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Objective: Inflammation is crucial to limiting vascular disease. Previously we reported that acrolein, a known toxin in tobacco smoke, might play an important role in the progression of atherosclerosis via an inflammatory response involving cyclooxygenase-2 (COX-2) and prostaglandin production in human umbilical vein endothelial cells (HUVECs). Curcumin has been known to improve vascular function and have anti-inflammatory properties. In this study, we investigated whether curcumin prevents the induction of inflammatory response caused by acrolein. Methods: Anti-inflammatory effects of curcumin were examined in acrolein-stimulated HUVECs. Induction of proteins, mRNA, prostaglandin and reactive oxygen species (ROS) were measured using immunoblot analysis, real-time reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay and flow cytometry, respectively. Results: Curcumin attenuates inflammatory response via inhibition of COX-2 expression and prostaglandin production in acrolein-induced human endothelial cells. This inhibition by curcumin results in the abolition of phosphorylation of protein kinase C, p38 mitogenactivated protein kinase, and cAMP response element-binding protein. Furthermore, curcumin suppresses the production of ROS and endoplasmic reticulum stress via phosphorylation of eukaryotic initiation factor-2α caused by acrolein. Conclusion: These results suggest that curcumin might be a useful agent against endothelial dysfunction caused by acrolein-induced inflammatory response.

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancer cases, with more than 850,000 new diagnoses per year globally. Recent trends in the United States have shown that liver cancer mortality has continued to increase in both men and women, while 5-year survival remains below 20%. Understanding key mechanisms that drive chronic liver disease progression to HCC can reveal new therapeutic targets and biomarkers for early detection of HCC. In that regard, many studies have underscored the importance of alternative splicing as a source of novel HCC prognostic markers and disease targets. Alternative splicing of pre-mRNA provides functional diversity to the genome, and endows cells with the ability to rapidly remodel the proteome. Genes that control fundamental processes, such as metabolism, cell proliferation, and apoptosis, are altered globally in HCC by alternative splicing. This review highlights the major splicing factors, RNA binding proteins, transcriptional targets, and signaling pathways that are of key relevance to HCC. We highlight primary research from the past 3–5 years involving functional interrogation of alternative splicing in rodent and human liver, using both large-scale transcriptomic and focused mechanistic approaches. Because this is a rapidly advancing field, we anticipate that it will be transformative for the future of basic liver biology, as well as HCC diagnosis and management.

Abstract Cell‐type‐specific, activity‐dependent electrophysiology can allow in‐depth analysis of functional connectivity inside complex neural circuits composed of various cell types. To date, optics‐based fluorescence recording devices enable monitoring cell‐type‐specific activities. However, the monitoring is typically limited to a single brain region, and the temporal resolution is significantly low. Herein, a multimodal multi‐shank fluorescence neural probe that allows cell‐type‐specific electrophysiology from multiple deep‐brain regions at a high spatiotemporal resolution is presented. A photodiode and an electrode‐array pair are monolithically integrated on each tip of a minimal‐form‐factor silicon device. Both fluorescence and electrical signals are successfully measured simultaneously in GCaMP6f expressing mice, and the cell type from sorted neural spikes is identified. The probe's capability of combined electro‐optical recordings for cell‐type‐specific electrophysiology at multiple brain regions within a neural circuit is demonstrated. The new experimental paradigm to enable the precise investigation of functional connectivity inside and across complex neural circuits composed of various cell types is expected.

Recently, supplying healthcare services with wearable devices has been investigated. To realize this for true wireless stereo (TWS), which has limited resources (e.g. space, power consumption, and area), implementing multiple functions with one sensor simultaneously is required. The Photoplethysmography (PPG) sensor is a representative healthcare sensor that measures repeated data according to the heart rate. However, since the PPG data are biological, they are influenced by motion artifact and subject characteristics. Hence, noise reduction is needed for PPG data. In this paper, we propose the distance estimation algorithm for PPG signals of TWS. For distance estimation, we designed a waveform adjustment (WA) filter that minimizes noise while maintaining the relationship between before and after data, a lightweight deep learning model called MobileNet, and a PPG monitoring testbed. The number of criteria for distance estimation was set to three. In order to verify the proposed algorithm, we compared several metrics with other filters and AI models. The highest accuracy, precision, recall, and f1 score of the proposed algorithm were 92.5%, 92.6%, 92.8%, and 0.927, respectively, when the signal length was 15. Experimental results of other algorithms showed higher metrics than the proposed algorithm in some cases, but the proposed model showed the fastest inference time.

Early detection and proper management of chronic kidney disease (CKD) can delay progression to end-stage kidney disease. We applied metabolomics to discover novel biomarkers to predict the risk of deterioration in patients with different causes of CKD. We enrolled non-dialytic diabetic nephropathy (DMN, n = 124), hypertensive nephropathy (HTN, n = 118), and polycystic kidney disease (PKD, n = 124) patients from the KNOW-CKD cohort. Within each disease subgroup, subjects were categorized as progressors (P) or non-progressors (NP) based on the median eGFR slope. P and NP pairs were randomly selected after matching for age, sex, and baseline eGFR. Targeted metabolomics was performed to quantify 188 metabolites in the baseline serum samples. We selected ten progression-related biomarkers for DMN and nine biomarkers each for HTN and PKD. Clinical parameters showed good ability to predict DMN (AUC 0.734); however, this tendency was not evident for HTN (AUC 0.659) or PKD (AUC 0.560). Models constructed with selected metabolites and clinical parameters had better ability to predict CKD progression than clinical parameters only. When selected metabolites were used in combination with clinical indicators, random forest prediction models for CKD progression were constructed with AUCs of 0.826, 0.872, and 0.834 for DMN, HTN, and PKD, respectively. Select novel metabolites identified in this study can help identify high-risk CKD patients who may benefit from more aggressive medical treatment.

Objectives In this study the relationship between neighborhood deprivation and the unmet health care needs of elderly individuals (≥ 65 years) was examined. Some previous studies suggested that neighborhood characteristics affect access to health care, yet research on the unmet needs of older individuals is limited. Methods Multilevel logistic regression analysis was used to assess the relationship of neighborhood-level factors with unmet health care needs due to costs, adjusting for individual-level factors, in individuals ≥ 65 years in the 2017 Korean Community Health Survey (n = 63,388). Results There were 2.6% of elderly individuals who experienced unmet health care needs due to costs. Following adjustment for individual and neighborhood characteristics, the neighborhood deprivation in urban areas was found to have an inverse association with unmet needs (odds ratio = 0.50; 95% confidence interval = 0.24–1.06) for the most deprived quartile versus the least deprived quartile). However, in rural areas neighborhood deprivation was not a significant variable. Among the individual-level variables, household income was one of the strongest correlates with unmet needs in both urban and rural areas. Conclusion The present findings suggest that targeted policy interventions reflecting both neighborhood and individual characteristics, should be implemented to reduce the unmet health care needs of elderly individuals.

