxitin was dissolved in 50 ml of normal saline and administered using a commercialised TCI syringe pump until the end of surgery. It was administered at a target concentration of 80 μg/ml using the total concentration pharmacokinetic model of cefoxitin. In all groups, 2 g of cefoxitin was administered using the standard administration method 12 h after the end of surgery. The primary outcome will be the incidence of SSI. The secondary outcome will be the administered dose of cefoxitin. Preoperative, intraoperative, and postoperative data were collected. Discussion This study will provide evidence for the effectiveness of administering cefoxitin using the TCI method compared to the standard method. Trial registration ClinicalTrials.gov, NCT05253339 , Registered on February 23, 2022 {2a, 2b}.

Abstract Articular cartilage has a limited regenerative capacity, resulting in poor spontaneous healing of damaged tissue. Despite various scientific efforts to enhance cartilage repair, no single method has yielded satisfactory results. With rising drug development costs, drug repositioning has emerged as a viable alternative. This study aimed to identify a drug capable of improving cartilage defects by analyzing chondrogenesis-related microarray data from the Gene Expression Omnibus (GEO) public database. We utilized datasets GSE69110, GSE107649, GSE111822, and GSE116173 to identify genes associated with cartilage differentiation, employing StringTie for differential gene expression analysis and extracting drug data from the Drug-Gene Interaction database. Additionally, we aimed to verify the cartilage regeneration potential of the identified drug through experiments using cellular and animal models. We evaluated the effects of aripiprazole on adipose-derived mesenchymal stem cells (ADMSCs) and chondrocytes using qRT-PCR and a 3D pellet culture system. In vivo, we assessed cartilage restoration by combining aripiprazole with a scaffold and implanting it into artificially induced cartilage defects in Sprague-Dawley rats. Subsequent mRNA sequencing provided insights into the mechanistic pathways involved. Our results showed that aripiprazole significantly increased mRNA expression of COL2A1 and SOX9, markers of chondrogenesis, and promoted chondrogenic condensation in vitro. Furthermore, aripiprazole effectively enhanced cartilage regeneration in the rat model. KEGG pathway and Gene Ontology Biological Processes (GOBP) analyses of the mRNA sequencing data revealed that aripiprazole upregulated genes related to ribosomes and cytoplasmic translation, thereby facilitating chondrogenesis. In conclusion, our findings suggest that aripiprazole is a promising candidate for improving damaged cartilage, offering a novel approach to cartilage regeneration.

High-yield production of therapeutic protein using Chinese hamster ovary (CHO) cells requires stable cell line development (CLD). CLD typically uses random integration of transgenes; however, this results in clonal variation and subsequent laborious clone screening. Therefore, site-specific integration of a protein expression cassette into a desired chromosomal locus showing high transcriptional activity and stability, referred to as a hot spot, is emerging. Although positional effects are important for therapeutic protein expression, the sequence-specific mechanisms by which hotspots work are not well understood. In this study, we performed whole-genome sequencing (WGS) to locate randomly inserted vectors in the genome of recombinant CHO cells expressing high levels of monoclonal antibodies (mAbs) and experimentally validated these locations and vector compositions. The integration site was characterized by active histone marks and potential enhancer activities, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) mediated indel mutations in the region upstream of the integration site led to a significant reduction in specific antibody productivity by up to 30%. Notably, the integration site and its core region did not function equivalently outside the native genomic context, showing a minimal effect on the increase in exogenous protein expression in the host cell line. We also observed a superior production capacity of the mAb expressing cell line compared to that of the host cell line. Collectively, this study demonstrates that developing recombinant CHO cell lines to produce therapeutic proteins at high levels requires a balance of factors including transgene configuration, genomic locus landscape, and host cell properties.

Exposure to toxic molecules from food or oral medications induces toxicity in colon cells that cause various human diseases; however, in vitro monitoring systems for colon cell toxicity are not well established. Stress granules are nonmembranous foci that form in cells exposed to cellular stress. When cells sense toxic environments, they acutely and systemically promote stress granule formation, with Ras GTPase-activating protein-binding protein 1 (G3BP1) acting as a core component to protect their mRNA from abnormal degradation. Here, we knocked in green fluorescent protein (GFP)-coding sequences into the C-terminal region of the G3BP1 gene in a human colon cell line through CRISPR-Cas9-mediated homologous recombination and confirmed the formation of stress granules with the G3BP1-GFP protein in these cells under cellular stress exposure. We demonstrated the formation and dissociation of stress granules in G3BP1-GFP expressing colon cells through real-time monitoring using a fluorescence microscope. Furthermore, we validated the toxicity monitoring system in the established colon cell line by observing stress granule formation following exposure to dihydrocapsaicin, bisphenol A, and sorbitol. Taken together, we established a stress granule reporter system in a colon cell line, providing a novel assessment for the real-time monitoring of colon toxicity in response to various chemicals.

Abstract Background Antipsychotic drugs (APDs) are used for treating mental illnesses and are also used by cancer patients. This study aimed to evaluate APD use in adult cancer patients who received radiotherapy (RT) in South Korea and assess the effects of APD use during RT on survival. Methods This retrospective cohort study utilized the National Health Insurance Service database database of Korea. We included adult cancer patients who underwent RT or chemotherapy (CTx, cisplatin, or 5-Fluorouracil) between 2010 and 2020. The APDs included in the analysis were aripiprazole, quetiapine, olanzapine, risperidone, haloperidol, and chlorpromazine. Results Overall, 725,897 patients received RT, and 115,500 received concomitant chemo-radiotherapy (CCRT). Of them, 41,118 (5.6%) took APDs during RT, and 8,129 (7%) took APDs during CCRT. Overall, 27,789 (67.58%) patients who took APDs during RT were men, and 28,004 (68.2%) were aged ≥ 60 years. The most frequently used APD during RT was quetiapine (64.93%). Patients who took APDs during RT and during CCRT had higher mortality rates (HR: 3.45 and 1.72, p

Abstract In this study, we aimed to investigate the nationwide utilization of antipsychotic drugs (APDs) during radiotherapy and evaluate their association with survival in patients with breast cancer. This retrospective cohort study used the National Health Insurance Service database in Korea and included patients diagnosed with breast cancer from 2010 to 2020 who received radiotherapy. The APDs included in the analysis were aripiprazole, quetiapine, olanzapine, risperidone, haloperidol, and chlorpromazine, and the APD prescription details included prescription time, dosage, and duration. Among 170,226 patients with breast cancer treated with radiotherapy, 3361 (1.97%) received APD during radiotherapy. Use of APDs was significantly associated with higher mortality in all patients and in a subgroup of patients excluding those with metastasis or other cancers. Among patients taking APD during radiotherapy, those with accompanied psychiatric history and long-term APD use for ≥ 3 months were associated with lower mortality, whereas patients who started APD during radiotherapy had higher mortality than those who started APD before radiotherapy. The high mortality observed in breast cancer patients using APDs during radiotherapy could be influenced by the underlying conditions that necessitated APD use. Further studies are needed to determine the effects of APDs during radiotherapy in patients with breast cancer.

