Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Background: Preeclampsia (PE) is known to arise from insufficient trophoblast invasion as uterine spiral arteries lack remodeling. A significant reduction in placental perfusion induces an ischemic placental microenvironment due to reduced oxygen delivery to the placenta and fetus, leading to oxidative stress. Mitochondria are involved in the regulation of cellular metabolism and the production of reactive oxygen species (ROS). NME/NM23 nuceloside diphosphate kinase 4 (NME4) gene is known to have the ability to supply nucleotide triphosphate and deoxynucleotide triphosphate for replication and transcription of mitochondria. Our study aimed to investigate changes in NME4 expression in PE using trophoblast stem-like cells (TSLCs) from induced pluripotent stem cells (iPSCs) as a model of early pregnancy and peripheral blood mononuclear cells (PBMNCs) as a model of late preterm pregnancy. Methods: Transcriptome analysis using TSLCs was performed to identify the candidate gene associated with the possible pathophysiology of PE. Then, the expression of NME4 associated with mitochondrial function, p53 associated with cell death, and thioredoxin (TRX) linked to ROS were investigated through qRT-PCR, western blotting and deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) assay. Results: In patients with PE, NME4 was significantly downregulated in TSLCs but upregulated in PBMNCs. p53 was shown to be upregulated in TSLCs and PBMNCs of PE. In addition, western blot analysis confirmed that TRX expression had the tendency to increase in TSLCs of PE. Similarly, TUNEL analysis confirmed that the dead cells were higher in PE than in normal pregnancy. Conclusion Our study showed that the expression of the NME4 differed between models of early and late preterm pregnancy of PE, and suggests that this expression pattern may be a potential biomarker for early diagnosis of PE.

Purpose: Mycoplasma pneumoniae pneumonia (MP) is a major cause of community-acquired pneumonia (CAP) in children and is associated with extrapulmonary manifestations (EPM). The incidence and risk factors for EPM in children are unknown. Methods: This was a retrospective study involving 65,243 pediatric patients with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Medical records were reviewed to collect information regarding the clinical characteristics, radiological results, and laboratory findings. Logistic regression with multivariate analysis was performed to evaluate the risk factors associated with EPM in MP. Results: The incidence of EPM was 23.9%, including elevation of liver enzymes (18.1%), mucocutaneous manifestations (4.4%), proteinuria (4.1%), cardiovascular and neurological manifestations (0.4%), hematologic manifestations (0.2%), and arthritis (0.2%). Statistical analysis showed that mucocutaneous manifestations significantly increased with elevated alanine aminotransferase (adjusted odds ratio [aOR], 3.623; 95% confidence interval [CI], 1.933-6.790) and atopic sensitization (aOR, 2.973; 95% CI, 1.615–5.475) and decreased with respiratory virus coinfection (aOR, 0.273; 95% CI, 0.084–0.887). Elevated liver enzymes were significantly associated with elevated lactate dehydrogenase (aOR, 3.055; 95% CI, 2.257–4.137), presence of pleural effusion (aOR, 2.635; 95% CI, 1.767–3.930), and proteinuria with respiratory virus coinfection (aOR, 2.245; 95% CI, 1.113–4.527). Conclusion Approximately 24% of pediatric patients with MP had various EPM. As the risk factors associated with each EPM were different, it is necessary to evaluate the various clinical aspects and findings of MP to predict and prepare for the occurrence of EPM.

Cell therapeutic agents for treating degenerative brain diseases using neural stem cells are actively being developed. However, few systems have been developed to monitor in real time whether the transplanted neural stem cells are actually differentiated into neurons. Therefore, it is necessary to develop a technology capable of specifically monitoring neuronal differentiation in vivo. In this study, we established a system that expresses cell membrane-targeting red fluorescent protein under control of the Synapsin promoter in order to specifically monitor differentiation from neural stem cells into neurons. In order to overcome the weak expression level of the tissue-specific promoter system, the partial 5′ UTR sequence of Creb was added for efficient expression of the cell surface-specific antigen. This system was able to track functional neuronal differentiation of neural stem cells transplanted in vivo, which will help improve stem cell therapies.
Antigens, Surface* ; Brain Diseases ; Neural Stem Cells ; Neurons* ; Stem Cells