BackgroundBased on reported results of three large cardiovascular outcome trials (CVOTs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), we aimed to investigate the overall effect of GLP-1 RAs on major adverse cardiovascular events (MACEs) and to identify subpopulations exhibiting the greatest cardiovascular (CV) benefit.MethodsThree CVOTs reporting effects of long-acting GLP-1 RAs were included: LEADER (liraglutide), SUSTAIN-6 (semaglutide), and EXSCEL (exenatide once weekly). In all studies, the primary endpoint was three-point MACE, comprising CV death, non-fatal myocardial infarction, and non-fatal stroke. Overall effect estimates were calculated as hazard ratios and 95% confidence intervals (CIs) using the random-effects model; subgroup analyses reported in the original studies were similarly analyzed.ResultsOverall, statistically significant risk reductions in MACE and CV death were observed. Subgroup analysis indicated a significant racial difference with respect to CV benefit (P for interaction

Kidney disease: stem cells to the rescue Stem cells can halt the progression of kidney damage owing to diabetes by reducing inflammation and improving energy production in kidney cells. Eun Hee Koh at the University of Ulsan College of Medicine in Seoul, South Korea, and colleagues found that adult stem cells, known as mesenchymal stem cells (MSCs), derived from human umbilical cord blood had a protective effect on the kidneys of diabetic mice. Repeated administration of MSCs prevented the recruitment of pro-inflammatory cells into the kidney and increased the levels of arginase-1, a marker of cells with anti-inflammatory activity. Experiments in cells showed that MSCs stimulated the production of arginase-1 in that, in turn, were able to increase the production and activity of mitochondria in kidney cells. This study confirms an important role for MSCs in organ repair.

Background/Aims The impact of malnutrition on the outcome of hospitalized adults with community-acquired pneumonia (CAP) has not been fully investigated. This study evaluated the prevalence and prognostic significance of malnutrition in a Korean population with CAP. Methods In total, 198 patients with CAP from November 2014 to September 2015 were analyzed retrospectively. We assessed the prevalence of malnutrition and the risk factors for 2-year mortality. Furthermore, we divided the patients into two groups: elderly (age ≥ 65 years, n = 131) and non-elderly (age < 65 years, n = 67). Subgroup analyses were performed in the elderly group through propensity score matching. Results The prevalence of malnutrition was 39.4%, and the proportion of patients with malnutrition was significantly higher (53.4% vs. 11.9%, p < 0.001) in the elderly group than in the non-elderly group. In-hospital mortality, 1-year mortality, and 2-year mortality rates were 4.5%, 19.2%, and 26.8%, respectively. Multivariate Cox regression analyses revealed that malnutrition (odds ratio [OR], 2.52; 95% confidence interval [CI], 1.39 to 4.60; p = 0.002) and the Charlson comorbidity index score (OR, 1.30; 95% CI, 1.17 to 1.45; p < 0.001) were associated with 2-year mortality. Conclusions Malnutrition was common and associated with a poor long-term outcome in patients with CAP, particularly the elderly. A routine nutritional assessment at admission is mandatory as a first step for appropriate nutritional therapy.

Desmoid-type fibromatosis (extra-abdominal desmoid tumor) arising in the breast is a rare benign disease entity, accounting for 0.2% of all breast tumors. The etiology of mammary fibromatosis is unknown, but has been reported to be associated with genetic factors, hormonal effects, Gardner syndrome, breast trauma or surgery, and breast implants. Fibromatosis associated with breast implants is extremely rare, and only 34 cases have been reported so far. We report the ultrasonographic, computed tomographic, and pathologic findings of breast fibromatosis in a 29-year-old woman, who underwent bilateral augmentation mammoplasty with silicone implants.

Adipose tissue inflammation is considered a major contributing factor in the development of obesity-associated insulin resistance and cardiovascular diseases. However, the cause of adipose tissue inflammation is presently unclear. The role of mitochondria in white adipocytes has long been neglected because of their low abundance. However, recent evidence suggests that mitochondria are essential for maintaining metabolic homeostasis in white adipocytes. In a series of recent studies, we found that mitochondrial function in white adipocytes is essential to the synthesis of adiponectin, which is the most abundant adipokine synthesized from adipocytes, with many favorable effects on metabolism, including improvement of insulin sensitivity and reduction of atherosclerotic processes and systemic inflammation. From these results, we propose a new hypothesis that mitochondrial dysfunction in adipocytes is a primary cause of adipose tissue inflammation and compared this hypothesis with a prevailing concept that “adipose tissue hypoxia” may underlie adipose tissue dysfunction in obesity. Recent studies have emphasized the role of the mitochondrial quality control mechanism in maintaining mitochondrial function. Future studies are warranted to test whether an inadequate mitochondrial quality control mechanism is responsible for mitochondrial dysfunction in adipocytes and adipose tissue inflammation.

Granulocytic sarcoma is a form of extramedullary involvement of primitive myeloid cells. A 69-year-old male patient, with history of acute myeloid leukemia (AML) in remission state for 4 years, presented numbness, radiating pain and progressive motor weakness in left leg. MRI showed perineural thickening of the left sciatic nerve with increased signal intensity on fat-saturated T2-weighted image. The patient underwent surgical excision and the pathology was confirmed as granulocytic sarcoma. Its involvement of the peripheral nerve is extremely rare and also unusual to be the only evidence of AML relapse. In this case, we figured out the MRI feature of granulocytic sarcoma involving sciatic nerve, emerged as a sole manifestation of AML relapse.

Mitochondria are highly dynamic cellular organelles that perform crucial functions such as respiration, energy production, metabolism, and cell fate decisions. Mitochondrial damage and dysfunction critically lead to the pathogenesis of various diseases including cancer, diabetes, and neurodegenerative and cardiovascular disorders. Mitochondrial damage in response to environmental contaminant exposure and its association with the pathogenesis of diseases has also been reported. Recently, persistent pollutants, such as micro- and nanoplastics, have become growing global environmental threats with potential health risks. In this review, we discuss the impact of micro- and nanoplastics on mitochondria and review current knowledge in this field.

