Search

An estimated four to 11% of reported coronavirus disease 2019 (COVID-19) cases occurs in healthcare personnel (HCP). HCP are at high risk of acquiring and transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) given their close contact with individuals with recognized and unrecognized COVID-19. We summarize the literature to date describing the epidemiology, identifying risk factors associated with COVID-19, and analyzing clinical characteristics and outcomes of SARS-CoV-2 infection in HCP.The prevalence of SARS-CoV-2 antibodies among HCP ranges from 0.7 to 45%. Although there is heterogeneity in the seroprevalence rate reported in the literature, HCP may be at increased risk of SARS-CoV-2 infection from exposure to patients with COVID-19. The literature supports that this can be minimized with adequate personal protective equipment (PPE) supply, proper hand hygiene, appropriate PPE use, and other infection prevention measures. In addition, infections in HCP are commonly acquired in the community as well as in nonclinical care settings including break rooms or work rooms.While much focus has been on minimizing patient-to-HCP transmission of SARS-CoV-2, additional efforts are needed to prevent exposures in nonclinical care settings and in the community.

Fiber electronics is a key research area for realizing wearable microelectronic devices. Significant progress has been made in recent years in developing the geometry and composition of electronic fibers. In this review, we present that recent progress in the architecture and electrical properties of electronic fibers, including their fabrication methods. We intensively investigate the structural designs of fiber-shaped devices: coaxial, twisted, three-dimensional layer-by-layer, and woven structures. In addition, we introduce remarkable applications of fiber-shaped devices for energy harvesting/storage, sensing, and light-emitting devices. Electronic fibers offer high potential for use in next-generation electronics, such as electronic textiles and smart integrated textile systems, which require excellent deformability and high operational reliability.

Aims In this study, we investigated the vasodilatory effects of trelagliptin (a dipeptidyl peptidase-4 inhibitor) and its related mechanisms using rabbit aortic rings. Main methods Arterial tone measurement was performed in rabbit thoracic aortic rings. Key findings Trelagliptin induced vasodilation in a dose-dependent manner. Pretreatment with the ATP-sensitive K+ channel inhibitor glibenclamide, large-conductance Ca2+-activated K+ channel inhibitor paxilline, and inwardly rectifying K+ channel inhibitor Ba2+ did not affect the vasodilatory effect of trelagliptin. However, pretreatment with the voltage-dependent K+ (Kv) channel inhibitors 4-aminopyridine and tetraethylammonium significantly attenuated the vasodilatory effect of trelagliptin, suggesting that the vasodilatory effect of trelagliptin is associated with Kv channel activation. Although pretreatment with Kv1.5 and Kv2.1 subtype inhibitors did not affect the response to trelagliptin, pretreatment with a Kv7.X subtype inhibitor effectively reduced the vasodilatory effect of trelagliptin. Furthermore, sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump inhibitors also significantly attenuated the vasodilatory effect of trelagliptin. These effects, however, were not affected by pretreatment with Ca2+ channel inhibitors, adenylyl cyclase/PKA inhibitors, guanylyl cyclase/PKG inhibitors, or removal of the endothelium. Significance From these results, we concluded that the vasodilatory effect of trelagliptin was associated with the activation of Kv channels (primary the Kv7.X subtype) and SERCA pump regardless of other K+ channels, Ca2+ channels, cAMP/PKA-related or cGMP/PKG-related signaling pathways, and the endothelium. Therefore, caution is required when prescribing trelagliptin to the patients with hypotension and diabetes.

Objectives The purpose of this study was to examine associations of sociodemographic and lifestyle factors with diet quality in a multiethnic population. Methods The analysis included 160 353 African American, Native Hawaiian, Japanese American, Latino, and non-Hispanic white participants aged 45 to 75 y who entered the Multiethnic Cohort study by completing a comprehensive questionnaire in 1993 to 1996 and did not report cancer or heart disease. Diet quality was assessed using four diet quality indexes (DQIs): the Healthy Eating Index 2010, the Alternative Healthy Eating Index 2010, the alternate Mediterranean Diet, and the Dietary Approaches to Stop Hypertension. Results For three DQIs, the Healthy Eating Index 2010, Alternative Healthy Eating Index 2010, and Dietary Approaches to Stop Hypertension, mean scores were significantly higher in women than men, whereas the mean score of the alternate Mediterranean Diet was significantly higher in men than women. In both men and women, older age, higher education, being physically active, and multivitamin use were associated with scores above the median of DQIs, whereas overweight/obesity, current smoking, and heavy alcohol consumption (≥2 drinks/d) were associated with scores less than the median of DQIs. Race/ethnicity had inconsistent associations according to the DQIs. Being widowed, being a previous smoker, and having a low body mass index ( Conclusions Diet quality was associated with sociodemographic and lifestyle characteristics in men and women. The associations with several factors, such as marital status, body mass index, and smoking status, differed by sex. These findings may help to identify at-risk populations for nutritional screening and to develop nutritional intervention strategies and educational materials.

Background/objectives The aim of this study was to analyze specific foods influencing absolute nutrient intake and between-person variations of nutrient intake among Korean preschoolers. Subjects/methods This study included 2,766 participants aged 1-5 years in the 2009-2013 Korea National Health and Nutrition Examination Surveys. Dietary data were obtained from a 24-h dietary recall method. Major food sources of absolute nutrient intake were evaluated based on percent contribution of each food. To assess the contribution of specific foods to between-person variations in nutrient intake, stepwise multiple regressions were performed and cumulative R2 was used. Results White rice and milk were main food sources of energy, protein, carbohydrate, phosphorus, iron, potassium, thiamin, riboflavin, and niacin. The percentage of fat contributed by milk was 21.3% which was the highest, followed by pork, soybean oil, and egg. White rice accounted for 25% and 40% of total variability in total energy and carbohydrate intakes, respectively. About 39% of variation in calcium intake was explained by milk while 40% of variation in phosphorous intake was explained by cheese. The top 10 foods contributing to between-person variations in nutrient intakes were similar with food items that mainly contributed to absolute nutrient intakes. The number of foods explaining 90% of absolute amounts of nutrient intakes varied from 28 for vitamin A to 80 for iron. Conclusions This study identified specific foods that contributed to absolute nutrient intakes and between-person variations in nutrient intakes among Korean preschoolers. Our findings can be used to develop dietary assessment tools and establish food-based dietary guidelines for young children.

Wearable technology offers new ways to be more proactive about our health and surroundings in real time. For next-generation wearable systems, robust storage and recording media are required to monitor and process the essential electrical signals generated under various unpredictable strain conditions. Here, we report the first fibriform organic transistor memory integrated on a thin and flexible metal wire. A capillary tube coating system allows the formation of a thin and nanograined organic ferroelectric film on the wire. The uniform morphology imparts excellent switching stability (∼100 cycles), quasi-permanent retention (over 5 × 104 s), and low-voltage operation (below 5 V) to the fiber-shaped memory devices. When sewn in a stretchable textile fabric, the memory fiber achieves long retention time of more than 104 s with negligible degradation of memory window even under a constant diagonal strain of 100% that exhibits reliable data storage under tough environments. These results illustrate the possibility of the practical, wearable fiber memory for recording electronic signals in smart garment applications.

