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Abstract Objective: A growing number of Korean adolescents consume energy drinks, which may increase the risk of obesity, anxiety and insomnia. We examined whether poor sleep was associated with energy drink consumption among study participants. Design: We used a cross-sectional design. Setting: The Korea Youth Risk Behavior Web-Based Survey data from 2019. Participants: To determine the association between sleep and energy drink consumption, we compared the independent variables for 50,455 adolescents in Korea (aged 14–19 years) using multivariate logistic regression and sensitivity analyses. Results: In Korea, 69·5 % adolescents consumed energy drinks, 17·1 % slept for less than 5 h, 22·4 % slept for 5–6 h, 23·8 % slept for 6–7 h, 19·9 % slept for 7–8 h and 16·7 % slept for 8 h or more. Regarding sleep satisfaction, 21·0 % reported sufficient, 32·6 % reported just enough and 46·5 % reported insufficient. Regarding sleep duration, it was found that less than 5 h (OR, 2·36; 95 % CI (2·14, 2·60)) and lower sleep satisfaction (OR, 1·12; 95 % CI (1·03, 1·21)) were highly associated with energy drink consumption, with statistical significance at P < 0·05. Adolescents with lower sleep duration (adjusted OR (aOR), 6·37; 95 % CI (4·72, 8·61)) and a lack of sleep satisfaction (aOR, 1·44; 95 % CI (1·16, 1·78)) reported drinking a high amount of energy drinks, that is, at least once a day. Conclusion: In addition to efforts to decrease the amount of energy drinks consumed, sleep hygiene education needs to be strengthened.

Abstract Background Frequent Emergency Department (ED) visitors are identified by the policymakers to reduce avoidable ED visits and lessen the financial and operational burden. This study aimed to identify the factors related to the frequent use of ED services. Methods This nationwide, cross-sectional observational study was conducted using information obtained from the 2019 National Emergency Department Information System (NEDIS) database. Frequent ED users were defined as patients with four or more ED visits a year. We performed multiple logistic regression analyses to verify the relationship among sociodemographic characteristics, residential characteristics, clinical characteristics, and frequency of ED visits. Results Among 4,063,640 selected patients, 137,608 patients visited the ED four or more times a year (total number of visits = 735,502 times), which accounted for 3.4% and 12.8% of the total number of ED users and ED visits, respectively. A high ED visit frequency was associated with male sex, age 19 years with level 1 severity (resuscitation). Conclusions Health service accessibility factors, including low income and medical resource imbalance, were associated with frequent ED visits. Future large-scale prospective cohort studies are warranted to establish an efficient emergency medical system.

Abstract It remains uncertain whether albuminuria can identify elderly patients with diabetes at a high risk of incident end-stage kidney disease (ESKD) or mortality. 3065 patients (aged ≥ 65 years) with type 2 diabetes were included. We examined the association between albuminuria stages (normoalbuminuria, A1; microalbuminuria, A2; and macroalbuminuria, A3) and the risk of incident ESKD and all-cause mortality for each age group (65–69, 70–74, and ≥ 75 years). A2 and A3 were observed in 25.5% and 9.4% of the subjects, respectively. For A1, A2, and A3, the probabilities of ESKD at 8 years were 1.0%, 6.3%, and 29.7% (P

The objective was to determine the association between health-related behaviour with overweight and obesity in South Korean adults by using the Korean National Health and Nutritional Examination Survey (KNHANES) 2018-2020. The study participants were 16,784 aged ≥ 20years. The variables were socio-demographic, lifestyle, food habits and metabolic conditions. The logistic regression analysis performed to find the association by the odds ratio (OR, 95% CI). MCA performed to identify risk factors were computed for overweight and obesity. Overweight and obesity were significantly associated with health behaviour, high income (OR = 1.26; 95% CI: 1.15-1.39), smoking(OR = 1.29; 95% CI: 1.08-1.53), low physical activity(OR = 3.23; 95% CI: 1.79-4.69), diabetes(OR = 2.70; 95% CI: 1.62-4.50), high cholesterol and low HDL(OR = 3.98; 95%CI:2.65-5.97). The high discriminant variables of MCA were aged over 60years, lower education, high income, diabetes, lack of physical activity, and high cholesterol. The findings confirm that the OR of obesity and overweight was likely associated with health behaviour patterns. Besides, it indicates the MCA would be very effective to identify the population-based data context than individual data and it may suggest that more research on association between health behaviours and obesity prevention interventions should be developed for each age group for better health outcomes.

