Search

Seung Yeon Lee,1,2 Ji Hye Ham,3 Hyun-Kyung Park,4 Deok Hyun Jang,5 Won Mo Jang6,7 1Department of Administration, Seoul National University Hospital, Seoul, South Korea; 2Office of External Affairs, Seoul Metropolitan Government-Seoul National University Boramae Medical Centre, Seoul, South Korea; 3Seoul Public Health Research Institute, Seoul Medical Center, Seoul, South Korea; 4Health Insurance Research Institute, National Health Insurance Service, Wonju, South Korea; 5Research Analytics & Communications, Gallup Korea, Seoul, South Korea; 6Department of Public Health and Community Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Centre, Seoul, South Korea; 7Department of Health Policy and Management, Seoul National University College of Medicine, Seoul, South KoreaCorrespondence: Won Mo Jang, Department of Public Health and Community Medicine, Seoul Metropolitan Government – Seoul National University Boramae Medical Center, Seoul, 07061, South Korea, Tel +82-2-870-2165, Email thomasj@snu.ac.krPurpose: After the declaration by the World Health Organization signaling the conclusion of the COVID-19 pandemic, most countries lifted mandatory mask-wearing regulations. This study aimed to investigate factors such as risk perception and political ideology associated with continued adherence to mask-wearing among specific populations, particularly when it is no longer deemed necessary.Methods: We conducted a cross-sectional study including a sample of 1001 respondents stratified by sex, age (≥ 18 years), and region from January 31 to February 2, 2023, after the mandatory mask regulation was lifted in South Korea. Multivariate logistic regression models were applied to estimate the relationships between risk perceptions, political ideology, and mask-wearing maintenance, adjusting for factors such as sex, age, occupation, and trust in the government.Results: Our results indicated significant associations between age, self-reported household economic status, political ideology, affective risk perception, and perceived effectiveness of the government’s COVID-related measures with indoor mask-wearing. Specifically, liberals were more likely to keep mask-wearing indoors than conservatives (adjusted odds ratio [aOR]: 2.19; 95% confidence interval [CI]: 1.33– 3.59); and those who perceived a greater affective risk of COVID-19 (aOR: 2.47; 95% CI: 1.96– 3.10), along with those who perceived the government’s countermeasures as inadequate, were more inclined to maintain the habit of wearing masks indoors (aOR: 1.90; 95% CI: 1.19– 3.03).Conclusion: Our study highlighted the multifaceted factors influencing mask-wearing behavior in the post-COVID-19 era. Even after adjusting for various confounding factors, such as age, sex, and trust in the government, an association remained between affective risk perception, political ideology, and mask-wearing behavior. However, further research for psychological mechanisms is needed to foster a culture of preventive behaviors proportional to the risk of infection.Keywords: risk perception, mask-wearing behaviors, political ideology

Storytelling is a well-established literary practice in language classrooms. However, approaches influencing its effectiveness and efficiency have rarely been investigated. This study compared the effects of three storytelling approaches on the vocabulary acquisition and response patterns of third-grade students of English as a foreign language (EFL). The storytelling approaches we considered are commonly used in schools, including storytelling alone (S), storytelling with word focus (S+W), and storytelling with activities (S+A). Our research comprised a three-week pilot study and a nine-week main study. For both studies, a pretest-posttest design involving a delayed test was used. Video recordings were also captured to facilitate the categorization of in-class response patterns. Results indicated that storytelling alone achieved the best performance. Vocabulary improvement with word focus or follow-up activities faded over the long term. The groups (S and S+W) which heard more stories generated more responses based on their own knowledge and life experience (as opposed to simply recalling facts) than did the group which completed more supplementary activities (S+A). This article provides both pedagogical implications and invitations for future empirical research.

Eun Kyung Kim,1,&ast; Eunyoung Lee,2,&ast; Ji Eun Park,3,&ast; Jae Seung Lee,4 Hye Sook Choi,5 Bumhee Park,6,7 Seung Soo Sheen,3 Kwang Joo Park,3 Chin Kook Rhee,8 Sang Yeub Lee,9 Kwang Ha Yoo,10 Joo Hun Park3 1Department of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea; 2Department of Neurology, McGovern Medical School at UTHealth, Houston, TX, USA; 3Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, Republic of Korea; 4Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 5Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea; 6Office of Biostatistics, Medical Research Collaborating Center, Ajou Research Institute for Innovative Medicine, Ajou University Medical Center, Suwon, Republic of Korea; 7Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea; 8Department of Internal Medicine, Seoul St. Mary’s Hospital, Catholic University of Korea, Seoul, Republic of Korea; 9Department of Internal Medicine, Korea University Anam Hospital, Seoul, Republic of Korea; 10Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Joo Hun Park, Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Worldcup Road 164, Suwon, Gyeonggi-do, 16499, Republic of Korea, Tel +82-31-219-5116, Fax +82-31-219-5124, Email jhpamc@naver.com; jhpamc@hanmail.netBackground: COPD coexists with many concurrent comorbidities. Cardiovascular complications are deemed to be major causes of death in COPD. Although inhaler therapy is the main therapeutic intervention in COPD, cardiovascular events accompanying inhaler therapy require further investigation. Therefore, this study aimed to investigate new development of cardiovascular events according to each inhaler therapy and comorbidities.Methods: This study analyzed COPD patients (age ≥ 40 years, N = 199,772) from the Health Insurance Review and Assessment Service (HIRA) database in Korea. The development of cardiovascular events, from the index date to December 31, 2020, was investigated. The cohort was eventually divided into three arms: the LAMA/LABA group (N = 28,322), the ICS/LABA group (N = 11,812), and the triple group (LAMA/ICS/LABA therapy, N = 6174).Results: Multivariable Cox analyses demonstrated that, compared to ICS/LABA therapy, triple therapy was independently associated with the development of ischemic heart disease (HR: 1.22, 95% CI: 1.04– 1.43), heart failure (HR: 1.45, 95% CI: 1.14– 1.84), arrhythmia (HR: 1.72, 95% CI: 1.41– 2.09), and atrial fibrillation/flutter (HR: 2.31, 95% CI: 1.64– 3.25), whereas the LAMA/LABA therapy did not show a significant association. Furthermore, emergency room visit during covariate assessment window was independently associated with the development of ischemic heart disease, heart failure, arrhythmia, and atrial fibrillation/flutter (p < 0.05).Conclusion: Our data suggest that cardiovascular risk should be considered in COPD patients receiving triple therapy, despite the confounding bias resulting from disparities in each group.Keywords: COPD, inhaler therapy, cardiovascular event, comorbidities