Background and Objectives: Type 2 diabetes (T2D) is an independent risk factor for the development of atrial fibrillation (AF). Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have recently been shown to decrease the incidence of AF through several mechanisms, including the reduction of atrial dilatation via diuresis and the lowering of body weight. In observational studies of diabetic patients, the use of thiazolidinedione (TZD) was found to have a protective effect on new-onset AF. In this study, we aimed to compare the effect of SGLT-2i and TZD on the risk of AF in patients with T2D. Methods: We enrolled 69,122 patients newly prescribed SGLT-2i and 94,262 patients prescribed TZD from January 2014 to December 2018, using the Korean National Health Insurance Service database. We compared new-onset AF events (hospitalizations and outpatient events) in SGLT-2i and TZD groups after having taken medication for greater than 90 days. Results: During a mean follow-up of 1.8 years, 397 (0.72%) new-onset AF events occurred in the SGLT-2i group and 432 (0.79%) events in the TZD group following propensity score matching (each group n = 54,993). The hazard ratio (HR) of AF was 0.918 (95% confidence interval: 0.783–1.076, p = 0.29) in SGLT-2i-treated patients compared with TZD-treated patients. Conclusions: In this study, the risk of new-onset AF is comparable in patients treated with SGLT-2i and TZD in T2D. Either SGLT-2i or TZD would be a reasonable choice for T2D patients who are at risk for AF.

OBJECTIVES This study aimed to identify relapse patterns in smokers who participated in an inpatient treatment program and to investigate factors related to relapse. METHODS The participants comprised 463 smokers who participated in an inpatient treatment operated by the Daejeon Tobacco Control Center from 2015 to 2018. Participants received high-intensity smoking cessation intervention for 5 consecutive days, including pharmacotherapy and behavioral support, and continued with follow-up for 1 year to determine whether they maintained smoking cessation after discharge from inpatient treatment. Kaplan-Meier and Cox proportional hazard models were used in the analysis. RESULTS Participants’ relapse rate within 1 year was 72.8%, and 59.8% of participants smoked again within 6 months after participation. A higher number of counseling sessions was significantly associated with a lower risk of relapse (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.17 to 0.32 for ≥9 vs. ≤5 counseling sessions). Conversely, higher relapse rates were significantly associated with the use of nicotine replacement therapy (NRT) (HR, 1.91; 95% CI, 1.43 to 2.55 for use vs. no use), and higher levels of baseline expired carbon monoxide (CO) (HR, 1.58; 95% CI, 1.21 to 2.06 for expired CO concentrations of 10-19 ppm vs. expired CO concentrations

We describe a case of Lemierre’s syndrome (LS) caused by a hypervirulent strain of Klebsiella pneumoniae in a 63-year-old female with hypertension, hyperlipidemia, and diabetes mellitus, who presented with right neck pain and fevers. Computerized tomography of the neck and chest revealed an occluded right internal jugular vein secondary to thrombosis and septic emboli in lungs. Blood cultures grew K. pneumoniae. The patient was treated with ampicillin-sulbactam and then transitioned to amoxicillin-clavulanate to complete a 6-week course of antibiotics, and a 3-month course of rivaroxaban. String test of the K. pneumoniae isolate was positive at 2 cm. Whole genome sequencing identified several genes associated with the hypervirulent strain, notably the genes encoding for aerobactin (iucA and iucB) and salmochelin (iroB) iron acquisition systems. LS can rarely be caused by K. pneumoniae. Clinicians should monitor for known complications, such as septic emboli in patients with LS.

Most NTRK fusions occur at very low frequencies in various common cancers. Recent recommendations on NTRK testing recommend immunohistochemistry (IHC) as the initial test for tumor types with a low frequency of NTRK fusions. This study investigated the accuracy of an IHC assay to detect NTRK fusions and characterize the clinicopathological and molecular features of NTRK-rearranged tumors. This retrospective study was conducted on 1113 solid tumor samples known to harbor no oncogenic driver alterations, including 510 non-small cell lung cancers (NSCLC), 503 colorectal cancers (CRC), and 79 inflammatory myofibroblastic tumors (IMT). Additionally, 21 ALK expression-positive cases were included. TRK expression was evaluated using a pan-Trk IHC assay, and positive cases were validated using NGS. TRK expression was observed in three NSCLCs (0.6%), six CRCs (1.2%), and six IMTs (6%). NTRK fusions were finally detected in two NSCLCs (0.4%), six CRCs (1.2%), and one IMT (1%). In NSCLC and CRC, the majority of NTRK fusions were readily discernible due to diffuse moderate-to-strong cytoplasmic staining on pan-Trk IHC. In IMT, focal weak nuclear staining indicated the presence of NTRK fusion. Therefore, the utility of pan-Trk IHC should be assessed considering that the difference in performance depends on tumor type.

Diclofenac, a nonsteroidal anti-inflammatory drug (NSAID) used to treat inflammatory diseases induces cellular toxicity by increasing the production of reactive oxygen species (ROS) and impairing autophagic flux. In this study, we investigated whether diclofenac induces cancer cell death and the mechanism by which diclofenac causes cell death. We observed that diclofenac induces mitotic arrest with a half-maximal effective concentration of 170 μM and cell death with a half-maximal lethal dose of 200 µM during 18-h incubation in HeLa cells. Cellular microtubule imaging and in vitro tubulin polymerization assays demonstrated that treatment with diclofenac elicits microtubule destabilization. Autophagy relies on microtubule-mediated transport and the fusion of autophagic vesicles. We observed that diclofenac inhibits both phagophore movement, an early step of autophagy, and the fusion of autophagosomes and lysosomes, a late step of autophagy. Diclofenac also induces the fragmentation of mitochondria and the Golgi during cell death. We found that diclofenac induces cell death further in combination with 5-fuorouracil, a DNA replication inhibitor than in single treatment in cancer cells. Pancreatic cancer cells, which have high basal autophagy, are particularly sensitive to cell death by diclofenac. Our study suggests that microtubule destabilization by diclofenac induces cancer cell death via compromised spindle assembly checkpoints and increased ROS through impaired autophagy flux. Diclofenac may be a candidate therapeutic drug in certain type of cancers by inhibiting microtubule-mediated cellular events in combination with clinically utilized nucleoside metabolic inhibitors, including 5-fluorouracil, to block cancer cell proliferation.

DNA replicase polymerase ε (POLE) is critical in proofreading and correcting errors of DNA replication. Low POLE expression plays a pivotal role in accumulation of mutations and onset of cancer, contributing to development and growth of tumor cells. The aim of this study is to reveal the survival, alternative genes and antitumoral immune activities in non-small cell lung cancer (NSCLC) patients with low POLE expression and provide treatment strategies that can increase their survival rates. This study investigated the clinicopathologic parameters, various tumor-infiltrating lymphocytes (TILs), endogenous retrovirus, molecular interactions and in vitro drug screen according to POLE mutation/expression in 168 and 1,019 NSCLC patients from the Konkuk University Medical Center (KUMC) and the Cancer Genome Atlas, respectively. We identified mutations of 75 genes in the sequencing panels, with POLE frame shift p.V1446fs being the most frequent (56.8%) in KUMC based on 170 targeted sequencing panels. Mutant and high expression of POLE correlated with favorable prognosis with increased TILs and tumor mutation burden, compared with wild type and low expression of POLE. We found specific molecular interactions associated with cell cycle and antigen presentation. An in vitro drug screen identified dasatinib that inhibited growth of the NSCLC cell line with low POLE expression. POLE could contribute to the future development of anticancer drugs for patients with NSCLC.

