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Highlights • Evaluation of Engerer Model for derving DNI from GHI at minute scale in the Korean Peninsula. • Producing the prediction interval of DNI estimates by using Monte-Carlo simulation. • Comparison of Monte-Carlo simulation with multi-model ensembles and bootstrap technique. Abstract Solar resource assessment is carried out in a feasibility study using reliable meteorological elements including solar irradiance. In concentrating solar power plants, the direct normal irradiance is the key variable in the system operation. However, direct normal irradiance is rarely measured as compared to global horizontal irradiance. There are several models that can be used to derive the direct normal irradiance from global horizontal irradiance. In this study, the Engerer model is used as a decomposition model, then evaluated against in situ observations at three ground stations: Seoul, Buan, and Jeju ground stations. The relative root mean square errors between the observed and direct normal irradiance estimated by the Engerer model are 15.0%, 19.4%, and 17.1% at Seoul, Buan, and Jeju ground stations, respectively. The uncertainty of estimates is represented by the prediction interval from probabilistic prediction through Monte-Carlo simulation that employs the bias between estimation and ground truth for training datasets. The prediction interval for 90% confidence level is 117.9 W m−2 at the Seoul station, resulting from Monte-Carlo simulation. The prediction interval coverage probability is 92.8%, implying that the probability that observed DNI is not included in the prediction interval is 7.2%. The error metrics for probabilistic prediction indicates that Monte-Carlo simulation provides both valid and more informative estimations. [ABSTRACT FROM AUTHOR]

Objective: Polysomnography (PSG) is unique in diagnosing sleep disorders, notably obstructive sleep apnea (OSA). Despite its advantages, manual PSG data grading is time-consuming and laborious. Thus, this research evaluated a deep learning-based automated scoring system for respiratory events in sleep-disordered breathing patients., Methods: A total of 1000 case PSG data were enrolled to develop a deep learning algorithm. Of the 1000 data, 700 were distributed for training, 200 for validation, and 100 for testing. The respiratory events scoring deep learning model is composed of five sequential layers: an initial layer of perceptrons, followed by three consecutive layers of long short-term memory cells, and ultimately, an additional two layers of perceptrons., Results: The PSG data of 100 patients (simple snoring, mild, moderate, and severe OSA; n = 25 in each group) were selected for validation and testing of the deep learning model. The algorithm demonstrated high sensitivity (95% CI: 98.06-98.51) and specificity (95% CI: 95.46-97.79) across all OSA severities in detecting apnea/hypopnea events, compared to manual PSG analysis. The deep learning model's area under the curve values for predicting OSA in apnea-hypopnea index ≥ 5, 15, and 30 groups were 0.9402, 0.9388, and 0.9442, respectively, showing no significant differences between each group., Conclusion: The deep learning algorithm employed in our study showed high accuracy in identifying apnea/hypopnea episodes and assessing the severity of OSA, suggesting the potential for enhancing both the efficiency and accuracy of automated respiratory event scoring in PSG through advanced deep learning techniques., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Marn Joon Park and Shin Young Kim declare no conflicts of interest. Ji Ho Choi is the principal investigator (PI) of the current study, and is currently serving as the nonexecutive board of Honeynaps Co. Ltd., appointed from March 2024. Tae Kyoung Ha is the president of Honeynaps Co. Ltd. The current investigation was independently conceptualized and designed by Ji Ho Choi, utilizing Dr. Choi's patient data from 2017 to 2019, and received IRB approval from Dr. Choi's institution at 2020. The company had no role in the decision to publish the results., (© The Author(s) 2024.)

Glomerulonephritis (GN) is characterized by podocyte injury or glomerular filtration dysfunction, which results in proteinuria and eventual loss of kidney function. Progress in studying the mechanism of GN, and developing an effective therapy, has been limited by the absence of suitable in vitro models that can closely recapitulate human physiological responses. We developed a microfluidic glomerulus-on-a-chip device that can recapitulate the physiological environment to construct a functional filtration barrier, with which we investigated biological changes in podocytes and dynamic alterations in the permeability of the glomerular filtration barrier (GFB) on a chip. We also evaluated the potential of GN-mimicking devices as a model for predicting responses to human GN. Glomerular endothelial cells and podocytes successfully formed intact monolayers on opposite sides of the membrane in our chip device. Permselectivity analysis confirmed that the chip was constituted by a functional GFB that could accurately perform differential clearance of albumin and dextran. Reduction in cell viability resulting from damage was observed in all serum-induced GN models. The expression of podocyte-specific marker WT1 was also decreased. Albumin permeability was increased in most models of serum-induced IgA nephropathy (IgAN) and membranous nephropathy (MN). However, sera from patients with minimal change disease (MCD) or lupus nephritis (LN) did not induce a loss of permeability. This glomerulus-on-a-chip system may provide a platform of glomerular cell culture for in vitro GFB in formation of a functional three-dimensional glomerular structure. Establishing a disease model of GN on a chip could accelerate our understanding of pathophysiological mechanisms of glomerulopathy.

Colistimethate sodium (CMS) nebulization is associated with reduced systemic toxicity compared to intravenous injection, with potentially enhanced clinical efficacy. This study aimed to assess the pharmacokinetic (PK) properties of colistin during low-dose CMS nebulization in patients with ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii . A nonlinear mixed-effects modeling approach was applied to develop population PK models for colistin in both epithelial lining fluid (ELF) and plasma. Twenty patients participated, and 80 ELF and 100 plasma samples were used for model development. Median colistin concentrations measured in ELF were 614-fold, 408-fold, and 250-fold higher than in plasma at 1, 3, and 5 h, respectively. Time courses in both ELF and plasma were best described by a one-compartment model with a Weibull absorption process. When the final model was simulated, the maximum free concentration and area under the free colistin concentration-time curve at steady state over 24 h in the plasma were approximately 1/90 and 1/50 of the corresponding values in ELF at steady state, respectively. For an A. baumannii MIC of 1 mg/L, inhaling 75 mg of CMS at 6 h intervals was deemed appropriate, with dose adjustments needed for MICs exceeding 2 mg/L. Using a nebulizer for CMS resulted in a notably higher exposure of colistin in the ELF than plasma, indicating the potential of nebulization to reduce systemic toxicity while effectively treating VAP.

We developed a 3D glomeruli tissue chip for glomerulonephritis (GN) testing, featuring a gravity-driven glomerular filtration barrier (GFB) with human podocytes and endothelial cells with a bidirectional flow in the bottom channel. Using puromycin-induced GN, we observed decreased cell viability, increased albumin permeability, and reduced WT1 and nephrin compared to the normal GFB. Tacrolimus restored cell viability, reduced albumin permeability, and increased WT1 expression. Using serum from five membranous nephropathy (MN) patients, we created MN models using a GFB-mimicking chip. A notable decline in cell viability was observed in the serum-induced MN1 and MN2 models. However, tacrolimus restored it. Albumin permeability was reduced in the MN1, MN2, and MN5 models by tacrolimus treatment. MN1 displayed the best clinical response to tacrolimus, exhibiting increased expression of WT1 in chip-based evaluations after tacrolimus treatment. We successfully evaluated the efficacy of tacrolimus using puromycin-induced and serum-induced GN models on a chip that mimicked the structure and function of the GFB. The GFB-mimicking chip holds promise as a personalized platform for assessing drug efficacy using patient serum samples.

