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Abstract It has been reported that a scenario-based cognitive behavioral therapy mobile app including Todac Todac was effective in improving depression in the general public. However, no study has been conducted on whether Todac Todac is effective in dialysis patients. Therefore, this study was intended to determine whether the use of this app was effective in improving depression in dialysis patients. Sixty-five end-stage kidney disease patients receiving dialysis at Soonchunhyang University Cheonan Hospital were randomly assigned to the Todac Todac app program (experimental group) or an E-moods daily mood chart app program (control group) for 3 weeks. The degree of depression was measured before and after using the app.After the end of the 3-week program, a small but significant improvement was observed in the Trait anxiety (p

Background This study investigates the impact of fluctuating lipid levels on endothelial dysfunction. Methods Human aortic and umbilical vein endothelial cells were cultured under varying palmitic acid (PA) concentrations: 0, 50, and 100 μM, and in a variability group alternating between 0 and 100 μM PA every 8 hours for 48 hours. In the lipid variability group, cells were exposed to 100 μM PA during the final 8 hours before analysis. We assessed inflammation using real-time polymerase chain reaction, Western blot, and cytokine enzyme-linked immunosorbent assay (ELISA); reactive oxygen species (ROS) levels with dichlorofluorescin diacetate assay; mitochondrial function through oxygen consumption rates via XF24 flux analyzer; and endothelial cell functionality via wound healing and cell adhesion assays. Cell viability was evaluated using the MTT assay. Results Variable PA levels significantly upregulated inflammatory genes and adhesion molecules (Il6, Mcp1, Icam, Vcam, E-selectin, iNos) at both transcriptomic and protein levels in human endothelial cells. Oscillating lipid levels reduced basal respiration, adenosine triphosphate synthesis, and maximal respiration, indicating mitochondrial dysfunction. This lipid variability also elevated ROS levels, contributing to a chronic inflammatory state. Functionally, these changes impaired cell migration and increased monocyte adhesion, and induced endothelial apoptosis, evidenced by reduced cell viability, increased BAX, and decreased BCL2 expression. Conclusion Lipid variability induce endothelial dysfunction by elevating inflammation and oxidative stress, providing mechanistic insights into how lipid variability increases cardiovascular risk.

Abstract Aims/Introduction To investigate the long‐term efficacy of various encapsulated xenogeneic islet transplantation, and to explore the impact of different donor porcine genetic traits on islet transplantation outcomes. Materials and Methods Donor porcine islets were obtained from wild‐type, α1,3‐galactosyltransferase knockout (GTKO) and GTKO with overexpression of membrane cofactor protein genotype. Naked, alginate, alginate‐chitosan (AC), alginate‐perfluorodecalin (A‐PFD) and AC‐perfluorodecalin (AC‐PFD) encapsulated porcine islets were transplanted into diabetic mice. Results In vitro assessments showed no differences in the viability and function of islets across encapsulation types and donor porcine islet genotypes. Xenogeneic encapsulated islet transplantation with AC‐PFD capsules showed the most favorable long‐term outcomes, maintaining normal blood glucose levels for 180 days. A‐PFD capsules showed comparable results to AC‐PFD capsules, followed by AC capsules and alginate capsules. Conversely, blood glucose levels in naked islet transplantation increased to >300 mg/dL within a week after transplantation. Naked islet transplantation outcomes showed no improvement based on donor islet genotype. However, alginate or AC capsules showed delayed increases in blood glucose levels for GTKO and GTKO with overexpression of membrane cofactor protein porcine islets compared with wild‐type porcine islets. Conclusion The AC‐PFD capsule, designed to ameliorate both hypoxia and inflammation, showed the highest long‐term efficacy in xenogeneic islet transplantation. Genetic modifications of porcine islets with GTKO or GTKO with overexpression of membrane cofactor protein did not influence naked islet transplantation outcomes, but did delay graft failure when encapsulated.

Abstract BackgroundThe bidirectional encoder representations from transformers (BERT) model has attracted considerable attention in clinical applications, such as patient classification and disease prediction. However, current studies have typically progressed to application development without a thorough assessment of the model’s comprehension of clinical context. Furthermore, limited comparative studies have been conducted on BERT models using medical documents from non–English-speaking countries. Therefore, the applicability of BERT models trained on English clinical notes to non-English contexts is yet to be confirmed. To address these gaps in literature, this study focused on identifying the most effective BERT model for non-English clinical notes. ObjectiveIn this study, we evaluated the contextual understanding abilities of various BERT models applied to mixed Korean and English clinical notes. The objective of this study was to identify the BERT model that excels in understanding the context of such documents. MethodsUsing data from 164,460 patients in a South Korean tertiary hospital, we pretrained BERT-base, BERT for Biomedical Text Mining (BioBERT), Korean BERT (KoBERT), and Multilingual BERT (M-BERT) to improve their contextual comprehension capabilities and subsequently compared their performances in 7 fine-tuning tasks. ResultsThe model performance varied based on the task and token usage. First, BERT-base and BioBERT excelled in tasks using classification ([CLS]) token embeddings, such as document classification. BioBERT achieved the highest F1F1 ConclusionsThis study highlighted the effectiveness of various BERT models in a multilingual clinical domain. The findings can be used as a reference in clinical and language-based applications.

Summary: Background: Interstitial lung disease (ILD) poses a serious threat in patients with rheumatoid arthritis (RA). However, the impact of cornerstone drugs, including methotrexate (MTX) and TNF inhibitor, on RA-associated ILD (RA-ILD) remains controversial. Methods: Using an SKG mouse model and single-cell transcriptomics, we investigated the effects of MTX and TNF blockade on ILD. Findings: Our study revealed that MTX exacerbates pulmonary inflammation by promoting immune cell infiltration, Th17 activation, and fibrosis. In contrast, TNF inhibitor ameliorates these features and inhibits ILD progression. Analysis of data from a human RA-ILD cohort revealed that patients with ILD progression had persistently higher systemic inflammation than those without progression, particularly among the subgroup undergoing MTX treatment. Interpretation: These findings highlight the need for personalized therapeutic approaches in RA-ILD, given the divergent outcomes of MTX and TNF inhibitor. Funding: This work was funded by GENINUS Inc., and the National Research Foundation of Korea, and Seoul National University Hospital.

Background Chronic kidney disease is a significant health burden worldwide, with increasing incidence. Although several genome-wide association studies (GWAS) have investigated single nucleotide polymorphisms (SNP) associated with kidney trait, most studies were focused on European ancestry. Methods We utilized clinical and genetic information collected from the Korean Genome and Epidemiology Study (KoGES). Results More than five million SNPs from 58,406 participants were analyzed. After meta-GWAS, 1,360 loci associated with estimated glomerular filtration rate (eGFR) at a genome-wide significant level (p = 5 × 10–8) were identified. Among them, 399 loci were validated with at least one other biomarker (blood urea nitrogen [BUN] or eGFRcysC) and 149 loci were validated using both markers. Among them, 18 SNPs (nine known ones and nine novel ones) with 20 putative genes were found. The aggregated effect of genes estimated by MAGMA gene analysis showed that these significant genes were enriched in kidney-associated pathways, with the kidney and liver being the most enriched tissues. Conclusion In this study, we conducted GWAS for more than 50,000 Korean individuals and identified several variants associated with kidney traits, including eGFR, BUN, and eGFRcysC. We also investigated functions of relevant genes using computational methods to define putative causal variants.

