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Although the individual consumption of medicinal mushrooms, including Phellinus linteus (PL), Ganoderma lucidum (GL), and Inonotus obliquus (IO), is known to be neuroprotective, the associated mechanisms underlying their therapeutic synergism on focal cerebral ischemia (fCI) have yet to be elucidated. This study aimed to demonstrate the neuroprotective effects of mixed mushroom mycelia (MMM) against experimental fCI. The water-fractions, ethanolic-fractions, and ethyl acetate-fractions of the MMM (PL, GL, and IO) grown in a barley medium using solid-state fermentation techniques were prepared and their protective effects against glutamate-induced excitotoxicity were compared in PC-12 cells. After the identification of the water extracts of MMM (wMMM) as the most suitable form, which possessed the lowest toxicity and highest efficacy, further analyses for evaluating the anti-apoptotic effects of wMMM, including Hoechst 33258-based nuclear staining, fluorescence-activated cell sorting, and reactive oxygen species (ROS) detection assays, were performed. Rats were subjected to a 90 min middle cerebral artery occlusion and reperfusion, after which a wMMM treatment resulted in significant dose-dependent improvements across a number of parameters. Furthermore, measurements of intracellular ROS and levels of antioxidant enzymes revealed a wMMM-mediated ROS attenuation and antioxidant enzyme upregulation. We suggest that wMMM is neuroprotective against fCI through its anti-apoptotic and anti-oxidative effects.

Background and Objectives Endoscopic prelacrimal recess approach (PLRA) was introduced to treat maxillary sinus inverted papilloma (IP) without sacrificing the inferior turbinate and nasolacrimal duct. This study aimed to compare surgical outcomes of prelacrimal recess approach with the conventional Caldwell-Luc approach (CLA) to remove IP of maxillary sinus and to evaluate the usefulness of the PLRA.Subjects and Method We retrospectively reviewed medical records of 51 patients who were treated in our institution for IP of nasal cavity and sinuses between March 2010 and June 2019. Twenty patients had maxillary sinus IP. Sixteen patients underwent endoscopic sinus surgery combined with either CLA (n=8) or PLRA (n=8). Demographic data, surgical technique, site of IP origin, intra- and postoperative complications, duration of follow-up, recurrence rate and pathologic diagnosis were reviewed.Results IP was the pathologic diagnosis for all 16 cases. Gross total removal was achieved in all cases. The mean follow-up period was 20.1 months in CLA group and 12.5 months in PLRA group. There was one case of massive bleeding during operation requiring transfusion and postoperative ICU care in CLA group. On postoperative follow-up, two patients from the CLA group had recurrence during the follow-up period. One patient had numbness around the gingival area, another patient had transient wound dehiscence, and another had persistent oro-antral fistula. In PLRA group, one patient had periorbital swelling after blowing nose; otherwise, no other patient from the PLRA group developed subjective complaints after surgery.Conclusion Endoscopic prelacrimal recess approach showed lower complication rates and recurrence rates compared to CLA. PLRA is a safe and effective method for the excision of primary maxillary sinus IP.

Purpose This study sought to identify changes in anthropometric values among Korean school students by comparing the most recent nationwide data with previous data. Methods Data from the Korea School Health Examination Survey 2018 were used. The study population consisted of 107,954 Korean school students ranging from the 1st grade in elementary school through the 3rd year of high school. The difference in height and weight values for each sex and school grade was analyzed by comparison with the Korea School Health Examination Survey 2010. Results The mean heights of the 3rd-year high school students were 173.8 cm and 160.9 cm for boys and girls, respectively. The mean height of the 3rd-year high school students showed no difference between 2010 and 2018 for either sex. However, the mean height of the age group from the 3rd grade in elementary school through the 1st year in high school was significantly taller in 2018 compared to 2010 for both sexes. The mean weights of the 3rd-year high school students were 71.3 kg and 57.5 kg for boys and girls, respectively. The mean weight of students in 2018 was significantly higher compared to students in 2010 for most school grades. Conclusions Although no significant change was found in near-final height between 2010 and 2018 among high school seniors, the mean height during the growth spurt was significantly higher in 2018 compared to 2010. Weight was significantly higher in almost all school grades in 2018 compared to 2010.

High cochlear signal intensity on three-dimensional (3D) T2 fluid-attenuated inversion recovery (FLAIR) sequences in patients with sudden sensorineural hearing loss (SSNHL) has been reported. Here, we evaluated the cochlear T2 relaxation time differences in patients with idiopathic SSNHL using quantitative synthetic MRI (SyMRI). Twenty-four patients with unilateral SSNHL who underwent precontrast conventional 3D FLAIR and SyMRI were retrospectively included. T1 and T2 relaxation times and the proton density (PD) of the bilateral ears were measured by manually drawn regions of interest. Wilcoxon signed-rank tests and intra- and interobserver correlation analyses were performed. Qualitative analysis was also performed to determine the presence and laterality of the asymmetric high signal intensity on synthetic FLAIR (SyFLAIR) images. The T2 relaxation time was significantly lower in the affected (basal and apico-middle turns) than in the unaffected cochlea (basal turn: 519 ± 181.3 vs. 608.8 ± 203.6, p = 0.042; apico-middle turn: 410.8 ± 163.8 vs. 514.5 ± 186.3, p = 0.037). There were no significant differences in the T1 relaxation time and PD between the affected and unaffected ears (p > 0.05). Additionally, three patients without asymmetric signal intensity on conventional MRI showed asymmetric increased signal intensity in the affected ear on SyFLAIR. The T2 relaxation time was significantly shorter in the affected than in the unaffected cochlea of patients with idiopathic SSNHL. The SyMRI-derived T2 relaxation time may be a promising imaging marker, suggesting that the changes in inner ear fluid composition are implicated in the idiopathic SSNHL development. • T2 relaxation time was significantly lower in the affected than in the unaffected cochlea. • SyFLAIR showed increased lesion conspicuity compared to conventional 3D-FLAIR in detecting asymmetric high signal intensity of the affected side. • SyMRI-derived T2 relaxation time may be a promising imaging marker of the affected ear in patients with idiopathic SSNHL.

Growth hormone (GH) treatment preference and adherence are affected by delivery device convenience, injection-site pain, confidence in correct dose administration, and device satisfaction. This survey investigated if switching device to NordiFlex® improved treatment experience in pediatric patients in South Korea.Patients aged 4-≤18 years were surveyed. Participants were NordiFlex® users who previously used NordiLet®/other devices. Participants compared preference, self-reported adherence, satisfaction, perceived ease of use, and device subjective benefits (across four domains:Ninety-four patients were enrolled, of which 91.5% previously used NordiLet®. Significantly more patients preferred, and were more satisfied with NordiFlex® vs. previous device; mean score: 0.65 (95% confidence interval [CI]:0.41;0.88) and 0.61 (95% CI:0.36;0.85), respectively. Participants reported greater perceived ease of use (0.49 [95% CI:0.26;0.72]) and fewer missed injections (0.20 [95% CI:0.06;0.34], with NordiFlex® vs. previous device. Bivariate analysis showed significant associations between preference for NordiFlex® and higher scores onThese results suggest that improvements in device features could be associated with improved treatment experience.