Purpose: The aim of this study was to investigate the efficacy of ethanol extracts of Cornus alba (ECA) against benign prostatic hyperplasia (BPH) in vitro and in vivo. Materials and Methods: The prostate stromal cells (WPMY-1) and epithelial cells (RWPE-1) were used to examine the action mechanism of ECA in BPH in vitro. ECA efficacy was evaluated in vivo using a testosterone propionate (TP)-induced BPH rat model. Results: Treatment with ECA inhibited the proliferation of prostate cells by inducing G1-phase cell cycle arrest through the regulation of positive and negative proteins. Treatment of prostate cells with ECA resulted in alterations in the mitogenactivated protein kinases and protein kinase B signaling pathways. The transcriptional binding activity of the NF-κB motif was suppressed in both ECA-treated prostate cells. In addition, treatment with ECA altered the level of BPH-associated axis markers (5α-reductase, fibroblast growth factor-2, androgen receptor, epidermal growth factor, Bcl-2, and Bax) in both cell lines. Finally, the administration of ECA attenuated the enlargement of prostatic tissues in the TP-induced BPH rat model, accompanied by histology, immunoblot, and serum dihydrotestosterone levels. Conclusions: These results demonstrated that ECA exerted beneficial effects on BPH both in vitro and in vivo and might provide valuable information in the development of preventive or therapeutic agents for improving BPH.

Abstract Background Toothbrushing is the most commonly used method to physically remove dental plaque. However, there are many areas of the mouth that are difficult to reach with a toothbrush. The type of toothbrush is a critical factor influencing the effectiveness of oral care. The purpose of the study was to evaluate a toothbrush with a thin head, slender-neck and super-tapered bristles to target hard-to-reach areas in the oral cavity for reducing dental plaque and gingivitis. Methods This crossover study included 58 adults aged 20 years and older. All participants were randomly assigned to use test and control toothbrushes (the latter had a normal head and round bristles) for two 4-week phases. Participants brushed their teeth twice daily in their habitual manner. At the start and end of each phase the Silness-Lӧe plaque index (PI), Lӧe -Silness gingival index (GI) and bleeding-on-probing index (BOP) were assessed and performed plaque fluorescence tests using quantitative light-induced fluorescence technology. Results After using the test toothbrush, PI, GI and BOP decreased by 25%, 30% and 48%, respectively (P

Background: Identifying the underlying etiology of developmental delay/intellectual disability (DD/ID) is challenging but important. The genetic diagnosis of unexplained DD/ID helps in the treatment and prognosis of the disability in patients. In this study, we reported our experience of using whole exome sequencing (WES) of children with unexplained DD/ID. Methods: We conducted a retrospective analysis of WES results of children under 19 years of age with unexplained DD/ID between January 2020 and December 2021. The demographic data of all patients and variants identified through WES were evaluated. Furthermore, we evaluated the clinical characteristics that influenced the identification of genetic causes. Results: Forty-one patients with DD/ID were included, of whom 21 (51.2 %) were male. The average age at symptom onset was 1.6 ± 1.3 years, and the duration from symptom onset to diagnosis was 3.1 ± 3.7 years. Hypotonia was the most common symptom (17 patients, 41.5 %), and epilepsy was confirmed in 10 patients (24.4 %). Twenty-two pathogenic/likely pathogenic variants were identified in 20 patients, and three variants of uncertain significance were identified in three patients. Family-based trio Sanger sequencing for candidate variants of 12 families was conducted; 10 variants were de novo, one variant paternally inherited, and two variants compound heterozygous. The diagnostic yield of WES for DD/ID was 48.8 % and was significantly high in patients with an early onset of DD/ID and facial dysmorphism. In contrast, patients with autism spectrum disorder (ASD) were more likely to have negative WES results compared with others without ASD. Conclusion: The diagnostic yield of WES was 48.8 %. We conclude that patients’ characteristics, such as dysmorphic features and the age of symptom onset, can predict the likelihood that WES will identify a causal variant of a phenotype.

Abstract The demand for high-capacity batteries with long cycle life and safety has been increasing owing to the expanding mid-to-large battery market. Li–S batteries are suitable energy-storage devices because of their reversibility, high theoretical capacity, and inexpensive construction materials. However, their performance is limited by various factors, including the shuttle effect and dendrite growth at the anode. Here, an integrated electrode for use in all-solid-state (ASS) Li–S batteries was formed via hot pressing. In detail, S particles dispersed in a functionalized reduced graphite oxide (rGO) cathode with a binder-less polymer electrolyte (PE) and a dual-anion ionic liquid-containing cross-linked poly(ethylene oxide)–Li bis(fluoromethanesulfonyl)imide–N-butyl-N-methylpyrrolidinium bis(trifluoromethanesulfonyl) imide-based solid polymer electrolyte (SPE, PEO–LiFSI0.1(Pyr14TFSI)0.4) were hot-pressed into an integrated electrode, which serves as both the cathode and electrolyte. The resulting S/rGO-based solid-state Li–S batteries exhibited more stable performance than Li–S batteries using liquid electrolytes did, indicating that the dual-anion SPE layer effectively suppressed dendritic Li formation and the shuttle effect with high ionic conductivity. At 0.1 C, the battery discharge capacities were 957 and 576 mAh g−1 in the first cycle and after 100 cycles, respectively. At 1 C, the reversible capacity was 590 and 417 mAh g−1 in the first cycle and after 100 cycles, respectively (capacity retention = 71%). Therefore, the proposed S/rGO/PE//LiFSI0.1(Pyr14TFSI)0.4-integrated electrodes are beneficial for ASS Li–S batteries.

Objectives: Lack of physical activity has a critical effect on the physical and mental health of adolescents. This study examined the influence of family adversities on the longitudinal changes in physical inactivity among adolescents during the coronavirus disease 2019 (COVID-19) pandemic. Methods: The study used multi-wave data from the Korean Children and Youth Panel Survey, including 2590 Korean adolescents aged 12-14 years. The longitudinal trajectory of physical inactivity among adolescents and the effects of related factors were estimated using a latent growth modeling method. Results: Our results revealed a significant increase in physical inactivity among adolescents over time. At the onset of the pandemic, approximately one-seventh of Korean middle schoolers reported a lack of physical activity. However, 3 years later, during the quarantine, nearly one-fifth of these adolescents reported a significant increase in their physical inactivity. Initially, low level parental education was predictive of adolescents’ physical inactivity, but this effect diminished over time, becoming statistically insignificant by the end of the 3-year period. Moreover, the increase in physical inactivity over the 3 years was significantly influenced by parental rejection. Conclusions: These findings suggest that adolescents who experience parental rejection are more likely to report an increase in sedentary behaviors in contexts such as the COVID-19 pandemic.

