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Background: Clinical manifestations and risk factors associated with systemic lupus erythematosus (SLE) flares, including recurrent lupus nephritis (LN), in patients with LN who undergo kidney transplantation have been unclear. Methods: Kidney transplant recipients with LN from January 1995 to December 2021 were included in this study. A disease flare was defined as either an increase in the non‐renal SLE disease activity index score or the presence of biopsy‐proven recurrent LN. Results: Among a total of 93 patients with LN who underwent kidney transplantation, 11 patients (11.8%) experienced SLE flares during a median follow‐up period of 76.9 months (IQR, 43.0–122.4). The most common clinical manifestations of SLE flares were recurrent LN (4/11, 36.4%) and hematologic manifestations (4/11, 36.4%). Patients who had flares had significantly higher anti‐double‐stranded DNA (anti‐dsDNA) antibody titers both before and after transplantation. Furthermore, an increased anti‐dsDNA antibody level before transplantation was associated with a high risk of an SLE flare (HR, 1.030; p =.008). Conversely, preemptive transplantation was associated with a lower risk of a flare (HR, 0.617; p =.026). The rate of patient death‐censored graft survival was found to be considerably lower in patients with recurrent LN than in those without LN. Conclusions: Approximately 10% of patients with LN experienced an SLE flare after transplantation, with recurrent LN being the most frequent manifestation. Anti‐dsDNA antibody titers before transplantation were significantly related to the risk of an SLE flare. Notably, preemptive transplantation was associated with a reduced risk of flares following transplantation. [ABSTRACT FROM AUTHOR]

Background: Acute lung injury (ALI) following pneumonia involves uncontrolled inflammation and tissue injury, leading to high mortality. We previously confirmed the significantly increased cargo content and extracellular vesicle (EV) production in thrombin-preconditioned human mesenchymal stromal cells (thMSCs) compared to those in naïve and other preconditioning methods. This study aimed to investigate the therapeutic efficacy of EVs derived from thMSCs in protecting against inflammation and tissue injury in an Escherichia coli (E. coli)-induced ALI mouse model. Methods: In vitro, RAW 264.7 cells were stimulated with 0.1 µg/mL liposaccharides (LPS) for 1 h, then were treated with either PBS (LPS Ctrl) or 5 × 107 particles of thMSC-EVs (LPS + thMSC-EVs) for 24 h. Cells and media were harvested for flow cytometry and ELISA. In vivo, ICR mice were anesthetized, intubated, administered 2 × 107 CFU/100 µl of E. coli. 50 min after, mice were then either administered 50 µL saline (ECS) or 1 × 109 particles/50 µL of thMSC-EVs (EME). Three days later, the therapeutic efficacy of thMSC-EVs was assessed using extracted lung tissue, bronchoalveolar lavage fluid (BALF), and in vivo computed tomography scans. One-way analysis of variance with post-hoc TUKEY test was used to compare the experimental groups statistically. Results: In vitro, IL-1β, CCL-2, and MMP-9 levels were significantly lower in the LPS + thMSC-EVs group than in the LPS Ctrl group. The percentages of M1 macrophages in the normal control, LPS Ctrl, and LPS + thMSC-EV groups were 12.5, 98.4, and 65.9%, respectively. In vivo, the EME group exhibited significantly lower histological scores for alveolar congestion, hemorrhage, wall thickening, and leukocyte infiltration than the ECS group. The wet-dry ratio for the lungs was significantly lower in the EME group than in the ECS group. The BALF levels of CCL2, TNF-a, and IL-6 were significantly lower in the EME group than in the ECS group. In vivo CT analysis revealed a significantly lower percentage of damaged lungs in the EME group than in the ECS group. Conclusion: Intratracheal thMSC-EVs administration significantly reduced E. coli-induced inflammation and lung tissue damage. Overall, these results suggest therapeutically enhanced thMSC-EVs as a novel promising therapeutic option for ARDS/ALI. [ABSTRACT FROM AUTHOR]

Paralytic shellfish toxins (PSTs) are potent neurotoxins produced by certain microalgae, particularly dinoflagellates, and they can accumulate in shellfish in coastal seawater and thus pose significant health risks to humans. To explore the relationship between toxicity and PST profiles in seawater and mussels, the spatiotemporal variations in PST concentrations and profiles were investigated along the southern coast of Korea under peak PST levels during spring. Seawater and mussel samples were collected biweekly from multiple stations, and the toxin concentrations in the samples were measured. Moreover, the dinoflagellate community composition was analyzed using next-generation sequencing to identify potential PST-producing species. The PST concentrations and toxin profiles showed substantial spatiotemporal variability, with GTX1 and GTX4 representing the dominant toxins in both samples, and C1/2 tending to be higher in seawater. Alexandrium species were identified as the primary sources of PSTs. Environmental factors such as water temperature and salinity influenced PST production. This study demonstrates that variability in the amount and composition of PSTs is due to intricate ecological interactions. To mitigate shellfish poisoning, continuous monitoring must be conducted to gain a deeper understanding of these interactions. [ABSTRACT FROM AUTHOR]