Hye Ran Kim,1 So Yeon Lee,1 Ga Eun You,2 Hye One Kim,1 Chun Wook Park,1 Bo Young Chung1 1Department of Dermatology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 07441, Korea; 2Research and Development Institute, Biosolution, Seoul Technopark, Seoul, 01811, KoreaCorrespondence: Bo Young Chung, Department of Dermatology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, 1 Singil-ro, Yeongdeungpo-gu, Seoul, 07441, Korea, Tel +82-2-829-5221, Fax +82-2-832-3237, Email victoryby@hallym.or.krIntroduction: Exosomes play a key role in cell communication and are involved in both pathological and physiological processes. Autophagy dysfunction and oxidative stress are linked to immune-mediated inflammatory diseases such as psoriasis. Stem cell-derived exosomes exhibit immunomodulatory and antioxidant efficacy.Methods: We aimed to investigate the impact of psoriasis serum-derived exosomes on inflammation, oxidative stress, and autophagy in keratinocytes. Additionally, we explored the therapeutic potential of adipose-derived stem cell (ADSC) exosomes against inflammation induced by psoriasis serum exosomes. To validate psoriasis patient serum-derived exosomes and ADSC exosomes, we used nanoparticle tracking analysis, Western blotting, flow cytometry, and immunofluorescence. qPCR was used to study changes in the gene expression of proinflammatory cytokines and oxidative stress markers in HaCaT cells treated with psoriasis serum-derived exosomes or ADSC exosomes. The effects of these exosomes on autophagy in HaCaT cells were evaluated by Western blotting and immunofluorescence.Result: The treatment of HaCaT cells with psoriasis serum-derived exosomes increased proinflammatory cytokine production and oxidative stress-related factor (Nox2 and Nox4) expression and decreased Nrf2 expression via P65/NF-κB and P38/MAPK activation. Compared with healthy control serum-derived exosomes, psoriasis serum-derived exosomes decreased ATG5, P62, Beclin1, and LC3 expression and autophagosome production in HaCaT cells. Conversely, ADSC exosomes suppressed proinflammatory cytokine and oxidative stress production, and restored autophagy in HaCaT cells treated with psoriasis serum-derived exosomes.Discussion: These findings suggest that ADSC exosomes exhibit a suppressive effect on psoriasis serum exosome-induced inflammation and oxidative stress by regulating autophagy in keratinocytes.Keywords: exosomes, adipose-derived stem cell, psoriasis, autophagy, oxidative stress

Bryan Vincent Mballa Yene,1 Sang-Yeob Lee,2 Ki-Soo Park,3 Yang Jae Kang,4 Sung Hyo Seo,2 Jun-Il Yoo5 1Department of Bio & Medical Big Data, Gyeongsang National University Hospital, Jinju, South Korea; 2Department of Biomedical Research Institute, Gyeongsang National University Hospital, Jinju, South Korea; 3Department of Preventive Medicine, School of Medicine, Gyeongsang National University, Jinju, South Korea; 4Division of Life Science Department, Gyeongsang National University, Jinju, South Korea; 5Department of Orthopaedic Surgery, Inha University Hospital, Incheon, South KoreaCorrespondence: Jun-Il Yoo, Department of Orthopaedic Surgery, Inha University Hospital, 27 Inhang-ro, Jung-gu, Incheon, 22332, South Korea, Tel +82-32-890-3663, Email furim@hanmail.netObjective: The world population gradually getting older, age-related sarcopenia is becoming more frequent. Known to be highly prevalent in high income countries, relative data in Africa are still scarce. This review aims to estimate the prevalence of sarcopenia in Africa and its characteristics.Study Design and Setting: A literature search in PubMed, Web of Science, Google Scholar, and Scopus was conducted in October 2022. All studies reporting the prevalence of sarcopenia in Africa within 15 years were included, and we did an assessment of bias with Hoy et al’s risk bias assessment tool. The estimated prevalence of sarcopenia was the outcome and we performed secondary analyses by age, gender, and diagnostic criteria. The random effect model was used for the prevalence estimation. The prevalence of sarcopenia and 95% confidence interval (95% CI) were calculated using the inverse-variance method.Results: A total of 17 studies met our eligibility criteria, for a study population of 12,690 participants with 44.3% males and 55.7% females. The overall prevalence of sarcopenia was 25% (95% CI: 19– 30%). The prevalence of sarcopenia among 50 years old and older was 23% (95% CI: 17– 29%). We had a higher prevalence of sarcopenia among males (30%, %95 IC: 20– 39%) than females (29%, %95 IC: 21– 36%). The prevalence of sarcopenia was different depending on the diagnosis criteria used.Conclusion: The prevalence of sarcopenia in Africa was relatively high. However, the fact that the majority of included studies were hospital-based studies shows the necessity of further community-based studies in order to have a more accurate representation of the situation in the general population.Keywords: sarcopenia, prevalence, Africa, meta-analysis

Understanding what contributes to success of community-based participatory research (CBPR) partnerships is essential to ensuring their effectiveness in addressing health disparities and health inequities. Synergy, the concept of accomplishing more together than separately, is central to partnership effectiveness. However, synergy specific to long-standing, equity-focused CBPR partnerships has not been closely examined. To address this, we defined and developed measures of partnership synergy as one dimension of a participatory mixed methods study, Measurement Approaches to Partnership Success (MAPS), to develop a validated instrument to measure success in long-standing CBPR partnerships. Framed by a conceptual model and scoping literature review, we conducted in-depth interviews with a national panel of academic and community experts in CBPR and equity to develop partnership synergy measures. Items were refined through an iterative process, including a three-stage Delphi process, comparison with existing measures, cognitive interviews, and pilot testing. Seven questionnaire items were developed to measure synergy arising from equitable partnerships bringing together diverse partners across power differences to promote equity. Defining and measuring synergy in the context of long-standing partnership success is central to understanding the role of synergy in collaborative approaches to research and action and can strengthen CBPR partnerships to promote healthy communities and advance health equity.

ObjectivesEvaluating children's oral health status and treatment needs is challenging. We aim to build oral health assessment toolkits to predict Children's Oral Health Status Index (COHSI) score and referral for treatment needs (RFTN) of oral health. Parent and Child toolkits consist of short-form survey items (12 for children and 8 for parents) with and without children's demographic information (7 questions) to predict the child's oral health status and need for treatment.MethodsData were collected from 12 dental practices in Los Angeles County from 2015 to 2016. We predicted COHSI score and RFTN using random Bootstrap samples with manually introduced Gaussian noise together with machine learning algorithms, such as Extreme Gradient Boosting and Naive Bayesian algorithms (using R). The toolkits predicted the probability of treatment needs and the COHSI score with percentile (ranking). The performance of the toolkits was evaluated internally and externally by residual mean square error (RMSE), correlation, sensitivity and specificity.ResultsThe toolkits were developed based on survey responses from 545 families with children aged 2 to 17 y. The sensitivity and specificity for predicting RFTN were 93% and 49% respectively with the external data. The correlation(s) between predicted and clinically determined COHSI was 0.88 (and 0.91 for its percentile). The RMSEs of the COHSI toolkit were 4.2 for COHSI (and 1.3 for its percentile).ConclusionsSurvey responses from children and their parents/guardians are predictive for clinical outcomes. The toolkits can be used by oral health programs at baseline among school populations. The toolkits can also be used to quantify differences between pre- and post-dental care program implementation. The toolkits' predicted oral health scores can be used to stratify samples in oral health research.Knowledge transfer statementThis study creates the oral health toolkits that combine self- and proxy- reported short forms with children's demographic characteristics to predict children's oral health and treatment needs using Machine Learning algorithms. The toolkits can be used by oral health programs at baseline among school populations to quantify differences between pre and post dental care program implementation. The toolkits can also be used to stratify samples according to the treatment needs and oral health status.

It is crucial to suppress lithium dendrite formation in lithium metal batteries. Formation of a good solid-electrolyte interphase (SEI) has been considered to be effective in limiting lithium dendrite growth. However, how the SEI may be modified during lithium deposition is hard to resolve due to challenges in in situ investigation of the SEI with fine details. We report an in situ study that uncovers the lithium dendrite suppression mechanism arising from SEI modification by a poly(diallyldimethylammonium chloride) (PDDA) cationic polymer film, using electrochemical liquid cell transmission electron microscopy (TEM). Lithium nanogranules are obtained in the presence of the polymer film. Chemical mapping of the deposits provides remarkable details of the SEI on individual nanogranules. It shows that lithium fluorides are uniformly distributed within the inner SEI layer of individual lithium nanogranules, arising from the instantaneous reaction of the deposited lithium with PF6- ions accumulated by the cationic polymer film, and thus the dendritic growth of lithium is prohibited. The ability to directly measure SEI chemistry at the nanoscale down to the individual nanograins in situ and unveil its correlation with the lithium deposition behavior opens future opportunities to explore unsolved mechanisms in batteries.

