Background: Hepatic steatosis, which involves the excessive accumulation of lipid droplets in hepatocytes, presents a significant global health concern due to its association with obesity and metabolic disorders. Inflammation plays a crucial role in the progression of hepatic steatosis; however, the precise molecular mechanisms responsible for this process remain unknown. Methods: This study investigated the involvement of the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome and the forkhead box O6 (FoxO6) transcription factor in the pathogenesis of hepatic steatosis. We monitored the NLRP3 inflammasome and lipogenesis in mice overexpressing the constitutively active (CA)-FoxO6 allele and FoxO6-null mice. In an in vitro study, we administered palmitate to liver cells overexpressing CA-FoxO6 and measured changes in lipid metabolism. Results: We administered palmitate treatment to clarify the mechanisms through which FoxO6 activates cytokine interleukin (IL)-1β through the NLRP3 inflammasome. The initial experiments revealed that dephosphorylation led to palmitate-induced FoxO6 transcriptional activity. Further palmitate experiments showed increased expression of IL-1β and the hepatic NLRP3 inflammasome complex, including adaptor protein apoptotic speck protein containing a caspase recruitment domain (ASC) and pro-caspase-1. Furthermore, thioredoxin-interacting protein (TXNIP), a key regulator of cellular redox conditions upstream of the NLRP3 inflammasome, was induced by FoxO6 in the liver and HepG2 cells. Conclusion The findings of this study shed light on the molecular mechanisms underpinning the FoxO6-NLRP3 inflammasome axis in promoting inflammation and lipid accumulation in the liver.

Background: Unlike conventional T cells, innate and virtual-memory CD8 T cells in naïve mice acquire their memory phenotypes and functions in the absence of antigenic encounters in a cytokine-dependent manner. The relevant cytokines include interleukin-4 (IL-4), type I interferon, and interleukin-15 (IL-15). Moreover, exogenous IL-4 can also induce de novo generation and/or expansion of the virtual-memory CD8 T cell population. In this study, we investigated whether exogenous IL-4 could enhance the immune response to a viral infection. Results: In vivo administration of IL-4 and an anti-IL-4 antibody complex (IL-4C) increased CXCR3 expression in both memory and naïve phenotype CD8 T cells in the absence of antigenic stimulation, and protected mice from lethal influenza infection. Flow cytometric analysis of lung-infiltrating immune cells on day 5 after virus infection revealed higher numbers of antigen-specific and bystander CD8 T cells in IL-4C-treated mice than in control mice. In particular, the bystander CD8 T cells were a naïve or evident memory phenotypes. Crucially, an anti-CXCR3 blocking antibody abrogated this IL-4C effect, reflecting that the increased accumulation of CD8 T cells in the lungs after IL-4C treatment is dependent on CXCR3. Conclusions These data demonstrate that exogenous IL-4C plays a protective role by enhancing CXCR3-dependent migration of CD8 T cells into influenza-infected lungs.

