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Abstract Background Human placental hydrolysate (hPH) contains anti-inflammatory substances. This study aimed to analyze whether injecting hPH into the subacromial space could reduce pain in patients with shoulder impingement syndrome. Methods This single-blind, randomized controlled study enrolled 50 patients with shoulder impingement syndrome who were randomly assigned to either the hPH or placebo groups. All patients received three ultrasound-guided subacromial space injections of 4 mL hPH or normal saline every week. Outcome measurements included the Visual Analog Scale (VAS) score during daily activity, Shoulder Pain and Disability Index (SPADI), and EuroQoL 5-Dimension 5-Level (EQ-5D-5L) utility index. Patients were followed up for nine weeks after the last injection. Results Significant differences were noted in the VAS (p

Abstract Introduction Patients with cancer experience physical, mental, and social pain that affects themselves and their families. The increasing cancer incidence and advances in treatment have increased the number of cancer survivors in Korea, and there is an influx of patients in Seoul and other metropolitan areas, leading to shortages of continuous care and comprehensive life support facilities. Patients must travel long distances for treatment, which poses logistical and quality-of-life challenges. Methods This prospective cohort study targets patients with incurable cancer (n = 720) and their families (n = 288) from ten regional cancer centers and two affiliated hospitals in Korea. The sub-cohorts are based on treatment refusal, spinal metastasis with symptoms, catheter-related symptoms, and skeletal-related events. Medical records and patient-reported outcomes will be collected every three months and for up to three years, with surveys for guardians conducted for one-year post-patient demise. Discussion The dynamic nature of cancer significantly affects patients and their caregivers. It is necessary to identify the factors that affect their quality of life to integrate them into society. Conclusion The findings of this study will inform the establishment of a regional cancer center consortium. This will address the unmet needs of local cancer patients and their families, enhance their overall quality of life, and contribute to the well-being of the local community. Trial registration KCT0009177 (registered at https//cris.nih.go.kr/ on 2024/02/16).

Abstract Background Organizational adoption is a key but understudied step in translating evidence-based interventions into practice. The purpose of this study was to report recruitment strategies and factors associated with church enrollment and intervention adoption in a national implementation study of the Faith, Activity, and Nutrition (FAN) program. Methods We worked with partners using multiple strategies to disseminate intervention availability. Interested churches completed an online form. To enroll, the church coordinator (FAN coordinator) and pastor completed baseline surveys and then received intervention online training access. We compared enrolled vs. non-enrolled churches on how they heard about the study and church characteristics. We compared intervention-adopting vs. non-adopting churches on Consolidated Framework for Implementation Research (CFIR) constructs using Fisher’s exact tests, χ2, or independent sample t-tests and reported differences where p

Abstract Background Whole-genome sequencing (WGS) analyses have found higher genetic burden in autistic females compared to males, supporting higher liability threshold in females. However, genomic evidence of sex differences has been limited to European ancestry to date and little is known about how genetic variation leads to autism-related traits within families across sex. Methods To address this gap, we present WGS data of Korean autism families (n = 2255) and a Korean general population sample (n = 2500), the largest WGS data of East Asian ancestry. We analyzed sex differences in genetic burden and compared with cohorts of European ancestry (n = 15,839). Further, with extensively collected family-wise Korean autism phenotype data (n = 3730), we investigated sex differences in phenotypic scores and gene-phenotype associations within family. Results We observed robust female enrichment of de novo protein-truncating variants in autistic individuals across cohorts. However, sex differences in polygenic burden varied across cohorts and we found that the differential proportion of comorbid intellectual disability and severe autism symptoms mainly drove these variations. In siblings, males of autistic females exhibited the most severe social communication deficits. Female siblings exhibited lower phenotypic severity despite the higher polygenic burden than male siblings. Mothers also showed higher tolerance for polygenic burden than fathers, supporting higher liability threshold in females. Conclusions Our findings indicate that genetic liability in autism is both sex- and phenotype-dependent, expanding the current understanding of autism’s genetic complexity. Our work further suggests that family-based assessments of sex differences can help unravel underlying sex-differential liability in autism.

Abstract Background The cholinergic neurotransmitter system is crucial to cognitive function, with the basal forebrain (BF) being particularly susceptible to Alzheimer’s disease (AD) pathology. However, the interaction of white matter hyperintensities (WMH) in cholinergic pathways and BF atrophy without amyloid pathology remains poorly understood. Methods We enrolled patients who underwent neuropsychological tests, magnetic resonance imaging, and 18F-florbetaben positron emission tomography due to cognitive impairment at the teaching university hospital from 2015 to 2022. Among these, we selected patients with negative amyloid scans and additionally excluded those with Parkinson’s dementia that may be accompanied by BF atrophy. The WMH burden of cholinergic pathways was quantified by the Cholinergic Pathways Hyperintensities Scale (CHIPS) score, and categorized into tertile groups because the CHIPS score did not meet normal distribution. Segmentation of the BF on volumetric T1-weighted MRI was performed using FreeSurfer, then was normalized for total intracranial volume. Multivariable regression analysis was performed to investigate the association between BF volumes and CHIPS scores. Results A total of 187 patients were enrolled. The median CHIPS score was 12 [IQR 5.0; 24.0]. The BF volume of the highest CHIPS tertile group (mean ± SD, 3.51 ± 0.49, CHIPSt3) was significantly decreased than those of the lower CHIPS tertile groups (3.75 ± 0.53, CHIPSt2; 3.83 ± 0.53, CHIPSt1; P = 0.02). In the univariable regression analysis, factors showing significant associations with the BF volume were the CHIPSt3 group, age, female, education, diabetes mellitus, smoking, previous stroke history, periventricular WMH, and cerebral microbleeds. In multivariable regression analysis, the CHIPSt3 group (standardized beta [β std] = -0.25, P = 0.01), female (β std = 0.20, P = 0.04), and diabetes mellitus (β std = -0.22, P