For the construction of well-defined hierarchical superstructures of pristine [60]fullerene (C60) arrays, pyrene-based molecular tweezers (PT) were used as host molecules for catching and arranging C60 guest molecules. The formation of host-guest complexes was systematically studied in solution as well as in the solid state. Two-dimensional proton nuclear magnetic resonance spectroscopic studies revealed that PT-host and C60-guest complexes were closely related to the molecular self-assembly of PT. Ultraviolet and fluorescence spectroscopic titrations indicated the formation of stable 1:1 and 2:1 (PT/C60) complexes. From the nonlinear curve-fitting analysis, equilibrium constants for the 1:1 (log K1) and 2:1 (log K2) complexes were estimated to be 4.96 and 5.01, respectively. X-ray diffraction results combined with transmission electron microscopy observations clearly exhibited the construction of well-defined layered superstructures of the PT-host and C60-guest complexes. From electron mobility measurements, it was demonstrated that the well-defined hierarchical hybrid nanostructure incorporating a C60 array exhibited a high electron mobility of 1.7 × 10-2 cm2 V-1 s-1. This study can provide a guideline for the hierarchical hybrid nanostructures of host-guest complex and its applications.

Quorum sensing (QS) inhibitor-based therapy is an attractive strategy to inhibit bacterial biofilm formation without excessive induction of antibiotic resistance. Thus, we designed Ca2+-binding poly(lactide- co-glycolide) (PLGA) microparticles that can maintain a sufficient concentration of QS inhibitors around hydroxyapatite (HA) surfaces in order to prevent biofilm formation on HA-based dental or bone tissues or implants and, therefore, subsequent pathogenesis. Poly(butyl methacrylate- co-methacryloyloxyethyl phosphate) (PBMP) contains both Ca2+-binding phosphomonoester groups and PLGA-interacting butyl groups. The PBMP-coated PLGA (PLGA/PBMP) microparticles exhibited superior adhesion to HA surfaces without altering the sustained release properties of uncoated PLGA microparticles. PLGA/PBMP microparticle-encapsulating furanone C-30, a representative QS inhibitor, effectively inhibited the growth of Streptococcus mutans and its ability to form biofilms on HA surface for prolonged periods of up to 100 h, which was much longer than either furanone C-30 in its free form or when encapsulated in noncoated PLGA microparticles.

The rapid increase in carbapenemase-producing Enterobacterales is a global health concern. During 2017-2020, a total of 44 Escherichia coli isolates co-harbouring blaNDM-5 and blaOXA-181 were collected from patients at 17 hospitals in Seoul and characterized based on antimicrobial susceptibility, resistance genes and plasmid replicons detected using polymerase chain reaction (PCR). Clonal relatedness was estimated using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). All isolates had an identical multidrug resistance profile, including resistance to carbapenems, cephalosporins, ciprofloxacin, tetracycline, and trimethoprim/sulfamethoxazole, and susceptibility to amikacin, colistin, and tigecycline. Resistance genes (blaCTX-M-15, blaCMY-2, blaTEM-1B, blaOXA-1, aac(6’)-Ib-cr, and qnrS) and plasmid replicons (IncFIA, IncFIB, and IncX3) was observed in almost all isolates. All isolates belonged to ST410 and were genetically similar (>88% similarity), with some PFGE types shared among isolates from different hospitals. Analysis of the whole genome revealed that the isolates clustered together with other strains of the international high-risk clone ST410 B4/H24RxC from other countries. These findings underline the ongoing spread of the high-risk clone of NDM-5- and OXA-181-producing E. coli ST410 B4/H24RxC among hospitals in Seoul. Continuous monitoring and implementation of infection control measures are crucial to track and prevent further spread of these resistant strains.

Olanzapine, an FDA-approved atypical antipsychotic, is widely used to treat schizophrenia and bipolar disorder. In this study, the inhibitory effect of olanzapine on voltage-dependent KElectrophysiological recordings were performed in freshly isolated coronary arterial smooth muscle cells.Olanzapine inhibited the Kv channels in a concentration-dependent manner with an ICFrom these results, we suggest that olanzapine inhibits the Kv channels in a concentration-dependent, but state-independent, manner by affecting the gating properties of Kv channels. The primary Kv channel target of olanzapine is the Kv1.5 subtype.

In September 2018, an outbreak of Listeriosis cases in Korea was traced to food involved, using retrospective cohort studies and PFGE analyses. This study aimed to describe the first L.monocytogenes outbreak identified in Korea. We confirmed the presence of Serovar (4C) and virulence genes, and evaluated the genetic correlation between isolates by restriction digestion patterns of ApaI and AscI. Based on the epidemiological association, it is presumed that the seasoned crab meat with bean sprouts are contaminated by cross contamination during the bean sprouts washing (relative risk was 1.24; p-value: 0.0021 and they possessed virulence genes. Therefore, active laboratory surveillance is necessary to recognize the risk of L. monocytogenes in Korea.

The aim of this study was to examine the validity and reproducibility of a food frequency questionnaire (FFQ) developed in Korea for breast cancer survivors.Ninety-nine breast cancer survivors who completed an FFQ twice and three 3-day dietary records (DRs) between 2016-2017 were included. Energy and 14 nutrient intakes were calculated from FFQs and DRs. To determine the validity of the FFQ, energy-adjusted de-attenuated Pearson correlations between two FFQ assessments and the average of the three 3-day DRs were calculated, and to determine reproducibility, energy-adjusted Pearson correlations and degrees of agreement were calculated between the first and second FFQ assessments.Correlation coefficients of validity ranged from 0.29 (protein) to 0.47 (fat) (median value = 0.36) for the FFQ assessment and from 0.20 (riboflavin) to 0.53 (calcium) (median value = 0.37) for the second. Correlation coefficients of reproducibility ranged from 0.22 (sodium) to 0.62 (carbohydrate) (median value = 0.36). Regarding FFQ reproducibilities, percentage classifications of exact agreements for energy-adjusted nutrients ranged from 27.3% (sodium) and 45.5% (fat). A median 76.8% of participants were classified into the same or adjacent quartiles, while a median of 5.6% of participants were classified in extreme quartiles. Bland-Atman plots for the majority of data points of three macronutrients, calcium and vitamins A and C fell within limits of agreement.These results indicated that the newly developed FFQ for Korean breast cancer survivors has acceptable validity and reproducibility as compared with three 3-day DRs collected over a one-year period.

