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Background: Koenigia alpina (All.) T.M.Schust. & Reveal (alpine knotweed) is a perennial herb belonging to the Polygonaceae family. Several studies have examined Polygonaceae species' potential applications as cosmeceutical materials; however, the potential of K. alpina as a cosmeceutical has not yet been studied., Materials and Methods: Hydrogen peroxide (H 2 O 2 ) and lipopolysaccharide were used to induce an inflammatory response in RAW 264.7 cells. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radicals and H 2 O 2 were used to evaluate the free-radical scavenging activity of K. alpina extract and its protective effect against reactive oxygen species (ROS)-induced cell damage. The whitening, antiaging, and cell proliferation/migration effects of the extracts were evaluated via tyrosinase inhibition, collagenase/elastase inhibition, and wound healing assays, respectively. The anti-inflammatory effect was confirmed by evaluating nitric oxide (NO) production in RAW 264.7 cells. High-performance liquid chromatography (HPLC), UV, and MS/MS were used to determine the main components of the extract and fractions., Results: The ethyl acetate (EA) fraction and its aglycone fraction showed very high free-radical scavenging activities (47.5 and 47.1 µg/mL, respectively). The extract/fractions also showed significant tyrosinase inhibition (IC 50 = 0.38 mg/mL in EA fraction), collagenase inhibition (IC 50 = 0.21 mg/mL in EA fraction), and elastase inhibition (IC 50 = 0.57 mg/mL in aglycone fraction). NO production in lipopolysaccharide-induced RAW 264.7 cells was inhibited by the extract/fractions. The extract also promoted the closure of scratch wounds in HaCaT cells. The K. alpina extract/fractions contained cardamonin, quercetin, and quercitrin., Conclusion: K. alpina extracts/fractions showed antioxidant, antiaging, whitening, and anti-inflammatory activities, suggesting they may have potential as antiaging cosmeceuticals., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Objectives: To analyze the sizes of the stapedius and tensor tympani (TT) muscles using a temporal bone CT (TBCT) scan in patients with middle ear myoclonic tinnitus (MEMT) and investigate their value for the diagnosis of this rare cause of tinnitus., Methods: Medical records and TBCT of patients with MEMT or vascular tinnitus (VT) at Seoul St. Mary's Hospital from January 2012 to December 2022 were reviewed. The stapedius and TT muscles were analyzed., Results: Thirty-eight patients with unilateral MEMT and 39 patients with VT were included. More males were in the MEMT group compared to the VT group (MEMT: n  = 24, VT: n  = 8, p  = .001). The mean age of the MEMT group was younger compared to the VT group (MEMT: 35 ± 12 years, VT: 44 ± 14.3 years, p  = .005). The mean BMI for the MEMT group was less than the VT group (MEMT: 22.3 ± 2.5, VT: 24.8 ± 4.36, p  = .010). The mean length and width of the stapedius in the MEMT group were larger than those of the VT group ( Length MEMT: 1.47 ± 0.60 mm, VT: 0.98 ± 0.24 mm, p  = .001; Width MEMT: 0.89 ± 0.32 mm, VT: 0.72 ± 0.19 mm, p  = .009). The mean length and width of the TT in the MEMT group were larger than that of the VT group ( Length MEMT: 3.10 ± 0.50 mm, VT: 2.27 ± 0.42, p  = .001; Width MEMT: 2.02 ± 0.36, VT: 1.75 ± 0.26 p  = .001)., Conclusion: The mean length and width of the stapedius and TT muscles measured in the MEMT group were longer and wider than the VT group. This suggests the use TBCT scan as a diagnostic tool for MEMT. Further studies with a larger study group to validate the results of this study are recommended.Level of Evidence: 4., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Purpose: This study is descriptive research aiming to identify factors influencing the stigma experienced by college students with coronavirus disease 2019 (COVID-19), focusing on COVID-19 pandemic stress, depression, and fear of negative evaluation as the main variables., Methods: An online survey was administered to 175 college students who had been diagnosed with COVID-19 from January to May 2022 and were enrolled in universities in Seoul, Cheongju, and Daegu, South Korea. The survey collected data on pandemic stress, depression, fear of negative evaluation, and stigma. The data were analyzed using the t-test, ANOVA, the Scheffé test, Pearson's correlation coefficients, and stepwise multiple regression in SPSS/WIN 26.0., Results: We analyzed differences in stigma scores based on general characteristics of the college students and found significant differences in stigma scores by age, major satisfaction, interpersonal satisfaction, date of COVID-19 confirmation, treatment modality, and recent subjective health condition. Factors influencing stigmatization were identified as COVID-19 pandemic stress, depression, date of COVID-19 confirmation, treatment modality, recent subjective health condition, and major satisfaction, with an overall explanatory power of 37.6%., Conclusion: This study is significant as it identifies emotional changes across various aspects of pandemic stress, depression, fear of negative evaluation, and stigma among college students who have been diagnosed with COVID-19. The findings of this study suggest the development of programs to reduce psychological distress and enhance mental health management skills among these students.

Fusobacterium nucleatum (Fn), a bacterium present in the human oral cavity and rarely found in the lower gastrointestinal tract of healthy individuals 1 , is enriched in human colorectal cancer (CRC) tumours 2-5 . High intratumoural Fn loads are associated with recurrence, metastases and poorer patient prognosis 5-8 . Here, to delineate Fn genetic factors facilitating tumour colonization, we generated closed genomes for 135 Fn strains; 80 oral strains from individuals without cancer and 55 unique cancer strains cultured from tumours from 51 patients with CRC. Pangenomic analyses identified 483 CRC-enriched genetic factors. Tumour-isolated strains predominantly belong to Fn subspecies animalis (Fna). However, genomic analyses reveal that Fna, considered a single subspecies, is instead composed of two distinct clades (Fna C1 and Fna C2). Of these, only Fna C2 dominates the CRC tumour niche. Inter-Fna analyses identified 195 Fna C2-associated genetic factors consistent with increased metabolic potential and colonization of the gastrointestinal tract. In support of this, Fna C2-treated mice had an increased number of intestinal adenomas and altered metabolites. Microbiome analysis of human tumour tissue from 116 patients with CRC demonstrated Fna C2 enrichment. Comparison of 62 paired specimens showed that only Fna C2 is tumour enriched compared to normal adjacent tissue. This was further supported by metagenomic analysis of stool samples from 627 patients with CRC and 619 healthy individuals. Collectively, our results identify the Fna clade bifurcation, show that specifically Fna C2 drives the reported Fn enrichment in human CRC and reveal the genetic underpinnings of pathoadaptation of Fna C2 to the CRC niche., (© 2024. The Author(s).)