Objectives: Tracheostomy is an important procedure for critically ill patients in the intensive care unit (ICU), and percutaneous dilatational tracheostomy (PDT) has gained popularity due to its safety and effectiveness. However, there are limited data comparing ultrasound-guided PDT (US-PDT) with surgical tracheostomy (ST). In our previous study, we reported that US-PDT had similar safety and effectiveness to ST, with a shorter procedure time. However, the study design was retrospective, and the sample size was small. Therefore, we conducted a randomized controlled trial to demonstrate the safety and efficacy of US-PDT compared to ST., Methods: A total of 70 patients who underwent either US-PDT (n=35) or ST (n=35) were enrolled in the study between October 20, 2020 and July 26, 2022. The patients were randomly assigned to their respective procedures. The data collected included patient clinical characteristics, procedure time and details, complications, duration of ICU stay, time taken for weaning from mechanical ventilation, and hospital mortality., Results: The procedure time of US-PDT was shorter than that of ST (4.0±2.2 minutes vs. 10.1±4.6 minutes). The incision length of US-PDT was also shorter than that of ST (1.5±0.5 cm vs. 1.8±0.4 cm). There were no statistically significant differences in demographics, procedure details, complications, length of ICU stay, ventilator weaning time, and hospital mortality., Conclusion: US-PDT has a similar complication rate and shorter procedure time compared with ST. It can be safely and effectively performed in critically ill patients and can serve as a potential alternative to ST.

Drug-induced liver injury (DILI) is a major cause of acute liver failure and drug withdrawal. Cytochrome P450 (CYP) 2E1 is involved in the metabolism of several drugs, and can induce liver injury through the production of toxic metabolites and the generation of reactive oxygen species. This study aimed to elucidate the role of Wnt/β-catenin signaling in CYP2E1 regulation for drug-induced hepatotoxicity. To achieve this, mice were administered cisplatin or acetaminophen (APAP) 1 h after treatment with the CYP2E1 inhibitor dimethyl sulfoxide (DMSO), and histopathological and serum biochemical analyses were performed. APAP treatment induced hepatotoxicity, as evidenced by an increase in liver weight and serum ALT levels. Moreover, histological analysis indicated severe injury, including apoptosis, in the liver tissue of APAP-treated mice, which was confirmed by TUNEL assay. Additionally, APAP treatment suppressed the antioxidant capacity of the mice and increased the expression of the DNA damage markers γ-H2AX and p53. However, these effects of APAP on hepatotoxicity were significantly attenuated by DMSO treatment. Furthermore, the activation of Wnt/β-catenin signaling using the Wnt agonist CHIR99021 (CHIR) increased CYP2E1 expression in rat liver epithelial cells (WB-F344), whereas treatment with the Wnt/β-catenin antagonist IWP-2 inhibited nuclear β-catenin and CYP2E1 expression. Interestingly, APAP-induced cytotoxicity in WB-F344 cells was exacerbated by CHIR treatment and suppressed by IWP-2 treatment. Overall, these results showed that the Wnt/β-catenin signaling is involved in DILI through the upregulation of CYP2E1 expression by directly binding the transcription factor β-cat/TCF to the Cyp2e1 promoter, thus exacerbating DILI., Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00180-6., Competing Interests: Conflict of InterestThe authors declare that they have no competing financial interests with respect to this study., (© The Author(s) under exclusive licence to Korean Society of Toxicology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Breast cancer is one of the most common cancers and causes several complications in females. Currently, MRI is a necessary method for preoperative studies in patients with breast cancer. A high frequency of breast MRI can lead to an increase in the number of incidental extramammary findings. Moreover, it can provide accurate preoperative workup; therefore, the prognosis of patients can be improved. Herein, we provide several extramammary findings, including the mediastinum, lung, upper abdomen, bone, and soft tissue, correlating with US, chest CT, liver MRI, PET-CT, and bone scan., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2023 The Korean Society of Radiology.)

Gap junctional intercellular communication (GJIC) is considered a key biological mechanism to maintain homeostasis in cell differentiation and growth. In addition, as another major signaling pathway associated with cell proliferation and differentiation, Wnt/β-catenin signaling appears to trigger several cellular responses against injury. The purpose of the present study was to investigate the effects of a known toxic agent, benzo[a]pyrene (BaP), on the regulation and interaction between GJIC and Wnt/β-catenin signaling. BaP treatment resulted in GJIC inhibition and decreases the major GJIC protein connexin 43 (Cx43) in WB-F344 rat liver epithelial cells. We also found BaP-mediated downregulation of Wnt/β-catenin signaling related to the PI3K-Akt pathway. To identify the relationship between GJIC and Wnt/β-catenin signaling, we treated WB-F344 cells with the Wnt agonist CHIR99021 and found that it inhibited GJIC while causing a significant reduction in Cx43 expression at both the mRNA and protein levels, through the repression of promoter activity. This Wnt agonist-mediated GJIC inhibition was confirmed using a small interfering RNA directed against the Wnt antagonist Dact2, indicating that Wnt/β-catenin signaling negatively regulates GJIC. Despite the inverse correlation between Wnt/β-catenin signaling and Cx43 promoter activation as indicated by downregulation of β-catenin nuclear translocation and upregulation of Cx43 promoter activation involving HNF3β, BaP treatment decreased the Cx43 protein expression, which was associated with protein degradation, possibly through protein kinase C activation. In conclusion, our results revealed the mechanism of BaP-induced inhibition of GJIC and Wnt/β-catenin signaling. More importantly, linking Wnt/β-catenin signaling to Cx protein expression will have profound implications in understanding the relationships among different major signaling pathways associated with cell proliferation and differentiation in toxicity., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: This research measures the regional GMV (rGMV) of the cerebellum, attention, Executive Function (EF) and we aimed to identify their correlation and sex differences in children and adolescents., Methods: Subjects comprised 114 children (male = 62, female = 52, 12.44 ± 2.99 years old) from South Korea. Participants were divided into three groups by age (age 6-9, 10-13, and 14-17). The Stroop Color and Word Test (SCWT), Wisconsin Card Sorting Test (WCST), and Advanced Test of Attention (ATA) were used to estimate executive function. Magnetic resonance imaging (MRI) images were analyzed with Regional Voxel-Based Morphometry Analysis., Results: The correlations between cerebellar rGMV and SCWT, WCST, and ATA subcategories showed difference by age and sex. In 6-9 age group, girls showed more overall correlations with cerebellar regions than boys, in WCST Categories Completed and ATA results. In age 10-13 group, more regions of cerebellum corresponded to SCWT subcategories in girls. Nevertheless, more correlation between cerebellar rGMV, WCST subcategories and some ATA subtests were observed in boys in the same age group. In the adolescent group, aged 14-17, boys showed more correlation with cerebellar rGMV, while girls showed little correlation., Conclusion: This study highlights that sex-different cerebellum maturation in adolescence might be correlated with EF and attention. These results provides evidence that cerebellum modulates higher cognitive functioning during child development.