ObjectiveThis study examined whether pandemic related family economic hardships influenced adolescents' mental health during the COVID-19 pandemic in Korea.MethodsData were collected from 54,948 adolescents who participated in the 2020 Korea Youth Risk Behavior Web-Based Survey. We performed a multiple logistic regression analysis to examine the association between family economic hardship and mental health (anxiety, depressive symptoms, and suicidal ideation).ResultsAmong the adolescents, 39.7, 24.7, and 5.9% reported slight, moderate, and severe economic hardship, respectively. COVID-19 related family economic hardship was significantly associated with higher odds of adolescents reporting anxiety, depressive symptoms, and suicidal ideation. This association was stronger among adolescents with low to middle family economic status.ConclusionsThis study suggests that adolescents from more economically vulnerable families are likely to be at a higher risk for long-term mental health effects due to the financial consequences of the COVID-19 pandemic.

This study aimed to investigate the association between socioeconomic status (SES) and healthcare utilization by children with allergic diseases. We determined SES based on parental occupation and household income. A cross-sectional study was conducted using the Korean National Health and Nutritional Examination Survey (KNHANES) between 2015 and 2019 with participants who were under 18 years of age. The presence of allergic conditions was determined by a self-reported survey of parental response and healthcare utilization data (such as inpatient and outpatient visits). Moreover, we categorized SES into four quantiles (Q1–Q4) based on household income per annum. Then, the data were analyzed using chi-square tests and multivariate logistic regression analysis with confidence intervals (CIs) of 95%, and p < 0.05 was considered significant. A total of 3250 participants were involved in this study. The percentage of allergic diseases was 67.9% for allergic asthma and 32.1% for atopic dermatitis. It was found that the participants who were over 13 years old had atopic dermatitis and were more likely to visit the hospital than younger children. Additionally, the highest SES group in Q4 demonstrated higher healthcare utilization (OR = 1.58; 95% CI, 1.14–1.76) than other SES groups. Our study reveals that parental socioeconomic characteristics are related to the use of healthcare services for children with allergic disorders in Korea. These results highlight the need for public health actions and research to overcome the SES gap among children with allergic diseases.

Abstract Background Although urinary angiotensinogen (AGT) and renin reflect intrarenal renin-angiotensin system activity and are enhanced in proteinuric chronic kidney disease, the clinical value of urinary AGT and renin levels during antiproteinuric treatment has yet to be determined. We investigated the clinical usefulness of initial urinary AGT or renin to determine the antiproteinuric effects of angiotensin receptor blockers (ARBs). Methods This multicenter, prospective, single-arm study included 205 patients with overt proteinuria (urinary protein/creatinine ratio [uPCR] ≥ 1 mg/mg) enrolled between April 2009 and December 2011. All patients were treated with valsartan. The urinary AGT/creatinine ratio (uAGT/Cr) was measured at the baseline and 24 weeks, and the renin/creatinine ratio (uR/Cr) was measured at the baseline. Fifty-six patients were followed-up for 5 years. Results The mean age was 47.6 years and 51.2% were male. The mean uPCR was 2.32 mg/mg and the mean eGFR was 63.2 mL/min/1.73m2. Natural logarithms (ln) (uAGT/Cr), ln(uR/Cr), and diabetes mellitus were associated with proteinuria decrement (decrease in uPCR ≥1 mg/mg). Ln(uAGT/Cr) was an independent predictor for proteinuria decrement (OR 1.372, 95% CI, 1.068–1.762, P = 0.013). Among the 56 patients followed-up for 5 years, Δln(uAGT/Cr) at 24 weeks was an independent predictor for uPCR

Abstract Objectives AXL‐mediated activation of aberrant tyrosine kinase drives various oncogenic processes and facilitates an immunosuppressive microenvironment. We evaluated the anti‐tumor and anti‐metastatic activities of SKI‐G‐801, a small‐molecule inhibitor of AXL, alone and in combination with anti‐PD‐1 therapy. Methods In vitro pAXL inhibition by SKI‐G‐801 was performed in both human and mouse cancer cell lines. Immunocompetent mouse models of tumor were established to measure anti‐metastatic potential of SKI‐G‐801. Furthermore, SKI‐G‐801, anti‐PD‐1 or their combination was administered as an adjuvant or neoadjuvant in the 4T1 tumor model to assess their potential for clinical application. Results SKI‐G‐801 robustly inhibited pAXL expression in various cell lines. SKI‐G‐801 alone or in combination with anti‐PD‐1 potently inhibited metastasis in B16F10 melanoma, CT26 colon and 4T1 breast models. SKI‐G‐801 inhibited the growth of B16F10 and 4T1 tumor‐bearing mice but not immune‐deficient mice. An antibody depletion assay revealed that CD8+ T cells significantly contributed to SKI‐G‐801‐mediated survival. Anti‐PD‐1 and combination group were observed the increased CD8+Ki67+ and effector T cells and M1 macrophage and decreased M2 macrophage, and granulocytic myeloid‐derived suppressor cell (G‐MDSC) compared to the control group. The neoadjuvant combination of SKI‐G‐801 and anti‐PD‐1 therapy achieved superior survival benefits by inducing more profound T‐cell responses in the 4T1 syngeneic mouse model. Conclusion SKI‐G‐801 significantly suppressed tumor metastasis and growth by enhancing anti‐tumor immune responses. Our results suggest that SKI‐G‐801 has the potential to overcome anti‐PD‐1 therapy resistance and allow more patients to benefit from anti‐PD‐1 therapy.