Ji Young Yoon,1 Keum-Jin Yang,2 Shi-Nae Park,3 Dong-Kee Kim,3 Jong-Duk Kim1 1Department of Chemical and Biomolecular Engineering, BK 21 Plus Program, Korea Advanced Institute of Science and Technology, Guseong-Dong, Yuseong-Gu, Daejeon, 2Clinical Research Institute, St Mary’s Hospital, Daejeon, 3Department of Otolaryngology – Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Abstract: Dexamethasone (Dex)-loaded PHEA-g-C18-Arg8 (PCA) nanoparticles (PCA/Dex) were developed for the delivery of genes to determine the synergistic effect of Dex on gene expression. The cationic PCA nanoparticles were self-assembled to create cationic micelles containing an octadecylamine (C18) core with Dex and an arginine 8 (Arg8) peptide shell for electrostatic complexation with nucleic acids (connexin 26 [Cx26] siRNA, green fluorescent protein [GFP] DNA or brain-derived neurotrophic factor [BDNF] pDNA). The PCA/Dex nanoparticles conjugated with Arg8, a cell-penetrating peptide that enhances permeability through a round window membrane in the inner ear for gene delivery, exhibited high uptake efficiency in HEI-OC1 cells. This potential carrier co-delivering Dex and the gene into inner ear cells has a diameter of 120–140 nm and a zeta potential of 20–25 mV. Different types of genes were complexed with the Dex-loaded PCA nanoparticle (PCA/Dex/gene) for gene expression to induce additional anti-inflammatory effects. PCA/Dex showed mildly increased expression of GFP and lower mRNA expression of inflammatory cytokines (IL1b, IL12, and INFr) than did Dex-free PCA nanoparticles and Lipofectamine® reagent in HEI-OC1 cells. In addition, after loading Cx26 siRNA onto the surface of PCA/Dex, Cx26 gene expression was downregulated according to real-time polymerase chain reaction for 24 h, compared with that using Lipofectamine reagent. After loading BDNF DNA into PCA/Dex, increased expression of BDNF was observed for 30 h, and its signaling pathway resulted in an increase in phosphorylation of Akt, observed by Western blotting. Thus, Dex within PCA/Dex/gene nanoparticles created an anti-inflammatory effect and enhanced gene expression. Keywords: cell-penetrating peptide, nanoparticle, dexamethasone, gene delivery, brain-derived neurotrophic factor

Background: Hearing rehabilitation with auditory training (AT) is necessary to improve speech perception ability in patients with hearing loss. However, face-to-face AT has not been widely implemented due to its high cost and personnel requirements. Therefore, there is a need for the development of a patient-friendly, mobile-based AT program., Objective: In this study, we evaluated the effectiveness of hearing rehabilitation with our chat-based mobile AT (CMAT) program for speech perception performance among experienced hearing aid (HA) users., Methods: A total of 42 adult patients with hearing loss who had worn bilateral HAs for more than 3 months were enrolled and randomly allocated to the AT or control group. In the AT group, CMAT was performed for 30 minutes a day for 2 months, while no intervention was provided in the control group. During the study, 2 patients from the AT group and 1 patient from the control group dropped out. At 0-, 1- and 2-month visits, results of hearing tests and speech perception tests, compliance, and questionnaires were prospectively collected and compared in the 2 groups., Results: The AT group (n=19) showed better improvement in word and sentence perception tests compared to the control group (n=20; P=.04 and P=.03, respectively), while no significant difference was observed in phoneme and consonant perception tests (both P>.05). All participants were able to use CMAT without any difficulties, and 85% (17/20) of the AT group completed required training sessions. There were no changes in time or completion rate between the first and the second month of AT. No significant difference was observed between the 2 groups in questionnaire surveys., Conclusions: After using the CMAT program, word and sentence perception performance was significantly improved in experienced HA users. In addition, CMAT showed high compliance and adherence over the 2-month study period. Further investigations are needed to validate long-term efficacy in a larger population., Trial Registration: Clinical Research Information Service (CRiS) KCT0006509; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22110&search_page=L., (© Jae Sang Han, Ji Hyung Lim, Yeonji Kim, Aynur Aliyeva, Jae-Hyun Seo, Jaehyuk Lee, Shi Nae Park. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org).)