Abstract Background Chronic kidney disease (CKD) poses a significant health challenge, yet early detection remains difficult. Resting heart rate (RHR) has been shown to be a reliable indicator of type 2 diabetes, prompting interest in its potential as an independent predictor of CKD. This study aimed to investigate the association between RHR and CKD prevalence, as well as explore potential interactions between RHR and other risk factors for CKD in a sample of 25,246 adults. Methods Data from the Korean National Health and Nutrition Examination Survey (2011–2014) were utilized for this study, with 19,210 participants included after screening. Logistic regression analysis was employed to examine the relationship between RHR and CKD prevalence. Stratified analyses were conducted based on known risk factors for CKD. Results Participants with an RHR ≥ 90 bpm exhibited a 2.07-fold [95% confidence interval (CI): 1.28–3.34] and 2.22-fold (95% CI: 1.42–3.48) higher prevalence of CKD in men and women, respectively, compared to those with an RHR

In response to the increase in the prevalence of chronic kidney disease (CKD) in Korea, the growth of patients requiring renal replacement therapy and the subsequent increase in medical costs, the rapid expansion of patients with end-stage kidney disease (ESKD), and the decrease in patients receiving home therapy, including peritoneal dialysis, the Korean Society of Nephrology has proclaimed the new policy, Kidney Health Plan 2033 (KHP 2033). KHP 2033 would serve as a milestone to bridge the current issues to a future solution by directing the prevention and progression of CKD and ESKD, particularly diabetic kidney disease, and increasing the proportion of home therapy, thereby reducing the socioeconomic burden of kidney disease and improving the quality of life. Here, we provide the background for the necessity of KHP 2033, as well as the contents of KHP 2033, and enlighten the Korean Society of Nephrology’s future goals. Together with patients, healthcare providers, academic societies, and national policymakers, we need to move forward with goal-oriented drive and leadership to achieve these goals.

Abstract Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is currently the leading cause of chronic liver disease worldwide. Metabolic Dysfunction-Associated Steatohepatitis (MASH), an advanced form of MASLD, can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Based on recent findings by our team that liver 5HT2A knockout male mice suppressed steatosis and reduced fibrosis-related gene expression, we developed a peripheral 5HT2A antagonist, compound 11c for MASH. It shows good in vitro activity, stability, and in vivo pharmacokinetics (PK) in rats and dogs. Compound 11c also shows good in vivo efficacy in a diet-induced obesity (DIO) male mice model and in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) male mice model, effectively improving histologic features of MASH and fibrosis. According to the tissue distribution study using [14C]-labeled 11c, the compound was determined to be a peripheral 5HT2A antagonist. Collectively, first-in-class compound 11c shows promise as a therapeutic agent for the treatment of MASLD and MASH.

The Kribi-Campo sub-basin, located in the Gulf of Guinea, constitutes the southeastern segment of the Cameroon Atlantic Margin. Drilling in the Aptian salt unit revealed a sparse hydrocarbon presence, contrasting with modest finds in its counterparts like the Ezanga Salt in Gabon and the Rio Muni Salt in Equatorial Guinea. This discrepancy prompted a reassessment of the depositional context and hydrocarbon potential of the Mundeck salt unit. By integrating 2D seismic reflection and borehole data analysis, this study established the structural and stratigraphic framework of the area, emphasizing the salt unit’s significance. Borehole data indicate a localized salt unit offshore Kribi, with seismic reflection data revealing distinct forms of diapir and pillow. This salt unit displays a substantial lateral extent with thicknesses ranging from 4000 m to 6000 m. The depositional context is linked to the following two major geological events: a significant sea-level drop due to margin uplift during the Aptian and thermodynamic processes driven by transfer faults related to mid-oceanic ridge formation. These events were crucial in forming and evolving the Mundeck Salt. Regarding hydrocarbon prospects, this study identifies the unit as being associated with potential petroleum plays, supported by direct hydrocarbon indicators and fault-related structures. The findings suggest that untapped hydrocarbon resources may still exist, underscoring the need for further exploration and analysis.

Background Fabry nephropathy is characterized by a deficiency of lysosomal alpha-galactosidase A, which results in proteinuria and kidney disease. The ineffectiveness of enzyme replacement therapy (ERT) for severe kidney failure highlights the need for early detection and meaningful markers. However, because the diagnosis and treatment of Fabry disease can vary according to the expertise of physicians, we evaluated the opinions of Korean specialists. Methods A questionnaire regarding the management of Fabry nephropathy was emailed to healthcare providers with the experience or ability to treat individuals with Fabry nephropathy. Results Of the 70 experts who responded to the survey, 43 were nephrologists, and 64.3% of the respondents reported having treated patients with Fabry disease. Pediatricians are treating primarily patients with classic types of the disease, while nephrologists and cardiologists are treating more patients with variant types. Only 40.7% of non-nephrologists agreed that a kidney biopsy was required at the time of diagnosis, compared with 81.4% of nephrologists. Thirty-eight of 70 respondents (54.3%) reported measuring globotriaosylsphingosine (lyso-Gb3) as a biomarker. The most common period to measure lyso-Gb3 was at the time of diagnosis, followed by after ERT, before ERT, and at screening. For the stage at which ERT should begin, microalbuminuria and proteinuria were chosen by 51.8% and 28.6% of respondents, respectively. Conclusion Nephrologists are more likely to treat variant Fabry disease rather than classic cases, and they agree that ERT should be initiated early in Fabry nephropathy, using lyso-Gb3 as a biomarker.

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and Kmbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5–12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13–16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

This study employed 1D numerical pseudo models to examine the Upper Jurassic carbonate succession, focusing on the Mikulov Formation in the Vienna Basin region. It addresses the protracted and complex history of the Jurassic source rock play, revealing a transition from rapid syn-rift (>200 m/Ma) to slower post-rift sedimentation/subsidence of the overlying layers during extensional deformation (up to 120 m/Ma with a thickness of 1300 m). This provides valuable insights into the rift-to-drift stage of the central Alpine Tethys margin. The Mikulov marls exhibit characteristics of a post-rift passive margin with slow sedimentation rates. However, a crustal stretching analysis using syn-rift heat flow sensitivity suggested that thermal extension of the basement alone cannot fully explain the mid-Jurassic syn-rift stage in this segment of the Alpine Tethys. The sensitivity analysis showed that the mid-late Jurassic differential syn-rift sequences were exposed to slightly cooler temperatures than the crustal stretching model predicted. Heat flow values below 120 mW/m2 aligned with measurements from deeply settled Mesozoic successions, suggesting cold but short gravity-driven subsidence. This may account for the relatively low thermal maturation of the primary source rock interval identified by the time-chart analysis, despite the complex tectonic history and considerable sedimentary burial. The post-Mesozoic changes in the compaction trend are possibly linked to the compressional thrusting of the Alpine foreland and postdating listric faulting across the Vienna Basin.