Abstract Background Although one’s socioeconomic status affects health outcomes, limited research explored how South Korea’s National Health Insurance (NHI) system affects mortality rates. This study investigated whether health insurance type and insurance premiums are associated with mortality. Methods Based on the National Health Insurance Service-Health Screening cohort, 246,172 men and 206,534 women aged ≥ 40 years at baseline (2002–2003) were included and followed until 2019. Health insurance type was categorized as employee-insured (EI) or self-employed-insured (SI). To define low, medium, and high economic status groups, we used insurance premiums at baseline. Death was determined using the date and cause of death included in the cohort. Cox proportional hazard models were used to analyze the association between insurance factors and the overall and cause-specific mortality. Results The SI group had a significantly higher risk of overall death compared to the EI group (adjusted hazard ratio (HR) [95% confidence interval]: 1.13 [1.10–1.15] for men and 1.18 [1.15–1.22] for women), after adjusting for various factors. This trend extended to death from the five major causes of death in South Korea (cancer, cardiovascular disease, cerebrovascular disease, pneumonia, and intentional self-harm) and from external causes, with a higher risk of death in the SI group (vs. the EI group). Further analysis stratified by economic status revealed that individuals with lower economic status faced higher risk of overall death and cause-specific mortality in both sexes, compared to those with high economic status for both health insurance types. Conclusion This nationwide study found that the SI group and those with lower economic status faced higher risk of overall mortality and death from the five major causes in South Korea. These findings highlight the potential disparities in health outcomes within the NHI system. To address these gaps, strategies should target risk factors for death at the individual level and governments should incorporate such strategies into public health policy development at the population level. Trial registration This study was approved by the Institutional Review Board of Chungbuk National University Hospital (CBNUH-202211-HR-0236) and adhered to the principles of the Declaration of Helsinki (1975).

Abstract Background We aimed to evaluate the association of anticholinergic burden and chronic polypharmacy with the incidence of functional decline and all-cause mortality, and to determine the difference between anticholinergic burden and chronic polypharmacy among Korean older people. Methods This nationwide cohort study included 42,132 older people aged ≥ 65 years who underwent Korean National Health Insurance Service health examinations from 2007 to 2008. Odds ratios (ORs) and 95% confidence intervals (CIs) for abnormal Timed Up and Go (TUG) test results were assessed using multivariate logistic regression analyses. Hazard ratios (HRs) and 95% CIs for all-cause mortality until the end of 2015 were estimated using multivariable Cox proportional hazards regression analysis. Results Of the participants, 37.19% had abnormal TUG test results, and 7.66% of those died during the 5.7-year mean follow-up. The abnormal TUG test results OR increased by 27% among individuals with Korean Anticholinergic Burden Scale (KABS) scores ≥ 3 (OR 1.27, 95% CI 1.02–1.58) compared to those with KABS scores of 0. The HRs for all-cause mortality increased for individuals with higher KABS scores (P for trend

Abstract Background The maintenance of spindle pole integrity is essential for spindle assembly and chromosome segregation during mitosis. However, the underlying mechanisms governing spindle pole integrity remain unclear. Methods ENSA was inhibited by siRNA or MKI-2 treatment and its effect on cell cycle progression, chromosome alignment and microtubule alignment was observed by immunohistochemical staining and western blotting. PP2A-B55α knockdown by siRNA was performed to rescue the phenotype caused by ENSA inhibition. The interaction between ENSA and Aurora A was detected by in situ PLA. Furthermore, orthotopic implantation of 4Tl-luc cancer cells was conducted to confirm the consistency between the in vitro and in vivo relationship of the ENSA-Aurora A interaction. Results During mitosis, p-ENSA is localized at the spindle poles, and the inhibition of ENSA results in mitotic defects, such as misaligned chromosomes, multipolar spindles, asymmetric bipolar spindles, and centrosome defects, with a delay in mitotic progression. Although the mitotic delay caused by ENSA inhibition was rescued by PP2A-B55α depletion, spindle pole defects persisted. Notably, we observed a interaction between ENSA and Aurora A during mitosis, and inhibition of ENSA reduced Aurora A expression at the mitotic spindle poles. Injecting MKI-2-sensitized tumors led to increased chromosomal instability and downregulation of the MASTL-ENSA-Aurora A pathway in an orthotopic breast cancer mouse model. Conclusions These findings provide novel insights into the regulation of spindle pole integrity by the MASTL-ENSA-Aurora A pathway during mitosis, highlighting the significance of ENSA in recruiting Aurora A to the spindle pole, independent of PP2A-B55α.