Based on the fact that substances with a β-phenyl-α,β-unsaturated carbonyl (PUSC) motif confer strong tyrosinase inhibitory activity, benzylidene-3-methyl-2-thioxothiazolidin-4-one (BMTTZD) analogs 1–8 were prepared as potential tyrosinase inhibitors. Four analogs (1–3 and 5) inhibited mushroom tyrosinase strongly. Especially, analog 3 showed an inhibitory effect that was 220 and 22 times more powerful than kojic acid in the presence of l-tyrosine and l-dopa, respectively. A kinetic study utilizing mushroom tyrosinase showed that analogs 1 and 3 competitively inhibited tyrosinase, whereas analogs 2 and 5 inhibited tyrosinase in a mixed manner. A docking simulation study indicated that analogs 2 and 5 could bind to both the tyrosinase active and allosteric sites with high binding affinities. In cell-based experiments using B16F10 cells, analogs 1, 3, and 5 effectively inhibited melanin production; their anti-melanogenic effects were attributed to their ability to inhibit intracellular tyrosinase activity. Moreover, analogs 1, 3, and 5 inhibited in situ B16F10 cellular tyrosinase activity. In three antioxidant experiments, analogs 2 and 3 exhibited strong antioxidant efficacy, similar to that of the positive controls. These results suggest that the BMTTZD analogs are promising tyrosinase inhibitors for the treatment of hyperpigmentation-related disorders. [ABSTRACT FROM AUTHOR]

Objective We investigated the incidence of and risk factors for myelodysplastic syndrome (MDS) in patients with rheumatologic disease. Methods We conducted a retrospective cohort study of patients who were diagnosed with rheumatologic diseases at a tertiary care hospital between May 2009 and July 2022 and identified the patients who were subsequently diagnosed with MDS. Each patient with MDS was matched with five age- and sex-matched controls chosen from the cohort of patients with each specific rheumatologic disease. Results During a total follow-up of 55 841 person-years (PY), MDS occurred in 64 patients, yielding an incidence rate of 1.15/1000 PY {median age 57.0 years [interquartile range (IQR) 41.0–69.0], median duration to MDS diagnosis 6.5 years (IQR 3.0–9.0)]. In an age-matched analysis, SLE was a significant risk factor for MDS [adjusted hazard ratio 2.61 (CI 1.19, 36.06), P  = 0.01]. Refractory cytopenia with multilineage dysplasia was the most common phenotype of MDS (35.9%), and more than half of the patients had karyotypes with a favourable prognosis (54.7%). Compared with matched controls, RA, SLE and AS patients with MDS had lower levels of haemoglobin at the time of diagnosis of rheumatologic disease. Furthermore, the MDS patients with SLE and Behçet's disease had higher levels of glucocorticoid use in terms of frequency of use and mean dose than control patients. Conclusion SLE is a significant risk factor for MDS among patients with rheumatologic diseases. A lower haemoglobin level at the time of diagnosis of rheumatologic disease was associated with the future development of MDS. [ABSTRACT FROM AUTHOR]

We established a protocol for the traditional Korean medicine examination (KME) and methodically gathered data following this protocol. Potential indicators for KME were extracted through a literature review; the first KME protocol was developed based on three rounds of expert opinions. The first KME protocol's feasibility was confirmed, and data were collected over four years from traditional Korean medicine (KM) hospitals, focusing on healthy adults, using the final KME protocol. A literature review identified 175 potential core indicators, condensed into 73 indicators after three rounds of expert consultation. The first KME protocol, which was categorized under questionnaires and medical examinations, was developed after the third round of expert opinions. A pilot study using the first KME protocol was conducted to ensure its validity, leading to modifications resulting in the development of the final KME protocol. Over four years, data were collected from six KM hospitals, focusing on healthy adults; we obtained a dataset comprising 11,036 healthy adults. This is the first protocol incorporating core indicators of KME in a quantitative form and systematically collecting data. Our protocol holds potential merit in evaluating predisposition to diseases or predicting diseases. [ABSTRACT FROM AUTHOR]

