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Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.

This study investigated the antioxidant activities of Sasa quelpaertensis Nakai extract (SQE), p-coumaric acid (PCA) and myricetin (MY), and their effects on the in vitro maturation and developmental ability of porcine oocytes. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed that 1 mg of SQE contained 3.92 μg of PCA and 0.19 μg of MY. The concentrations required to inhibit 50% of DPPH radicals were 2732.8 ppm, 38.8 mg/mL, and 0.110 mg/mL for SQE, PCA, and MY, respectively. The reducing power increased as the concentration increased, and the reducing power of MY was higher than that of PCA. The polar body extrusion rate was highest upon treatment with 1250 ppm SQE and 10 μM MY. The reactive oxygen species and glutathione levels were significantly decreased and increased, respectively. In a normal or peroxidative environment, the embryo development rate upon parthenogenetic activation was increased, and the total cell number, apoptosis rate, and development-related gene expression were altered to enhance embryonic development. The embryo development rate and total cell number upon somatic cell nuclear transfer did not differ between the groups. These results show that the antioxidant effects of SQE and MY enhance the in vitro maturation and subsequent embryonic development.

Background NMDAR hypofunction has been implicated in several psychiatric disorders with an impairment of cognitive flexibility. However, the molecular mechanism of how NMDAR hypofunction with decreased NMDAR tone causes the impairment of cognitive flexibility has been minimally understood. Furthermore, it has been unclear whether hippocampal astrocytes regulate NMDAR tone and cognitive flexibility. Methods We employed cell-type specific genetic manipulations, ex vivo electrophysiological recordings, sniffer patch recordings, cutting-edge biosensor for norepinephrine, and behavioral assays to investigate whether astrocytes can regulate NMDAR tone by releasing D-serine and glutamate. Subsequently, we further investigated the role of NMDAR tone in the heterosynaptic long-term depression, metaplasticity and cognitive flexibility. Results We found that hippocampal astrocytes regulate NMDAR tone via Best1-mediated co-release of D-serine and glutamate. Best1 knockout mice (Best1 KO) exhibited reduced NMDAR tone and impairments of homosynaptic and α1-adrenergic receptor-dependent heterosynaptic long-term depression, which leads to the defects in metaplasticity and cognitive flexibility. These impairments in Best1 KO can be rescued by hippocampal astrocyte-specific Best1 expression or enhanced NMDAR tone through D-serine supplement. Importantly, D-serine injection in Best1 KO during initial learning rescues subsequent reversal learning. Conclusions These findings indicate that NMDAR tone during initial learning is important for subsequent learning, and hippocampal NMDAR tone regulated by astrocytic Best1 is critical for heterosynaptic long-term depression, metaplasticity and cognitive flexibility.

To improve mesophase formation in petroleum-based pitch, the PET (polyethylene terephthalate) additive reaction was studied. PFO (pyrolysis fuel oil) was used to prepare the petroleum pitch, and PET was added at a weight ratio of 0.33–1.50%. The chemical structure of PET-added pitch was analyzed by Fourier transform infrared spectroscopy, and the thermal properties were characterized by thermogravimetric analysis and the softening point method. Added PET provides oxygen during the pitch synthesis reaction, and the polycondensation of the pitch was accelerated by oxygen crosslinking. Thus, the softening point and carbonization value increased with the amount of PET added; moreover, the mesophase content increased by more than three times with 0.33 wt% PET addition. However, at more than 0.67 wt% PET addition, the fluidity rapidly decreased, so the mesophase spheres decreased in size and were independently distributed.

Background IPNB is very rare disease and most previous studies on IPNB were case series with a small number due to low incidence. The aim of this study is to validate previously known clinicopathologic features of intraductal papillary neoplasm of bile duct (IPNB) based on the first largest multicenter cohort. Methods Among 587 patients previously diagnosed with IPNB and similar diseases from each center in Korea, 387 were included in this study after central pathologic review. We also reviewed all preoperative image data. Results Of 387 patients, 176 (45.5%) had invasive carcinoma and 21 (6.0%) lymph node metastasis. The 5-year overall survival was 80.9% for all patients, 88.8% for IPNB with mucosal dysplasia, and 70.5% for IPNB with invasive carcinoma. According to the “Jang & Kim's modified anatomical classification,” 265 (68.5%) were intrahepatic, 103 (26.6%) extrahepatic, and 16 (4.1%) diffuse type. Multivariate analysis revealed that tumor invasiveness was a unique predictor for survival analysis. (p = 0.047 [hazard ratio = 2.116, 95% confidence interval 1.010–4.433]). Conclusions This is the first Korean multicenter study on IPNB through central pathologic and radiologic review process. Although IPNB showed good long-term prognosis, relatively aggressive features were also found in invasive carcinoma and extrahepatic/diffuse type.