Colistin is often used as a drug of last resort against infections caused by multi-drug-resistant Gram-negative bacteria, including carbapenem-resistant Enterobacterales (CRE). Recently, the acquisition of mobile colistin resistance (mcr) genes by CRE has become a cause for concern. This study investigated the prevalence of mcr genes in CRE isolates in Seoul, Republic of Korea. In total, 3675 CRE strains were collected from patients between 2018 and 2019, and initially screened for mcr genes using multiplex polymerase chain reaction assays. Upon the identification of mcr-harbouring strains, colistin susceptibility tests, identification of carbapenemase and β-lactamase genes, and plasmid replicon typing were performed. Clonal analysis was conducted using pulsed-field gel electrophoresis. mcr genes were detected in 2.2% (80/3675) of CRE strains. There were three mcr-1 carriers, one mcr-4.3 carrier, one mcr-4.3/mcr-9 carrier, 58 mcr-9 carriers, one mcr-9/mcr-10 carrier and 16 mcr-10 carriers among various Enterobacterales species, of which 60 were Enterobacter cloacae complex (ECC) strains. The prevalence of mcr genes in ECC strains was 20.5%. Molecular detection confirmed that 21.3% and 13.8% of mcr-harbouring strains shared blaNDM-1 or blaKPC-2, respectively. In addition, an IncHI2 replicon was identified in 71.7% of mcr-9 strains. Comparative analysis revealed not only a notable diversity of mcr carriers, but also clonal spreading or nosocomial outbreaks of some ECC strains. These findings revealed a silent distribution of mcr genes in CRE strains with high genetic heterogeneity in Seoul, underscoring the urgent need for timely intervention to control and prevent mcr dissemination.

GPCR proteins belong to diverse families of proteins that are defined at multiple hierarchical levels. Inspecting relationships between GPCR proteins on the hierarchical structure is important, since characteristics of the protein can be inferred from proteins in similar hierarchical information. However, modeling of GPCR families has been performed separately for each of the family, subfamily, and sub-subfamily level. Relationships between GPCR proteins are ignored in these approaches as they process the information in the proteins with several disconnected models. In this study, we propose DeepHier, a deep learning model to simultaneously learn representations of GPCR family hierarchy from the protein sequences with a unified single model. Novel loss term based on metric learning is introduced to incorporate hierarchical relations between proteins. We tested our approach using a public GPCR sequence dataset. Metric distances in the deep feature space corresponded to the hierarchical family relation between GPCR proteins. Furthermore, we demonstrated that further downstream tasks, like phylogenetic reconstruction and motif discovery, are feasible in the constructed embedding space. These results show that hierarchical relations between sequences were successfully captured in both of technical and biological aspects.

Tegaserod, a gastroprokinetic agent, is used to treat irritable bowel syndrome. Despite its extensive clinical use, little is known about the effects of tegaserod on vascular ion channels, especially K

Our previous research showed that N-carboxy-phenylsulfonyl hydrazide (scaffold A) could reduce LPS-stimulated PGE

The importance of intellectual property rights (IPRs) for innovation has grown and the protection of intellectual property in international trade has also been strengthened. AI-related patent applications have been increasing rapidly and many AI patents are being filed in various industries. Intellectual property also represents one of the main controversies of U.S.-China trade relations in the past three decades and remains one of the core issues behind the two countries’ recent trade conflicts. As a result, global protection for IPRs has been expanded in recent decades. This article investigates changes in the trend regarding the IP protection level in FTA and how the IP protection through FTAs has affected the composition of aggregate trade flows of member countries in order to provide basic findings necessary to formulate the FTA policies regarding the protection of IPRs in Korea.

Background As of June 2, 2020, 67,113 cases and 321 deaths due to Coronavirus Disease 19 (COVID-19) have been reported in healthcare personnel (HCP) in the United States. Given the close contact of HCP with individuals with COVID-19, it is important to quantify the risk of acquiring COVID-19 in the healthcare setting. Methods We conducted a retrospective cohort study of HCP exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at our academic medical center from March 15, 2020 to May 16, 2020. Exposure during the study period was defined as having contact with patients or other HCP with COVID-19 within 6 feet of distance for at least 90 seconds when HCP’s eyes, nose, or mouth were not covered. HCP with exposures were monitored for symptoms consistent with COVID-19 for 14 days from last exposure and those who developed symptoms were tested for SARS-CoV-2 using RT-PCR. Results We identified 33 exposure events; 19 of which were patient-to-HCP exposures and 14 of which were HCP-to-HCP exposures. These 33 events resulted in 959 exposed HCP among whom 238 (25%) developed one or more symptoms of COVID-19 and required SARS-CoV-2 RT-PCR testing. Testing was performed at 7.1 ± 5.0 (mean ± SD) days from exposure. Of the 238 HCP who were tested, 82% were female and 49% were registered nurses (Table 1). Five HCP tested positive for SARS-CoV-2 by RT-PCR, but one was presumed to have acquired the disease from a household member with confirmed COVID-19. Among the four HCP who were infected due to occupational exposure, three were nurses while one was an environmental service worker (Table 1). Conclusion Despite exposures among HCP, the risk of acquiring symptomatic COVID-19 in the healthcare setting was low with less than 1% of HCP with occupational exposure subsequently diagnosed with COVID-19. With the definition of exposure now changed to at least 15 minutes of close contact without personal protective equipment, we anticipate fewer exposures at our healthcare facility and that much of COVID-19 transmission affecting HCP are due to community exposures. Disclosures All Authors: No reported disclosures

Background Early reports have indicated widespread empiric antimicrobial usage in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As data regarding bacterial complications in patients with Coronavirus Disease 2019 (COVID-19) are limited and emerging, it is important to delineate the burden of complications with bacterial pneumonia in patients with COVID-19 and its implication on antimicrobial usage. Methods We conducted a retrospective cohort study of all hospitalized patients diagnosed with COVID-19 based on detection of SARS-CoV-2 on RT-PCR from March 1, 2020 to May 10, 2020. Data were collected retrospectively to determine the presence of bacterial pneumonia among patients hospitalized with COVID-19 and to identify demographics, comorbidities, or laboratory values that may help to distinguish patients with bacterial pneumonia. Fisher’s exact test was used to analyze categorical data and Student’s t test was used to analyze differences between means. Results Among 99 patients hospitalized with COVID-19 during the study period, complication with bacterial pneumonia was seen in 17 (17%) based on sputum, tracheal aspirate or lower respiratory tract cultures performed 8.9 ± 7.8 (mean ± SD) days from the detection of SARS-CoV-2 on RT-PCR. Staphylococcus aureus was the causative organism in 8 (47%) cases while Enterobacteriaceae were isolated in 7 (41%) cases, Burkholderia cepacia in one (6%) and Rahnella aqualitis in one (6%) case. There were no significant differences in demographics, comorbidities, or laboratory findings between patients with or without complication with bacterial pneumonia. However, those with complication with bacterial pneumonia were more likely to be intubated (24% vs. 88%, p< 0.01), on vasopressors (23% vs. 82%, p < 0.01), and require intensive care unit admission (37% vs. 94%, p< 0.01). Conclusion Nosocomial and ventilator-associated pneumonia were commonly seen among hospitalized patients with COVID-19 requiring intubation and intensive care use admission. With complications of bacterial pneumonia common among critically-ill patients infected with SARS-CoV-2, widespread antimicrobial usage may increase the selective pressure for antibiotic resistance in this patient population. Disclosures All Authors: No reported disclosures