Primary cilia are microtubule-based sensory and signaling organelles on the surfaces of most eukaryotic cells. Despite their early description by microscopy studies, islet cilia had not been examined in the functional context until recent decades. In pancreatic islets as in other tissues, primary cilia facilitate crucial developmental and signaling pathways in response to extracellular stimuli. Many human developmental and genetic disorders are associated with ciliary dysfunction, some manifesting as obesity and diabetes. Understanding the basis for metabolic diseases in human ciliopathies has been aided by close examination of cilia action in pancreatic islets at cellular and molecular levels. In this article, we review the evidence for ciliary expression on islet cells, known roles of cilia in pancreas development and islet hormone secretion, and summarize metabolic manifestations of human ciliopathy syndromes. We discuss emerging data on primary cilia regulation of islet cell signaling and the structural basis of cilia-mediated cell crosstalk, and offer our interpretation on the role of cilia in glucose homeostasis and human diseases.

Abstract Glutaminase 2 (GLS2), a master regulator of glutaminolysis that is induced by p53 and converts glutamine to glutamate, is abundant in the liver but also exists in pancreatic β-cells. However, the roles of GLS2 in islets associated with glucose metabolism are unknown, presenting a critical issue. To investigate the roles of GLS2 in pancreatic β-cells in vivo, we generated β-cell-specific Gls2 conditional knockout mice (Gls2 CKO), examined their glucose homeostasis, and validated the findings using a human islet single-cell analysis database. GLS2 expression markedly increased along with p53 in β-cells from control (RIP-Cre) mice fed a high-fat diet. Furthermore, Gls2 CKO exhibited significant diabetes mellitus with gluconeogenesis and insulin resistance when fed a high-fat diet. Despite marked hyperglycaemia, impaired insulin secretion and paradoxical glucagon elevation were observed in high-fat diet-fed Gls2 CKO mice. GLS2 silencing in the pancreatic β-cell line MIN6 revealed downregulation of insulin secretion and intracellular ATP levels, which were closely related to glucose-stimulated insulin secretion. Additionally, analysis of single-cell RNA-sequencing data from human pancreatic islet cells also revealed that GLS2 expression was elevated in β-cells from diabetic donors compared to nondiabetic donors. Consistent with the results of Gls2 CKO, downregulated GLS2 expression in human pancreatic β-cells from diabetic donors was associated with significantly lower insulin gene expression as well as lower expression of members of the insulin secretion pathway, including ATPase and several molecules that signal to insulin secretory granules, in β-cells but higher glucagon gene expression in α-cells. Although the exact mechanism by which β-cell-specific GLS2 regulates insulin and glucagon requires further study, our data indicate that GLS2 in pancreatic β-cells maintains glucose homeostasis under the condition of hyperglycaemia.

Background: Grounded in intersectionality theory, this study examined the 6-year prevalence trend and correlates in meeting Canada's 24-Hour Movement Guidelines (Guidelines hereafter) in a nationally representative adolescent samples of South Korea (officially the Republic of Korea). Methods: Self-reported, annually repeated cross-sectional data collected between 2013 and 2018 were used (n = 372,433, 12–17 years old, 47.9% females). Adolescents were categorized as meeting or not meeting different sets of physical activity, screen time (ST), and sleep recommendations within the Guidelines, separately for weekdays and weekend days. Intersectional correlates included sex and social class (i.e., family economic status, parental education level, and academic performance). Multiple logistic regression analyses were performed. Results: Overall, the proportion of adolescents meeting physical activity, ST, and sleep recommendations were 5.3%, 60.3%, and 10.2% on weekdays and 5.3%, 28.2%, and 46.4% on weekend days, respectively. Between 2013 and 2018, no substantial changes were observed for meeting the physical activity or sleep recommendation, while meeting the ST recommendation was markedly lower in 2018. The proportion of meeting all 3 recommendations were 0.5% for weekdays and 0.8% for weekend days. Overall, compared to female adolescents, male adolescents were consistently associated with more favorable patterns of meeting different sets of recommendations, regardless of social class. Among females only, social class appeared to be not important or even detrimental in meeting different sets of recommendations. Being male, compounded with social class, was associated with meeting the ST recommendation. Conclusion: Less than 1% of Korean adolescents met the overall Guidelines. Intersectionality-based analysis and intervention may be important in promoting healthy active lifestyles among South Korean adolescents.

Abstract Background Clonal haematopoiesis of indeterminate potential (CHIP) is a predisposition to haematological malignancy whose relationship with chronic inflammatory diseases, such as cardiovascular diseases, has been highlighted. Here, we aimed to investigate the CHIP emergence rate and its association with inflammatory markers in Behçet’s disease (BD). Methods We performed targeted next-generation sequencing to detect the presence of CHIP using peripheral blood cells from 117 BD patients and 5004 healthy controls between March 2009 and September 2021 and analysed the association between CHIP and inflammatory markers. Results CHIP was detected in 13.9% of patients in the control group and 11.1% of patients in the BD group, indicating no significant intergroup difference. Among the BD patients of our cohort, five variants (DNMT3A, TET2, ASXL1, STAG2, and IDH2) were detected. DNMT3A mutations were the most common, followed by TET2 mutations. CHIP carriers with BD had a higher serum platelet count, erythrocyte sedimentation rate, and C-reactive protein level; older age; and lower serum albumin level at diagnosis than non-CHIP carriers with BD. However, the significant association between inflammatory markers and CHIP disappeared after the adjustment for various variables, including age. Moreover, CHIP was not an independent risk factor for poor clinical outcomes in patients with BD. Conclusions Although BD patients did not have higher CHIP emergence rates than the general population, older age and degree of inflammation in BD were associated with CHIP emergence.