Abstract Atopic dermatitis (AD) presents significant therapeutic challenges due to its poorly understood etiology. Eosinophilia, a hallmark of allergic inflammation, is implicated in AD pathogenesis. Interleukin-10 (IL-10)-producing regulatory B (Breg) cells exhibit potent anti-inflammatory effects. However, their role in controlling AD-related eosinophilia is not well understood. To investigate the impact of eosinophils on AD, we employed IL-5Rα-deficient (Il5ra −/− ) mice, which lack functional eosinophils. Induction of AD in these mice resulted in attenuated disease symptoms, underscoring the critical role of eosinophils in AD development. Additionally, the adoptive transfer of purified Breg cells into mice with AD significantly alleviated disease severity. Mechanistic studies revealed that IL-10 produced by Breg cells directly inhibits eosinophil activation and infiltration into the skin. In vitro experiments further confirmed that Breg cells inhibited eosinophil peroxidase secretion in an IL-10-dependent manner. Our collective findings demonstrate that IL-10 from Breg cells alleviates AD by suppressing eosinophil activation and tissue infiltration. This study elucidates a novel regulatory mechanism of Breg cells, providing a foundation for future Breg-mediated therapeutic strategies for AD.

Policies for early childhood inclusion in South Korea have been enacted and implemented over 3 decades. However, early childhood educators' experiences and perceptions toward inclusion in early childhood education settings have been understudied. In this qualitative study, we interviewed 11 early childhood educators with inclusive teaching experiences using a semi-structured format. The teachers conceptualized the definition of and suggestions for inclusion in early childhood education settings and discussed the benefits of and challenges for inclusion in current South Korean education settings. We use their suggestions to provide implications for research and practice.

Despite the importance of inclusion in education, studies that clearly define and operationalize the concept of early childhood inclusive education in South Korea remain scarce. In this study, we aimed to translate and validate a comprehensive measurement scale to assess Korean early childhood teachers' attitudes and perceptions regarding inclusion. We analyzed data from a group of 224 respondents from 82 daycare centers in South Korea and tested the inclusion scale's internal consistency, subscale reliability, and content and construct validity. The exploratory factor analysis identified four factors with varying number of items in each factor. Researchers could use this instrument to better understand Korean teachers' beliefs about themselves with respect to inclusive education. Implications for research include the utility of the survey instrument with Korean early childhood teachers.

IntroductionAn effective vaccination policy must be implemented to prevent foot-and-mouth disease (FMD). However, the currently used vaccines for FMD have several limitations, including induction of humoral rather than cellular immune responses.MethodsTo overcome these shortcomings, we assessed the efficacy of levamisole, a small-molecule immunomodulator, as an adjuvant for the FMD vaccine. We conducted in vitro studies using murine peritoneal exudate cells (PECs) and porcine peripheral blood mononuclear cells (PBMCs) and in vivo studies using mice (experimental animals) and pigs (target animals). We evaluated levamisole-mediated modulation of the innate and adaptive immune responses; early, mid-term, and long-term immune-inducing effects; modes of action; and host defense against viral infection.ResultsLevamisole treatment promoted IFNγ secretion in murine PECs and porcine PBMCs. Additionally, it induced robust and long-lasting immune responses by eliciting high antibody titers and high virus-neutralizing antibody titers. By activating downstream signaling pathways of various pattern-recognition receptors, levamisole stimulated the expression of multiple cytokines and costimulatory molecules. Owing to these immunostimulatory effects, levamisole elicited host defense against viral infections in pigs. Our findings demonstrate the potential of levamisole as an immunostimulatory agent.DiscussionThe results also indicate that levamisole, as an adjuvant for animal vaccines, can elicit robust innate and adaptive immune responses, thereby enhancing host defense against viral infections. This study provides a promising approach for the development of improved FMD vaccine strategies in the future.

The literature on minimally invasive techniques specifically targeting reflux in symptomatic femoral vein duplication (FVD) is limited. We present a rare case of symptomatic reflux in FVD, successfully treated with cyanoacrylate glue ablation under ultrasonographic guidance. Our findings suggest that the unique anatomy of FVD can be effectively addressed through percutaneous endovenous glue ablation, providing a technically safe and feasible alternative without open surgery. Our patient experienced symptom resolution, no post-procedural complications, and maintained stable occlusion at a 1-year follow-up. This outcome highlights the potential of endovenous glue ablation as an innovative approach in managing deep vein reflux, particularly in cases involving FVD. To broaden its application in clinical practice, further research is crucial to establish appropriate patient selection criteria and refine treatment protocols.

ABSTRACT Aim The purpose of this study was to summarise the current state of the science on diabetes mellitus education programs for nursing students. Design A systematic review and meta‐analysis. Methods Eligible studies were identified by searching PubMed, EMBASE, CINAHL, and Cochrane Library databases. Randomised controlled trials and quasi‐experimental studies, published in English between 2013 and 2022, that examined diabetes education programs for nursing students were considered in the review. The quality of the articles was evaluated using the Joanna Briggs Institute's Critical Appraisal Checklist. Key information such as authors, study focus, population, sample size, details of intervention and control group treatments, outcome variables, and main findings were extracted and summarised in a data extraction form for further analyses and syntheses. Results The literature search identified 464 articles, from which 13 studies were evaluated in the systematic review. Most studies (n = 12, 92.3%) used technology‐based teaching methods, such as high‐fidelity simulations, mobile applications, and virtual reality simulations. Regarding the evaluation of diabetes education program effectiveness, the majority of studies showed significant improvements in knowledge (n = 8, 61.5%), followed by satisfaction with learning (n = 4, 30.8%), nursing skill performance (n = 3, 23.1%), and self‐confidence (n = 3, 23.1%) in nursing students. In meta‐analyses, technology‐based teaching interventions, compared to traditional education, showed no statistically significant improvement in diabetes knowledge (standard mean difference 9.52, 95% CI [−0.18, 19.21], p = 0.05) and self‐efficacy (standard mean difference 24.09, 95% CI [−10.75, 58.92], p = 0.18). Despite this, technology‐based methods demonstrated favourable effects on knowledge and self‐efficacy against traditional education. Findings highlight the importance of emerging technology‐based diabetes education programs tailored for nursing students, crucial for enhancing positive educational outcomes. No Patient or Public Contribution.

Gelatin methacryloyl (GelMA) hydrogels are used for stem cell encapsulation in bone tissue engineering due to their fast and stable photo-crosslinking. However, cell viability and ability to induce osteogenesis are reduced by reactive oxygen species (ROS) produced during the crosslinking reaction. In this study, we developed biomimetic nanoparticles (TMNs) by combining tannic acid (TA) and simulated body fluid (SBF) minerals, and used them to synthesize GelMA-based composite hydrogels for addressing those limitations. The optimal concentrations of TA and SBF were investigated to create nanoparticles that can effectively scavenge ROS and induce osteogenesis. The incorporation of TMNs into composite hydrogels (G-TMN) significantly enhanced the survival and proliferation of encapsulated human adipose-derived stem cells (hADSCs) by providing resistance to oxidative conditions. In addition, the ions that were released, such as Ca2+ and PO43−, stimulated stem cell differentiation into bone cells. The hADSCs encapsulated in G-TMN had 2.0 ± 0.8-fold greater viability and 1.3 ± 1.8 times greater calcium deposition than those encapsulated in the hydrogel without nanoparticles. Furthermore, the in vivo transplantation of G-TMN into a subcutaneous mouse model demonstrated the rapid degradation of the gel-network while retaining the osteoinductive particles and cells in the transplanted area. The increased cellular activity observed in our multifunctional composite hydrogel can serve as a foundation for novel and effective therapies for bone deformities.