BACKGROUND Existing bacterial culture test results for infectious diseases are written in unrefined text, resulting in many problems, including typographical errors and stop words. Effective spelling correction processes are needed to ensure the accuracy and reliability of data for the study of infectious diseases, including medical terminology extraction. If a dictionary is established, spelling algorithms using edit distance are efficient. However, in the absence of a dictionary, traditional spelling correction algorithms that utilize only edit distances have limitations. OBJECTIVE In this research, we proposed a similarity-based spelling correction algorithm using pretrained word embedding with the BioWordVec technique. This method uses a character-level N-grams–based distributed representation through unsupervised learning rather than the existing rule-based method. In other words, we propose a framework that detects and corrects typographical errors when a dictionary is not in place. METHODS For detected typographical errors not mapped to Systematized Nomenclature of Medicine (SNOMED) clinical terms, a correction candidate group with high similarity considering the edit distance was generated using pretrained word embedding from the clinical database. From the embedding matrix in which the vocabulary is arranged in descending order according to frequency, a grid search was used to search for candidate groups of similar words. Thereafter, the correction candidate words were ranked in consideration of the frequency of the words, and the typographical errors were finally corrected according to the ranking. RESULTS Bacterial identification words were extracted from 27,544 bacterial culture and antimicrobial susceptibility reports, and 16 types of spelling errors and 914 misspelled words were found. The similarity-based spelling correction algorithm using BioWordVec proposed in this research corrected 12 types of typographical errors and showed very high performance in correcting 97.48% (based on F1 score) of all spelling errors. CONCLUSIONS This tool corrected spelling errors effectively in the absence of a dictionary based on bacterial identification words in bacterial culture and antimicrobial susceptibility reports. This method will help build a high-quality refined database of vast text data for electronic health records.

PURPOSE: We examined post-diagnostic diet quality in relation to all-cause and cancer-specific mortality among adults diagnosed with invasive cancer between cohort entry (45-75 years) and their 10-year follow-up, in comparison with those without invasive cancer during that period, in the Multiethnic Cohort. METHODS: Data were from 70,045 African Americans, Native Hawaiians, Japanese Americans, Latinos, and Whites (6,370 with cancer, 63,675 without cancer). Diet quality was measured by the Healthy Eating Index (HEI)-2015, the Alternative HEI-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED), and the Dietary Approaches to Stop Hypertension (DASH) scores, using a food frequency questionnaire. Multivariable Cox models estimated the association of the dietary indexes at 10-year follow-up and changes since baseline with subsequent mortality. RESULTS: Post-diagnostic scores from all four indexes were associated with lower mortality: for the highest vs. lowest quartiles, hazard ratio (HR) for all-cause mortality was 0.74 (95% CI: 0.67-0.82) for HEI-2015, 0.82 (0.74-0.92) for AHEI-2010, 0.74 (0.66-0.84) for aMED, and 0.82 (0.74-0.91) for DASH. The corresponding HRs for cancer mortality were 0.84 (0.71-1.00), 0.85 (0.71-1.00), 0.71 (0.59-0.85), and 0.84 (0.71-1.00). Compared to stable scores over 10 years (

Klompas and colleagues report an investigation of a SARS-CoV-2 cluster in an acute care hospital with transmission between patients and staff. The editorialists remind us of the need to reinforce and reeducate to improve practice of and adherence to important strategies that protect the entire health care ecosystem.

Electronic textiles have been considered one of the desired device platforms due to their dimensional compatibility with fabrics by weaving them with yarn. However, the existing electronic textile platforms are generally composed of only one type of electronic component with a single function on a fiber substrate because of processing challenges. A precise connecting process between each electronic fiber is essential to configure the desired electronic circuits or systems. Here we present a chip on a fiber, a new electronic fiber platform, by introducing large scale integration of electronic device or circuit components onto a one-dimensional microfiber substrate. The electronic components such as transistors, inverters, ring oscillators, and thermocouples were integrated together onto the outer surface of a fiber substrate with precise semiconductor and electrode patterns. Our results show that the electronic components can be integrated on a single fiber with reliable operation. We evaluate the electronic properties of the chip on a fiber as a multifunctional electronic textile platform by testing their switching and data processing, as well as sensing or transducing units for detecting optical/thermal signals. The demonstration of the chip on a fiber suggests significant proof of concepts for realization of high performance with wearable electronic textile systems.

Imipramine, a tricyclic antidepressant, is used in the treatment of depressive disorders. However, the effect of imipramine on vascular ion channels is unclear. Therefore, using a patch-clamp technique we examined the effect of imipramine on voltage-dependent K+ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells. Kv channels were inhibited by imipramine in a concentration-dependent manner, with an IC50 value of 5.55 ± 1.24 µM and a Hill coefficient of 0.73 ± 0.1. Application of imipramine shifted the steady-state activation curve in the positive direction, indicating that imipramine-induced inhibition of Kv channels was mediated by influencing the voltage sensors of the channels. The recovery time constants from Kv-channel inactivation were increased in the presence of imipramine. Furthermore, the application of train pulses (of 1 or 2 Hz) progressively augmented the imipramine-induced inhibition of Kv channels, suggesting that the inhibitory effect of imipramine is use (state) dependent. The magnitude of Kv current inhibition by imipramine was similar during the first, second, and third depolarizing pulses. These results indicate that imipramine-induced inhibition of Kv channels mainly occurs in the closed state. The imipramine-mediated inhibition of Kv channels was associated with the Kv1.5 channel, not the Kv2.1 or Kv7 channel. Inhibition of Kv channels by imipramine caused vasoconstriction. From these results, we conclude that imipramine inhibits vascular Kv channels in a concentration- and use (closed-state)-dependent manner by changing their gating properties regardless of its own function.

Background: Preterm birth is a known leading cause of neonatal mortality and morbidity. The underlying causes of pregnancy-associated complications are numerous, but infection and inflammation are the essential high-risk factors. However, there are no safe and effective preventive drugs that can be applied to pregnant women. Objective: The objectives of the study were to investigate a natural product, Abeliophyllum distichum leaf (ADL) extract, to examine the possibility of preventing preterm birth caused by inflammation. Methods: We used a mouse preterm birth model by intraperitoneally injecting lipopolysaccharides (LPS). ELISA, Western blot, real-time PCR and immunofluorescence staining analyses were performed to confirm the anti-inflammatory efficacy and related mechanisms of the ADL extracts. Cytotoxicity and cell death were measured using Cell Counting Kit-8 (CCK-8) analysis and flow cytometer. Results: A daily administration of ADL extract significantly reduced preterm birth, fetal loss, and fetal growth restriction after an intraperitoneal injection of LPS in mice. The ADL extract prevented the LPS-induced expression of TNF-&alpha, in maternal serum and amniotic fluid and attenuated the LPS-induced upregulation of placental proinflammatory genes, including IL-1&beta, IL-6, IL-12p40, and TNF-&alpha, and the chemokine gene CXCL-1, CCL-2, CCL3, and CCL-4. LPS-treated THP-1 cell-conditioned medium accelerated trophoblast cell death, and TNF-&alpha, played an essential role in this effect. The ADL extract reduced LPS-treated THP-1 cell-conditioned medium-induced trophoblast cell death by inhibiting MAPKs and the NF-&kappa, B pathway in macrophages. ADL extract prevented exogenous TNF-&alpha, induced increased trophoblast cell death and decreased cell viability. Conclusions: We have demonstrated that the inhibition of LPS-induced inflammation by ADL extract can prevent preterm birth, fetal loss, and fetal growth restriction.