Background When students with intellectual disability (ID) experience pain, the pain may limit the extent to which they may engage in school activities. Although school nurses are primarily responsible for addressing students’ pain, there are many barriers to identifying pain in students with ID. Aims The purpose of the present study was to describe pain assessment practices of school nurses for students with and without ID. Design A retrospective review was conducted of 4,660 school health office visit records for elementary school students presenting to the health office with headache, stomachache, or sore throat. Methods Data were extracted and transcribed to a matrix. Data extracted included school grade, referral source, visit month, gender, cognitive ability, chief concern, pain assessment, external contact, and disposition. Descriptive statistics were calculated. Results School nurses spent more time on average addressing pain in neurotypical students than in students with ID. Neurotypical students more often presented with a teacher and were dismissed from school, but parents and guardians were contacted less often for these students, when compared to students with ID. Quantified pain ratings were documented for 1% of visits. Conclusions Because pain intensity ratings were rarely documented, the utility of such ratings in the school setting may be low. Alternatively, obtaining pain intensity ratings from younger children may be challenging without the use of appropriate tools. Nurses, teachers, and other staff providing education and care to students with ID may require pain training. Implementation of tools that elicit student pain information from parents/guardians in the school setting could decrease point-of-care contact during the school day and proactively provide information on unique child pain behaviors.

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.

The purpose of this study was three-fold: to (1) synthesize evidence from experimental studies regarding educational interventions for developing nursing students' and nurses' assertiveness, (2) examine such interventions and identify their effective components, and (3) recommend future research considerations in this area.A systematic review of the literature.Literature searches were conducted using three electronic databases (PubMed, CINAHL, and PsycINFO) in addition to hand searches to identify original research articles published between 2012 and 2022.Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed for the systematic review and reporting process. Included studies were critically appraised using the Joanna Briggs Institute Critical Appraisal Checklists.Fourteen articles were included in this review, with most of the studies conducted in Asian countries. Four intervention methods were used for assertiveness education across the studies: (1) simulation-based learning, (2) classroom-based learning, (3) classroom-based learning with peer support, and (4) hybrid learning. Classroom-based learning interventions were the most common. Among all types of interventions, key concepts included assertiveness, differentiating between assertive and non-assertive behaviors, and assertive communication skills. Most studies measured participants' speaking-up behaviors by self-report. Mixed results were observed in terms of intervention effectiveness, but providing participants with opportunities to practice assertive communication skills benefited their speaking-up.Educational interventions can strengthen the skills, confidence, and capacity of current and future nurses to employ assertive communication. Intervention developers should create programs that involve classroom teaching and provide participants with opportunities for practice, either through simulation or role-play. Also, researchers should observe participants' post-intervention use of assertive communication in simulations or clinical practice as opposed to surveying participants' intention to speak up.

The survival rate of patients with cancer has been increasing because of the sustained anticancer effect of new drugs, such as immune checkpoints inhibitors (ICI). Unlike the existing cytotoxic chemotherapies, immunotherapy causes immune system disturbance, such as hypothyroidism. Comparative studies on hypothyroidism following administration of ICI alone and in combination with other drugs are scarce. Therefore, we investigated the incidence of hypothyroidism after ICI in patients with cancer using a national population-based database.Using the claims data from the Health Insurance Review and Assessment service in Korea, we retrospectively investigated patients with cancer who received chemotherapy between January 1, 2014 and February 28, 2021.Of all patients with cancer (n = 665,445) who received all kinds of chemotherapy, those who have received ICI accounted for 1.91 %. Compare with cytotoxic chemotherapy and angiogenesis inhibitors (AIs), ICI was associated with earlier (236.1 ± 248.4 vs. 811.1 ± 661.7, P 0.01) and more frequent (7.7 % vs. 4.4 %, P 0.01) occurrence of hypothyroidism, as well as an increased risk of developing hypothyroidism (odds ratio [OR] 1.69, 95 % confidence interval [CI] 1.58-1.80). However, the incidence of grade 2 or higher hypothyroidism was similar in both groups of patients who received ICI (3.3 %) and AI (3.1 %). The incidence of hypothyroidism was 4.4 times higher in patients who received both AI and ICI than in those who were treated with ICI alone (OR 4.41, 95 % CI 3.40-5.71).This study showed a synergistic effect in patients who received multiple administrations of a drug that might be associated with thyroid dysfunction. Therefore, special attention should be paid to the treatment-related side effects when using drugs, such as AIs, concomitant with ICI treatment.