Abstract Introduction This study aimed to assess the role of adenosine triphosphate (ATP) bioluminescence level monitoring for identifying reservoirs of the outbreak pathogen during two consecutive outbreaks caused by Enterococcus faecium and Staphylococcus capitis at a neonatal intensive care unit (NICU). The secondary aim was to evaluate the long-term sustainability of the infection control measures employed one year after the final intervention measures. Methods Two outbreaks occurred during a 53-day period in two disconnected subunits, A and B, that share the same attending physicians. ATP bioluminescence level monitoring, environmental cultures, and hand cultures from healthcare workers (HCW) in the NICU were performed. Pulsed-field gel electrophoresis (PFGE) typing was carried out to investigate the phylogenetic relatedness of the isolated strains. Results Four cases of E. faecium sepsis (patients A-8, A-7, A-9, B-8) and three cases of S. capitis sepsis (patients A-16, A-2, B-8) were diagnosed in six preterm infants over a span of 53 days. ATP levels remained high on keyboard 1 of the main station (2076 relative light unit [RLU]/100 cm2) and the keyboard of bed A-9 (4886 RLU/100 cm2). By guidance with the ATP results, environmental cultures showed that E. faecium isolated from the patients and from the main station’s keyboard 1 were genotypically indistinguishable. Two different S. capitis strains caused sepsis in three patients. A total 77.8% (n = 7/9) of S. capitis cultured from HCW's hands were genotypically indistinguishable to the strains isolated from A-2 and A-16. The remaining 22.2% (n = 2/9) were genotypically indistinguishable to patient B-8. Three interventions to decrease the risk of bacterial transmission were applied, with the final intervention including a switch of all keyboards and mice in NICU-A and B to disinfectable ones. Post-intervention prospective monitoring up to one year showed a decrease in blood culture positivity (P = 0.0019) and catheter-related blood stream infection rate (P = 0.016) before and after intervention. Conclusion ATP monitoring is an effective tool in identifying difficult to disinfect areas in NICUs. Non-medical devices may serve as reservoirs of pathogens causing nosocomial outbreaks, and HCWs' hands contribute to bacterial transmission in NICUs.

Abstract Background The frequency, clinical characteristics, and associated symptoms of comorbid tic disorders in individuals with autism spectrum disorder (ASD) remain unclear. Methods We included subsets of individuals from a larger genetic study who were diagnosed with ASD (n = 679; age: 4–18 years) and completed the Yale Global Tic Severity Scale (YGTSS) questionnaire. Based on the YGTSS score, the individuals were divided into two groups: ASD only (n = 554) and ASD with tics (n = 125). Individuals were assessed using the verbal and non-verbal intelligence quotient (IQ), Vineland Adaptive Behavior Scale (VABS-2), Social Responsiveness Scale-2 (SRS-2), Child Behavior Checklists (CBCL), and Yale-Brown Obsessive–Compulsive Scale (YBOCS), followed by between-group comparisons. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 26. Results Tic symptoms were observed in 125 (18.4%) participants; among them, most participants presented both motor and vocal tics (n = 40, 40.0%). The ASD with tics group had a significantly higher average age and full-scale IQ score than the ASD only group. After adjusting for age, the ASD with tics group had significantly higher scores in the SRS-2, CBCL, and YBOCS subdomains than the ASD only group. Furthermore, all variables except the non-verbal IQ and VABS-2 scores were positively correlated with the YGTSS total score. Finally, the proportion of tic symptoms was significantly higher among individuals with a higher IQ score (≥ 70). Conclusions The IQ score was positively correlated with the proportion of tic symptoms among individuals with ASD. Moreover, the severity of the core and comorbid symptoms of ASD was associated with the occurrence and severity of tic disorders. Our findings suggest the need for appropriate clinical interventions for individuals with ASD. Trial registration This study retrospectively registered participants

Abstract Objectives There is little research examining transnational prenatal care (TPC) (i.e., prenatal care in more than one country) among migrant women. Using data from the Migrant-Friendly Maternity Care (MFMC) - Montreal project, we aimed to: (1) Estimate the prevalence of TPC, including TPC-arrived during pregnancy and TPC-arrived pre-pregnancy, among recently-arrived migrant women from low- and middle-income countries (LMICs) who gave birth in Montreal, Canada; (2) Describe and compare the socio-demographic, migration and health profiles and perceptions of care during pregnancy in Canada between these two groups and migrant women who received no TPC (i.e., only received prenatal care in Canada); and (3) Identify predictors of TPC-arrived pre-pregnancy vs. No-TPC. Methods The MFMC study used a cross-sectional design. Data were gathered from recently-arrived (