Na metal is an attractive anode material for rechargeable Na ion batteries, however, the dendritic growth of Na can cause serious safety issues. Along with modifications of solid-electrolyte interphase (SEI), engineering the electrode has been reported to be effective in suppressing Na dendritic growth, likely by reducing localized current density accumulation. However, fundamental understanding of Na growth at the nanoscale is still limited. Here, we report an in-situ study of Na electrodeposition in electrochemical liquid cells with the electrodes in different surface roughness, e.g., flat or sharp curvature. Real time observation using transmission electron microscopy (TEM) reveals the Na electrodeposition with remarkable details. Relatively large Na grains (in the micrometer scale) are achieved on the flat electrode surface. The local SEI thickness variations impact the growth rate, thus the morphology of individual grains. In contrast, small Na grains (in tens of nanometers) grow explosively on the electrode at the point with sharp curvature. The newly formed Na grains preferentially deposit at the base of existing grains close to the electrode. Further studies using continuum-based computational modeling suggest that the growth mode of an alkali metal (e.g. Na) is strongly influenced by the transport properties of SEI. Our direct observation of Na deposition in combination with the theoretical modeling provides insights for comprehensive understanding of electrode roughness and SEI effects on Na electrochemical deposition.

The sea surface temperature (SST) contrast between the Northern Hemisphere (NH) and Southern Hemisphere (SH) influences the location of the intertropical convergence zone (ITCZ) and the intensity of the monsoon systems. This study examines the contributions of external forcing and unforced internal variability to the interhemispheric SST contrast in HadSST3 and ERSSTv5 observations, and 10 models from phase 5 of the Coupled Model Intercomparison Project (CMIP5) from 1881 to 2012. Using multimodel mean fingerprints, a significant influence of anthropogenic, but not natural, forcing is detected in the interhemispheric SST contrast, with the observed response larger than that of the model mean in ERSSTv5. The forced response consists of asymmetric NH–SH SST cooling from the mid-twentieth century to around 1980, followed by opposite NH–SH SST warming. The remaining best-estimate residual or unforced component is marked by NH–SH SST maxima in the 1930s and mid-1960s, and a rapid NH–SH SST decrease around 1970. Examination of decadal shifts in the observed interhemispheric SST contrast highlights the shift around 1970 as the most prominent from 1881 to 2012. Both NH and SH SST variability contributed to the shift, which appears not to be attributable to external forcings. Most models examined fail to capture such large-magnitude shifts in their control simulations, although some models with high interhemispheric SST variability are able to produce them. Large-magnitude shifts produced by the control simulations feature disparate spatial SST patterns, some of which are consistent with changes typically associated with the Atlantic meridional overturning circulation (AMOC).

Structural colors of 2D gratings are iridescent, color-tunable, and never fade, which renders them appealing for anti-counterfeiting applications. However, for advanced security, it still remains a challenge to completely hide the encrypted color patterns and reveal them on demand. In this work, a water-responsive photonic grating consisting of a micropillar array and a hydrogel overcoat with a similar refractive index, termed “hydrocipher”, is presented. The joint effect of stimuli-reversible refractive-index (mis)match and reconfigurable grating-based diffraction coloration enables a complete encryption of the structural color and rapid decryption. The photonic structure shows a strong iridescence due to the angle-dependent diffraction when the hydrogel overcoat is swollen from water. Upon drying, the micropillars bend and the refractive index contrast disappears, which dramatically lessens the diffraction intensity and renders the surface highly transparent. The dehydrated-to-hydrated state transition can occur within 1 s, enabling fast decryption. The color switching is highly reversible over a prolonged hydration/dehydration cycle, and the dehydrated hydrogel layer protects the delicate micropillar array from external mechanical stress. The creative combination of hydrogel material and the 2D grating structure offers a new and simple strategy for realizing reversible, durable, and fast-response cryptography with potentially broad impact on the anti-counterfeiting technology market.

Research has shown that a multiliteracies pedagogy creates more chance for students to meaningfully read and write to develop their critical perspective on cultural issues. This study experimented such a practice in an EFL college context applying a problem-based approach. Sophomore English majors were engaged in recursive reading and writing processes to relearn Taiwan through orchestrating the collected multimodal resources and creating a multimodal text so as to awaken the target audience's interest. Findings from both corpus and qualitative analyses revealed that (1) students developed language richness in vocabulary use, sentential complexity, and overall expressive fluency through the practice and (2) the interactive and recursive reading-writing processes had a great impact on the design of the project with multimodal materials, which exerted intertextuality among texts and enhanced the quality of the final project. By supporting with a meticulous scaffolding mechanism, such a multiliteracies project indeed encouraged more autonomous learning among students who experienced a full authorship during the process and finally created works that were authentic and unique.

With the fast-paced development of technology in today's society, there has been emerging a shift from paper-based reading to digital online reading. While the benefits of exposure to print have been well-established in previous studies, how online reading may impact individuals' literacy development is largely underexplored. The current study investigated if the amount of English reading experience on the Internet could predict EFL students' lexical knowledge and reading comprehension ability. Participants were ninety-seven Vietnamese undergraduate students who were administered a website checklist and a vocabulary size test. Their reading comprehension scores were also collected as measures of their reading abilities. Descriptive statistics, hierarchical linear regression and structural equation modelling were utilized for data analysis. The results indicated that exposure to L2 online text was a significant predictor of the participants' vocabulary size as well as their reading comprehension growth during a course of two years. Pedagogical implications are discussed.

In this article, we presented a case study in an EFL context that investigated how a magazine was transformed into a digital video involving a target audience. A group of fifty international students responded to a survey questionnaire developed based on the multimodality framework and some were interviewed to express their preferences for the content and format of the video and to evaluate different versions of the video product. The results show that the transforming process consisted of four stages including (1) collecting target audience's preferences for the video content and format, (2) converting the discourse type from textual to oral, (3) creating multimodal materials for the video, and (4) (re-)composing the video. The target audience's responses revealed that effective multimodal orchestration could provide a better engagement and viewing experience for the target audience. The multiliteracies competency of the video creators and viewers was deepened and expanded through the digital transforming processes and interdisciplinary collaboration, which enabled EFL learners to experience, conceptualize, analyze, and apply the learned and new knowledge. With the ultimate goal to cultivate EFL learners to become multimodal literate citizens in the global society, this study advances our understanding of multimodality and yields significant pedagogical implications for multiliteracies education and educational technology in the EFL context.

OBJECTIVE:To examine child and parent reports about the child's oral health and assess the associations of these reports with clinical assessments of oral health status by dental examiners. METHODS:Surveys with 139 items for children and 133 items for parents were administered by Audio Computer-Assisted Self-Interview Software. In addition, the Children's Oral Health Status Index (COHSI) was computed from a dental examination. RESULTS:A total of 334 families with children ages 8 to 17 y participated at 12 dental practices in Los Angeles County. Ordinary least squares regression models were estimated separately for child and parent surveys to identify items uniquely associated with the COHSI. Ten of 139 items the children reported regarding their oral health were associated with the COHSI. The strongest associations were found for child's age, aesthetic factors (straight teeth and pleased with teeth), and cognitive factors related to perception of dental appearance (pleased/happy with the look of the child's mouth, teeth, and jaws). Nine of 133 parent items about the child's oral health were associated with the COHSI in the parent model, notably being a single parent, parent's gender, parent born in the United States, pleased or happy with the look of their child's teeth, and accessing the Internet. CONCLUSION:These child and parent survey items have potential to be used to assess oral health status for groups of children in programs and practices in lieu of dental screenings. KNOWLEDGE TRANSLATION STATEMENT:The paper's results inform the development of a toolkit that can be used by schools, public health agencies, and dental programs to identify children with low oral health status based on parents' and children's responses to survey items across demographic, physical, mental, and social domains. These survey items can be used to inform parents of the desirability of proactively addressing inadequacies in their child's oral health status, enabling them to more rationally address dental needs.