This study aimed to identify the characteristics of walk-in patients who visited a dental university hospital more than once (returning patient). The factors affecting walk-in visits were analyzed in relation to demographic, appointment, and treatment characteristics among 146,567 cases treated between 1 March 2019 and 29 February 2020. Multiple logistic regression was used to assess factors influencing walk-in visits. The walk-in rate was 14.1%. The likelihood of walk-in visits was higher in men, patients aged 20–39 years, patients residing in Seoul, and hospital employees or their family members. Walk-in visits were more likely to take place from 8:00 to 9:59 and on Saturdays and Mondays. The walk-in odds ratios differed depending on the treatment department and diagnosis. Return patients had higher odds of walk-in visits for treatments not covered by insurance. The probability of being a walk-in patient was lower among patients who also received treatment in other departments on the same day than among those who did not. These results indicate that each examined factor has a predictable pattern. The findings also suggest a relatively high percentage of walk-in cases in dental university hospitals and that walk-in patients differ in their characteristics from patients with appointments.

Purpose In Kawasaki disease (KD) patients, coronary artery complications, incomplete and refractory types occur more frequently in patients with streptococcal or other bacterial/viral infections. Recently, we observed a higher incidence of coronary lesions in KD patients with high anti-streptolysin O (ASO) titer. Therefore, we hypothesized that KD patients diagnosed with concurrent streptococcal infection have poor prognoses, with respect to treatment response and development of coronary artery lesions. Methods A retrospective review was performed in 723 patients with KD who were admitted to 2 major hospitals between June 2010 and September 2017. Results Among 723 patients with KD, 11 initially showed an elevated ASO titer (>320 IU/mL) or elevated follow-up ASO titer after treatment. Of these patients, 5 showed no response to the first intravenous immunoglobulin treatment, 3 had abnormalities of the coronary arteries. This is a significantly higher proportion of patients with a high ASO titer (n=3, 27.3%) than those with a normal ASO titer (n=53 [7.4%], P=0.047). A severe clinical course was seen in 81.8% of patients in the high ASO group versus 14.5% of patients in the normal ASO group. Conclusion It is not certain whether acute streptococcal infection may cause KD, but this study revealed that KD with high ASO titers showed higher rates of severe clinical course. It may be helpful to analyze concurrent streptococcal infection in patients with a severe clinical course.

Leukocyte adhesion deficiency is a rare primary immunodeficiency and autosomal recessive disorder caused by a mutation in the gene encoding CD18, which is a constituent of leukocyte integrins. Clinical features usually begin with a delay in the separation of the umbilical cord in the neonatal period, and are characterized by marked leukocytosis with infection, delayed wound healing, and repeated bacterial and fungal infections. We experienced a case of leukocyte adhesion deficiency diagnosed in the neonatal period, in which a late preterm infant admitted to neonatal intensive care unit presented with a septic hip. Flow cytometry analysis of whole blood showed a decrease in the expression of CD11b/CD18. This is the first case of leukocyte adhesion deficiency with neonatal septic hip diagnosed in Korea.