This study aims to evaluate whether incorporating gender differences in portion sizes as part of quantifying a food frequency questionnaire influences the association of total energy intake with mortality. The analysis included 156,434 participants (70,142 men and 86,292 women) in the Multiethnic Cohort Study, aged 45&ndash, 75 years at baseline. A total of 49,728 deaths were identified during an average follow-up of 18.1 years. Total energy intake and percentage energy from macronutrients were calculated using original portion sizes (PSs) and gender specific (GS)-PS and were divided into quintiles for men and women. The associations of total energy intake and percentage energy from macronutrients with all-cause, cardiovascular disease (CVD), and cancer mortality were examined using Cox regression with adjustment for potential confounders. Mean &plusmn, standard deviation daily total energy intake using original-PS was 2449 &plusmn, 1135 kcal for men and 1979 &plusmn, 962 kcal for women, using GS-PS was 1996 &plusmn, 884 kcal for men and 1595 &plusmn, 731 kcal for women. For men, the hazard ratios (HRs) (95% confidence intervals) for all-cause, CVD, and cancer comparing the highest to the lowest quintile of total energy intake were 1.05 (1.00&ndash, 1.10), 1.07 (0.99&ndash, 1.16), 1.03 (0.95&ndash, 1.13) using original-PS and 1.07 (1.02&ndash, 1.12), 1.11 (1.03&ndash, 1.20), 1.02 (0.94&ndash, 1.12) using GS-PS, respectively. For women, the corresponding HRs were 1.03 (0.98&ndash, 1.09), 0.99 (0.91&ndash, 1.08), 1.10 (1.00&ndash, 1.21) using original-PS and 1.06 (1.01&ndash, 1.12), 1.02 (0.94&ndash, 1.12), 1.07 (0.97&ndash, 1.18) using GS-PS. Both versions of percentage energy from total fat were associated with an increased risk of all-cause, CVD, and cancer mortality, on the other hand, both versions of percentage energy from carbohydrate showed inverse associations with all-cause, CVD, and cancer mortality in both men and women. When using original-PS and GS-PS, the estimated total energy intake differed, resulting in marginal differences in the associations of total energy intake with all-cause, CVD, and cancer mortality.

Background: Preterm birth is a known leading cause of neonatal mortality and morbidity. The underlying causes of pregnancy-associated complications are numerous, but infection and inflammation are the essential high-risk factors. However, there are no safe and effective preventive drugs that can be applied to pregnant women. Objective: The objectives of the study were to investigate a natural product, Abeliophyllum distichum leaf (ADL) extract, to examine the possibility of preventing preterm birth caused by inflammation. Methods: We used a mouse preterm birth model by intraperitoneally injecting lipopolysaccharides (LPS). ELISA, Western blot, real-time PCR and immunofluorescence staining analyses were performed to confirm the anti-inflammatory efficacy and related mechanisms of the ADL extracts. Cytotoxicity and cell death were measured using Cell Counting Kit-8 (CCK-8) analysis and flow cytometer. Results: A daily administration of ADL extract significantly reduced preterm birth, fetal loss, and fetal growth restriction after an intraperitoneal injection of LPS in mice. The ADL extract prevented the LPS-induced expression of TNF-α in maternal serum and amniotic fluid and attenuated the LPS-induced upregulation of placental proinflammatory genes, including IL-1β, IL-6, IL-12p40, and TNF-α and the chemokine gene CXCL-1, CCL-2, CCL3, and CCL-4. LPS-treated THP-1 cell-conditioned medium accelerated trophoblast cell death, and TNF-α played an essential role in this effect. The ADL extract reduced LPS-treated THP-1 cell-conditioned medium-induced trophoblast cell death by inhibiting MAPKs and the NF-κB pathway in macrophages. ADL extract prevented exogenous TNF-α-induced increased trophoblast cell death and decreased cell viability. Conclusions: We have demonstrated that the inhibition of LPS-induced inflammation by ADL extract can prevent preterm birth, fetal loss, and fetal growth restriction.

Metabotropic glutamate receptor 7 (mGlu7) is an inhibitory heterotrimeric G-protein-coupled receptor that modulates neurotransmitter release and synaptic plasticity at presynaptic terminals in the mammalian central nervous system. Recent studies have shown that rare mutations in glutamate receptors and synaptic scaffold proteins are associated with neurodevelopmental disorders (NDDs). However, the role of presynaptic mGlu7 in the pathogenesis of NDDs remains largely unknown. Recent whole-exome sequencing (WES) studies in families with NDDs have revealed that several missense mutations (c.1865G>A:p.R622Q; c.461T>C:p.I154T; c.1972C>T:p.R658W and c.2024C>A:p.T675K) or a nonsense mutation (c.1757G>A:p.W586X) in the GRM7 gene may be linked to NDDs. In the present study, we investigated the mechanistic links between GRM7 point mutations and NDD pathology. We find that the pathogenic GRM7 I154T and R658W/T675K mutations lead to the degradation of the mGlu7 protein. In particular, the GRM7 R658W/T675K mutation results in a lack of surface mGlu7 expression in heterologous cells and cultured neurons isolated from male and female rat embryos. We demonstrate that the expression of mGlu7 variants or exposure to mGlu7 antagonists impairs axon outgrowth through the mitogen-activated protein kinase (MAPK)-cAMP-protein kinase A (PKA) signaling pathway during early neuronal development, which subsequently leads to a decrease in the number of presynaptic terminals in mature neurons. Treatment with an mGlu7 agonist restores the pathologic phenotypes caused by mGlu7 I154T but not by mGlu7 R658W/T675K because of its lack of neuronal surface expression. These findings provide evidence that stable neuronal surface expression of mGlu7 is essential for neural development and that mGlu7 is a promising therapeutic target for NDDs. SIGNIFICANCE STATEMENT Neurodevelopmental disorders (NDDs) affect brain development and function by multiple etiologies. Metabotropic glutamate receptor 7 (mGlu7) is a receptor that controls excitatory neurotransmission and synaptic plasticity. Since accumulating evidence indicates that the GRM7 gene locus is associated with NDD risk, we analyzed the functional effects of human GRM7 variants identified in patients with NDDs. We demonstrate that stable neuronal surface expression of mGlu7 is essential for axon outgrowth and presynaptic terminal development in neurons. We found that mitogen-activated protein kinase (MAPK)-cAMP-protein kinase A (PKA) signaling and subsequent cytoskeletal dynamics are defective because of the degradation of mGlu7 variants. Finally, we show that the defects caused by mGlu7 I154T can be reversed by agonists, providing the rationale for proposing mGlu7 as a potential therapeutic target for NDDs.