Objective The purpose of this review was to identify methods for incorporating medication administration safety in undergraduate nursing education. Design The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines directed this review. Data Sources A search of four electronic databases (Cumulative Index to Nursing and Allied Health Literature, Education Resources Information Center, Google Scholar, and MedLine/PubMed MedLine/PubMed) as well as hand searches were conducted to identify original research published between 2005 and 2018. Review Methods Original empirical research describing a method for incorporating medication administration safety concepts in nursing education and examining its effectiveness on undergraduate nursing students' outcomes were selected for review. Articles describing medication safety education for graduate students, students other than those in nursing, and practicing nurses were excluded. Results Twelve original research articles were included for review. Three methods for incorporating medication administration safety in undergraduate nursing education were identified: simulation experiences, technology aids, and online learning modules. Most studies were conducted in North America. The use of different interventions as well as different outcome measures was noted as a limitation to the collective body of research in this area. Also, there was a lack of information regarding psychometric properties of instruments used among the studies reviewed. Conclusion Simulation experiences, use of technology aids, and online learning modules helped increase medication safety competence of nursing students. However, simulation equipment, select technology aids, and online learning may not be available for all nursing programs; therefore, educators should consider developing and testing classroom-based educational interventions. Moreover, future researchers should use or develop psychometrically sound instruments to measure nursing students' outcomes including competencies about medication administration safety.

Background: Diaphragmatic movement affects dyspnea in the COPD patient.Research Question: Which of the diaphragm-related factors are closely related to Pulmonary Function test in the COPD patients? Study design and Methods: We enrolled 60 patients with COPD who attend respiratory outpatients. The diaphragm evaluation was performed using ultrasound, and PFT, 6MWT was performed in a respiratory outpatient clinic. Dyspnea scare, BMI, PFT, 6MWT and diaphragmatic factors collected and statistically analyzed. Results:In total patients, the right forced-excursion at supine positon was 6.9 ±2.000, left forced-excursion at supine position was 7.6 ±1.649. Right forced-excursion at supine position (p=0.003, R 2 =0.137), left forced-excursion at supine position (p=0.048, R 2 =0.074) and thickness of right end-expiratory (p=0.016, R 2 =0.094) were significantly associated with FEV1. When the group with right diaphragmatic excursion ≥ 6.7 was further divided into groups according to FEV1 (< 50% or ≥ 50%) , FEV1/FVC, MIP , portable peak flow meter, 6-minute walk distance, SpO2 before and after the 6MWT, and right diaphragmatic thickness at end-expiration subgroups were significantly different between the two groups. Interpretation: Right diaphragmatic forced excursion was closely related to FEV1, and analysis according to cut-off value which based on Right diaphragmatic forced excursion showed a large difference between groups. W hen the diaphragm function was maintained, MIP , portable peak flow meter, 6-minute walk distance, SpO2 before and after the 6 MWT, and right diaphragmatic thickness at end-expiration were different between the two FEV1 groups. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: The study procedures were reviewed and approved by our institutional review board [IRB No. 05-2020-217].

The COVID-19 pandemic has accelerated demands for a shift from traditional face-to-face learning to online learning. Visual Thinking Strategies (VTS) is an inquiry-based teaching method using various visual artworks to improve critical thinking and interpersonal skills. VTS has been studied in health professional education mostly in art gallery settings. Implementing VTS during online learning in nursing education has not yet been investigated.This study evaluated the feasibility of incorporating VTS into an undergraduate nursing health assessment course and explored students' perceptions and experiences of VTS.A single-group, posttest-only, concurrent mixed-methods design was used.This study was conducted in an urban nursing college in Seoul, Korea.A convenience sample of 60 second-year undergraduate nursing students enrolled in a health assessment course.We integrated VTS into three skills lab sessions (assessment of older adults, skin assessment, and musculoskeletal system assessment) via on-site sessions or real-time online videoconferencing sessions. Through an online survey, we obtained sociodemographic information, previous VTS experience, measures of teaching orientation, perception of arts-based learning, and VTS evaluation. Additionally, participants were asked to comment on their VTS experiences through free-response questions.Participants rated VTS as an interesting and easy-to-concentrate learning method compared with traditional classes during a COVID-19 pandemic. In participants' narratives, being able to learn diverse perspectives, expanding the scope of thoughts and observations, and sustainable learning were the most commonly positive experiences. A lack of familiarity and the open-ended nature of observations were reported as the most common challenges.Applying VTS in undergraduate nursing education may help students develop critical thinking, communication, and collaboration skills. As an alternative to traditional teaching, implementing VTS via online may have potential to motivate students' engagement to active learning. Future randomized controlled trials are warranted to build evidence on the benefits of VTS.