Abstract Background Despite aggressive application of continuous renal replacement therapy (CRRT) in critically ill patients with acute kidney injury (AKI), there is no consensus on diuretic therapy when discontinuation of CRRT is attempted. The effect of diuretics on discontinuation of CRRT in critically ill patients was evaluated. Methods This retrospective cohort study enrolled 1176 adult patients who survived for more than 3 days after discontinuing CRRT between 2009 and 2014. Patients were categorized depending on the re-initiation of renal replacement therapy within 3 days after discontinuing CRRT or use of diuretics. Changes in urine output (UO) and renal function after discontinuing CRRT were outcomes. Predictive factors for successful discontinuation of CRRT were also analyzed. Results The CRRT discontinuation group had a shorter duration of CRRT, more frequent use of diuretics after discontinuing CRRT, and greater UO on the day before CRRT discontinuation [day minus 1 (day − 1)]. The diuretics group had greater increases in UO and serum creatinine elevation after discontinuing CRRT. In the CRRT discontinuation group, continuous infusion of furosemide tended to increase UO more effectively. Multivariable regression analysis identified high day − 1 UO and use of diuretics as significant predictors of successful discontinuation of CRRT. Day − 1 UO of 125 mL/day was the cutoff value for predicting successful discontinuation of CRRT in oliguric patients treated with diuretics following CRRT. Conclusions Day − 1 UO and aggressive diuretic therapy were associated with successful CRRT discontinuation. Diuretic therapy may be helpful when attempting CRRT discontinuation in critically ill patients with AKI, by inducing a favorable fluid balance, especially in oliguric patients.

Sirt1, a member of the sirtuin gene family, encodes the most conserved mammalian NAD+-dependent deacetylase enzyme responsible for removing acetyl groups from many proteins. The Sirt1 gene is known as a longevity gene whose knockout in mice leads to decreased lifespan relative to the wild type. This study aimed to explore phenotypic changes in zebrafish Sirt1-knockouts and to investigate the function of the Sirt1 gene. Targeted knockout of Sirt1 in zebrafish (Danio rerio) was achieved using the CRISPR-Cas9 genome editing system. We created a 4-bp insertion-homozygote Sirt1-knockout zebrafish. Although there was no evident difference in appearance in the early stages of development, a significant increase in reactive oxygen species and in the extent of apoptosis in Sirt1-knockout zebrafish was observed. Sirt1 knockout caused inflammatory genes, including IL-1b, IL-6 and TNF-α to be highly expressed. Additionally, the lack of Sirt1 caused chronic inflammation and intestinal atrophy, thereby increasing pro-apoptotic events, which ultimately reduced the lifespan of transgenic zebrafish. Overall, our data demonstrate that lack of Sirt1 caused a significantly increased generation of reactive oxygen species that resulted in chronic inflammation and regeneration. Continuous repetition of these events played an important role in accelerating aging, thereby decreasing lifespan. Our findings using the knockout zebrafish model confirmed the association of the Sirt1 gene to aging processes and lifespan. Furthermore, the Sirt1-knockout mutant zebrafish developed in our study will surely be a valuable model to explore the mechanism of chronic inflammation.

Visceral pain frequently produces referred pain at somatic sites due to the convergence of somatic and visceral afferents. In skin overlying the referred pain, neurogenic spots characterized by hyperalgesia, tenderness and neurogenic inflammation are found. We investigated whether neurogenic inflammatory spots function as acupoints in the rat model of bile duct ligation-induced liver injury. The majority of neurogenic spots were found in the dorsal trunk overlying the referred pain and matched with locations of acupoints. The spots, as well as acupoints, showed high electrical conductance and enhanced expression of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP). Electroacupuncture at neurogenic spots reduced serum hepatocellular enzyme activities and histological patterns of acute liver injury in bile duct ligation (BDL) rats. The results suggest that the neurogenic spots have therapeutic effects as acupoints on hepatic injury in bile-duct ligated rats.

Severe combined immunodeficiency (SCID) mice have widely been used as hosts for human tumor cell xenograft study. This animal model, however, is labor intensive. As zebrafish is largely emerging as a promising model system for studying human diseases including cancer, developing efficient immunocompromised strains for tumor xenograft study are also demanded in zebrafish. Here, we have created the Prkdc-null SCID zebrafish model which provides the stable immune-deficient background required for xenotransplantation of tumor cell. In this study, the two transcription activator-like effector nucleases that specifically target the exon3 of the zebrafish Prkdc gene were used to induce a frame shift mutation, causing a complete knockout of the gene function. The SCID zebrafish showed susceptibility to spontaneous infection, a well-known phenotype found in the SCID mutation. Further characterization revealed that the SCID zebrafish contained no functional T and B lymphocytes which reflected the phenotypes identified in the mice SCID model. Intraperitoneal injection of human cancer cells into the adult SCID zebrafish clearly showed tumor cell growth forming into a solid mass. Our present data show the suitability of using the SCID zebrafish strain for xenotransplantation experiments, and in vivo monitoring of the tumor cell growth in the zebrafish demonstrates use of the animal model as a new platform of tumor xenograft study.