This study was aimed to evaluate the association between urinary bisphenol A (BPA) levels and risk of obesity in Korean adults. We analyzed data from the Korean National Environmental Health Survey (KoNEHS) Cycle 2 (2012–2014) and Cycle 3 (2015–2017). A total of 10,021 participants aged ≥ 19 years were included. Urine dilution was corrected by the covariate-adjusted standardization (CAS) method. We performed meta-analysis, logistic regression analysis by matching all covariates with a 1:1 propensity score, and a 4-knot restricted cubic spline plot model to calculate the odds ratios (ORs) for obesity according to natural log-transformed BPA levels. Mean urinary BPA concentration was 1.12 µg/L in KoNEHS Cycle 2 and 1.32 µg/L in Cycle 3. BPA levels were significantly higher among obese adults than among non-obese adults in both KoNEHS Cycles 2 and 3. In pooled data of KoNEHS Cycles 2 and 3, BPA showed significant positive associations with ORs for obesity in both sexes, which were more prominent in females (linear) than in males (non-linear). These associations were confirmed in spline analyses. CAS-applied BPA concentrations were positively associated with obesity in nationwide representative samples of Korean adults. Further studies are warranted to confirm and elucidate the underlying mechanism.

To compare the validity of the conventional continuous metabolic syndrome score (ccMS) and pediatric simple metabolic syndrome score (PsiMS) for the prediction of MS in Korean adolescents.A total of 2983 adolescents aged 10-18 years who participated in the Korea National Health and Nutrition Examination Survey (2013-2017) were enrolled. The ccMS was calculated by aggregating the sex and age-specific z-scores of body mass index, systolic blood pressure (SBP), glucose, high-density lipoprotein cholesterol (HDL-C), and triglycerides. The PsiMS was calculated using the following formula: 〔2x(waist/height (cm)〕+〔glucose (mg/dL)/100〕+〔triglycerides (mg/dL)/150〕+〔SBP (mmHg)/130〕-〔HDL-C (mg/dL)/40〕.Mean PsiMS was significantly higher in subjects with MS compared with those without MS (3.24 vs. 1.93 in boys, 3.11 vs. 1.80 in girls; P0.001). Both ccMS and PsiMS were significantly higher in subjects with more MS components compared to adolescents with fewer components (P-for-trend0.001). Among the adolescents without MS but in the PsiMS quintile 5, 33.5% presented two or more MS components. The receiver operating characteristic analysis demonstrated an equally good performance of ccMS (AUC = 0.975) and PsiMS (AUC = 0.958) for identifying adolescent MS risk. PsiMS showed a good stratification of MS risk in the generalized linear model.PsiMS is an accurate and efficient scoring system to assess and monitor the risk of adolescent MS in the research and clinical practice.

Objective:To date, there have been few studies on dietary supplement (DS) use in Korean children and adolescents, using nationally representative data. This study aimed to investigate the current status of DS use and its related factors, among Korean children and adolescents from the Korean National Health and Nutrition Examination Survey (KNHANES) data.Design:A cross-sectional study.Setting:Data from the KNHANES 2015–2017. Participants completed 24-h dietary recall interviews, including DS products that the subjects consumed.Participants:The study population was 4380 children and adolescents aged 1–18 years.Results:Approximately 2013 % of children and adolescents were using DS; the highest use was among children aged 1–3 years old, and the lowest use was among adolescents aged 16–18 years. The most frequently used DS was prebiotics/probiotics, followed by multivitamin/mineral supplements. Factors that were associated with DS use were lower birth weight in children aged Conclusions:We report that over 20 % of children and adolescents use DS. Nutritional education for parents and children about proper DS consumption is needed.

Purpose To investigate the associations between the urinary levels of polycyclic aromatic hydrocarbons (PAHs) and diabetes mellitus in Korean adults. Materials and Methods We examined the data of 6478 participants aged ≥19 years from the Korean National Environmental Health Survey (KoNEHS) cycle 2 (2012–2014). The urinary levels of 1-hydroxypyrene (1-OHP), 2-naphthol (2-NAP), 1-hydroxyphenathrene (1-OHPhe), and 2-hydroxyfluorene (2-OHFlu) were measured by gas chromatography-mass spectrometry. Diabetes mellitus was defined as a self-report of physician-diagnosed diabetes mellitus or the use of oral hypoglycemics or insulin. Analyses were adjusted for sex, age, body mass index, household income, alcohol consumption, physical activity, urinary creatinine and cotinine, menopausal status, and quartiles of all other PAHs. Results The prevalence of diabetes was 6.5% in the study population. In men, the geometric means of the 2-NAP and 2-OHFlu levels were higher in participants with diabetes mellitus than in those without diabetes mellitus [4.11 vs 3.26 μg/L (P

The recombinant human growth hormone (GH) has been used for the treatment of growth hormone deficiency (GHD) and diverse short stature state, and its physiological and therapeutic effects are well documented. However, since the effect of GH treatment on metabolic disorders has not been well characterized, we injected GH to Western diet-fed low-density lipoprotein receptor-deficient (Ldlr−/−) mice to understand the exact effect of GH on metabolic diseases including atherosclerosis, hepatic steatosis, and obesity. Exogenous GH treatment increased plasma IGF-1 concentration and decreased body weight without affecting serum lipid profiles. GH treatment changed neither atherosclerotic lesion size nor collagen and smooth muscle cells accumulation in the lesion. GH treatment reduced macrophage accumulation in adipose tissue. Importantly, GH treatment attenuated hepatic steatosis and inflammation. The hepatic expression IL-1β mRNA were decreased by GH treatment. The mRNA and protein levels of CD36 were markedly decreased in GH treated mice without significant changes in other molecules related to lipid metabolism. Therefore, the treatment of GH treatment could attenuate hepatic steatosis and inflammation with downregulation of CD36 expression in hyperlipidemic condition.

Childhood obesity is a global health concern. Air pollution is also a crucial health threat, especially in developing countries. Over the past decade, a number of epidemiologic and animal studies have suggested a possible role of pre- or postnatal exposure to air pollutants on childhood obesity. Although no clear mechanism has been elucidated, physical inactivity, oxidative stress, and epigenetic modifications have been suggested as possible mechanisms by which obesity develops due to air pollution. In this review, we summarize and review previous epidemiologic studies linking air pollution and childhood obesity and discuss the possible mechanisms underlying air pollution-induced obesity based on in vivo and in vitro evidence.

Purpose This study was conducted to investigate the distributions of the triglyceride (TG) to high-density lipoprotein-cholesterol (HDL-C) ratio and total cholesterol (TC) to HDL-C ratio, and to explore their usefulness as markers of metabolic syndrome (MetS) in Korean adolescents. Methods We obtained data for 2,721 adolescents (1,436 boys and 1,285 girls) aged 10–18 years who participated in the Korean National Health and Nutrition Examination Surveys from 2008 to 2010. International Diabetes Federation criteria were used to define MetS. Results There were no significant gender-related differences in TG/HDL-C or TC/HDL-C ratios. These lipid ratios showed significant associations with homeostatic model assessment for insulin resistance (HOMA-IR) and waist circumference. Areas under the receiver operating characteristic curve to identify MetS were 0.947 for TG/HDL-C and 0.924 for TC/HDL-C, which were higher than that of HOMA-IR (0.822). Optimal cutoff values (sensitivity, specificity) of TG/HDL-C and TC/HDL-C ratios for MetS prediction were 3.3 (85.7%, 89.9%), and 3.8 (92.9%, 82.8%), respectively. Odds ratio (OR; 95% confidence intervals [CIs]) for MetS in adolescents with TC/HDL-C ratio above the cutoff value was 14.8 (2.8–77.4), while that for TG/HDL-C ratio about the cutoff value was 30.6 (6.0–157.6). In adolescents who had both lipid ratios above the cutoff values, the OR (95% CI) for MetS was 36.2 (7.2–186.2). Conclusion TG/HDL-C and TC/HDL-C ratios are useful markers of metabolic syndrome with high predictive value in Korean adolescents.