Background: Tinnitus is a bothersome condition associated with various symptoms. However, the mechanisms of tinnitus are still uncertain, and a standardized assessment of the diagnostic criteria for tinnitus is required. We aimed to reach a consensus on diagnosing tinnitus with professional experts by conducting a Delphi study with systematic review of the literature., Methods: Twenty-six experts in managing tinnitus in Korea were recruited, and a two-round modified Delphi study was performed online. The experts evaluated the level of agreement of potential criteria for tinnitus using a scale of 1-9. After the survey, a consensus meeting was held to establish agreement on the results obtained from the Delphi process. Consensus was defined when over 70% of the participants scored 7-9 (agreement) and fewer than 15% scored 1-3 (disagreement). To analyze the responses of the Delphi survey, the content validity ratio and Kendall's coefficient of concordance were evaluated., Results: Consensus was reached for 22 of the 38 statements. For the definition of tinnitus, 10 out of 17 statements reached consensus, with three statements achieving complete agreement including; 1) Tinnitus is a conscious perception of an auditory sensation in the absence of a corresponding external stimulus, 2) Tinnitus can affect one's quality of life, and 3) Tinnitus can be associated with hearing disorders including sensorineural hearing loss, vestibular schwannoma, Meniere's disease, otosclerosis, and others. For the classification of tinnitus, 11 out of 18 statements reached consensus. The participants highly agreed with statements such as; 1) Vascular origin is expected in pulse-synchronous tinnitus, and 2) Tinnitus can be divided into acute or chronic tinnitus. Among three statements on the diagnostic tests for tinnitus only Statement 3, "There are no reliable biomarkers for sensory or emotional factors of tinnitus." reached consensus. All participants agreed to perform pure-tone audiometry and tinnitus questionnaires, including the Tinnitus Handicap Inventory and Tinnitus Questionnaire., Conclusion: We used a modified Delphi method to establish a consensus-based definition, a classification, and diagnostic tests for tinnitus. The expert panel reached agreement for several statements, with a high level of consensus. This may provide practical information for clinicians in managing tinnitus., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Introduction: Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases., Methods: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response., Results: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population., Conclusions: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: The risk of disasters and infectious diseases continues to persist in modern times. Children are a vulnerable group in disaster prevention and management due to their limited ability to cope on their own. Hence, the role and disaster preparedness capacity of early childhood teachers (ECTs) is vital for children's protection., Objectives: This study aims to explore how ECTs can improve their personal resilience to adapt to and overcome disasters as part of early childhood education and care (ECEC). To this end, this study examined the effects of ECTs' self-efficacy, resilience, disaster awareness, COVID-19 stress, and work-related stress on their disaster preparedness., Results: According to the outcomes of disaster preparedness of ECTs based on their general and job characteristics, full-time employees and principals scored significantly higher in work-related disaster preparedness (WrDP) compared to part-time workers and general and assistant teachers, respectively. Resilience and WrDP were identified as influencing factors of general disaster preparedness (GdP), with an explanatory power of 26.4%. GdP and self-efficacy were identified as influencing factors of WrDP, with an explanatory power of 25.7%., Discussion: According to the findings, ECTs' self-efficacy and GdP must be improved, followed by developing strategies to strengthen their resilience and WrDP. Doing so would ensure the safety and disaster preparedness of ECTs and infants who have low self-care capacity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Park, Lee and Nam.)

Objectives: Sigmoid sinus resurfacing (SS-R) is one of the most effective surgical treatments for patients with pulsatile tinnitus (PT) originating from anatomical variants of the vascular walls in the temporal bone. This study aimed to provide updated information on the clinical outcomes of SS-R and evaluate the efficacy of the water occlusion test (WOT) as an additional diagnostic modality., Methods: We retrospectively reviewed medical records including tinnitus questionnaires, temporal bone computed tomography (TBCT) scans, audiologic tests, and preoperative WOT., Results: from patients who underwent SS-R., Results: In total, 26 patients were included in the study. The mean age was 44 years, and the mean symptom duration was 3 months. Fourteen patients (53.8%) were completely cured, seven (26.9%) significantly improved, and five (19.2%) remained stable. The mean visual analog scale loudness score decreased from 5.26 to 1.34 (P<0.001) and the mean Tinnitus Handicap Inventory score also improved from 50.23 to 5.5 (P<0.001) after SS-R surgery. In 10 patients with discrepancies between the preoperative TBCT and intraoperative findings, WOT showed a significant additive effect in predicting surgical outcomes. No patients experienced severe intraoperative or postoperative complications during the entire follow-up period., Conclusion: SS-R provides significant symptom improvement in patients with sigmoid sinus dehiscence who had a positive WOT without other sigmoid sinus variants. A combined diagnostic approach with TBCT, WOT, and intraoperative findings is crucial for achieving better surgical outcomes in patients with PT caused by sigmoid sinus variants.

Objectives: The aim of this study was to determine the most effective treatment approach by comparing the impacts of various otolith reduction techniques in patients with apogeotropic lateral semicircular canal benign paroxysmal positional vertigo (LC-BPPV)., Methods: We performed a multicenter randomized prospective study from January to December 2015, involving 72 consecutive patients with apogeotropic LC-BPPV. The patients were divided into three treatment groups: therapeutic head-shaking (group A), the Gufoni-Appiani maneuver (group B), and the cupulolith repositioning maneuver (CuRM; group C). Each group underwent evaluation and treatment up to the fourth week. Treatment success was defined as the disappearance of positional vertigo and nystagmus., Results: This study included 72 patients (49 male and 23 female), with a mean (±standard deviation) age of 55.4±13.5 years. The mean duration of vertigo experienced prior to treatment was 3.9±4.4 days. The mean latency and duration of nystagmus were 2.7±3.0 seconds and 47.9±15.8 seconds, respectively. The overall treatment frequency was 2.0±0.9. The number of treatments differed significantly among the three groups (P<0.05). After 4 weeks, the success rates for groups A, B, and C were 90.5%, 92.3%, and 100%, respectively. No significant difference was observed in the success rate across treatment., Methods: and periods (P>0.05). However, CuRM was the only method with a 100% treatment success rate., Conclusion: While no clear difference was observed among the three treatments for LC-BPPV, CuRM was found to be superior to the other approaches in the long term.

We present an integrating hemisphere-based (i.e., a variant of integrating spheres) implementation of the indirect illumination method for absolute photoluminescence quantum yield measurements, which is a recommended method in the international standard IEC 62607-3-1:2014. We rigorously formulated a mathematical model and a measurement procedure for the absolute photoluminescence quantum yield measurement in the integrating hemisphere-based system. The measurement system was calibrated using an Hg-Ar discharge lamp and spectral irradiance standard lamps for wavelength and relative spectral radiant flux scales, respectively. Furthermore, we identified and evaluated uncertainty components involved in the photoluminescence quantum yield (PLQY) measurement. To validate our measurement system, we applied it to the two de facto standard dyes: quinine bisulfate (QBS) and fluorescein (FLS). Consequently, their PLQY values were determined to be 0.563±0.024 ( k =2) and 0.876±0.032 ( k =2) for, respectively, QBS and FLS, which are consistent with previous reports.