Successful clinical translation of stem cell-based therapy largely relies on the scalable and reproducible preparation of donor cells with potent therapeutic capacities. In this study, midbrain organoids were yielded from human pluripotent stem cells (hPSCs) to prepare cells for Parkinson's disease (PD) therapy. Neural stem/precursor cells (NSCs) isolated from midbrain organoids (Og-NSCs) expanded stably and differentiated into midbrain-type dopamine(mDA) neurons, and an unprecedentedly high proportion expressed midbrain-specific factors, with relatively low cell line and batch-to-batch variations. Single cell transcriptome analysis followed by in vitro assays indicated that the majority of cells in the Og-NSC cultures are ventral midbrain (VM)-patterned with low levels of cellular senescence/aging and mitochondrial stress, compared to those derived from 2D-culture environments. Notably, in contrast to current methods yielding mDA neurons without astrocyte differentiation, mDA neurons that differentiated from Og-NSCs were interspersed with astrocytes as in the physiologic brain environment. Thus, the Og-NSC-derived mDA neurons exhibited improved synaptic maturity, functionality, resistance to toxic insults, and faithful expressions of the midbrain-specific factors, in vitro and in vivo long after transplantation. Consequently, Og-NSC transplantation yielded potent therapeutic outcomes that are reproducible in PD model animals. Collectively, our observations demonstrate that the organoid-based method may satisfy the demands needed in the clinical setting of PD cell therapy.

One-dimensional (1D) devices are becoming the most desirable format for wearable electronic technology because they can be easily woven into electronic (e-) textile(s) with versatile functional units while maintaining their inherent features under mechanical stress. In this study, we designed 1D fiber-shaped multi-synapses comprising ferroelectric organic transistors fabricated on a 100-μm Ag wire and used them as multisynaptic channels in an e-textile neural network for wearable neuromorphic applications. The device mimics diverse synaptic functions with excellent reliability even under 6000 repeated input stimuli and mechanical bending stress. Various NOR-type textile arrays are formed simply by cross-pointing 1D synapses with Ag wires, where each output from individual synapse can be integrated and propagated without undesired leakage. Notably, the 1D multi-synapses achieved up to ~90 and ~70% recognition accuracy for MNIST and electrocardiogram patterns, respectively, even in a single-layer neural network, and almost maintained regardless of the bending conditions.

BACKGROUND Tongue pressure is an effective index of swallowing function, and it decreases with aging and disease progression. Previous research has shown beneficial effects of swallowing exercises combined with myofunctional tongue-strengthening therapy on tongue function. Tongue exercises delivered through mobile health (mHealth) technologies have the potential to advance health care in the digital age to be more efficient for people with limited resources, especially older adults. OBJECTIVE The purpose of this study is to explore the immediate and long-term maintenance effects of an 8-week home-based mHealth app intervention with biweekly (ie, every 2 weeks) human mediation aimed at improving the swallowing tongue pressure in older adults. METHODS We developed an mHealth app intervention that was used for 8 weeks (3 times/day, 5 days/week, for a total of 120 sessions) by 11 community-dwelling older adults (10 women; mean age 75.7 years) who complained of swallowing difficulties. The app included a swallowing monitoring and intervention protocol with 3 therapy maneuvers: effortful prolonged swallowing, effortful pitch glide, and effortful tongue rotation. The 8-week intervention was mediated by biweekly face-to-face meetings to monitor each participant’s progress and ability to implement the training sessions according to the given protocol. Preintervention and postintervention isometric and swallowing tongue pressures were measured using the Iowa Oral Performance Instrument. We also investigated the maintenance effects of the intervention on swallowing tongue pressure at 12 weeks postintervention. RESULTS Of the 11 participants, 8 adhered to the home-based 8-week app therapy program with the optimal intervention dosage. At the main trial end point (ie, 8 weeks) of the intervention program, the participants demonstrated a significant increase in swallowing tongue pressure (median 17.5 kPa before the intervention and 26.5 kPa after the intervention; P=.046). However, long-term maintenance effects of the training program on swallowing tongue pressure at 12 weeks postintervention were not observed. CONCLUSIONS Swallowing tongue pressure is known to be closely related to dysphagia symptoms. This is the first study to demonstrate the effectiveness of the combined methods of effortful prolonged swallowing, effortful pitch glide, and effortful tongue rotation using mobile app training accompanied by biweekly human mediation in improving swallowing tongue pressure in older adults. The mHealth app is a promising platform that can be used to deliver effective and convenient therapeutic service to vulnerable older adults. To investigate the therapeutic efficacy with a larger sample size and observe the long-term effects of the intervention program, further studies are warranted. INTERNATIONAL REGISTERED REPORT RR2-10.2196/19585

Darifenacin, an anticholinergic agent, has been used to treat overactive bladder syndrome. Despite its extensive clinical use, there is little information about the effect of darifenacin on vascular ion channels, specifically K

Metabotropic glutamate receptor 7 (mGlu7) regulates neurotransmitter release at the presynaptic active zone in the mammalian brain. The regulation of mGlu7 trafficking into and out of the plasma membrane by binding proteins within the C-terminal region of mGlu7 governs the bidirectional synaptic plasticity. However, the functional importance of the extracellular domain of mGlu7 has not yet been characterized. N-glycosylation is an abundant posttranslational modification that plays crucial roles in protein folding and forward trafficking, but the role of N-glycosylation in mGlu7 function remains unknown. In this study, we find that mGlu7 is N-glycosylated at four asparagine residues in heterologous cells and rat cultured neurons. We demonstrate that N-glycosylation is essential for forward transport and surface expression of mGlu7. Deglycosylated mGlu7 is retained in the ER, obstructing expression on the cell surface, and is degraded through the autophagolysosomal degradation pathway. In addition, we identify the binding domain of mGlu7 to Elfn1, a transsynaptic adhesion protein. We find that N-glycosylation of mGlu7 promotes its interaction with Elfn1, thereby enabling proper localization and stable surface expression of mGlu7 at the presynaptic active zone. These findings provide evidence that N-glycans act to modulate the surface expression, stability, and function of mGlu7.

We investigated the effect of ziprasidone, a widely used treatment for schizophrenia, on voltage-dependent K

OBJECTIVES: We examined the association of postdiagnostic diet quality with all-cause and cancer-specific mortality in older adults diagnosed with invasive cancer, in comparison with those without invasive cancer, in the Multiethnic Cohort. METHODS: Data were from 66,374 African American, Native Hawaiian, Japanese American, Latino, and White men and women, who had no prevalent cancer, heart disease, or stroke at baseline (1993–1996, 45–75 years) and completed a quantitative food frequency questionnaire at both baseline and 10-year follow-up (2003–2007). Overall diet quality was measured by the Healthy Eating Index (HEI)-2015, the Alternative HEI-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED), and the Dietary Approaches to Stop Hypertension (DASH) scores. Invasive cancer cases between the baseline and 10-year surveys and deaths after the 10 year survey were identified through linkage to cancer registries and to state death files and the National Death Index. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in multivariate Cox models for the dietary indexes at 10-year follow-up with subsequent mortality. RESULTS: Age-adjusted mean scores of the 4 dietary indexes at baseline (prediagnosis) and 10-year follow-up (postdiagnosis) were similar or slightly lower in participants with cancer (n = 5998), compared to those without cancer (n = 60,376). Among participants with cancer (71.5 ± 8.0 years), 2006 all-cause and 1005 cancer-specific deaths were identified during a mean follow-up of 8 years after the 10-year survey. Postdiagnostic scores from all 4 indexes were associated with lower risk of all-cause and cancer mortality: for the highest vs. lowest quartiles, HR (95% CI) for all-cause mortality was 0.72 (0.62–0.82) for HEI-2015, 0.84 (0.73–0.96) for AHEI-2010, 0.74 (0.63–0.86) for aMED, and 0.76 (0.66–0.87) for DASH. The corresponding HRs (95% CIs) for cancer mortality were 0.81 (0.66–0.99), 0.81 (0.66–0.99), 0.72 (0.58–0.89), and 0.79 (0.65–0.97). These HRs were similar to those for participants without cancer. CONCLUSIONS: Postdiagnostic high-quality diet was related to lower all-cause and cancer mortality in older adults with invasive cancer, with risk reduction comparable to that among participants without cancer. FUNDING SOURCES: National Cancer Institute.