Inherited metabolic disease: Restoring motor function by reducing cholesterol An acid secreted by stem cells can reduce the excess cholesterol caused by a genetic metabolic disorder. Niemann–Pick type C disease is a rare, inherited condition that causes defective muscular development and progressive neurological degeneration. A key disease mechanism is the excessive accumulation of cholesterol within cells. Kyung-Sun Kang at Seoul National University, South Korea, and co-workers have demonstrated that a metabolite molecule called 14,15-epoxyeicosatrienoic acid (14,15-EET) derived from stem cells from human umbilical cord blood significantly reduced cholesterol in Neimann-Pick Type C mouse models and human cell samples. The team administered the stem cell therapy non-invasively via the nose, and observed significant improvements in motor function in the mice. Experiments in both animals and cells showed that the treatment resulted in reduced cholesterol levels and the correction of defective signalling within cells.

Abstract Background Sarcomas are challenging to study because of their rarity and histomorphological complexity. PD1 and PD-L1 inhibitors showed a promising anti-tumor effect in solid tumors, where a relationship between PD-L1 expression and the objective response has been evidenced. Methods In this study, we examined PD-L1 expression in 16 bone and soft tissue sarcoma cell lines of 11 different subtypes by means of western blot, flow cytometry and immunocytochemistry, and in 230 FFPE patient-derived tumor tissues by means of immunohistochemistry using three different antibody clones. The association between PD-L1 expression and clinicopathological features was evaluated. Results We demonstrated that PD-L1 protein is highly expressed in pleomorphic rhabdomyosarcoma, fibrosarcoma, and dedifferentiated liposarcoma (DDLPS) cell lines. From the tissue microarray, undifferentiated pleomorphic sarcoma showed ≥ 1% immunoreactivity in 20%, 17.6%, and 16.3% of the cases with PD-L1 22C3, SP263, and SP142 antibodies, respectively. In whole sections stained with a PD-L1 22C3 antibody, DDLPS showed ≥ 1% immunoreactivity in 21.9% of the cases. In DDLPS group, cases with ≥ 1% PD-L1 expression showed statistically significantly worse recurrence-free survival (P = 0.027) and overall survival (P = 0.017) rates. Upon interferon–gamma treatment, the mRNA expression levels of PD-L1 were elevated in the HS-RMS-1, LIPO-224B, MLS1765, RH30, and RH41 cell lines. Conclusions We found that the expression of PD-L1 in sarcoma differs depending on the histologic subtype and the PD-L1 antibody clones. These results may serve as primary data for the selection of appropriate patients when applying PD1/PD-L1 inhibitor therapy in sarcoma.

Stem cell therapy: Finding the best cells Stem cells from some donors have a stronger therapeutic effect than others, and can be identified by genetic markers. Adult or mesenchymal stem cells (MSCs), which can differentiate into many other cell types, show promise to treat many diseases. Kyung-Sun Kang at Seoul National University and co-workers investigated whether MSCs from some donors show better therapeutic efficacy than others. They tested MSCs from several donors in a mouse model simulating a stroke in a hindlimb, and measured regrowth of blood vessels. MSCs from one donor showed higher regenerative efficacy, triggering regrowth of many blood vessels and allowing the limb to be saved. Kang and co-workers used genetic analysis to identify genes that showed higher expression in these MSCs. This gene expression profile could be used to select MSCs with a higher regenerative capacity.

Objective: To investigate anti-quorum sensing (anti-QS) and anti-biofilm formation (anti- BF) activities of the ethanol extracts of 388 plants. Methods: The anti-QS activity of the plant extracts was evaluated by disc-diffusion assays using the bio-reporter strain, Chromobacterium violaceum CV017. Pseudomonas aeruginosa PAO1, Yersinia enterocolitica ATCC 9610, and Agrobacterium tumefaciens C58, which possess QS systems, were used to evaluate the anti- BF activity of the plant extracts. Results: Among 388 plant extracts, the Cornus controversa (C. controversa) and Cynanchum wilfordii extracts exhibited the strongest anti-QS activity. The C. controversa extract exhibited anti-BF activity against Pseudomonas aeruginosa, Yersinia enterocolitica and Agrobacterium tumefaciens, whereas the Cynanchum wilfordii extract exhibited no anti-BF activity against Pseudomonas aeruginosa. In addition, the C. controversa extract suppressed soft rot of cabbage. Conclusions: The C. controversa extract inhibits bacterial QS and BF, and is capable of controlling soft rot. Therefore, this extract has potential for the prevention and treatment of bacterial infections and for the development of alternatives to antibiotics.

Growing interest in intelligent vehicles is leading automotive systems to include numerous electronic control units (ECUs) inside. As a result, efficient implementation and management of automotive systems is gaining importance. Flexible updating and reconfiguration of ECUs is one appropriate strategy for these goals. Software updates to the ECUs are expected to improve performance and bug handling, but there are limitations due to the fixed hardware circuit. By applying hardware-reconfigurable ECUs to the automotive system, patches that are not able to be handled with only software updates are enabled. In this paper, a remotely hardware-reconfigurable ECU for automotive systems is proposed. The proposed ECU is implemented with a field programmable gate array (FPGA) and microcontroller unit (MCU) to support in-system reconfiguration (ISR). The communication interface between the FPGA and MCU employs Zipwire communication for high speed and resilient communication. For the Zipwire communication, a Zipwire controller is designed and implemented in the FPGA. The proposed hardware-reconfigurable ECU was successfully implemented, and feasibility was demonstrated.

Artificial intelligence algorithms need an external computing device such as a graphics processing unit (GPU) due to computational complexity. For running artificial intelligence algorithms in an embedded device, many studies proposed light-weighted artificial intelligence algorithms and artificial intelligence accelerators. In this paper, we propose the ASimOV framework, which optimizes artificial intelligence algorithms and generates Verilog hardware description language (HDL) code for executing intelligence algorithms in field programmable gate array (FPGA). To verify ASimOV, we explore the performance space of k-NN algorithms and generate Verilog HDL code to demonstrate the k-NN accelerator in FPGA. Our contribution is to provide the artificial intelligence algorithm as an end-to-end pipeline and ensure that it is optimized to a specific dataset through simulation, and an artificial intelligence accelerator is generated in the end.