On orbital timescales, higher summer insolation is thought to strengthen the continental monsoon while weakening the maritime monsoon in the Northern hemisphere. Through simulations using the Community Earth System Model, we evaluated the relative influence of perihelion precession and high obliquity in the early Holocene during the Asian summer monsoon. The major finding was that precession dominates the atmospheric heating change over the Tibetan Plateau–Himalayas and Maritime Continent, whereas obliquity is responsible for the heating change over the equatorial Indian Ocean. Thus, precession and obliquity can play contrasting roles in driving the monsoons on orbital timescales. In late spring–early summer, interior Asian continental heating drives the South and East Asian monsoons. The broad-scale monsoonal circulation further expands zonally in July–August, corresponding to the development of summer monsoons in West Africa and the subtropical Western North Pacific (WNP) as well as a sizable increase in convection over the equatorial Indian Ocean. Tropical and oceanic heating becomes crucial in late summer. Over South Asia–Indian Ocean (50°E−110°E), the precession maximum intensifies the monsoonal Hadley cell (heating with an inland/highland origin), which is opposite to the meridional circulation change induced by high obliquity (heating with a tropical origin). The existence of the Tibetan Plateau–Himalayas intensifies the precessional impact. During the late-summer phase of the monsoon season, the effect of obliquity on tropical heating can be substantial. In addition to competing with Asian continental heating, obliquity-enhanced heating over the equatorial Indian Ocean also has a Walker-type circulation impact, resulting in suppression of precession-enhanced heating over the Maritime Continent.

A recent hypothesis postulated that paleoclimate changes to the Southern Hemisphere westerlies were characterized by the modulation of the wintertime South Pacific Split Jet. We explore this hypothesis further through simulating changes to the ocean circulation from Split Jet modulation, contrasting them against changes associated with the wintertime Southern Annular Mode (SAM). Three responses distinguish the Split Jet from the SAM impact on ocean circulation. (i) A weaker Split Jet strengthens the South Pacific subtropical gyre, leading to stronger western boundary currents and warming of the sea surface temperatures (SSTs) surrounding New Zealand. (ii) A positive SAM leads to an increase in the Antarctic Circumpolar Current and specifically Drake Passage throughflow. And (iii) a weaker Split Jet leads to increased formation of Subantartic Mode Water, whereas a positive SAM leads to increased Antarctic Intermediate Water. Both a weaker Split Jet and positive SAM lead to increased Southern Ocean meridional overturning circulation, though it is more pronounced for the latter. However, enhanced ventilation of deep water in both cases increases atmospheric pCO2 by only 1–3 ppm, because the associated cooling and efficient nutrient utilization in the model effectively negates the venting of deep ocean carbon. Both a weaker Split Jet and positive SAM enhance oxygenation of the deep ocean and intermediate waters but diminish oxygenation of the eastern equatorial Pacific. Our results provide guidance to distinguish SAM-like changes from Split Jet-like changes in paleoceanographic records, and we discuss the case of early deglacial transition to Heinrich 1.

The early Holocene climatic optimum is associated with perihelion precession and high obliquity, though most studies emphasize the former over the latter. Asian monsoon proxy records only decisively show the precessional impact. To explore the obliquity effect, four climate simulations are conducted by fixing orbital parameters of present-day (0K), early Holocene (11K), the lowest obliquity (31K), and 11K's precession and eccentricity with 31K's obliquity (11Kp31Ko). We show that high obliquity significantly augments the precessional impact by shifting the Asian monsoon farther north than present. By contrast, the present-day monsoon seasonality can still be identified in the simulations with low obliquity. We argue that the upper tropospheric (South Asian) and lower tropospheric (North Pacific) high-pressure systems are affected by the subtropical atmospheric heating changes responding to obliquity. As a consequence, associated with the changes in meridional gradients of geopotential height and temperature made by the heating, midlatitude transient eddies and monsoon-midlatitude interactions are modulated.

Orbital forcing exerts a strong influence on global monsoon systems, with higher summer insolation leading to stronger summer monsoons in the Northern Hemisphere. However, the associated regional and seasonal changes, particularly the interaction between regional monsoon systems, remain unclear. Simulations using the Community Earth System Model demonstrate that the western North Pacific (WNP) summer monsoon responds to orbital forcing opposite to that of other major Northern Hemisphere monsoon systems. Compared with its current climate state, the simulated WNP monsoon and associated lower-tropospheric trough is absent in the early Holocene when the precession-modulated Northern Hemisphere summer insolation is higher, whereas the summer monsoons in South and East Asia are stronger and shift farther northward. We attribute the weaker WNP monsoon to the stronger diabatic heating of the summer Asian monsoon—in particular over the southern Tibetan Plateau and Maritime Continent—that in turn strengthens the North Pacific subtropical high through atmospheric teleconnections. By contrast, the impact of the midlatitude circulation changes on the WNP monsoon is weaker when the solar insolation is higher. Prior to the present WNP monsoon onset, the upper-tropospheric East Asian jet stream weakens and shifts northward; the monsoon onset is highly affected by the jet-induced high potential vorticity intrusion. In the instance of the extreme perihelion-summer, the WNP monsoon is suppressed despite a stronger midlatitude precursor than present-day, and the midlatitude circulation response to the enhanced South Asian precipitation is considerable. These conditions indicate internal monsoon interactions of an orbital scale, implying a potential mechanistic control of the WNP monsoon.

Hye Yun Jeong,1 So-Young Lee,1 Sang Hoon Kim,2,* Jinkwon Kim3,* 1Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea; 2Division of Cardiology, Department of Internal Medicine CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea; 3Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si, Korea*These authors contributed equally to this workCorrespondence: Jinkwon KimDepartment of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, 363, Dongbaekjukjeon-daero, Giheung-gu, Yongin-si 16995, KoreaTel +82-31-5189-8152Fax +82-31-5189-8208Email antithrombus@gmail.comSang Hoon KimDivision of Cardiology, Department of Internal Medicine, CHA University School of Medicine, CHA Bundang Medical Center, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, KoreaTel +82-31-780-5585Fax +82-31-780-5857Email kimsang978@naver.comPurpose: Despite indubitable evidence for the cardiovascular benefits of statins, there have been concerns that statin discontinuation may cause negative effects known as “statin withdrawal syndrome.” This study aimed to assess the benefit and the withdrawal effect of statins after percutaneous coronary intervention (PCI).Patients and Methods: We conducted a retrospective cohort study on 5218 patients who underwent PCI between 2002 and 2013 using the nationwide health insurance claim data in Korea. Based on the prescription data, the use of statins during follow-up was classified into three risk periods: “statin period” (period with statin cover), “statin withdrawal period” (withdrawal of statin within 30 days), and “no statin period” (no exposure to statin for longer than 30 days). The primary outcome was the composite outcome of myocardial infarction, coronary revascularization, stroke, and all-cause death. We performed multivariate Cox proportional regression analyses which treated the use of statins as a time-dependent variable.Results: During the follow-up period of 3.54 ± 2.91 years (mean ± standard deviation), 1515 (29.0%) patients sustained a primary outcome. Compared with the “no statin period,” the “statin period” was associated with lower risk of the primary outcome (adjusted hazard ratio [HR] 0.72, 95% confidence interval [CI, 0.63– 0.81]). While the “statin withdrawal period” posed a significantly increased risk (adjusted HR 1.87, 95% CI [1.52– 2.29]). With respect to the intensity of statins associated with withdrawal, dose-dependent increased risk was observed for withdrawal of low-, moderate-, and high-intensity statins; adjusted HR [95% CI] were 1.45 [0.74– 2.86], 1.86 [1.49– 2.32], and 2.61 [1.41– 4.81], respectively.Conclusion: After PCI, there was an increased cardiovascular risk during the statin withdrawal period, especially with the use of high-intensity statins. To maximize the beneficial effect and to avoid the withdrawal effect of statins, high-risk patients need to adhere to taking statins without discontinuation.Keywords: statin, percutaneous coronary intervention, statin withdrawal, adherence