Abstract Background This study aimed to examine factors associated with postpartum depression (PPD) symptoms during the COVID-19 pandemic among postpartum women in five countries, a subject that has not been investigated thus far. Methods A multi-country, cross-sectional, online survey was conducted with a convenience sample of 3,523 postpartum women in Brazil, South Korea, Taiwan, Thailand, and the United Kingdom, from July to November 2021. Sociodemographic and obstetric data, food insecurity, COVID-19 positive status, COVID-19 vaccination, infant feeding, breastfeeding belief score, and social support were investigated. PPD and social support were measured using the Edinburgh Postnatal Depression Scale and Maternal Social Support Scale, respectively. Descriptive statistics, chi-squared tests, and t-tests were used to identify associations with PPD symptoms. A binary logistic regression model was used to identify explanatory factors associated with PPD and adjusted odds ratios (OR) and 95% confidence intervals (CIs) were calculated. Results Women in Taiwan (AOR = 0.5; 95%CI 0.34, 0.73) and Thailand (AOR = 0.68; 95%CI 0.46, 0.99) had a lower risk of PPD symptoms than those in Brazil. In addition, women with planned pregnancies had a lower risk of PPD (AOR = 0.74; 95%CI 0.60, 0.91). Younger women (AOR = 1.62; 95%CI 1.05, 2.51), health problems during pregnancy, delivery, or postpartum (AOR = 1.71; 95%CI 1.42, 2.06), and no change or worse food insecurity during COVID-19 (AOR = 1.66; 95%CI 1.21, 1.27 for no change and AOR = 1.68; 95%CI 1.27, 1.23, respectively) presented a higher likelihood of having PPD. Feeding babies with expressed human milk (AOR = 1.25; 95%CI 1.03, 1.50) and/or complementary food (AOR = 1.51; 95%CI 1.17, 1.94) were associated with PPD symptoms. Women who received low (AOR = 7.74; 95%CI 5.43, 11.03) or medium support (AOR = 3.25; 95%CI 2.71, 3.88) had higher likelihoods of PPD. Conclusion PPD symptoms during the pandemic were high in young women, particularly Brazilian women, with health problems in the puerperal pregnancy cycle who fed their babies expressed breast milk and/or complementary food. Low social support also impacted PPD symptoms. This study highlights the need for the professional screening for PPD and provision of virtual or personal support.

Objectives This study aims to investigate COVID-19 epidemiological data in patients with autoimmune inflammatory rheumatic diseases (AIRDs) during Omicron wave and to identify clinical factors associated with infection, including COVID-19 vaccination.Methods This prospective longitudinal study was performed between January and October 2022 in South Korea. Patients were classified into AIRD and non-AIRD groups according to their underlying diseases. COVID-19 status, date of confirmed infection and vaccination status were captured from the patient survey and national database. The COVID-19 incidence during the study period was examined and compared between the two groups. The effect of clinical factors on the infection rate was analysed in the AIRD group.Results A total of 1814 patients (1535 and 279 in the AIRD and non-AIRD groups, respectively) were analysed. During the study period, 857 COVID-19 cases were reported in 834 patients (46.0%). The infection rates in the AIRD and non-AIRD groups were comparable. In the AIRD group, older age (≥70 years) and glucocorticoid use were significantly associated with a lower rate of COVID-19 infection. The third booster vaccination significantly lowered the incidence of COVID-19 (adjusted HR 0.85 (95% CI 0.73 to 0.99)), and the prophylactic effect was more evident in patients aged

Background/Aims We investigated the prevalence, associated factors, and comorbidities of high-risk obstructive sleep apnea (OSA) as determined by the STOP-BANG questionnaire in a Korean adult population. Methods Data were obtained from 7,650 adults (aged ≥ 40 years) who participated in the Korea National Health and Nutrition Examination Survey (2019–2020). Multiple logistic regression analyses were used to evaluate the association of socioeconomic status, lifestyle related factors, and comorbidities with high-risk OSA (STOP-BANG score, 5–8). Results The prevalence of high-risk OSA according to the STOP-BANG questionnaire was 12.0 %. Older age, male, current smoking, heavy alcohol consumption, and more comorbidities were associated with higher STOP-BANG scores. In multivariable adjusted analysis, diabetes mellitus (DM) (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.25 to 1.97), hypertension (OR, 4.81; 95% CI, 3.88 to 5.97), and obesity (OR, 2.02; 95% CI, 1.60 to 2.56) were associated with high risk of OSA, and when hypertension, DM, and obesity were combined, the risk increased synergistically (OR, 3.88; 95% CI, 2.94 to 5.11). Conclusions According to the STOP-BANG questionnaire, the high risk of OSA was more common in males, and was associated with chronic metabolic disease, particularly in those with DM, hypertension, and obesity combined. Active OSA screening, prevention, and management may be beneficial to improving health outcomes related to OSA in these populations.

The effect of combined Korean medicine treatment including facial chuna manual therapy was retrospectively investigated in patients with Bell’s palsy. There were 16 patients (14 males) who received 2 months outpatient treatment following > 14 days of hospitalization. The Yanagihara score and House-Brackmann grade were used to measure the severity of symptoms and recovery. The patients (mean age 58.5 ± 24.74 years) were categorized based on their medical history of hypertension (n = 10), diabetes millitus (n = 10), or oral intake of steroids early in the diagnosis of Bell’s palsy (n = 10). There was no difference between patients who had or did not have a previous history of diabetes mellitus or oral steroid. Both the Yanagihara-score and House-Brackmann grade improved significantly in the total patient sample after treatment (p < 0.001). Combined Korean medicine including facial chuna manual therapy may have a beneficial effect on patient symptoms and recovery.

Abstract Background There is limited information regarding disease-modifying antirheumatic drug (DMARD)-dependent risks of overall, incident, and recurrent herpes zoster (HZ) during first-line biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD) treatment among patients with seropositive rheumatoid arthritis (RA) in terms of HZ risk. Methods A total of 11,720 patients with seropositive RA who were prescribed bDMARD or tofacitinib between January 2011 and January 2019 from the Korean Health Insurance Review & Assessment Service database were studied. A multivariate Cox proportional hazards regression model was adopted to evaluate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for the risk of HZ dependent on the choice of first-line bDMARDs or tsDMARD, including etanercept, infliximab, adalimumab, golimumab, tocilizumab, rituximab, tofacitinib, and abatacept. Results During the 34,702 person-years of follow-up, 1686 cases (14.4%) of HZ were identified, including 1372 (11.7%) incident and 314 (2.7%) recurrent HZs. Compared with that of the abatacept group, tofacitinib increased the overall risk (aHR, 2.46; 95% CI, 1.61–3.76; P

Abstract Background Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease (ILD) featuring dense fibrosis of the visceral pleura and subpleural parenchyma, mostly in the upper lobes. PPFE can present in other ILDs, including rheumatoid arthritis-associated ILD (RA-ILD). The aim of this retrospective study was to investigate the prevalence and clinical implications of coexistent PPFE in RA-ILD. Methods Overall, 477 patients with RA-ILD were recruited from two cohorts; their clinical data and HRCT images were analysed. The criteria for diagnosing PPFE were (1) pleural thickening with bilateral subpleural dense fibrosis in the upper lobes, (2) evidence of disease progression, and (3) absence of other identifiable aetiologies. Results The median follow-up duration was 3.3 years. The mean age of the patients was 63.4 years, and 60.0% were women. PPFE was identified in 31 patients (6.5%). The PPFE group showed significantly lower body mass index and forced vital capacity (FVC) and more frequent usual interstitial pneumonia (UIP)-like pattern on HRCT than no-PPFE group. The risk factors for all-cause mortality were older age, lower FVC, and the presence of UIP-like pattern on HRCT; PPFE was not significantly associated with mortality in both all patients and a subgroup with a UIP-like pattern. The presence of PPFE was associated with a significantly increased risk of pneumothorax and greater decline in diffusing capacity. Conclusions PPFE was not rare in patients with RA-ILD and was significantly associated with an increased risk of pneumothorax and greater lung function decline, though we found no significant association with mortality.