Recent advances in artificial intelligence (AI) technology encourage the adoption of AI systems for various applications. In most deployments, AI-based computing systems adopt the architecture in which the central server processes most of the data. This characteristic makes the system use a high amount of network bandwidth and can cause security issues. In order to overcome these issues, a new AI model called federated learning was presented. Federated learning adopts an architecture in which the clients take care of data training and transmit only the trained result to the central server. As the data training from the client abstracts and reduces the original data, the system operates with reduced network resources and reinforced data security. A system with federated learning supports a variety of client systems. To build an AI system with resource-limited client systems, composing the client system with multiple embedded AI processors is valid. For realizing the system with this architecture, introducing a controller to arbitrate and utilize the AI processors becomes a stringent requirement. In this paper, we propose an embedded AI system for federated learning that can be composed flexibly with the AI core depending on the application. In order to realize the proposed system, we designed a controller for multiple AI cores and implemented it on a field-programmable gate array (FPGA). The operation of the designed controller was verified through image and speech applications, and the performance was verified through a simulator.

Purpose To evaluate the results of two-injection ethanol sclerotherapy in simple renal cysts performed with 5-minute ethanol exposure time. Materials and Methods We retrospectively reviewed 30 renal cysts in 30 patients treated by ethanol sclerotherapy between November 2002 and October 2015. Under ultrasound guidance, the renal cyst was punctured and a 7 Fr pigtail catheter was inserted, and then complete aspiration of the cystic fluid was performed. Then, 99.9% ethanol in a quantity amounting to 1/3–1/2 of the aspirated volume was infused into the cyst and it was immediately removed. The same amount of ethanol was re-infused and removed after 5 minutes. Follow-up examination was performed using ultrasound or CT images at least 3 months after the procedure and pre- and post-treatment cyst volumes were estimated. The therapeutic response was classified as either complete success (volume reduction, ≥ 95%), partial success (volume reduction, 50–95%), or failure (volume reduction, < 50%) based on the volume reduction rate. Results The average volume reduction rate was 96.3%. The rates of complete success, partial success and failure were 80% (n = 24), 20% (n = 6), and 0% (n = 0), respectively. There was no complication except for minor flank pain. Conclusion Two-injection ethanol sclerotherapy with 5-minute exposure time represents a simple and effective treatment for simple renal cysts.

Background The risk of bleeding during extracorporeal membrane oxygenation (ECMO) is a potential deterrent in performing tracheostomy at many centers. To evaluate the safety of surgical tracheostomy (ST) in critically ill patients supported by ECMO, we reviewed the clinical correlation between preoperative coagulation status and bleeding complication-related ST during ECMO. Methods From April 1, 2012 to March 31, 2016, ST was performed on 38 patients supported by ECMO. We retrospectively reviewed and analyzed the medical records including complications related to ST. Results Heparin was administered to 23 patients (60.5%) for anticoagulation during ECMO, but 15 patients (39.5%) underwent ECMO without anticoagulation. Of the 23 patients administered anticoagulation therapy, heparin infusion was briefly paused in 13 prior to ST. The median platelet count, international normalized ratio, and activated partial thromboplastin time before ST were 126 × 109/L (range, 46 to 434 × 109/L), 1.2 (range, 1 to 2.3) and 62 seconds (27 to 114.2 seconds), respectively. No peri-procedural clotting complications related to ECMO were observed. Two patients (5.3%) suffering from ST-related major bleeding required surgical hemostasis. Minor bleeding after ST occurred in two cases (5.3%). No significant difference was found according to anticoagulation management (P = 0.723). No fatality was attributable to ST. Conclusions The complication rates of ST in the patients supported by ECMO were low. Therefore, ST performed by an experienced operator, and with careful optimization of coagulation status, is a relatively safe procedure; the use of ST with ECMO should thus not be dismissed on account of the potential for bleeding caused by the administration of anticoagulants.

Summary: The underlying mechanisms of how positive emotional valence (e.g., pleasure) causes preference of an associated context is poorly understood. Here, we show that activation of astrocytic μ-opioid receptor (MOR) drives conditioned place preference (CPP) by means of specific modulation of astrocytic MOR, an exemplar endogenous Gi protein-coupled receptor (Gi-GPCR), in the CA1 hippocampus. Long-term potentiation (LTP) induced by a subthreshold stimulation with the activation of astrocytic MOR at the Schaffer collateral pathway accounts for the memory acquisition to induce CPP. This astrocytic MOR-mediated LTP induction is dependent on astrocytic glutamate released upon activation of the astrocytic MOR and the consequent activation of the presynaptic mGluR1. The astrocytic MOR-dependent LTP and CPP were recapitulated by a chemogenetic activation of astrocyte-specifically expressed Gi-DREADD hM4Di. Our study reveals that the transduction of inhibitory Gi-signaling into augmented excitatory synaptic transmission through astrocytic glutamate is critical for the acquisition of contextual memory for CPP. : Nam et al. demonstrate that activation of hippocampal astrocytic μ-opioid receptor causes glutamate release, which increases the release probability by neuronal presynaptic mGluR1 activation and potentiates synaptic plasticity at the SC-CA1 pathway. This enhanced synaptic transmission and synaptic plasticity account for the acquisition of memory associated with CPP. Keywords: astrocyte, hippocampus, μ-opioid receptor, conditioned place preference, long-term potentiation opioid

ObjectiveThe current paradigm in the treatment of patients with non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a diagnostic lobectomy rather than complete thyroidectomy and postoperative radioiodine treatment. Consequently, preoperative diagnosis of NIFTP is considered to be important.MethodsWe performed the comprehensive analysis for diagnosis of preoperative 20 NIFTPs in comparison with 41 invasive encapsulated follicular papillary thyroid carcinomas (I-EFVPTCs) using the Korean Thyroid Imaging Reporting and Data System (K-TIRADS), Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), and molecular analysis for BRAF and RAS mutations.ResultsK-TIRADS 3 was identified as the most common sonographic diagnosis in both NIFTP and I-EFVPTC. Unlike I-EFVPTC, K-TIRADS 5 was not identified in NIFTP. AUS/FLUS was the most common cytopathological diagnosis and none of the cases were classified as malignant category in both groups, although the difference in distribution was not significant between the groups. BRAF mutation was not found in NIFTP but was present in 9.8% of cases in I-EFVPTC. The frequency of RAS mutation in I-EFVPTCs was twice as high as that of NIFTP. Wild-type BRAF and RAS in NIFTP was significantly higher than I-EFVPTC.ConclusionThe existence of overlapping features between the groups was evident, hence conclusive distinction between radiology, cytology and molecular analysis could not be achieved. Apparently, the diagnosis of NIFTP based on comprehensive analysis was not confirmable but could perceive or at least favor the diagnosis of NIFTP.