The purposes of this study were to examine the compositional changes in the salivary microbiota according to the severity of periodontal disease and to verify whether the distribution of specific bacterial species in saliva can distinguish the severity of disease. Saliva samples were collected from 8 periodontally healthy controls, 16 patients with gingivitis, 19 patients with moderate periodontitis, and 29 patients with severe periodontitis. The V3 and V4 regions of the 16S rRNA gene in the samples were sequenced, and the levels of 9 bacterial species showing significant differences among the groups by sequencing analysis were identified using quantitative real-time PCR (qPCR). The predictive performance of each bacterial species in distinguishing the severity of disease was evaluated using a receiver operating characteristic curve. Twenty-nine species, including Porphyromonas gingivalis, increased as the severity of disease increased, whereas 6 species, including Rothia denticola, decreased. The relative abundances of P. gingivalis, Tannerella forsythia, Filifactor alocis, and Prevotella intermedia determined by qPCR were significantly different among the groups. The three bacterial species P. gingivalis, T. forsythia, and F. alocis were positively correlated with the sum of the full-mouth probing depth and were moderately accurate at distinguishing the severity of periodontal disease. In conclusion, the salivary microbiota showed gradual compositional changes according to the severity of periodontitis, and the levels of P. gingivalis, T. forsythia , and F. alocis in mouth rinse saliva had the ability to distinguish the severity of periodontal disease. IMPORTANCE Periodontal disease is one of the most widespread medical conditions and the leading cause of tooth loss, imposing high economic costs and an increasing burden worldwide as life expectancy increases. Changes in the subgingival bacterial community during the progression of periodontal disease can affect the entire oral ecosystem, and bacteria in saliva can reflect the degree of bacterial imbalance in the oral cavity. This study explored whether the specific bacterial species in saliva can distinguish the severity of periodontal disease by analyzing the salivary microbiota and suggested P. gingivalis, T. forsythia , and F. alocis as biomarkers for distinguishing the severity of periodontal disease in saliva., Competing Interests: The authors declare a conflict of interest. All authors are co-applicants on patent application 10-2021-0138897 entitled “Composition for diagnosing periodontal disease using microbiome in saliva and use thereof”.

One of the bottlenecks to building semiconductor chips is the increasing cost required to develop chemical plasma processes that form the transistors and memory storage cells 1,2 . These processes are still developed manually using highly trained engineers searching for a combination of tool parameters that produces an acceptable result on the silicon wafer 3 . The challenge for computer algorithms is the availability of limited experimental data owing to the high cost of acquisition, making it difficult to form a predictive model with accuracy to the atomic scale. Here we study Bayesian optimization algorithms to investigate how artificial intelligence (AI) might decrease the cost of developing complex semiconductor chip processes. In particular, we create a controlled virtual process game to systematically benchmark the performance of humans and computers for the design of a semiconductor fabrication process. We find that human engineers excel in the early stages of development, whereas the algorithms are far more cost-efficient near the tight tolerances of the target. Furthermore, we show that a strategy using both human designers with high expertise and algorithms in a human first-computer last strategy can reduce the cost-to-target by half compared with only human designers. Finally, we highlight cultural challenges in partnering humans with computers that need to be addressed when introducing artificial intelligence in developing semiconductor processes., (© 2023. The Author(s).)

Purpose: We developed a virtual reality (VR) program for use in pediatric nursing practicums to help nursing students learn to measure vital signs in children., Methods: The analysis, design, development, implementation, and evaluation model was employed between July 2021 and December 2021 at a university in South Korea. In the analysis phase, in-depth interviews were conducted with four nursing students, two nursing school graduates, and four experts. The topic and contents of the VR program were settled in the design phase. The VR program was developed and subsequently used and evaluated by 20 nursing students and four experts., Results: The contents of the VR program for pediatric nursing practicums included the measurement of vital signs in a newborn baby and a young child, as well as an evaluation system. The mean score for the nursing students' satisfaction with practice was 4.02 out of 5 points. The mean scores for overall satisfaction with the VR program were 4.15 and 4.79 out of 5 points for nursing students and experts, respectively., Conclusion: The VR program developed in this study allows nursing students to practice measuring vital signs in children, thus improving the students' clinical performance in pediatric nursing.

Objectives: The impacts of ventilation tube (VT) type and effusion composition on the VT extrusion rate and complications in children with otitis media remain unclear. This part II study evaluated the factors affecting the extrusion rate, recurrence rate, and complications of VT insertion., Methods: A prospective study was conducted between June 2014 and December 2016 (the EVENT study [analysis of the effectiveness of ventilation tube insertion in pediatric patients with chronic otitis media]), with follow-up data collected until the end of 2017. Patients aged <15 years diagnosed with otitis media with effusion who received VT insertion were recruited at 15 tertiary hospitals. The primary outcomes were time to extrusion of VT, time to effusion recurrence, and complications., Results: Data from 401 patients were analyzed. After excluding the., Results: of long-lasting tubes (Paparella type II and T-tubes), silicone tubes (Paparella type I) exhibited a significantly longer extended time to extrusion (mean, 400 days) than titanium tubes (collar-button-type 1.0 mm: mean, 312 days; P<0.001). VT material (hazard ratio [HR], 2.117, 95% confidence interval [CI], 1.254-3.572; P=0.005), age (HR, 3.949; 95% CI, 1.239-12.590; P=0.02), and effusion composition (P=0.005) were significantly associated with the time to recurrence of middle ear effusion. Ears with purulent (mean, 567 days) and glue-like (mean, 588 days) effusions exhibited a shorter time to recurrence than ears with serous (mean, 846 days) or mucoid (mean, 925 days) effusions. The revision VT rates during follow-up were 3.5%, 15.5%, 10.4%, and 38.9% in ears with serous, mucoid, glue-like, and purulent effusions, respectively (P<0.001). The revision surgery rates were higher among patients aged <7 years than among those aged ≥7 years., Conclusion: Silicone tubes (Paparella type I) were less prone to early extrusion than titanium 1.0 mm tubes. VT type, patient age, and effusion composition affected the time to recurrence of effusion.

The safety and efficacy of intratympanic (IT) histamine (HIS) injection as an adjuvant to increase the inner ear penetration of dexamethasone (DEX) was investigated in this study. IT injections of DEX-only, 1% HIS+DEX and 4% HIS+DEX were performed in mice with noise-induced hearing loss. An inflammatory reaction in the middle ear was observed only in the 4% HIS+DEX group although no serious cytotoxic effects on the organ of Corti (OC) were observed at that concentration. Compared with the DEX-only group, the perilymphatic concentration of DEX was approximately two times higher in the 1% HIS+DEX group and approximately five times higher in the 4% HIS+DEX group. The expression of the DEX receptor in the cochlea was significantly increased in the 4%-HIS+DEX group. HIS appeared to induce transient damage the microstructure of the RWM with recovery observed within 3 weeks. The 1 and 4% HIS + DEX groups showed a significant recovery of the OC compared with the control group and they also achieved significantly better hearing restoration at 8 kHz in the DPOAE hearing test (P < .05) when compared to the DEX-only group. IT HIS temporarily disrupts the structure of the RWM and middle ear mucosa and significantly enhances the inner ear penetration of DEX. Therefore, IT HIS injection could be a simple and effective adjuvant therapy to increase perilymph concentration of DEX and achieve OC recovery after cochlear damage., (Copyright © 2022. Published by Elsevier B.V.)

