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Background: Despite the proven effectiveness of oral antivirals against severe acute respiratory syndrome coronavirus 2 in randomized trials, their clinical reevaluation is vital in the context of widespread immunity and milder prevalent variants. This study aimed to assess the effectiveness of oral antivirals for coronavirus disease 2019 (COVID-19)., Methods: This retrospective cohort study utilized a target trial emulation framework to analyze patients with COVID-19 aged 60+ from January to December 2022. Data were obtained from the Korea Disease Control and Prevention Agency and Health Insurance Review and Assessment Service. The study involved 957,036 patients treated with nirmatrelvir/ritonavir and 243,360 treated with molnupiravir, each compared with the matched control groups. Primary outcome was progression to critical COVID-19 requiring advanced respiratory support. Secondary outcomes included progression to severe COVID-19, need for supplemental oxygen, and death within 30 days of the onset of COVID-19. Number needed to treat (NNT) derived from the absolute risk reduction., Results: Nirmatrelvir/ritonavir was significantly associated with a reduced risk of severe (adjusted odds ratio [aOR], 0.823; 95% confidence interval [CI], 0.803-0.843), critical (aOR, 0.560; 95% CI, 0.503-0.624), and fatal COVID-19 (aOR, 0.694; 95% CI, 0.647-0.744). Similarly, molnupiravir reduced the risk of severe (aOR, 0.895; 95% CI, 0.856-0.937), critical (aOR, 0.672; 95% CI, 0.559-0.807), and fatal cases (aOR, 0.679; 95% CI, 0.592-0.779). NNTs for nirmatrelvir/ritonavir were 203.71 (severe), 1,230.12 (critical), and 691.50 (death); for molnupiravir, they were 352.70 (severe), 1,398.62 (critical), and 862.98 (death). Higher effectiveness was associated with older adults, unvaccinated individuals, and the late pandemic phase., Conclusion: Nirmatrelvir/ritonavir and molnupiravir are effective in preventing progression to severe disease in elderly adults with COVID-19., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

There had been concerns about the acute complications during or shortly after coronavirus disease 2019 (COVID-19) treatment with nirmatrelvir/ritonavir (NMVr) and molnupiravir (MOL). This study aimed to compare the risks of selected acute safety events in patients treated with or without NMVr or MOL using the COVID-19 oral treatment safety assessment data, constructed through the linkage of nationwide databases: National COVID-19 registry, Real-time Prescription Surveillance, and National Health Insurance data. We identified all adults diagnosed with COVID-19 between January and November 2022, and then constructed two cohorts by matching up to four patients without antiviral treatment records to NMVr or MOL users using propensity score matching. Outcomes of interest were incident-selected cardiac (i.e., atrial fibrillation, other arrhythmia, bradycardia), neurological (i.e., seizure, neuropathy, encephalomyelitis), and miscellaneous (i.e., acute pancreatitis, acute liver injury, dysgeusia) events. A total of 739,935 NMVr users were matched with 2,951,690 comparators and 150,431 MOL users with 759,521 comparators. NMVr users were at lower risk for developing selected cardiac events (hazard ratio 0.74 [95% CI 0.65-0.87] for atrial fibrillation, 0.81 [0.65-0.99] for other arrhythmia, and 0.82 [0.70-0.96] for bradycardia) and dysgeusia (0.58 [0.45-0.74]). For MOL users, the risk was lower for atrial fibrillation (0.72 [0.53-0.96]) and dysgeusia (0.34 [0.18-0.65]). Overall, there were no increased risks of acute complications during and shortly after treatment with oral COVID-19 antivirals. Rather, the findings underscore their effectiveness in attenuating the risk of potential acute sequelae of COVID-19., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Asthma is a widespread pediatric chronic disease, but there is limited understanding of its impact on participation (other than physical activity) and the conceptualization of participation. We conducted a scoping review to explore the evidence on the relationship between pediatric asthma and participation in several domains of occupation outlined in the Occupational Therapy Practice Framework 4th Edition. A structured literature search was implemented in PubMed/MEDLINE, Elsevier EMBASE, CINAHL, SCOPUS, Clarivate Web of Science Core Collection, and APA PsycINFO. Data were extracted by occupational domain and analyzed using a stoplight categorization. Of the 3444 identified articles, 10 met inclusion criteria, five of which were categorized as green (addressing specific occupational activities). No article explicitly defined participation. Asthma's influence on nonphysical activity occupations remains unclear. Future research must clarify both the meaning and measures that best capture participation, and further explore the relationship between asthma and participation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Occupational therapists address physical environments, which can improve outcomes for youth with asthma, a prevalent chronic childhood illness. This study examines pediatric occupational therapists' perceptions of their role supporting youth with asthma, perceived usability of an occupational therapy asthma home assessment, and the impact of asthma on participation. A cross-sectional exploratory survey of 171 participants found that despite lack of tools for asthma trigger reduction assessment and intervention, therapists believe it is within their scope of practice and that they would benefit from an occupational therapy-based asthma tool. Occupational therapists should be members of multidisciplinary asthma teams, and assess and address environmental triggers.