Despite numerous studies on individual charitable donations and cause-related marketing have been conducted, the framing of the donation amount has not been studied. This research suggests that people's intention to donate to charity differs depending on whether the donation amount is framed as all-inclusive or partitioned. The main effect of partitioned framing was moderated by individual differences in the need for cognition and regulatory focus. The results of our research are threefold. First, people responded more positively to engage in prosocial behavior in the partitioned donation amount condition than in the all-inclusive condition, even when the total amounts were the same. Second, the framing effect of the donation amount differed according to the need for cognition. Individuals with a high need for cognition (NFC) had a higher intention to donate in the partitioned donation amount condition than in the all-inclusive condition, while individuals with low NFC did not show differences in either condition. Third, the framing effect of the donation amount differed according to regulatory focus. Prevention-focused individuals were more willing to donate in the partitioned condition than in the all-inclusive condition, while promotion-focused individuals did not show differences in either condition. In addition, the interaction of framing and regulatory focus on donation intention was mediated by the perceived authenticity of the donation organization. This research has several academic and practical implications for effective corporate social responsibility activities.

Background Diabetic nephropathy (DN) is characterized by albuminuria and accumulation of extracellular matrix (ECM) in kidney. Transforming growth factor-β (TGF-β) plays a central role in promoting ECM accumulation. We aimed to examine the effects of EW-7197, an inhibitor of TGF-β type 1 receptor kinase (ALK5), in retarding the progression of DN, both in vivo, using a diabetic mouse model (db/db mice), and in vitro, in podocytes and mesangial cells. Methods In vivo study: 8-week-old db/db mice were orally administered EW-7197 at a dose of 5 or 20 mg/kg/day for 10 weeks. Metabolic parameters and renal function were monitored. Glomerular histomorphology and renal protein expression were evaluated by histochemical staining and Western blot analyses, respectively. In vitro study: DN was induced by high glucose (30 mM) in podocytes and TGF-β (2 ng/mL) in mesangial cells. Cells were treated with EW-7197 (500 nM) for 24 hours and the mechanism associated with the attenuation of DN was investigated. Results Enhanced albuminuria and glomerular morphohistological changes were observed in db/db compared to that of the nondiabetic (db/m) mice. These alterations were associated with the activation of the TGF-β signaling pathway. Treatment with EW-7197 significantly inhibited TGF-β signaling, inflammation, apoptosis, reactive oxygen species, and endoplasmic reticulum stress in diabetic mice and renal cells. Conclusion EW-7197 exhibits renoprotective effect in DN. EW-7197 alleviates renal fibrosis and inflammation in diabetes by inhibiting downstream TGF-β signaling, thereby retarding the progression of DN. Our study supports EW-7197 as a therapeutically beneficial compound to treat DN.

Background An increased pericoronary fat attenuation index (FAI) on computed tomography angiography (CTA) is associated with increased all-cause and cardiac mortality in the general population. However, the ability of pericoronary FAI to predict long-term outcomes in chronic kidney disease (CKD) patients is unknown. Methods In this single-center retrospective longitudinal cohort study, we assessed the utility of CTA-based pericoronary FAI measurement to predict mortality of CKD patients, including those with end-stage renal disease (ESRD). Mapping and analysis of pericoronary FAI involved three major proximal coronary arteries. The prognostic value of pericoronary FAI for long-term mortality was assessed with multivariable Cox regression models. Results Among 268 CKD participants who underwent coronary CTA, 209 participants with left anterior descending artery (LAD) FAI measurements were included. The pericoronary FAI measured at the LAD was not significantly associated with adjusted risk of all-cause mortality (hazard ratio [HR], 2.08; 95% confidence interval [CI], 0.94–3.51) in any CKD group. However, ESRD patients with elevated pericoronary FAI values had a greater adjusted risk of all-cause mortality compared with the low-FAI group (HR, 2.26; 95% CI, 1.11–4.61). Conclusion The pericoronary FAI measured at the LAD predicted long-term mortality in patients with ESRD, which could provide an opportunity for early primary intervention in ESRD patients.

Vertical stratification preconditions marine heat wave (MHW) events in marginal seas. The major events since 1982 in the marginal sea area west and south of the Korean Peninsula have been led by abnormally strong stratification in the vicinity, which was detected at least two months in advance. This robust coincidence provides substantial control over mid-summer events through local stratification in early summer. Such heatwave-leading stratification can be attributed to various oceanic factors during early summers, including anomalous sea surface temperature, freshwater flux, and wind mixing. Knockout-style experiments using a 1-dimensional ocean model revealed that the upper ocean stratification in the preceding months, mostly through wind mixing, is capable of regulating MHWs. Meanwhile, in the longer historical records, gradual decreases in the intensity and frequency of the daily wind gusts were found, possibly as a mixed result of anthropogenically induced climate change and strong natural variability of the midlatitudes. This might have dominated in enhancing the occurrence of MHWs, combined with the rising background surface temperature.

The aim of this study was to introduce the implemented MEDBIZ platform based on the internet of medical things (IoMT) supporting real-time digital health services for precision medicine. In addition, we demonstrated four empirical studies of the digital health ecosystem that could provide real-time healthcare services based on IoMT using real-world data from in-hospital and out-hospital patients. Implemented MEDBIZ platform based on the IoMT devices and big data to provide digital healthcare services to the enterprise and users. The big data platform is consisting of four main components: IoMT, core, analytics, and services. Among the implemented MEDBIZ platform, we performed four clinical trials that designed monitoring services related to chronic obstructive pulmonary disease, metabolic syndrome, arrhythmia, and diabetes mellitus. Of the four empirical studies on monitoring services, two had been completed and the rest were still in progress. In the metabolic syndrome monitoring service, two studies were reported. One was reported that intervention components, especially wearable devices and mobile apps, made systolic blood pressure, diastolic blood pressure, waist circumference, and glycosylated hemoglobin decrease after 6 months. Another one was presented that increasing high-density lipoprotein cholesterol and triglyceride levels were prevented in participants with the pre-metabolic syndrome. Also, self-care using healthcare devices might help prevent and manage metabolic syndrome. In the arrhythmia monitoring service, during the real-time monitoring of vital signs remotely at the monitoring center, 318 (15.9%) general hikers found abnormal signals, and 296 (93.1%) people were recommended for treatment. We demonstrated the implemented MEDBIZ platform based on IoMT supporting digital healthcare services by acquiring real-world data for getting real-world evidence. And then through this platform, we were developing software as a medical device, digital therapeutics, and digital healthcare services, and contributing to the development of the digital health ecosystem.

