• Korean Journal of Radiology
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• v.24 no.7
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• pp.647-659
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• 2023

Objective: The study was conducted to investigate the effect of correct occlusion of the left atrial appendage (LAA) on intracardiac blood flow and thrombus formation in patients with atrial fibrillation (AF) using four-dimensional (4D) flow magnetic resonance imaging (MRI) and three-dimensional (3D)-printed phantoms. Materials and Methods: Three life-sized 3D-printed left atrium (LA) phantoms, including a pre-occlusion (i.e., before the occlusion procedure) model and correctly and incorrectly occluded post-procedural models, were constructed based on cardiac computed tomography images from an 86-year-old male with long-standing persistent AF. A custom-made closed-loop flow circuit was set up, and pulsatile simulated pulmonary venous flow was delivered by a pump. 4D flow MRI was performed using a 3T scanner, and the images were analyzed using MATLAB-based software (R2020b; Mathworks). Flow metrics associated with blood stasis and thrombogenicity, such as the volume of stasis defined by the velocity threshold ($\left|\vec{V}\right|$ < 3 cm/s), surface-and-time-averaged wall shear stress (WSS), and endothelial cell activation potential (ECAP), were analyzed and compared among the three LA phantom models. Results: Different spatial distributions, orientations, and magnitudes of LA flow were directly visualized within the three LA phantoms using 4D flow MRI. The time-averaged volume and its ratio to the corresponding entire volume of LA flow stasis were consistently reduced in the correctly occluded model (70.82 mL and 39.0%, respectively), followed by the incorrectly occluded (73.17 mL and 39.0%, respectively) and pre-occlusion (79.11 mL and 39.7%, respectively) models. The surfaceand-time-averaged WSS and ECAP were also lowest in the correctly occluded model (0.048 Pa and 4.004 Pa^-1, respectively), followed by the incorrectly occluded (0.059 Pa and 4.792 Pa^-1, respectively) and pre-occlusion (0.072 Pa and 5.861 Pa^-1, respectively) models. Conclusion: These findings suggest that a correctly occluded LAA leads to the greatest reduction in LA flow stasis and thrombogenicity, presenting a tentative procedural goal to maximize clinical benefits in patients with AF.

• IMMUNE NETWORK
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• v.22 no.2
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• pp.16.1-16.20
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• 2022

The gastrointestinal tract is the first organ directly affected by fasting. However, little is known about how fasting influences the intestinal immune system. Intestinal dendritic cells (DCs) capture antigens, migrate to secondary lymphoid organs, and provoke adaptive immune responses. We evaluated the changes of intestinal DCs in mice with short-term fasting and their effects on protective immunity against Listeria monocytogenes (LM). Fasting induced an increased number of CD103⁺CD11b^- DCs in both small intestinal lamina propria (SILP) and mesenteric lymph nodes (mLN). The SILP CD103⁺CD11b^- DCs showed proliferation and migration, coincident with increased levels of GM-CSF and C-C chemokine receptor type 7, respectively. At 24 h post-infection with LM, there was a significant reduction in the bacterial burden in the spleen, liver, and mLN of the short-term-fasted mice compared to those fed ad libitum. Also, short-term-fasted mice showed increased survival after LM infection compared with ad libitum-fed mice. It could be that significantly high TGF-β2 and Aldh1a2 expression in CD103⁺CD11b^- DCs in mice infected with LM might affect to increase of Foxp3⁺ regulatory T cells. Changes of major subset of DCs from CD103⁺ to CD103^- may induce the increase of IFN-γ-producing cells with forming Th1-biased environment. Therefore, the short-term fasting affects protection against LM infection by changing major subset of intestinal DCs from tolerogenic to Th1 immunogenic.

• IMMUNE NETWORK
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• v.21 no.4
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• pp.26.1-26.28
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• 2021

Asthma exacerbations are a major cause of intractable morbidity, increases in health care costs, and a greater progressive loss of lung function. Asthma exacerbations are most commonly triggered by respiratory viral infections, particularly with human rhinovirus (hRV). Respiratory viral infections are believed to affect the expression of indoleamine 2,3-dioxygenase (IDO), a limiting enzyme in tryptophan catabolism, which is presumed to alter asthmatic airway inflammation. Here, we explored the detailed role of IDO in the progression of asthma exacerbations using a mouse model for asthma exacerbation caused by hRV infection. Our results reveal that IDO is required to prevent neutrophilic inflammation in the course of asthma exacerbation caused by an hRV infection, as corroborated by markedly enhanced Th17- and Th1-type neutrophilia in the airways of IDO-deficient mice. This neutrophilia was closely associated with disrupted expression of tight junctions and enhanced expression of inflammasome-related molecules and mucin-inducing genes. In addition, IDO ablation enhanced allergen-specific Th17- and Th1-biased CD4⁺ T-cell responses following hRV infection. The role of IDO in attenuating Th17- and Th1-type neutrophilic airway inflammation became more apparent in chronic asthma exacerbations after repeated allergen exposures and hRV infections. Furthermore, IDO enzymatic induction in leukocytes derived from the hematopoietic stem cell (HSC) lineage appeared to play a dominant role in attenuating Th17- and Th1-type neutrophilic inflammation in the airway following hRV infection. Therefore, IDO activity in HSC-derived leukocytes is required to regulate Th17- and Th1-type neutrophilic inflammation in the airway during asthma exacerbations caused by hRV infections.