We investigated the vasodilatory effects of empagliflozin (a sodium-glucose co-transporter 2 inhibitor) and the underlying mechanisms using rabbit aorta. Empagliflozin induced vasodilation in a concentration-dependent manner independently of the endothelium. Likewise, pretreatment with the nitric oxide synthase inhibitor L-NAME or the SKca inhibitor apamin together with the IKca inhibitor TRAM-34 did not impact the vasodilatory effects of empagliflozin. Pretreatment with the adenylyl cyclase inhibitor SQ22536 or a guanylyl cyclase inhibitor ODQ or a protein kinase A (PKA) inhibitor KT5720 also did not alter the vasodilatory response of empagliflozin. However, the vasodilatory effects of empagliflozin were significantly reduced by pretreatment with the protein kinase G (PKG) inhibitor KT5823. Although application of the ATP-sensitive K

BackgroundARID2 belongs to the Switch/sucrose non-fermenting complex, in which the genetic defects have been found in patients with dysmorphism, short stature and intellectual disability (ID). As the phenotypes of patients with ARID2 mutations partially overlap with those of RASopathy, this study evaluated the biochemical association between ARID2 and RAS-MAPK pathway.MethodsThe phenotypes of 22 patients with either an ARID2 heterozygous mutation or haploinsufficiency were reviewed. Comprehensive molecular analyses were performed using somatic and induced pluripotent stem cells (iPSCs) of a patient with ARID2 haploinsufficiency as well as using the mouse model of Arid2 haploinsufficiency by CRISPR/Cas9 gene editing.ResultsThe phenotypic characteristics of ARID2 deficiency include RASopathy, Coffin-Lowy syndrome or Coffin-Siris syndrome or undefined syndromic ID. Transient ARID2 knockout HeLa cells using an shRNA increased ERK1 and ERK2 phosphorylation. Impaired neuronal differentiation with enhanced RAS-MAPK activity was observed in patient-iPSCs. In addition, Arid2 haploinsufficient mice exhibited reduced body size and learning/memory deficit. ARID2 haploinsufficiency was associated with reduced IFITM1 expression, which interacts with caveolin-1 (CAV-1) and inhibits ERK activation.DiscussionARID2 haploinsufficiency is associated with enhanced RAS-MAPK activity, leading to reduced IFITM1 and CAV-1 expression, thereby increasing ERK activity. This altered interaction might lead to abnormal neuronal development and a short stature.

Iloperidone, a second-generation atypical antipsychotic drug, is widely used in the treatment of schizophrenia. However, the side-effects of iloperidone on vascular K

This study investigated the vasodilatory effects and acting mechanism of gemigliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor. Tests were conducted in aortic rings pre-contracted with phenylephrine. Gemigliptin induced dose-dependent vasodilation of the aortic smooth muscle. Several pre-treatment groups were used to investigate the mechanism of action. While pre-treatment with paxilline, a large-conductance Ca