Summing fault heaves is the most commonly used method to evaluate upper crustal thinning. However, since fault deformation width (W) is often assumed as a constant in the range of 75–150 km, the stretching factor estimated from fault geometry (βf) accompanies significant uncertainty. Here we propose a new approach to determine brittle stretching factors on the foundation of numerical analyses of W and further compare our results to previous methods, with specific reference to the central part of Qiongdongnan Basin, South China Sea (SCS). Our results suggest that the value of W is generally less than 80 km and mostly less than 50 km in the northern SCS margin. We confirm that applying an overestimated value of W can lead to an underestimated amount of fault-related extension and overstatement of extension discrepancy in the rifted margin. Results also indicate an inverse discrepancy with our new method in the southeast of the basin. The difference in syn-rift sediment thickness across the rifted margin likely drove the lower crust flow causing a transition between inverse and positive extension discrepancies.

Objectives This study was conducted to investigate the applicability of plant growth promoting microorganisms during restoration through re-vegetation of damaged topsoil. Methods As the vegetation to be applied to the restoration site, Weigela subsessilis, Spiraea prunifolia, Pine densiflora, Pennisetum alopecuroides were selected. An attempt was made to isolate plant growth promoting microorganisms from the root zone of plants of the same species inhabiting domestic park sites and hiking trails. Plant growth promoting activities such as phosphate solubilization ability, siderophore production ability, IAA production ability, and ACC deaminase production ability were examined, and the species to be finally applied was selected and then identified. Among the strains whose plant growth promoting activity was confirmed, Arthrobacter sp. 1B2 and Paraburkholderia terrae 1P2 were applied to the genitalia and pine, respectively, and a pot experiment was conducted to confirm the activity. Results and Discussion Forty-five strains were isolated from Weigela subsessilis, Spiraea prunifolia, Pine densiflora, Pennisetum alopecuroides and the IAA-producing ability and ACC deaminase-producing ability were confirmed for 16 strains whose phosphate solubilizing ability and siderophore-producing ability were confirmed. After selecting and identifying strains with excellent plant growth promoting ability, strains such as Cupriavidus sp, Arthrobacter sp., Pseudomonas fluorescens, Pseudomonas sp., Paraburkholderia terrae were obtained. Among them, Arthrobacter sp. 1B2 and Paraburkholderia terrae 1P2 strains were applied to genitalia and pine, respectively, and it was confirmed that plant growth was promoted. Conclusions Bioassay experiments and field applications using plant growth promoting microorganisms have been mainly studied for herbaceous species (Grandaceae, corn, oats, etc.). However, in this study, the applied plants are shrubs class, which do not significantly grow in length, targeting damaged areas with high subsoil content, which are poor in environment and insufficient in organic and inorganic matter. Therefore, it is meaningful in that the activity of plant growth promoting microorganisms focused on absorption of inorganic substances, such as phosphate solubilization activity and siderophore ability, was investigated and the activity was confirmed by performing a bioassay.

Background Activation of the intrarenal renin-angiotensin system (RAS) is implicated in the pathogenesis of kidney injury and hypertension. We aimed to investigate the protective effect of tetrahydrocurcumin (THU) on intrarenal RAS expression, kidney injury, and systolic blood pressure (SBP) in high-fat diet (HFD)-induced type 2 diabetic mice. Methods Eight-week-old male mice were fed a regular diet (RD) or HFD for 12 weeks, and THU (50 or 100 mg/kg/day) was intragastrically administered with HFD. Physiological and metabolic changes were monitored and the expression of RAS components and markers of kidney injury were assessed. Results HFD-fed mice exhibited hyperglycemia, insulin resistance, and dyslipidemia compared to those in the RD group (P

BackgroundA system that combines technology and web-based coaching can help treat chronic conditions such as diabetes. However, the effectiveness of apps in mobile health (mHealth) interventions is inconclusive and unclear due to heterogeneous interventions and varying follow-up durations. In addition, randomized controlled trial data are limited, and long-term follow-up is lacking, especially for apps integrated into electronic medical records. ObjectiveWe aimed to assess the effect of an electronic medical record–integrated mobile app for personalized diabetes self-care, focusing on the self-monitoring of blood glucose and lifestyle modifications, on glycemic control in patients with type 2 diabetes mellitus. MethodsIn a 26-week, 3-arm, randomized, controlled, open-label, parallel group trial, patients with type 2 diabetes mellitus and a hemoglobin A1c (HbA1c) level of ≥7.5% were recruited. The mHealth intervention consisted of self-monitoring of blood glucose with the automatic transfer of glucose, diet, and physical activity counseling data (iCareD system). Participants were randomly assigned to the following three groups: usual care (UC), mobile diabetes self-care (MC), and MC with personalized, bidirectional feedback from physicians (MPC). The primary outcome was the change in HbA1c levels at 26 weeks. In addition, diabetes-related self-efficacy, self-care activities, and satisfaction with the iCareD system were assessed after the intervention. ResultsA total of 269 participants were enrolled, and 234 patients (86.9%) remained in the study at 26 weeks. At 12 weeks after the intervention, the mean decline in HbA1c levels was significantly different among the 3 groups (UC vs MC vs MPC: −0.49% vs −0.86% vs −1.04%; P=.02). The HbA1c level decreased in all groups; however, it did not differ among groups after 26 weeks. In a subgroup analysis, HbA1c levels showed a statistically significant decrease after the intervention in the MPC group compared with the change in the UC or MC group, especially in patients aged

Background: Using a genetic risk score (GRS) to predict coronary heart disease (CHD) may detect disease earlier. The current study aims to assess whether GRS is associated with CHD incidence and whether it is clinically useful for improving prediction using traditional risk factors (TRFs) as well as family history. Methods: Data from a total of 48,941 participants in the Korean Genome and Epidemiology Study were analyzed in the current study. The weighted GRS was constructed using 55 single-nucleotide polymorphisms based on published genome-wide association studies. The association of GRS with incident CHD was analyzed using Cox proportional hazard model. Discrimination and reclassification were assessed to demonstrate the clinical utility of GRS. The analyses were performed separately by sex. Results: After adjusting for family history and TRFs, GRS was significantly associated with CHD incidence in men; compared to the low GRS group, men in the high GRS group had a 2.07-fold increased risk of CHD (95% confidence interval [CI]: 1.51–2.85). In men, the combination of TRFs, family history, and GRS had better performance than TRFs alone (C statistics for TRF-only model, 0.66, 95% CI, 0.64–0.69; C statistics for combination model, 0.68, 95% CI, 0.65–0.71; category-free reclassification index, 15%). In women, however, there was no significant association between GRS and CHD and no improvement between models. Conclusions: GRS was associated with CHD incidence and contributed to a small improvement of CHD prediction in men. The potential clinical use of GRS may not outweigh the value of family history.