Purpose: To elicit perceptions of oral health in children and adolescents as an initial step in the development of oral health item banks for the Patient-Reported Oral Health Outcomes Measurement Information System project. Methods: We conducted focus groups with ethnically, socioeconomically, and geographically diverse youth (8–12, 13–17 years) to identify perceptions of oral health status. We performed content analysis, including a thematic and narrative analysis, to identify important themes. Results: We identified three unique themes that the youth associated with their oral health status: (1) understanding the value of maintaining good oral health over the life course, with respect to longevity and quality of life in the adult years; (2) positive association between maintaining good oral health and interpersonal relationships at school, and dating, for older youth; and (3) knowledge of the benefits of orthodontic treatment to appearance and positive self-image, while holding a strong view as to the discomfort associated with braces. Conclusions: The results provide valuable information about core domains for the oral health item banks to be developed and generated content for new items to be developed and evaluated with cognitive interviews and in a field test.

The last glacial maximum was marked by maximum land ice extent and lowest greenhouse gases concentration during the last ice age. We explore the impact of glacial continental ice sheet topography on the large-scale tropical ocean–atmosphere climate, in particular the tropical Pacific, in an intermediate complexity coupled model. Increasing the thickness of continental ice sheets causes a southward displaced Pacific Intertropical Convergence Zone (ITCZ) and a strengthening (weakening) of northern (southern) hemisphere winter Hadley cell. The equatorial zonal sea surface temperature gradient weakened with an increased continental ice sheets thickness, the reduction being caused by cooling in the western equatorial Pacific and warming in the eastern equatorial Pacific. The evolution of the tropical climate with changing ice thickness has distinct quasi-linear and nonlinear parts. While the linear part is a direct response to the ice topographic changes, the nonlinear part was a result of the tropical thermocline adjustment. Our analysis of a fully-coupled transient deglacial simulation strongly indicates the dominant role of ice sheet topography in determining the deglacial evolution of the simulated Pacific climate. The thickness of continental ice sheet, separate from ice albedo effect, has significant impact on the tropical ocean–atmosphere climate in particular with the meridional displacement in the Pacific ITCZ. The altered circulation states seen in the model may aid understanding of the relationship between tropical and high-latitude climate records in glacial-interglacial cycles.

Anthropogenic water management can change surface energy budgets and the water cycle. In this study, we focused on impacts of Asian low-latitude irrigation on regional and global climates during boreal wintertime. A state-of-the-art Earth system model is used to simulate the land-air interaction processes affected by irrigation and the consequent responses in atmospheric circulation. Perturbed experiments show that wet soil moisture anomalies at low latitudes can reduce the surface temperature on a continental scale through atmospheric feedback. The intensity of prevailing monsoon circulation becomes stronger because of larger land-sea thermal contrast. Furthermore, anomalous upper level convergence over South Asia and midlatitude climatic changes indicate tropical-extratropical teleconnections. The wintertime Aleutian low is deepened and an anomalous warm surface temperature is found in North America. Previous studies have noted this warming but left it unexplained, and we provide plausible mechanisms for these remote impacts coming from the irrigation over Asian low-latitude regions. Key Points Model simulation without considering irrigation underestimates ET over Indo-Gangetic Plain Irrigation at Asian low latitudes has the potential to induce PNA teleconnection Irrigation results in interhemispheric thermal gradient, thereby modifying Pacific subtropical jet

A number of key paleoclimate records in the Southern Hemisphere midlatitudes exhibit climate changes synchronous with abrupt climate changes in the North Atlantic. We advance a hypothesis - argued from consideration of model evidence, observational climate diagnostics, and atmospheric dynamics - that attributes said climate changes in the Southern Hemisphere to a modulation in the strength of the South Pacific Split Jet, a pronounced zonally asymmetric feature of the wintertime Southern Hemisphere westerlies. North Atlantic cooling is associated with a weaker Split Jet, characterized by weaker South Pacific subtropical and subpolar jets and a strengthened midlatitude jet. It leads to climate impacts over the South Pacific sector that coincides with regions with observed paleoclimate changes timed to the North Atlantic. These circulation changes are envisioned to operate in addition to the climate impacts resulting from the oceanic bipolar seesaw.A proposed global atmospheric teleconnection links North Atlantic cooling to the weakening of the Split Jet. North Atlantic cooling induces a southward shift of the marine Intertropical Convergence Zone and weakening of the Asian monsoon. The resulting Hadley circulation change weakens the wintertime South Pacific subtropical jet, and which in turn leads to a weaker South Pacific Split Jet. A weaker Split Jet leads to a southward shift of the zero wind-stress curl line, implying a shift in the same sense for the South Pacific subtropical front. Over land, it leads to winter warming over New Zealand, winter cooling over subtropical South America, drying over Western Patagonia, and winter warming and wetting of southernmost Patagonia. Our hypothesis also predicts reduced storminess over West Antarctica. Similar changes but of opposite sign occur in the Northern Hemisphere, where a stronger wintertime North Pacific subtropical jet increases precipitation over the Western United States.

Rihwa Choi,1,2 Hye In Woo,1 Hyung-Doo Park,1 Soo-Youn Lee1,31Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 2Department of Laboratory Medicine, Green Cross Laboratories, Yongin, Gyeonggi, Republic of Korea; 3Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaPurpose: The current status of therapeutic drug monitoring (TDM) assay utilization by clinical laboratories in South Korea remains little known. We investigated the TDM status of five antibiotics known for nephrotoxicity (vancomycin, amikacin, gentamicin, tobramycin, and teicoplanin) for the improvement of TDM in South Korea among patients with infectious diseases using a cross-sectional nationwide survey.Patients and methods: We developed an online questionnaire and collected responses using a user-friendly web-based platform. The survey included questions about laboratory characteristics, implementation and operation of drug assays, implementation and operation of TDM consulting services, patient needs, and barriers to providing better TDM service including expectations and concerns about other platform-based drug assays.Results: Among a total of 235 clinical laboratories, 112 (47.7%) responded, and 62 of the responding laboratories (55.4%) possessed drug assay facilities. Only 41.2% to 58.1% of respondents were providing TDM consulting services for each antibiotic. Respondents indicated that there are unmet needs regarding drug assays and TDM consultation as well as barriers to TDM utilization including high operating costs, lack of knowledge about TDM, lack of user-friendly software, lack of medical and laboratory information systems that can access patient information critical for TDM dose calculation, and reimbursement issues.Conclusion: This study, the first nationwide survey addressing these questions, showed that there are barriers against the utilization of TDM in South Korea. These barriers may be addressed by improving drug assays and TDM consulting services with the goals of new analytical method development, better interpretation of results, consultation services, and quality control.Keywords: questionnaire, TDM service, TDM consulting, point-of-care