Background: Ultrasound-guided percutaneous dilatational tracheostomy (US-PDT) has been adapted for use in intensive care units (ICU). US-PDT is comparable to bronchoscopy-assisted tracheostomy. However, compared to surgical tracheostomy (ST), its safety and effectiveness have not been well studied., Objectives: To determine the efficacy and safety of US-PDT compared to ST., Materials and Methods: A total of 90 patients who underwent US-PDT ( n  = 36) or ST ( n  = 54) between July 2019 and September 2020 were enrolled. US-PDT was performed in the ICU without a surgical assistant or bronchoscope. Data were collected retrospectively and analyzed regarding clinical characteristics, procedure times and details, complications, and mortality rate., Results: The success rate of US-PDT was 97.4% and the procedure time was shorter than ST (5.2 ± 3.1 vs. 10.5 ± 5.0 min). There were no significant differences in clinical characteristics and procedure details. There was no procedure-related mortality in either of the groups., Conclusions: US-PDT is time-efficient and as safe as ST. Based on our results, US-PDT may be considered a potential alternative to ST in high-risk patients and in those who cannot be transported., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Hyun Tag Kang et al.)

Background/aims: The risk factors and clinical impacts of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) remain controversial, and no data have been reported in Korea. This study aimed to investigate the epidemiology and importance of CAPA diagnostic efforts and to identify the predictors of CAPA and the impacts on clinical outcomes., Methods: Between January 2020 and May 2021, data of severely to critically ill COVID-19 patients were extracted from seven hospitals of the Catholic Medical Center through a clinical data warehouse. Corticosteroid use was subcategorized into total cumulative dose, early 7-day dose, mean daily dose, and duration of use., Results: A total of 2,427 patients were screened, and 218 patients were included. CAPA was diagnosed in 4.6% (10/218) of all hospitalized and 11.2% (10/89) of intensive care unit patients. Total cumulative dose (over 1,000 mg as methylprednisolone) and daily high-dose corticosteroid use (over 60 mg/day) were independent predictors but not early 7-day high-dose corticosteroid use (over 420 mg/week) (odds ratio [OR], 1.731; 95% confidence interval [CI], 0.350 to 8.571) nor prolonged use (OR, 2.794; 95% CI, 0.635 to 13.928). In-hospital overall mortality was 11.9% (26 of 218). CAPA itself did not affect the outcome; rather, daily high-dose steroid use significantly increased the 30-day mortality (hazard ratio, 5.645; 95% CI, 1.225 to 26.091)., Conclusion: CAPA was not uncommon, especially in critically ill patients. Daily high-dose corticosteroid use was the predictor of CAPA and associated with high mortality rates. High-dose corticosteroids use after early inflammatory phase should be avoided, and active surveillance methods for CAPA are essential for those high-risk patients.

Background: Sudden sensorineural hearing loss (SSNHL) has several aetiologies and may be a presenting symptom of vestibular schwannoma (VS)., Objectives: The aim of this study was to investigate the recovery rate after steroid treatment and the prognostic factors of SSNHL with VS., Materials and Methods: This was a retrospective observational study wherein 32 patients with VS who presented with SSNHL were analysed at a tertiary referral centre. Hearing gain and prognostic factors were the main outcome measures for steroid treatment intervention., Results: Among the 1698 patients presenting with SSNHL, VS was found in 43 (2.5%) patients. Eleven cases (34.3%) showed good recovery, with significant improvements in the pure-tone audiometry values. Even though age was a significant factor, there were no associations between steroid response and initial hearing level, presence of vertigo, tumour size, and tumour extension., Conclusions and Significance: Our study showed that hearing recovery of SSNHL does not exclude a VS diagnosis. We suggest that steroid treatment be considered in patients with VS presenting SSNHL.

Purpose: This study aimed to investigate the diagnostic performance of features suggestive of nodal metastasis on preoperative MRI in patients with invasive breast cancer., Materials and Methods: We retrospectively reviewed the preoperative breast MRI of 192 consecutive patients with surgically proven invasive breast cancer. We analyzed MRI findings of axillary lymph nodes with regard to the size, long/short ratio, cortical thickness, shape and margin of the cortex, loss of hilum, asymmetry, signal intensity (SI) on T2-weighted images (T2WI), degree of enhancement in the early phase, and enhancement kinetics. Receiver operating characteristic (ROC) analysis, chi-square test, t test, and McNemar's test were used for statistical analysis., Results: Increased shorter diameter, uneven cortical shape, increased cortical thickness, loss of hilum, asymmetry, irregular cortical margin, and low SI on T2WI were significantly suggestive of metastasis. ROC analysis revealed the cutoff value for the shorter diameter and cortical thickness as 8.05 mm and 2.75 mm, respectively. Increased cortical thickness (> 2.75 mm) and uneven cortical shape showed significantly higher sensitivity than other findings in McNemar's test. Irregular cortical margins showed the highest specificity (100%)., Conclusion: Cortical thickness > 2.75 mm and uneven cortical shape are more sensitive parameters than other findings, and an irregular cortical margin is the most specific parameter for predicting axillary metastasis in patients with invasive breast cancer., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2022 The Korean Society of Radiology.)

Objective: Delirium and agitation can be devastating and prolong the length of hospitalization. As part of our continuous improvement efforts, we implemented the use of intermittent chlorpromazine therapy to target refractory agitation associated with hyperactive or mixed delirium (RAA-D). The purpose of this study was to evaluate the effectiveness of chlorpromazine on RAA-D and delirium symptoms as well as any adverse effects in critically ill children., Methods: Retrospective chart review was conducted for children admitted to the pediatric intensive care unit who were treated with chlorpromazine for RAA-D from March 2017 to January 2019. The primary end point was to determine differences in Cornell Assessment for Pediatric Delirium (CAPD) and State Behavioral Scale (SBS) scores 24 hours before and after chlorpromazine administration. The secondary end points were the 24-hour cumulative dosing of narcotic and sedative agents before and after chlorpromazine administration and adverse events associated with chlorpromazine use., Results: Twenty-six patients were treated with chlorpromazine for RAA-D; 16 (61.5%) were male with a median age of 14.5 months (IQR, 6-48). The mean CAPD (n = 24) and median SBS (n = 23) scores were significantly lower 24 hours after chlorpromazine use when compared to baseline scores, 12 vs 8.9 (p = 0.0021) and 1 vs -1, (p = 0.0005) respectively. No significant adverse effects were observed., Conclusions: Chlorpromazine use in critically ill children with RAA-D was helpful for managing symptoms without adverse events. Further investigation is needed to evaluate the use of chlorpromazine to treat RAA-D to avoid long-term use of an antipsychotic., Competing Interests: Disclosures. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. This work has been presented at the Society of Critical Care Medicine Critical Care Congress in 2019., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email membershipo@pediatricpharmacy.org 2022.)