Abstract Although Ki67 labeling index is a potential predictive marker for chemotherapy benefit, its clinical utility has been limited by the lack of a standard scoring method resulting in poor interobserver reproducibility. Especially, there is no consensus on the use of average versus hotspot score for reporting. In order to determine the best method for Ki67 scoring and validate manual scoring method proposed by the International Ki67 Working Group (IKWG), we systematically compared average versus hotspot score in 240 cases with a public domain image analysis program QuPath. We used OncotypeDx Recurrence Score (RS) as a benchmark to compare the potential clinical utility of each scoring methods. Both average and hotspot scores showed statistically significant but only modest correlation with OncotypeDx RS. Only hotspot score could meaningfully distinguish RS low-risk versus high-risk patients. However, hotspot score was less reproducible limiting its clinical utility. In summary, our data demonstrate that utility of the Ki67 labeling index is influenced by the choice of scoring method.

Abstract The introduction of massively parallel sequencing (MPS) in forensic investigation enables sequence-based large-scale multiplexing beyond size-based analysis using capillary electrophoresis (CE). For the practical application of MPS to forensic casework, many population studies have provided sequence data for autosomal short tandem repeats (STRs). However, SE33, a highly polymorphic STR marker, has little sequence-based data because of difficulties in analysis. In this study, 25 autosomal STRs were analyzed, including SE33, using an in-house MPS panel for 350 samples from four populations (African–American, Caucasian, Hispanic, and Korean). The barcoded MPS library was generated using a two-step PCR method and sequenced using a MiSeq System. As a result, 99.88% genotype concordance was obtained between length- and sequence-based analyses. In SE33, the most discordances (eight samples, 0.08%) were observed because of the 4 bp deletion between the CE and MPS primer binding sites. Compared with the length-based CE method, the number of alleles increased from 332 to 725 (2.18-fold) for 25 autosomal STRs in the sequence-based MPS method. Notably, additional 129 unique alleles, a 4.15-fold increase, were detected in SE33 by identifying sequence variations. This population data set provides sequence variations and sequence-based allele frequencies for 25 autosomal STRs.

Abstract Amphiregulin (AREG) is a transmembrane glycoprotein recently implicated in kidney fibrosis. Previously, we reported that the AREG-targeting Self-Assembled-Micelle inhibitory RNA (SAMiRNA-AREG) alleviated fibrosis by stably silencing the AREG gene, and reduced the side effects of conventional siRNA treatment of pulmonary fibrosis. However, the therapeutic effect of SAMiRNA-AREG in renal fibrosis has not been studied until now. We used two animal models of renal fibrosis generated by a unilateral ureteral obstruction (UUO) and an adenine diet (AD) to investigate whether SAMiRNA-AREG inhibited renal fibrosis. To investigate the delivery of SAMiRNA-AREG to the kidney, Cy5-labeled SAMiRNA-AREG was injected into UUO- and AD-induced renal fibrosis models. In both kidney disease models, SAMiRNA-AREG was delivered primarily to the damaged kidney. We also confirmed the protective effect of SAMiRNA-AREG in renal fibrosis models. SAMiRNA-AREG markedly decreased the UUO- and AD-induced AREG mRNA expression. Furthermore, the mRNA expression of fibrosis markers, including α-smooth muscle actin, fibronectin, α1(I) collagen, and α1(III) collagen in the UUO and AD-induced kidneys, was diminished in the SAMiRNA-AREG-treated mice. The transcription of inflammatory markers (tumor necrosis factor-α and monocyte chemoattractant protein-1) and adhesion markers (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1) was attenuated. The hematoxylin and eosin, Masson’s trichrome, and immunohistochemical staining results showed that SAMiRNA-AREG decreased renal fibrosis, AREG expression, and epidermal growth factor receptor (EGFR) phosphorylation in the UUO- and AD-induced models. Moreover, we studied the effects of SAMiRNA-AREG in response to TGF-β1 in mouse and human proximal tubule cells, and mouse fibroblasts. TGF-β1-induced extracellular matrix production and myofibroblast differentiation were attenuated by SAMiRNA-AREG. Finally, we confirmed that upregulated AREG in the UUO or AD models was mainly localized in the distal tubules. In conclusion, SAMiRNA-AREG represents a novel siRNA therapeutic for renal fibrosis by suppressing EGFR signals.

IntroductionAlbuminuria is a well-known risk factor for end-stage kidney disease, all-cause mortality, and cardiovascular mortality, even when the albumin-to-creatinine ratio is

Podocyte loss is well known to play a critical role in the early progression of diabetic nephropathy. A growing number of studies are paying attention to necroptosis, a programmed form of cell necrosis as a mechanism of podocyte loss. Although necroptosis is a recently established concept, the significance of receptor interacting serine/threonine kinase 3 (RIPK3), a gene that encodes for the homonymous enzyme RIPK3 responsible for the progression of necroptosis, is well studied. Curcumin, a natural hydrophobic polyphenol compound responsible for the yellow color of Curcuma longa, has drawn attention due to its antioxidant and anti-inflammatory effects on cells prone to necroptosis. Nonetheless, effects of curcumin on high glucose-induced podocyte necroptosis have not been reported yet. Therefore, this study investigated RIPK3 expression in high glucose-treated podocytes to identify the involvement of necroptosis via the RIPK3 pathway and the effects of curcumin treatment on RIPK3-dependent podocytopathy in a hyperglycemic environment. The study discovered that increased reactive oxygen species (ROS) in renal podocytes induced by high glucose was improved after curcumin treatment. Curcumin treatment also significantly restored the upregulated levels of VEGF, TGF-β, and CCL2 mRNAs and the downregulated level of nephrin mRNA in cultured podocytes exposed to a high glucose environment. High glucose-induced changes in protein expression of TGF-β, nephrin, and CCL2 were considerably reverted to their original levels after curcumin treatment. Increased expression of RIPK3 in high glucose-stimulated podocytes was alleviated by curcumin treatment as well as N-acetyl cysteine (NAC, an antioxidant) or GSK′872 (a RIPK3 inhibitor). Consistent with this, the increased necroptosis-associated molecules, such as RIPK3, pRIPK3, and pMLKL, were also restored by curcumin in high glucose-treated mesangial cells. DCF-DA assay confirmed that such a result was attributed to the reduction of RIPK3 through the antioxidant effect of curcumin. Further observations of DCF-DA-sensitive intracellular ROS in NAC-treated and GSK′872-treated podocyte groups showed a reciprocal regulatory relationship between ROS and RIPK3. The treatment of curcumin and GSK′872 in podocytes incubated with high glucose protected from excessive intracellular superoxide anion production. Taken together, these results indicate that curcumin treatment can protect against high glucose-induced podocyte injuries by suppressing the abnormal expression of ROS and RIPK3. Thus, curcumin might be a potential therapeutic agent for diabetic nephropathy as an inhibitor of RIPK3.