Background Type 2 diabetes and asthma share a common pathophysiology: “chronic inflammation.” However, it is unclear whether patients with type 2 diabetes are at increased risk of asthma. Objective To investigate the effect of type 2 diabetes on asthma using data from a large population-based study in Korea. Methods Data from the Korean National Health Insurance Service identified 13,154,348 participants who underwent regular health checkups from 2005 to 2008. Subjects were classified according to status of diabetes mellitus (DM) and diabetic retinopathy (DR), and followed until the date of asthma development, death, or December 31, 2013. Cox proportional hazard regression analysis was used to evaluate the effect of diabetes, with or without retinopathy, on asthma development. Results The incidences of asthma in the non-DM, DM without DR, and DR groups were 27.1, 30.1, and 38.4 per 1,000 person-years, respectively. Cox proportional hazard multiple regression models revealed that diabetic patients without retinopathy had a significantly lower risk of developing asthma than non-DM subjects (hazard ratio, 0.943; 95% confidence interval, 0.939-0.948). By contrast, diabetic patients with retinopathy had a higher risk of developing asthma (hazard ratio, 1.067; 95% confidence interval, 1.053-1.081). Conclusion Type 2 diabetes without retinopathy is not a risk factor for asthma development. However, patients with DR are at a greater risk of incident asthma, supporting the notion that the lung is a target organ for diabetic injury. Future studies will address whether proper glycemic control mitigates the risk of asthma.

Malignant pheochromocytoma and paraganglioma can be defined only after the development of metastases in nonchromaffin tissues. There is no single clinical parameter that is sufficiently reliable to predict metastatic potential, so our goal was to develop a prediction model based on multiple clinical parameters.The baseline age, size, extra-adrenal location, secretory type score was calculated in a retrospective cohort study comprising 333 patients with pheochromocytoma and paraganglioma. In each patient, each variable for age ≤35 years, tumor size ≥ 6.0 cm, extra-adrenal, and norepinephrine-secretory type was coded as 1 point (otherwise 0 point); these points were summed to yield age, size, extra-adrenal location, secretory type score.Metastases occurred in 23 of 333 patients (6.9%). Metastatic pheochromocytoma and paraganglioma was associated with age ≤35 years (hazard ratio [HR] 2.74, 95% confidence interval [95% CI] 1.19-6.35), tumor size ≥6.0 cm (HR 2.43, 95% CI 1.06-5.56), extra-adrenal location (HR 2.73, 95% confidence interval 1.10-7.40), and tumor producing only norepinephrine (HR 2.96, 95% CI 1.30-6.76). The area under the curve of the age, size, extra-adrenal location, secretory type score was 0.735. There was a significant difference in metastasis-free survival between participants with age, size, extra-adrenal location, secretory type score ≥2 and score2 (P.0001 by the log rank test). The negative predictive value of this system was 96.5% for a cutoff point of 2.We developed a new prediction model, the age, size, extra-adrenal location, secretory type score, based on multiple clinical parameters to assess the metastatic potential of pheochromocytoma and paraganglioma.

Vitamin D has an immunoregulatory effect on both innate and adaptive immunity. Contradictory results regarding vitamin D and natural killer (NK) cell functions have been reported with in vitro studies, but little is known about this in vivo. We investigated whether vitamin D levels (50, 1000 or 10,000 IU/kg of diet: DD, DC or DS) affect NK cell functions in mice fed a control or high-fat diet (10% or 45% kcal fat: CD or HFD) for 12 weeks. The splenic NK cell activity was significantly higher in the CD-DS group than the HFD-DS group, and the CD-DS group showed significantly higher NK cell activity compared with the CD-DD and CD-DC groups. However, no difference in NK cell activity was observed among the HFD groups fed different levels of vitamin D. The splenic population of NK cells was significantly higher in the CD-DS group than the HFD-DS group. There was no difference in the intracellular expression of IFN-γ and the surface expression of NKG2D and CD107a in NK cells by both dietary fat and vitamin D content. The splenic mRNA expression of Ifng and Ccl5 was significantly lower in the HFD groups compared with the CD groups, but there was no difference in the mRNA levels of Vdup1 and Vdr among the groups. Taken together, these results suggest that dietary vitamin D supplementation can modulate innate immunity by increasing NK activity in control mice but not in obese mice. This effect might be mediated through alternation of the splenic NK cell population.

Aims Because of the development of new classes of antidiabetic drugs, hypoglycemic events were expected to decrease. We investigated the trends and risk factors for severe hypoglycemia in subjects with type 2 diabetes in Korea. Methods We conducted repeated cross-sectional analyses using a Korean National Health Insurance Service–National Sample Cohort from 2006 to 2015. Severe hypoglycemia was defined as hospitalization or a visit to an emergency department with diagnosis of hypoglycemia using ICD-10 codes. Results During the study period, the prevalence of type 2 diabetes continuously increased. The percentage of patients prescribed metformin and dipeptidyl peptidase-4 inhibitor increased, while the use of sulfonylurea decreased considerably, especially since 2009. The proportion of patients prescribed ≥3 classes of drugs continually increased. Age-standardized incidence of severe hypoglycemia per 1000 patients with diabetes increased from 6.00 to 8.24 between 2006 and 2010, and then fell to 6.49 in 2015. Predictors of severe hypoglycemia included female, older age, comorbidities, polypharmacy, and sulfonylurea or insulin usage. Conclusions Trends of severe hypoglycemia were associated with changes in drug classes rather than number of antidiabetic drugs. Relentless efforts to reduce the prescription of drugs with a high risk of hypoglycemia should be implemented, particularly for older women with multiple comorbidities.