Vascular diseases are major causes of death worldwide, causing pathologies including diabetes, atherosclerosis, and chronic obstructive pulmonary disease (COPD). Exposure of the vascular system to a variety of stressors and inducers has been implicated in the development of various human diseases, including chronic inflammatory diseases. In the vascular wall, antioxidant enzymes form the first line of defense against oxidative stress. Recently, extensive research into the beneficial effects of phytochemicals has been conducted; phytochemicals are found in commonly used spices, fruits, and herbs, and are used to prevent various pathologic conditions, including vascular diseases. The present review aims to highlight the effects of dietary phytochemicals role on antioxidant enzymes in vascular diseases.

The development of the mobile industry brings about the demand for high-performance embedded systems in order to meet the requirement of user-centered application. Because of the limitation of memory resource, employing compressed data is efficient for an embedded system. However, the workload for data decompression causes an extreme bottleneck to the embedded processor. One of the ways to alleviate the bottleneck is to integrate a hardware accelerator along with the processor, constructing a system-on-chip (SoC) for the embedded system. In this paper, we propose a lossless decompression accelerator for an embedded processor, which supports LZ77 decompression and static Huffman decoding for an inflate algorithm. The accelerator is implemented on a field programmable gate array (FPGA) to verify the functional suitability and fabricated in a Samsung 65 nm complementary metal oxide semiconductor (CMOS) process. The performance of the accelerator is evaluated by the Canterbury corpus benchmark and achieved throughput up to 20.7 MB/s at 50 MHz system clock frequency.

Infantile myofibromatosis is a rare, benign mesenchymal disorder of early childhood characterized by solitary or multiple benign myofibroblastic tumors. The tumors may involve the skin, subcutaneous tissue, muscle, bone and visceral organs. We report magnetic resonance imaging findings of solitary infantile myofibromatosis arising in the temporal bone of a ten-month-old boy, and the diagnosis was confirmed by surgical excision and histopathological examination.

Objectives The objective of this study is to investigate associations between contextual characteristics and unmet healthcare needs in South Korea after accounting for individual factors. Methods The present study used data from the 2012 Korean Community Health Survey (KCHS) of 228 902 adults residing within 253 municipal districts in South Korea. A multilevel analysis was conducted to investigate how contextual characteristics, defined by variables that describe the regional deprivation, degree of urbanity, and healthcare supply, are associated with unmet needs after controlling for individual-level variables. Results Of the surveyed Korean adults, 12.1% reported experiencing unmet healthcare needs in the past. This figure varied with the 253 districts surveyed, ranging from 2.6% to 26.2%. A multilevel analysis found that the association between contextual characteristics and unmet needs varied according to the factors that caused the unmet needs. The degree of urbanity was associated with unmet need due to “financial burden” (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.42 to 0.66 for rural vs. metropolitan), but not unmet need due to “service not available when needed.” There were no significant associations between these unmet need measures and regional deprivation. Among individual-level variables, income level showed the highest association with unmet need due to “financial burden” (OR, 5.63; 95% CI, 4.76 to 6.66), while employment status showed a strong association with unmet need due to “service not available when needed.” Conclusions Our finding suggests that different policy interventions should be considered for each at-risk population group to address the root cause of unmet healthcare needs.

Background: The ginsenoside Rb1 (Rb1) is the most abundant compound in the root of Panax ginseng. Recent studies have shown that Rb1 has a neuroprotective effect. However, the mechanisms underlying this effect are still unknown. Methods: We used stable isotope labeling with amino acids in cell culture, combined with quantitative mass spectrometry, to explore a potential protective mechanism of Rb1 in β-amyloid-treated neuronal cells. Results: A total of 1,231 proteins were commonly identified from three replicate experiments. Among these, 40 proteins were significantly changed in response to Rb1 pretreatment in β-amyloid-treated neuronal cells. Analysis of the functional enrichments and protein interactions of altered proteins revealed that actin cytoskeleton proteins might be linked to the regulatory mechanisms of Rb1. The CAP1, CAPZB, TOMM40, and DSTN proteins showed potential as molecular target proteins for the functional contribution of Rb1 in Alzheimer's disease (AD). Conclusion: Our proteomic data may provide new insights into the protective mechanisms of Rb1 in AD.

The outbreak of Middle East Respiratory Syndrome Corona Virus (MERS-CoV) infection in South Korea originated from Saudi Arabia. This virus shows high infectivity, and causes outbreaks of severe febrile respiratory infections in health care-associated settings. Herein, we reported a fatal case of MERS-CoV infection with a focus on the pulmonary radiologic findings. The initial chest computed tomography and radiographs of our patient showed ground-glass opacity in patchy distribution, followed by rapid progression of consolidation and pleural effusion in serial studies.

Background: Korean Red Ginseng (KRG) is a herbal medicine used in Asian countries and is very popular for its beneficial biological properties. Diabetes mellitus (DM) and its complications are rapidly becoming a global public health concern. The literature on transcriptional changes induced by KRG in rat models of diabetic retinopathy is limited. Considering these facts, we designed this study to determine whether retinopathy-associated genes are altered in retinas of rats with DM and whether the induced changes are reversed by KRG. Methods: Male Sprague–Dawley rats were intravenously injected with streptozotocin (50 mg/kg body weight) to induce DM, following which, KRG powder (200 mg/kg body weight) was orally administered to the KRG-treated DM rat group for 10 wks. The rats were then sacrificed, and their retinas were harvested for total RNA extraction. Microarray gene expression profiling was performed on the extracted RNA samples. Results: From among > 31,000 genes investigated, the expression of 268 genes was observed to be upregulated and that of 58 genes was downregulated, with twofold altered expression levels in the DM group compared with those in the control group. Moreover, 39 genes were upregulated more than twofold and 84 genes were downregulated in the KRG-treated group compared to the DM group. The expression of the genes was significantly reversed by KRG treatment; some of these genes were analyzed further to verify the results of the microarray experiments. Conclusion: Taken together, our data suggest that reversed changes in the gene expression may mediate alleviating activities of KRG in rats with diabetic retinopathy.