Background Solid organ transplant recipients (SOTRs) are at higher risk for severe infection. However, the risk for severe COVID-19 and vaccine effectiveness among SOTRs remain unclear. Methods This retrospective study used a nationwide health care claims database and COVID-19 registry from the Republic of Korea (2020 to 2022). Adult SOTRs diagnosed with COVID-19 were matched with up to 4 non-SOTR COVID-19 patients by propensity score. Severe COVID-19 was defined as treatment with high-flow nasal cannulae, mechanical ventilation, or extracorporeal membrane oxygenation. Results Among 6783 SOTRs with COVID-19, severe COVID-19 was reported with the highest rate in lung transplant recipients (13.16%), followed by the heart (6.30%), kidney (3.90%), and liver (2.40%). SOTRs had a higher risk of severe COVID-19 compared to non-SOTRs, and lung transplant recipients showed the highest risk (adjusted odds ratio, 18.14; 95% confidence interval [CI], 8.53–38.58). Vaccine effectiveness against severe disease among SOTRs was 47% (95% CI, 18%–65%), 64% (95% CI, 49%–75%), and 64% (95% CI, 29%–81%) for 2, 3, and 4 doses, respectively. Conclusions SOTRs are at significantly higher risk for severe COVID-19 compared to non-SOTRs. Vaccination is effective in preventing the progression to severe COVID-19. Efforts should be made to improve vaccine uptake among SOTRs, while additional protective measures should be developed. [ABSTRACT FROM AUTHOR]

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/β-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/β-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health. Microbiome-secreted proteins act as key modulators of host-microbiome crosstalk. Here, the authors show that Amuc_1409 protein, secreted from Akkermansia muciniphila, plays a key role in intestinal homeostasis by regulating intestinal stem cells through interaction with E-cadherin, indicating its potential as a biomolecule for improving gut health. [ABSTRACT FROM AUTHOR]

With the recent acceleration in AI adoption and significant investments being made by many countries, the concern regarding the AI divide is becoming increasingly prevalent. We attempt to determine whether countries that have fallen behind in AI development can catch up to those leading the charge over time. Specifically, this study examines the dynamics of the AI divide on AI investments, robotics, AI start-ups, and AI patents in 34–57 countries, analyzing the data sets from Stanford AI Index Report, World Robotics Report, and the OECD Statistics website. We have used the methods of the relative AI divide (RAID) and absolute AI divide (AAID) for the two categories of income and adoption levels. Also, we have tested both γ convergence for the AI divide and σ convergence for the divide over time. We find that for all four AI categories, the relative AI divide between the leading and lagging countries has narrowed rapidly and the divide between the high- and middle-income subgroups has also narrowed at a slower pace. In terms of the micro convergence analysis of the AI divides for individual countries within the respective income and adoption subgroups, a change in the active ranking among countries was evident in nearly all of the subgroups. This study contributes to the literature by presenting not only the absolute AI divide but also the relative AI divide clarifying the changing trends systematically. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Lower urinary tract symptoms (LUTS) are frequently observed in patients with Parkinson's disease (PD), but the underlying mechanism remains elusive. The concept of “body‐first” and “brain‐first” subtypes in PD has been proposed, but the correlation of PD subtype with LUTS remains unclear. We aimed to investigate the disparities in urological dysfunctions between body‐first and brain‐first subtypes of PD using urodynamic studies (UDS).We reviewed patients with PD (disease duration <3 years) who had undergone UDS and completed urological questionnaires (Overactive Bladder Symptom Score [OABSS] and International Prostate Symptom Score [IPSS]) and a voiding diary. Patients were categorized as having body‐first or brain‐first PD based on cardiac sympathetic denervation (CSD) using cardiac meta‐iodobenzylguanidine (MIBG) uptake and the presence of rapid eye movement sleep behavior disorder (RBD), assessed using a questionnaire (PD with CSD and RBD indicating the body‐first subtype).A total of 55 patients with PD were categorized into body‐first PD (n = 37) and brain‐first PD (n = 18) groups. The body‐first PD group exhibited smaller voiding volume and first desire volume (FDV) than the brain‐first PD group (p < 0.05 in both). Also, the body‐first PD group had higher OABSS and IPSS scores, and higher prevalence of overactive bladder diagnosed by OABSS, compared to the brain‐first PD group. In multiple linear regression, cardiac MIBG uptake was positively correlated with FDV and voiding volume and negatively correlated with OABSS and IPSS (p < 0.05 in all).Patients with the body‐first PD subtype exhibited more pronounced overactive bladder symptoms and impaired storage function in the early stage of disease. Additionally, cardiac MIBG was significantly associated with urological dysfunction. [ABSTRACT FROM AUTHOR]