Oxidative stress plays important roles in inflammatory responses during acute lung injury (ALI). Recently, nanoconstruct (Nano)-based drug-delivery systems have shown promise in many models of inflammation. In this study, we evaluated the anti-inflammatory effects of N-acetylcysteine (NAC) loaded in a biocompatible Nano using a rat model of ALI. We synthesized a Nano with a good NAC-releasing capacity using porous silica Nano, which was used to produce Nano/NAC complexes. For in vivo experiments, Sprague-Dawley rats were intraperitoneally administered NAC or Nano/NAC 30 min after intratracheal instillation of lipopolysaccharide. After 6 h, bronchoalveolar lavage fluids and lung tissues were collected. The anti-oxidative effect of the Nano/NAC complex was confirmed by demonstrating reduced levels of reactive oxygen species after treatment with the Nano/NAC in vitro. In vivo experiments also showed that the Nano/NAC treatment may protect against LPS-induced ALI thorough anti-oxidative and anti-inflammatory effects, which may be attributed to the inactivation of the NF-κB and MAPK pathways. In addition, the effects of Nano/NAC treatment were shown to be superior to those of NAC alone. We suggest the therapeutic potential of Nano/NAC treatment as an anti-inflammatory agent against ALI. Furthermore, our study can provide basic data for developing nanotechnology-based pharmacotherapeutics for ALI., (© 2021. The Author(s).)

The hippocampus, which engages in the process of consolidating long-term memories and learning, shows active development during childhood and adolescence. The hippocampus also functionally influences attention. Based on the influence of hippocampal function on attention, it was expected that the volume of the hippocampus would be associated with the difference in attention during childhood and adolescence, in which the brain develops actively. Thus, this study examined the association between hippocampal volume and attention metrics measured by the continuous performance test (CPT) in 115 children and adolescents (mean age = 12.43 ± 3.0, 63 male and 52 female). In association studies with both auditory and visual attention, we found that the bilateral hippocampal volumes showed negative relationships with auditory omission errors. A smaller volume of the left hippocampus also led to a longer auditory response time. However, visual attention did not show any significant relationship with the hippocampal volume. These findings were consistent even after adjusting for the effects of the related covariates (e.g., age, insomnia, and depression). Taken together, this study suggested that the increase in hippocampal volume during childhood and adolescence was associated significantly with better auditory attention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kim, Choi, Kim, Kim, Kim, Kim, Park, Jung, Park and Park.)

PDE4 inhibitors are involved in anti-inflammatory and immunomodulatory responses. Recently, they have been getting attention as a new class of drugs treating inflammatory airway diseases. The T lymphocyte is a major cell type present in the inflammatory infiltrate in the airway wall in patients with chronic obstructive pulmonary disease (COPD), and a previous study found that treatment with a PDE4 inhibitor significantly suppressed T cell proliferation. However, the mechanism of action of PDE4 inhibitors has not been elucidated. The present study aimed to investigate major signal transduction pathways of T lymphocyte and identify the phase, during which PDE4 inhibitors affect T cell proliferation. Isolated splenic CD4+ T cells were grown under stimulation with an anti-CD3/CD28 antibody, and/or treated with roflumilast-n-oxide (RNO). A western blot assay was performed using major antibodies including anti-p-38, anti-p-PI3K, anti-p-JNK, anti-p-ERK 1/2, anti-NFAT1 (NFATc2), and anti-NF-kB antibodies. Additional experiments conducted on the pathway showed significant change following RNO treatment, thus providing further evidence for signal transduction pathway concerning PDE4 inhibitors. T cell proliferation was suppressed by RNO treatment. In the pathways involved in T cell proliferation, only expression of anti-NFAT1 antibody was suppressed by RNO treatment. In additional experiments on the NFAT pathway, the very first phase (TCR signalling) remained unchanged on treatment with RNO, but RNO treatment increased IP3R expression and suppressed calcineurin activity. Calcineurin activity, reduced by RNO, increased on treatment with an IP3 receptor agonist. PED4 inhibitor, roflumilast is speculated to suppress T cell proliferation by interfering with IP3-IP3R binding to inhibit calcium emission, blocking pathway activation from this phase onward, eventually decreasing the level of a growth factor for T cell proliferation, IL-2., (© 2020 John Wiley & Sons Australia, Ltd.)

Background: Influenza is a global public health problem causing considerable morbidity and mortality. Although vaccination is the most effective way to prevent infection, vaccination coverage is insufficient in people with chronic disease under 65 years, especially diabetes. The purpose of this study was to evaluate influenza vaccination coverage and identify factors associated with influenza vaccination in Korean diabetic adults under 65 years., Methods: Data were obtained from 24,821 subjects in the Korea National Health and Nutrition Examination Survey (2014 to 2017). Socioeconomic, health-related, and diabetic factors were investigated for their relations with influenza vaccination in diabetic patients under 65 years using univariate and multivariate analyses., Results: Among 24,821 subjects, 1,185 were diabetic patients under 65 years and their influenza vaccination rate was 36.5%. Socioeconomic (older age, female gender, non-smoker, light alcohol drinker, lower educational level, and employed status), health-related factors (lower fasting glucose and glycosylated hemoglobin level, good self-perceived health status, more comorbidities, recent health screening, more outpatient visits, and diet therapy), and diabetic factors (more awareness and getting treated) were associated with influenza vaccination. In multivariate analysis, more awareness and getting treated for diabetes were associated with influenza vaccination in diabetic patients under 65 years (odds ratio, 1.496 and 1.413; 95% confidence interval, 1.022 to 2.188 and 1.018 to 2.054, respectively)., Conclusion: Influenza vaccination rate was low in diabetic patients under 65 years, especially in those with unawareness and not getting treated for diabetes. Active screening and treatment for diabetes may be helpful to improve the influenza vaccination rate in these patients.

Adverse childhood experiences (ACEs) are known to be closely related to depression, anxiety and sleep problems. However, it remains unclear whether adolescents with ACEs have sleep problems regardless of depression or anxiety or under a mediating effect from depression or anxiety. Therefore, our aim was to examine whether depression or anxiety mediates the relationship between ACEs and sleep problems in adolescents by using a community sample. The Early Trauma Inventory Self Report-Short Form (ETISR-SF) and List of Threatening Experiences Questionnaire (LTE-Q) were used to assess traumatic ACEs. Ultimately, data from 737 students (M = 448, F = 289, 15.1 ± 1.4 years old) were included in the statistical analysis. A total of 576 (78.1%) participants reported that they had experienced one or more ACEs. Adolescents with ACEs had higher levels of depression, anxiety and sleep problems than did adolescents without ACEs, and boys tended to experience more trauma than girls. Depression and anxiety partially mediated the relationship between ACEs and sleep problems. The results of this study suggest the need for depression and anxiety interventions for adolescents with ACEs to reduce the long-term consequences, including sleep problems and physical health problems.