Huntington’s disease (HD) is an autosomal-dominant inherited neurodegenerative disorder characterized by motor, psychiatric and cognitive symptoms. HD is caused by an expansion of CAG repeats in the huntingtin (HTT) gene in various areas of the brain including striatum. There are few suitable animal models to study the pathogenesis of HD and validate therapeutic strategies. Recombinant adeno-associated viral (AAV) vectors successfully transfer foreign genes to the brain of adult mammalians. In this article, we report a novel mouse model of HD generated by bilateral intrastriatal injection of AAV vector serotype DJ (AAV-DJ) containing N171-82Q mutant HTT (82Q) and N171-18Q wild type HTT (18Q; sham). The AAV-DJ-82Q model displayed motor dysfunctions in pole and rotarod tests beginning 4 weeks after viral infection in juvenile mice (8 weeks after birth). They showed behaviors reflecting neurodegeneration. They also showed increased apoptosis, robust glial activation and upregulated representative inflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6), mediators (cyclooxygenase-2 and inducible nitric oxide synthase) and signaling pathways (nuclear factor kappa B and signal transducer and activator of transcription 3 (STAT3)) in the striatum at 10 weeks after viral infection (14 weeks after birth) via successful transfection of mutant HTT into neurons, microglia, and astrocytes in the striatum. However, little evidence of any of these events was found in mice infected with the AAV-DJ-18Q expressing construct. Intrastriatal injection of AAV-DJ-82Q might be useful as a novel in vivo model to investigate the biology of truncated N-terminal fragment (N171) in the striatum and to explore the efficacy of therapeutic strategies for HD.

Human adult stem cells, including umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs), have recently been considered a promising alternative treatment for inflammatory bowel disease (IBD) due to their unique immunomodulatory properties and ability to promote tissue regeneration. However, despite many years of research and pre-clinical studies, results from clinical trials using these cells have been diverse and conflicting. This discrepancy is caused by several factors, such as poor engraftment, low survival rate, and donor-dependent variation of the cells. Enhancement of consistency and efficacy of MSCs remains a challenge for the feasibility of cell-based therapy. In this study, we investigated whether administration of MIS416, a novel microparticle that activates NOD2 and TLR9 signaling, could enhance the therapeutic efficacy of hUCB-MSCs against Crohn’s disease, using dextran sulfate sodium (DSS)-induced colitis model. Colitis was experimentally induced in mice by using 3% DSS, and mice were administered a retro-orbital injection of MIS416 and subsequent intraperitoneal injection of hUCB-MSCs. Mice were examined grossly, and blood, spleen, and colon tissues were subsequently collected for further ex vivo analyses. To explore the effects of MIS416 on the therapeutic process, hUCB-MSCs and primary isolated immune cells were cultured with MIS416, and in vitro assays were performed. Compared to the single administration of hUCB-MSCs, co-administration with MIS416 improved the therapeutic efficiency of the stem cells by significantly alleviating the symptoms of IBD. Interestingly, MIS416 did not exert any direct effect on the immunomodulatory capacity of hUCB-MSCs. Instead, systemically injected MIS416 altered the immune milieu in the colon which caused hUCB-MSCs to be more readily recruited toward the lesion site and to suppress inflammation more efficiently. In addition, considerable numbers of regulatory immune cells were stimulated as a result of the cooperation of MIS416 and hUCB-MSCs. These findings indicate that co-administration with MIS416 enhances the therapeutic potential of hUCB-MSCs by systemically regulating the immune response, which might be an effective strategy for overcoming the current obstacles to stem cell therapy in clinical practice.

The prevalence of metabolic syndrome has markedly increased worldwide. However, studies in the United States show that it has remained stable or slightly declined in recent years. Whether this applies to other countries is presently unclear.We examined the trends in the prevalence of metabolic syndrome and its components in Korea.The prevalence of metabolic syndrome and its components was estimated in adults aged >30 years from the Korean National Health Insurance Service data from 2009 to 2013. The revised National Cholesterol Education Program criteria were used to define metabolic syndrome.Approximately 10 million individuals were analyzed annually. The age-adjusted prevalence of metabolic syndrome increased from 28.84% to 30.52%, and the increasing trend was more prominent in men. Prevalence of hypertriglyceridemia, low HDL-cholesterol, and impaired fasting plasma glucose significantly increased. However, the prevalence of hypertension decreased in both genders. The prevalence of abdominal obesity decreased in women over 50 years-of-age but significantly increased in young women and men (

Objectives: Receiving proper dental care plays a significant role in maintaining good oral health. We investigated the relationship between regional deprivation and dental care utilization. Methods: Multilevel logistic regression was used to identify the relationship between the regional deprivation level and dental care utilization purpose, adjusting for individual-level variables, in adults aged 19+ in the 2008 Korean Community Health Survey (n=220 258). Results: Among Korean adults, 12.8% used dental care to undergo examination and 21.0% visited a dentist for other reasons. In the final model, regional deprivation level was associated with significant variations in dental care utilization for examination (p

Metabolically healthy obese (MHO) phenotype describes an obese state with a favorable metabolic profile. However, the prognosis of this subpopulation remains controversial. We aimed to examine whether MHO phenotype is associated with progression of atherosclerotic activity, reflected as the changes in coronary artery calcification (CAC) over time. If so, we sought to determine the role of fatty liver disease (FLD), the hallmark of hepatic steatosis, in this progression.We enrolled 1,240 asymptomatic subjects who underwent repeated CAC score measurement during routine health examinations. CAC score progression was defined as either incident CAC in a population free of CAC at baseline, or an increase by ≥2.5 units between the baseline and final square root of CAC scores in participants with detectable CAC at baseline. Subjects were stratified by body mass index (cut-off, 25.0 kg/m2) and metabolic health state using Adult Treatment Panel-III criteria. FLD was assessed via ultrasonography.Over 2.9 years of follow-up, 25.2% of total subjects exhibited CAC score progression. The MHO phenotype was not significantly associated with CAC score progression (multivariate adjusted-odds ratio [OR], 1.45; 95% confidence interval [CI], 0.93-2.25), as compared to the metabolically healthy non-obese (MHNO) phenotype. However, subgroup analysis indicated that the MHO/FLD phenotype was significantly associated with CAC score progression (multivariate adjusted-OR, 2.37; 95% CI, 1.34-4.16), as compared to the MHNO/no FLD phenotype, whereas the MHO/no FLD phenotype was not (multivariate adjusted OR, 1.25; 95% CI, 0.71-2.24).Obese individuals with FLD have an increased risk of atherosclerosis progression, despite their healthy metabolic profile. Preventive interventions targeting cardiometabolic risk factors should be considered in such individuals, regardless of the weight status.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) strategy is proposed to reduce the ventilator-induced lung injury in acute respiratory distress syndrome (ARDS). As ECMO use has increased, a number of studies on prognostic factors have been published. Age is estimated to be an important prognostic factor. However, clinical evidences about ECMO use in elderly patients are limited. Therefore, we investigated clinical courses and outcomes of ECMO in elderly patients with ARDS. METHODS: We reviewed medical records of patients with severe ARDS who required ECMO support. Study patients were classified into an elderly group (> or = 65 years) and a non-elderly group (< 65 years). Baseline characteristics, ECMO related outcomes and associated factors were retrospectively analyzed according to group. RESULTS: From February 2011 to June 2013, a total of 31 patients with severe ARDS were treated with ECMO. Overall, 14 (45.2%) were weaned from ECMO, 9 (29.0%) survived to the general ward and 7 (22.6%) survived to discharge. Among the 18 elderly group patients, 7 (38.9%) were weaned from ECMO, 4 (22.2%) were survived to the general ward and 2 (11.1%) were survived to discharge. Overall intensive care unit survival was inversely correlated with concomitant acute kidney injury or septic shock. CONCLUSIONS: In this study, ECMO outcome was poor in severe ARDS patients aged over 65 years. Therefore, the routine use of ECMO in elderly patients with severe ARDS is not warranted except in highly selective cases.