Improvement of bone formation is necessary for successful treatment of the bone defects associated with osteoporosis. In this study, we sought to elucidate the osteogenic activity of peanut sprouts and their bioactive components. We found that peanut sprout water extract (PSWE) enhanced bone morphogenetic protein-2-mediated osteoblast differentiation in a dose-dependent manner by stimulating expression of runt-related transcription factor 2 (Runx2) via activation of AKT/MAP kinases. We identified a major component of PSWE, soyasaponin Bb, as the bioactive compound responsible for improvement of anabolic activity. Soyasaponin Bb from PSWE enhanced expression of the osteogenic transcription factor Runx2 and alkaline phosphatase. The soyasaponin Bb content depended on sprouting time of peanut, and the anabolic action of PSWE was dependent on soyasaponin Bb content. Thus, PSWE and soyasaponin Bb have the potential to protect against bone disorders, including osteoporosis.

Bone morphogenetic protein 2 (BMP-2) is considered an effective growth factor for bone formation, and is used for making osteo-inductive scaffolds, but the related clinical investigations have shown low success rates. In this study, we genetically manipulated teratoma-derived fibroblast (TDF) cells by simultaneous introduction of BMP-2 and herpes simplex virus-thymidine kinase (HSV-tk) encoding genes. Self-production of BMP-2 in TDF cells strongly enhanced the alkaline phosphatase (ALP) activity, calcium content, and elevated the mRNA expression of osteogenic marker genes during in vitro osteogenesis. The bone formation volume was also remarkably enhanced in calvarial and femoral critical-size defect models. Ganciclovir (GCV) treatment induced apoptosis in TDF cells co-expressing HSV-tk and BMP-2, implying that HSV-tk suicide gene can modulate the side-effects of stem cell therapy, e.g., development of uncontrollable teratoma and tumor formation. Altogether, our findings revealed a safe and highly efficient technique with potential therapeutic applications for bone regeneration.

Purpose Suboptimal frequency of glycosylated hemoglobin (HbA1c) monitoring is associated with poor diabetes control. We aimed to analyze compliance to HbA1c testing guidelines and explore associated individual and area-level determinants, focusing on regional variation. Methods This cross-sectional study between the period of 2012–2013 was conducted by using the Korean National Health Insurance Research Database, and included 45,634 patients diagnosed with diabetes mellitus, who were prescribed any anti-diabetic medications, including insulin. We calculated the proportion of each HbA1c testing frequency (≥1, ≥2, or ≥4 times per year) stratified by 17 administrative regions. Multilevel and multivariate logistic analyses were performed with regional (proportion of farmer population) and individual characteristics (age, sex, income level, duration of diabetes, and most visited medical institution). Results Overall, 67.3% of the patients received ≥ 1 HbA1c test per year; 37.8% and 6.1% received ≥2 and ≥4 tests per year, respectively. Those managed in secondary-level hospitals or clinics and those living in rural areas were less likely to receive HbA1c testing. Even after adjusting for individual and regional level characteristics, significant area level variation was observed (variance participant coefficients were 7.91%, 9.58%, and 14.43% for testing frequencies of ≥1, ≥2, and ≥4 times a year, respectively). Conclusions The frequency of HbA1c monitoring is suboptimal in Korea, especially in rural areas. Moreover, significant regional variation was observed, implying a contextual effect. This suggests the need for developing policy actions to improve HbA1c monitoring. In particular, access to HbA1c testing in rural primary care clinics must be improved.

This study describes a new approach to rapidly detecting of human papillomavirus (HPV) DNA using desorption electrospray ionization mass spectrometry (DESI-MS) without sample preparation such as extraction or purification. Our strategy utilizes the ambient ionization mass spectrometry for ionizing and detecting oligonucleotides from restriction fragment mass polymorphism (RFMP) assay, and is to identify which HPV genotype from combinations of multiply charged ions of oligonucleotides. In DESI-MS, the spray solvent system operates at the stage of washing a complex mixture of polymerase chain reaction (PCR) products, so that the oligonucleotides can be detected without sample treatment. The study was verified to rapid diagnosis of cervical cancer by detecting and genotyping of HPV DNA based RFMP assay using DESI-MS.

Postural dysfunction is one of the most common community health symptoms and frequent chief complaints in hospitals. Sarcopenia is a syndrome characterized by degenerative loss of skeletal muscle mass, muscle quality, and muscle strength, and is the main contributor to musculoskeletal impairment in the elderly. Previous studies reported that loss of muscle mass is associated with a loss of diverse functional abilities. Meanwhile, there have been limited studies concerning postural dysfunction among older adults with sarcopenia. Although sarcopenia is primarily a disease of the elderly, its development may be associated with conditions that are not exclusively seen in older persons. Also, recent studies recognize that sarcopenia may begin to develop earlier in life. The objective of this paper was to investigate the association between the prevalence of sarcopenia and postural dysfunction in a wide age range of adults using data from a nationally representative cohort study in Korea. Korean National Health & Nutrition Exhibition Survey V (KNHANES V, 2010-2012) data from the fifth cross-sectional survey of the South Korean population performed by the Korean Ministry of Health and Welfare were used. Appendicular skeletal muscle mass (ASM)/height (ht)2 was used to define sarcopenia, and the Modified Romberg test using a foam pad ("foam balance test") was performed to evaluate postural dysfunction. ASM/ht2 was lower in women and significantly decreased with age in men. Subjects with sarcopenia were significantly more likely to fail the foam balance test, regardless of sex and age. Regression analysis showed a significant relationship between sarcopenia and postural dysfunction (OR: 2.544, 95% CI: 1.683-3.846, p

Background Menarcheal age has been decreasing worldwide. However, few recent studies have observed trends in menarcheal age in larger populations, and the cutoff age for early menarche remains unclear. Therefore, we aimed to analyze recent trends of menarcheal age and to determine the cutoff age of early menarche based on nationally representative data. Methods We conducted a cross-sectional study of 351,006 Korean girls aged 12–18 years who were born in 1988–2003 based on the data of the 2006–2015 Korea Youth Risk Behavior Survey. We identified the distribution of age at menarche using the complex sample Cox regression model. Trends in the prevalence of early menarche were determined using the complex sample linear model. Results Ninety-five percent of all the participants reported they had experienced menarche. The mean menarcheal age was 13.0 years (95% confidence intervals [CIs], 12.92–13.04) for girls born in 1988 and decreased to 12.6 years (95% CI, 12.54–12.61) for girls born in 2003. The cutoff age (the 3rd percentile value) for early menarche was 10.5 years during the study period. The prevalence of early menarche significantly increased from 1.8% in 2006 to 3.2% in 2015 (P-for-trend < 0.001). Downward trends of menarcheal age were noted across all body mass index groups, and this trend was most prominent in the obese group. Conclusion We reported an ongoing downward trend in menarcheal age in Korean girls born in 1988–2003, decreasing by 0.4 years over the 15 years., Graphical Abstract

Adults with short stature have been previously reported to have increased risk of cardiovascular events and hyper-LDL-cholesterolemia. We aimed to assess the association between height and lipid profiles among Korean adolescents and adults. We analyzed data from the Korea National Health and Nutrition Examination Survey from 2007 to 2015, from 37,889 individuals (aged 12–59 years). In adolescents, total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) levels had profound associations with height in both boys and girls, while high density lipoprotein-cholesterol (HDL-C) levels had an inverse association with height only in boys. Height was inversely associated with TC, triglycerides (TG), and LDL-C concentrations in men and women and positively correlated with HDL-C concentration in women. In boys, the odds ratios (ORs) for hypercholesterolemia, hypertriglyceridemia, hyper-LDL-cholesterolemia were higher for shorter subjects (ORs = 2.38~7.01), while only the OR of hyper-LDL-cholesterolemia was significantly higher in girls with short stature (OR = 3.12). In adults, the ORs for hypercholesterolemia, hypo-HDL-cholesterolemia, and hyper-LDL-cholesterolemia were significantly higher in short subjects than in tall subjects after controlling for covariates (ORs = 1.50~2.61). Also, short men showed significantly higher ORs for hypertriglyceridemia (OR = 1.85) than tall men. Short stature was significantly associated with adverse lipid profiles in both adolescents and adults.