• IMMUNE NETWORK
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• v.20 no.5
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• pp.41.1-41.11
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• 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a positive-sense single-stranded RNA (+ssRNA) that causes coronavirus disease 2019 (COVID-19). The viral genome encodes twelve genes for viral replication and infection. The third open reading frame is the spike (S) gene that encodes for the spike glycoprotein interacting with specific cell surface receptor - angiotensin converting enzyme 2 (ACE2) - on the host cell membrane. Most recent studies identified a single point mutation in S gene. A single point mutation in S gene leading to an amino acid substitution at codon 614 from an aspartic acid 614 into glycine (D614G) resulted in greater infectivity compared to the wild type SARS-CoV2. We were interested in investigating the mutation region of S gene of SARS-CoV2 from Korean COVID-19 patients. New mutation sites were found in the critical receptor binding domain (RBD) of S gene, which is adjacent to the aforementioned D614G mutation residue. This specific sequence data demonstrated the active progression of SARS-CoV2 by mutations in the RBD of S gene. The sequence information of new mutations is critical to the development of recombinant SARS-CoV2 spike antigens, which may be required to improve and advance the strategy against a wide range of possible SARS-CoV2 mutations.

• IMMUNE NETWORK
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• v.20 no.6
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• pp.48.1-48.11
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• 2020

Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 Abs. However, the immunological characteristics have not been fully elucidated in patients with HPD. We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 Abs between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment. Peripheral blood mononuclear cells were analyzed by multi-color flow cytometry to phenotype the immune cells. Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (p<0.001) and overall survival (p<0.001). When peripheral blood immune cells were examined, the pre-treatment frequency of CD39⁺ cells among CD8⁺ T cells was significantly higher in patients with HPD compared to those with NHPD, although it showed borderline significance to predict HPD. Other parameters regarding regulatory T cells or myeloid derived suppressor cells did not significantly differ among patient groups. Our findings suggest high pre-treatment frequency of CD39⁺CD8⁺ T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.

• Annals of Occupational and Environmental Medicine
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• v.35
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• pp.50.1-50.11
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• 2023

Background: The rise in telecommuting or non-face-to-face work owing to the coronavirus disease 2019 pandemic has fueled conversations regarding the "right to disconnect." Although evidence suggests that receiving work-related communications through telecommunication devices outside of work hours may lead to various symptoms and illnesses, limited research has been undertaken on these symptoms. This study therefore aims to investigate the correlation between receiving work communications through telecommunication devices after work hours and the occurrence of work-related headaches and eyestrain in full-time, non-shift white-collar workers. Methods: This study used data from the 6th Korean Working Conditions Survey. The frequency of using telecommunication devices for work purposes outside of working hours was divided into five categories: "Every day," "Several times a week," "Several times a month," "Rarely," and "Never." Work-related headaches and eyestrain were categorized based on a "yes" or "no" response to the survey questions. Descriptive statistics, χ² tests, and multiple logistic regression analyses were performed using SPSS 27.0. Results: After adjusting for sex, age, income level, education, occupation, workplace size, work hours, and sleep disorders, the odds ratio (OR) of work-related headaches and eyestrain based on frequency of telecommunication device usage were as follows: "rarely" (OR: 1.292; 95% confidence interval [CI]: 1.111-1.503), "several times a month" (OR: 1.551; 95% CI: 1.249-1.926), "several times a week" (OR: 1.474; 95% CI: 1.217-1.784), and "every day" (OR: 1.548; 95% CI: 1.321-1.813). Conclusions: Employees who use telecommunication devices for work after regular hours are more susceptible to experiencing work-related headaches and eyestrain compared to those who do not. However, there is a dearth of research examining the physical and mental health impacts of using telecommunication devices for after-hours work. Furthermore, the existing preventative measures in Korea are insufficient. Consequently, it is imperative to develop effective measures and conduct additional research to address this issue.