Summary Background CT radiation is arguably carcinogenic. Results from single-centre studies, mostly retrospective, have advocated lowering the CT radiation dose for the diagnosis of appendicitis. However, adoption of low-dose CT has been slow. We aimed to assess the effectiveness of low-dose CT compared with standard-dose CT in the diagnosis of appendicitis in adolescents and young adults. Methods We did this pragmatic, multicentre, randomi s ed controlled non-inferiority trial at 20 South Korean teaching hospitals with little experience with low-dose CT. Patients aged 15–44 years with suspected appendicitis were randomly assigned (1:1), via computer-generated random assignments (permuted block sizes of two, four, six, and eight) concealed in sequentially numbered envelopes, to receive low-dose CT (2 mSv) or standard-dose CT (≤8 mSv). Randomisation was stratified by site. Group allocation was concealed from patients, outcome assessors, and adverse event adjudicators; care providers, site pathologists, and data collectors were aware of allocation. The primary endpoint was the negative (unnecessary) appendectomy rate among all appendectomies, with a non-interiority margin of 4·5% for low-dose versus standard-dose CT. Primary analy s is was by modified intention to treat, which included all patients who received an appendectomy in the group to which they were assigned. This trial is registered with ClinicalTrials.gov, number NCT01925014. Findings Between Dec 4, 2013, and Aug 18, 2016, we assigned 1535 patients to the low-dose CT group and 1539 patients to the standard-dose CT group. 22 (3·9%) of 559 patients had a negative appendectomy in the low-dose group versus 16 (2·7%) of 601 patients in the standard-dose group (difference 1·3%, 95% CI −0·8 to 3·3; p=0·0022 for the non-inferiority test). We recorded 43 adverse events in 43 (2·8%) of 1535 patients in the low-dose group and 41 adverse events in 40 (2·6%) of 1539 patients in the standard-dose group. One life-threatening adverse event of anaphylaxis caused by an iodinated contrast material occurred in the low-dose group. Interpretation Radiation dose of appendiceal CT for adolescents and young adults can be reduced to 2 mSv without impairing clinical outcomes. In view of the vast number of appendiceal CT examinations done worldwide, use of low-dose CT could prevent a sizeable number of radiation-associated cancers in the future. Funding Korea Health Industry Development Institute, Seoul National University Bundang Hospital, Dasol Life Science, and Bracco Imaging Korea.

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since jeudi 5 octobre 2017

Background Because severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) rarely occur, clinical data based on large-scale studies are still lacking. Objective To provide information on culprit drugs and clinical characteristics, including morbidity and mortality of SCARs based on a nationwide registry. Methods SCAR cases that occurred from 2010 to 2015 were recruited to the Korean SCAR registry from 34 tertiary referral hospitals. Demographics, causative drugs, causality, and clinical outcomes were collected by reviewing the medical record. Results A total of 745 SCAR cases (384 SJS/TEN cases and 361 DRESS cases) due to 149 drugs were registered. The main causative drugs were allopurinol (14.0%), carbamazepine (9.5%), vancomycin (4.7%), and antituberculous agents (6.3%). A strong preference for SJS/TEN was observed in carbonic anhydrase inhibitors (100%), nonsteroidal anti-inflammatory drugs (84%), and acetaminophen (83%), whereas dapsone (100%), antituberculous agents (81%), and glycopeptide antibacterials (78%) were more likely to cause DRESS. The mortality rate was 6.6% (SJS/TEN 8.9% and DRESS 4.2%). The median time to death was 19 days and 29 days in SJS/TEN and DRESS respectively, and 89.8% of deaths occurred within 60 days after the onset of the skin symptoms. Conclusion Allopurinol, carbamazepine, vancomycin, and antituberculous agents were the leading causes of SCARs in Korea. Some drugs preferentially caused a specific phenotype. The mortality rate of SCARs was 6.6%, and most of the deaths occurred within 2 months.

Postcholecystectomy pain (PCP) is characterized by abdominal pain after cholecystectomy. However, prevention of PCP is not well known yet. The purpose of this study was to determine whether Rowachol might be useful in preventing PCP.Between May 2013 and January 2014, a total of 138 patients with gallbladder disease who were scheduled to undergo laparoscopic cholecystectomy were randomly assigned to orally receive 100 mg Rowachol or placebo three times daily for 3 months after surgery. Abdominal pain was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire.Incidence of PCP in the placebo group (n = 9, 14.3%) was higher than that in the Rowachol group (n = 3, 4.7%) with statistically marginal significance (P = 0.08). Risk factor analysis implicated PCP with increased difficulty in performing LC, more frequent pathology with acute cholecystitis, and absence of postoperative Rowachol treatment. Multivariate analysis revealed that greater difficulty of laparoscopic cholecystectomy (HR = 5.78, 95% CI 1.36-24.40, P 0.05), and absence of postoperative Rowachol treatment (HR = 2.54, 95% CI 1.10-10.39, P 0.05) were independent risk factors for development of PCP.Rowachol might be beneficial for prevention of PCP after laparoscopic cholecystectomy.