Background: Influenza A viruses (IAVs) have long posed a threat to humans, occasionally causing significant morbidity and mortality. The initial immune response is triggered by infected epithelial cells, alveolar macrophages and dendritic cells. However, an exaggerated innate immune response can result in severe lung injury and even host mortality. One notable pathology observed in hosts succumbing to severe influenza is the excessive influx of neutrophils and monocytes into the lung. In this study, we investigated a strategy for controlling lung immunopathology following severe influenza infection. Results: To evaluate the impact of innate immunity on influenza-associated lung injury, we employed CB17.SCID and NOD.SCID mice. NOD.SCID mice exhibited slower weight loss and longer survival than CB17.SCID mice following influenza infection. Lung inflammation was reduced in NOD.SCID mice compared to CB17.SCID mice. Bulk RNA sequencing analysis of lung tissue showed significant downregulation of 827 genes, and differentially expressed gene analysis indicated that the cytokine-cytokine receptor interaction pathway was predominantly downregulated in NOD.SCID mice. Interestingly, the expression of the Cxcl14 gene was higher in the lungs of influenza-infected NOD.SCID mice than in CB17.SCID mice. Therefore, we induced overexpression of the Cxcl14 gene in the lung using the adeno-associated virus 9 (AAV9)-vector system for target gene delivery. However, when we administered the AAV9 vector carrying the Cxcl14 gene or a control AAV9 vector to BALB/c mice from both groups, the morbidity and mortality rates remained similar. Both groups exhibited lower morbidity and mortality than the naive group that did not receive the AAV9 vector prior to IAV infection, suggesting that the pre-administration of the AAV9 vector conferred protection against lethal influenza infection, irrespective of Cxcl14 overexpression. Furthermore, we found that pre-inoculation of BALB/c mice with AAV9 attenuated the infiltration of trans-macrophages, neutrophils and monocytes in the lungs following IAV infection. Although there was no difference in lung viral titers between the naive group and the AAV9 pre-inoculated group, pre-inoculation with AAV9 conferred lung injury protection against lethal influenza infection in mice. Conclusions Our study demonstrated that pre-inoculation with AAV9 prior to IAV infection protected mouse lungs from immunopathology by reducing the recruitment of inflammatory cells.

OBJECTIVES: Studies evaluating weight changes during the coronavirus disease 2019 (COVID-19) pandemic have yielded inconsistent results, and most of those studies were based on self-reported anthropometric measures. We investigated changes in body mass index (BMI), professionally measured waist circumference (WC), and metabolic syndrome components from before to during the pandemic in a sample of the adult population in Korea. METHODS: This retrospective study included 1,118 male and female (age≥18 years) who underwent health checkups at a university medical center between January 1, 2016 and March 31, 2022. Changes in BMI, lifestyles, and metabolic syndrome components during the pandemic were analyzed using the paired t-test, McNemar test, generalized estimating equations, and repeated-measures analysis of variance. RESULTS: Changes in body weight, BMI, and body fat percentage during the pandemic were not clinically significant. However, statistically significant results were found for decreased physical activity (p<0.001) and WC (p<0.001), and exacerbation of all metabolic syndrome components (except serum triglyceride levels). Moreover, the metabolic syndrome prevalence increased significantly from 20.2% to 31.2% during the pandemic (p<0.001). The prevalence of abdominal obesity and high fasting blood glucose levels also significantly increased from 2019 to 2021. CONCLUSIONS Metabolic syndrome, its components, and fat distribution worsened significantly after the implementation of social distancing and lockdowns, despite no clinically significant changes in body weight and BMI. Further studies on the post- pandemic period should investigate the long-term impact of social lockdowns on BMI and the prevalence of metabolic syndrome.

Purpose: This study aimed to describe nurses’ perceived needs and barriers to pediatric palliative care (PPC). Methods: Mixed methods with an embedded design were applied. An online survey was conducted for nurses who participated in the End-of-Life Nursing Education Consortium- Pediatric Palliative Care (ELNEC-PPC) train-the-trainer program, of whom 63 responded. Quantitative data were collected with a survey questionnaire developed through the Delphi method. The 47 items for needs and 15 items for barriers to PPC were analyzed with descriptive statistics. Qualitative data were collected through openended questions and analyzed with topic modeling techniques. Results: The mean scores of most subdomains of the PPC needs were 3.5 or higher out of 4, and those of PPC barriers ranged from 3.22 to 3.56, indicating the items in the questionnaire developed in this study properly reflect each factor. The needs for PPC were divided into 4 categories: “children and adolescents,” “families,” “PPC management system,” and “community-based PPC.” Meanwhile, PPC barriers were divided into 3 categories: “healthcare delivery system,” “healthcare provider,” and “client.” The keywords derived from the topic modeling were perception, palliative, children, and education for necessities and lack, perception, medical care, professional care providers, service, and system for barriers to PPC. Conclusion In this study, by using mixed-methods, items of nurses’ perceived needs and barriers to PPC were identified, categorized, and weighted, and their meanings were explored. For the stable establishment of PPC, the priority should be given to improving perceptions of PPC, establishing an appropriate system, and training professional care providers.