IntroductionMany countries use commercial foot-and-mouth disease (FMD) vaccines to prevent FMD pandemics, but these vaccines have disadvantages, such as repeated vaccinations due to the short persistence of antibody (Ab) titers and incomplete host defense despite high Ab titers. To address these shortcomings, we aimed to develop a novel FMD vaccine containing furfurman as an adjuvant.MethodTo demonstrate the efficacy of the test vaccine, adaptive immunity was evaluated by measuring Ab and neutralizing Ab titers and host defense against viral infections in experimental and target animals. In addition, the expression levels of cytokines [interferon (IFN)α, IFNβ, IFNγ, interleukin (IL)-1β, IL-2, and IL-12p40] were evaluated at the early stages of vaccination to confirm the simultaneous induction of cellular and humoral immune responses induced by the test vaccine.ResultThe groups that received vaccine containing furfurman showed a strong early, mid-term, and long-term immune response and host defense against viral infections compared to the control groups. The significant upregulation observed in cytokine levels in the furfurman group compared to those in the control groups strongly suggest that the test vaccine strengthens cellular immune response and effectively induces a humoral immune response.ConclusionOur study demonstrated that furfurman, as an FMD vaccine adjuvant, achieves long-lasting immunity and host defense against viral infections by eliciting potent cellular and humoral immune responses. Therefore, our findings contribute to the design of next-generation FMD vaccines and highlight the potential application of furfurman as an adjuvant for other viral diseases.

During the 2021/2022 winter season, we isolated highly pathogenic avian influenza (HPAI) H5N1 viruses harbouring an amino acid substitution from Asparagine(N) to Aspartic acid (D) at residue 193 of the hemagglutinin (HA) receptor binding domain (RBD) from migratory birds in South Korea. Herein, we investigated the characteristics of the N193D HA-RBD substitution in the A/CommonTeal/Korea/W811/2021[CT/W811] virus by using recombinant viruses engineered via reverse genetics (RG). A receptor affinity assay revealed that the N193D HA-RBD substitution in CT/W811 increases α2,6 sialic acid receptor binding affinity. The rCT/W811-HA193N virus caused rapid lethality with high virus titres in chickens compared with the rCT/W811-HA193D virus, while the rCT/W811-HA193D virus exhibited enhanced virulence in mammalian hosts with multiple tissue tropism. Surprisingly, a ferret-to-ferret transmission assay revealed that rCT/W811-HA193D virus replicates well in the respiratory tract, at a rate about 10 times higher than that of rCT/W811-HA193N, and all rCT/W811-HA193D direct contact ferrets were seroconverted at 10 days post-contact. Further, competition transmission assay of the two viruses revealed that rCT/W811-HA193D has enhanced growth kinetics compared with the rCT/W811-HA193N, eventually becoming the dominant strain in nasal turbinates. Further, rCT/W811-HA193D exhibits high infectivity in primary human bronchial epithelial (HBE) cells, suggesting the potential for human infection. Taken together, the HA-193D containing HPAI H5N1 virus from migratory birds showed enhanced virulence in mammalian hosts, but not in avian hosts, with multi-organ replication and ferret-to-ferret transmission. Thus, this suggests that HA-193D change increases the probability of HPAI H5N1 infection and transmission in humans.

Extracellular vesicles (EVs) are involved in cell-to-cell communication. Following uptake, EV cargo molecules, including DNA, RNA, lipids, and proteins, influence gene expression and molecular signaling in recipient cells. Although various studies have identified disease-specific EV molecules, further research into their biogenesis and secretion mechanisms is needed for clinical application. Here, we investigated the role of UPF2 in regulating the biogenesis and components of EVs. Notably, UPF2 promoted the expression of CD81, a membrane protein marker of EVs, as UPF2 silencing decreased CD81 levels in EVs, both inside the cell and secreted. In contrast, the expression levels of CD63 increased, without altering the size or numbers of EVs. In addition, reducing UPF2 levels did not affect the total number of EVs but lowered production of CD81-positive EVs and reduced the efficiency of uptake by recipient cells. Collectively, our findings uncover a novel function for UPF2 in regulating the production of CD81 and changing EV properties.

Background This study examines integrating physical and mental healthcare for disadvantaged persons with type 2 diabetes mellitus and mild-to-moderate depression in the community, using a mobile application within a public-private-academic partnership. Methods The Korean Diabetes Association has developed a mobile application combining behavioral activation for psychological well-being and diabetes self-management, with conventional medical therapy. Participants were randomly assigned to receive the application with usual care or only usual care. Primary outcomes measured changes in psychological status and diabetes self-management through questionnaires at week 12 from the baseline. Secondary outcomes assessed glycemic and lipid control, with psychological assessments at week 16. Results Thirty-nine of 73 participants completed the study (20 and 19 in the intervention and control groups, respectively) and were included in the analysis. At week 12, the intervention group showed significant reductions in depression severity and perceived stress compared to the control group. Additionally, they reported increased perceived social support and demonstrated improved diabetes self-care behavior. These positive effects persisted through week 16, with the added benefit of reduced anxiety. While fasting glucose levels in the intervention group tended to improve, no other significant differences were observed in laboratory assessments between the groups. Conclusion This study provides compelling evidence for the potential efficacy of a mobile application that integrates physical and mental health components to address depressive symptoms and enhance diabetes self-management in disadvantaged individuals with type 2 diabetes mellitus and depression. Further research involving larger and more diverse populations is warranted to validate these findings and solidify their implications.

Abstract Globally, hip fractures represent a significant and growing public health concern, particularly as the elderly population increases. The timing for surgery following hospitalization for hip fractures is a crucial indicator of acute quality care following recommended surgical guidelines of within two days to minimize complications and mortality. However, factors influencing delayed surgery and its outcomes remain debated. This study, used a national administrative database in South Korea, aimed to examine surgery performed within two days of hospitalization and investigate factors affecting delayed surgical interventions and associated outcomes. Of the hip fracture patients analyzed, 40.6% underwent surgery within two days of hospitalization. Factors associated with delayed surgery included: male patients (OR 1.190; 95% CI 1.022 ~ 1.385), medical aid beneficiary (OR 1.385; 95% CI 1.120 ~ 1.713), higher comorbidity index (OR 1.365; 95% CI 1.163 ~ 1.603, OR 1.612, 95% CI 1.327 ~ 1.958), weekends admission (OR 2.384; 95% CI 2.804 ~ 2.729), admission via outpatient department (OR 1.298, 95% CI 1.071 ~ 1.574). ORIF (OR 0.823, 95% CI 0.691 ~ 0.980) was associated with a significantly low risk of late surgery. While early surgery did not significantly impact in-hospital mortality or complications, it was associated with short and postoperative lengths of stay. This study underscores the need for prompt surgical intervention, particularly in high-risk patient populations, as well as highlights the importance of further research to elucidate the relationship between the timing of surgery and postoperative outcomes.