Min-Hee Yi,1 Juhee Shin,2,3 Nara Shin,2,3 Yuhua Yin,2,4 Sun Yeul Lee,4 Cuk-Seong Kim,3,5 Sang Ryong Kim,6 Enji Zhang,7 Dong Woon Kim2,31Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA; 2Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon 301-747, Republic of Korea; 3Department of Medical Science, Chungnam National University School of Medicine, Daejeon 301-747, Republic of Korea; 4Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, Daejeon 301-747, South Korea; 5Department of Physiology, Chungnam National University School of Medicine, Daejeon 301-747, Republic of Korea; 6School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Institute of Life Science & Biotechnology, Brain Science and Engineering Institute, Kyungpook National University, Daegu 41566, Republic of Korea; 7Department of Anesthesia Medicine, Yanbian University Hospital, Yanbian 133000, People’s Republic of ChinaBackground: Mitophagy is the selective engulfment of mitochondria by autophagosomes and the subsequent mitochondrial catabolism by lysosomes. Evidence has suggested an important role for mitochondrial dynamics and mitophagic flux in the development of many different neurodegenerative diseases.Objectives: The potential role of the mechanism underlying mitochondrial dynamics and mitophagic flux as it may relate to neuropathic pain is not well understood. This is a disease that largely remains an area of mechanistic uncertainty. PINK1 is a PTEN-induced mitochondrial kinase that can be selectively activated under mitochondrial stress conditions and lead to the induction of mitophagy.Materials and methods: A neuropathic pain rat model was established via spinal nerve ligation (SNL) and nociception was assayed via the von Frey filament method. Increased expression of PINK1 and the mechanism of mitophagy was detected in GABAergic interneurons of dorsal horn neurons of mice that underwent L5 SNL in comparison to control mice counterparts (n=8, P

Juwhan Choi, Jee Youn Oh, Young Seok Lee, Gyu Young Hur, Sung Yong Lee, Jae Jeong Shim, Kyung Ho Kang, Kyung Hoon MinDivision of Respiratory, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of KoreaIntroduction: The use of antibiotics is based on the clinician’s experience and judgment, and antibiotics may often be overused in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Eosinophils have been studied as biomarkers of bacterial infection and prognostic factors in chronic obstructive pulmonary disease and AECOPD. Thus, the purpose of this study was to determine whether eosinophils could be used to determine bacterial infection in AECOPD events.Methods: We retrospectively analyzed the medical records of patients admitted to Korea University Guro Hospital for AECOPD between January 2011 and May 2017. Data pertaining to baseline characteristics, results of previous pulmonary function tests, treatment information during the admission period, and history of pulmonary treatment were collected before admission.Results: A total of 736 AECOPD events were eligible for inclusion and were divided into two groups based on the eosinophil count: those involving eosinophil counts of less than 2% (546 events) and those involving counts of 2% or more (190 events). In univariate analysis, the only bacterial pathogen identification events and bacterial-viral pathogen co-identification events were significantly more frequent in the group with eosinophil counts of less than 2% (P=0.010 and P=0.001, respectively). In logistic regression analysis, the rates of only bacterial pathogen identification [odds ratios =1.744; 95% confidence interval, 1.107–2.749; P=0.017] and bacterial-viral pathogen co-identification [odds ratios=2.075; 95% confidence interval, 1.081–3.984; P=0.028] were higher in the group with eosinophil count less than 2%.Conclusion: In conclusion, eosinophil counts of less than 2% are potential indicators of a bacterial infection in AECOPD events. Eosinophils could thus serve as a reference for the use of antibiotics in AECOPD treatment.Keywords: chronic obstructive pulmonary disease, acute exacerbation, bacterial infection, eosinophil

Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Jae Jeong Shim1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Republic of Korea Purpose: Improvement in the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO), and identification of biomarkers for phenotype recognition will encourage good patient care by providing optimal therapy. We investigated club cell secretory protein (CC-16), a protective and anti-inflammatory mediator, as a new candidate biomarker for diagnosing ACO.Patients and methods: We performed a multicenter cohort study. A total of 107 patients were divided into three groups – asthma, COPD, and ACO – according to the Spanish guidelines algorithm, and enrolled into the study. Serum CC-16 levels were measured using commercial ELISA kits.Results: Serum CC-16 levels were the lowest in patients with ACO. Low serum CC-16 levels were a significant marker for the ACO even after adjustment for age, sex, and smoking intensity. Serum CC-16 levels were positively correlated with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25%–75% of FVC, FEV1/FVC, vital capacity, and diffusing capacity of the lung for carbon monoxide, and were negatively correlated with smoking amount (pack-years), bronchodilator response, fractional residual capacity, residual volume, and number of exacerbations per year. FEV1 and serum CC-16 levels were significantly lower in patients with frequent exacerbations.Conclusion: Serum CC-16 has the potential to be a biomarker for ACO diagnosis and also treat frequent exacerbations in patients with chronic inflammatory airway diseases. Keywords: asthma, COPD, ACO, exacerbation, club cell secretory protein-16, smoking

Yeon-Mok Oh,1,* Keu Sung Lee,2,* Yoonki Hong,3,* Sung Chul Hwang,2 Jae Yeol Kim,4 Deog Keom Kim,5 Kwang Ha Yoo,6 Ji-Hyun Lee,7 Tae-Hyung Kim,8 Seong Yong Lim,9 Chin Kook Rhee,10 Hyoung Kyu Yoon,11 Sang Yeub Lee,12 Yong Bum Park,13 Jin Hee Jung,14 Woo Jin Kim,3 Sang-Do Lee,1 Joo Hun Park2 1Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, Korea; 3Department of Internal Medicine and Environmental Health Center, Kangwon National University, Kangwon National University Hospital, Chuncheon, Korea; 4Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea; 6Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea; 7Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea; 8Division of Pulmonology, Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea; 9Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea; 10Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, Catholic University of Korea, Seoul, Korea; 11Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University Anam Hospital, Seoul, Korea; 12Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University Anam Hospital, Seoul, Korea; 13Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea; 14Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea *These authors contributed equally to this work Background: High blood eosinophil count is a predictive biomarker for response to inhaled corticosteroids in prevention of acute exacerbation of COPD, and low blood eosinophil count is associated with pneumonia risk in COPD patients taking inhaled corticosteroids. However, the prognostic role of blood eosinophil count remains underexplored. Therefore, we investigated the associated factors and mortality based on blood eosinophil count in COPD.Methods: Patients with COPD were recruited from 16 hospitals of the Korean Obstructive Lung Disease cohort (n=395) and COPD in Dusty Area cohort (n=234) of Kangwon University Hospital. The two merged cohorts were divided based on blood eosinophil count into three groups: high (≥5%), middle (2%–5%), and low (

Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Jae Jeong Shim1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, Republic of Korea Purpose: Tuberculosis-associated COPD (T-COPD) has clinical characteristics similar to those of smoking-associated COPD (S-COPD), such as dyspnea, sputum production, and acute exacerbation (AE). However, the degree of systemic inflammation and prognosis might be different because of difference in the pathophysiology. The aim of this study was to compare the lung function, systemic inflammatory markers, and their impacts on AE in patients with S-COPD and T-COPD.Patients and methods: We performed a multicenter cross-sectional cohort study. We evaluated clinical characteristics, pulmonary function tests, levels of inflammatory markers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IL-6, and the association of these markers with AE in patients with S-COPD and T-COPD.Results: Patients with T-COPD included more women and had lesser smoking history and higher St George Respiratory Questionnaire score than did patients with S-COPD. Although the FEV1 of both groups was similar, FVC, vital capacity, total lung capacity, and functional residual capacity were lower in patients with T-COPD than in those with S-COPD. CRP, ESR, and IL-6 levels were significantly higher in patients with T-COPD compared to patients with S-COPD. According to a multivariate logistic regression analysis, FEV1 was a significant factor predicting AE in S-COPD, and IL-6 was a significant factor predicting AE in T-COPD. IL-6 level greater than 2.04 pg/mL was a cutoff for predicting exacerbation of T-COPD (sensitivity 84.8%, specificity 59.3%, P

