Objectives: . The recent expansion of eligibility for cochlear implantation (CI) by the U.S. Food and Drug Administration (FDA) to include infants as young as 9 months has reignited debates concerning the clinically appropriate cut-off age for pediatric CI. Our study compared the early postoperative trajectories of receptive and expressive language development in children who received CI before 9 months of age with those who received it between 9 and 12 months. This study involved a unique pediatric cohort with documented etiology, where the timing of CI was based on objective criteria and efforts were made to minimize the influence of parental socioeconomic status. Methods: . A retrospective review of 98 pediatric implantees recruited at a tertiary referral center was conducted. The timing of CI was based on auditory and language criteria focused on the extent of delay corresponding to the bottom 1st percentile of language development among age-matched controls, with patients categorized into very early (CI at <9 months), early (CI at 9–12 months) and delayed (CI at 12–18 months) CI groups. Postoperative receptive/expressive language development was assessed using the Sequenced Language Scale for Infants receptive and expressive standardized scores and percentiles. Results: . Only the very early CI group showed significant improvements in receptive language starting at 3 months post-CI, aligning with normal-hearing peers by 9 months and maintaining this level until age 2 years. During this period (<2 years), all improvements were more pronounced in receptive language than in expressive language. Conclusion . CI before 9 months of age significantly improved receptive language development compared to later CI, with improvements sustained at least up to the age of 2. This study supports the consideration of earlier CI, beyond pediatric Food and Drug Administration labeling criteria (>9 months), in children with profound deafness who have a clear deafness etiology and language development delays (<1st percentile).

Background: Zinc (Zn) is an essential cofactor for physiological homeostasis in the body.Zn oxide (ZnO), an inorganic compound that supplies Zn, exists in various sizes, and its bioavailability may vary depending on the size in vivo. However, comparative studies on the nutritional effects of micro-sized ZnO (M-ZnO) and nano-sized ZnO (N-ZnO) supplementation on Zn deficiency (ZnD) animal models have not been reported. Objectives: This study investigated the nutritional bioavailability of N-ZnO and M-ZnO particles in dietary-induced ZnD mice. Methods: Animals were divided into six experimental groups: normal group, ZnD control group, and four ZnO treatment groups (Nano-Low, Nano-High, Micro-Low, and MicroHigh). After ZnD induction, N-ZnO or M-ZnO was administered orally every day for 4 weeks. Results: ZnD-associated clinical signs almost disappeared 7 days after N-ZnO or M-ZnO administration. Serum Zn concentrations were higher in the Nano-High group than in the ZnD and M-ZnO groups on day 7 of ZnO treatment. In the liver and testis, Nano-Low and Nano-High groups showed significantly higher Zn concentrations than the other groups after 14-day treatment. ZnO supplementation increased Mt-1 mRNA expression in the liver and testis and Mt-2 mRNA expression in the liver. Based on hematoxylin-and-eosin staining results, N-ZnO supplementation alleviated histological damage induced by ZnD in the testis and liver. Conclusions This study suggested that N-ZnO can be utilized faster than M-ZnO for nutritional restoration at the early stage of ZnD condition and presented Mt-1 as an indicator of Zn status in the serum, liver, and testis.

Evidence suggests that the human respiratory tract, as with the gastrointestinal tract, has evolved to its current state in association with commensal microbes. However, little is known about how the airway microbiome affects the development of airway immune system. Here, we uncover a previously unidentified mode of interaction between host airway immunity and a unique strain (AIT01) of Staphylococcus epidermidis, a predominant species of the nasal microbiome. Intranasal administration of AIT01 increased the population of neutrophils and monocytes in mouse lungs. The recruitment of these immune cells resulted in the protection of the murine host against infection by Pseudomonas aeruginosa, a pathogenic bacterium.Interestingly, an AIT01-secreted protein identified as GAPDH, a well-known bacterial moonlighting protein, mediated this protective effect. Intranasal delivery of the purified GAPDH conferred significant resistance against other Gram-negative pathogens (Klebsiella pneumoniae and Acinetobacter baumannii) and influenza A virus. Our findings demonstrate the potential of a native nasal microbe and its secretory protein to enhance innate immune defense against airway infections. These results offer a promising preventive measure, particularly relevant in the context of global pandemics.