Abstract The direct access of olfactory afferents to memory-related cortical systems has inspired theories about the role of the olfactory pathways in the development of cortical neurodegeneration in Alzheimer’s disease (AD). In this study, we used baseline olfactory identification measures with longitudinal flortaucipir and PiB PET, diffusion MRI of 89 cognitively normal older adults (73.82 ± 8.44 years; 56% females), and a transcriptomic data atlas to investigate the spatiotemporal spreading and genetic vulnerabilities of AD-related pathology aggregates in the olfactory system. We find that odor identification deficits are predominantly associated with tau accumulation in key areas of the olfactory pathway, with a particularly strong predictive power for longitudinal tau progression. We observe that tau spreads from the medial temporal lobe structures toward the olfactory system, not the reverse. Moreover, we observed a genetic background of odor perception-related genes that might confer vulnerability to tau accumulation along the olfactory system.

Purpose The rapid expansion of robotic surgical equipment necessitates a review of the needs and challenges faced by hospitals introducing robots for the first time to compete with experienced institutions. The aim of this study was to analyze the impact of robotic surgery on our hospital compared to open and laparoscopic surgery, examine internal transformations, and assess regional, domestic, and international implications. Methods A retrospective review was conducted of electronic medical records (EMRs) from 2019 to 2022 at Inha University Hospital, including patients who underwent common robotic procedures and equivalent open and laparoscopic operations. The study investigated clinical and operational performance changes in the hospital after the introduction of robotic technology. It also evaluated the operational effectiveness of robot implementation in local, national, and international contexts. To facilitate comparison with other hospitals, the data were transmitted to Intuitive Surgical, Inc. for analysis. The study was conducted in compliance with domestic personal information regulations and received approval from our Institutional Review Board. Results We analyzed EMR data from 3,147 patients who underwent surgical treatment. Over a period of 3.5 years, the adoption of robotic technology in a hospital setting significantly enhanced the technical skills of all professors involved. The introduction of robotic systems led to increased patient utilization of conventional surgical techniques, as well as a rise in the number of patients choosing robotic surgery. This collective trend contributed to an overall increase in patient numbers. This favorable evaluation of the operational effectiveness of our hospital’s robot implementation in the context of local, national, and global factors is expected to positively influence policy changes. Conclusions Stakeholders should embrace data science and evidence-based techniques to generate valuable insights from objective data, assess the health of robot-assisted surgery programs, and identify opportunities for improvement and excellence.

Abstract This study evaluated an oscillometric device (OD), Microlife WatchBP Office AFIB, and a hybrid manual auscultatory device (AD), Greenlight 300TM, to determine a suitable blood pressure (BP) measurement device for the Korea National Health and Nutrition Examination Survey in a mercury‐free context. Adhering to the 2018 Universal Standard's suggested consensus, the study involved 800 subjects (mean age 51.2 ± 17.5 years; 44.3% male), who underwent triplicate BP measurements following 5 min of rest in a randomized order (OD‐first: 398 participants; AD‐first: 402 participants). BP difference was calculated as OD value minus AD value, with results stratified by measurement sequence. The overall BP difference and tolerable error probability were ‐1.1 ± 6.5/‐2.6 ± 4.9 mmHg and 89.2%/92.5% for systolic/diastolic BP (SBP/DBP), respectively. Lin's concordance correlation coefficient was 0.907/0.844 for SBP/DBP (OD‐first/AD‐first: 0.925/0.892 for SBP, 0.842/0.845 for DBP). The overall agreement for hypertension (BP ≥ 140 and/or 90 mmHg) was 0.71 (p

Abstract Background Several PD-1 antibodies approved as anti-cancer therapies work by blocking the interaction of PD-1 with its ligand PD-L1, thus restoring anti-cancer T cell activities. These PD-1 antibodies lack inter-species cross-reactivity, necessitating surrogate antibodies for preclinical studies, which may limit the predictability and translatability of the studies. Results To overcome this limitation, we have developed an inter-species cross-reactive PD-1 antibody, GNUV201, by utilizing an enhanced diversity mouse platform (SHINE MOUSE™). GNUV201 equally binds to human PD-1 and mouse PD-1, equally inhibits the binding of human PD-1/PD-L1 and mouse PD-1/PD-L1, and effectively suppresses tumor growth in syngeneic mouse models. The epitope of GNUV201 mapped to the “FG loop” of hPD-1, distinct from those of Keytruda® (“C’D loop”) and Opdivo® (N-term). Notably, the structural feature where the protruding epitope loop fits into GNUV201’s binding pocket supports the enhanced binding affinity due to slower dissociation (8.7 times slower than Keytruda®). Furthermore, GNUV201 shows a stronger binding affinity at pH 6.0 (5.6 times strong than at pH 7.4), which mimics the hypoxic and acidic tumor microenvironment (TME). This phenomenon is not observed with marketed antibodies (Keytruda®, Opdivo®), implying that GNUV201 achieves more selective binding to and better occupancy on PD-1 in the TME. Conclusions In summary, GNUV201 exhibited enhanced affinity for PD-1 with slow dissociation and preferential binding in TME-mimicking low pH. Human/monkey/mouse inter-species cross-reactivity of GNUV201 could enable more predictable and translatable efficacy and toxicity preclinical studies. These results suggest that GNUV201 could be an ideal antibody candidate for anti-cancer drug development.

Abstract Social Network Analysis (SNA) provides a dynamic framework for examining interactions and connections within networks, elucidating how these relationships impact behaviors and outcomes. This study targeted small residential communities in Gangwon State, South Korea, to explore network formation theories and derive strategies for enhancing health promotion services in rural communities. Conducted in 12 small residential areas, the survey led to a network categorization model distinguishing networks as formal, informal, or non-existent. Key findings demonstrated that demographic and socio-economic factors, specifically age, income, living environment, leisure activities, and education level, significantly influence network formation. Importantly, age, environmental conditions, satisfaction with public transportation, and walking frequency were closely associated with the evolution of formal networks. These results highlight the importance of early community network assessments, which must consider distinct network traits to develop effective health promotion models. Utilizing SNA early in the assessment process can improve understanding of network dynamics and optimize the effectiveness of health interventions.

Mucopolysaccharidosis (MPS) IVA (Morquio A syndrome) is an autosomal recessive lysosomal storage disorder caused by a mutation affecting the enzyme N-acetylgalactosamine-6-sulfatase (EC 3.1.6.4, GALNS). Enzyme replacement therapy (ERT) has been shown to improve physical performance, quality of life, and respiratory function in patients with MPS IVA; however, owing to the rarity of MPS IVA, data on Korean patient characteristics are limited. This retrospective study reports clinical, radiographic, biochemical, and molecular findings, and analyzes long-term clinical outcomes, from the largest cohort of Korean patients with MPS IVA in a single center. The analysis included 17 patients from 14 families (58.8 % females; median [range] age at diagnosis 5.2 [1.8–33.7] years). The majority of patients (64.7 %) were classified as having a severe phenotype, 23 % had an intermediate phenotype, and 11.8 % had an attenuated phenotype. Skeletal manifestations and radiologic abnormalities at initial diagnosis included gait abnormality (35.3 %), short stature (23.5 %), chest deformity (23.5 %), scoliosis (17.6 %), kyphosis (11.8 %), dysmorphic face (6 %), hip pain (6 %), and leg deformity (6 %). Twelve different GALNS mutations were identified. Patients received ERT for a median (range) 7.4 years (3.0–12.1). Twelve patients reached final adult height, and all patients with the severe/intermediate phenotype had short stature (

This study evaluated the physical and rheological properties of whole rice flour treated for different sonication times (0–15 min). Ultrasonication reduces the particle size of rice flour and improves its solubility. Viscosity tests using RVA and steady shear showed a notable decrease in the viscosity of the rehydrated pregelatinized rice flour. Although no unusual patterns were observed in the XRD analysis, the FT-IR and microstructure morphology findings suggest that ultrasonication led to structural changes in the rice flour. Overall, the study indicates that ultrasonication is a practical and clean method for producing plant-based drinks from rice flour, which could expand its limited applications in the beverage industry.