Objectives: This study aims to investigate the independent influence of maternal age on the risk of emergency cesarean section (CS) due to nonreassuring fetal heart rate or arrest disorder. Methods: This was a cross-sectional study on women with nulliparous pregnancies, who are attempting vaginal delivery at term and have a cephalic presentation without the indication of elective CS at the onset of labor. The primary outcome was the rate of emergency CS. Independent risk factors were elucidated using multivariate logistic regression analysis. Results: Of 3513 women, 541 (15.4%) delivered by emergency CS during a trial of vaginal delivery, with theses being due to nonreassuring fetal heart rate ( N  = 150) or arrest disorder ( N  = 391). In univariate analysis, both individual CS rate due to nonreassuring fetal heart rate or arrest disorder and total emergent CS rate increased with maternal age. The risk of emergency CS was also significantly higher when labor induction was performed (odds ratio (OR) 2.489, 95% confidence interval (CI) 2.043-3.033), while fetal weight was heavier (neonatal weight ≥3.5 kg; OR 2.396, 95% CI 1.956-2.934), and maternal BMI was higher (before pregnancy ≥25 kg/m 2 ; OR 2.751, 95% CI 1.980-3.823, at delivery ≥28 kg/m 2 ; OR 2.375 95% CI 1.915-2.946). Multivariate stepwise regression analysis showed a statistically significant increase in the risk of total emergency CS in mothers over 35 years of age, compared to that in women less than 30 years old (35-39 years group; adjusted OR 1.805 95% CI 1.347-2.418, ≥40 years group; adjusted OR 4.659 95% CI 2.709-8.013). CS due to nonreassuring fetal heart rate increased in mothers over 40 years of age (adjusted OR 5.354, 95% CI 2.386-12.017) and CS due to arrest disorder was also increased in mothers over 30 years of age (30-34 years group; adjusted OR 1.343, 95% CI 1.010-1.785, 35-39 years group; adjusted OR 1.906, 95% CI 1.357-2.679, ≥40 years group; adjusted OR 4.663, 95% CI 2.480-8.768). Similar to the result of univariate analysis, labor induction increased the risk of emergency CS (adjusted OR 2.241, 95% CI 1.828-2.747). Conclusions: Advanced maternal age is an independent risk factor of emergency CS due to nonreassuring fetal heart rate or arrest disorder during the trial of vaginal delivery. The risk of emergency CS was also increased when labor induction was performed. Therefore, the risk of emergency CS needs to be considered, especially when the labor induction is planned, in women aged 40 or more.

Purpose: The prevalence of chronic obstructive pulmonary disease (COPD) in females has increased, changing the concept of COPD as a disease mostly limited to males. In this study, the clinical characteristics of COPD in females were investigated., Patients and Methods: The study was based on a multicenter cohort of COPD patients recruited from 54 medical centers in South Korea. Sex-based differences in general characteristics, exposure risk factors, depression scores, results of pulmonary function tests, COPD exacerbation, symptom scores, and radiologic findings were evaluated. Sex-related differences in the annual FEV 1 change over 5 years were analyzed in a linear mixed model., Results: Of the 2515 patients enrolled in this study, 8.1% were female. Female patients who had a higher BMI and a lower level of education were less likely to be smokers, were more exposed to passive smoking/biomass, and were more depressed compared to males. The rates of bronchiectasis, previous childhood respiratory infection, and asthma were higher in females. Female patients also had more symptoms and a poorer exercise capacity than males, but no significant differences were observed in terms of exacerbations. Radiologic findings revealed that male patients had worse emphysema, and female patients had worse bronchiectasis, as determined based on chest X-ray and computed tomography findings. On pulmonary function tests, female patients had less obstruction and less annual FEV 1 loss over 5 years., Conclusion: This study revealed differences in the clinical parameters between male and female patients with COPD, including general characteristics, disease characteristics, and clinical outcomes., Competing Interests: The authors have no conflicts of interest., (© 2020 Choi et al.)

Objectives: Compared to adults, adolescents tend to prefer evening times developmentally. The orientation toward evening times is associated with behavioral and emotional problems. Thus, this study examined the association of circadian preference with sleep-related variables, depression, anxiety, and Internet addiction in Korean adolescents., Materials and Methods: Participants completed the questionnaires measuring sleep pattern, sleep problem, depression, anxiety, and Internet addiction., Results: Among 765 students (age range: 13-17 years), 211 students ( N male = 134) were allocated into morning types (MT) and 258 adolescents ( N male = 147) were allocated into evening types (ET) based on scores of the Morningness-Eveningness Scale. Adolescents without circadian preference ( N = 296) were defined as neither type (NT). ET, compared to MT and NT, woke up later in the weekend, showed delays in bedtimes, and spent shorter time sleeping. They also reported a higher level of daytime sleepiness, insomnia, and depression than NT. However, the group difference in wake time on school days was not significant, and adolescents showed mild insomnia regardless of their circadian preference. Although smartphone using time in the weekend was significantly different between groups, group difference in Internet addiction was significant only when gender was adjusted., Conclusion: Circadian preference was associated with sleep patterns and sleep problems in Korean adolescents. ET showed significantly different sleep patterns compared to MT and NT. ET not only reported a higher level of daytime sleepiness and insomnia but also more depressive symptoms compared to NT. These findings suggest that the uniqueness of adolescence and environmental factors seemed to influence the association of circadian preference with mental problem., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Psychiatry.)

Elevation of total cell-free DNA (cfDNA) in patients with preeclampsia is well-known; however, whether this change precedes the onset of symptoms remains inconclusive. Here, we conducted a nested case-control study to determine the elevation of cfDNA levels in women who subsequently developed preeclampsia. Methylated HYP2 (m-HYP2) levels were determined in 68 blood samples collected from women with hypertensive disorders of pregnancy, along with 136 control samples, using real-time quantitative PCR. The measured m-HYP2 levels were converted to multiples of the median (MoM) values for correction of maternal characteristics. The m-HYP2 levels and MoM values in patients with preeclampsia were significantly higher than in controls during the third trimester (P < 0.001, both), whereas those for women who subsequently developed preeclampsia did not differ during the second trimester. However, when patients with preeclampsia were divided based on the onset-time of preeclampsia or 10th percentile birth weight, both values were significantly higher in women who subsequently developed early-onset preeclampsia (P < 0.05, both) and preeclampsia with small-for-gestational-age (SGA) neonate (P < 0.01, both) than controls. These results suggested that total cfDNA levels could be used to predict early-onset preeclampsia or preeclampsia with SGA neonate.

Obstructive sleep apnea (OSA) is highly related to mental health problems, such as depression and anxiety. However, previous studies on OSA and depression and anxiety have mostly been conducted in the adult population. We aimed to (1) screen for risk of OSA in a sample of adolescents from the general population using self-report questionnaires and (2) examine whether there are differences between the high- and low-risk groups for OSA in depressive and anxiety symptoms, self-esteem, and sleep-related variables. The data of 793 students (age range: 12-17 years old) were analyzed. The participants were assigned to the high-risk (n = 202, 25.5%) or the low-risk group (n = 591, 74.5%) of OSA. The participants in the high-risk group had more severe anxiety symptoms, lower self-esteem, insomnia, excessive daytime sleepiness, and higher BMI compared those in the low-risk group. This study shows that it is possible to efficiently screen for risks of various problems associated with OSA in adolescents using an easy and simple screening tool., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The hydrophilicity of bone graft material generally used as a carrier can play an important role in regulating bone morphogenetic protein (BMP) expression at the bone graft site. The hydrophilicity, altering physicochemical properties, and enhancing biological capabilities, can be increased via surface modification through ultraviolet (UV) photofunctionalization and the effect on de novo osteogenesis could be further improved. Therefore, this study aimed to assess the effects of UV-irradiated TiO 2 -coated hydroxyapatite (HA) in combination with rhBMP-2 on bone regeneration in rabbit calvarial defects. The hydrophilicity of HA and TiO 2 -coated HA pellets was evaluated by measuring the contact angle of water droplets with UV irradiation. To compare de novo osteogenesis in rabbit calvarial defects, the rabbits were segregated into four different groups: negative control, HA, TiO 2 -coated HA, and TiO 2 -coated HA with UV; histomorphometric analysis and micro-computed tomography (μCT) imaging were performed after 4 and 8 weeks. In vivo analysis revealed that de novo osteogenesis occurred on the critical size defects in all groups and was significantly increased in the TiO 2 -coated HA with UV group than in other groups (p < 0.05). The present results indicate that UV photofunctionalization promotes de novo osteogenesis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1953-1959, 2019., (© 2018 Wiley Periodicals, Inc.)