Abstract Background N-methyl-d-aspartate receptors (NMDARs) are considered to be involved in several physiological and pathophysiological processes in addition to the progression of neurological disorders. However, how NMDARs are involved in the glycolytic phenotype of M1 macrophage polarization and the possibility of using them as a bio-imaging probe for macrophage-mediated inflammation remain unclear. Methods We analyzed cellular responses to NMDAR antagonism and small interfering RNAs using mouse bone marrow-derived macrophages (BMDMs) treated with lipopolysaccharide (LPS). An NMDAR targeting imaging probe, N-TIP, was produced via the introduction of NMDAR antibody and the infrared fluorescent dye FSD Fluor™ 647. N-TIP binding efficiency was tested in intact and LPS-stimulated BMDMs. N-TIP was intravenously administered to mice with carrageenan (CG)- and LPS-induced paw edema, and in vivo fluorescence imaging was conducted. The anti-inflammatory effects of dexamethasone were evaluated using the N-TIP-mediated macrophage imaging technique. Results NMDARs were overexpressed in LPS-treated macrophages, subsequently inducing M1 macrophage polarization. Mechanistically, NMDAR-mediated Ca2+ accumulation resulted in LPS-stimulated glycolysis via upregulation of PI3K/AKT/mTORC1 signaling. In vivo fluorescence imaging with N-TIP showed LPS- and CG-induced inflamed lesions at 5 h post-inflammation, and the inflamed lesions could be detected until 24 h. Furthermore, our N-TIP-mediated macrophage imaging technique helped successfully visualize the anti-inflammatory effects of dexamethasone in mice with inflammation. Conclusion This study demonstrates that NMDAR-mediated glycolysis plays a critical role in M1 macrophage-related inflammation. Moreover, our results suggest that NMDAR targeting imaging probe may be useful in research on inflammatory response in vivo.

Abstract Background Although metastasis is the foremost cause of cancer-related death, a specialized mechanism that reprograms anchorage dependency of solid tumor cells into circulating tumor cells (CTCs) during metastatic dissemination remains a critical area of challenge. Methods We analyzed blood cell-specific transcripts and selected key Adherent-to-Suspension Transition (AST) factors that are competent to reprogram anchorage dependency of adherent cells into suspension cells in an inducible and reversible manner. The mechanisms of AST were evaluated by a series of in vitro and in vivo assays. Paired samples of primary tumors, CTCs, and metastatic tumors were collected from breast cancer and melanoma mouse xenograft models and patients with de novo metastasis. Analyses of single-cell RNA sequencing (scRNA-seq) and tissue staining were performed to validate the role of AST factors in CTCs. Loss-of-function experiments were performed by shRNA knockdown, gene editing, and pharmacological inhibition to block metastasis and prolong survival. Results We discovered a biological phenomenon referred to as AST that reprograms adherent cells into suspension cells via defined hematopoietic transcriptional regulators, which are hijacked by solid tumor cells to disseminate into CTCs. Induction of AST in adherent cells 1) suppress global integrin/ECM gene expression via Hippo-YAP/TEAD inhibition to evoke spontaneous cell–matrix dissociation and 2) upregulate globin genes that prevent oxidative stress to acquire anoikis resistance, in the absence of lineage differentiation. During dissemination, we uncover the critical roles of AST factors in CTCs derived from patients with de novo metastasis and mouse models. Pharmacological blockade of AST factors via thalidomide derivatives in breast cancer and melanoma cells abrogated CTC formation and suppressed lung metastases without affecting the primary tumor growth. Conclusion We demonstrate that suspension cells can directly arise from adherent cells by the addition of defined hematopoietic factors that confer metastatic traits. Furthermore, our findings expand the prevailing cancer treatment paradigm toward direct intervention within the metastatic spread of cancer.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is frequently accompanied by comorbidities, with the management of these comorbidities crucial for clinical outcomes. This study investigated the prevalence, incidence, changes over time, and clinical impact of comorbidities in IPF patients, based on nationwide claims data in South Korea. Methods This retrospective cohort study utilised nationwide health claim data in South Korea between 2011 and 2019. Patients with IPF were defined as those with ICD-10 code J84.1 and Rare Intractable Disease code V236 who made at least one claim per year. Patients were classified by sex, age, pirfenidone use and burden of comorbidities, and differences among groups were determined. Results The yearly prevalence rate of IPF increased from 7.50 to 23.20 per 100,000 people, and the yearly incidence rate increased from 3.56 to 7.91 per 100,000 person-years over time. The most common respiratory comorbidity was chronic obstructive pulmonary disease (37.34%), followed by lung cancer (3.34%), whereas the most common non-respiratory comorbidities were gastro-oesophageal reflux disease (70.83%), dyslipidaemia (62.93%) and hypertension (59.04%). The proportion of some comorbidities differed by sex, age and use of pirfenidone. The proportion of lung cancer was higher in patients treated with pirfenidone, whereas the proportion of anxiety and depression were lower in patients not treated with pirfenidone. Charlson comorbidity index ≥ 4 was associated with increases in hospitalisations and total medical costs. Conclusions The yearly prevalence and incidence of IPF and comorbidities in Korea increased over time. These comorbidities affected the use of pirfenidone and medical resources.

