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Abstract Objective The effect of body composition change on the risk of dementia is not clear. This study analyzed the associations of changes in predicted lean body mass index (pLBMI), predicted appendicular skeletal muscle mass index (pASMI), and predicted body fat mass index (pBFMI) with the risk of dementia. Methods In this nationwide cohort study, data were obtained from the Korean National Health Insurance Service database. The exposure was defined as changes in pLBMI, pASMI, and pBFMI derived from validated prediction equations. The outcome was dementia, defined based on the dementia diagnosis with prescription of anti‐dementia medication. Cox proportional hazards regression analyses were performed to obtain the hazard ratio with a 95% confidence interval for risk of dementia according to changes in predicted body composition. Results A total of 13,215,208 individuals with no prior record of dementia who underwent health screenings twice between 2009–2010 and 2011–2012 were included. A 1‐kg/m2 increase in pLBMI and pASMI had an association with reduced risk of dementia (aHR: 0.85, 95% CI 0.84–0.87; aHR: 0.70, 95% CI 0.69–0.72, respectively for men, and aHR: 0.69, 95% CI 0.67–0.71; aHR: 0.59, 95% CI 0.57–0.61, respectively for women). A 1‐kg/m2 increase in pBFMI had an association with a raised risk of dementia (aHR: 1.19, 95% CI 1.17–1.21 for men and aHR: 1.53, 95% CI 1.48–1.57 for women). These results remained consistent regardless of sex or weight change. Interpretation Increase in pLBMI or pASMI, or reduction in pBFMI was linked to lower risk of dementia.

Abstract Increased production of reactive oxygen species (ROS) leads to oxidative stress, with its damaging effect extending to the mitochondria and plasma membrane. Further, prolonged inflammation can result in chronic disease development. The marine microdiatom Odontella aurita is recognized for its potential in food and pharmaceutical development. Moreover, it contains antioxidant and anti-inflammatory properties. However, studies regarding the efficacy of their varying extract forms and their underlying mechanisms remain scarce. Therefore, this study aims to explore the antioxidant and anti-inflammatory effects of Odontella aurita extracts obtained using various extraction methods (hot water, 70% ethanol, and chloroform:methanol (CM)). Among the three Odontella aurita extracts, the CM extract demonstrated superior efficacy in protecting RAW 264.7 cells from H2O2-induced cytotoxicity. It significantly lowered the levels of ROS and enhanced the expression of superoxide dismutase and glutathione peroxidase. Furthermore, the CM extract outperformed other extracts in inhibiting LPS-induced nitric oxide production, reducing mRNA levels in nitric oxide synthase, cyclooxygenase, and the proinflammatory cytokines interleukin IL-1β, IL-6, TNFα. Additionally, CM extract effectively suppressed the activation of NF-κB/IκBα and JAK2-STAT3 in LPS-induced RAW 264.7 cells. HPLC–UV analysis revealed a remarkable 33-fold higher fucoxanthin content in CM compared to the ethanol extract. GC–MS analysis identified elevated levels of cholest-5-en-3-ol, phytol, eicosapentaenoic acid methyl ester, methyl palmitate, palmitoleic acid methyl ester, and neophytadiene in the CM extract. These findings suggest that Odontella aurita CM extract is a promising antioxidant candidate for preventing or treating inflammatory diseases, consequently emphasizing its potential for further development. Graphical Abstract

Background There is still a lack of research on which diabetic drugs are more effective in preventing stroke. Our network metaanalysis aimed to compare cerebrovascular benefits among glucose-lowering treatments. Methods We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry for clinical trials from inception through May 25, 2021. We included both prespecified cerebrovascular outcomes and cerebrovascular events reported as severe adverse events. Subgroup analyses were conducted by stroke subtype, publication type, age of patients, baseline glycosylated hemoglobin (HbA1c), duration of type 2 diabetes mellitus, and cardiovascular risks. Results Of 2,861 reports and 1,779 trials screened, 79 randomized controlled trials comprising 206,387 patients fulfilled the inclusion criteria. In the pairwise meta-analysis, the use of glucagon-like peptide-1 (GLP-1) agonist was associated with a lower risk of total stroke compared with placebo (relative risk [RR], –0.17; 95% confidence interval [CI], –0.27 to –0.07). In the network meta-analysis, only the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitor was associated with a reduction of total stroke, compared with placebo (RR, 0.81; 95% CI, 0.67 to 0.98). In the subgroup analyses, the use of SGLT-2 inhibitor and GLP-1 agonist was associated with a lower risk of stroke in those with high HbA1c (≥8.0) and low-risk of cardiovascular disease, respectively. Conclusion SGLT-2 inhibitors and GLP-1 agonists were shown to be beneficial for stroke prevention in patients with type 2 diabetes mellitus.