Here, we present the outcomes of four patients with COVID-19 who underwent hematopoietic stem cell transplantation (HSCT) at the National Cancer Center in South Korea. Despite concerns about the unfavorable course of COVID-19 in HSCT recipients, none of our patients experienced severe COVID-19. Moreover, extended viral shedding in case 1, lasting over 100 days, was resolved after successful engraftment. Contracting the virus when the host could not mount enough of an immune reaction might result in a paradoxically favorable course. Vaccination, monoclonal antibodies, and antiviral agent usage against COVID-19 might also be effective. We suggest, if necessary, HSCT should not be deferred in COVID-19 patients.

Dual leucine zipper kinase (DLK) mediates multiple neuronal stress responses, and its expression levels are constantly suppressed to prevent excessive stress signaling. We found that Wallenda (Wnd), the Drosophila ortholog of DLK, is highly enriched in the axon terminals of Drosophila sensory neurons in vivo and that this subcellular localization is necessary for Highwire-mediated Wnd protein turnover under normal conditions. Our structure-function analysis found that Wnd palmitoylation is essential for its axon terminal localization. Palmitoylation-defective Wnd accumulated in neuronal cell bodies, exhibited dramatically increased protein expression levels, and triggered excessive neuronal stress responses. Defective intracellular transport is implicated in neurodegenerative conditions. Comprehensive dominant-negative Rab protein screening identified Rab11 as an essential factor for Wnd localization in axon terminals. Consequently, Rab11 loss-of-function increased the protein levels of Wnd and induced neuronal stress responses. Inhibiting Wnd activity significantly ameliorated neuronal loss and c-Jun N-terminal kinase signaling triggered by Rab11 loss-of-function. Taken together, these suggest that DLK proteins are constantly transported to axon terminals for protein turnover and a failure of such transport can lead to neuronal loss. Our study demonstrates how subcellular protein localization is coupled to protein turnover for neuronal stress signaling.

IntroductionEmerging evidence highlights the potential advantages of the Mediterranean diet (MD) in preserving kidney function and slowing chronic kidney disease (CKD) progression. However, interventional studies on the MD are scarce in East Asian populations.MethodsThis randomized crossover trial aimed to assess the safety and short-term impact of the Mediterranean Proper Optimal Balance (MEDi-POB) diet in Korean patients with stage 3–4 CKD. Kidney function was assessed using the estimated glomerular filtration rate, which was calculated using the CKD Epidemiology Collaboration equation. Fifty patients with CKD were randomly assigned to two groups, each starting with a different 4-week intervention, followed by a 4-week washout period, followed by a switch to the other 4-week intervention. During the MEDi-POB intervention, patients received home delivery of meals twice daily, 5 days a week, while the control intervention comprised a conventional diet. Forty-six patients successfully completed the entire 12-week trial. Paired t-tests were conducted to assess mean differences between the two groups. A linear mixed model was used to adjust for sequence and period.ResultsDietary fat, fiber, and niacin intake were significantly higher following the MEDi-POB diet than following the control diet (p = 0.001 for fat, p < 0.001 for fiber, and p = 0.007 for niacin). The MEDi-POB diet also yielded slightly increased total CO2 levels (p = 0.043), indicating effective management of metabolic acidosis. Conversely, sodium and copper intake were significantly lower with the MEDi-POB diet (p = 0.032 and p = 0.037, respectively). Caloric intake increased, but body mass index slightly decreased from baseline after consuming the MEDi-POB diet. Dietary potassium intake exhibited a non-significant increase (p = 0.053), and no significant changes in serum (p = 0.883) and urine potassium levels (p = 0.087) occurred. Kidney function remained well-preserved following the MEDi-POB diet.ConclusionThese results indicate that the MEDi-POB diet is safe even in patients with advanced CKD, as it does not adversely affect serum and urine potassium levels and helps maintain kidney function.

Introduction Randomised controlled trials (RCTs) of early childhood home-visiting interventions led by nurses have been conducted mainly in Western countries, whereas such trials have been limited in non-Western cultures, including Asia. In South Korea, a national nurse home visit programme (Korea Early Childhood Home-visiting Intervention (KECHI)) was developed in 2020 and launched throughout the country. We designed a pragmatic RCT to evaluate the effectiveness of KECHI on child health and development and maternal health.Methods and analysis Eligible participants will be pregnant women at

Chronic low-grade inflammation is a hallmark of aging, aka “inflammaging”, which is linked to a wide range of age-associated diseases. Immune dysfunction increases disease susceptibility, and increases morbidity and mortality of aging. Innate immune cells, including monocytes, macrophages and neutrophils, are the first responders of host defense and the key mediators of various metabolic and inflammatory insults. Currently, the understanding of innate immune programming in aging is largely fragmented. Here we investigated the phenotypic and functional properties of innate immune cells in various peripheral tissues of young and aged mice under normal and endotoxic conditions. Under the steady state, aged mice showed elevated pro-inflammatory monocytes/macrophages in peripheral blood, adipose tissue, liver, and colon. Under lipopolysaccharide (LPS)-induced inflammatory state, the innate immune cells of aged mice showed a different response to LPS stimulus than that of young mice. LPS-induced immune responses displayed differential profiles in different tissues and cell types. In the peripheral blood, when responding to LPS, the aged mice showed higher neutrophils, but lower pro-inflammatory monocytes than that in young mice. In the peritoneal fluid, while young mice exhibited significantly elevated pro-inflammatory neutrophils and macrophages in response to LPS, aged mice exhibited decreased pro-inflammatory neutrophils and variable cytokine responses in macrophages. In the adipose tissue, LPS induced less infiltrated neutrophils but more infiltrated macrophages in old mice than young mice. In the liver, aged mice showed a more robust increase of pro-inflammatory macrophages compared to that in young mice under LPS stimulation. In colon, macrophages showed relatively mild response to LPS in both young and old mice. We have further tested bone-marrow derived macrophages (BMDM) from young and aged mice, we found that BMDM from aged mice have impaired polarization, displaying higher expression of pro-inflammatory markers than those from young mice. These data collectively suggest that innate immunity in peripheral tissues is impaired in aging, and the dysregulation of immunity is tissue- and cell-dependent. Our findings in the rodent model underscore the complexity of aging immunity. Further investigation is needed to determine whether the immune profile observed in aged mice is applicable in age-associated diseases in humans.