Sensory discrimination is essential for survival. However, how sensory information is finely controlled in the brain is not well defined. Here, we show that astrocytes control tactile acuity via tonic inhibition in the thalamus. Mechanistically, diamine oxidase (DAO) and the subsequent aldehyde dehydrogenase 1a1 (Aldh1a1) convert putrescine into GABA, which is released via Best1. The GABA from astrocytes inhibits synaptically evoked firing at the lemniscal synapses to fine-tune the dynamic range of the stimulation-response relationship, the precision of spike timing, and tactile discrimination. Our findings reveal a novel role of astrocytes in the control of sensory acuity through tonic GABA release.

Vitamin D has been reported to regulate the maturation and function of dendritic cells (DCs). Obesity was shown to be associated with the dysregulation of vitamin D metabolism and malfunction of DCs. We investigated the effects of in vitro 1,25(OH)2D3 treatment (0, 1, or 10 nM) on phenotype and expression of genes related to function of bone marrow-derived DCs (BMDCs) from control and obese mice. C57BL/6 N mice were fed a control or high-fat (10% or 45% kcal fat: CON or HFD) diets for 15 weeks. Differentiation toward DCs was induced with GM-CSF (20 ng/ml) and maturation was induced by LPS (50 ng/ml); 10 nM 1,25(OH)2D3 treatment inhibited BMDC differentiation (CD11c+) and decreased the percentage of mature DCs (MHCIIhighCD11c+ and CD86highCD11c+) in both CON and HFD groups. The Il10 expression in stimulated BMDCs from the CON group increased with the 10 nM 1,25(OH)2D3 treatment, but not in those from the HFD group. The Il12b mRNA levels in stimulated BMDCs were lower in the HFD group than in the CON group. In conclusion, lower levels of Cd 40, Cd83 and Il12 mRNA in LPS-stimulated BMDCs from obese mice suggest malfunction of DCs as antigen presenting cells. 1,25(OH)2D3 treatment inhibited the differentiation and maturation of BMDCs in both control and obese mice. Differential effects of 1,25(OH)2D3 on the expression of Il10 between control and obese mice suggest that regulation of immune response by vitamin D could be influenced by obesity.

Graphene oxide membrane (GOM) has attracted extensive attraction as a molecular sieve for the separation of water, ions, and gases. However, A-level control of the GOM interlayer spacing for separating the specific size of gas molecule is difficult and the vertical transport mechanism of molecules through the GOM is highly complex because of the existence of several possible pathways. Here we fabricated GOMs with different A-scale interlayer spacing through heat treatment and made them allow horizontal entrance and transport of gas molecules. The GOMs with angstrom channels exhibited superior performance in permeance in horizontal mode and moderate selectivity for H2/CO2 and He/CO2 by tuning the sieving size of the channels. Molecular dynamics (MD) simulations reveal that the precisely controlled interlayer spacing plays a primary role as a molecular sieve indeed, but increased graphitic area, a result of heat treatment, also affects observed selectivity. Our results provide insight into the transport mechanism of gas molecules through GO nanochannel, which has not been accurately identified due to its complex behavior and suggest the possibility of studying nanochannels as effective vehicle for separating molecules precisely.

In this study, we aimed to isolate chemical compounds from the aerial parts of Aster koraiensis Nakai and to determine their proprotein convertase/kexin type 9 (PCSK9) mRNA expression inhibitory activities. Two new eudesmane-type sesquiterpenes, 1β,4β,13-trihydroxy-trans-eudesm-6-ene-1-O-β-glucopyranoside (1) and 6″-O-(syringoyl)-1β,6β,9β,11-tetrahydroxy-trans-eudesm-3-en-6-O-β- d -glucopyranoside (2), along with 20 known compounds were isolated. All the isolated structures were confirmed by measuring 1D and 2D NMR spectroscopic data and comparing with their reported values. Among the isolates, gymnasterkoreayne B (21) and gymnasterkoreayne E (22) exhibited potent inhibitory effects on PCSK9 expression with IC50 values of 47.9 and 42.9 µM, respectively, and also increased LDLR expression. Our study provides insights into the use of these polyacetylenes or A. koraiensis extracts for cholesterol-lowering treatment.