Abstract Although some studies conducted about the risk of cholecystectomy and cardiovascular disease, there was a limit to explaining the relationship. We investigated the short-term and long-term relationship between cholecystectomy and cardiovascular disease, and evidence using the elements of the metabolic index as an intermediate step. It was a retrospective cohort study and we used the National Health Insurance Service database of South Korea between 2002 and 2015. Finally, 5,210 patients who underwent cholecystectomy and 49,457 at 1:10 age and gender-matched controls of subjects were collected. The main results was estimated by Multivariate Cox proportional hazard regression to calculate the hazard ratio (HR) with 95% confidence interval (CI) for risk of cardiovascular disease after cholecystectomy. Regarding short-term effects of cholecystectomy, increased risk of cardiovascular disease (aHR 1.35, 95% CI 1.15–1.58) and coronary heart disease (aHR 1.77, 95% CI 1.44–2.16) were similarly seen within 2 years of surgery. When analyzing the change in metabolic risk factors, cholecystectomy was associated with a change in systolic blood pressure (adjusted mean [aMean]: 1.51, 95% CI: [− 1.50 to − 4.51]), total cholesterol (aMean − 14.14, [− 20.33 to 7.95]) and body mass index (aMean − 0.13, [− 0.37 to 0.11]). Cholecystectomy patients had elevated risk of cardiovascular disease in the short-term, possibly due to the characteristics of the patient before surgery. The association of cholecystectomy and cardiovascular disease has decreased after 2 years in patients who underwent cholecystectomy, suggesting that because of improvement of metabolic health, cholecystectomy-associated elevation of cardiovascular disease risk may be ameliorated 2 years after cholecystectomy.

Introduction Kidney transplantation is the preferred therapy for children with stage 5 chronic kidney disease (CKD-5). However, there is a wide variation in access to kidney transplantation across the UK for children. This study aims to explore the psychosocial factors that influence access to and outcomes after kidney transplantation in children in the UK using a mixed-methods prospective longitudinal design.Methods Qualitative data will be collected through semistructured interviews with children affected by CKD-5, their carers and paediatric renal multidisciplinary team. Recruitment for interviews will continue till data saturation. These interviews will inform the choice of existing validated questionnaires, which will be distributed to a larger national cohort of children with pretransplant CKD-5 (n=180) and their carers. Follow-up questionnaires will be sent at protocolised time points regardless of whether they receive a kidney transplant or not. Coexisting health data from hospital, UK renal registry and National Health Service Blood and Transplant registry records will be mapped to each questionnaire time point. An integrative analysis of the mixed qualitative and quantitative data will define psychosocial aspects of care for potential intervention to improve transplant access.Analysis Qualitative data will be analysed using thematic analysis. Quantitative data will be analysed using appropriate statistical methods to understand how these factors influence access to transplantation, as well as the distribution of psychosocial factors pretransplantation and post-transplantation.Ethics and dissemination This study protocol has been reviewed by the National Institute for Health Research Academy and approved by the Wales Research Ethics Committee 4 (IRAS number 270493/ref: 20/WA/0285) and the Scotland A Research Ethics Committee (ref: 21/SS/0038). Results from this study will be disseminated across media platforms accessed by affected families, presented at conferences and published in peer-reviewed journals.

Oleic acid, found in a variety of food sources, is beneficial to health. However, studies on its anticancer effects on cancer stem cells resistant to conventional treatments and on the mechanisms underlying such effects are scarce. Here, we evaluated the anticancer effects of oleic acid against breast cancer cells with stemness characteristics. Oleic acid inhibited the proliferation of breast cancer stem-like cells more significantly than that of their respective parental cells, and reduced the expression of stem cell markers and migration and invasion propensity. It also repressed the phosphorylation of FAK, AKT, and NF-κB, proteins involved in cell migration and invasion. Oleic acid-induced increase in reactive oxygen species levels mediated the inhibition of the FAK/AKT/NF-κB signaling axis. Our study demonstrates that oleic acid-induced oxidative stress plays an important role in inhibiting the metastatic behavior of breast cancer cells with stemness characteristics and is relevant for management of treatment-resistant breast cancer.

Abstract Background The most effective way to halt the advancement of COPD is smoking cessation. However, limited data are available on the question of whether quitting smoking within two years after COPD diagnosis reduces the risk of mortality. The goal of our research was to analyze the relationship between quitting smoking after COPD diagnosis and the risks of all-cause and cause-specific mortality, using the Korean National Health Insurance Service (NHIS) database. Methods This study included 1,740 male COPD patients aged 40 years or more who had been newly diagnosed within the 2003–2014 time period and had smoked prior to their COPD diagnosis. The patients were categorized into two groups according to their smoking status after COPD diagnosis: (i) persistent smokers (ii) quitters (smoking cessation within two years of COPD diagnosis). Multivariate Cox proportional hazard regression was performed to determine the adjusted hazard ratio (HR) and 95% confidence interval (CI) for both all-cause and cause-specific mortality. Results Among 1,740 patients (mean age, 64.6 years; mean follow-up duration, 7.6 years), 30.5% stopped smoking after COPD diagnosis. Quitters gained a 17% risk reduction in all-cause mortality (aHR, 0.83; 95% CI, 0.69–1.00) and a 44% risk reduction in cardiovascular mortality (aHR, 0.56; 95% CI, 0.33–0.95) compared with persistent smokers. Conclusion Our study found that patients who quit smoking within two years after COPD diagnosis had lower risks of all-cause and cardiovascular mortality relative to persistent smokers. These results can be used to encourage newly diagnosed COPD patients to stop smoking.