Background The Korean Otologic Society developed guidelines for treatment of acute otitis media (AOM) in 2010, which advocated limiting the prescription of antibiotics. However, it is not known whether this has influenced the antibiotic prescription rate. Thus, this study aimed to examine the impact of these guidelines on the patterns in antibiotic prescription for AOM in Korean children. Methods AOM patients aged less than 15 years, included in the Korean Health Insurance Review and Assessment Service database from 2009 to 2017, were retrospectively identified. We estimated the overall antibiotic prescription rate, antibiotic prescription rates for suppurative and non-suppurative AOM, and types of antibiotics prescribed. Moreover, we analyzed differences in antibiotic prescription rates according to age group, hospital type, and medical department. Results The overall antibiotic prescription rate decreased significantly from 2009 to 2017. The antibiotic prescription rate for non-suppurative AOM decreased much more than the rate for suppurative AOM. Overall, amoxicillin/clavulanate was the most commonly prescribed antibiotic, followed by cephalosporin. The antibiotic prescription rate decreased by a similar margin in all age groups. Tertiary referral hospitals and otorhinolaryngology department showed the lowest antibiotic prescription rate every year. Conclusions This study demonstrated the changes in antibiotic prescription rates for AOM following implementation of the Korean AOM treatment guidelines. The practice of antibiotic prescription for children with AOM appears to have decreased every year. However, the overall antibiotic prescription rate is still high. Therefore, clinicians should understand and adhere to the guidelines, and merely observe children with mild AOM symptoms.

Objectives Slight/mild hearing loss is detrimental to communication and academic achievements. This study aimed to describe the prevalence of hearing loss, and to investigate the factors related to noise-induced hearing loss among South Korean adolescent. Methods As a population-based retrospective study, 1845 South Korean adolescents aged from 12 to 19 years were analyzed using the data from Korea National Health and Nutrition Examination Survey V (KNHANES V, 2010–2012). The prevalence of hearing loss according to the side, severity, and frequency was calculated. For assessing the noise-induced hearing loss in adolescent, the prevalence of hearing loss only in high-frequency (onlyHFHL, defined as 1) thresholds at 0.5 and 1 kHz of ≤15 dB HL, and 2) maximal thresholds at 3, 4, or 6 kHz ≥ 15 dB HL higher than the highest threshold for 0.5 and 1 kHz) was analyzed. Moreover, the relevance of onlyHFHL in context of sociodemographic factors and noise exposure history was evaluated. Results The prevalence of unilateral and bilateral hearing loss based on the average of six frequencies (0.5, 1, 2, 3, 4, and 6 kHz) in South Korean adolescents were 8.56% and 1.03%, respectively, and most cases were hearing loss with slight/mild degree. The prevalence of unilateral and bilateral onlyHFHL were 32.74% and 5.53%, respectively. Factors found to be associated with onlyHFHL were sex (female) and household income (high). Conclusions According to this population-based study, the prevalence of slight/mild hearing loss and onlyHFHL in the South Korean adolescents were considerably high. With knowledge of the factors related with onlyHFHL, paying more attention to slight/mild hearing loss will be helpful in preventing hearing loss in adolescents.

Dysregulation of glucocorticoid metabolism is known to be a causative factor of obesity. However, only a few studies have evaluated the enzymatic activities involved in glucocorticoid metabolism in the pediatric population.To examine whether circulating glucocorticoid metabolites and their ratios reflecting the activities of metabolic enzyme are associated with obesity and body composition in girls.A total of 227 girls aged 7-13 years (131 control, 45 overweight, 51 obese) were enrolled in this study. Serum concentrations of glucocorticoids (11-deoxycortisol, cortisol, tetrahydrocortisol [THF], allo-THF, allo-dihydrocortisol [allo-DHF], and cortisone) were evaluated by gas chromatography-mass spectrometry. Enzyme activities corresponding to the ratios of cortisol and cortisone to their respective precursors and metabolites were also assessed.Serum levels of allo-THF were significantly higher in obese girls compared with those in overweight and control girls (P = 0.018); however, concentrations of other cortisol metabolites were not significantly different between the groups studied. According to the severity of obesity, increasing trends in the metabolic ratios reflecting the activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) [(cortisol + allo-DHF + allo-THF + THF)/cortisone], relative 5α/5β-reductase [allo-THF/THF] activity, and 3α-HSD [allo-THF/allo-DHF] activity, were noted (P-for-trend0.05). Body fat percentage and waist-to-height ratio positively correlated with the activities of 11β-HSD1 and 3α-HSD (P 0.05). Following covariate control, girls with central obesity demonstrated significantly higher metabolic ratios reflecting 11β-HSD1, relative 5α/5β-reductase, and 3α-HSD activities (P 0.05).We found an altered glucocorticoid metabolism suggesting increased production of cortisol by 11β-HSD1 and increased metabolic clearance of cortisol catalyzed by 3α-HSD in girls with central obesity.

Off-vertical axis rotation (OVAR) is a laboratory test to assess the otolith function. This study aimed to analyze the parameters of OVAR in patients with unilateral vestibular hypofunction (UVH) and bilateral vestibulopathy (BVP), and to correlate the parameters of OVAR with those of VEMPs. Ten healthy volunteers, 41 UVH, and 13 BVP patients performed OVAR. Bias component (BIC) and modulation component (MOC) of UVH and BVP patients were compared with those of healthy controls. BIC and MOC were correlated with amplitude and interaural difference (IAD) of cervical VEMP (cVEMP) and ocular VEMP (oVEMP). In UVH patients, the direction of BICs to affected side rotation were reversed and the absolute value of BICs were decreased when they were compared to healthy controls. In BVP patients, BICs were markedly attenuated. MOCs were not changed in UVH and BVP patients. There was no statistically significant correlation between VEMPs and OVAR.

Pediatric obesity has been related to hyperandrogenism and premature adrenarche in previous studies. However, little is known regarding the association between body fat mass and steroidogenic enzyme activities in children.To examine whether body fat mass is associated with serum steroid profiles in girls.We enrolled 242 girls (125 prepubertal, 117 pubertal; age, 7-13 years). Early morning blood samples were drawn at a university hospital to measure serum steroid profiles using gas chromatography-mass spectrometry, and steroidogenic enzyme activities were assessed from the ratios of steroid metabolites.We evaluated serum steroid profiles and estimated steroidogenic enzyme activities and their association with anthropometric indices and body composition.Prepubertal obese girls demonstrated significantly higher progestin, androgens (dehydroepiandrosterone [DHEA], androstenedione [A-dione], T, androsterone), and ratio of steroid metabolites reflecting 17,20-lyase activity [(DHEA + A-dione)/17-hydroxypregnenolone] compared with prepubertal controls. Pubertal obese girls demonstrated significantly higher serum T and androsterone than pubertal controls; however, serum steroid metabolite ratios reflecting steroidogenic enzyme activities did not significantly differ among obese and non-obese girls. Partial correlation analysis revealed that body fat mass was positively correlated with pregnenolone, DHEA, A-dione, T, androsterone, and ratio of (DHEA + A-dione)/17-hydroxypregnenolone in prepubertal girls only. Prepubertal girls with increased body fat mass had significantly higher serum DHEA and ratio of (DHEA + A-dione)/17-hydroxypregnenolone than controls.Increased androgen production in prepubertal obese girls could be at least partly due to increased body fat mass and 17,20-lyase activity.