Backgrounds/Aims: Gallstones are being increasingly diagnosed in pediatric patients. The purpose of this study was to determine characteristics of pediatric patients who underwent cholecystectomy because of symptomatic gallstone disease unrelated to hemolytic disorder. Methods: We reviewed cases of pediatric patients (under 18 years old) who underwent cholecystectomy between May 2005 and December 2015. Results: A total 20 pediatric patients (under 18 years old) underwent cholecystectomy during the study period. One patient was excluded because cholecystectomy was performed due to gall stones caused by hemolytic anemia. The 19 cases comprised 9 male (47.3%) and 10 female (52.7%) subjects. The mean age was 14.9 years (range, 5-18), and 66.7% of patients were older than 12 years of age. Mean body weight was 65.0 kg (range, 13.9-93.3), and mean body mass index was 21.7 kg/㎡ (range, 12.3-35.1), with 26.37% of patients being overweight. All 19 patients underwent laparoscopic cholecystectomy. There were no postoperative complications and no mortality. Comparison between overweight and non-overweight patients indicated that significantly more overweight patients had cholesterol stones (5/5 vs. 7/14, p=0.036) and were classified as complicated disease (3/5 vs. 1/14, p=0.037). Conclusions: The more frequent occurrence of complications such as choledocholithiasis or gallstone pancreatitis, in overweight patients indicates the need for more careful evaluation and management in these patients. Pediatricians and surgeons should always consider gallstone disease in pediatric patients despite difficulty in suspecting symptomatic gallstones in cases who present with abdominal pain that is rarely clear-cut.

In this study, stub columns subjected to concentric and eccentric loads were tested to check the applicability of the current local stability criteria to 800 MPa high-strength steel (HSA800) recently developed in Korea. The key test variables in the concentrically loaded tests included the plate-edge restraints and the width-to-thickness ratio. Specimens made of ordinary steel (SM490) were also tested for comparison purposes. Eccentrically loaded stub column tests were conducted for a range of the P–M combinations by controlling the loading eccentricity. All the concentrically loaded specimens with non-compact and slender sections developed sufficient strengths according to the current local stability criteria. All the eccentrically loaded specimens with non-compact H-sections also exhibited a sufficient P–M interaction strength even higher than that of compact H-section counterparts. The experimental P–M interaction strength was very accurately predicted with the strain compatibility method by using the measured stress–strain curve, or by explicitly considering early strain-hardening property of high strength steel. Residual stresses were also measured by using the non-destructive indentation method to see their dependency or independency on the yield stress of steel material. The measured results of this study again indicated that the magnitude of residual stresses bears no strong relation to the yield stress of steel material, implying that the impact of residual stress on inelastic local buckling of high strength steels is less.

Atopic dermatitis (AD) is a multifactorial chronic skin disorder that is increasing in prevalence globally. In NC/Nga mice, repetitive epicutaneous applications of 2-4-dinitrofluorobenzene (DNFB) induces AD-like clinical symptoms. Bioflanonol fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary component found in plants, fruits and vegetables. Fisetin has various physiological effects that include anti-oxidation, anti-angiogenesis, anti-carcinogenesis and anti-inflammation. In this study, we investigated whether fisetin relieves AD-like clinical symptoms induced by repeated DNFB treatment in NC/Nga mice. Fisetin significantly inhibited infiltration of inflammatory cells including eosinophils, mast cells and CD4(+) T and CD8(+) T cells, and suppressed the expressions of cytokines and chemokines associated with dermal infiltrates in AD-like skin lesions. Total serum immunoglobulin E (IgE) levels and the ratio of phospho-NF-κB p65 to total NF-κB p65 were markedly reduced by fisetin. Fisetin also reduced the production of interferon-gamma and interleukin-4 by activated CD4(+) T cells in a dose-dependent manner, whereas the anti-inflammatory cytokine, interleukin-10 was increased. These results implicate fisetin as a potential therapeutic for AD.

This study examined the user gratifications obtained from Pinterest, an image-sharing social networking site, by applying the traditional mixed-method approach of the uses and gratifications framework (U&G). In the first phase of the study, using a qualitative questionnaire, a preliminary list of descriptive terms was collected from 27 college students who use Pinterest. From the list, an item analysis extracted 54 descriptive terms, which served as the basis for the item generation in the second phase of the study. In the second phase, using a quantitative online survey method, data was analyzed from 243 college students who use Pinterest. A confirmatory factor analysis revealed five dimensions of uses and gratifications obtained from the image-sharing SNS: 'fashion', 'creative projects', 'entertainment', 'virtual exploration', and 'organization'. Furthermore, the results propose new measures for the uses and gratifications of Pinterest.