Background: Although recent studies indicated that antibiotics may be a risk factor for lung cancer, further understanding is needed. We investigated the association of long-term antibiotic exposure with lung cancer risk. Methods: This population-based retrospective cohort study investigated 6,214,926 participants aged ≥ 40 years who underwent health screening examinations (2005–2006) from the Korean National Health Insurance Service database. The date of the final follow-up was December 31, 2019. Exposures were the cumulative days of antibiotics prescription and the number of antibiotics classes. The adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for lung cancer risk according to antibiotic use were assessed using multivariable Cox proportional hazards regression. Results: Compared with the antibiotic non-user group, participants with ≥ 365 days of antibiotics prescribed had a significantly increased risk of lung cancer (aHR, 1.21; 95% CI, 1.16–1.26). Participants with ≥ 365 days of antibiotics prescribed also had a significantly increased risk of lung cancer (aHR, 1.21; 95% CI, 1.17–1.24) than 1–14 days of the antibiotic user group. The results were also consistent in competing risk analyses and adjusted Cox regression models that fitted restricted cubic spline. Compared with the antibiotic non-user group, ≥ 5 antibiotic classes prescribed group had a higher lung cancer risk (aHR, 1.15; 95% CI, 1.10–1.21). Conclusion: The long-term cumulative days of antibiotic use and the increasing number of antibiotics classes were associated with an increased risk of lung cancer in a clear duration-dependent manner after adjusting for various risk factors.

Abstract Background Spatiotemporal regulation is one of the major considerations for developing a controlled and targeted drug delivery system to treat diseases efficiently. Light-responsive plasmonic nanostructures take advantage due to their tunable optical and photothermal properties by changing size, shape, and spatial arrangement. Results In this study, self-integrated plasmonic hybrid nanogels (PHNs) are developed for spatiotemporally controllable drug delivery through light-driven conformational change and photothermally-boosted endosomal escape. PHNs are easily synthesized through the simultaneous integration of gold nanoparticles (GNPs), thermo-responsive poly (N-isopropyl acrylamide), and linker molecules during polymerization. Wave-optic simulations reveal that the size of the PHNs and the density of the integrated GNPs are crucial factors in modulating photothermal conversion. Several linkers with varying molecular weights are inserted for the optimal PHNs, and the alginate-linked PHN (A-PHN) achieves more than twofold enhanced heat conversion compared with others. Since light-mediated conformational changes occur transiently, drug delivery is achieved in a spatiotemporally controlled manner. Furthermore, light-induced heat generation from cellular internalized A-PHNs enables pinpoint cytosolic delivery through the endosomal rupture. Finally, the deeper penetration for the enhanced delivery efficiency by A-PHNs is validated using multicellular spheroid. Conclusion This study offers a strategy for synthesizing light-responsive nanocarriers and an in-depth understanding of light-modulated site-specific drug delivery. Graphical Abstract

Abstract The present study evaluated the potential of carrot (Daucus carota L.) leaf, a non-edible part of carrots, which are among the most consumed vegetables worldwide. The antioxidant activities of 70% ethanol extract (EEC) and hot water extract (HEC) of carrot leaves were compared. The results revealed that the total polyphenol content, total flavonoid content, and DPPH and ABTS radical scavenging activities were higher in EEC than in HEC. Both extracts protected the cells against H2O2-induced toxicity and markedly reduced the levels of reactive oxygen species in RAW 264.7 cells. Moreover, pretreatment of RAW 264.7 cells with EEC and HEC prior to H2O2 (500 μM) exposure increased superoxide dismutase and glutathione peroxidase activities in these cells. Notably, EEC and HEC increased intracellular catalase activity by 36.77 and 6.39 times, respectively. Compared to HEC, EEC remarkably inhibited the production of lipopolysaccharide-induced nitric oxide and reduced the gene expression of IL-6, IL-1β, iNOS, COX-2, and TNF-α. Comparative analysis of the composition of the extracts using HPLC–UV suggested notably higher contents of catechin, chlorogenic acid, caffeic acid, rutin, quercetin, and cynaroside in EEC than in HEC. Collectively, these results imply that carrot leaves are a potentially beneficial natural source of antioxidants and anti-inflammatory compounds in functional foods.

Abstract Metal nanoclusters (NCs), an important class of nanoparticles (NPs), are extremely small in size and possess quasi-molecular properties. Due to accurate stoichiometry of constituent atoms and ligands, NCs have strong structure-property relationship. The synthesis of NCs is seemingly similar to that of NPs as both are formed by colloidal phase transitions. However, they are considerably different because of metal-ligand complexes in NC synthesis. Reactive ligands can convert metal salts to complexes, actual precursors to metal NCs. During the complex formation, various metal species occur, having different reactivity and fraction depending on synthetic conditions. It can alter their degree of participation in NC synthesis and the homogeneity of final products. Herein, we investigate the effects of complex formation on the entire NC synthesis. By controlling the fraction of various Au species showing different reactivity, we find that the extent of complex formation alters reduction kinetics and the uniformity of Au NCs. We demonstrate that this concept can be universally applied to synthesize Ag, Pt, Pd, and Rh NCs.

IntroductionCardiovascular disease (CVD) remains a leading cause of death in breast cancer survivors, a growing population. The aim of this study was to determine whether changes in body composition, commonly observed in breast cancer survivors, is associated with subsequent CVD risk.MethodsThis cohort study used the Korean National Health Insurance Service database. The study population included 73,271 5-year breast cancer survivors aged 40 years or above. To assess changes in body composition and its effect on the risk of CVD, validated prediction equations and multivariate Cox proportional hazards regression were used. Changes in metabolic markers (blood pressure, total cholesterol, and fasting serum glucose) according to changes in body composition were calculated by multiple linear regression.ResultsHaving persistently high predicted lean body and appendicular skeletal muscle mass percentages (LBMP and ASMP, respectively) among breast cancer survivors was associated with 32% and 40% lower CVD risks than a persistently low predicted LBMP or ASMP, respectively. Conversely, persistently high predicted body fat mass percentage (BFMP) was associated with a higher CVD risk than persistently low predicted BFMP. Additionally, those with a low to high change in predicted BFMP had a higher risk of CVD than those with persistently low predicted BFMP. Changes in body composition were accompanied by changes in metabolic markers.DiscussionMaintaining high percentages of lean body and appendicular skeletal muscle mass and preventing an increase in fat mass may be beneficial in preventing CVD in breast cancer survivors.