An Electron Cyclotron Emission (ECE) modeling code has been developed to model ECE radiation with an arbitrary electron momentum distribution, a small oblique angle, both ordinary (O-mode) and extraordinary polarizations (X-mode), and multiple cyclotron frequency harmonics. The emission and absorption coefficients are calculated using the Poynting theorem from the cold plasma dispersion and the electron-microwave interaction from the full anti-Hermitian tensor. The modeling shows several ECE radiation signatures that can be used to diagnose the population of suprathermal electrons in a tokamak. First, in an n = 2 X-mode (X2) optically thick plasma and oblique ECE view, the modeling shows that only suprathermal electrons, which reside in a finite region of the velocity and space domains, can effectively generate cyclotron emissions to the ECE receiver. The code also finds that the O1 mode is sensitive to suprathermal electrons of both a high v⊥ and v‖, while the X2 mode is dominantly sensitive to suprathermal electrons of a high v⊥. The modeling shows that an oblique ECE system with both X/O polarization and a broad frequency coverage can be used to effectively yield information of the suprathermal electron population in a tokamak., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: This study was conducted to assess the efficacy of nirmatrelvir/ritonavir treatment in patients with coronavirus disease 2019 (COVID-19), particularly those aged 60 years and older. Using real-world data, the period during which the BN.1 Omicron variant was dominant was compared to the period dominated by the BA.5 variant., Methods: In this retrospective cohort study, data were collected regarding 2,665,281 patients infected with severe acute respiratory syndrome coronavirus 2 between July 24, 2022, and March 31, 2023. Propensity score matching was utilized to match patients who received nirmatrelvir/ ritonavir in a 1:4 ratio between BN.1 and BA.5 variant groups. Multivariable logistic regression analysis was employed to assess the effects of nirmatrelvir/ritonavir within these groups., Results: Compared to the prior period, the efficacy of nirmatrelvir/ritonavir did not significantly differ during the interval of Omicron BN.1 variant dominance in the Republic of Korea. Among patients treated with nirmatrelvir/ritonavir, a significantly lower risk of mortality was observed in the BN.1 group (odds ratio [OR], 0.698; 95% confidence interval [CI], 0.557-0.875) compared to the BA.5 group. However, this treatment did not significantly reduce the risk of severe or critical illness, including death, for those in the BN.1 group (OR, 0.856; 95% CI, 0.728-1.007)., Conclusion: Nirmatrelvir/ritonavir has maintained its effectiveness against COVID-19, even with the emergence of the BN.1 Omicron subvariant. Consequently, we strongly recommend the administration of nirmatrelvir/ritonavir to patients exhibiting COVID-19-related symptoms, irrespective of the dominant Omicron variant or their vaccination status, to mitigate disease severity and decrease the risk of mortality.

Background: COVID-19 remains an ongoing public health crisis. Black Americans remain underrepresented among those vaccinated and overrepresented in both COVID-19 morbidity and mortality. Medical misinformation, specifically related to COVID-19, has exacerbated the impact of the disease in Black American communities. Communication tools and strategies to build relationships and disseminate credible and trustworthy diagnostic and preventative health information are necessary to improve outcomes and equity for historically oppressed populations., Objective: As the initial phase of a larger mixed methods project to develop, pilot, and evaluate a mobile health (mHealth) intervention among a population at high risk for COVID-19 and cardiovascular comorbidities, this study sought to explore COVID-19 information behavior among Black Americans. Specifically, this study examined (1) preferences for COVID-19 education via mHealth, (2) barriers and facilitators to COVID-19 education and diagnostic testing and routine care for associated cardiovascular and respiratory comorbidities in the local community, and (3) key content for inclusion in a COVID-19 mHealth app., Methods: This qualitative study used principles of community-based participatory research and information systems research to conduct 7 focus groups across 3 sites. Focus groups were audio recorded and transcribed for thematic analysis using an abductive approach., Results: The study sample included 54 individuals across sites with a mean age of 50.24 (SD 11.76; range 20-71) years. Participants were primarily female (n=42, 78%) and Black (n=54, 100%) with varied education levels. Over half (n=29, 54%) of the participants were employed full-time, and nearly three-fourths (n=40, 74%) had household incomes

Background: The MOVe-OUT (efficacy and safety of molnupiravir [MK-4482] in non-hospitalized adult participants with COVID-19 [MK-4482-002]) trial reported that the administration of molnupiravir in unvaccinated patients with coronavirus disease 2019 (COVID-19) before the Omicron epidemic showed a preventive effect of 31% against hospitalization and death. However, studies on the preventive effect of molnupiravir against progression to severe disease and death in patients with COVID-19 during the Omicron epidemic are limited. This study aimed to evaluate the preventive effect of molnupiravir against severe/critical illness or death and death in Korean patients with COVID-19 who were vaccinated mostly during the Omicron epidemic., Materials and Methods: This study used large-scale retrospective cohort data to select patients with COVID-19 who were either treated or not treated with molnupiravir, between August 2022 and March 2023, at a ratio of 1 : 4 using the propensity score matching method. In total, 762,768 patients comprised the non- administered group, and 190,692 patients comprised the molnupiravir-administered group. The preventive effect of molnupiravir against severe/critical illness or death and death was analyzed using logistic regression analysis., Results: The preventive effect of molnupiravir against severe/critical illness or death and death, represented by the odds ratio (OR) and 95% confidence interval (CI), in the molnupiravir-administered and non-administered group was (OR: 0.714; CI: 0.667 - 0.764) and (OR: 0.749; CI: 0.682 - 0.823), respectively. As age increased, the preventive effect against severe/critical illness or death and death increased. The preventive effect against severe/critical illness or death at ≥60 years was (OR: 0.669; CI: 0.624 - 0.717), at ≥70 years was (OR: 0.614; CI: 0.570 - 0.661), and at ≥80 years was (OR: 0.563; CI: 0.515 - 0.615). The preventive effect against death at ≥60 years was (OR: 0.729; CI: 0.663 - 0.802), at ≥70 years was (OR: 0.676; CI: 0.612 - 0.747), and at ≥80 years was (OR: 0.622; CI: 0.554 - 0.698)., Conclusion: Although molnupiravir showed a relatively weak preventive effect against severe/critical illness or death (29%) and death (25%) among patients with COVID-19, it exhibited a stronger protective effect in older patients than in younger patients. In particular, the preventive effect against severe/critical illness or death (44%) and death (38%) in those aged ≥80 years was pronounced. This study strongly suggests that molnupiravir administration can alleviate the burden on the medical system, and treat patients with COVID-19 effectively by reducing its progression to severe disease and death., Competing Interests: No conflict of interest, (Copyright © 2023 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Climate change may be the most pressing existential threat to human health and wellbeing in the twenty first century. In this paper, the authors provide context and critique on barriers to climate action in the United States and other high-income countries, including the profit-driven approach to health, consumerism, and the climate change countermovement. The reciprocal connections between occupational engagement and climate damage are examined from a lens of collective and irresponsible occupations and subsequent accountability. The authors propose the United Nations' Sustainable Development Goals as a basis for recommendations occupational therapy practitioners could implement within the priorities of adaptation, mitigation, and resilience.