Background: Complex regional pain syndrome (CRPS) is an intractable pain disease with various symptoms. Here, we investigated the disease status, work life, sleep problems, medical insurance, economic status, psychological problems, and quality of life (QOL) of CRPS patients. Methods: CRPS patients from 37 university hospitals in South Korea were surveyed.The survey questionnaire consisted of 24 questions on the following aspects of CRPS patients: sex, age, occupation, cause of injury, activities of daily living (ADL), pain severity, sleep disturbance, level of education, economic status, therapeutic effect, and suicidal ideation. Additionally, the abbreviated World Health Organization Quality of Life (WHOQOL-BREF) questionnaire, consisting of 26 questions, was used to identify the status of QOL. Results: A total of 251 patients completed the questionnaire. According to the survey, 54.2% patients could not perform ADL on their own. Over the previous week, the mean pain score was 7.15 ± 1.78 (out of a total of 10 points); 92.1% of patients had sleep disorders and 80.5% had suicidal ideation, with most patients suffering from psychological problems. The average for each domain of WHOQOL-BREF was as follows: 21.74 ± 14.77 for physical, 25.22 ± 17.66 for psychological, 32.02 ± 22.36 for social relationship, and 30.69 ± 15.83 for environmental (out of a total of 100 points each). Occupation, ADL, sleep time, therapeutic effect, and suicidal ideation were statistically correlated with multiple domains. Conclusions Most patients had moderate to severe pain, economic problems, limitations of their ADL, sleep problems, psychological problems, and a low QOL score.

Background: Complex regional pain syndrome (CRPS) is an intractable pain disease with various symptoms. Here, we investigated the disease status, work life, sleep problems, medical insurance, economic status, psychological problems, and quality of life (QOL) of CRPS patients. Methods: CRPS patients from 37 university hospitals in South Korea were surveyed.The survey questionnaire consisted of 24 questions on the following aspects of CRPS patients: sex, age, occupation, cause of injury, activities of daily living (ADL), pain severity, sleep disturbance, level of education, economic status, therapeutic effect, and suicidal ideation. Additionally, the abbreviated World Health Organization Quality of Life (WHOQOL-BREF) questionnaire, consisting of 26 questions, was used to identify the status of QOL. Results: A total of 251 patients completed the questionnaire. According to the survey, 54.2% patients could not perform ADL on their own. Over the previous week, the mean pain score was 7.15 ± 1.78 (out of a total of 10 points); 92.1% of patients had sleep disorders and 80.5% had suicidal ideation, with most patients suffering from psychological problems. The average for each domain of WHOQOL-BREF was as follows: 21.74 ± 14.77 for physical, 25.22 ± 17.66 for psychological, 32.02 ± 22.36 for social relationship, and 30.69 ± 15.83 for environmental (out of a total of 100 points each). Occupation, ADL, sleep time, therapeutic effect, and suicidal ideation were statistically correlated with multiple domains. Conclusions Most patients had moderate to severe pain, economic problems, limitations of their ADL, sleep problems, psychological problems, and a low QOL score.

PURPOSE: The aim of this study was to understand and describe difficulties and needs experienced by head nurses in the clinical practice education of nursing students. METHODS: A qualitative descriptive method was employed. A convenience sampling method was used to recruit participants from four hospitals in South Korea. Twenty-one head nurses participated in the first interview and 17 of them participated in the second interview. Data were collected through two in-depth interviews and field notes were written. Qualitative content analysis method was utilized for data analysis using ATLAS.ti 6.2 software. RESULTS: Thirty-one codes and twelve categories were identified. Four themes emerged from data analysis, which included ‘too many tasks’, ‘limitations of student education’, ‘many differences’, and ‘lack of support and resources.’ CONCLUSION: This qualitative study described head nurses' many difficulties and needs in the clinical practice education of nursing students. The results of this study provide valuable understanding and knowledge of head nurses' experiences in students' clinical education, which leads to improvement of the quality of clinical education for nursing students.
Education* ; Head* ; Humans ; Korea ; Methods ; Nursing* ; Nursing, Supervisory ; Qualitative Research* ; Statistics as Topic ; Students, Nursing*