Seven-day administration of systemic steroids was more effective in preserving hearing for 12 weeks after cochlear implantation (CI) than a 3-day delivery.To determine the effectiveness of extended delivery of systemic steroids to preserve hearing in guinea pigs after CI.Dexamethasone (4 mg/ml) was delivered parenterally via a mini-osmotic pump for either 3 or 7 days. A dummy CI electrode was inserted via cochleostomy approach in 8-week-old guinea pigs. Auditory thresholds were assessed from tone burst auditory brainstem responses (2, 8, 16, 24, and 32 kHz) at 1 day prior to CI, and 1, 4, and 12 weeks after implantation. Histologic evaluation of the cochleae was carried out.No differences were observed in hearing thresholds among groups before CI. Significant hearing preservation was achieved at 8, 16, 24, and 32 kHz only in the 7-day infusion group compared with the control group at 1 week after CI. The same trend was maintained at 4 weeks (16, 24 kHz) and 12 weeks (16, 24, and 32 kHz). Histologic review of the 7-day infusion group revealed less fibrosis and ossification in the scala tympani and the preservation of more spiral ganglion cells, compared with the control group.

Objective Auditory neuropathy spectrum disorder (ANSD) is a hearing disorder with impaired signal transmission from the inner ear to the brain. The electrophysiological characteristics of auditory neuropathy (AN characteristics) are marked with presence of otoacoustic emissions (OAE) or cochlear microphonics (CM) in the absence of auditory brainstem response (ABR). This study aimed to review etiologies related to AN characteristics from infants with profound hearing loss (HL), either unilaterally or bilaterally. Study design Prospective cohort study for thirty infants with prelingual profound HL. Methods ABR, OAE, and/or CM were analyzed to identify electrophysiological characteristics. Temporal bone computed tomography and/or internal acoustic canal magnetic resonance imaging were reviewed to identify anatomical abnormalities. The electrophysiological characteristics and cochlear nerve status were analyzed according to the laterality of deafness (unilateral vs bilateral). Results Among the total 41 ears (from 30 infants) with profound HL, 13 ears (7 (36.8%) of 19 ears with unilateral HL and 6 (27.3%) of 22 ears associated with bilateral HL) showed AN characteristics (37.1%), and 21 ears showed cochlear nerve deficiency (CND) (51.2%). AN characteristics was detected about two times more frequently in cases with CND (38.1%) than with anatomically normal cochlear nerve (20.0%), the difference not reaching a statistical significance probably due to a small sample size. Detection of AN characteristics did not differ between unilateral and bilateral profound HL, even though presence of CND was more frequently detected in cases with unilateral profound HL than with bilateral cases. There were at least five types of etiologies related to AN characteristics in 13 ears (from 10 infants) in our series depending on the laterality of deafness and presence of CND. Conclusions This study demonstrates that there were diverse etiologies related to AN characteristics from infants with unilateral or bilateral profound HL. Association between CND and AN characteristics is suggestive but not solid at this moment and AN characteristics is not a fully penetrant feature of CND.

We aimed to compare the diagnostic yield between temporal bone computed tomography (TBCT) and internal auditory canal MRI (IAC MRI) for the etiologic diagnosis of children with congenital single-sided deafness (SSD) and the evaluation of cochlear implant (CI) candidacy. In the original cohort, 24 subjects with congenital SSD were enrolled and underwent both TBCT and IAC MRI. We recruited an additional 22 consecutive infants with congenital SSD (the supplementary cohort) and evaluated in particular the cochlear nerve (CN) integrity using IAC MRI. Cochlear nerve deficiency (CND) was classified as &lsquo, absent&rsquo, &lsquo, small&rsquo, and &lsquo, indeterminate&rsquo, via mutual comparison between optical and parameters based on the MRI results. The most common etiologies were CND in the original cohort (19 out of 24). Notably, accurate evaluations of CN status (&lsquo, small CN&rsquo, = 2, &lsquo, indeterminate CN&rsquo, = 2), inner ear malformations, and brain abnormalities were possible only with MRI. The &lsquo, tended to be more frequently detected in SSD ears than in unaffected ears. MRI appeared to be more accurate than TBCT in a meticulous differentiation of CN, which is crucial for the selection of appropriate CI candidacy among congenital SSD children. Additionally, we introduced the novel concept of &lsquo, of which the causal relationship with SSD awaits confirmation.

The number of patients with bone metabolic disorders including osteoporosis is increasing worldwide. These disorders often facilitate bone fractures, which seriously impact the patient&rsquo, s quality of life and could lead to further health complications. Bone homeostasis is tightly regulated to balance bone resorption and formation. However, many anti-osteoporotic agents are broadly categorized as either bone forming or anti-resorptive, and their therapeutic use is often limited due to unwanted side effects. Therefore, safe and effective therapeutic agents are needed for osteoporosis. This study aims to clarify the bone protecting effects of oat bran water extract (OBWE) and its mode of action. OBWE inhibited RANKL (receptor activator of nuclear factor-&kappa, B ligand)-induced osteoclast differentiation by blocking c-Fos/NFATc1 through the alteration of I-&kappa, B. Furthermore, we found that OBWE enhanced BMP-2-stimulated osteoblast differentiation by the induction of Runx2 via Smad signaling molecules. In addition, the anti-osteoporotic activity of OBWE was also evaluated using an in vivo model. OBWE significantly restored ovariectomy-induced bone loss. These in vitro and in vivo results showed that OBWE has the potential to prevent and treat bone metabolic disorders including osteoporosis.

Osteoporosis is frequently induced following menopause, and bone fractures result in serious problems including skeletal deformity, pain, and increased mortality. Therefore, safe and effective therapeutic agents are needed for osteoporosis. This study aimed to clarify the bone protecting effects of germinated soy germ extracts (GSGE) and their mode of action. GSGE increased expression of alkaline phosphatase (ALP) and osteocalcin (OCL) by stimulating the expression of runt-related transcription factor 2 (Runx2) and osterix (Osx) through activation of Smad signaling molecules. Furthermore, germination of soy germ increased levels of nutritional components, especially soyasaponin Ab. The anabolic activity of soyasaponin Ab in GSGE was also evaluated. GSGE and soyasaponin Ab significantly protected against ovariectomy (OVX)-induced bone loss and improved bone-specific alkaline phosphatase (BALP) level in mouse serum. These in vitro and in vivo study results demonstrated that GSGE and soyasaponin Ab have potential as therapeutic candidate agents for bone protection in postmenopausal osteoporosis.

The detrimental outcomes of white matter hyperintensity (WMH) are known to be proportional to WMH volume. This study aimed to evaluate the association between kidney dysfunction and white matter hyperintensity (WMH) volume. A total of 2,203 subjects who underwent brain magnetic resonance imaging (MRI) as part of a screening health check-up was included in this study. WMH was defined as hyperintensity signals without cavity formation in the white matter on fluid-attenuated inversion recovery images. WMH volume was measured quantitatively, and data were normalized by square root transformation prior to analysis. Mean age of the subjects was 56.9 years and mean WMH volume was 2.7 cm3. Mean estimated glomerular filtration rate (eGFR) level was 78.0 ml/min/1.73 m2, and 172 subjects (7.8%) were diagnosed with moderate-to-severe kidney dysfunction (eGFR p p

Lead is a ubiquitous metal in the environment, but no studies have examined lead toxicity on the middle ear. Here, we investigated lead toxicity and its mechanism in human middle ear epithelial cells (HMEECs). Moreover, we investigated the protective effects of amniotic membrane extract (AME) and chorionic membrane extract (CME) against lead toxicity in HMEECs. Cell viability was analyzed using the cell counting kit, and reactive oxygen species (ROS) activity was measured using a cellular ROS detection kit. After lead(II) acetate trihydrate treatment, mRNA levels of various genes were assessed by semiquantitative real-time polymerase chain reaction. Following treatment with AME or CME after lead exposure, the changes in cell viability, ROS activity, and gene expression were analyzed. Exposure to >100 μg/mL of lead(II) acetate trihydrate caused a significant decrease in cell viability and increased ROS production in HMEECs. Lead exposure significantly increased the mRNA expression of genes encoding inflammatory cytokines and mucins. Administration of AME or CME restored cell viability, reduced ROS activity, and ameliorated mRNA levels. Our findings suggest that environmental lead exposure is related to the development of otitis media, and AME and CME may have antioxidative and anti-inflammatory effects against lead toxicity.