Background: Glutamate is a major neurotransmitter, although it causes cytotoxicity and inflammation in nonneuronal organs. This study aimed to investigate the metabolic disorders in which glutamate, associated with type 2 diabetes onset, is induced in the liver., Methods: An analysis of Korean community-based Ansan-Ansung cohort study data as well as functional research using in vitro and mouse models were performed., Results: Groups with high plasma glutamate levels (T2, T3) had a significantly increased risk of diabetes incidence after 8 years, compared to the group with relatively low glutamate levels (T1). Analysis of the effect of glutamate on diabetes onset in vitro showed that glutamate induces insulin resistance by increasing glucose-related protein 78 (GRP78) and phosphoenolpyruvate carboxykinase (PEPCK) expression in SK-Hep-1 human liver cells. In addition, three different genes, FRMB4B, PLG, and PARD3, were significantly associated with glutamate and were identified via genome-wide association studies. Among glutamate-related genes, plasminogen (PLG) levels were most significantly increased in several environments in which insulin resistance was induced, and was also upregulated by glutamate. Glutamate-induced increase in PLG in liver cells was caused by metabotropic glutamate receptor 5 activation, and PLG levels were also upregulated after extracellular secretion. Moreover, glutamate increased the expression of plasminogen activator inhibitor-1 (PAI-1). Thus, extracellular secreted PLG cannot be converted to plasmin (fibrinolytic enzyme) by increased PAI-1., Conclusions: Increased glutamate is closely associated with the development of diabetes, and it may cause metabolic disorders by inhibiting the fibrinolytic system, which plays an important role in determining blood clots, a hallmark of diabetes., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Paxlovid is an oral antiviral drug that received emergency use authorization in South Korea for the treatment of patients with mild-to-moderate coronavirus disease 2019 (COVID-19) on January 14, 2022. Since the onset of the severe acute respiratory syndrome coronavirus 2 pandemic, the virus has continued to evolve. The emergence of new variants has raised concerns about possible reductions in the effectiveness of vaccines and drugs. The effectiveness of Paxlovid in patients infected with the omicron variant and subvariants has not yet been determined. This study assessed the effectiveness of Paxlovid at reducing the risk of severe/critical illness or death and death in patients with mild-to-moderate COVID-19 caused by omicron subvariant BA.5., Methods: In this nationwide retrospective cohort study, data on 8,902,726 patients were collected from four sources (the Drug Utilization Review database, COVID-19 Patient Information Management System, confirmed patient information, and basic epidemiological investigation data) between July 1 and November 30, 2022. Multivariable logistic regression analysis was conducted, with adjustment for age, sex, severe acute respiratory syndrome coronavirus 2 immunity (vaccination), and comorbidities., Results: A total of 1,936,925 patients with COVID-19 were included in the analysis, including 420,996 patients treated with Paxlovid, and 1,515,959 patients not treated with Paxlovid. Paxlovid treatment in patients aged ≥ 60 years of age was associated with significantly reduced risk of severe/critical illness or death (46.0%), and death rate (32.5%), and its effectiveness was high, regardless of vaccination status., Conclusion: Paxlovid is effective at reducing the risk of death due to COVID-19 in patients with omicron BA.5 infection, especially in older patients, regardless of vaccination status. This suggests that older patients with COVID-19-related symptoms should be administered Paxlovid, regardless of their vaccination status, to reduce severity and risk of death., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Scrub typhus is an acute febrile, mite-borne disease endemic to the Asia-Pacific region. In South Korea, it is a seasonal disease that occurs frequently in the autumn, and its incidence has increased steadily. In this study, we used a liquid chromatography and flow injection analysis-tandem mass spectrometry-based targeted urine metabolomics approach to evaluate the host response to Orientia tsutsugamushi infection. Balb/c mice were infected with O. tsutsugamushi Boryong, and their urine metabolite profile was examined. Metabolites that differed significantly between the experimental groups were identified using the Kruskal-Wallis test. Sixty-five differential metabolites were identified. The principal metabolite classes were acylcarnitines, glycerophospholipids, biogenic amines, and amino acids. An ingenuity pathway analysis revealed that several toxic (cardiotoxic, hepatotoxic, and nephrotoxic) metabolites are induced by scrub typhus infection. This is the first report of urinary metabolite biomarkers of scrub typhus infection and it enhances our understanding of the metabolic pathways involved.