Juwhan Choi, Jee Youn Oh, Young Seok Lee, Gyu Young Hur, Sung Yong Lee, Jae Jeong Shim, Kyung Ho Kang, Kyung Hoon Min Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea Introduction: Acute exacerbation of COPD (AECOPD) leads to rapid deterioration of pulmonary function and quality of life. It is unclear whether the prognosis for AECOPD differs depending on the bacterium or virus identified. The purpose of this study is to determine whether readmission of patients with severe AECOPD varies according to the bacterium or virus identified.Methods: We performed a retrospective review of medical records of 704 severe AECOPD events at Korea University Guro Hospital from January 2011 to May 2017. We divided events into two groups, one in which patients were readmitted within 30 days after discharge and the other in which there was no readmission.Results: Of the 704 events, 65 were followed by readmission within 30 days. Before propensity score matching, the readmission group showed a higher rate of bacterial identification with no viral identification and a higher rate of identification with the Pseudomonas aeruginosa (P=0.003 and P=0.007, respectively). Using propensity score matching, the readmission group still showed a higher P. aeruginosa identification rate (P=0.030), but there was no significant difference in the rate of bacterial identification, with no viral identification (P=0.210). In multivariate analysis, the readmission group showed a higher P. aeruginosa identification rate than the no-readmission group (odds ratio, 4.749; 95% confidence interval, 1.296–17.041; P=0.019).Conclusion: P. aeruginosa identification is associated with a higher readmission rate in AECOPD patients. Keywords: acute exacerbation of COPD, Pseudomonas aeruginosa, readmission, bacterium, virus

Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Adnan Khan,4 Jinhyuk Na,4 Youngja H Park,4 Jae Jeong Shim1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, Republic of Korea; 4Metabolomics Laboratory, College of Pharmacy, Korea University, Sejong, Republic of Korea Purpose: Asthma–COPD overlap (ACO) is heterogeneous in nature and requires a unified diagnostic approach. We investigated the urinary levels of L-histidine, a precursor of histamine related to inflammatory responses, as a new candidate biomarker for diagnosing this condition.Patients and methods: We performed a prospective multicenter cohort study with retrospective analysis of 107 patients, who were divided into three groups: asthma, COPD, and ACO, according to the Spanish guidelines algorithm. Urinary L-histidine levels were measured using liquid chromatography-mass spectrometry. High-resolution metabolomic analysis, coupled with liquid chromatography-mass spectrometry and followed by multivariate statistical analysis, was performed on urine samples to discriminate between the metabolic profiles of the groups.Results: Urinary L-histidine levels were significantly higher in patients with ACO than in those with asthma or COPD, but the subgroups of ACO, classified according to disease origin, did not differ significantly. High urinary L-histidine level was a significant factor for the diagnosis of ACO even after adjusting for age, sex, and smoking amount. Among patients with airflow obstruction, the urinary L-histidine levels were elevated in patients with a documented history of asthma before the age of 40 years or bronchodilator responsiveness ≥400 mL; bronchodilator responsiveness ≥200 mL of forced expiratory volume in 1 second and exceeding baseline values by 12% on two or more visits; blood eosinophil count ≥300 cells·mm−3; and frequent exacerbations (P < 0.05).Conclusion: Urinary l-histidine could be a potential biomarker for ACO, regardless of the diversity of diagnostic definitions used. Keywords: asthma, COPD, ACO, urinary L-histidine, metabolomics, inhaled corticosteroid

Sun Hye Shin,1 Danbee Kang,2 Juhee Cho,2 Haseong Chang,3 Min Sun Kim,3 Su Yeon Lee,3 Hyun Lee,1 Hojoong Kim,1 Duk-Kyung Kim,3 Eun Kyoung Kim,3,* Hye Yun Park1,* 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 2Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea; 3Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea *These authors contributed equally to this work Background: COPD is a well-known risk factor for venous thromboembolism (VTE) development. However, recent data showed that it was not associated with VTE recurrence risk, which excluded cancer patients. This study investigated the association of airflow limitation and VTE recurrence in cancer patients with pulmonary embolism (PE). Methods: This is a retrospective cohort study of cancer patients with newly diagnosed PE at a university hospital. PE was confirmed using contrast-enhanced computed tomography scan. Airflow limitation was defined as pre-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC)

Weon Sup Lee,1 Sang Ryeol Shim,1 Seon Young Lee,1 Jin San Yoo,1 Sung Kweon Cho2 1PharmAbcine, Inc., Daejeon, Republic of Korea; 2Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea Background: VEGF is a highly selective mitogen that serves as the central regulator of tumor angiogenesis by mediating endothelial proliferation, permeability, and survival. Tanibirumab (TTAC-0001) is a fully human IgG1 monoclonal antibody derived from a fully human naïve single-chain variable fragment (ScFv) phage library that was developed to inhibit the effects of VEGF in the treatment of solid tumors, especially those of the brain. Methods: In the present study, we conducted intravenous pharmacokinetic studies of TTAC-0001 in mice, rats, and cynomolgus monkeys. At the doses studied (3 mg/kg, 10 mg/kg, 30 mg/kg), TTAC-0001 exhibited dose proportionality in mice and monkeys. At a dose of ~10 mg/kg, the clearance of TTAC-0001 from serum was 0.017 mL/h in mice, 0.35 mL/h in rats, and 2.19 mL/h in cynomolgus monkeys, and the terminal half-life ranged from 20–30 h among the three species. Pharmacokinetic data in mice, rats, and cynomolgus monkeys were used to predict the pharmacokinetics of TTAC-0001 in humans using allometric scaling. The predicted serum clearance of TTAC-0001 in humans was 102.45 mL/h and the terminal half-life was 27.52 h. Results: The maximum life span-corrected clearance value was 72.92 mL/h. The observed clearance in humans was more similar to the predicted scaled clearance. Conclusion: We investigated the pharmacokinetics of TTAC-0001 in mice, rats, and cynomolgus monkeys after intravenous administration. At the doses studied, TTAC-0001 exhibited dose proportionality in mice and monkeys. The scaled pharmacokinetics of TTAC-0001 reported here was useful for designing first-in-human studies. Allometric scaling in the therapeutic antibody is feasible. Keywords: VEGF2, tanibirumab, pharmacokinetics, allometry, clearance, biodistribution

Juwhan Choi, Jee Youn Oh, Young Seok Lee, Kyung Hoon Min, Gyu Young Hur, Sung Yong Lee, Kyung Ho Kang, Jae Jeong Shim Division of Respiratory, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea Introduction: Particulate matter and air pollution in Korea are becoming worse. There is a lack of research regarding the impact of particulate matter on patients with COPD. Therefore, the purpose of this study was to investigate the effects of various air pollution factors, including particulate matter, on the incidence rate of severe acute exacerbations of COPD (AECOPD) events. Methods: We analyzed the relationship between air pollutants and AECOPD events that required hospitalization at Guro Hospital in Korea from January 1, 2015 to May 31, 2017. We used general linear models with Poisson distribution and log-transformation to obtain adjusted relative risk (RR). We conducted further analysis through the Comprehensive Air-quality Index (CAI) that is used in Korea. Results: Among various other air pollutants, particulate matter was identified as a major source of air pollution in Korea. When the CAI score was over 50, the incidence rate of severe AECOPD events was statistically significantly higher [RR 1.612, 95% CI, 1.065–2.440, P=0.024]. Additionally, the particulate matter levels 3 days before hospitalization were statistically significant [RR 1.003, 95% CI, 1.001–1.005, P=0.006]. Conclusion: Particulate matter and air pollution increase the incidence rate of severe AECOPD events. COPD patients should be cautioned against outdoor activities when particulate matter levels are high. Keywords: air pollution, particulate matter, air quality index, acute exacerbation, COPD