RNA granules and exosomes produced by tumour cells under various stresses in the microenvironment act as critical determinants of cell survival by promoting angiogenesis, cancer metastasis, chemoresistance, and immunosuppression. Meanwhile, developmental cancer/testis (CT) antigens that are normally sequestered in male germ cells of the testes, but which are overexpressed in malignant tumour cells, can function as tumour antigens triggering immune responses. As CT antigens are potential vaccine candidates for use in cancer immunotherapy, they could be targeted together with crosstalk between stress granules, exosomes, and immune cells for a synergistic effect. In this review, we describe the effects of exosomes and exosomal components presented to the recipient cells under different types of stresses on immune cells and cancer progression. Furthermore, we discuss their significance for cancer immunity, as well as the outlook for their future application.

Fanconi syndrome (FS) is a rare condition that is characterized by defects in the proximal tubular function. A 48-year-old woman was admitted for evaluation of proteinuria. The patient showed normal anion gap acidosis, normoglycemic glycosuria, hypophosphatemia, and hypouricemia. Thus, her condition was compatible with FS. The M peak was found behind the beta globulin region in urine protein electrophoresis. Upon bone marrow examination, we found that 24% of cells were CD138+ plasma cells with kappa restriction. From a kidney biopsy, we found crystalline inclusions within proximal tubular epithelial cells. Thereafter, she was diagnosed with FS accompanied by multiple myeloma. The patient received chemotherapy and autologous stem cell transplantation, and obtained very good partial hematologic response. However, proximal tubular dysfunction was persistent until 1 year after autologous stem cell transplantation. In short, we report a case of FS accompanied by multiple myeloma, demonstrating crystalline inclusion in proximal tubular cells on kidney biopsy.

Peptide-based therapeutics have traditionally faced challenges, including instability in the bloodstream and limited cell membrane permeability. However, recent advancements in α-helix stapled peptide modification techniques have rekindled interest in their efficacy. Notably, these developments ensure a highly effective method for improving peptide stability and enhancing cell membrane penetration. Particularly in the realm of antimicrobial peptides (AMPs), the application of stapled peptide techniques has significantly increased peptide stability and has been successfully applied to many peptides. Furthermore, constraining the secondary structure of peptides has also been proven to enhance their biological activity. In this review, the entire process through which hydrocarbon-stapled antimicrobial peptides attain improved drug-like properties is examined. First, the essential secondary structural elements required for their activity as drugs are validated, specific residues are identified using alanine scanning, and stapling techniques are strategically incorporated at precise locations. Additionally, the mechanisms by which these structure-based stapled peptides function as AMPs are explored, providing a comprehensive and engaging discussion.

Iron is crucial for the metabolism and growth of most prokaryotic cells. The ferric uptake regulator (Fur) protein plays a central role in regulating iron homeostasis and metabolic processes in bacteria. It ensures the proper utilization of iron and the maintenance of cellular functions in response to environmental cues. Fur proteins are composed of an N-terminal DNA-binding domain (DBD) and a C-terminal dimerization domain (DD), typically existing as dimers in solution. Fur proteins have conserved metal-binding sites named S1, S2, and S3. Among them, site S2 serves as a regulatory site, and metal binding at S2 results in conformational changes. Additionally, as a transcriptional regulator, Fur specifically binds to a consensus DNA sequence called the Fur box. To elucidate the structural and functional properties of Fur proteins, various structures of metal- or DNA-bound Fur proteins or apo-Fur proteins have been determined. In this review, we focus on the structural properties of Fur proteins according to their ligand-bound state and the drug development strategies targeting Fur proteins. This information provides valuable insights for drug discovery.

Alzheimer's disease (AD) is characterized by the deposition of aggregated beta-amyloid (Abeta), which triggers a cellular stress response called the unfolded protein response (UPR). The UPR signaling pathway is a cellular defense system for dealing with the accumulation of misfolded proteins but switches to apoptosis when endoplasmic reticulum (ER) stress is prolonged. ER stress is involved in neurodegenerative diseases including AD, but the molecular mechanisms of ER stress-mediated Abeta neurotoxicity still remain unknown. Here, we show that treatment of Abeta triggers the UPR in the SK-N-SH human neuroblastoma cells. Abeta mediated UPR pathway accompanies the activation of protective pathways such as Grp78/Bip and PERK-eIF2alpha pathway, as well as the apoptotic pathways of the UPR such as CHOP and caspase-4. Knockdown of PERK enhances Abeta neurotoxicity through reducing the activation of eIF2alpha and Grp8/Bip in neurons. Salubrinal, an activator of the eIF2alpha pathway, significantly increased the Grp78/Bip ER chaperone resulted in attenuating caspase-4 dependent apoptosis in Abeta treated neurons. These results indicate that PERK-eIF2alpha pathway is a potential target for therapeutic applications in neurodegenerative diseases including AD.