Kawasaki disease (KD) is an acute febrile vasculitis predominately affecting infants and children. The dominant incidence age of KD is from 6 months to 5 years of age, and the incidence is unusual in those younger than 6 months and older than 5 years of age. We tried to identify genetic variants specifically associated with KD in patients younger than 6 months or older than 5 years of age. We performed an age-stratified genome-wide association study using the Illumina HumanOmni1-Quad BeadChip data (296 cases vs. 1,000 controls) and a replication study (1,360 cases vs. 3,553 controls) in the Korean population. Among 26 candidate single nucleotide polymorphisms (SNPs) tested in replication study, only a rare nonsynonymous SNP (rs4365796: c.1106C>T, p.Thr369Met) in the lymphoid enhancer binding factor 1 (LEF1) gene was very significantly associated with KD in patients younger than 6 months of age (odds ratio [OR], 3.07; p(combined) = 1.10 × 10⁻⁵), whereas no association of the same SNP was observed in any other age group of KD patients. The same SNP (rs4365796) in the LEF1 gene showed the same direction of risk effect in Japanese KD patients younger than 6 months of age, although the effect was not statistically significant (OR, 1.42; p = 0.397). This result indicates that the LEF1 gene may play an important role as a susceptibility gene specifically affecting KD patients younger than 6 months of age.
Asian Continental Ancestry Group ; Child ; Genome-Wide Association Study ; Humans ; Incidence ; Infant ; Lymphoid Enhancer-Binding Factor 1 ; Mucocutaneous Lymph Node Syndrome* ; Polymorphism, Single Nucleotide ; Vasculitis

In the adult mammalian brain, neural-lineage cells are continuously generated in the subventricular zone (SVZ) and dentate gyrus of the hippocampus. These cells in vivo arising from the adult SVZ may be regulated by environmental enrichment (EE). EE is a method of raising animals in a huge cage containing novel objects, running wheels and social interaction with a complex combination of physical, cognitive, and social stimulations. EE can affect neural plasticity via overexpression of growth factors such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), fibroblast growth factor-2 (FGF-2), and synaptic activity-regulating genes. EE also have advanced effects on brain functions including the enhancement of motor and cognitive functions in normal and pathological states. Additionally, behavioral changes by EE are related with molecular changes including neurogenesis, gliogenesis, angiogenesis, axonal sprouting, and dendritic branching in the adult brain. In this review, we focus on brain plasticity and neurorestoration associated with molecular changes of neurotrophic growth factors such as BDNF, VEGF, IGF-1, FGF-2 and synaptic activity-regulating genes that occurs in interaction to EE.
Adult ; Animals ; Axons ; Brain* ; Brain-Derived Neurotrophic Factor ; Dentate Gyrus ; Fibroblast Growth Factor 2 ; Hippocampus ; Humans ; Insulin-Like Growth Factor I ; Intercellular Signaling Peptides and Proteins ; Interpersonal Relations ; Neurogenesis ; Plastics* ; Running ; Vascular Endothelial Growth Factor A

PURPOSE: p21-activated kinases (PAKs) are involved in cytoskeletal reorganization, gene transcription, cell proliferation and survival, and oncogenic transformation. Therefore, we hypothesized that PAK expression levels could predict the sensitivity of pancreatic cancer cells to gemcitabine treatment, and PAKs could be therapeutic targets. MATERIALS AND METHODS: Cell viability inhibition by gemcitabine was evaluated in human pancreatic cancer cell lines (Capan-1, Capan-2, MIA PaCa-2, PANC-1, Aspc-1, SNU-213, and SNU-410). Protein expression and mRNA of molecules was detected by immunoblot analysis and reverse transcription polymerase chain reaction. To define the function of PAK4, PAK4 was controlled using PAK4 siRNA. RESULTS: Capan-2, PANC-1, and SNU-410 cells were resistant to gemcitabine treatment. Immunoblot analysis of signaling molecules reported to indicate gemcitabine sensitivity showed higher expression of PAK4 and lower expression of human equilibrative nucleoside transporter 1 (hENT1), a well-known predictive marker for gemcitabine activity, in the resistant cell lines. Knockdown of PAK4 using siRNA induced the upregulation of hENT1. In resistant cell lines (Capan-2, PANC-1, and SNU-410), knockdown of PAK4 by siRNA resulted in restoration of sensitivity to gemcitabine. CONCLUSION: PAK4 could be a predictive marker of gemcitabine sensitivity and a potential therapeutic target to increase gemcitabine sensitivity in pancreatic cancer.
Cell Line* ; Cell Proliferation ; Cell Survival ; Equilibrative Nucleoside Transporter 1 ; Humans ; p21-Activated Kinases ; Pancreatic Neoplasms* ; Phosphotransferases* ; Polymerase Chain Reaction ; Reverse Transcription ; RNA, Messenger ; RNA, Small Interfering ; Up-Regulation