Korean Abstract: 본 연구는 국영기업·산업보조금·보조금 통보와 관한 WTO 개혁 논의 동향을 파악하고, 현행 WTO 협정과 지역무역협정에서의 관련 규범에 대한 분석을 통해 미국·유럽연합·일본이 향후 공개할 WTO 보조금협정 개정안의 방향과 내용을 예측하였다. 아울러 WTO 보조금협정 개정 협상과정에서 우리나라의 지지를 얻기 위한 3개 회원국의 아웃리치가 있을 경우를 대비하여, WTO 보조금협정 개정에 대한 우리나라의 대외적 입장 정립에 관한 정책적 시사점을 도출하고자 하였다. 제2장에서는 중국의 국영기업 지원에 관련된 WTO 협정 개정 논의를 살펴보았다. 중국의 국영기업의 현황을 살펴보고, 중국의 국영기업 문제를 다루는 데 현행 WTO 협정이 가지는 문제점을 적시하였다. GATT 제17조는 ‘국영무역기업’ 정의 규정의 부재, 국영무역기업 투명성 메커니즘의 저조한 이행률 등 많은 한계를 노정해왔으며, WTO 보조금협정에서는 중국 국영기업을 보조금의 공여주체인 ‘공공기관’으로 볼 수 있는지를 두고 미국과 중국 사이에 이견이 있어 왔다. 미국은 소유지분, 의결권과 같은 객관적 기준에 따라 공공기관 여부를 결정할 것을 주장하면서, 상소기구가 도입한 ‘정부권한’ 및 ‘유의미한 통제’ 기준의 경우 조사당국에게 과도한 입증책임을 요구하여 중국 국영기업이 공공기관임을 증명하는 데 어려움이 있다고 비판해왔다. CPTPP 및 USMCA 등 최근의 지역무역협정에서는 정부의 소유나 통제 여부에 기초하여 국영기업을 정의하고 있다. 미국·유럽연합·일본의 WTO 보조금협정 개정안에는 국영기업 문제와 관련하여 (ⅰ) ‘공공기관’의 판단기준 신설, (ⅱ) 공공기관으로 분류되지 않으나 정부의 영향을 받는 기업에 적용되는 규칙 마련, (ⅲ) 공공기관과 국영기업에 적용될 추가적인 의무와 규칙의 신설이 포함될 것으로 예상되며, 아직 공식 개정안이 발표되지는 않았으므로 CPTPP, USMCA 등을 살펴 개정 방향을 전망하였다. 제3장에서는 미국 등이 문제삼고 있는 공급과잉을 유발하는 산업보조금, 이른바 ‘유해보조금’에 관한 WTO 보조금협정 개정 가능성을 논의하였다. 중국정부는 특히 철강, 석탄, 시멘트 등 제조업과 에너지 등 상류 부문에서 국영기업에 보조금을 집중적으로 공여하고 있으나, 상류부문에 대한 보조금이 하류부문으로 ‘이전’되었음을 제소국이 증명하는 데 어려움이 있는 상태이다. 따라서 (ⅰ) 상류보조금 및 혜택의 이전에 관한 규정 신설이 예상된다. 또한 (ⅱ) 수출보조금과 수입대체보조금 외에도 부정적 외부효과를 야기하는 보조금에 대해서 금지보조금으로 추가하는 방안을 논의할 것으로 보이며, (ⅲ) 보조금의 사용을 통하여 부정적 효과 중 심각한 손상을 입증하기 용이하도록 과거의 심각한 손상 간주규정을 재도입하는 안이 논의될 가능성이 있다. 그 밖에 (ⅳ) 혜택 산정기준에 있어 국외가격 또는 구성가격의 사용가능성 및 조건, (ⅴ) 국영기업에 관련된 기업(군)·산업(군) 특정성 판단 기준 신설 등이 논의될 것으로 보인다. 제4장에서는 보조금 통보와 관련된 WTO 협정 개정 논의를 살펴보았다. 현재 산업보조금과 국영기업에 관한 WTO 회원국들의 통보 이행률은 상당히 저조한 상태이다. 특히 중국의 경우 중앙·지방정부 차원뿐 아니라 국영기업이 보조금 공여행위에 적극 가담하고 있는데 이에 대한 통보가 제대로 이루어지고 있지 않아 문제가 되고 있다. 통보의무와 관련하여 현재 다수의 제안서가 WTO에 제출되고 있으며 통보의무 불이행국에게 행정조치를 부과하는 안, 무역정책검토에서 통보이행 여부를 검토하는 안 등이 공통적으로 제안되고 있다. 통보의무 불이행에 대한 행정조치의 경우 각 단계별 조치의 내용과 적절성, 실효성에 대한 의견대립이 예상되며, 무역정책검토를 통한 통보의무 제고 방안은 향후 보조금 통보 관련 개정 논의가 WTO 회원국 전반으로 확대되는 과정에서 주요 의제로 다루어질 것으로 예상된다. 제5장 결론에서는 국영기업 보조금 문제에 관한 향후 전망과 함께 다양한 WTO 보조금협정 개정 요소들의 우선순위화 및 단계적 개정을 제안하고, (ⅰ) 공공기관 판단기준 신설, (ⅱ) 국영기업에 대한 추가 의무 신설, (ⅲ) 상류보조금에 대한 혜택의 이전 관련 규정 신설, (ⅳ) 공급과잉을 유발하는 산업보조금의 금지, (ⅴ) 비시장 지향조건 및 비시장경제국 판단기준 신설, (ⅵ) 투명성 관련 개정 가능성을 두고 한국의 입장 정립 및 대응방안에 관해 정책적 시사점을 도출하였다. 나아가 우리 국내 산업과 국내 보조금 지원 정책에 미칠 법적·경제적 영향을 사전 분석하여 WTO 보조금협정 개정 논의에 대한 우리의 포지셔닝을 확립할 필요가 있음을 강조하였다. English Abstract: The present study deals with the issue of state-owned enterprises (SOEs), industrial subsidies, and subsidy notifications in the context of “WTO Reform”; examines relevant provisions of WTO agreements in comparison with those under a select number of recent regional trade agreements; and predicts directions for future WTO amendment proposals to be made by the United States, European Union, and Japan (hereinafter referred to as “US-EU-Japan”). Further, in preparation for a situation where these three Members reach out to obtain Korea's support for the amendments, this study seeks to provide policy implications that the Korean government could take into account in defining its strategic positioning in WTO Reform negotiations. Chapter 2 discusses possible WTO amendments related to industrial subsidization “for” and/or “by” China’s SOEs. To this end the present study firstly sheds light on the current situation with China’s SOEs, its industrial subsidization policy, and possible market distortion arising therefrom. Secondly it discusses practical and normative limits of the current WTO agreements in addressing this trade issue. Article XVII of the GATT has long been criticized for a lack of a definition of “state-trading enterprises (STEs)” and for Members’ insufficient implementation of STEs transparency obligations under the same provision. Further, under the WTO Subsidies Agreement there has been a long-standing disagreement between the United States and China on whether China's SOEs can be viewed as a “public body”, i.e., the granting authorities of subsidies. The United States has consistently objected to the “government authority” and “significant control” standards and criticized that the Appellate Body’s interpretation of the term “public body” would place too much burden on the investigating authorities in proving China’s SOE under investigation constitute a public body. Against this background a few recent RTAs including the CPTPP and the USMCA contain more concrete definition of SOEs based on ownership and control. On a similar note it is probable that US-EU-Japan would propose under WTO agreements to (ⅰ) introduce detailed criteria in determining a public body in cases where SOE subsidization is concerned; (ⅱ) adopt a set of rules which apply to entities which are not public bodies but still under influence of the government; and (ⅲ) add additional obligations and rules which apply specifically to SOE subsidization. For a more detailed analysis, this study examines similarities and differences in relevant provisions of the current WTO Subsidies Agreement, the CPTPP, and the USMCA. Chapter 3 analyzes a possible WTO Subsidies Agreement revision with respect to industrial subsidies leading to overcapacity or “harmful subsidies.” A future proposal by US-EU-Japan is most likely to provide for (ⅰ) introduction of explicit rules on benefit pass-through, given that GATT/WTO jurisprudence has consistently required a high degree of burden of proof to the investigating authorities in establishing that benefits provided to upstream industries have “passed through” to downstream industries. Additionally the following elements may be proposed: (ⅱ) expansion of boundary of the “prohibited subsidies” beyond export subsidies and import substitution subsidies to include harmful subsidies; (ⅲ) reintroduction of rebuttable presumption of adverse effects (as in now-defunct Article 6.1 of the WTO Subsidies Agreement); (ⅳ) introduction of more detailed rules for out-of-country benchmark for countervailing duty calculation under Article 14 of the same Agreement ; and (ⅴ) adoption of additional fast-track rules specifically for disputed SOE subsidization between WTO Members. Chapter 4 discusses possible WTO amendments as regards subsidy notifications. While the compliance rate with notification obligations has generally been very low for most WTO Members, the main criticism has been directed at China. It has been repeatedly pointed out at the WTO that while China is actively involved in domestic subsidization both at the central and local government level, it still has not completed notification on all of its domestic subsidies. On this matter, primarily two proposals are being discussed: (ⅰ) introduction of “administrative measures” to be applied to WTO Members who failed to comply with their notification obligations, and (ⅱ) utilization of Trade Policy Reviews (TPRs) in monitoring such non-compliance. In Chapter 5 this study suggests that WTO Members should adopt a “stepped” approach by prioritizing among multiple revision elements. Further it draws policy implications for the Korean government to take into account in future WTO negotiations, with regard to introduction of (ⅰ) new definition of “public bodies” where SOEs are concerned; (ⅱ) additional obligations and rules for SOE subsidization; (ⅲ) explicit benefit pass-through provision for upstream subsidies, (ⅳ) prohibited industrial subsidies leading to overcapacity; (ⅴ) criteria for determining the Non-market-oriented conditions and/or Non-Market Economies (NMEs) under WTO agreements; and (ⅵ) rules to strengthen transparency and enhance Members’ subsidy notifications including administrative measures. Lastly, this study stresses that the Korean government closely monitor the ongoing discussion between US-EU-Japan for a thorough legal and economic analysis on any further developments, and prepare multiple scenarios for all possible outcomes in setting its positioning and negotiation strategies with respect to each revision element.