The EYA4 gene encodes a 640-amino-acid protein that serves as a transcription factor. This protein contains a highly conserved Eya domain (eya-HR) and a variable domain (eya-VR). Mutations of this gene are known to cause postlingual and progressive sensorineural hearing loss, either as non-syndromic (DFNA10) or syndromic hearing loss, depending on the location of truncation of the mutant protein. Since our previous report, we have recruited 14 families segregating autosomal dominant moderate SNHL. A thorough medical history and physical examination including evaluation of heart problems ruled out any syndromic features in these families. Screening of EYA4 was performed by targeted exome sequencing of 134 known deafness genes (TES-134) from the probands. After basic filtering of the variants, we identified one proband who carried a novel truncation mutation, c.1194delT (p.Met401TrpfsX3) of EYA4, making the frequency of DFNA10 to be 7.14 % (1/14) in Koreans. The variant co-segregated perfectly with a slightly down-sloping, moderate degree of SNHL in the family (SH117), and was not detected in any of the 592 normal control chromosomes. This variant is likely to generate protein products that are truncated just downstream of the eya-VR domain. None of the three affected family members showed any syndromic features, including cardiac problems, which was compatible with a previous genotype-phenotype correlation. The identification of a novel EYA4 truncation mutation associated with DFNA10, rather than syndromic hearing loss, supports a previously reported genotype-phenotype correlation in this gene. Considering its detection rate, EYA4 mutations should be suspected in hereditary moderate hearing loss with a corresponding audiologic configuration, and a cardiac examination should be included in the initial evaluation.

Lead is a ubiquitous metal in the environment, but no studies have examined lead toxicity on the middle ear. Here, we investigated lead toxicity and its mechanism in human middle ear epithelial cells (HMEECs). Moreover, we investigated the protective effects of amniotic membrane extract (AME) and chorionic membrane extract (CME) against lead toxicity in HMEECs. Cell viability was analyzed using the cell counting kit, and reactive oxygen species (ROS) activity was measured using a cellular ROS detection kit. After lead(II) acetate trihydrate treatment, mRNA levels of various genes were assessed by semiquantitative real-time polymerase chain reaction. Following treatment with AME or CME after lead exposure, the changes in cell viability, ROS activity, and gene expression were analyzed. Exposure to100

Introduction Auricular Arteriovenous Malformation of the external ear is a rarely encountered disease; in particular, arteriovenous malformation arising from the auricle, with spontaneous bleeding, has seldom been reported. Objective In the current study, we report an unusual case of late-onset auricular arteriovenous malformation originating from the posterior auricular artery that was confirmed by computed tomographic angiography. The case was successfully managed by pre-surgical intravascular embolization followed by total lesion excision. Prompted by this case, we also present a scoping review of the literature. Methods A case of a 60 year-old man with right auricular arteriovenous malformation treated in our tertiary care center, and 52 patients with auricular arteriovenous malformation described in 10 case reports and a retrospective review are presented. Auricular arteriovenous malformation can manifest as swelling of the ear, pulsatile tinnitus, pain, and/or bleeding. On physical examination, a pulsatile swelling and/or a tender mass is evident. When arteriovenous malformation is suspected, the lesions should be visualized using imaging modalities that optimally detect vascular lesions, and managed via embolization, mass excision, or auricular resection. Effectiveness of the various diagnostic methods used and the treatment outcomes were analyzed. Results Various imaging modalities including Doppler sonography, computed tomographic angiography, magnetic resonance angiography, and/or transfemoral cerebral angiography were used to diagnose 38 cases reported in the literature. In another 15 cases, no imaging was performed; treatment was determined solely by physical examination and auscultation. Of the total of 53 cases, 12 were not treated (their symptoms were merely observed) whereas 20 underwent therapeutic embolization. In total, 32 patients, including 1 patient who was not treated and 10 with persistent or aggravated arteriovenous malformation after previous embolization, underwent mass excision or auricular resection depending on the extent of the lesion. No major postoperative complication was recorded. The postoperative follow-up duration varied from 1 month to 19 years, and only one case of unresectable, residual cervicofacial arteriovenous malformation was recorded. Conclusion Auricular arteriovenous malformation is a rarely encountered disease, but should be suspected if a patient presents with a swollen ear and pulsatile tinnitus. Appropriate imaging is essential for diagnosis and evaluation of the extent of disease. As embolization affords only relatively poor control, total surgical removal of the vascular mass is recommended.

The treatment options for Lennox-Gastaut syndrome (LGS), a pediatric epileptic syndrome, are limited, especially in younger children. Rufinamide tablets were safe and effective as an add-on treatment in Korean children and adolescents20 years of age with LGS. This subgroup analysis aimed to evaluate the efficacy and safety of rufinamide tablets in LGS pediatric patients aged 1-4 years.This was a retrospective, observational study in LGS patients aged 1-4 years who received 12 weeks of treatment with rufinamide orally as an adjuvant treatment between April and June 2010. The proportion of responders (patients with a ≥50% reduction in seizure frequency after rufinamide treatment) was evaluated according to the type of seizure. The proportion of patients who were seizure-free was also evaluated. Adverse events (AEs) were evaluated after 12 weeks of treatment.Among the 15 patients evaluated, one discontinued treatment because of worsening seizures 4 weeks after administration of rufinamide. Seven (46.67%) patients were responders and four patients were seizure-free. There were four responders with convulsive seizures, one each for myoclonic seizures and drop attacks, and spasms. The responder rate was increased to 69.23% by long-term treatment of rufinamide. AEs were experienced by three patients. One patient each experienced somnolence, fatigue, and rash.Rufinamide tablets were efficacious and well tolerated in LGS patients aged 1-4 years, at doses up to 1000 mg per day, when given as add-on therapy to other antiepileptic drugs.

Formaldehyde (FA) is a familiar indoor air pollutant found in everything from cosmetics to clothing, but its impact on the middle ear is unknown. This study investigated whether FA causes cytotoxicity, inflammation, or induction of apoptosis in human middle ear epithelial cells (HMEECs). Cell viability was investigated using the trypan blue assay and a cell counting kit (CCK-8) in HMEECs treated with FA for 4 or 24 h. The expression of genes encoding the inflammatory cytokine tumor necrosis factor alpha (TNF-α) and mucin (MUC5AC) was analyzed using RT-PCR. Activation of the apoptosis pathway was determined by measuring mitochondrial membrane potential (MMP), cytochrome oxidase, caspase-9/Mch6/Apaf 3, and Caspase-Glo® 3/7 activities. The CCK-8 assay and trypan blue assay results showed a reduction in cell viability in FA-treated HMEECs. FA also increased the cellular expression of TNF-α and MUC5AC and reduced the activities of MMP and cytochrome oxidase. Caspase-9 activity increased in cells stimulated for 4 h, as well as caspase-3/7 activity in cells stimulated for 24 h. The decreased cell viability, the induction of inflammation and mucin gene expression, and the activation of the apoptosis pathway together indicate a link between environmental FA exposure and the development of otitis media.