A tokamak, a torus-shaped nuclear fusion device, needs an electric current in the plasma to produce magnetic field in the poloidal direction for confining fusion plasmas. Plasma current is conventionally generated by electromagnetic induction. However, for a steady-state fusion reactor, minimizing the inductive current is essential to extend the tokamak operating duration. Several non-inductive current drive schemes have been developed for steady-state operations such as radio-frequency waves and neutral beams. However, commercial reactors require minimal use of these external sources to maximize the fusion gain, Q, the ratio of the fusion power to the external power. Apart from these external current drives, a self-generated current, so-called bootstrap current, was predicted theoretically and demonstrated experimentally. Here, we reveal another self-generated current that can exist in a tokamak and this has not yet been discussed by present theories. We report conclusive experimental evidence of this self-generated current observed in the KSTAR tokamak., (© 2022. The Author(s).)

Alcohol consumption is associated with a high increased lipid profile and this association may depend on genetic risk factors. In this study, we aimed to assess the effects of genetic variation associated with alcohol consumption on lipid profiles using data from two Korean population studies. We performed a genotype association study using the HEXA (n = 51,349) and KNHANES (n = 9158) data. Genotype analyses of the two sets of Korean population data showed associations of increased total cholesterol and high-density lipoprotein (HDL)-cholesterol with CETP rs708272. The HEXA and KNHANES populations revealed differences in HDL cholesterol according to the presence of CETP rs708272, independent of ALDH2 rs671 and alcohol consumption. In contrast, total cholesterol levels were associated with alcohol consumption and ALDH2 rs671 in men with CETP rs708272 (CT and TT genotypes). Furthermore, in drinkers with ALDH2 rs671 (GA and AA genotypes), higher total cholesterol was associated with the CETP rs708272 TT minor homozygous genotype based on both HEXA and KNHANES data. Our findings demonstrated that alcohol consumption and genetic variation in either CETP or ALDH2 may be associated with cholesterol levels. We hope these findings will provide a better understanding of the relationship between alcohol consumption and cholesterol according to each individual's genetic background., (© 2022. The Author(s).)

Excessive alcohol intake is an important cause of major public health problem in East Asian countries. Growing evidence suggests that genetic factors are associated with alcohol consumption and the risk for alcohol-associated disease, and these factors contribute to the risk of developing chronic diseases, including diabetes. This study aims to investigate the association of type 2 diabetes with genetic polymorphisms within HECTD4 based on alcohol exposure. We performed a genome-wide association study involving the cohorts of the KoGES-HEXA study (n = 50,028) and Ansan and Ansung study (n = 7,980), both of which are prospective cohort studies in Korea. The top three single-nucleotide polymorphisms (SNPs) of the HECTD4 gene, specifically rs77768175, rs2074356 and rs11066280, were found to be significantly associated with alcohol consumption. We found that individuals carrying the variant allele in these SNPs had lower fasting blood glucose, triglyceride, and GGT levels than those with the wild-type allele. Multiple logistic regression showed that statistically significant associations of HECTD4 gene polymorphisms with an increased risk of type 2 diabetes were found in drinkers. Namely, these SNPs were associated with decreased odds of diabetes in the presence of alcohol consumption. As a result of examining the effect of alcohol on the expression of the HECTD4 gene, ethanol increased the expression of HECTD4 in cells, but the level was decreased by NAC treatment. Similar results were obtained from liver samples of mice treated with alcohol. Moreover, a loss of HECTD4 resulted in reduced levels of CYP2E1 and lipogenic gene expression in ethanol-treated cells, while the level of ALDH2 expression increased, indicating a reduction in ethanol-induced hepatotoxicity., (© 2022. The Author(s).)

Potassium voltage-gated channel subfamily Q member 1 (KCNQ1) is one of the strongest susceptibility genes for type 2 diabetes mellitus (T2DM). Association studies between KCNQ1 genetic variants and T2DM have been reported. The multifactorial disease T2DM is caused by interactions between genetic susceptibility and environmental factors. In this study, we examined the associations between the KCNQ1 haplotype, which consists of the major alleles rs3852528, rs11024175, and rs2237892 (ht: ACC), and environmental factors such as alcohol consumption, which are related to the risk of T2DM, in two independent Korean populations. Data from health examination studies, i.e., HEXA (n = 50,357 subjects) and the Ansung-Ansan community-based Korean cohort study (n = 7603), were analyzed. In both cohorts, fasting blood glucose levels were significantly increased in moderate-to-heavy drinkers and carriers of the homozygous ACC haplotype. A significant association between the KCNQ1 haplotype and alcohol consumption in the risk of diabetes was observed in the HEXA (OR 1.587; 95% CI 1.128-2.234) and Ansung-Ansan (OR 2.165; 95% CI 1.175-3.989) cohorts compared with abstainers not carrying the KCNQ1 haplotype. Associations of the KCNQ1 haplotype with alcohol consumption and β-cell function were observed in the Ansung-Ansan cohort. Moderate-to-heavy drinkers with the ACC haplotype had lower fasting insulin levels and mean 60 min insulinogenic index (IGI 60 ) compared with light drinkers and abstainers not carrying the ACC haplotype. These findings indicate that KCNQ1 variants play a synergistic role with alcohol consumption in the development of T2DM and impaired β-cell function., (© 2021. The Author(s).)