IntroductionNocardia farcinica is an opportunistic bacterium that causes bovine mastitis and pulmonary, cutaneous, and central nervous system infections in humans. Bovine abortion caused by N. farcinica has been sporadically reported. The purpose of this study was to analyze the pathological findings of bovine abortions caused by N. farcinica in the Republic of Korea and determine the antimicrobial resistance and genotypical characteristics of N. farcinica isolates.Case presentationThree cases of bovine abortions were submitted to the Animal and Plant Quarantine Agency for differential diagnosis. Grossly, one fetus showed severe lung consolidation following palpation of the entire lobes. Histologically, necrotizing granulomatous interstitial pneumonia was observed in all fetuses; a fetus with a gross lesion demonstrated necrotizing lymphadenitis in the mesenteric lymph nodes and necrotizing dermatitis in the ear. N. farcinica isolates were isolated from the abomasal contents and lungs of all fetuses. Finally, two cases were diagnosed as abortions due to N. farcinica, and one was diagnosed as an N. farcinica abortion coinfected with bovine viral diarrhea virus. According to the multilocus sequence analysis, all isolates were identified as N. farcinica and were determined to be genetically related to isolates from humans. Two N. farcinica isolates were resistant to trimethoprim-sulfamethoxazole, which is recommended as the first treatment for human nocardial infections.ConclusionThis is the first pathological report of bovine abortion caused by N. farcinica in the Republic of Korea. Further studies are needed to phenotypically and genotypically characterize N. farcinica isolates with various sources and continuously monitor antimicrobial resistance patterns.

Abstract This retrospective study aimed to determine risk factors associated with post-operative bleeding after dentoalveolar surgery in patients taking anticoagulants. Patients taking anticoagulants who were planned to undergo periodontal flap operation, tooth extraction or implant surgery were included. Patients were divided into two subgroups according to the maintenance of anticoagulants following medical consultation: (1) maintenance group and (2) discontinuation group. The analysed patient-related factors included systemic diseases, maintenance of anticoagulants and types of anticoagulant. Intra- and post-operative treatment-related factors, haemostatic methods and post-operative bleeding were collected for statistical analyses. There were 35 post-operative bleeding complications (6.5%) in the 537 included patients: 21 (8.6%) in maintenance group and 14 (4.8%) in discontinuation group. The type of anticoagulant (p = 0.037), tooth extraction combined with bone grafting (p = 0.016) and type of implant surgery (p = 0.032) were significantly related to the post-operative bleeding rate. In the maintenance group, atrial fibrillation [odds ratio (OR) = 6.051] and vitamin K inhibitors (OR = 3.679) were associated with a significantly higher bleeding risk. From this result, it can be inferred that the decision to continue anticoagulants should be made carefully based on the types of anticoagulant and the characteristics of dentoalveolar surgeries performed: extraction with bone grafting, multiple implantations and involvement of maxillary arch.

Abstract Background Unawareness is a behavioral condition characterized by a lack of self-awareness of objective memory decline. In the context of Alzheimer’s Disease (AD), unawareness may develop in predementia stages and contributes to disease severity and progression. Here, we use in-vivo multi-modal neuroimaging to profile the brain phenotype of individuals presenting altered self-awareness of memory during aging. Methods Amyloid- and tau-PET (N = 335) and resting-state functional MRI (N = 713) imaging data of individuals from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4)/Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study were used in this research. We applied whole-brain voxel-wise and region-of-interest analyses to characterize the cortical intersections of tau, amyloid, and functional connectivity networks underlying unawareness in the aging brain compared to aware, complainer and control groups. Results Individuals with unawareness present elevated amyloid and tau burden in midline core regions of the default mode network compared to aware, complainer or control individuals. Unawareness is characterized by an altered network connectivity pattern featuring hyperconnectivity in the medial anterior prefrontal cortex and posterior occipito-parietal regions co-locating with amyloid and tau deposition. Conclusions Unawareness is an early behavioral biomarker of AD pathology. Failure of the self-referential system in unawareness of memory decline can be linked to amyloid and tau burden, along with functional network connectivity disruptions, in several medial frontal and parieto-occipital areas of the human brain.

Purpose Electroencephalography (EEG) is useful for clarifying the association between cortical activity and cognitive processes in children. We investigated whether EEG abnormalities were correlated with developmental delay/intellectual disability (DD/ID) in the absence of clinical seizures. Methods We retrospectively identified 166 children with DD/ID who underwent EEG at Pusan National University Hospital between January 2011 and December 2021. We compared clinical characteristics and test results between those with normal and those with abnormal EEGs. Additionally, we analyzed EEG abnormalities in relation to neurodevelopmental disorders, specifically autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Results Of the 166 patients, 39 (23.5%) displayed abnormal EEGs, while 127 (76.5%) had normal EEGs. Of the former, 25 (64.1%) patients exhibited epileptiform discharges, including 22 (56.3%) with focal and three (7.7%) with generalized discharges. Focal discharges most frequently affected the central area (35.9%). Twenty patients (51.3%) exhibited rhythmic slowing patterns. Epilepsy diagnoses were significantly more common among patients with abnormal EEGs (n=8, 20.5%) than among those with normal EEGs (n=9, 7.1%) (P

Purpose The clinical characteristics of headaches vary by age among pediatric patients. Red flag signs are key factors in differentiating secondary headaches and should be considered in the context of the patient’s age. Methods This study involved a retrospective chart review of pediatric patients presenting with headaches. Patients were categorized by age into three groups: pre-school age (under 6 years), school-age (6 to 12 years), and adolescence (over 12 years). Demographic data, headache characteristics, laboratory findings, and neuroimaging results were evaluated. Overall, 17 potential red flags were assessed. Results A total of 687 patients were included, of whom 102 were of pre-school age, 314 were school-aged, and 271 were adolescents. The frequency of overweight/obesity was found to increase with age. The pre-school age group experienced a shorter period from symptom onset to presentation and a briefer duration of pain. In contrast, adolescents displayed a longer period from symptom onset, a greater frequency of headaches occurring at least three times per week, and a higher rate of headache episodes lasting over 3 days. Children under 6 years old were more commonly diagnosed with secondary headaches than older children. Across age groups, secondary headaches were suspected when systemic symptoms such as fever were present, when the headache had a sudden onset, when the patient responded poorly to medication, or when abnormal neurological signs and symptoms were observed. Conclusion The clinical features of pediatric patients vary by age group. Clinicians should consider red flag signs in the context of patient age and individual characteristics.