Alpha-lipoic acid (ALA) is an antioxidant with oto-protective effects. In the present study, the safety and effectiveness of ALA therapy after noise-induced hearing loss was confirmed based on the administration method. The safety of intratympanic ALA (IT-ALA) was evaluated with oto-endoscopy and middle ear mucosa morphologic study. Perilymph ALA concentrations according to the administration routes were compared, and the efficacy of ALA was investigated through hearing tests and cochlear histological studies. The middle ear mucosa was swollen 1 week after IT-ALA but completely recovered within 3 weeks. ALA concentration in the perilymph was significantly higher in the IT-ALA group. Recovery of organ of Corti morphology and hearing levels were predominant in the IT-ALA group compared with the intraperitoneal injection group (IP-ALA) and showed similar rescue effects in the IT-dexamethasone group (IT-DEX). Interleukin-1 beta and nuclear factor-kappa B expression was significantly downregulated in the IT-ALA group. IT-ALA showed better cochlear recovery from acoustic trauma with higher inner ear penetration rate than IP-ALA. The rescue effect of IT-ALA after noise-induced hearing loss was similar to IT-DEX; however, the ALA and DEX mechanisms are different. IT-ALA appears to be another safe and effective treatment modality after acoustic trauma and comparable to IT-DEX.

Objectives: Despite sufficient hearing gains, many patients with hearing loss have difficulty using hearing aids due to poor word recognition ability. This study was performed to introduce our hearing rehabilitation therapy (HRT) program for hearing aid users and to evaluate its effect on hearing improvement., Methods: In this prospective randomized case-control study, 37 participants with moderate or moderate-severe sensorineural hearing loss who had used bilateral hearing aids for more than 3 months with sufficient functional hearing gain were enrolled in this study. Nineteen participants were randomly assigned to the control group (CG) and 18 patients were assigned to participate in our HRT program once a week for 8 consecutive weeks (hearing rehabilitation therapy group [HRTG]). Their hearing results and questionnaire scores for hearing handicap and hearing aid outcomes were prospectively collected and compared between the two groups., Results: After completing 8 weeks of the HRT program, the HRTG showed a significantly greater improvement in scores for consonant-only and consonant-vowel sound perception than the CG (P<0.05). In addition, the HRTG showed a significant improvement in hearing ability as measured by two questionnaires (p<0.05), while no differences were observed in the CG. However, word and sentence recognition test results did not show significant differences between the two groups., Conclusion: Even after short-term HRT, patients had subjectively better hearing outcomes and improved phoneme perception ability; this provides scientific evidence regarding a possible positive role for HRT programs in hearing aid users. Further validation in a larger population through a long-term follow-up study is needed.

Objectives: This study was conducted to evaluate the user satisfaction, efficacy, and safety of round window (RW) vibroplasty using the Vibrant Soundbridge (VSB) in patients with persistent mixed hearing loss after mastoidectomy., Methods: The study included 27 patients (mean age, 58.7 years; age range, 28-76 years; 11 men and 16 women) with mixed hearing loss after mastoidectomy from 15 tertiary referral centers in Korea. The VSB was implanted at the RW. The Korean translation of the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire and the Korean version of the International Outcome Inventory for Hearing Aids (K-IOI-HA) questionnaire were used to evaluate user satisfaction as the primary outcome. The secondary outcome measures were audiological test results and complication rates., Results: The mean scores for ease of communication (61.3% to 29.7% to 30.2%), reverberation (62.1% to 43.1% to 37.4%), and background noise (63.3% to 37.7% to 34.3%) subscales of the APHAB questionnaire significantly decreased after VSB surgery. The mean K-IOI-HA scores at 3 and 6 months after surgery were significantly higher than the mean preoperative score (18.6 to 27.2 to 28.1). The postoperative VSB-aided thresholds were significantly lower than the preoperative unaided and hearing aid (HA)-aided thresholds. There was no significant difference between preoperative unaided, preoperative HA-aided, and postoperative VSB-aided maximum phonetically balanced word-recognition scores. None of the 27 patients experienced a change in postoperative bone conduction pure tone average. One patient developed temporary facial palsy and two developed surgical wound infections., Conclusion: RW vibroplasty resulted in improved satisfaction and audiological test results in patients with mixed hearing loss after mastoidectomy, and the complication rate was tolerable.

Objectives: The aims of this study were to investigate the test-retest reliability of measurements of loudness discomfort levels (LDLs), to suggest cut-off values for diagnosing patients with hyperacusis, and to evaluate the clinical value of-LDL measurements as a test for monitoring hyperacusis., Methods: For the test-retest reliability of LDL measurements (study 1), a total of 68 patients who sought consultations at our clinic were subcategorized into four groups: patients with tinnitus (group 1), tinnitus and hearing loss (group 2), hyperacusis (group 3), and normal controls (group 4). Inter-hour and inter-day test-retest reliability values using different stimuli were investigated. For study 2, the clinical value of LDL measurements using pure tone stimuli was analyzed by comparing changes after sound generator use in patients with hyperacusis., Results: In study 1, the group 3 patients showed significantly lower LDLs than the other groups. High test-retest reliability of LDL tests was demonstrated, regardless of the type of stimulus used. The cut-off values for screening patients with hyperacusis were 90 dB HL using pure tone stimuli and 62 dB HL using white-band noise stimuli. In study 2, significantly increased LDLs were correlated with improved symptoms and improved scores on tinnitus questionnaires after sound generator use, indicating that LDL measurement is a reliable test for monitoring hyperacusis during an intervention., Conclusion: LDL measurement is a reliable diagnostic tool to reflect the condition of hyperacusis, especially during the course of treatment.