Recovery from DNA damage is critical for cell survival. However, serious damage cannot be repaired, leading to cell death for prevention of abnormal cell growth. Previously, we demonstrated that 4N-DNA accumulates via the initiation of an abnormal interphase without cytokinesis and that re-replication occurs during a prolonged recovery period in the presence of severe DNA damage in mitotic cells. Mitotic phosphorylated Plk1 is typically degraded during mitotic exit. However, Plk1 has unusually found to be dephosphorylated in mitotic slippage without cytokinesis during recovery from mitotic DNA damage. Here, we investigated how Plk1 dephosphorylation is established during recovery from mitotic DNA damage. Mitotic DNA damage activated ATM and Chk1/2 and repressed Cdk1 and Greatwall protein kinase, followed by PP2A activation through the dissociation of ENSA and PP2A-B55. Interaction between Plk1 and PP2A-B55α or PP2A-B55δ was strongly induced during recovery from mitotic DNA damage. Moreover, the depletion of PP2A-B55α and/or PP2A-B55δ by siRNA transfection led to the recovery of Plk1 phosphorylation and progression of the cell cycle into the G 1 phase. Therefore, to adapt to severe DNA damage, the activated Greatwall/ENSA signaling pathway was repressed by ATM/Chk1/2, even in mitotic cells. Activation of the PP2A-B55 holoenzyme complex induced the dephosphorylation of Plk1 and Cdk1, and finally, mitotic slippage occurred without normal chromosome segregation and cytokinesis.

Purpose: Gastric adenoma (GA) is a premalignant lesion that precedes intestinal-type gastric carcinoma (GC). However, genetic progression mechanisms from GA to GC have not been clarified. Experimental Design: We performed whole-exome sequencing-based mutational analyses for 15 synchronous pairs of attached GAs and GCs. Results: There was no significant difference in the number of driver mutations or copy-number alterations between GAs and GCs. Well-known mutations of TP53, APC, RNF43, and RPL22 were recurrently detected in synchronous GA/GC pairs. In addition, we discovered novel KDM6A, PREX2, FAT1, KMT2C, GLI3, and RPL22 mutations and hypermutation in GAs, but did not identify recurrent drivers for GA-to-GC progression. Clonal structure analyses revealed that most GA/GC pairs exhibit parallel evolution with early divergence rather than stepwise evolution during GA-to-GC progression. Of note, three cases were identified as clonally nonrelated GA/GC pairs despite the lack of histologic differences. We found differences in dominant mutational signatures 1, 6, 15, and 17 in GA/GC trunks, GA branches, and GC branches. Compared with our previous work on synchronous colon adenoma/carcinoma genome structures, where most drivers were in the trunk with parallel evolution, synchronous GA/GC genomes showed a different model of parallel evolution, with many drivers in the branches. Conclusions: The preferred sequence of mutational events during GA-to-GC progression might be more context-dependent than colon adenoma progression. Our results show that nonclonal synchronous GA/GC is common and that GA genomes have already acquired distinct genomic alterations, suggesting caution in the diagnosis of synchronous GA and GC, especially in residual or recurrent cases. Clin Cancer Res; 24(19); 4715-25. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Metaplastic carcinoma is a rare subtype of breast cancer that comprises histologically diverse malignancies. Metaplastic carcinoma tends to have an aggressive clinical presentation, high metastatic potential, and more chances of local recurrence, as compared with intraductal carcinoma. Although many clinical and pathologic finding have been reported, to our knowledge, there are few reports of imaging findings for this type of tumor.In this study, we reviewed data of 5 patients with histopathologically proven metaplastic breast carcinoma. Multimodality imaging findings including those from mammography, ultrasonography, magnetic resonance imaging, and positron emission tomography-computed tomography were recorded.The results indicated that metaplastic carcinomas tend to show more benign imaging features such as round or oval shape with circumscribed margins and less axillary lymph node metastasis compared with invasive ductal carcinoma. High signal intensity on T2-weighted magnetic resonance imaging due to its cystic or necrotic component may be useful for diagnosis of metaplastic carcinoma.

Objective: We compared the expression levels of Müllerian inhibiting substance (MIS)/anti-Müllerian hormone type II receptor (AMHRII) in uterine myoma and adenomyosis to evaluate the possibility of using MIS/anti-Müllerian hormone (AMH) as a biological regulator or therapeutic agent in patients with uterine leiomyoma and adenomyosis., Methods: We studied normal uterine myometrium, leiomyoma, endometrial tissue, and adenomyosis from 57 patients who underwent hysterectomy for uterine leiomyoma (22 cases) or adenomyosis (28 cases) and myomectomy for uterine myoma (7 cases). Immunohistochemical staining was used to confirm the MIS/AMHRII protein expression level in each tissue. Reverse transcription-polymerase chain reaction was performed to quantify MIS/AMHRII mRNA expression., Results: The MIS/AMHRII protein was more strongly expressed in uterine myoma (frequency of MIS/AMHRII expressing cells: 51.95%±13.96%) and adenomyosis (64.65%±4.85%) tissues than that in the normal uterine myometrium (3.15%±1.69%) and endometrium (31.10%±7.19%). In the quantitative analysis of MIS/AMHRII mRNA expression, MIS/AMHRII mRNA expression levels in uterine myoma (mean density: 4.51±0.26) and adenomyosis (6.84±0.20) tissues were higher than that in normal uterine myometrial tissue (0.08±0.09) and endometrial tissue (1.63±0.06)., Conclusion: This study demonstrated that MIS/AMHRII was highly and strongly expressed on uterine myoma and adenomyosis. Our data suggest that MIS/AMH may be evaluated as a biological modulator or therapeutic agent on MIS/AMHRII expressing uterine myoma and adenomyosis., Competing Interests: Conflict of interest: No potential conflict of interest relevant to this article was reported.

Breast lymphoma is uncommon, and it usually involves breast parenchyma and ipsilateral axillary lymph nodes. We report rare cases of cutaneous T-cell lymphoma involving the skin and subcutaneous fat layers mimicking panniculitis of the breasts in a 33-year-old male patient who presented with a growing palpable mass and pain in both breasts and in 17-year-old female patient who presented with an indolent palpable breast mass for 1 year. Extranodal natural killer/T-cell nasal-type and subcutaneous panniculitis-like T-cell lymphomas were diagnosed after skin punch biopsies. Here we report the clinical manifestations, mammographic and ultrasound findings, and the difficulties in histological diagnosis of the cases.