Background: Streptococcus pneumoniae colonize the human nasopharynx in the form of biofilms. The biofilms act as bacterial Background: Streptococcus pneumoniae colonize the human nasopharynx in the form of biofilms. The biofilms act as bacterial reservoirs and planktonic bacteria from these biofilms can migrate to other sterile anatomical sites to cause pneumonia, otitis media (OM), bacteremia and meningitis. Human amniotic membrane contains numerous growth factors and antimicrobial activity; however, these have not been studied in detail. In this study, we prepared amniotic membrane extract and chorionic membrane extract (AME/CME) and evaluated their antibacterial and antibiofilm activities against S. pneumoniae using an in vitro biofilm model and in vivo OM rat model. Materials and Methods: The AME/CME were prepared and protein was quantified using DC™ (detergent compatible) method. The Minimum inhibitory concentrations (MICs) were determined using broth dilution method, and the synergistic effect of AME/CME with Penicillin-streptomycin was detected checkerboard. The in vitro biofilm and in vivo colonization of S. pneumoniae were studied using microtiter plate assay and OM rat model, respectively. The AME/CME-treated biofilms were examined using SEM and confocal microscopy. To examine the constituents of AME/CME, we determined the proteins and peptides of AME/CME using tandem mass tag (TMT)-based quantitative mass spectrometry (MS). Results: AME/CME treatment significantly (p

The cell-penetrating peptide GV1001 has been investigated as an anticancer agent and recently demonstrated anti-oxidant and anti-inflammatory effects. It has shown a protective effect on a kanamycin (KM)-induced ototoxicity mouse model. In the present study, we administered GV1001 at different time points after inducing hair cell damage, and examined if it rescues hair cell loss and restores hearing. A deaf mouse model was created by intraperitoneal injection of KM and furosemide. First, to test the early temporal change of hearing and extent of hair cell damage after KM and furosemide injection, hearing and outer hair cells (OHCs) morphology were evaluated on day 1, day 2 and day 3 after injection. In the second experiment, following KM and furosemide injection, GV1001, dexamethasone, or saline were given for three consecutive days at different time points: D0 group (days 0, 1, and 2), D1 group (days 1, 2, and 3), D3 group (days 3, 4, and 5) and D7 group (days 7, 8, and 9). The hearing thresholds were measured at 8, 16, and 32 kHz before ototoxic insult, and 7 days and 14 days after KM and furosemide injection. After 14 days, each turn of the cochlea was imaged to evaluate OHCs damage. GV1001-treated mice showed significantly less hearing loss and OHCs damage than the saline control group in the D0, D1 and D3 groups (p < 0.0167). However, there was no hearing restoration or intact hair cell in the D7 group. GV1001 protected against cochlear hair cell damage, and furthermore, delayed administration of GV1001 up to 3 days rescued hair cell damage and hearing loss in KM/furosemide-induced deaf mouse model.

This is the first study reporting on the incidence and clinical aspects of sudden sensorineural hearing loss (SSNHL) in South Korea. Using Health Insurance Review and Assessment Service data from 2011 to 2015, the monthly incidence of unilateral SSNHL and incidence according to patients’ sex, age, and month of diagnosis were investigated. The monthly incidence of unilateral SSNHL increased over the 5-year study period, with a mean annual incidence of 17.76 cases/ 100,000 of the population. The incidence increased with age, with most patients presenting in their 60s. There was a slight female preponderance, with a male-to-female ratio of 1: 1.35. Most new patients were diagnosed in October, and the fewest in January. In conclusion, this large-scale study indicates that unilateral SSNHL has a higher incidence among the elderly, women, and in autumn (i.e., along with colder weather).

Growth hormone (GH) is important for promotion of somatic growth and the regulation of substrate metabolism. Metabolic action of GH occurs in multiple tissues including the liver, muscle, fat and pancreas either directly or indirectly through insulin-like growth factor 1. The diabetogenic action of GH has been well-described in previous in vivo studies. In this paper, we review the metabolic effects of GH on peripheral tissues focusing on glucose metabolism and insulin resistance, and discuss results from human studies on the long-term effects of GH administration on insulin resistance and hyperglycemia.

OBJECTIVES About 60% of Korean pediatric cochlear implantees could be genetically diagnosed (GD) and we previously reported that a substantial portion of undiagnosed cases by deafness gene panel sequencing were predicted to have a nongenetic or complex etiology. We aimed to compare the outcomes of cochlear implantation (CI) in GD and genetically undiagnosed (GUD) patients and attempted to determine CI outcomes according to etiology. DESIGN Ninety-three pediatric cochlear implantees underwent molecular genetic testing. Fifty-seven patients carried pathogenic variants and 36 patients remained GUD after panel sequencing of 204 known or potential deafness genes (TRS-204). Among them, 55 cochlear implantees with reliable speech evaluation results with a follow-up of longer than 24 months were recruited. Longitudinal changes in the audiologic performance were compared between the GD (n = 31) and GUD (n = 24) groups. The GD group was subdivided into cochlear implantee with SLC26A4 mutations (group 1) and cochlear implantee with other genetic etiology (group 2), and the GUD group was subdivided into groups 3 and 4, that is, patients with or without inner ear anomaly, respectively. RESULTS Group 1 related to SLC26A4 mutations had the highest categories of auditory perception scores among all groups pre- and postoperatively. Group 4 with inner ear anomaly had the lowest categories of auditory perception scores. At 24 months post-CI, the group 2 with another genetic etiology had significantly better outcomes than molecularly undiagnosed group 3, which had with the same condition as group 2 except that the candidate gene was not detected. This finding was recapitulated when we limited cases to those that underwent CI before 24 months of age to minimize age-related bias at implantation. Furthermore, on extending the follow-up to 36 months postoperatively, this tendency became more prominent. Additionally, our preliminary clinical data suggest a narrower sensitive window period for good CI outcomes for implantees with OTOF mutation rather than the GJB2 and other genes. CONCLUSIONS Current molecular genetic testing including deafness panel sequencing helps to predict the 2-year follow-up outcomes after CI in prelingually deafened children. GD cochlear implantees show better functional outcomes after CI than undiagnosed cochlear implantees as determined by deafness panel sequencing, suggesting a genotype-functional outcome correlation. The genetic testing may provide a customized optimal window period in terms of CI timing for favorable outcome according to genetic etiology.

Organ development requires complex signaling by cells in different tissues. Epithelium and mesenchyme interactions are crucial for the development of skin, hair follicles, kidney, lungs, prostate, major glands, and teeth. Despite myriad literature on cell–cell interactions and ligand–receptor binding, the roles of extracellular vesicles in epithelium–mesenchyme interactions during organogenesis are poorly understood. Here, we discovered that ~100 nm exosomes were secreted by the epithelium and mesenchyme of a developing tooth organ and diffused through the basement membrane. Exosomes were entocytosed by epithelium or mesenchyme cells with preference by reciprocal cells rather than self-uptake. Exosomes reciprocally evoked cell differentiation and matrix synthesis: epithelium exosomes induce mesenchyme cells to produce dentin sialoprotein and undergo mineralization, whereas mesenchyme exosomes induce epithelium cells to produce basement membrane components, ameloblastin and amelogenenin. Attenuated exosomal secretion by Rab27a/b knockdown or GW4869 disrupted the basement membrane and reduced enamel and dentin production in organ culture and reduced matrix synthesis and the size of the cervical loop, which harbors epithelium stem cells, in Rab27aash/ash mutant mice. We then profiled exosomal constituents including miRNAs and peptides and further crossed all epithelium exosomal miRNAs with literature-known miRNA Wnt regulators. Epithelium exosome-derived miR135a activated Wnt/β-catenin signaling and escalated mesenchymal production of dentin matrix proteins, partially reversible by Antago-miR135a attenuation. Our results suggest that exosomes may mediate epithelium–mesenchyme crosstalk in organ development, suggesting that these vesicles and/or the molecular contents they are transporting may be interventional targets for treatment of diseases or regeneration of tissues.