• Annals of Occupational and Environmental Medicine
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• v.35
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• pp.4.1-4.11
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• 2023

Background: Shift work has been shown to increase the risk of cardiovascular disease (CVD) based on several evidences. The classic risk factors of CVD include age, hypertension, smoking, obesity and diabetes. Recently, the serum homocysteine level has been reported to be a valuable indicator of CVD risk. This study aimed to determine the variation in serum homocysteine level as a cardiovascular risk indicator among female workers according to shift work. Methods: The data of regular health examination of workers at an electronic manufacturing services company in Yeongnam region, South Korea in 2019 were examined in this study. The investigation was based on a cross-sectional study conducted on 697 female workers (199 day workers and 498 shift workers). The sociodemographic and biochemical characteristics were compared between day workers and shift workers. Through a logistic regression analysis, the odds ratio (OR) of the increased serum homocysteine level in relation to shift work was determined. Results: Compared to female day workers, female shift workers showed significantly higher level of serum homocysteine (8.85 ± 2.16 vs. 9.42 ± 2.04 μmol/mL; p = 0.001). The OR of day workers against shift workers was 1.81 (95% confidence interval [CI]: 1.25-2.63). With the adjustment of variables that may influence the level of serum homocysteine, the adjusted OR was 1.68 (95% CI: 1.09-2.60). Conclusions: The serum homocysteine level was significantly higher in shift workers than in day workers. It is thus likely to be a useful predictor of CVD in shift workers.

• Annals of Occupational and Environmental Medicine
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• v.35
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• pp.41.1-41.11
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• 2023

Background: Shift work has been reported to have several harmful effects on the human body. However, a small number of studies have evaluated the association between shift work and adverse effects on the thyroid. In our longitudinal study, we examined the causal association between shift work and the risk of hypothyroidism. Methods: A Kangbuk Samsung Cohort Study was conducted on 112,648 men without thyroid disease at baseline who were followed up at least once between 2012 and 2019. Shift work status and shift schedule types were categorized using standardized questionnaires. Hypothyroidism was defined using the reference ranges of serum thyroid-stimulating hormones and free thyroxine levels. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident hypothyroidism were estimated using Cox proportional hazards regression analyses with the daytime work group as the reference. Results: During the 501,237 person-years of follow-up, there were 6,306 incident cases of hypothyroidism (incidence density, 1.26 per 100 person-years). The multivariable-adjusted HR of incident hypothyroidism for the shift work total group that included all shifts compared with the daytime work group was 1.27 (95% CI: 1.15-1.40). For the fixed evening, fixed night, rotating shift, and other shift workers, the multivariable-adjusted HRs (95% CI) were 1.11 (0.76-1.61), 2.18 (1.20-3.93), 1.39 (1.23-1.56), and 1.00 (0.82-1.22), respectively. In subgroup analyses by age, the association between shift work and hypothyroidism was more pronounced in younger participants (< 40 years; HR: 1.31; 95% CI: 1.16-1.47). Conclusions: Our large-scale cohort study showed an association between shift work and the incidence of hypothyroidism, especially in younger workers with night shifts.

• Pediatric Infection and Vaccine
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• v.30 no.3
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• pp.139-144
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• 2023

Purpose: Children with incomplete Kawasaki disease (KD) and pyuria may be misdiagnosed with urinary tract infection (UTI) during the early phase of the prodrome. We investigated the percentage of UTI diagnoses preceding a KD diagnosis. Methods: Using the National Health Insurance data of South Korea, we assessed differences in UTI diagnoses made during the week preceding a KD diagnosis, according to demographic and geographic factors from November 2007-October 2019. Results: A total of 53,822 KD cases were identified, including 304 patients (0.56%) diagnosed with a UTI during the week preceding a KD diagnosis. The younger age group (0-11 months) showed the highest percentage of preceding UTI diagnoses (0.95%), with higher odds than 4-year-old children (3.12; 95% confidence interval, 2.05-4.77). Conclusions: These findings suggest a potentially misleading presentation of incomplete KD, a clinical conundrum requiring further investigation and validation, particularly in infants.

• Pediatric Infection and Vaccine
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• v.30 no.3
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• pp.152-158
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• 2023

Staphylococcus aureus (SA) is a common cause of skin and soft tissue infections. Panton-Valentine leukocidin (PVL) toxin-producing strain of SA has been discovered worldwide and is known to cause serious infections. However, reports of neonatal infections caused by PVL-positive SA are rare. Here, we report a case of severe skin and soft tissue infection caused by PVL-positive SA in a 7-day-old neonate. The patient was admitted to the emergency room with a history of fever for one day, tenderness, and sensation of buttocks heating. The infant presented with fever, tachycardia, poor general health, progressive tenderness, and edema of the buttocks on the day of admission. Ultrasonography and magnetic resonance imaging revealed necrotizing fasciitis involving the skin, soft tissue, and muscles. Specimens drained from the buttock lesions confirmed the presence of PVL-positive methicillin-resistant SA (MRSA), and there was no bacteremia. She recovered after one month of intravenous antibiotics and surgical drainages. One month after discharge, she was rehospitalized for otitis externa and was infected with MRSA again. Considering the PVL-positive strain, the patient was treated with intravenous linezolid and dressing. The patient underwent decolonization therapy in a 0.5% chlorhexidine bath and recovered completely without sequelae. This case suggests that aggressive drainage and antibiotic treatment are essential for PVL-producing MRSA infections, and additional decolonization is needed to prevent recurrence and community spread.