Purpose This study aimed to conduct a scoping review of studies on interventions for the prevention of safety accidents involving infants. Methods The scoping review method by Arksey and O'Malley was used to conduct an overview based on information spanning a wide range of fields. Multiple electronic databases, PubMed, CINAHL, RISS, and KISS, were searched for articles written in English or Korean published from 2012 to the present on safety accident prevention interventions. A total of 2,137 papers were found, and 20 papers were ultimately analyzed. Results Most studies were conducted in the United States (55.0%) and in the medical field (45.0%), and most were experimental studies (35.0%). The results were organized across five categories: 1) preventive precautions, 2) characteristics of children's developmental stages, 3) encouraging voluntary participation, 4) continuity of interventions, and 5) teaching methods. Conclusion Safety accident prevention interventions should cover the establishment of a safe home environment, include voluntary participation, and provide routine follow-up interventions. Additionally, practical training and teaching methods that incorporate feedback rather than a lectureoriented approach should be adopted.

Abstract Background Transcatheter arterial chemoembolization (TACE) via the inferior phrenic artery has been recognized to have its own therapeutic role without causing serious procedural complications. We report a case of diaphragmatic perforation after repeated TACE sessions conducted via the right inferior phrenic artery. Case presentation A 43-year-old man diagnosed with hepatocellular carcinoma was admitted to the hospital with a chief complaint of cough. The patient underwent TACE via the right inferior phrenic artery 3 months prior and was discharged without specific complications. Physical examination revealed decreased breathing sounds in the right lower lung zone. Chest radiograph demonstrated a small right pleural effusion. Chest CT scan revealed a small diaphragmatic perforation. The patient was unable to undergo surgical exploration, and a follow-up CT scan after 2 months revealed progression of the right diaphragmatic perforation with massive herniation of omental fat into the thoracic cavity. Conclusions Although TACE via the inferior phrenic artery is a relatively safe procedure, it can be associated with rare but serious complications after repeated procedures. This is a rare case report of diaphragmatic perforation after TACE via the right inferior phrenic artery. Early recognition and prompt surgical management are essential to prevent catastrophic outcomes.

Abstract Background Scleroderma is a serious chronic autoimmune disease in which a patient’s disease state manifests in several irregularly spaced longitudinal measures of lung, heart, skin, and other organ systems. Threshold crossings of pulmonary and cardiac measures indicate potentially life-threatening key clinical events including interstitial lung disease (ILD), cardiomyopathy, and pulmonary hypertension (PH). The statistical challenge is to accurately and precisely predict these events by using all of the clinical history for the patient at hand and for a reference population of patients. Methods We use a Bayesian mixed model approach to simultaneously characterize each individual’s future trajectories for several biomarkers. We estimate this model using a large population of patients from the Johns Hopkins Scleroderma Center Research Registry. The joint probabilities of critical lung and heart events are then calculated as a byproduct of the mixed model. Results The performance of this approach is substantially better than standard, more common alternatives. In order to predict an individual’s risks in a clinical setting, we also develop a cross-validated, sequential prediction (CVSP) algorithm. As additional data are observed during a patient’s visit, the algorithm sequentially produces updated predictions for the future longitudinal trajectories and for ILD, cardiomyopathy, and PH. The updated prediction distributions with little additional computing, for example within an electronic health record (EHR). Conclusions This method that generates real-time personalized risk estimates has been implemented within the electronic health record system for clinical testing. To our knowledge, this work represents the first approach to compute personalized risk estimates for multiple scleroderma complications.

Abstract To investigate the visual/anatomical outcome of diabetic macular edema (DME) patients lost to follow-up (LTFU) for more than 1 year during intravitreal anti-VEGF treatment. A retrospective review of 182 treatment-naïve DME patients was performed. Among them, we identified patients LTFU for more than 1 year during anti-VEGF treatment. Visual acuity and anatomic outcomes at the first visit, last visit before being LTFU, return visit, and after re-treatment were analyzed and compared with those of DME patients with regular follow-up. Patients who had continuous follow-up visits were assigned to the control group. Sixty patients (33%) with DME were LTFU for more than 1 year during anti-VEGF treatment. Multivariate analysis revealed that the ratio of male (p = 0.004), diabetes mellitus (DM) duration less than 5 years (p = 0.015), and poor early anatomic response (p = 0.012) were higher compared to the control group. Eighteen patients returned to the clinic and received re-treatment. After re-treatment with anti-VEGF, central subfield thickness (CST) was significantly improved to the CST of before LTFU. However, visual acuity did not recover to the level before LTFU (0.63 ± 0.26 vs. 0.45 ± 0.28, p = 0.003). About thirty percent of DME patients were LTFU for more than 1 year. Permanent visual loss was observed in these LTFU patients. Patients with a high risk of LTFU such as male, early DM, and poor response after initial injections should be treated more aggressively to improve the visual outcomes.