Abstract Background Metabolic syndrome (MetS) status changes over time, but few studies have investigated the relationship between the extent or duration of exposure to MetS and the risk of cardiovascular disease (CVD). We investigated the cumulative effects of MetS and its components on the risk of myocardial infarction (MI) and stroke. Methods From the Korean National Health Insurance database, 2,644,851 people who received annual health examinations from 2010 to 2013 were recruited. Exposure-weighted scores for MetS during this 4-year period were calculated in two ways: cumulative number of MetS diagnoses (MetS exposure score, range: 0–4) and the composite of its five components (MetS component exposure score, range: 0–20). The multivariable Cox proportional-hazards model was used to assess CVD risk according to the exposure-weighted scores for MetS. Results MetS was identified at least once in 37.6% and persistent MetS in 8.2% of subjects. During the follow-up (median, 4.4 years), 10,522 cases of MI (0.4%) and 10,524 cases of stoke (0.4%) occurred. The risk of MI and stroke increased gradually with increasing exposure scores of MetS and its components (each P for trend

Background : : Proteinuria is a significant risk factor for progression of IgA nephropathy (IgAN) and has a positive correlation with severity of foot process effacement (FPE). We evaluated the relationship of FPE with proteinuria and histologic characteristics, including the Oxford classification. Methods : : Patients who underwent renal biopsy and were diagnosed with IgAN at a single center were retrospectively reviewed. Patients aged less than 18 years and those with the possibility of secondary causes were excluded from the study. Subsequently, we evaluated the association between degree of proteinuria, severity of FPE, and histologic characteristics, including the Oxford classification and other immunofluorescence stains. Results : : A total of 805 cases of renal biopsy was performed at our institution, and 327 patients were diagnosed with IgAN. Among them, 82 patients were excluded. Severity of FPE had an impact on the degree of proteinuria. Notably, the group with diffuse FPE had more than about 1.3 g/day of urine protein compared to those with rare FPE. Among the histologic characteristics, M1 score and immune deposition of IgG affected severity of FPE (hazard ratios [95% confidence interval], 1.90 [1.10 to 3.26], and 3.77 [1.66 to 8.54], respectively). Conclusion : : Severity of FPE had an impact on the degree of proteinuria and may be associated with the pathogenesis of IgAN.

Cancer chemotherapy: treatment prolongs resistance caused by DNA modification Cancer cells that are transiently resistant to drug therapies owing to changes in their gene expression patterns can become resistant for longer durations if exposed to the drug treatments. A team led by Kyeong-Man Hong and Hyonchol Jang from the National Cancer Center in Goyang, South Korea, used cellular reprogramming technologies to induce changes in the DNA markers that regulate gene expression. Working with lung and gastric cancer cell lines, the researchers found that such epigenetic alterations caused many cells to become resistant to the chemotherapy drugs cisplatin and paclitaxel. In the absence of treatment, the cells soon lost their drug resistance. In the presence of the chemotherapeutics, however, the resistance trait lasted longer, a finding that could inform best practice for how to administer cancer-fighting agents in the face of epigenetic-driven drug resistance.

Abstract Objectives Histone deacetylase (HDAC) 6 promotes inflammation. We investigated the anti-arthritic effects of CKD-506, a novel HDAC6 inhibitor, in vitro and in a murine model of arthritis as a novel treatment option for rheumatoid arthritis (RA). Methods HDAC6 was overexpressed in mouse peritoneal macrophages and RAW 264.7 cells, and the effects of a HDAC6 inhibitor CKD-506 on cytokine production and activity of NF-κB and AP-1 signaling were examined. Peripheral blood mononuclear cells (PBMCs) from RA patients and fibroblast-like synoviocytes (FLS) were activated in the presence of CKD-506. Next, regulatory T cells (Tregs) were induced from RA patients and co-cultured with healthy effector T cells (Teffs) and cell proliferation was analyzed by flow cytometry. Finally, the effects of the inhibitor on the severity of arthritis were assessed in a murine model of adjuvant-induced arthritis (AIA). Results Overexpression of HDAC6 induced macrophages to produce TNF-α and IL-6. The inhibitory effect of CKD-506 was mediated via blockade of NF-κB and AP-1 activation. HDAC6 inhibition reduced TNF-α and IL-6 production by activated RA PBMCs. CKD-506 inhibited production of MMP-1, MMP-3, IL-6, and IL-8 by activated FLS. In addition, CKD-506 inhibited proliferation of Teffs directly and indirectly by improving iTreg function. In AIA rats, oral CKD-506 improved clinical arthritis in a dose-dependent manner. A combination of sub-therapeutic CKD-506 and methotrexate exerted a synergistic effect. Conclusion The novel HDAC6 inhibitor CKD-506 suppresses inflammatory responses by monocytes/macrophages, improves Treg function, and ameliorates arthritis severity in a murine model of RA. Thus, CKD-506 might be a novel and effective treatment option for RA.

Purpose This study aimed to compare the brain perfusion status of patients with chronic kidney disease to a normal control group to identify any significant differences. Materials and Methods The perfusion state of the brain was measured by MRI using the arterial spin labeling technique in 36 patients undergoing hemodialysis due to chronic kidney disease and 36 normal controls. Images were then analyzed in a voxel-wise manner to detect brain areas showing significant perfusion differences between the two groups. Results Patients with chronic kidney disease showed increased perfusion in the form of large clusters across the right fronto-parieto-temporal lobe and the left parieto-occipital lobe. In addition, perfusion increased in the bilateral thalami, midbrain, pons, and cerebellum (p < 0.01, familywise error corrected). Conclusion Brain perfusion appears to increase in patients with chronic kidney disease compared to normal controls. Uremic toxicity is thought to be the cause of this increase as it can cause damage to the microscopic blood vessels and their surrounding structures.

Abstract Background Stress is an important cause of skin disease, including hair loss. The hormonal response to stress is due to the HPA axis, which comprises hormones such as corticotropin releasing factor (CRF), adrenocorticotropic hormone (ACTH), and cortisol. Many reports have shown that CRF, a crucial stress hormone, inhibits hair growth and induces hair loss. However, the underlying mechanisms are still unclear. The aim of this study was to examine the effect of CRF on human dermal papilla cells (DPCs) as well as hair follicles and to investigate whether the HPA axis was established in cultured human DPCs. Results CRF inhibited hair shaft elongation and induced early catagen transition in human hair follicles. Hair follicle cells, both human DPCs and human ORSCs, expressed CRF and its receptors and responded to CRF. CRF inhibited the proliferation of human DPCs through cell cycle arrest at G2/M phase and induced the accumulation of reactive oxygen species (ROS). Anagen-related cytokine levels were downregulated in CRF-treated human DPCs. Interestingly, increases in proopiomelanocortin (POMC), ACTH, and cortisol were induced by CRF in human DPCs, and antagonists for the CRF receptor blocked the effects of this hormone. Conclusion The results of this study showed that stress can cause hair loss by acting through stress hormones. Additionally, these results suggested that a fully functional HPA axis exists in human DPCs and that CRF directly affects human DPCs as well as human hair follicles under stress conditions.