We conducted a retrospective study of Middle East respiratory syndrome coronavirus (MERS-CoV) viral load kinetics using data from patients hospitalized with MERS-CoV infection between 19 May and 20 August 2015. Viral load trajectories were considered over the hospitalization period using 1714 viral load results measured in serial respiratory specimens of 185 patients. The viral load levels were significantly higher among nonsurvivors than among survivors (P = .003). Healthcare workers (P = .001) and nonspreaders (P < .001) had significantly lower viral loads. Viral RNA was present on the day of symptom onset and peaked 4-10 days after symptom onset., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Chronic alcohol consumption is known to be associated with type 2 diabetes (T2D), which is developed by two underlying mechanisms, β-cell dysfunction and insulin resistance. Identification of genetic variants in association with the development of T2D may help explain the genetic risk factors of T2D. In this study, we tried to find out some genetic variations, which interact with alcohol consumption and also are associated with β-cell function through 12 year's follow-up study in Korean population. We performed a genotype association study using the community-based Ansung-Ansan Cohort data (baseline n = 3120; follow-up n = 433). Genotype association analyses of the baseline data showed that alcohol consumption is associated with the decreases of blood insulin levels and insulin secretion in participants with the KCNJ11 rs5219 risk allele. Moreover, multivariate logistic regression analyses revealed that the risk allele group is vulnerable to impairment of β-cell function in response to alcohol consumption (OR 1.450; 95% CI 1.061-1.982). Furthermore, 12-year' follow-up results showed that alcohol consumption synergistically decreases insulin secretion in participants with KCNJ11 rs5219 risk alleles. Our findings demonstrate that the KCNJ11 rs5219 risk allele in combination with alcohol consumption could be a potential risk factor of β-cell dysfunction. We hope that this new findings could be helpful to further understand the development of T2D depending on individual genetic background in association with alcohol consumption.

Background: Alcohol consumption is associated with hypertension, and this association depends on the alcohol consumption pattern and alcohol flushing response. In this 12-year follow-up study, we investigated the relationship between the alcohol consumption pattern and incidence of hypertension in the Korean population., Methods: We analyzed 1,366 Korean participants in the Ansung-Ansan cohort study without hypertension at baseline. The subjects were classified into four alcohol consumption patterns: never-drinking, light alcohol consumption, moderate alcohol consumption, and heavy alcohol consumption, and as flushers or non-flushers in response to alcohol., Results: In flushers, moderate and heavy alcohol consumption patterns increased the risk of incident hypertension compared with never-drinkers [moderate: HR 1.811 (95% CI 1.084-3.028); heavy: HR 2.494 (95% CI 1.185-5.247)], but non-flushers were not associated with increased risk of incident hypertension according to the alcohol consumption pattern. In addition, a heavy alcohol consumption pattern increased the risk of hypertension among flushers compared with non-flushers [HR 2.232 (95% CI 1.054-4.728)]., Conclusion: In this 12-year follow-up study, we observed that moderate and heavy alcohol consumption was associated with an increased risk of hypertension in flushers. Especially, a heavy alcohol consumption pattern in flushers markedly increased the risk of hypertension., Competing Interests: Declaration of competing interests None., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The discovery of metabolomics-based biomarkers has been a focus of recent kidney dysfunction research. In the present study, we aimed to identify metabolites associated with chronic kidney disease (CKD) in the general population using a cross-sectional study design. At baseline, 6.5% of subjects had CKD. Pearson correlation analysis showed that 28 metabolites were significantly associated with estimated glomerular filtration rate (eGFR) after Bonferroni correction. Among these metabolites, 4 acylcarnitines, 12 amino acids, 4 biogenic amines, 1 phosphatidylcholine, and 1 sphingolipid were associated with CKD ( p < 0.05). After eight years, 13.5% of subjects had CKD. Three amino acid metabolites were positively associated with new-onset CKD: citrulline [odds ratio (OR): 2.41, 95% confidence interval (CI): 1.26-4.59], kynurenine (OR: 1.98, 95% CI: 1.05-3.73), and phenylalanine (OR: 2.68, 95% CI: 1.00-7.16). The kynurenine:tryptophan ratio was also associated with CKD (OR: 3.20; 95% CI: 1.57-6.51). The addition of multiple metabolites significantly improved the CKD prediction by C statistics (0.756-0.85, p < 0.0001), and the net reclassification improvement was 0.84 (95% CI: 0.72-0.96). Elevated hs-C reactive protein (CRP) was associated with new-onset CKD (OR: 1.045, 95% CI: 1.005-1.086); however, this association disappeared following adjustment with the kynurenine:tryptophan ratio. The levels of citrulline and kynurenine and their ratio to tryptophan in CKD patients with proteinuria were worse than those with one or neither characteristic. Together, the results of this study demonstrate that amino acid metabolites are associated with CKD eight years after initial metabolite assessment. These results could improve the identification of subjects at high risk of CKD who have modified amino acid metabolism.