Abstract Background The detection rate of hand-arm vibration syndrome (HAVS) is very low in South Korea compared with other countries. The absence of uniform consensus and guidelines for diagnosing HAVS has been presumed to be one of the reasons. The HAVS has various manifestations including cold intolerance and its severity can be measured using the cold intolerance symptom severity (CISS) questionnaire. This study aimed to determine whether the CISS questionnaire, being used as a screening tool, can aid in the early detection of HAVS. Methods A total of 76 male workers with vibration-induced symptoms were enrolled as the final study participants. To compare the CISS score of healthy individuals, 41 men who had never been exposed to local vibration were included in the study. In addition to the former medical questionnaire, the participants answered the CISS questionnaire. A statistical analysis was conducted to identify the association of CISS scores with vibration induced symptom and to determine its cut off value. Results The reliability of the CISS questionnaire was proven to be good, with a total Cronbach’s alpha of 0.922. The mean CISS score of the exposed group increased in every vascular stage [stage 0 = 42.6 (18.5); stage 1 = 59.4 (14.1); and over stage 2 = 60.2 (21.6)]. They were significantly higher than that of the non-exposed group. The result was fairly consistent with those in the sensorineural stage. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve (AUC) of 30 were 88.5, 65.3, 76.1, 82.1 and 0.769, respectively. From the result of logistic regression, the adjusted odds ratio of both components increased by the CISS score grouped by 30s. Conclusions The self-reported CISS questionnaire, used to measure the degree of cold intolerance, showed high agreement with the Stockholm classification of HAVS. Hence, we recommend the use of this questionnaire to assess the level of cold intolerance among vibration-exposed workers and detect individuals who are at risk of vibration-induced impairment with a cutoff value of 30. Trial registration IRB No. 2018–07–040-001. Registered on 4 September 2018.

The present study was conducted to investigate recent trends of refractive surgery rates and analyze subjects undergoing refractive surgery using large-scale population studies over the past 8 years. We used the dataset of the Korean National Health and Nutrition Examination Surveys, a nationwide population-based cross-sectional study which were performed from 2008 to 2015. Of the 21,415 participants aged 20 to 49 years, 1,621 had refractive surgeries. Seventy three percent of them were females and 81% of them were aged under 40 years old. Over the past 8 years, cumulative prevalence of refractive surgery rate increased more than 10%. Although young (< 40 years, odds ratio (OR) 0.31, P

This study aimed to evaluate the genotoxic potential of the fruit and seed powder, fruit puree, and aqueous extracts of Morinda citrifolia (Rubiaceae, noni). The genotoxic potential of the noni substances was evaluated using in vitro Ames, in vitro chromosomal aberration, and in vivo micronucleus tests. All test procedures were conducted per Organization for Economic Cooperation and Development guidelines, and good laboratory practice. None of the noni fruit test substances showed genotoxic signs up to 5000 and 2000 μg/plate in the Ames and micronucleus tests, respectively. In the chromosomal aberration test, neither the fruit puree nor aqueous extract showed structural and numerical aberrations up to 5000 and 4650 μg/mL, respectively, irrespective of metabolic activation, in both 6 h and 24 h treatment groups. The safe ranges of noni fruit and seed powders were up to 2500 and 2100 μg/mL, respectively, in the 6 h treatment group and up to 1600–4100 and 370–450 μg/mL, respectively, in both 6 h and 24 h treatment groups in the presence of metabolic activation. Noni fruit and seeds were safe in terms of genotoxicity under our experimental conditions. Our data are the first to provide valuable genotoxic information on Morinda citrifolia.

Despite increasing research on the gut-skin axis, there is a lack of comprehensive studies on the improvement of skin health through the regulation of the intestinal condition in humans. In this study, we investigated the benefits of Lactobacillus plantarum HY7714 (HY7714) consumption on skin health through its modulatory effects on the intestine and ensuing immune responses. HY7714 consumption led to differences in bacterial abundances from phylum to genus level, including increases in Actinobacteria followed by Bifidobacterium and a decrease in Proteobacteria. Additionally, HY7714 significantly ameliorated inflammation by reducing matrix metallopeptidases (MMP-2 and MMP-9), zonulin, and calprotectin in plasma, all of which are related to skin and intestinal permeability. Furthermore, RNA-seq analysis revealed its efficacy at restoring the integrity of the gut barrier by regulating gene expression associated with the extracellular matrix and immunity. This was evident by the upregulation of IGFBP5, SERPINE1, EFEMP1, COL6A3, and SEMA3B and downregulation of MT2A, MT1E, MT1X, MT1G, and MT1F between TNF- α and TNF- α plus HY7714 treated Caco-2 cells. These results propose the potential mechanistic role of HY7714 on skin health by the regulation of the gut condition.