Graphene oxide (GO) membranes have attracted attention as a promising candidate for selective ion permeation due to narrow interlayer spacing. Among several methods to control the interlayer spacing, the reduction of GO membranes has great potential for desalination and water purification. To apply GO membranes for ion separation, investigating ion transport of sub-nanometer channels of reduced GO membranes is needed. In this study, thermally and chemically reduced GO membranes were fabricated with different interlayer spacing ranging from 3.7 to 8.0 A in a dry state. It was experimentally determined that the minimum spacing allowing water permeation was 5.7 A (9.6 A in water), and no water permeated at 5.0 A or less. For ion permeation, a pure GO membrane exhibited similar permeability for most ions, while the permeability of GO membrane with 5.7 A spacing was strongly dependent of the size and charge of ions. The permeability of cations significantly changed along with the ionic radius, while there was a noticeable cutoff for permeability of multivalent anions such as SO42− and Fe(CN)63−. Our reduced GO membrane could be used to effectively block the permeation of large ions and multivalent anions.

Highlights • We successfully resected 4.2 cm-sized cystic mass of pancreas through laparoscopic approach. • Pathologic examination revealed a dermoid cyst of pancreas. • Literature review showed that dermoid cysts of the pancreas are rare benign, and congenital tumors. • Preoperative diagnosis is challenging, and surgical resection is the standard treatment., Introduction Dermoid cyst of the pancreas, also called cystic teratoma, is a benign, well-differentiated, and extremely rare germ cell neoplasm. Preoperative diagnosis is challenging since there are no definitive preoperative diagnostic tests or pathognomonic findings. Presentation of case We report a case of a 54-year-old male who presented with an incidentally detected pancreatic cystic mass at the tail of the pancreas. Computerized tomography revealed a benign cystic mass such as oligocystic serous cystadenoma or a hemorrhagic cyst. However, a high CEA level from EUS guided aspirated fluid suggested mucinous cystic neoplasm. After laparoscopic spleen-preserving distal pancreatectomy, the final diagnosis was confirmed as a dermoid cyst of the pancreas. Conclusion Despite the benign nature of the dermoid cyst, complete surgical resection is mostly inevitable due to the difficulty of preoperative diagnosis as in the present case.

Pedestrian recognition is an emerging visual computing application for embedded systems. In one usage model, a vehicle mounted camera acquires image from road and a pedestrian recognition system automatically recognizes and alarms information on the road preventing traffic accidents. Achieving this in software on embedded systems requires significant compute processing for object recognition. In this paper, we identify the hotspot function of the workload on an embedded system that motivates acceleration and present the detailed design of a hardware accelerator for Histograms of Oriented Gradients descriptor extraction. We also quantify the performance and area efficiency of the hardware accelerator. Our analysis shows that hardware acceleration has the potential to improve the hotspot function. As a result, user response time can be reduced significantly.

The objectives of this study were to understand that factors affecting consumer intention to shop in a virtual world and to analyze the relationships among these factors. Particularly, this study explored consumer innovativeness (consumer novelty seeking, consumer independent judgment making) as an external variable that influences consumer intention indirectly through its effects on consumer experiences with the virtual world application (ease of use, control, concentration, enjoyment). The findings indicated that consumers’ perceived enjoyment and control positively influenced their shopping intentions. While consumer novelty seeking had no significant effect on shopping intention consumer independent judgment making significantly affected consumers’ intention to shop in a virtual world indirectly through its positive effects on perceived control, enjoyment, and ease of use.

This study was conducted to evaluate the effects of natural bioactive products such as Manda enzyme (T1), Yangmyeongwon (T2), effective microorganisms (T3), and Kelpak (T4) on the growth and ginsenoside contents of Panax ginseng cultured in an aeroponic system using a two-layer vertical type of nutrient bath under natural light conditions. The growth of ginseng plants showed specific characteristics according to the positions in which they were cultured due to the difference of light transmittance and temperature in the upper and lower layers during aeroponic culture in a two-layer vertical type of system. The growth of the aerial part of the leaves and stems of ginseng plants cultured in the lower layer (4,000 to 6,000 lx, 23℃ to 26℃) of the nutrient bath was observed to be superior to that of the ginseng plants cultured in the upper layer (12,000 to 15,000 lx, 25℃ to 28℃). The leaf area was significantly larger in the treatment of T2 and T4 (46.70 cm(2)) than with other treatments. Conversely, the values of the root weight and root diameter were higher in ginseng plants cultured in the upper layer of the nutrient bath. The root weight was significantly heavier in the treatment of T4 (6.46 g) and T3 (6.26 g) than with other treatments. The total ginsenoside content in the leaves and roots was highest in the ginseng plants cultured by the treatment of T1, at 16.20%, while the total ginsenoside content obtained by other treatments decreased in the order of T4, T5 (control), T2, and T3, at 13.21%, 12.30%, 14.84%, and 14.86%, respectively. The total ginsenoside content of the ginseng leaves was found to be significantly higher in the treatment of T1 in the lower layer of the nutrient bath, at 15.30%, while the content of the ginseng roots in the treatments of T3 and T4, at 1.27% and 1.23%, respectively, was significantly higher than in other treatments in the upper layer of the nutrient bath.