Background: Obesity, the prevalence of which is increasing due to the lack of exercise and increased consumption of Westernized diets, induces various complications, including ophthalmic diseases. For example, obesity is involved in the onset of cataracts. Methods: To clarify the effects and mechanisms of midodrine, an α1-adrenergic receptor agonist, in cataracts induced by obesity, we conducted various analytic experiments in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a rat model of obesity. Results: Midodrine prevented cataract occurrence and improved lens clearance in OLETF rats. In the lenses of OLETF rats treated with midodrine, we observed lower levels of aldose reductase, tumor necrosis factor-α, and sorbitol, but higher levels of hexokinase, 5’-adenosine monophosphate-activated protein kinase-alpha, adenosine 5´-triphosphate, peroxisome proliferator-activated receptordelta, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, superoxide dismutase, and catalase. Conclusion The ameliorating effects of midodrine on cataracts in the OLETF obesity rat model are exerted via the following three mechanisms: direct inhibition of the biosynthesis of sorbitol, which causes cataracts; reduction of reactive oxygen species and inflammation; and (3) stimulation of normal aerobic glycolysis.

Purpose: Since diabetes and hypertension frequently occur together, it is thought that these conditions may have a common pathogenesis. This study was designed to evaluate the anti-diabetic function of the anti-hypertensive drug fimasartan on C2C12 mouse skeletal muscle and HepG2 human liver cells in a high glucose state. Materials and Methods: The anti-diabetic effects and mechanism of fimasartan were identified using Western blot, glucose uptake tests, oxygen consumption rate (OCR) analysis, adenosine 5'-triphosphate (ATP) enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining for diabetic biomarkers in C2C12 cells. Protein biomarkers for glycogenolysis and glycogenesis were evaluated by Western blotting and ELISA in HepG2 cells. Results: The protein levels of phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK), p-AKT, insulin receptor substrate-1 (IRS-1), and glucose transporter type 4 (Glut4) were elevated in C2C12 cells treated with fimasartan. These increases were reversed by peroxisome proliferator-activated receptor delta (PPARδ) antagonist. ATP, OCR, and glucose uptake were increased in cells treated with 200 μM fimasartan. Protein levels of glycogen phosphorylase, glucose synthase, phosphorylated glycogen synthase, and glycogen synthase kinase-3 (GSK-3) were decreased in HepG2 cells treated with fimasartan. However, these effects were reversed following the addition of the PPARδ antagonist GSK0660. Conclusion In conclusion, fimasartan ameliorates deteriorations in glucose metabolism as a result of a high glucose state by regulating PPARδ in skeletal muscle and liver cells.

Background: Previous studies have presented evidence to support the significant association between red meat intake and colon cancer, suggesting that heme iron plays a key role in colon carcinogenesis. Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, exhibits anti-oxidative and anti-cancer effects. However, the effect of EGCG on red meatassociated colon carcinogenesis is not well understood. Objectives: We aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action. Methods: Hemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model. Results: In Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression.Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model. Conclusions We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.