Unfertilized oocytes age inevitably after ovulation, which limits their fertilizable life span and embryonic development. Rapamycin affects mammalian target of rapamycin (mTOR) expression and cytoskeleton reorganization during oocyte meiotic maturation. The goal of this study was to examine the effects of rapamycin treatment on aged porcine oocytes and their in vitro development. Rapamycin treatment of aged oocytes for 24 h (68 h in vitro maturation [IVM]; 44 h+10 μM rapamycin/24 h, 47.52±5.68) or control oocytes (44 h IVM; 42.14±4.40) significantly increased the development rate and total cell number compared with untreated aged oocytes (68 h IVM, 22.04±5.68) (p

ObjectivesTo date, studies have not comprehensively demonstrated the relationship between stroke incidence and socioeconomic status. This study investigated stroke incidence by household income level in conjunction with age, sex, and stroke subtype in Korea.MethodsContributions by the head of household were used as the basis for income levels. Household income levels for 21 766 036 people were classified into 6 groups. The stroke incidences were calculated by household income level, both overall within income categories and further by age group, sex, and stroke subtype. To present the inequalities among the six ranked groups in a single value, the slope index of inequality and relative index of inequality were calculated.ResultsIn 2005, 57 690 people were first-time stroke patients. The incidences of total stroke for males and females increased as the income level decreased. The incidences of stroke increased as the income level decreased in those 74 years old and under, whereas there was no difference by income levels in those 75 and over. Intracerebral hemorrhage for the males represented the highest inequality among stroke subtypes. Incidences of subarachnoid hemorrhage did not differ by income levels.ConclusionsThe incidence of stroke increases as the income level decreases, but it differs according to sex, age, and stroke subtype. The difference in the relative incidence is large for male intracerebral hemorrhage, whereas the difference in the absolute incidence is large for male ischemic stroke.

Cigarette smoke is considered a major risk factor for vascular diseases. There are many toxic compounds in cigarette smoke, including acrolein and other α,β-unsaturated aldehydes, which are regarded as mediators of inflammation and vascular dysfunction. Furthermore, recent studies have revealed that acrolein, an α,β-unsaturated aldehyde in cigarette smoke, induces inflammatory mediator expression, which is known to be related to vascular diseases. In this study, we investigated whether Korean Red Ginseng (KRG) water extract suppressed acrolein-induced cyclooxygenase (COX)-2 expression in human umbilical vein endothelial cells (HUVECs). Acrolein-induced COX-2 expression was accompanied by increased levels of phosphorylated p38 in HUVECs and KRG inhibited COX-2 expression in HUVECs. These results suggest that KRG suppresses acrolein-induced COX-2 expression via inhibition of the p38 mitogen-activated protein kinase signaling pathway. In addition, KRG exhibited an inhibitory effect on acrolein-induced apoptosis, as demonstrated by annexin V–propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Consistent with these results, KRG may exert a vasculoprotective effect through inhibition of COX-2 expression in acrolein-stimulated human endothelial cells.

Crotonaldehyde is an extremely toxic α,β-unsaturated aldehyde found in cigarette smoke, and it causes inflammation and vascular dysfunction. Autophagy has been reported to play a key role in the pathogenesis of vascular diseases. However, the precise mechanism underlying the role of acute exposure crotonaldehyde in vascular disease development remains unclear. In the present study, we aimed to investigate the effect of crotonaldehyde-induced autophagy in endothelial cells. Acute exposure to crotonaldehyde decreased cell viability and induced autophagy followed by cell death. In addition, inhibiting the autophagic flux markedly promoted the viability of endothelial cells exposed to high concentrations of crotonaldehyde. Crotonaldehyde activated the AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK) pathways, and pretreatment with inhibitors specific to these kinases showed autophagy inhibition and partial improvement in cell viability. These data show that acute exposure to high concentrations of crotonaldehyde induces autophagy-mediated cell death. These results might be helpful to elucidate the mechanisms underlying crotonaldehyde toxicity in the vascular system and contribute to environmental risk assessment.

PurposeTo examine the relationship between menarcheal age and anthropometric indices and menstrual irregularity in late adolescent girls in Seoul.MethodsWe surveyed 4,218 fertile adolescent girls between the ages of 16 and 18 years to determine their anthropometric indices and menarcheal age. Measurements were taken from June 2008 to October 2009 at seven girl's high schools in Seoul, Korea. Participants were offered self-report questionnaire as a survey tool that included questions on anthropometric indices (height, weight, waist circumference), menarcheal age, menstrual pattern, frequency of menstruation per year.ResultsThe participants were categorized into three groups based on menarcheal age: early menarche group (younger than 2 standard deviations [SD]), mid menarche group (within ±2 SD), late menarche group (older than 2 SD). The mean age of early menarche group was 9.9±0.2 years, mid menarche group 12.5±0.9 years, late menarche group 15.1±0.3 years (P < 0.001). Heights were recorded as 160.4±5.2 cm, 161.8±4.9 cm, 162.3±4.7 cm in early, mid, and late menarche group, respectively (P = 0.001). Body mass index (BMI) and waist circumference significantly were lager in early menarche group than mid and late menarche ones (P < 0.001). The menarcheal age had a positive correlation with height and negative correlations with weight, BMI, waist circumference (P < 0.001). The prevalence of oligomenorrhea was more frequent in late menarche group than early and mid menarche group.ConclusionThe menarcheal age have positive relationship with height and inverse relationship with BMI and waist circumference in late adolescent girls in Seoul. Late menarcheal girls are disposed to have menstrual irregularity compared to early menarcheal girls.

A 10-year-old girl presented with recurrent right upper abdominal pain and dyspepsia. Magnetic resonance cholangiopancreatography revealed a dilated common channel of intrahepatic bile duct of segment 3 (B3) and segment 4 (B4) drained into the gallbladder directly. The patient underwent laparoscopic cholecystectomy and Roux-en Y hepaticojejunostomy (B3-jejunostomy). Among the anatomical variability of the biliary system, the cholecystohepatic ducts are controversial in existence and incidence. We report a very rare variant of a cholecystohepatic duct in which the B3 duct drained into gallbladder directly and to the best of our knowledge this is the first report.