Background Hemorrhage is the major cause of traumatic death and the leading cause of preventable death. Hyperfibrinolysis is associated with trauma severity. Viscoelastic hemostatic assays show complete clot formation dynamics. The present study was designed to identify the relationship between hyperfibrinolysis and mortality, metabolic acidosis, and coagulopathy in patients with trauma. Methods Patients with severe trauma (injury severity score [ISS] of 15 or higher) who were assessed using rotational thromboelastometry (ROTEM) were included in the present study from January 2017 to December 2017. Variables were obtained from the Korea Trauma Database or the medical charts of the patients. To identify whether hyperfibrinolysis is an independent predictor of mortality, univariate and multivariate Cox regression analyses were performed. Results During the 1-year study period, 190 patients were enrolled. In total, 21 (11.1%) had hyperfibrinolysis according to the ROTEM analysis and 46 (24.2%) died. Patients with hyperfibrinolysis had a higher ISS (P=0.014) and mortality rate (P

This study aimed to investigate the characteristics of exosomes isolated from synovial fluid and their role in osteoclast differentiation in different types of inflammatory arthritis. Exosomes isolated from synovial fluid of rheumatoid arthritis (RA), ankylosing spondylitis (AS), gout, and osteoarthritis (OA) patients were co-incubated with CD14+ mononuclear cells from healthy donors without macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL). Osteoclast differentiation was evaluated via tartrate-resistant acid phosphatase (TRAP) staining and activity and F-actin ring formation. RANKL expression on synovial exosomes was assessed using flow cytometry and an enzyme-linked immunosorbent assay (ELISA). Synovial exosomes were the lowest in OA patients; these induced osteoclastogenesis in the absence of M-CSF and RANKL. Osteoclastogenesis was significantly higher with more exosomes in RA (p = 0.030) than in OA patients, but not in AS or gout patients. On treating macrophages with a specified number of synovial exosomes from RA/AS patients, exosomes induced greater osteoclastogenesis in RA than in AS patients. Synovial exosomal RANKL levels were significantly higher in RA (p = 0.035) than in AS patients. Synovial exosome numbers vary with the type of inflammatory arthritis. Synovial exosomes from RA patients may bear the disease-specific “synovial signature of osteoclastogenesis.”

Purpose: Emergency department (ED) nurses suffer from persistent stress after experiencing the traumatic event of exposure to Middle East respiratory syndrome coronavirus (MERS-CoV), which can subsequently lead to burnout. This study aimed to assess ED nurses' burnout level during an outbreak of MERS-CoV and to identify influencing factors in order to provide basic information for lowering and preventing the level of burnout. Methods: Study participants were ED nurses working in eight hospitals designated for treating MERS-CoV-infected patients in Korea. We performed multiple regression analysis to explore the factors influencing burnout. Results: The ED nurses' burnout was affected by job stress (β = 0.59, p

Purpose: The purpose of this study was to survey the current state of measles vaccination in university nursing students during a measles outbreak and to identify factors influencing nursing students' vaccination rate. Methods: In 2014, this study used a self-administered questionnaire to survey 380 university nursing students. Factors influencing measles vaccination were identified through logistic regression analysis using variables between the vaccinated and nonvaccinated groups. Results: Measles vaccination rate was 52.1%. The vaccination rate was significantly higher in juniors, seniors, and those who had heard about measles. In relation to health beliefs, the measles vaccination rate was higher when perceived benefits were high and perceived barriers were low. Conclusions: A systematic measles vaccination program targeting nursing students upon their entry to university is needed. In order to increase the measles vaccination rate, application of effective promotion campaigns and education programs is necessary.

The COVID-19 pandemic was caused by a highly contagious coronavirus that has triggered worldwide control actions such as social distancing and lockdowns. COVID-19 control actions have resulted in improved air quality locally and around the world in the short-term by limiting human activity. We analyzed the impacts of social distancing and transboundary pollutants on air quality changes using open data and examined the corresponding health benefits focusing on two domestic cities (Seoul and Daegu) in Korea where the spread of coronavirus was severe. During the COVID-19 pandemic, PM2.5, PM10, and NO2 concentrations decreased significantly by 31%, 61%, and 33%, respectively, compared to the previous three years. In particular, the PM2.5/PM10 ratio fell 24.5% after the implementation of social distancing, suggesting a decrease in anthropogenic emissions. Moreover, we found that the air quality index (AQI) also improved significantly, with a focus on reducing exposure to sensitive groups. In Seoul and Daegu, improved air quality prevented 250 and 78 premature deaths, and health costs were USD 884 million and USD 278 million, respectively. On the other hand, health loss due to COVID-19 deaths was in sharp contrast to USD 7.1 million and USD 543.6 million. Our findings indicate a significant association between COVID-19 prevalence patterns and health outcomes.

Immune complexes containing citrullinated fibrinogen are present in the sera and synovium of rheumatoid arthritis patients and potentially contribute to synovitis. However, fibrinogen can inhibit the osteoclastogenesis of precursor cells. We investigated the direct effect of citrullinated fibrinogen on osteoclastogenesis to understand the role of citrullination on bone erosion of rheumatoid arthritis patients. We evaluated the fibrinogen citrullination sites using mass spectrometry and quantified osteoclast-related protein and gene expression levels by Western blotting, microarray, and real-time polymerase chain reaction. Differences in spectral peaks were noted between fibrinogen and citrullinated fibrinogen at five sites in α-chains, two sites in β-chains, and one site in a γ-chain. Transcriptome changes induced by fibrinogen and citrullinated fibrinogen were identified and differentially expressed genes grouped into three distinctive modules. Fibrinogen was then citrullinated in vitro using peptidylarginine deiminase. When increasing doses of soluble fibrinogen and citrullinated fibrinogen were applied to human CD14+ monocytes, citrullination restored osteoclastogenesis-associated changes, including NF-ATc1 and ß3-integrin. Finally, citrullination rescued the number of osteoclasts by restoring fibrinogen-induced suppression of osteoclastogenesis. Taken together, the results indicate that the inhibitory function of fibrinogen on osteoclastogenesis is reversed by citrullination and suggest that citrullinated fibrinogen may contribute to erosive bone destruction in rheumatoid arthritis.