Background: Excessive alcohol consumption is a major public health problem in East Asian countries. Alcohol use leads to a cascade of problems including increased chances of risky behavior and a wide range of negative health consequences, from alcoholic liver disease to upper gastric and liver cancer. These alcohol effects are known to be influenced by ethnic variability and genetics., Methods: In this study, subjects were administered a single dose of alcohol (0.6 g/kg for men or 0.4 g/kg for women), and blood alcohol and acetaldehyde concentrations were measured eight times over 5 hours. To investigate genetically susceptible factors to alcohol metabolism, we selected single-nucleotide polymorphisms (SNP) of genes identified by prior genetic association studies for alcohol metabolism, alcohol consumption, alcohol dependence, and related traits, and performed genotyping on all subjects (n = 104)., Results: We identified variations in the ADH1A, SRPRB, and PGM1 genes, which are directly associated with blood alcohol or acetaldehyde concentrations. Namely, the T allele of SRPRB rs17376019 and the C allele of PGM1 rs4643 were associated with lower blood alcohol levels, while the ADH1 rs1229976 C allele group exhibited markedly higher blood acetaldehyde levels than those of the ADH1 rs1229976 T allele group., Conclusion: This study demonstrates that genetic variations in ADH1A, SRPRB, and PGM1 are associated with variations in blood alcohol and acetaldehyde concentration after alcohol intake., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Aims: Metabolites related to dietary factors can be used to identify biological markers to prevent metabolic disease. However, most studies have been conducted in the United States and Europe, and those in the Asian region are limited. We investigated the effects of dietary monounsaturated fatty acids (MUFAs) and metabolites on new-onset hypertension in the Korean Genome and Epidemiology Study., Method and Results: A total of 1529 subjects without hypertension were divided into tertiles of dietary MUFAs intake. After a 4-year follow-up, 135 serum metabolites were measured using the AbsoluteIDQ p180 kit. During the 4-year follow-up period, 193 new-onset hypertension incidences were observed. The highest MUFAs intake group was inversely associated with the risk of hypertension compared with the lowest MUFAs intake group (odds ratio (OR) = 0.49, (95% confidence interval (CI) = 0.29-0.82)). Of the 135 metabolites, eight were significantly associated with MUFAs intake. Phosphatidylcholine-diacyl (PC aa) C 38:1 and hydroxysphingomyelin (SM OH) C 16:1 were associated with a decrease in hypertension risk (PC aa C 38:1, OR = 0.60 (95% CI = 0.37-0.96); SM OH C 16:1, OR = 0.42 (95% CI = 0.20-0.90)). The highest MUFAs intake group had a significantly decreased risk of hypertension, even considering PC aa C 38:1 and SM (OH) C 16:1 as a mediator., Conclusion: We confirmed that dietary MUFAs intake, and PC aa C 38:1 and SM (OH) C 16:1 had protective effects against hypertension. Furthermore, high MUFAs intake combined with PC aa C 38:1 and SM (OH) C 16:1 has the most significant effect on reducing the risk hypertension.

Background and Aims: Alcohol consumption is generally associated with increased risk of hypertension. However, the effect of alcohol intake on the incidence of hypertension remains controversial due to inconsistent results across studies. We investigated the association between alcohol intake and hypertension in a Korean population., Methods and Results: The two studies that we evaluated herein, the CAVAS study (N = 6259) and the Ansan-Ansung study (N = 2461), were part of the Korean Genome and Epidemiology study on participants aged between 40 and 69 years who underwent community-based health checkups (2 years for the CAVAS study follow-up and 12 years for the Ansan-Ansung study follow-up). We categorized the participants into four groups based on baseline and follow-up period measurements. We found that baseline alcohol consumption increased the risk of incident hypertension in the CAVAS study [HR (95% CI), low: 1.094 (0.848-1.411); intermediate: 1.661 (1.227-2.141); high: 1.723 (1.274-2.330)]. Intermediate and high alcohol consumption were associated with increased risk of incident hypertension in men [2.086 (1.438-3.027) for intermediate, and 1.952 (1.294-2.944) for high], but only women had increased risk of incident hypertension with high consumption [1.950 (1.100-3.455)]. In addition, we found a positive association between the alcohol consumption pattern (over 10 years) and the risk of incident hypertension in the Ansan-Ansung study [HR (95% CI), light: 1.316 (1.126-1.539); moderate: 1.445 (1.193-1.750); heavy: 1.897 (1.488-2.419)]. Moderate and heavy consumption patterns carried higher risks of incident hypertension compared with never-drinking in men [moderate: 1.292 (1.033-1.617); heavy: 1.703 (1.293-2.242)], but women with light consumption patterns were at increased risk of incident hypertension [1.572 (1.302-1.899)]., Conclusions: This large prospective cohort study revealed a linear association between baseline alcohol consumption, subsequent alcohol consumption patterns (over more than 10 years), and hypertension risk in the Korean population., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Although gas breakdown phenomena have been intensively studied over 100 years, the breakdown mechanism in a strongly magnetized system, such as tokamak, has been still obscured due to complex electromagnetic topologies. There has been a widespread misconception that the conventional breakdown model of the unmagnetized system can be directly applied to the strongly magnetized system. However, we found clear evidence that existing theories cannot explain the experimental results. Here, we demonstrate the underlying mechanism of gas breakdown in tokamaks, a turbulent ExB mixing avalanche, which systematically considers multi-dimensional plasma dynamics in the complex electromagnetic topology. This mechanism clearly elucidates the experiments by identifying crucial roles of self-electric fields produced by space-charge that decrease the plasma density growth rate and cause a dominant transport via ExB drifts. A comprehensive understanding of plasma dynamics in complex electromagnetic topology provides general design strategy for robust breakdown scenarios in a tokamak fusion reactor.