Jeong Uk Lim,1 Kyungjoo Kim,2 Sang Hyun Kim,3 Myung Goo Lee,4 Sang Yeub Lee,5 Kwang Ha Yoo,6 Sang Haak Lee,1 Ki-Suck Jung,7 Chin Kook Rhee,2 Yong Il Hwang7 1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, St Paul’s Hospital, 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 3Big Data Division, Health Insurance Review and Assessment Service, Wonju, 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, 5Department of Internal Medicine, Korea University, Anam Hospital, 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, Republic of Korea Introduction: Patients with mild to moderate chronic obstructive pulmonary disease (COPD) are underdiagnosed and undertreated due to the asymptomatic nature of the disease. Previous studies on patients with mild COPD have focused on symptomatic patients. Therefore, in this study, we evaluated the treatment status of patients with early COPD in Korea.Materials and methods: We compared hospital visits, medical costs per person, and COPD medication use by patients with COPD screened from the general population and COPD cohort patients. Patients with COPD aged ≥40 years with the value of forced expiratory volume in 1 s (FEV1) ≥60% were selected from the 2007 to 2012 Korea National Health and Nutrition Examination Survey (KNHANES) data. Data including the number of outpatient clinic visits, admission to hospitals, COPD-related medications, and medical costs were obtained from the Health Insurance Review and Assessment Service and were compared with the data of patients with COPD with FEV1 ≥60% from the Korean COPD Subtype Study (KOCOSS) cohort.Results: Based on EuroQol 5-dimension questionnaire index scores of 0.9±0.14, we found that patients with COPD from the KNHANES group showed few symptoms compared to those from the KOCOSS cohort. In 2007, among the patients with COPD with an FEV1 value of ≥60%, only 3.6% from the KNHANES group and 30% from the KOCOSS cohort visited medical facilities. Total medical cost per person per year increased from 264.37±663.41 US Dollars (USD) in 2007 to 797.00±2,724.21 USD in 2012 for the KNHANES group. In 2012, only 20.7% of the patients from KNHANES database received long-acting muscarinic agonists (LAMA), whereas 78.7% of the patients from KOCOSS database received LAMA.Conclusion: Medical resource utilization and medical costs per person for patients with early COPD in Korea increased. However, asymptomatic patients with COPD represented by the KNHANES group do not receive adequate long-term treatment compared to relatively symptomatic patients, and require more clinical attention from physicians. Keywords: early COPD, medical cost, medical utilization

This article reports on a one-year EFL extensive reading programme involving blogging, and documents its effects on learners' literacy growth evaluated by their writing fluency (for example the number of words) and depth of reading (for example ideas reflected in the posts). While a great deal of research suggests that reading is the underlying cause of literacy growth, it is important to consider the role of blogging, a crucial mediation for reading in this programme. Results reporting the contribution and effect of blogging showed that readers wrote more in the second semester than the first and expressed more well-developed ideas as the extensive reading programme progressed. Most important of all, they had the chance to enjoy reading and writing for "real" purposes, have their own voices heard, and gain support in this "literacy club". Finally, most considered blogging useful in helping them read and write better.

Suh-Young Lee,1,* Hye Yun Park,2,* Eun Kyung Kim,3 Seong Yong Lim,4 Chin Kook Rhee,5 Yong Il Hwang,6 Yeon-Mok Oh,7 Sang Do Lee,7 Yong Bum Park1 On behalf of the KOLD Study Group 1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, 2Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 3Department of Internal Medicine, Bundang CHA Medical Center, CHA University College of Medicine, Seongnam, 4Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 5Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Gyeonggido, 7Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Ulsan, Republic of Korea *These authors contributed equally to this work Background: The efficacy of inhaled corticosteroids (ICSs)/long-acting beta2-agonist (LABA) treatment in patients with asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) compared to patients with COPD alone has rarely been examined. This study aimed to evaluate the clinical efficacy for the improvement of lung function after ICS/LABA treatment in patients with ACOS compared to COPD alone patients. Methods: Patients with stable COPD were selected from the Korean Obstructive Lung Disease (KOLD) cohort. Subjects began a 3-month ICS/LABA treatment after a washout period. ACOS was defined when the patients had 1) a personal history of asthma, irrespective of age, and wheezing in the last 12 months in a self-reported survey and 2) a positive bronchodilator response. Results: Among 152 eligible COPD patients, 45 (29.6%) fulfilled the criteria for ACOS. After a 3-month treatment with ICS/LABA, the increase in forced expiratory volume in 1 second (FEV1) was significantly greater in ACOS patients than in those with COPD alone (240.2±33.5 vs 124.6±19.8 mL, P=0.002). This increase in FEV1 persisted even after adjustment for confounding factors (adjusted P=0.002). According to severity of baseline FEV1, the ACOS group showed a significantly greater increase in FEV1 than the COPD-alone group in patients with mild-to-moderate airflow limitation (223.2±42.9 vs 84.6±25.3 mL, P=0.005), whereas there was no statistically significant difference in patients with severe to very severe airflow limitation. Conclusion: This study provides clinical evidence that ACOS patients with mild-to-moderate airflow limitation showed a greater response in lung function after 3 months of ICS/LABA combination treatment. Keywords: pulmonary disease, chronic obstructive, asthma, respiratory function tests

Ching-Han Lin,1,* Shang-Yu Lee,2,* Chun-Cheng Zhang,3 Ye-Fong Du,1 Hao-Chang Hung,1 Hung-Tsung Wu,4 Horng-Yih Ou1 1Department of Internal Medicine, Division of Endocrinology and Metabolism, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 2Department of Internal Medicine, Division of Endocrinology and Metabolism, Chi-Mei Medical Center, 3Department of Internal Medicine, Division of Holistic Care, Chi-Mei Medical Center, 4Research Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan, Taiwan *These authors contributed equally to this work Abstract: Fenretinide is a novel anticancer agent reported to exhibit anti-invasive and antimetastatic activities. It has also been shown to improve obesity and diabetes, although the effects of fenretinide on hypertension are still unknown, and the detailed mechanisms remain unclear. In this study, we have shown that treatment with lipopolysaccharide (LPS) decreased the expression of peroxisome proliferator-activated receptor γ (PPARγ) in RAW264.7 macrophages, and pretreatment with fenretinide reversed the effect of LPS on PPARγ expression. In addition, LPS-induced pro-inflammatory cytokine production, including tumor necrosis factor-α, interleukin 6, and monocyte chemoattractant protein 1 were dose-dependently reversed by fenretinide, and the effects of fenretinide on LPS-induced pro-inflammatory cytokine production were blocked by treatment with PPARγ antagonist. Moreover, fenretinide decreased LPS-induced inducible nitric oxide synthase expression and nitrogen oxide production. These effects were blocked by the pretreatment with PPARγ antagonist in a dose-dependent manner, indicating fenretinide activated PPARγ to exert anti-inflammation activity. In view of the role of inflammation in hypertension and the anti-inflammatory action of fenretinide, we found that administration of fenretinide in spontaneously hypertensive rats significantly decreased blood pressure. Taken together, these results indicate that fenretinide might be a potent antihypertensive agent that works by suppressing inflammation via activating PPARγ. Keywords: fenretinide, hypertension, inflammation, macrophage, peroxisome proliferator-activated receptor γ