Background: Superficial siderosis (SS) is a rare condition in which hemosiderin, an iron storage complex, is deposited in neural tissues because of recurrent subarachnoid bleeding. Hemosiderin deposition in the vestibulocochlear nerve (CN VIII), brain, spinal cord and peripheral nerve can cause sensorineural hearing loss (SNHL) and postural imbalance, but much remains unknown about the vestibular manifestations of SS.Objectives: To report the clinical course, cochleovestibular status, and patterns of vestibulopathy during follow-up of a relatively large case series, and to discuss the possible pathophysiological mechanism of vestibular deterioration.Methods: Six patients diagnosed with SS by magnetic resonance imaging (MRI) were enrolled. Their medical records and radiological findings were retrospectively reviewed, particularly in terms of progression of the vestibulocochlear manifestations and the radiological characteristics.Results: All six patients had SNHL. Five of them exhibited progressive hearing loss over years, which was asymmetric in four. On their most recent evaluations, patients showed cerebellar ataxia with combined central and peripheral vestibulopathy on both sides (n = 4), a bilateral peripheral vestibulopathy (n = 1) or isolated central vestibulopathy (n = 1). Notably, the former four patients showed an evolution of isolated central vestibulopathy into combined central and peripheral vestibulopathy. Hypo-intense lesions on T2 weighted MRIs were evident around the cerebellum in all patients, but such lesions were observed around the brainstem in five and the CN VIII in four. The cochlea-vestibular dysfunction generally progressed asymmetrically, but no left-right asymmetry was evident on MRI.Conclusions: SS typically presents as bilaterally asymmetric, progressive cochleovestibular dysfunction with cerebellar ataxia. The pattern of vestibular dysfunction is usually combined central and peripheral vestibulopathy on both sides. Thus, precise identification of audiovestibular dysfunction and central signs is essential in SS, and patients with SS should undergo regular, comprehensive neurotological evaluation to optimize their treatments and prognosis.

The GacS/GacA two component system regulates various traits related to the biocontrol potential of plant-associated pseudomonads. The role of the sensor kinase, GacS, differs between strains in regulation of motility. In this study, we determined how a gacS mutation changed cell morphology and motility in Pseudomonas chlororaphis O6. The gacS mutant cells were elongated in stationary-phase compared to the wild type and the complemented gacS mutant, but cells did not differ in length in logarithmic phase. The gacS mutant had a two-fold increase in the number of flagella compared with the wild type strain; flagella number was restored to that of the wild type in the complemented gacS mutant. The more highly flagellated gacS mutant cells had greater swimming motilities than that of the wild type strain. Enhanced flagella formation in the gacS mutant correlated with increased expression of three genes, fleQ, fliQ and flhF, involved in flagellar formation. Expression of these genes in the complemented gacS mutant was similar to that of the wild type. These findings show that this root-colonizing pseudomonad adjusts flagella formation and cell morphology in stationary-phase using GacS as a major regulator.

Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS), a very rare disease that is caused by the presence of antifactor II antibodies, is usually counterbalanced by the prothrombotic effect of lupus anticoagulant (LAC). Patients with LAHPS are treated using fresh frozen plasma, steroids, immunosuppressive agents, and immunoglobulins for managing the disease and controlling hemorrhages. Notably, steroids are the important treatment for treating hypoprothrombinemia and controlling the bleeding. However, some patients suffer from severe, life-threatening hemorrhages, when factor II levels remain very low in spite of treatment with steroids. Here, we report a case of LAHPS in a 15-year-old girl who experienced pulmonary hemorrhage with rapid progression. She was referred to our hospital owing to easy bruising and prolonged bleeding. She was diagnosed with LAHPS that presented with pancytopenia, positive antinuclear antibody, proloned prothrombin time, activated partial thromboplastin time, positive LAC antibody, and factor II deficiency. Her treatment included massive blood transfusion, high-dose methylprednisolone, vitamin K, and immunoglobulin. However, she died due to uncontrolled pulmonary hemorrhage.

The stationary-phase sigma factor, RpoS, influences the expression of factors important in survival of Pseudomonas chlororaphis O6 in the rhizosphere. A partial proteomic profile of a rpoS mutant in P. chlororaphis O6 was conducted to identify proteins under RpoS regulation. Five of 14 differentially regulated proteins had unknown roles. Changes in levels of proteins in P. chlororaphis O6 rpoS mutant were associated with iron metabolism, and protection against oxidative stress. The P. chlororaphis O6 rpoS mutant showed increased production of a pyoverdine-like siderophore, indole acetic acid, and altered isozyme patterns for peroxidase, catalase and superoxide dismutase. Consequently, sensitivity to hydrogen peroxide exposure increased in the P. chlororaphis O6 rpoS mutant, compared with the wild type. Taken together, RpoS exerted regulatory control over factors important for the habitat of P. chlororaphis O6 in soil and on root surfaces. The properties of several of the proteins in the RpoS regulon are currently unknown.