Severe adenovirus pneumonia that causes acute respiratory failure can occur in infants, children, and immunocompromised patients. However, severe adenovirus pneumonia is rare in adults with a normal immune system. Adenovirus pneumonia may progress to acute respiratory failure in a few hours or a few days, and its clinical course cannot be predicted. In addition, the mortality rate is very high (range, 50% to 66%). However, the optimal treatment of adenovirus pneumonia has not been established. Herein, we report the successful treatment of acute respiratory failure due to adenovirus pneumonia with extracorporeal membrane oxygenation.
Adenoviridae* ; Adult ; Child ; Extracorporeal Membrane Oxygenation* ; Humans ; Immune System ; Immunocompromised Host ; Infant ; Mortality ; Pneumonia* ; Respiratory Distress Syndrome, Adult ; Respiratory Insufficiency

OBJECTIVE: To evaluate the epidemiologic change of patients with spinal cord injury who were admitted to a Rehabilitation Hospital, Yonsei University College of Medicine, during 1987-1996 and 2004-2008. METHODS: Medical records of 629 patients with spinal cord injury admitted to the Rehabilitation Hospital, Yonsei University College of Medicine, from 2004 to 2008 were collected and reviewed retrospectively. RESULTS: The male-to-female ratio decreased to 2.86:1, the mean age at injury increased, nontraumatic etiology increased, traffic accident remained to be the most common in traumatic spinal cord injury, and falling increased significantly. Tumor was the most common etiology in nontraumatic spinal cord injury, tetraplegia and incomplete injuries occurred more than paraplegia and complete injuries, indwelling catheter was the most common voiding method, and the duration of hospitalization decreased. CONCLUSION: Many trends changed in epidemiology of spinal cord injury.
Accidents, Traffic ; Catheters, Indwelling ; Hospitalization ; Humans ; Medical Records ; Paraplegia ; Quadriplegia ; Spinal Cord ; Spinal Cord Injuries

OBJECTIVES: There are only a limited number of studies on instruments assessing fatigue in university students, although fatigue exerts negative influences on their health and academic performances and fatigue-related complaints are more frequently reported in young adults than middle-aged adults. The aim of this study was to validate the 9-item Fatigue Severity Scale (FSS) among university students including both undergraduate and graduate students in South Korea. METHODS: A total of 176 university students completed a battery of self-report questionnaires, including the FSS, the Brief Fatigue Inventory (BFI), the Beck Depression Inventory-II (BDI-II), the Beck Anxiety Inventory (BAI), the Medical Outcomes Study Short Form 36 version 2 (MOS-SF36v2), and the Inclusion of Community in the Self Scale (ICS). The data were collected from February of 2012 to June of 2012. The reliability, convergent validity, divergent validity, and exploratory factor analyses were conducted to assess psychometric properties of the FSS. RESULTS: The mean FSS score was 3.20 (standard deviation = 1.43). The FSS demonstrated an excellent internal consistency (Cronbach's alpha = 0.93) and item-total correlations ranged from 0.56 to 0.90. Correlations of the FSS with the BFI (r = 0.71, p < 0.01), BDI-II (r = 0.54, p < 0.01), BAI (r = 0.46, p < 0.01), MOS-SF36v2 physical component summary (r = -0.28, p < 0.01), MOS-SF36v2 mental component summary (r = -0.55, p < 0.01), and ICS (Spearman's rho = -0.07, p = 0.33) showed acceptable convergent and divergent validity. Exploratory factor analysis defined one underlying factor (eigenvalue = 5.67) that explained 93.50% of the total variance. CONCLUSIONS: To the best of our knowledge, this is the first study to investigate reliability and validity of the FSS in university students. The FSS exhibits good psychometric properties for evaluation of fatigue among university students in South Korea. Since the FSS is easy to administer, score, and interpret, it could be a useful tool in research and practice for assessing fatigue among university students.
Adult ; Anxiety ; Depression ; Fatigue ; Humans ; Psychometrics ; Reproducibility of Results ; Republic of Korea ; Young Adult ; Surveys and Questionnaires