Abstract Distant metastasis is a significant hallmark affecting to the high death rate of patients with triple-negative breast cancer (TNBC). Thus, it is crucial to identify and develop new therapeutic strategies to hinder cancer metastasis. While emerging studies have hinted a pivotal role of glucose-regulated protein 94 (GRP94) in tumorigenesis, the exact biological functions and molecular mechanisms of GRP94 in modulating cancer metastasis remain to be elucidated. Our study demonstrated an increased expression of GRP94 in TNBC correlated with metastatic progression and unfavorable prognosis in patients. Functionally, we identified that GRP94 depletion significantly diminished TNBC tumorigenesis and subsequent lung metastasis. In contrast, GRP94 overexpression exacerbated the invasiveness, migration, and lung metastasis of non-TNBC cells. Mechanistically, we found that casein kinase 2 alpha (CK2α) active in advanced breast cancer phosphorylated GRP94 at a conserved serine 306 (S306) residue. This phosphorylation increased the stability of GRP94 and enhanced its interaction with LRP6, leading to activation of canonical Wnt signaling. From a therapeutic standpoint, we found that benzamidine, a novel CK2α inhibitor, effectively suppressed GRP94 phosphorylation, LRP6 stabilization, and metastasis of TNBC. Our results point to the critical role of CK2α-mediated GRP94 phosphorylation in TNBC metastasis through activation of Wnt signaling, highlighting GRP94 as a therapeutic target to impede TNBC metastasis.

Abstract Objectives This study aimed to investigate arterial stiffness index, physical activity, and food and nutrient intake in middle-aged adults over 40 years when the incidence of cardiovascular disease begins to increase. Methods This study included 106 subjects (48 males and 58 females) aged between 40 and 64 years. The arterial stiffness index (brachial-ankle pulse wave velocity [baPWV], and ankle-brachial index [ABI]) were measured using a blood pressure pulse wave testing device. Physical activity was assessed using the Korean version of the Global Physical Activity Questionnaire, and food and nutrient intake was calculated using the Food Frequency Questionnaire. Results The mean age of the subjects was 54.4 years. Although the ABI of the subjects was within the normal range, they were divided into tertiles to compare physical activity and food and nutrient intake. In males, the time spent on moderate to vigorous physical activity (MVPA) was significantly higher in T3 (600.6 min/week) than in T1 (304.4 min/week). In females, the time spent in sedentary behavior was significantly lower in T3 (294.5 min/week) than in T1 (472.1 min/week). In addition, the frequency of fish consumption was significantly higher in T3 (1.27 frequency/day) than in T1 (0.64 frequency/day) in females. Polyunsaturated fatty acid (PUFA) and ω-3 fatty acid intake, adjusted for energy intake, were significantly positively correlated with ABI (r = 0.200 and r = 0.218, respectively). Conclusions High MVPA (in males), low sedentary behavior (in females), and PUFA and ω-3 fatty acid intake through fish consumption may be associated with low peripheral artery stiffness. Therefore, arteriosclerosis can be prevented through physical activity and proper dietary therapy.

Abstract Importance The burden of caring for children with complex medical problems such as major congenital anomalies falls principally on mothers, who in turn suffer a variety of potentially severe economic consequences. As well, health consequences of caregiving often further impact the social and economic prospects of mothers of children with major congenital anomalies (MCMCAs). Evaluating the long-term economic consequences of extensive in-home caregiving among MCMCAs can inform strategies to mitigate these effects. Objective To assess whether MCMCAs face reduced employment and increased need for disability benefits over a 20-year period. Design A population-based matched cohort study. Setting Denmark. Participants All women who gave birth to a singleton child with a major congenital anomaly in Denmark between January 1, 1997 and December 31, 2017 (n = 23,637) and a comparison cohort of mothers matched by maternal age, parity, and infant’s year of birth (n = 234,586). Exposures Liveborn infant with a major congenital anomaly. Main outcomes and measures The primary outcome was mothers’ employment status, stratified by their child’s age. Employment status was categorized as employed, outside the workforce (on temporary leave, holding a flexible job, or pursuing education), or unemployed; the number of weeks in each category was measured over time. The secondary outcome was time to receipt of a disability pension, which in Denmark implies permanent exit from the labor market. We used a negative binomial regression model to estimate the number of weeks in each employment category, stratified by the child’s age (i.e., 0–1 year, > 1–6 years, 7–13 years, 14–18 years). A Cox proportional hazards regression model was used to compute hazard ratios as a measure of the relative risk of receiving a disability pension. Rate ratios and hazard ratios were adjusted for maternal demographics, pregnancy history, health, and infant’s year of birth. Results During 1–6 years after delivery, MCMCAs were outside the workforce for a median of 50 weeks (IQR, 6–107 weeks), while members of the comparison cohort were outside the workforce for a median of 48 weeks (IQR, 4–98 weeks), corresponding to an adjusted rate ratio [ARR] of 1.05 (95% confidence interval [CI], 1.04–1.07). During the first year after delivery, MCMCAs were more likely to be employed than mothers in the comparison cohort (ARR, 1.08; 95% CI, 1.06–1.10). At all timepoints thereafter, MCMCAs had a lower rate of workforce participation. The rate of being outside the workforce was 5% higher than mothers in the comparison cohort during 1–6 years after delivery (ARR, 1.05; 95% CI, 1.04–1.07), 9% higher during 7–13 years after delivery (ARR, 1.09; 95% CI, 1.06–1.12), and 12% higher during 14–18 years after delivery (ARR, 1.12; 95% CI, 1.07–1.18). Overall, MCMCAs had a 20% increased risk of receiving a disability pension during follow-up than mothers in the matched comparison cohort [incidence rates 3.10 per 1000 person-years (95% CI, 2.89–3.32) vs. 2.34 per 1000 person-years (95% CI, 2.29–2.40), adjusted hazard ratio, 1.20; 95% CI, 1.11–1.29]. Conclusion and relevance MCMCAs were less likely to participate in the Danish workforce, less likely to be employed, and more likely to receive disability pensions than mothers of unaffected children. The rate of leaving the workforce intensified as their affected children grew older. The high demands of caregiving among MCMCAs may have long-term employment consequences even in nations with comprehensive and heavily tax-supported childcare systems, such as Denmark.

Abstract Clinical implication of a single abnormal value (SAV) in the 100 g oral glucose tolerance test during pregnancy has not been established. We aimed to evaluate the risk of postpartum type 2 diabetes mellitus (T2DM) and investigate adverse pregnancy outcomes in women with SAV, using a retrospective database, from seven medical centers of Korea. Based on the Carpenter-Coustan criteria using two-step approach, pregnancy and postpartum outcomes were compared, among normoglycemic, SAV, and gestational diabetes mellitus (GDM) groups. Among 9353 women, 342 (3.66%) and 418(4.47%) women were included in SAV and GDM groups, respectively. SAV and GDM groups showed significantly higher rates of postpartum T2DM than normoglycemic group (7.60%, 14.83%, and 1.82%, respectively, p

The prevalence of obesity in children and adolescents has been gradually increasing in recent years and has become a major health problem. Childhood obesity can readily progress to adult obesity. It is associated with obesity-related comorbidities, such as type 2 diabetes mellitus, hypertension, obstructive sleep apnea, non-alcoholic fatty liver disease, and the risk factor for cardiovascular disease. It is important to make an accurate assessment of overweight and obesity in children and adolescents with consideration of growth and development. Childhood obesity can then be prevented and treated using an appropriate treatment goal and safe and effective treatment strategies. This article summarizes the clinical practice guidelines for obesity in children and adolescents that are included in the 8th edition of the Clinical Practice Guidelines for Obesity of the Korean Society for the Study of Obesity.