Abstract Background The pathogenesis of diabetic kidney disease (DKD) is complex, involving metabolic and hemodynamic factors. Although DKD has been established as a heritable disorder and several genetic studies have been conducted, the identification of unique genetic variants for DKD is limited by its multiplex classification based on the phenotypes of diabetes mellitus (DM) and chronic kidney disease (CKD). Thus, we aimed to identify the genetic variants related to DKD that differentiate it from type 2 DM and CKD. Methods We conducted a large-scale genome-wide association study mega-analysis, combining Korean multi-cohorts using multinomial logistic regression. A total of 33,879 patients were classified into four groups—normal, DM without CKD, CKD without DM, and DKD—and were further analyzed to identify novel single-nucleotide polymorphisms (SNPs) associated with DKD. Additionally, fine-mapping analysis was conducted to investigate whether the variants of interest contribute to a trait. Conditional analyses adjusting for the effect of type 1 DM (T1D)-associated HLA variants were also performed to remove confounding factors of genetic association with T1D. Moreover, analysis of expression quantitative trait loci (eQTL) was performed using the Genotype-Tissue Expression project. Differentially expressed genes (DEGs) were analyzed using the Gene Expression Omnibus database (GSE30529). The significant eQTL DEGs were used to explore the predicted interaction networks using search tools for the retrieval of interacting genes and proteins. Results We identified three novel SNPs [rs3128852 (P = 8.21×10−25), rs117744700 (P = 8.28×10−10), and rs28366355 (P = 2.04×10−8)] associated with DKD. Moreover, the fine-mapping study validated the causal relationship between rs3128852 and DKD. rs3128852 is an eQTL for TRIM27 in whole blood tissues and HLA-A in adipose-subcutaneous tissues. rs28366355 is an eQTL for HLA-group genes present in most tissues. Conclusions We successfully identified SNPs (rs3128852, rs117744700, and rs28366355) associated with DKD and verified the causal association between rs3128852 and DKD. According to the in silico analysis, TRIM27 and HLA-A can define DKD pathophysiology and are associated with immune response and autophagy. However, further research is necessary to understand the mechanism of immunity and autophagy in the pathophysiology of DKD and to prevent and treat DKD.

Abstract Background Escherichia coli have both the Embden–Meyerhof–Parnas pathway (EMPP) and Entner–Doudoroff pathway (EDP) for glucose breakdown, while the EDP primarily remains inactive for glucose metabolism. However, EDP is a more favorable route than EMPP for the production of certain products. Results EDP was activated by deleting the pfkAB genes in conjunction with subsequent adaptive laboratory evolution (ALE). The evolved strains acquired mutations in transcriptional regulatory genes for glycolytic process (crp, galR, and gntR) and in glycolysis-related genes (gnd, ptsG, and talB). The genotypic, transcriptomic and phenotypic analyses of those mutations deepen our understanding of their beneficial effects on cellulosic biomass bio-conversion. On top of these scientific understandings, we further engineered the strain to produce higher level of lycopene and 3-hydroxypropionic acid. Conclusions These results indicate that the E. coli strain has innate capability to use EDP in lieu of EMPP for glucose metabolism, and this versatility can be harnessed to further engineer E. coli for specific biotechnological applications.

Abstract Background The atherogenic index of plasma (AIP) is composed of triglycerides and high-density lipoprotein cholesterol and is a novel marker for assessing the risk of atherogenicity and cardiometabolic health. An association between AIP and greater frequency of major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus and high cardiovascular (CV) disease risk has been reported. However, only few studies have examined the correlation between AIP and CV risk in general populations. We thus aimed to evaluate the relationship between AIP and CV diseases using a large-scale population dataset from the Korean National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). Methods A total of 514,866 participants were enrolled from the NHIS-HEALS and classified according to the AIP quartiles. We performed univariate and multivariate Cox proportional hazards regression analyses to determine the association between AIP and MACEs, CV events, and CV mortality. Results During follow-up, we documented 12,133, 11,055, and 1942 cases of MACEs, CV events, and CV mortality, respectively. The multivariate-adjusted hazard ratios [HRs; 95% confidence interval (CI)] for MACEs gradually and significantly increased with the AIP quartiles [1.113 (1.054–1.175) in Q2, 1.175 (1.113–1.240) in Q3, and 1.278 (1.209–1.350) in Q4], following an adjustment for the conventional CV risk factors, including age, sex, body mass index, smoking, alcohol drinking, physical activities, household income, fasting glucose, systolic blood pressure, low-density lipoprotein cholesterol, and estimated glomerular filtration rate. In subgroup analyses, the association of AIP with MACEs and CV events was particularly outstanding in patients with diabetes. Conclusions AIP was significantly associated with CV risks after adjusting for the traditional risk factors. Therefore, it may be used as an effective mass screening method to identify patients at a high risk of CV events.

Abstract The threat of COVID-19 outbreak in South Korea and around the globe challenged not only physical health but also mental health, increasing the chances of disorders such as posttraumatic stress disorder (PTSD). Such pandemic situation can be referred to a traumatic event for citizens. The present study aims to examine the psychometric properties of the PTSD Checklist (PCL-5), which is named the K-COVID-related-PTSD. The scale measures PTSD symptomology in the context of the COVID-19 pandemic in South Korea. A total of 1434 South Korean citizens were included in this study. The data were statistically analyzed using SPSS 21.0 and Mplus 8.0. The results of confirmatory factor analysis demonstrated a superior fit for the seven-factor hybrid model (x 2 = 1425.445 (df = 149), CFI = 0.950, TLI = 0.937, SRMR = 0.033, RMSEA = 0.077) consisting of re-experiencing, negative affect, anxious arousal, dysphoric arousal, avoidance, anhedonia, and externalizing behaviors. Furthermore, the K-COVID-related-PTSD showed a satisfactory level of internal consistency (α = 0.793 to α = 0.939) with good convergent and discriminant validity. Finally, concurrent validity was confirmed by the significant correlations with all the negative mental health outcomes, such as PTSD symptoms, somatization, depression, anxiety, anger, negative affect, job burnout, and suicidal ideation. Overall, the current results demonstrate the K-COVID-related-PTSD is a valid scale and therefore has important implications for future pandemic-related studies.