Purpose: Since 2012, acetaminophen can be accessed easily not only at pharmacies but also at convenience stores. The relationship between the easy access of acetaminophen and the risk of poisoning has been controversial. Several studies also reported different results regarding the risk of acetaminophen poisoning after access to acetaminophen was relaxed. This study examined the long-term effects on the risk of acetaminophen poisoning after easy access to acetaminophen was implemented. Methods: This was a retrospective analysis of an emergency department (ED)-based in-depth Injury Surveillance Cohort by the Korea Center for Disease Control and prevention from 2011 to 2018. Poisoning cases were selected from the Cohort, and the incidence of acetaminophen poisoning and the characteristics of the cases of acetaminophen poisoning were analyzed. The purchase path and the amount of ingestion in acetaminophen poisoning were sub-analyzed from data of six EDs. Results: Of 57,326 poisoning cases, 4.0% (2,272 cases) were acetaminophen poisoning. Of 2,272 cases of acetaminophen poisoning, 42.8% (974 cases) required in-patient care after ED management. Two hundred and sixty-four of these 964 cases required intensive care. The rates of cases that required in-patient treatment and the rates of cases that required intensive care increased from 29.4% in 2011 to 48.1% in 2018, and from 3.1% in 2011 to 15.2% in 2018, respectively (p<0.001, p<0.001). In the poisoning group with in-depth toxic surveillance (n=15,908), the incidence and proportion of acetaminophen (AAP) poisoning increased from 55 cases per year to 187 cases per year and 4.9% to 6.1%, respectively (p=0.009, p<0.001, respectively). The most common age group of acetaminophen poisoning was teenagers, which is different from the most common age group of other pharmaceutical agents: the middle age group of 40-49 years (p<0.001). Of 15,908 in-depth toxic surveillance patients, 693 patients had AAP poisoning, of whom 377 cases (54.2%) purchased acetaminophen from a non-pharmacy. The proportions of the purchase path from non-pharmacy were 41.4% at 2011-12 and 56.4% (2013-18) (p=0.004). The amount of acetaminophen ingestion was 13.5±14.3 g at 2011-12 and 13.9±15.1 g at 2013-18 (p=0.794). Conclusion Although the incidence of acetaminophen poisoning did not increase remarkably in the short term after the implementation of the new regulation, the incidence of acetaminophen poisoning has increased slightly during the study period of 2017-18. In addition, the proportion of the purchase path from non-pharmacies has increased since the emergence of new regulations for the easy access of acetaminophen in 2012. The incidence of acetaminophen poisoning might have been affected after the increasing accessibility of acetaminophen in convenience stores. Continuous control of acetaminophen poisoning is required. Furthermore, the prevention of acetaminophen poisoning should be focused on teenagers with specialized school education programs.

Purpose: Since 2012, acetaminophen can be accessed easily not only at pharmacies but also at convenience stores. The relationship between the easy access of acetaminophen and the risk of poisoning has been controversial. Several studies also reported different results regarding the risk of acetaminophen poisoning after access to acetaminophen was relaxed. This study examined the long-term effects on the risk of acetaminophen poisoning after easy access to acetaminophen was implemented. Methods: This was a retrospective analysis of an emergency department (ED)-based in-depth Injury Surveillance Cohort by the Korea Center for Disease Control and prevention from 2011 to 2018. Poisoning cases were selected from the Cohort, and the incidence of acetaminophen poisoning and the characteristics of the cases of acetaminophen poisoning were analyzed. The purchase path and the amount of ingestion in acetaminophen poisoning were sub-analyzed from data of six EDs. Results: Of 57,326 poisoning cases, 4.0% (2,272 cases) were acetaminophen poisoning. Of 2,272 cases of acetaminophen poisoning, 42.8% (974 cases) required in-patient care after ED management. Two hundred and sixty-four of these 964 cases required intensive care. The rates of cases that required in-patient treatment and the rates of cases that required intensive care increased from 29.4% in 2011 to 48.1% in 2018, and from 3.1% in 2011 to 15.2% in 2018, respectively (p<0.001, p<0.001). In the poisoning group with in-depth toxic surveillance (n=15,908), the incidence and proportion of acetaminophen (AAP) poisoning increased from 55 cases per year to 187 cases per year and 4.9% to 6.1%, respectively (p=0.009, p<0.001, respectively). The most common age group of acetaminophen poisoning was teenagers, which is different from the most common age group of other pharmaceutical agents: the middle age group of 40-49 years (p<0.001). Of 15,908 in-depth toxic surveillance patients, 693 patients had AAP poisoning, of whom 377 cases (54.2%) purchased acetaminophen from a non-pharmacy. The proportions of the purchase path from non-pharmacy were 41.4% at 2011-12 and 56.4% (2013-18) (p=0.004). The amount of acetaminophen ingestion was 13.5±14.3 g at 2011-12 and 13.9±15.1 g at 2013-18 (p=0.794). Conclusion Although the incidence of acetaminophen poisoning did not increase remarkably in the short term after the implementation of the new regulation, the incidence of acetaminophen poisoning has increased slightly during the study period of 2017-18. In addition, the proportion of the purchase path from non-pharmacies has increased since the emergence of new regulations for the easy access of acetaminophen in 2012. The incidence of acetaminophen poisoning might have been affected after the increasing accessibility of acetaminophen in convenience stores. Continuous control of acetaminophen poisoning is required. Furthermore, the prevention of acetaminophen poisoning should be focused on teenagers with specialized school education programs.