Aim: To evaluate and compare the utility of contrast-enhanced three-dimensional (3D) T1-weighted high-resolution isotropic volume examination (THRIVE), spin-echo (SE) T1-weighted magnetic resonance imaging (MRI), and computed tomography (CT) for detecting clinically occult primary tumours in patients with cervical lymph node metastases., Materials and Methods: Seventy-three consecutive patients with tumours that went undetected during endoscopic or physical examinations underwent preoperative contrast-enhanced CT and MRI (SE and 3D THRIVE) after gadolinium injection. Guided biopsy results served as reference standards. The diagnostic performances of the imaging techniques were compared with McNemar's tests., Results: Primary tumours were identified in 59 (80.8%) of the 73 patients after surgery. Of these, 36 were found in the palatine tonsil, 11 in the base of the tongue, seven in the nasopharynx, and five in the pyriform sinus. The sensitivity (72.9%) and accuracy (71.2%) of 3D THRIVE for detecting primary tumours were higher than were those of SE T1-weighted MRI (49.2% and 53.4%, p≤0.002) or CT (36.4% and 46.4%, p≤0.001). The specificities of these techniques did not differ. The diagnostic performance of 3D THRIVE (area under the curve [AUC]=0.681) for detecting tumours did not differ from that of SE T1-weighted MRI or CT (AUC=0.671 and 0.608, p>0.05)., Conclusion: 3D THRIVE was more sensitive at detecting primary tumours than was SE T1-weighted MRI or CT in patients with cervical metastases of unknown primary tumours. This sequence may improve biopsy and therapeutic planning in these patients., (Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study was to investigate the associations between microscopic abnormalities of transplanted kidneys and sonography-based imaging biomarkers, including elasticity, venous impedance index, arterial resistive index, and size., Materials and Methods: Between 2011 and 2015, 159 recipients underwent sonography and biopsy of a transplanted kidney at our institution; 104 adult patients were included in this study. The maximal longitudinal length on gray-scale images, arterial resistive index, and venous impedance index on Doppler images and shear wave velocity on acoustic radiation force impulse imaging or Young modulus on supersonic shear imaging were measured before biopsy. The Banff criteria (2009 update), an international standardized classification and scoring system for renal allograft pathology, were used to evaluate the biopsy samples. Sonography parameters and clinical variables were analyzed with individual and summed Banff scores., Results: Spearman rank correlation coefficients and ordinal logistic regression showed no association between sonography parameters and summed Banff scores. Only the interval between transplant and biopsy was significantly associated with summed Banff scores (p < 0.05). Univariate logistic regression analysis with individual Banff scores showed associations of one Banff feature with arterial resistive index, three with venous impedance index, and six with interval between transplant and biopsy (p < 0.05). Sonoelastography parameters were not associated with any individual Banff score., Conclusion: Neither sonoelastography parameter was associated with any histopathologic change of renal allografts. Although arterial resistive index and venous impedance index were related to a few individual Banff scores, length of time between transplant and biopsy showed stronger correlation than any imaging biomarkers with renal allograft deterioration.

Moderate alcohol consumption is generally associated with reduced risk of type 2 diabetes. However, this beneficial effects of alcohol intake remains controversial due to inconsistent results across studies. The analysis was performed using data from the Ansung-Ansan cohort study. We categorized the participants into four groups-based on the baseline (one-point measure; non-drinking, <5 g/day, ≥5, <30 g/day, and ≥30 g/day) and follow-up (consumption pattern; never-drinking, light, moderate, and heavy drinking) measurement. At baseline, ≥30 g/day alcohol consumption increased the risk of incident diabetes (HR: 1.42; 95% CI, 1.10-1.85), but ≥5, <30 g/day alcohol consumption had no effects on the incident diabetes. Meanwhile, when using the alcohol consumption pattern, a heavy-drinking pattern increased the risk of incident diabetes (HR = 1.32, 1.01-1.73), but the light and moderate consumption pattern was associated with a reduced risk of type 2 diabetes (HR: 0.66; 0.50-0.87 and HR: 0.74; 0.57-0.95, respectively). At the end point of follow-up, the insulinogenic index (IGI), but not the insulin sensitivity index (ISI), differed among the groups. Alcohol consumption pattern had a J-shaped association with the incident type 2 diabetes in Korean men. The IGI showed an inverted J-shaped association according to alcohol drinking pattern, but the ISI was not a J-shape.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) contributes to impaired glucose tolerance, leading to type 2 diabetes (T2D); however, the precise mechanisms and target molecules that are involved remain unclear. Activating transcription factor 3 (ATF3) is associated with β-cell dysfunction that is induced by severe stress signals in T2D. We aimed to explore the exact functional role of ATF3 as a mechanistic link between hepatic steatosis and T2D development., Methods: Zucker diabetic fatty (ZDF) rats were utilized for animal experiments. An in vivo-jetPEI siRNA delivery system against ATF3 was used for loss-of-function experiments. We analyzed the baseline cross-sectional data derived from the biopsy-proven NAFLD registry (n=322). Human sera and liver tissues were obtained from 43 patients with biopsy-proven NAFLD and from seven healthy participants., Results: ATF3 was highly expressed in the livers of ZDF rats and in human participants with NAFLD and/or T2D. Insulin resistance and hepatic steatosis were associated with increased ATF3 expression and decreased fatty acid oxidation via mitochondrial dysfunction and were attenuated by in vivo ATF3 silencing. Knockdown of ATF3 also ameliorated glucose intolerance, impaired insulin action, and inflammatory responses in ZDF rats. In patients with NAFLD and/or T2D, a significant positive correlation was observed between hepatic ATF3 expression and surrogate markers of T2D, mitochondrial dysfunction, and macrophage infiltration., Conclusions: Increased hepatic ATF3 expression is closely associated with hepatic steatosis and incident T2D; therefore, ATF3 may serve as a potential therapeutic target for NAFLD and hepatic steatosis-induced T2D., Lay Summary: Hepatic activating transcription factor 3 (ATF3) may play an important role in oxidative stress-mediated hepatic steatosis and the development of type 2 diabetes (T2D) in a Zucker diabetic fatty (ZDF) rat model and in human patients with non-alcoholic fatty liver disease (NAFLD). Therefore, ATF3 may be a useful biomarker for predicting the progression of NAFLD and the development of T2D. Furthermore, given the significant association between hepatic ATF3 expression and both hepatic steatosis and impaired glucose homeostasis, in vivo ATF3 silencing may be a potential central strategy for preventing and managing NAFLD and T2D., (Copyright © 2017 European Association for the Study of the Liver. All rights reserved.)