Policy and Program evaluation for maternal, newborn and child health is becoming increasingly complex due to changing contexts. Monitoring and evaluation efforts in this area can take advantage of large nationally representative household surveys such as DHS or MICS that are increasing in size and frequency, however, this analysis presents challenges on several fronts. We propose an approach with hierarchical models for cross-sectional survey data to describe evidence relating to program evaluation, and apply this approach to the recent scale up of iCCM in Malawi. We describe careseeking for children sick with diarrhea, pneumonia, or malaria with empirical Bayes estimates for each district of Malawi at two time points, both for careseeking from any source, and for careseeking only from health surveillance assistants (HSA). We do not find evidence that children in areas with more HSA trained in iCCM are more likely to seek care for pneumonia, diarrhea, or malaria, despite evidence that many indeed are seeking care from HSA. Children in areas with more HSA trained in iCCM are more likely to seek care from a HSA, with 100 additional trained health workers in a district corresponding to a 2% average increase in careseeking from HSA. The hierarchical models presented here provide a flexible set of methods that describe the primary evidence for evaluating iCCM in Malawi and which could be extended to formal causal analyses, and to analysis for other similar evaluations with national survey data.

Background. Cutting the sternothyroid (ST) muscle is a useful technique to expose the superior pole of thyroid gland during thyroidectomy. In this study, we evaluated the impact of partial cutting of the ST muscle on postoperative vocal outcomes after total thyroidectomy. Methods. A retrospective review of 57 patients who underwent total thyroidectomy with central neck dissection for micropapillary thyroid carcinoma was conducted. Group A (n=26) included those without cutting the ST muscle, while group B (n=31) included patients whose muscle was partially cut at the superior pole. All patients underwent voice analysis before the operation and 2 weeks and 1 month after the surgery, and the outcomes were compared between the two groups. Results. There were no differences between the two groups regarding the outcomes at each time of voice analysis. Group A showed a decrease of maximum frequency 2 weeks after surgery but showed no difference after 1 month. Group B showed a mild decrease in maximum frequency 2 weeks after surgery, but the difference was not significant. Conclusion. Partial cutting of ST muscle during thyroidectomy is useful to expose the superior pole without significant negative impact on postoperative outcomes of vocal analysis.

Introduction: Video head-impulse tests (video-HITs) often fail to detect anterior inferior cerebellar artery (AICA) infarction due to peripheral and central vestibular system involvement. Anecdotal studies suggest that video-HITs may reveal bilateral impairment in AICA infarction. However, the diagnostic utility of videoHITs has not been established, particularly when compared to labyrinthitis, which accounts for the majority of acute audiovestibular syndrome (AAVS) cases. Methods: We reviewed the medical records of consecutive patients presenting with new-onset acute hearing loss and spontaneous vertigo (i.e., AAVS) between March 2018 and July 2023 at a tertiary hospital in South Korea. Video-HIT patterns were categorized as follows: (1) ipsilaterally positive, (2) contralaterally positive, (3) bilaterally normal, and (4) bilaterally positive. Results: Twenty-eight patients with AICA infarction (mean age±standard deviation  =  67±15  years; 14 men) and 51 with labyrinthitis (63±17  years, 26 men) were included in the analyses. Among the 28 patients with AICA infarction, 15 presented with AAVS in isolation, without other co-morbid neurologic deficits (15/28, 54%). The vestibulo-ocular reflex (VOR) gains of ipsilesional horizontal canals (HCs) ranged from 0.21 to 1.22 (median  =  0.81, interquartile range [IQR]  =  0.50–0.89). However, those for contralateral HC gain ranged from 0.57 to 1.19 (median  =  0.89 [IQR  =  0.73–0.97]). Collectively, HITs were bilaterally positive in 13 patients (including 12 patients with bilaterally positive HITs for the horizontal canal), normal in eight, ipsilesionally positive in six, and contralesionally positive in one patient with AICA infarction. The VOR gains were typically decreased ipsilaterally in 28 (28/51, 55%), normal in 17 (17/51, 33%), and decreased bilaterally in six patients with labyrinthitis (6/51, 12%). Logistic regression analysis revealed that bilaterally positive HITs (p  =  0.004) and multiple vascular risk factors (p  =  0.043) were more frequently associated with AICA infarction than labyrinthitis. Discussion: Among patients presenting with AAVS, bilaterally positive HITs can be indicative of AICA infarction in patients with multiple vascular risk factors. [ABSTRACT FROM AUTHOR]

Objective: The rich botanical biodiversity resulting from diverse climates and geographical distinctiveness offers a plethora of biological resources that can be pivotal in developing innovative biomaterials. This investigation sought to evaluate the functional properties of indigenous Korean plant species. Methods: Forty-six indigenous plants during a year-long expedition across inhabited and uninhabited Korean islands were collected. The plant specimens were divided into 5 parts (flower, fruit, stem, leaf, and whole body) and subjected to extraction using water, 30% ethanol, and 70% ethanol, followed by characterizations of anti-inflammatory, immune response, and anti-bacterial activity. Results: Thirty-eight percent of the extracts (59 extracts from 31 species) exhibited statistically significant anti-inflammatory effects. Concurrently, 22% of the extracts (35 extracts from 24 species) demonstrated notable immune boosting effects. Additionally, 17 extracts exhibited significant inhibitory effects against the growth of pathogenic bacteria. Conclusion: This study highlights the potential utility of extracts of plants from Korean islands as natural agents for next-generation pharmaceutical and medical applications by emphasizing their effectiveness in combating inflammation, enhancing immune responses, and conferring anti-bacterial benefits. [ABSTRACT FROM AUTHOR]