Objective: To investigate the association between genetic polymorphisms of brain-derived neurotrophic factor (BDNF) or serotonin transporter gene-linked polymorphic region (5-HTTLPR) and tinnitus, and the mediating effects of psychological distress on this association., Methods: Eighty-six patients experiencing tinnitus and 252 controls were recruited. The Tinnitus Handicap Inventory was used to assess the severity of tinnitus and the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory-II (BAI-II), and the Korean version of the Brief Encounter Psychosocial Instrument (BEPSI-K) were used to assess psychological distress. We compared the association of BDNF rs6265 (Val66Met) and 5-HTTLPR variants in the two groups. The mediating effects of BDI-II, BAI-II, and BEPSI-K were examined using multiple regression analysis and validated by the Sobel test and bootstrapping., Results: No significant differences were found between the groups regarding BDNF Val66Met and 5-HTTLPR, but the 5-HTTLPR variants trended toward association. Depressive symptoms appeared to act as a mediator on the relationship within the 5-HTTLPR s/s genotype and the severity of tinnitus., Conclusion: Our findings provide a speculative idea on the association between the serotonergic system and tinnitus and suggest that depressive symptoms act as a mediator in tinnitus. Therefore, screening for depressive symptoms in patients with tinnitus is essential and intervention for depressive symptoms may help alleviate the severity of tinnitus.

Objectives: Amid the spread of coronavirus disease 2019 (COVID-19), with its high infectivity, we have relied on mathematical models to predict the temporal evolution of the disease. This paper aims to show that, due to active behavioral changes of individuals and the inherent nature of infectious diseases, it is complicated and challenging to predict the temporal evolution of epidemics., Methods: A modified susceptible-exposed-infectious-hospitalized-removed (SEIHR) compartment model with a discrete feedback-controlled transmission rate was proposed to incorporate individuals' behavioral changes into the model. To figure out relative uncertainties in the infection peak time and the fraction of the infected population at the peak, a deterministic method and 2 stochastic methods were applied., Results: A relatively small behavioral change of individuals with a feedback constant of 0.02 in the modified SEIHR model resulted in a peak time delay of up to 50% using the deterministic method. Incorporating stochastic methods into the modified model with a feedback constant of 0.04 suggested that the relative random uncertainty of the maximum fraction of infections and that of the peak time for a population of 1 million reached 29% and 9%, respectively. Even without feedback, the relative uncertainty of the peak time increased by up to 20% for a population of 100,000., Conclusions: It is shown that uncertainty originates from stochastic properties of infections. Without a proper selection of the evolution scenario, active behavioral changes of individuals could serve as an additional source of uncertainty.

Purpose: Temporal summation of pain, which is defined as the perception of greater pain evoked by repetitive painful stimuli, varies among individuals. This study aimed at determining the impact of the timing of rocuronium after induction with propofol on the temporal summation of pain., Methods: One hundred patients aged 19-60 years underwent gynecologic laparoscopic surgery. Patients were randomly assigned to one of the two groups: group PRi received immediate injections of rocuronium after propofol administration and group PRd received rocuronium injections when the bispectral index score (BIS) decreased to <60 after propofol administration. The grade of rocuronium-induced withdrawal movement (RIWM) according to the timing of propofol injection, the incidence and severity of propofol injection pain (PIP), rescue analgesics, visual analog scale (VAS) score after surgery for postoperative pain, patient-controlled analgesia (PCA) opioid consumption, association between PIP and the grade of RIWM, and associations between PIP, the grade of RIWM, and postoperative pain outcomes were measured., Results: The differences between the incidence and severity of PIP in the two groups were not significant. The grade of the RIWM in the PRd group was significantly reduced compared with the PRi group. Rescue analgesics, severity for postoperative pain, and PCA opioid consumption were not significant. Correlations between the incidence and severity of PIP and the grade of RIWM were weakly negative. Correlations between the grade of RIWM and pain outcomes were moderately positive, but correlations between the severity for PIP and the postoperative pain outcomes were negligible., Conclusion: The timing of rocuronium administration after propofol injection played a role in reducing RIWM. The grade of RIWM was significantly related to pain outcomes compared with the severity of PIP. Therefore, delayed rocuronium injection after induction with propofol reduced temporal summation of pain., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Jaehak Jung et al.)

The purpose of this study was to evaluate the clinical efficacy and safety of patient-specific additive-manufactured CaOSiO 2 -P 2 O 5 -B 2 O 3 glass-ceramic (BGS-7) implants for reconstructing zygomatic bone defects at a 6-month follow-up. A prospective, single-arm, single-center, clinical trial was performed on patients with obvious zygoma defects who needed and wanted reconstruction. The primary outcome variable was a bone fusion between the implant and the bone evaluated by computed tomography (CT) at 6 months post surgery. Secondary outcomes, including implant immobilization, satisfaction assessment, osteolysis, subsidence of the BGS-7 implant, and safety, were assessed. A total of eight patients were enrolled in the study. Two patients underwent simultaneous reconstruction of the left and right malar defects using a BGS-7 3D printed implant. Cone beam CT analysis showed that bone fusion at 6 months after surgery was 100%. We observed that the average fusion rate was 76.97%. Osteolysis around 3D printed BGS-7 implants was not observed. The mean distance displacement of all 10 implants was 0.4149 mm. Our study showed no adverse event in any of the cases. The visual analog scale score for satisfaction was 9. All patients who enrolled in this trial were aesthetically and functionally satisfied with the surgical results. In conclusion, this study demonstrates the safety and promising value of patient-specific 3D printed BGS-7 implants as a novel facial bone reconstruction method.

Background: The aim of this study was to evaluate the safety and efficacy of a flowable hemostatic matrix, and their effects for postoperative pancreatic fistula (POPF) after pancreatectomy., Methods: This was a randomized, clinical, single-center, single-blind (participant), non-inferiority, phase IV, and parallel-group trial. The primary endpoint was the incidence of POPF. The secondary endpoints were risk factors for POPF, drain removal days, incidence of complication, 90-day mortality, and length of hospital stay., Results: This study evaluated a total of 53 patients, of whom 26 patients were in the intervention group (flowable hemostatic matrix) and 27 patients were in the control group (thrombin-coated collagen patch). POPF was more common in the control group than in the intervention group (59.3% vs. 30.8%, p = 0.037). Among participants who underwent distal pancreatectomy, POPF (33.3% vs. 92.3%, p = 0.004), and clinically relevant POPF (8.3% vs. 46.2%, p = 0.027) was more common in the control group. A multivariate logistic regression model identified flowable hemostatic matrix use as an independent negative risk factor for POPF, especially in cases of distal pancreatectomy (DP) (odds ratio 17.379, 95% confidential interval 1.453-207.870, p = 0.024)., Conclusion: Flowable hemostatic matrix application is a simple, feasible, and effective method of preventing POPF after pancreatectomy, especially for patients with DP. Non-inferiority was demonstrated in the efficacy of preventing POPF in the intervention group compared to the control group.