Objectives: . This study aimed to elucidate the patterns of upper airway collapse in obstructive sleep apnea (OSA) patients with a low body mass index (BMI). Methods: . We designed and conducted a retrospective cohort study. Consecutive patients diagnosed with OSA who underwent drug-induced sleep endoscopy (DISE) were included. Patients were classified into four groups according to their BMI. Age, sex, and polysomnography data were investigated. The patterns of upper airway collapse were characterized by the structures involved (soft palate, tongue base, lateral pharyngeal wall, and epiglottis). We compared the patterns of upper airway collapse in the supine and lateral decubitus position among the four BMI groups using the chi-square test and multivariate binary logistic regression analysis. Results: . A total of 627 patients (male, 517; mean age, 47.6±12.8 years) were included, consisting of 45, 79, 151, and 352 patients who were underweight or lower normal-weight (defined as the low BMI group), upper normal-weight, overweight, and obese, respectively. Severity indicators of OSA, such as the overall apnea-hypopnea index and duration of SaO2 below 90%, were significantly lower in patients with a low BMI than in obese patients, while their average oxygen saturation was significantly higher. The most common obstruction site in the supine position was the tongue base in patients with a low BMI (100%), whereas this obstruction site was significantly less common in obese patients (54.8%). Tongue base obstruction was mostly relieved in the lateral position, with no discernible obstruction in 86.7% of the low BMI patients. Conclusion . Airway obstruction in OSA patients with a low BMI is mostly due to tongue base obstruction, which improves in the lateral position. These characteristics should be kept in mind when considering treatment options for this subgroup of OSA patients.

Background/Aims: Several clinical factors have been used to predict the response for concurrent chemoradiotherapy (CCRT); however, these factors are insufficient for prognostic predictions. We investigated clinical factors to assess whether they could be used to predict the response to CCRT and the survival of patients with esophageal cancer. Methods: Patients with esophageal cancer underwent CCRT from January 2005 to December 2015. Response to CCRT was classified as progressive disease (PD), stationary disease (SD), partial remission (PR), or complete remission (CR). Factors to predict the response to CCRT and patient survival were subsequently investigated. Results: A total of 535 esophageal cancer patients underwent CCRT. Four hundred ninety-three patients were followed up, and patient outcomes were investigated. In the adjusted analysis, patients with advanced stage disease (relative risk [RR], 0.28 in stage III and 0.12 in stage IV compared to stage I), poor performance status, circumferential involvement (RR, 0.61), and male sex (RR, 0.31) were less likely to achieve CR. Advanced stage disease (hazard ratio [HR], 1.71 in stage III/IV), poor CCRT response (HR, 2.82 in PR, 4.47 in SD, 4.77 in PD compared to CR), and poor performance status (HR, 1.38 in ECOG 2–4) were found to increase mortality. Conclusions Advanced stage disease, poor performance status, male sex, and circumferential involvement were independent predictive factors for a poor response to CCRT. Advanced stage, poor performance status, and poor CCRT response were independent factors for decreased survival.