Objectives Local administration of 3-nitropropionic acid (3-NP) to the inner ear induces sensorineural hearing loss. Several studies have shown the otoprotective effects of ginkgo biloba extract EGb 761. Moreover, EGb 761 has been reported to activate Sirtuin 1 (SIRT1). The present study was designed to investigate whether EGb 761 prevents 3-NP-induced sensorineural hearing loss and determine its effects on the expression of SIRT1. Methods Sprague Dawley rats were divided into four experimental groups: control group receiving vehicle of 3-NP, EGb group receiving EGb 761, 3-NP group receiving 3-NP, and EGb+3-NP group receiving EGb 761 and 3-NP. EGb 761 was given orally for 5 days. The 3-NP solution was injected into the tympanum 3 days after the start of EGb 761 administration. The auditory brainstem response was recorded before and after the injection. At 4 weeks after the administration of 3-NP or vehicle of 3-NP, cochleae were harvested, and hematoxylin and eosin staining and immunohistochemistry for SIRT1 antibody were performed. Results EGb+3-NP group showed significantly lower threshold shifts than 3-NP group. There was a significant preservation of type II fibrocytes and spiral ganglion cells in EGb+3-NP group than in 3-NP group. In EGb+3-NP group, there was a significantly greater number of SIRT1 immunopositive type II fibrocytes and spiral ganglion cells than in 3-NP group. Calculating the percentage of SIRT1 immunoreactive type II fibrocytes and spiral ganglion cells in viable type II fibrocytes and spiral ganglion cells, respectively, EGb+3-NP group showed significantly higher SIRT1 immunoreactive cells than 3-NP group. Conclusion These results suggest that EGb 761 may prevent hearing loss induced by 3-NP in an acute ototoxic animal model, which appears to be related with SIRT1 expression.

Objectives Globally, newborn hearing screening (NHS) is variably incorporated into national healthcare systems. The authors reviewed the set-up and evolution process of a hospital-based NHS program in South Korea, where screening costs for low-income families are paid by the National Health Authority. Methods The NHS process for 13805 newborns delivered in a tertiary referral center of South Korea from 2005 through 2014 was reviewed. Hearing screening was conducted using automated auditory brainstem response (AABR); hearing loss was confirmed by auditory brainstem response for newborns who did not pass the screening test. Results The mean screening rate for hearing loss was 53.6% (7403 of 13805 newborns), which plateaued at 79.6% over time. Of the 14806 ears (7403 newborns), 1030 (7.0%) were assessed as “refer” on the first AABR, with 204 (1.4%) being assessed as “refer” on the second AABR. In hearing confirmation tests, 74 infants (1.0% of 7403 newborns) were diagnosed with hearing loss, including 13 infants (0.2%) with bilateral moderate to profound sensorineural hearing loss (SNHL). Hearing rehabilitation with long-term follow-up was confirmed in 11 infants. Conclusions In this hospital-based NHS program, the screening rate plateaued at ∼50% when the National Health Authority was not involved, but increased to ∼70% when the cost for low-income families was covered by the government. Among infants needing active hearing rehabilitation due to bilateral moderate to profound SNHL, 15% were lost to follow-up. These results demonstrate the need for a universal, mandatory NHS program to systematically register hearing-impaired infants within the government-sponsored public healthcare system.

The number of patients with osteoporosis is increasing worldwide, and a decrease in bone mass is a main risk factor for fracture. The prevention of bone loss is critical for improving the quality of life for patients. However, the long-term use of antiosteoporotic agents is limited due to their side effects. Barley has been traditionally ingested for thousands of years as a safe, natural food with pharmaceutical properties, and its seedling can enhance the biological activity of the medicinal components found in food. This study aimed to clarify the antiresorptive activity of barley seedling and its mode of action. Barley seedling extracts (BSE) dose-dependently inhibited RANKL-induced osteoclast differentiation with alteration of IκB degradation, c-Fos, and NFATc1 molecules in the early-to-middle stages of osteoclastogenesis. In the late phase of osteoclastogenesis, BSE also prevented DC-STAMP and cathepsin K, which are required for cell fusion and bone degradation, such as osteoclast function. In conclusion, barley seedling from natural foods may provide long-term safety and be useful for the prevention or treatment of osteoclast-mediated bone metabolic diseases, including osteoporosis.

Background An increased incidence of central precocious puberty has been recently reported in South Korea, which suggests an ongoing downward trend in pubertal development in the Korean population. We aimed to verify the trend in age at menarche in young Korean women during the last decade and associated factors. Methods We analyzed a population-based sample of 3409 Korean girls, aged 10–18 years, using data from the Korean National Health and Nutrition Examination Surveys (KNHANES) II (2001), III (2005), IV (2007–2009), and V (2010 and 2011). Average age at menarche was studied using the Kaplan-Meier survival method and predictors were analyzed using Cox proportional hazards model. The percentage of subjects who had experienced menarche at each age level was compared by using the Cochran-Armitage test. Results Overall mean age at menarche was 12.7 years. The percentage of subjects who experienced menarche before the age of 12 years was 21.4 % in 2001 but increased to 34.6 % in 2010/2011 (p

Objective To assess blood cadmium levels in Korean adolescents with respect to demographic and lifestyle factors. Methods We analyzed data from the Korea National Health and Nutrition Examination Survey from 2010 to 2013, totaling 1472 adolescents aged 10–18 years. Geometric means of blood cadmium were calculated using a complex samples general linear model to compare blood levels in different demographic and lifestyle groups. Multivariate logistic regression analyses were also used to find predictors for high blood cadmium (>90th percentile). Results The geometric mean of the blood cadmium concentrations was 0.30 μg/L in Korean adolescents. Older age, type of housing (multifamily house and commercial building), smoking and alcohol consumption, and iron deficiency/iron deficiency anemia (IDA) were significantly associated with higher blood cadmium concentrations (P

Although tinnitus retraining therapy (TRT) is efficacious in most patients, the exact mechanism is unclear and no predictor of improvement is available. We correlated the extent of improvement with pre-TRT quantitative electroencephalography (qEEG) findings to identify neural predictors of improvement after TRT. Thirty-two patients with debilitating tinnitus were prospectively enrolled, and qEEG data were recorded before their initial TRT sessions. Three months later, these qEEG findings were correlated with the percentage improvements in the Tinnitus Handicap Inventory (THI) scores, and numeric rating scale (NRS) scores of tinnitus loudness and tinnitus perception. The THI score improvement was positively correlated with the pre-treatment activities of the left insula and the left rostral and pregenual anterior cingulate cortices (rACC/pgACC), which control parasympathetic activity. Additionally, the activities of the right auditory cortices and the parahippocampus, areas that generate tinnitus, negatively correlated with improvements in loudness. Improvements in the NRS scores of tinnitus perception correlated positively with the pre-TRT activities of the bilateral rACC/pgACC, areas suggested to form the core of the noise-canceling system. The current study supports both the classical neurophysiological and integrative models of tinnitus; our results serve as a milestone in the development of precision medicine in the context of TRT.