Background: Endometriosis, an estrogen-dependent inflammatory disease, is commonly observed in gynecologic practice. Spontaneous hemoperitoneum is a rare but serious complication of endometriosis. Most cases of endometriosis-induced hemoperitoneum are attributable to a ruptured endometrioma or utero-ovarian vessel hemorrhage. We report a case of massive hemoperitoneum secondary to intra-abdominal bleeding from the peritoneal endometriotic deposits with spontaneous abortion that was misdiagnosed as a ruptured ectopic pregnancy., Case Presentation: A 36-year-old Korean woman was admitted to our hospital for acute abdominal pain and vaginal bleeding. She was suspected of ruptured ectopic pregnancy on the basis of a positive serum human chorionic gonadotropin test result and ultrasonographic evidence of pelvic fluid collection. During hospitalization, her symptoms deteriorated with peritoneal irritation sign on physical examination, hypotension, and tachycardia. Emergency exploratory laparoscopy was performed and revealed active bleeding from the peritoneal endometriotic deposit, which was treated with laparoscopic electrocoagulation. The patient's postoperative course was uneventful. Spontaneous abortion was diagnosed on the basis of decreased serial serum human chorionic gonadotropin level estimation., Conclusions: Although rare, gynecologists should consider endometriosis-induced hemoperitoneum with spontaneous abortion in the differential diagnosis in women of reproductive age presenting with a positive serum human chorionic gonadotropin test result and acute abdomen with intra-abdominal bleeding.

Objective: Esterified collagen (EC) can be functionalized with heparin to enhance islet graft stability. Growth factors secreted by human adipose-derived stem cells (hADSCs) can bind efficiently to EC-heparin (EC-Hep), which enhances revascularization and cell protection. We investigated the therapeutic potential of a combined heparin-esterified collagen-hADSC (HCA)-islet sheet to enhance islet engraftment., Research Design and Methods: This study was designed to assess the efficiency of using EC-Hep as a scaffold for subcutaneous islet transplantation in diabetic athymic mice. After the hADSC-cocultured islets were seeded in the EC-Hep scaffold, islet function was measured by glucose-stimulated insulin secretion test and growth factors in the culture supernatants were detected by protein array. Islet transplantation was performed in mice, and graft function and survival were monitored by measuring the blood glucose levels. β-Cell mass and vascular densities were assessed by immunohistochemistry., Results: The EC-Hep composite allowed sustained release of growth factors. Secretion of growth factors and islet functionality in the HCA-islet sheet were significantly increased compared with the control groups of islets alone or combined with native collagen. In vivo, stable long-term glucose control by the graft was achieved after subcutaneous transplantation of HCA-islet sheet due to enhanced capillary network formation around the sheet., Conclusions: The findings indicate the potential of the HCA-islet sheet to enhance islet revascularization and engraftment in a hADSC dose-dependent manner, following clinical islet transplantation for the treatment of diabetes mellitus., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

High grade serous ovarian carcinoma (HGSOC) is the most common and aggressive ovarian malignancy. Accumulating evidence indicates that HGSOC may originate from human fallopian tube epithelial cells (FTECs), although the exact pathogen(s) and/or molecular mechanism underlying the malignant transformation of FTECs is unclear. Here we show that human papillomavirus (HPV), which could reach FTECs via retrograde menstruation or sperm-carrying, interacts with the yes-associated protein 1 (YAP1) to drive the malignant transformation of FTECs. HPV prevents FTECs from natural replicative and YAP1-induced senescence, thereby promoting YAP1-induced malignant transformation of FTECs. HPV also stimulates proliferation and drives metastasis of YAP1-transformed FTECs. YAP1, in turn, stimulates the expression of the putative HPV receptors and suppresses the innate immune system to facilitate HPV acquisition. These findings provide critical clues for developing new strategies to prevent and treat HGSOC., (© 2024. The Author(s).)

Telomere length (TL) is a prognostic indicator in Caucasian chronic lymphocytic leukemia (CLL), but its significance in Asian CLL remains unknown. To investigate the prognostic significance of TL and its correlation with cytogenetic aberrations and somatic mutations, we analyzed TL measurements at the cellular level by interphase fluorescence in situ hybridization in patients with CLL in Korea. The present study enrolled 110 patients (41 females and 69 males) diagnosed with CLL according to the World Health Organization criteria (2001-2017). TLs of bone marrow nucleated cells at the single-cell level were measured by quantitative fluorescence in situ hybridization (Q-FISH) in 71 patients. The correlations of TL with clinical characteristics, cytogenetic aberrations, genetic mutations, and overall survival were assessed. The median value of mean TL in CLL patients (T/C ratio 7.46 (range 1.19-18.14) was significantly shorter than that in the normal controls (T/C ratio 15.28 (range 8.59-24.93) (p < 0.001). Shorter TLs were associated with complex karyotypes (p = 0.030), del(11q22) (p = 0.023), presence of deletion and/or mutation in ATM and/or TP53 (p = 0.019), and SH2B3 mutation (p = 0.015). A shorter TL was correlated with lower hemoglobin levels and adverse survival (mean TL < 9.35, p = 0.021). When the proportion of cells with extremely short TLs (< 7.61) was greater than 90%, CLL patients showed poor survival (p = 0.002). Complex karyotypes, TP53 mutation, and the number of mutated genes were determined to be significant adverse variables by multivariable Cox analysis (p = 0.011, p = 0.002, and p = 0.002, respectively). TL was attrited in CLL, and attrited telomeres were correlated with adverse survival and other well-known adverse prognostic factors. We infer that TL is an independent adverse prognostic predictor in Korean CLL., Competing Interests: The authors have declared that no competing interests exist.