Background: Low muscle mass is associated with high insulin resistance and an increased risk of cardiovascular disease. This study aims to determine whether low muscle mass affects the alterations in myocardial substrate metabolism that are associated with the development of cardiovascular disease., Method: The study included 299 individuals (182 men and 117 women) who underwent examination at the Severance Health Check-up Center between January 2018 and February 2019. Myocardial glucose uptake was assessed using [18F]-fluorodeoxyglucose-positron emission tomography ( 18 F-FDG PET/CT) scanning. Direct segmental bioimpedance analysis was used to measure appendicular skeletal muscle mass (ASM)., Results: We analysed men and women separately owing to sex-related body composition differences. ASM/Ht 2 was significantly positively correlated with myocardial glucose uptake measured by 18 F-FDG PET/CT [ln (SUV heart/liver )] only in men (r = 0.154, P = 0.038 in men; r = -0.042, P = 0.652 in women, respectively). In men, myocardial glucose uptake was significantly associated with ASM/Ht 2 even after adjusting for multiple confounders in a multivariable linear regression model (standardized β = 0.397, P = 0.004, in men; β = - 0.051, P = 0.698, in women). In women, age (β = -0.424 P = 0.029) was independent determinants of myocardial glucose uptake., Conclusions: In men, ASM was strongly associated with myocardial glucose uptake as measured by 18 F-FDG PET/CT. In women, age was significantly correlated with myocardial substrate utilization, but not with ASM., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

This study investigates the impact of sodium channel protein type 1 subunit alpha (SCN1A) gene knockout (SCN1A KO) on brain development and function using cerebral organoids coupled with a multiomics approach. From comprehensive omics analyses, we found that SCN1A KO organoids exhibit decreased growth, dysregulated neurotransmitter levels, and altered lipidomic, proteomic, and transcriptomic profiles compared to controls under matrix-free differentiation conditions. Neurochemical analysis reveals reduced levels of key neurotransmitters, and lipidomic analysis highlights changes in ether phospholipids and sphingomyelin. Furthermore, quantitative profiling of the SCN1A KO organoid proteome shows perturbations in cholesterol metabolism and sodium ion transportation, potentially affecting synaptic transmission. These findings suggest dysregulation of cholesterol metabolism and sodium ion transport, with implications for synaptic transmission. Overall, these insights shed light on the molecular mechanisms underlying SCN1A-associated disorders, such as Dravet syndrome, and offer potential avenues for therapeutic intervention., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Introduction: Herbal medicines (HMs) are commonly used during the postpartum period in South Korea. However, the safety concerns associated with these medicines remain unresolved. This study aims to establish a registry of patients receiving HM treatment during the postpartum period and collect clinical data on treatments and adverse reactions to build evidence evaluating the safety of HM use., Methods and Analysis: This study will use a prospective observational registry, including patients admitted to the obstetrics and gynaecology department of the Woosuk University Korean Medicine Hospital's postpartum care centre. A total of 1000 eligible patients visiting the Korean medicine hospital to recover from various postchildbirth symptoms and opting for HM treatment will be enrolled in the registry. For safety assessment, demographic information, medical history, adverse events (AEs) and treatment details, including HM prescription and concomitant medication usage, will be collected throughout the patient's hospitalisation period at the postpartum care centre for analysis. Adverse reactions will be monitored daily during hospitalisation, and collected AEs will be analysed for causality using the WHO Uppsala Monitoring Centre causality assessment and the Naranjo Algorithm Score., Ethics and Dissemination: This study was approved by the Institutional Review Board of Woosuk University Korean Medicine Medical Center (WSOH IRB H2311-03-01). The results will be published in peer-reviewed journals or disseminated through conference presentations., Trial Registration Number: KCT0009060., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Diagnosing the current health status and disease burden in a population is crucial for public health interventions. The ability to compare the burden of different diseases through a single measure, such as disability-adjusted life years has become feasible and continues to be produced and updated through the Global Burden of Diseases (GBD) study. However, the disease burden values of the GBD study do not accurately reflect the unique situation in a specific country with various circumstances. In response, the Korean National Burden of Disease (KNBD) study was conducted to estimate the disease burden in Koreans by considering Korea's cultural context and utilizing the available data sources at the national level. Both studies identified non-communicable diseases, such as diabetes mellitus (DM), as the primary cause of disease burden among Koreans. However, the extent of public health interventions currently being conducted by the central and local governments does not align with the severity of the disease burden. This review suggests that despite the high burden of DM in South Korea, the current policies may not fully address its impact, underscoring the need for expanded chronic disease management programs and a shift towards prevention-focused healthcare paradigms.