This cross-sectional study was performed to examine the association between alcohol consumption and insulin secretion and sensitivity using the Korean Genome and Epidemiology Study. Alcohol consumption levels were categorized into four groups: (i) abstainers, (ii) low (<5 g/day), (iii) intermediate (<30 g/day), and (iv) high (≥30 g/day) alcohol consumption. β-cell function and insulin sensitivity were estimated using the insulinogenic index (IGI 60 ), and Matsuda insulin sensitivity index (ISI), respectively. IGI 60 and ISI were dichotomized into high and low groups using median cut-off values and four groups were defined (G-I: high IGI 60 /high ISI; G-II: high IGI 60 /low ISI; G-III: low IGI 60 /high ISI; and G-IV: low IGI 60 /low ISI). Men consumed 26.5 g alcohol per day on average, whereas women only consumed 5.7 g/day, so women were excluded from subsequent analyses due to their low drinking levels. Alcohol consumption was positively associated with high-density lipoprotein (HDL) cholesterol, aspartate aminotransferase (AST), and triglycerides (TG) in men, but was negatively associated with IGI 60 ( p < 0.05). TG levels were only increased in individuals with decreased insulin sensitivity (G-II) or decreased β-cell function (G-III) with high alcohol consumption. In addition, alcohol consumption increased HDL cholesterol in the four groups ( p < 0.001). In subjects with decreased insulin sensitivity (G-II), intermediate and high alcohol consumption increased the risk of high cholesterol and TG. In individuals with decreased β-cell function (G-III), alcohol consumption increased the risk of high TG and high AST levels. High alcohol consumption was significantly associated with reduced insulin secretion. In addition, alcohol consumption was related to some metabolic risk factors depending on insulin secretion or sensitivity., Competing Interests: The authors declare that they have no competing interests.

Our aim was to improve the detection of prostate cancer by evaluating whether contrast-enhanced ultrasound (CEUS) or sonoelastography (SE) is more helpful in guiding targeted biopsy (TB) performed before systematic biopsy (SB). A total of 52 patients suspected of having prostate cancer were prospectively included and randomly assigned to either the CEUS or SE group. Different, independent radiologists performed TB and twelve-core SB. Within each group, cancer detection rates based on core number were compared between SB and TB. We evaluated the effect of TB on core-based cancer detection rates between the CEUS and SE groups. Cancer detection was higher in overall TB cores 16.4% (28/171) than SB cores 11.4% (71/624) in both groups. In the SE group, TB cores revealed higher cancer detection than did SB cores from 4.49% (14/312) to 12.86% (9/70) (p = 0.01). Compared with CEUS, SE may improve detection rates when considering additional TB guidance methods., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. All rights reserved.)

Background: Keloids and hypertrophic scars represent excessive scarring. They require different therapeutic approaches, which can be hampered because of an apparent lack of morphologic difference between the two diseases., Objective: This study investigated the clinical and dermoscopic features of keloids and hypertrophic scars in order to help dermatologists distinguish these lesions better., Methods: A total of 41 keloids and hypertrophic scars in 41 patients were examined clinically and by performing dermoscopy with a digital imaging system. Lesions were evaluated for vascular structures., Results: Dermoscopy revealed vascular structures in most keloid lesions (90%) but in only 27% of hypertrophic scar lesions. The most common dermoscopic vascular structures in keloids were arborizing (52%), followed by linear irregular (33%) and commashaped (15%); these features were present but less evident in hypertrophic scars (9% for all types). The distribution frequency of the vascular structures differed significantly between diseases (p<0.001)., Conclusion: A strong association of vascular structures with keloids was observed on dermoscopic examination. The results suggest dermoscopic examination of vascular structures is a clinically useful diagnostic tool for differentiating between keloids and hypertrophic scars.

Background: Although intralesional methotrexate (MTX) is an effective, nonsurgical treatment of keratoacanthoma (KA), there have not been many reports of on the MTX treatment for KA in Korea., Objective: The purpose of this study was to evaluate the clinical efficacy of the intralesional MTX for the treatment of KA in Korean patients., Methods: We retrospectively studied seven patients with KA who received intralesional injection of MTX in our department. The efficacy was evaluated based on the physician assessment. Our review also included the cases of KA treated with intralesional MTX in Korean patients from the previous reports. We then analyzed the therapeutic regimens in the Korean patients by comparing them with the Caucasian patients., Results: We identified 11 cases of Korean KA patients treated with an intralesional MTX, including seven from our institution and four from the Korean literature. Ten of the 11 patients (91%) showed a complete resolution with an intralesional MTX. No adverse events were observed during the treatment and the follow-up periods. No recurrence was found during the follow-up. In therapeutic analysis, the Korean patients required 2 to 7 injections (mean 4.6 injections) to achieve a tumor resolution with the mean time to clearing at 7.6 weeks., Conclusion: Intralesional MTX can be an effective and safe non-operative treatment modality for most Koreans with KA.