Objective: We investigated the association of adipose tissue volume and metabolic activity with cardiometabolic risk factors., Methods: 232 healthy subjects (43.23±4.09y) having 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) results were included. Clinical information, anthropometry and laboratory results were obtained. Volume and metabolic activity of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) was obtained from FDG PET/CT. Metabolic activity was presented as mean standardised uptake value (SUV). Adipose tissue parameters were compared with clinical and biochemical factors. Independent factors affecting adipose tissue volume were assessed., Results: Both SAT and VAT volume showed strong positive correlation with most of cardiometabolic risk factors. Among them, lipid profiles, insulin and C-reactive protein (CRP) had more significant relationship with SUV of SAT than that of VAT. On the contrary, glucose, glycated hemoglobin, and degree of fatty liver showed more significant correlation with SUV of VAT. BMI, age, sex and CRP were independent predictors of SAT volume. BMI, age, triglyceride, CRP and fatty liver were independent variables predicting VAT volume. Adding SUV of adipose tissue improved the model performance., Conclusion: This study demonstrated that metabolic activities of SAT and VAT were differently correlated with risk factors, suggesting different biologic mechanism for obesity., (Copyright © 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: The purpose of the study was to investigate the frequencies and types of Y chromosome microdeletions in infertile men and to analyze the relationship between the levels of reproductive hormones and Y microdeletions., Methods: A total of 1,226 infertile men were screened for Y chromosome microdeletions using multiplex PCR assay. Karyotype analysis was performed on peripheral blood lymphocytes with standard G-banding. Serum reproductive hormone levels were measured., Results: Out of 1,226 infertile patients, 134 (10.93%) had Y microdeletions. One hundred seven of 765 (13.99%) non-obstructive azoospermic patients and 27 of 133 (20.30%) severe oligozoospermic patients had Y microdeletions. Among the 134 infertile men with Y microdeletions, the most frequent microdeletions were detected in the AZFc region, followed by AZFbc, AZFb, AZFa, AZFabc(Yq), Yp(SRY)+Yq, and partial AZFc regions. Karyotype analysis was available for 130 of the 134 patients with Y microdeletions. Of them, 36 (27.69%) patients had sex chromosomal abnormalities. Levels of FSH and LH in patients with AZFc microdeletion were significantly lower, while those in patients with Yp(SRY)+Yq were significantly higher than in patients without Y microdeletions. Level of testosterone in patients with AZFabc(Yq) or Yp(SRY)+Yq was significantly lower than that in patients without Y microdeletions. However, there was no significant difference in the levels of reproductive hormones between all patients with and without Y microdeletions., Conclusion: These results highlight the need for Y chromosome microdeletion screening for correct diagnosis of male infertility. Obtaining reliable genetic information for assisted reproductive techniques can prevent unnecessary treatment and vertical transmission of genetic defects to offspring.

Background: Recombinant human bone morphogenetic proteins (rhBMPs) have been widely used in regenerative therapies to promote bone formation. The production of rhBMPs using bacterial systems such as Escherichia coli ( E. coli ) is estimated to facilitate clinical applications by lowering the cost without compromising biological activity. In clinical practice, rhBMP-2 and osteoconductive carriers (e.g., hydroxyapatite [HA] and bovine bone xenograft) are used together. This study examined the effect of E. coli -derived rhBMP-2 combined with porous HA-based ceramics on calvarial defect in rabbits., Methods: Six adult male New Zealand white rabbits were used in this study. The experimental groups were divided into the following 4 groups: untreated (NC), bovine bone graft (BO), porous HA (HA) and porous HA with rhBMP-2 (HA-BMP). Four transosseous defects of 8 mm in diameter were prepared using stainless steel trephine bur in the frontal and parietal bones. Histological and histomorphometric analyses at 4 weeks after surgery revealed significant new bone formation by porous HA alone., Results: HA-BMP showed significantly higher degree of bone formation compared with BO and HA group ( P <0.05). The average new bone formation % (new bone area per total defect area) of NC, BO, HA, and HA-BMP at 4-week after surgery were 12.65±5.89%, 29.63±6.99%, 28.86±6.17% and 49.56±8.23%, respectively. However, there was no statistical difference in the bone formation between HA and BO groups., Conclusions: HA-BMP promoted more bone formation than NC, BO and HA alone. Thus, using E. coli -derived rhBMP-2 combined with porous HA-based ceramics can promote new bone formation., Competing Interests: No potential conflict of interest relevant to this article was reported.

Objective: Syphilis is a well-known sexually transmitted disease, and has multiple stages and various symptoms. However, it is difficult to diagnose syphilis in patients who may have no clinical symptoms. Because of these reasons, there have been several case reports on misdiagnosis of syphilis. Generalized lymphadenopathy could be an indication of various diseases including malignancies or infections., Conclusion: We report a case of a secondary syphilis in a patient with generalized lymphadenopathy detected by fluorine-18-fluorodeoxy glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) images without any clinical symptom. Clinical examination found an ulcer on his penis and serologic tests set the diagnosis of an early stage of secondary syphilis.

The aim of this study was to evaluate quantitative aberrations of novel fetal-specific epigenetic markers in maternal plasma of pregnancies with hypertensive disorders. We compared the concentrations of DSCR3, RASSF1A, and SRY as cell-free fetal DNA markers in 188 normal pregnancies, 16 pregnancies with early-onset preeclampsia (EO-PE), 47 pregnancies with late-onset preeclampsia (LO-PE), and 29 pregnancies with gestational hypertension (GH). The concentrations of all markers were significantly correlated with gestational age (p < 0.001 for all). Strong positive correlations were also observed between DSCR3 and SRY (r = 0.471, p < 0.001), as well as between RASSF1A and SRY (r = 0.326, p = 0.015) and between DSCR3 and RASSF1A (r = 0.673, p < 0.001). The concentrations of DSCR3 and RASSF1A in the EO-PE were significantly higher at 24-32 weeks and onwards (p < 0.05 for both). In the LO-PE, DSCR3 and RASSF1A concentrations were significantly higher only at 33-41 weeks compared with the controls. The concentrations of all markers in the GH group were not significantly different from those in the control group. This study is the first demonstration that DSCR3 is a novel epigenetic marker that can be an alternative to the RASSF1A for the prediction of EO-PE.

We report the case of a 60-year-old woman with left-sided breast cancer who showed lymphadenopathy mimicking metastatic lesions. She underwent surveillance (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) after treatment. PET/CT demonstrated multiple lymphadenopathies with increased FDG uptake, most notably in the right axilla. She had an eschar on the right axillary area, and her serologic test was positive for anti-Orientia tsutsugamushi IgM antibody. Ten months after the treatment, follow-up FDG PET/CT and ultrasonography showed improvement in generalized lymphadenopathy.

Purpose: The objective of this study was to discover a panel of microRNAs (miRNAs) as potential biomarkers for noninvasive prenatal testing (NIPT) of trisomy 21 (T21) and to predict the biological functions of identified biomarkers using bioinformatics tools., Methods: Using microarray-based genome-wide expression profiling, we compared the expression levels of miRNAs in whole blood samples from non-pregnant women, whole blood samples from pregnant women with euploid or T21 fetuses, and placenta samples from euploid or T21 fetuses. We analyzed the differentially expressed miRNAs according to disease and tissue type (P value <0.05 and two-fold expression change). To predict functions of target genes of miRNAs, the functional annotation tools were used., Results: We identified 299 miRNAs which reasonably separate the whole blood from the placenta. Among the identified miRNAs, 150 miRNAs were up-regulated in the placenta, and 149 miRNAs were down-regulated. Most of the up-regulated miRNAs in the placenta were members of the mir-498, mir-379, and mir-127 clusters. Among the up-regulated miRNAs in the placenta, mir-1973 and mir-3196 were expressed at higher levels in the T21 placenta than in the euploid placenta. The two miRNAs potentially regulate 203 target genes that are involved in development of brain, central nervous system, and nervous system. The genes are significantly associated with T21-related disorder such as congenital abnormalities, mental disorders, and nervous system diseases., Conclusions: Our study indicates placenta-specific miRNAs that may be potential biomarkers for NIPT of fetal T21 and provides new insights into the molecular mechanisms of T21 via regulation of miRNAs.