Background: Health-adjusted life expectancy (HALE) is an indicator of the average lifespan in good health. Through this study, we aimed to identify regional disparities in the gap between HALE and life expectancy, considering the trends that have changed over time in Korea., Methods: We employed a group-based multi-trajectory modeling approach to capture trends in the gap between HALE and life expectancy at the regional level from 2008 to 2019. HALE was calculated using incidence-based "years lived with disability." This methodology was also employed in the Korean National Burden of Disease Study., Results: Based on five different information criteria, the most fitted number of trajectory groups was seven, with at least 11 regions in each group. Among the seven groups, one had an exceptionally large gap between HALE and life expectancy compared to that of the others. This group was assigned to 17 regions, of which six were metropolitan cities., Conclusion: Based on the results of this study, we identified regions in which health levels have deteriorated over time, particularly within specific areas of metropolitan cities. These findings can be used to design comprehensive policy interventions for community health promotion and urban regeneration projects in the future., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: Healthy life expectancy is a well-recognized indicator for establishing health policy goals used in Korea's Health Plan. This study aimed to explore Koreans' healthy life expectancy and its gender, income, and regional disparities from 2008 to 2020., Methods: This study was conducted on the entire population covered by health insurance and medical aid program in Korea. The incidence-based "years lived with disability" for 260 disease groups by gender, income level, and region was calculated employing the methodology developed in the Korean National Burden of Disease Study, and it was used as the number of healthy years lost to calculate health-adjusted life expectancy (HALE)., Results: Koreans' HALE increased from 68.89 years in 2008 to 71.82 years in 2020. Although the gender disparity in HALE had been decreasing, it increased to 4.55 years in 2020. As of 2020, 5.90 years out of 8.67 years of the income disparity (Q5-Q1) in HALE were due to the disparity between Q1 and Q2, the low-income groups. Income and regional disparities in HALE exhibited an increasing trend, and these disparities were higher in men than in women., Conclusion: A subgroup with a low health level was identified through the HALE results, and it was confirmed that improving the health level of this population can reduce health inequalities and improve health at the national level. Further exploration of the HALE calculation methodology may help in the development of effective policies such as prioritizing interventions for health risk factors., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Objective: This is the first prospective cohort study of Huntington's disease (HD) in Korea. This study aimed to investigate the caregiver burden in relation to the characteristics of patients and caregivers., Methods: From August 2020 to February 2022, we enrolled patients with HD from 13 university hospitals in Korea. We used the 12-item Zarit Burden Interview (ZBI-12) to evaluate the caregiver burden. We evaluated the clinical associations of the ZBI-12 scores by linear regression analysis and investigated the differences between the low- and high-burden groups., Results: Sixty-five patients with HD and 45 caregivers were enrolled in this cohort study. The average age at onset of motor symptoms was 49.3 ± 12.3 years, with an average cytosine-adenine-guanine (CAG)n of 42.9 ± 4.0 (38-65). The median ZBI-12 score among our caregivers was 17.6 ± 14.2. A higher caregiver burden was associated with a more severe Shoulson-Fahn stage (p = 0.038) of the patients. A higher ZBI-12 score was also associated with lower independence scale (B = -0.154, p = 0.006) and functional capacity (B = -1.082, p = 0.002) scores of patients. The caregiving duration was longer in the high- than in the low-burden group. Caregivers' demographics, blood relation, and marital and social status did not affect the burden significantly., Conclusion: HD patients' neurological status exerts an enormous impact on the caregiver burden regardless of the demographic or social status of the caregiver. This study emphasizes the need to establish an optimal support system for families dealing with HD in Korea. A future longitudinal analysis could help us understand how disease progression aggravates the caregiver burden throughout the entire disease course.

Objective: Parkinson's disease (PD) patients often find it difficult to visit hospitals because of motor symptoms, distance to the hospital, or the absence of caregivers. Telemedicine is one way to solve this problem., Methods: We surveyed 554 PD patients from eight university hospitals in Korea. The questionnaire consisted of the clinical characteristics of the participants, possible teleconferencing., Methods: , and preferences for telemedicine., Results: A total of 385 patients (70%) expressed interest in receiving telemedicine. Among them, 174 preferred telemedicine whereas 211 preferred in-person visits. The longer the duration of disease, and the longer the time required to visit the hospital, the more patients were interested in receiving telemedicine., Conclusion: This is the first study on PD patients' preferences regarding telemedicine in Korea. Although the majority of patients with PD have a positive view of telemedicine, their interest in receiving telemedicine depends on their different circumstances.