Abstract Background Migrants commonly maintain transnational ties as they relocate and settle in a new country. There is a growing body of research examining transnationalism and health. We sought to identify how transnationalism has been defined and operationalized in migrant health research in high income countries and to document which populations and health and well-being outcomes have been studied in relation to this concept. Methods We conducted a scoping review using the methodology recommended by the Joanna Briggs Institute (JBI). We searched nine electronic databases; no time restrictions were applied. Studies published in English or French in peer-reviewed journals were considered. Studies were eligible if they included a measure of transnationalism (or one of its dimensions; social, cultural, economic, political and identity ties and/or healthcare use) and examined health or well-being. Results Forty-seven studies, mainly cross-sectional designs (81%), were included; almost half were conducted in the United States. The majority studied immigrants, broadly defined; 23% included refugees and/or asylum-seekers while 36% included undocumented migrants. Definitions of transnationalism varied according to the focus of the study and just over half provided explicit definitions. Most often, transnationalism was defined in terms of social connections to the home country. Studies and measures mainly focused on contacts and visits with family and remittance sending, and only about one third of studies examined and measured more than two dimensions of transnationalism. The operationalization of transnationalism was not consistent and reliability and validity data, and details on language translation, were limited. Almost half of the studies examined mental health outcomes, such as emotional well-being, or symptoms of depression. Other commonly studied outcomes included self-rated health, life satisfaction and perceived discrimination. Conclusion To enhance comparability in this field, researchers should provide a clear, explicit definition of transnationalism based on the scope of their study, and for its measurement, they should draw from validated items/questions and be consistent in its operationalization across studies. To enhance the quality of findings, more complex approaches for operationalizing transnationalism (e.g., latent variable modelling) and longitudinal designs should be used. Further research examining a range of transnationalism dimensions and health and well-being outcomes, and with a diversity of migrant populations, is also warranted.

Abstract Background Insulin resistance is associated with the incidence of diabetes and cardiovascular diseases such as myocardial infarction. The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) (TG/HDL-C ratio) is positively correlated with insulin resistance. This study aimed to investigate the relationship between the TG/HDL-C ratio and the incidence of diabetes in Korean adults. Methods This retrospective study used data from the National Health Insurance Service-National Health Screening Cohort. The TG/HDL-C ratio was divided into three tertiles, the T1, T2, and T3 groups, based on sex. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for diabetes using multivariate Cox proportional hazards regression analyses. Results A total of 80,693 subjects aged between 40 and 79 years were enrolled. The median follow-up period was 5.9 years. The estimated cumulative incidence of diabetes in the T1, T2, and T3 groups was 5.94%, 8.23%, and 13.50%, respectively, in men and 4.12%, 4.72%, and 6.85%, respectively, in women. Compared to T1, the fully adjusted HRs (95% CIs) of the T2 and T3 groups for new-onset diabetes were 1.17 (1.06–1.30) and 1.47 (1.34–1.62), respectively, in men and 1.20 (1.02–1.42) and 1.52 (1.30–1.78), respectively, in women. Conclusions Increased TG/HDL-C ratio was significantly associated with a higher risk of new-onset diabetes in both sexes.

Abstract Background Recent resting-state fMRI studies demonstrated functional dysconnectivity within the central pain matrix in migraineurs. This study aimed to investigate the spatial distribution and amplitude of low-frequency oscillations (LFOs) using fractional amplitude of low-frequency fluctuation (fALFF) analysis in migraine patients without aura, and to examine relationships between regional LFOs and clinical variables. Methods Resting-state fMRI data were obtained and preprocessed in 44 migraine patients without aura and 31 matched controls. fALFF was computed according to the original method, z-transformed for standardization, and compared between migraineurs and controls. Correlation analysis between regional fALFF and clinical variables was performed in migraineurs as well. Results Compared with controls, migraineurs had significant fALFF increases in bilateral ventral posteromedial (VPM) thalamus and brainstem encompassing rostral ventromedial medulla (RVM) and trigeminocervical complex (TCC). Regional fALFF values of bilateral VPM thalamus and brainstem positively correlated with disease duration, but not with migraine attack frequency or Migraine Disability Assessment Scale score. Conclusions We have provided evidence for abnormal LFOs in the brainstem including RVM/TCC and thalamic VPM nucleus in migraine without aura, implicating trigeminothalamic network oscillations in migraine pathophysiology. Our results suggest that enhanced LFO activity may underpin the interictal trigeminothalamic dysrhythmia that could contribute to the impairments of pain transmission and modulation in migraine. Given our finding of increasing fALFF in relation to increasing disease duration, the observed trigeminothalamic dysrhythmia may indicate either an inherent pathology leading to migraine headaches or a consequence of repeated attacks on the brain.

Abstract Histone modifications are a key mechanism underlying the epigenetic regulation of gene expression, which is critically involved in the consolidation of multiple forms of memory. However, the roles of histone modifications in cerebellum-dependent motor learning and memory are not well understood. To test whether changes in histone methylation are involved in cerebellar learning, we used heterozygous Kdm3b knockout (Kdm3b +/−) mice, which show reduced lysine 9 on histone 3 (H3K9) demethylase activity. H3K9 di-methylation is significantly increased selectively in the granule cell layer of the cerebellum of Kdm3b +/− mice. In the cerebellum-dependent optokinetic response (OKR) learning, Kdm3b +/− mice show deficits in memory consolidation, whereas they are normal in basal oculomotor performance and OKR acquisition. In addition, RNA-seq analyses revealed that the expression levels of several plasticity-related genes were altered in the mutant cerebellum. Our study suggests that active regulation of histone methylation is critical for the consolidation of cerebellar motor memory.