Epidemic keratoconjunctivitis (EKC) and acute hemorrhagic conjunctivitis (AHC) are common diseases caused by human adenoviruses (HAdV) and enteroviruses, respectively, in South Korea. However, there are limited studies on the molecular epidemiology of viral conjunctivitis in South Korea. The main objective of this study was to characterize the genotypes of adenoviruses and enteroviruses causing viral conjunctivitis in the southwest region of South Korea. We collected conjunctival swabs from 492 patients with suspected cases of viral conjunctivitis from 6 ophthalmic hospitals in Gwangju Metropolitan City, in South Korea, between 2012 and 2016. Of the 492 samples tested, HAdVs and enteroviruses were detected in 249 samples (50.6%) and 19 samples (3.9%), respectively. The genotype analysis detected HAdV-8 in 183 samples (73.5%), HAdV-37 in 14 samples (5.6%), and HAdV-3, and HAdV-4 in 9 samples (3.6%) each. We detected coxsackievirus A24 (CVA24) and coxsackievirus B1 (CVB1) in 8 samples (42.0%) and 4 samples (21.0%), respectively. We also reported for the first time HAdV-56-infected cases of EKC in South Korea. Furthermore, we found three cases of coinfection with HAdV and enterovirus genotypes in our samples. HAdV-8 and CVA24, the main causes of EKC and AHC, respectively, worldwide, were also found to be the predominant genotypes in our study.
Adenoviridae ; Adenoviruses, Human ; Coinfection ; Conjunctivitis, Acute Hemorrhagic ; Conjunctivitis, Viral* ; Enterovirus ; Genotype ; Gwangju ; Humans ; Keratoconjunctivitis ; Korea* ; Molecular Epidemiology*

BACKGROUND: Among the various signs and symptoms of orbital fractures, certain clinical findings warrant immediate surgical exploration, including gaze restriction, computed tomographic (CT) evidence of entrapment, and prolonged oculocardiac reflex. Despite proper surgical reconstruction, prolonged complications such as diplopia and gaze restriction can occur. This article evaluated the prognostic factors associated with prolonged complications of orbital fractures with muscle incarceration. METHODS: The medical records of 37 patients (37 orbits) with an orbital fracture with muscle incarceration from January 2001 to January 2015 were reviewed. The presence of Incarcerated muscle was confirmed via CT, as well as by intraoperative findings. Various factors potentially contributing to complications lasting for over 1 year after the injury were categorized and analyzed, including age, cause of injury, injury-to-operation time, operative time, fracture type, nausea, vomiting and other concomitant symptoms and injuries. RESULTS: All patients who presented with extraocular muscle limitations, positive CT findings, and/or a positive forced duction test underwent surgery. Of the 37 patients, 9 (24%) exhibited lasting complications, such as diplopia and gaze restriction. The mean follow-up period was 18.4 months (range, 1–108 months), while that of patients who experienced prolonged complications was 30.1 months (range, 13–36 months). Two factors were significantly associated with prolonged complications: injury-to-operation time and nausea/vomiting. Loss of vision, worsening of motility, and implant complication did not occur. CONCLUSIONS: Patients who present with gaze limitations, with or without other signs of a blow-out fracture, require a thorough evaluation and emergent surgery. A better prognosis is expected with a shorter injury-to-operation time and lack of nausea and vomiting at the initial presentation.
Diplopia ; Follow-Up Studies ; Humans ; Medical Records ; Nausea ; Operative Time ; Orbit* ; Orbital Fractures* ; Prognosis ; Reflex, Oculocardiac ; Vomiting