Spontaneous pneumothorax occurs in up to 35% of patients with Pneumocystis jirovecii pneumonia. However, spontaneous pneumomediastinum and pneumopericardium are uncommon complications in patients infected with human immunodeficiency virus, with no reported incidence rates, even among patients with acquired immunodeficiency syndrome (AIDS) and P. jirovecii pneumonia. We report a case of spontaneous pneumomediastinum, pneumopericardium, and pneumothorax with respiratory failure during treatment of P. jirovecii pneumonia in a patient with AIDS; the P. jirovecii infection was confirmed by performing methenamine silver staining of bronchoalveolar lavage specimens. This case suggests that spontaneous pneumomediastinum and pneumopericardium should be considered in patients with AIDS and P. jirovecii pneumonia.

Purpose: The aim of this study was to compare the diagnosability between (18)F-fluorodeoxyglucose (FDG) PET/CT and enhanced multi-detector CT (MDCT) for the detection of liver metastasis (LM) according to the size and location in liver and to evaluate standard maximum standardized uptake values (SUVmax) of all liver metastatic lesions., Materials and Methods: One hundred two consecutive patients with malignancy who underwent both FDG PET/CT and MDCT for LM evaluation were retrospectively reviewed. Among them, 56 patients with LM were enrolled in this study. LM was confirmed by follow-up imaging studies after at least 6 months or by histopathology. FDG PET/CT and MDCT images were visually analyzed using three-point scale by the consensus of two radiologists and two nuclear medicine physicians. The size and location (central vs. sub-capsular) of the all liver lesions were evaluated using MDCT images. Furthermore, SUVmax of all liver lesions on FDG PET/CT images were calculated., Results: A total of 146 liver lesions were detected by FDG PET/CT and MDCT and 142 of the lesions were diagnosed as LM. The detection rates of MDCT and FDG PET/CT for LM by visual analysis were 77 and 78%, respectively. There was no significant difference of detection rate according to the overall location and size of the lesions. However, FDG PET/CT was more sensitive than MDCT for detecting small and sub-capsular LM. The detection rate of FDG PET/CT for LM was 68% by the cutoff SUVmax of 2.7., Conclusions: Although the diagnosabilities of MDCT and FDG PET/CT for detecting LM were comparable, FDG PET/CT is superior to MDCT for detecting small LM located in the sub-capsular portion of liver.

The aim of this study was to develop a simple and effective method for noninvasively detecting fetal sex using circulating fetal DNA from first-trimester maternal plasma. A study was conducted with maternal plasma collected from 203 women between 5 and 12 wk of gestation. The presence of circulating fetal DNA was confirmed by a quantitative methylation-specific polymerase chain reaction of the unmethylated-PDE9A gene (U-PDE9A). Multiplex real-time PCR was used to simultaneously quantify the amount of DYS14 and GAPDH in maternal plasma. The results were confirmed by phenotype at birth. Pregnancy outcomes and U-PDE9A concentrations were obtained in all cases, including 99 male-bearing and 104 female-bearing participants. At equivalent specificity (100%), the false-negative rate was 9.1% for DYS14 quantification cycle, 7.1% for DYS14 concentration, and 0.0% for the concentration ratio of DYS14/GAPDH, respectively. In male-bearing participants, DYS14, U-PDE9A, and GAPDH concentrations were significantly lower in the false-negative case than in correct case (P<0.001 in all). Moreover, DYS14, U-PDE9A, and GAPDH concentrations showed significantly positive associations with each other (P≤0.001 in all). The ratio of DYS14/GAPDH in maternal plasma was an effective biomarker for noninvasive fetal sex detection during the first trimester, indicating that it could be useful for clinical application.

Purpose: To perform a reliable non-invasive detection of the fetal achondroplasia using maternal plasma., Methods: We developed a quantitative fluorescent-polymerase chain reaction (QF-PCR) method suitable for detection of the FGFR3 mutation (G1138A) causing achondroplasia. This method was applied in a non-invasive detection of the fetal achondroplasia using circulating fetal-DNA (cf-DNA) in maternal plasma. Maternal plasmas were obtained at 27 weeks of gestational age from women carrying an achondroplasia fetus or a normal fetus., Results: Two percent or less achondroplasia DNA was reliably detected by QF-PCR. In a woman carrying a normal fetus, analysis of cf-DNA showed only one peak of the wild-type G allele. In a woman expected an achondroplasia fetus, analysis of cf-DNA showed the two peaks of wild-type G allele and mutant-type A allele and accurately detected the fetal achondroplasia., Conclusions: The non-invasive method using maternal plasma and QF-PCR may be useful for diagnosis of the fetal achondroplasia.

Problem: The aim of this study was to investigate whether c.869T>C (Leu10Pro) and c.915G>C (Arg25Pro) polymorphisms in exon1 of the transforming growth factor-beta1 (TGF-beta1) gene are associated with development of pre-eclampsia (PE) in Korean women., Method of Study: We analyzed blood samples from 164 patients with PE and 182 healthy pregnant women using the polymerase chain reaction and DNA sequencing., Results: The frequencies of the 869CC and combined TC/CC genotypes were higher in patients with PE than in healthy controls. In the PE with intrauterine growth restriction (IUGR), the frequencies of these genotypes were also higher than that in controls. Furthermore, the 869C allele frequency was significantly higher in both PE and IUGR-complicated PE than in controls. Multivariate analysis showed that the 869TC, CC, and combined TC/CC genotypes were associated with an increased risk of PE compared with the 869TT genotype. In addition, the 869TC, CC, and combined TC/CC genotypes were significantly associated with an increased risk of IUGR-complicated PE compared with the 869TT genotype. The TGF-beta1 c.915G>C polymorphism was not detected in our population., Conclusion: Our findings indicate that the TGF-beta1 c.869T>C polymorphism may be a genetic risk factor for PE and IUGR-complicated PE.

Cd-doped alpha-MnS nanowires (av diam = 70 nm) were synthesized by the chemical vapor deposition of MnCl(2)/CdS powders. They all consisted of single-crystalline rock-salt MnS structures with the [111] growth direction. The X-ray diffraction pattern analysis indicates that 10% Cd doping would expand the lattice constants by 0.3%. As the content of Cd increases, the band edge emission band (2.9 eV) of photoluminescence becomes broader, and the Mn(2+) emission band (1.6 eV), which emerged at temperatures below approximately 150 K, decreases in intensity. The decay time of the 1.6 eV band decreases from 40 to 30 mus when the Cd doping is increased from 0 to 10%. In contrast to the bulk (T(N) = 150 K), the MnS nanowires were found to be paramagnetic with antiferromagnetic interactions. These distinctive magnetic properties of the nanowires have a strong correlation with their photoluminescence, which could be influenced by the nanosize effect and the Cd doping.