Abstract Background It is difficult to assess the impact of multiple comorbidities on clinical outcomes in chronic obstructive pulmonary disease (COPD). In this study, we aimed to investigate exacerbation-associated comorbidities, determine whether the number of comorbidities is an independent risk factor for exacerbation, and identify other exacerbation-associated factors in a Korean COPD population using a nationwide population-based cohort. This study focused on severe exacerbations that required hospitalisation or emergency room visits. Methods The National Health Insurance Service-National Sample Cohort, version 2.0, data sampled between 2002 and 2015 were analysed. Data from two years after the diagnosis of COPD were analysed for each participant (N = 12,554, entire cohort). Moreover, 42% of the participants underwent additional health examinations (N = 5306, health-screening cohort). Fifteen comorbidities that were previously reported as risk factors for exacerbations were examined. A logistic regression model was used to analyse association with exacerbations. Results Asthma (1.57 [1.39–1.76] and 1.24 [1.06–1.44]), lung cancer (1.84 [1.30–2.59] and 2.28 [1.54–3.37]), and heart failure (1.39 [1.16–1.67] and 1.52 [1.18–1.97]) were associated with exacerbation in both cohorts (odds ratio [95% confidence interval] in the entire cohort and health-screening cohort, respectively). The number of comorbidities was an independent risk factor, and old age, male sex, low body mass index, and current smoking were also independent risk factors. High cholesterol levels and body mass index exerted protective effects against exacerbation. Conclusions The number of comorbidities, certain comorbidities such as asthma, lung cancer and heart failure, and low BMI were associated with an increased risk of severe exacerbation in COPD patients.

Abstract Background The effects of comorbidities on chronic obstructive pulmonary disease (COPD) have been usually studied individually in the past. In this study, we aimed to investigate the comorbidities associated with mortality, the effect of multimorbidity on mortality and other factors associated with mortality among Korean COPD population. Methods The Korean National Health Insurance Service-National Sample Cohort version 2.0, collected between 2002 and 2015, was used. Among COPD patients [entire cohort (EC), N = 12,779], 44% of the participants underwent additional health examination, and they were analysed separately [health-screening cohort (HSC), N = 5624]. Fifteen comorbidities previously reported as risk factors for mortality were studied using Cox proportional hazards regression models. Results Total mortality rates were 38.6 per 1000 person-years (95% CI 37.32–40.01) and 27.4 per 1000 person-years (95% CI 25.68–29.22) in EC and HSC, respectively. The most common causes of death were disease progression, lung cancer, and pneumonia. Only some of the comorbidities had a direct impact on mortality. Multimorbidity, assessed by the number of comorbid diseases, was an independent risk factor of all-cause mortality in both cohorts and was a risk factor of respiratory mortality only in HSC. The Kaplan–Meier analysis showed significant differences in survival trajectories according to the number of comorbidities in all-cause mortality but not in respiratory mortality. Low BMI, old age and male sex were independent risk factors for both mortalities in both cohorts. Conclusions The number of comorbidities might be an independent risk factor of COPD mortality. Multimorbidity contributes to all-cause mortality in COPD, but the effect of multimorbidity is less evident on respiratory mortality.

Abstract Background Pulmonary alveolar proteinosis (PAP) is a very rare lung disease and its prevalence and incidence remain unclear. The prevalence and incidence of PAP were investigated by using nationwide claims data from the Korean Health Insurance Review and Assessment service. Methods Data were extracted for adults who visited any secondary or tertiary medical institute between 2010 and 2016 with the PAP-related Korean Classification of Disease, 7th edition code J84.0 and the Rare Intractable Disease exempted calculation code V222. To robust case definition, a narrow case definition was made when all following factors were met: 1) more than two PAP-coded visits within 1 year of the first claim, and 2) more than one claim for both chest computed tomography and diagnostic procedures (bronchoscopy or surgical lung biopsy) within 90 days before or after the first claim. Results A total of 182 patients (narrow, n = 82) with PAP-related codes were identified from 2010 to 2016 and 89 new patients (narrow, n = 66) visited medical institutes between 2012 and 2015. The prevalence of PAP was 4.44 (narrow: 2.27) per 106 population, with a peak age of 60–69 years. The incidence of PAP was 0.56 (narrow: 0.41) per 106 population at risk, with a peak age of 50–59 years. Among incident cases, the male-to-female ratio was 1.52 and about two-thirds had comorbidities, dyslipidaemia being the most common. Conclusions The prevalence and incidence of PAP in Korea are low, similar to those in other countries; however, Korean patients with PAP are characterized by older diagnostic age and a lower male-to-female ratio.

Abstract Background Although bronchodilator inhaler therapy can improve lung function in patients with tuberculous destroyed lung (TDL), its effect on mortality has not been studied. We evaluated the effect of tiotropium inhaler therapy on mortality in patients with TDL. Methods A retrospective cohort of 963 patients with TDL was followed for up to ten years by linking hospital and nationwide health insurance claims data. We compared patients receiving tiotropium inhaler with patients without tiotropium after matching with propensity scores. In addition, we elucidated the risk factors of mortality using Cox proportional hazards model. Results After the propensity score matching, the baseline characteristics were balanced in both the tiotropium group (n = 105) and the non-tiotropium group (n = 105); including mean age (63.9 vs. 64.4 years, P = 0.715), mean forced expiratory volume in 1 s (FEV1) (45.0 vs. 45.3%, P = 0.903), and others. After the propensity score matching, the tiotropium group showed better survival than the non-tiotropium group (median survival period: not reached for the tiotropium group vs. 7.24 years for the non-tiotropium group, Prentice-Wilcoxon test, P = 0.008). Multivariate Cox proportional hazard analysis revealed that tiotropium inhaler usage was associated with lower risk of mortality in the multivariate analysis (HR, 0.560; 95% CI, 0.380–0.824; P = 0.003) after adjusting age, sex, BMI, smoking history, mMRC dyspnea score, Charlson Comorbidity Index, concomitant COPD diagnosis, FEV1, X-ray severity score, and home oxygen usage. Conclusions Our results suggest that tiotropium inhaler is associated with decreased all-cause mortality in TDL. Further prospective study is required for validation.

Abstract Background The prevalence and incidence of sarcoidosis varies worldwide. We estimated the prevalence and incidence of sarcoidosis in Korea using nationwide claims data from the Korean Health Insurance Review and Assessment Service. Methods Cases of sarcoidosis were identified for any visit between 2007 to 2016 that listed the Korean Classification of Disease, 7th edition code of sarcoidosis and rare incurable disease exempted calculation code. A narrow case definition was used as follows: 1) ≥ two sarcoidosis-coded visits within 1 year of the first claim, 2) no claims for other diseases that could form granuloma. Results A total of 4791 patients (narrow, n = 2388) visited medical institutions for sarcoidosis during the study period; 2999 patients (narrow, n = 1696) were newly identified between 2009 and 2015. The sarcoidosis prevalence was 9.37 per 105 people (narrow, 4.69) and was highest between ages 60–69 years. The incidence rate was 0.85 per 105 population at risk (narrow, 0.48), with the highest incidence rate between ages 50–59 years. For incident cases (mean age: 48.5 year), the age distribution in whole population and females showed monophasic patterns peaking at aged 50–59 years, while males had biphasic incidence peak at aged 30–39 years and 60–69 years. The annual incidence rates showed increasing trends from 0.85 per 105 population at risk in 2009 to 0.97 per 105 population at risk in 2015. Conclusions In comparison with previous reports, the prevalence and incidence of sarcoidosis in Korea have increased and middle-aged women showed the highest risk.

Abstract Background Resistance to preoperative radiotherapy is a major clinical problem in the treatment for locally advanced rectal cancer. The role of NDRG1 in resistance to ionizing radiation in rectal cancer has not been fully elucidated. This study aimed to investigate the effect of the reduced intracellular NDRG1 expression on radio-sensitivity of human rectal cancer cells for exploring novel approaches for treatment of rectal cancer. Methods Three radio-resistant human rectal cancer cell lines (SNU-61R80Gy, SNU-283R80Gy, and SNU-503R80Gy) were established from human rectal cancer cell lines (SNU-61, SNU-283, and SNU-503) using total 80 Gy of fractionated irradiation. Microarray analysis was performed to identify differently expressed genes in newly established radio-resistant human rectal cancer cells compared to parental rectal cancer cells. Results A microarray analysis indicated the RNA expression of five genes (NDRG1, ERRFI1, H19, MPZL3, and UCA1) was highly increased in radio-resistant rectal cancer cell lines. Short hairpin RNA-mediated silencing of NDRG1 sensitized rectal cancer cell lines to clinically relevant doses of radiation by causing more DNA double strand breakages to rectal cancer cells when exposed to radiation. Conclusions Targeting NDRG1 represents a promising strategy to increase response to radiotherapy in human rectal cancer.

Abstract Background Heartworm disease in dogs is a life-threatening parasitic disease. Although adulticide treatment with melarsomine has been proven to be the most effective, complications associated with adulticide treatment are major concerns for clinicians. Methods This study evaluated the change in levels of D-dimer, interleukin-6, C-reactive protein and cardiac troponin I in 12 dogs with different severities of heartworm infection treated by the American Heartworm Society (AHS) recommended protocol during the treatment period. The serum levels of several markers were measured on the day of diagnosis (T-60), before the initiation of melarsomine therapy (T0), 1 day after the first injection (T1), 1 week after the first injection (T7), 1 month after the first injection (T30), 1 day after the second injection (T31), 1 day after the third injection (T32), 1 week after the third injection (T39), 1 month after the third injection (T62), 2 months after the third injection (T92), 3 months after the third injection (T122), and 6 months after the third injection (T182). Results The serum levels of these markers were significantly different at the test time point after melarsomine treatment and also differed significantly according to the stage of heartworm disease in the dogs. Conclusion This study found that monitoring of inflammatory and hemostatic markers in dogs with heartworm disease being treated with melarsomine might be beneficial in predicting the clinical outcomes and complications associated with melarsomine treatment.