For kesterite copper zinc tin sulfide/selenide (CZTSSe) solar cells to enter the market, in addition to efficiency improvements, the technological capability to produce flexible and large-area modules with homogeneous properties is necessary. Here, we report a greater than 10% efficiency for a cell area of approximately 0.5 cm 2 and a greater than 8% efficiency for a cell area larger than 2 cm 2 of certified flexible CZTSSe solar cells. By designing a thin and multi-layered precursor structure, the formation of defects and defect clusters, particularly tin-related donor defects, is controlled, and the open circuit voltage value is enhanced. Using statistical analysis, we verify that the cell-to-cell and within-cell uniformity characteristics are improved. This study reports the highest efficiency so far for flexible CZTSSe solar cells with small and large areas. These results also present methods for improving the efficiency and enlarging the cell area.

Background: Flowable hemostatic agents may be more advantageous than nonflowable hemostats, as they have capability to cover irregular wound surfaces, fill deep lesions, and easily remove excess materials with irrigation. In this study, we evaluated the hemostatic efficacy of the collagen hemostatic matrix (CHM) compared to FloSeal ® via incisions in the heart and cardiac vessels in a porcine model., Methods: In each of the two female pigs, a total of two incisions were made in seven locations: right atrium (RA), right ventricle (RV), and cardiac vessels, such as the innominate vein (IV), superior vena cava (SVC), pulmonary artery (PA), coronary artery (CA), and aorta. Hemostatic agents were applied directly to the bleeding wounds. In certain location, one incision was treated with the CHM and the other with FloSeal ® , and the time to hemostasis and the degree of bleeding of the two agents were assessed and compared. One week after surgery, the animals were sacrificed, and specimens were collected for histologic evaluation., Results: Bleeding from the vessels with relatively low pressure (the IV, SVC, and RA) was controlled within 1-2 minutes using both a CHM and FloSeal ® . Bleeding from the vessels with high blood pressure (the RV, PA, CA, and aorta) was controlled within 3-10 minutes with the CHM. However, hemostasis in the PA and CA was not achieved with FloSeal ® . Histological analysis revealed that the use of both the CHM and FloSeal ® resulted in foreign body reactions of similar severity., Conclusions: The hemostatic effect and safety of the CHM may be similar to that of FloSeal ® . Further clinical studies must be conducted to validate our results., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS., Methods: Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform., Results: Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations., Conclusions: This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS.

Objective: This study evaluated gender differences in the relationship between psychiatric distress and subjective tinnitus severity., Methods: This cross-sectional study included 134 female and 114 male patients who visited the otology outpatient clinic at Seoul St. Mary's Hospital for tinnitus from February to July 2015. Patients completed a series of instruments, including the Tinnitus Handicap Inventory, Beck Depression Inventory, Korean version of Brief Encounter Psychosocial Instrument (BEPSI-K), and visual analogue scales assessing various tinnitus characteristics (loudness, awareness, annoyance, and effect on life)., Results: Tinnitus severity did not significantly differ between the gender groups ( p =0.632), and it correlated significantly with tinnitus characteristics and psychiatric distress. Partial correlations between tinnitus severity and depressive symptoms were stronger in males (r=0.411, p ＜0.01) than in females (r=0.304, p ＜0.01) while controlling for duration of tinnitus and tinnitus characteristics. However, stress (BEPSI-K) was positively correlated with tinnitus severity in only males (r=0.463, p ＜0.01). A multiple regression analysis revealed that effect of tinnitus on life, depressive symptoms, and stress were significantly associated with tinnitus severity in males, whereas only tinnitus annoyance and depressive symptoms were associated with tinnitus severity in females., Conclusion: Tinnitus severity was significantly correlated with depressive symptoms and stress, and there were gender differences in the relationship between tinnitus severity and psychiatric components. It is necessary to be vigilant of psychiatric symptoms among patients with tinnitus who visit the otology outpatient clinic, especially for male patients.

The effects of Lavandula angustifolia extract fermented with Pediococcus pentosaceus DK1 on UVB-mediated MMP-1 expression and collagen decrease in human skin fibroblasts were determined, and the conversion of its components was also analyzed. Fermentation was performed at varying L. angustifolia extract and MRS medium concentrations, and optimal fermentation conditions were selected. L. angustifolia extracts showed decreased cytotoxicity after fermentation in the fibroblasts. UVB-irradiated fibroblasts treated with fermented L. angustifolia extract showed MMP-1 expression 8.2-14.0% lower than that in UVB-irradiated fibroblasts treated with non-fermented extract. This was observed even at fermented extract concentrations lower than those of non-fermented extracts. Fibroblasts treated with fermented L. angustifolia extract showed 20% less reduction in collagen production upon UVB irradiation than those treated with non-fermented extracts. UVB-irradiated fibroblasts treated with fermented L. angustifolia extracts showed 50% higher inhibition of ROS generation than those treated with non-fermented extract. Luteolin and apigenin glycosides of L. angustifolia were converted during fermentation, and identified using RP-HPLC and LC/ESI-MS. Therefore, the effects of L. angustifolia extract on MMP-1 expression and collagen decrease in UVB-irradiated human skin fibroblasts were increased through fermentation by P. pentosaceus .

Background: Coffee silverskin is a thin film that covers the raw coffee bean. In general, coffee silverskin, which detaches during the coffee roasting process, is disposed as firelighters or dispatched to landfills and can cause serious environmental pollution. The aim of this study was to investigate the feasibility of using coffee silverskin as a functional material in cosmetics by evaluating its bioactive ingredients, antioxidative activity, cytoprotective effect, matrix metalloproteinase-1 (MMP-1)-inhibiting effect, and anti-melanogenesis effect., Results: To this end, a 50% ethanol (EtOH) extract and its ethyl acetate (EtOAc) fraction were prepared from coffee silverskin; caffeine was found to be the major compound in the extract. Both the 50% EtOH extract and its EtOAc fraction exhibited antioxidant activities. However, the EtOAc fraction showed a greater radical-scavenging activity and reducing power than that shown by the 50% EtOH extract. Furthermore, the EtOAc fraction increased cell viability in a UVB-irradiated human keratinocyte injury model and significantly suppressed UVB-induced MMP-1 expression and α-melanocyte-stimulating hormone (α-MSH)-stimulated melanin production in HaCaT keratinocytes and B16F1 melanocytes, respectively. Interestingly, caffeine, the major component of the EtOAc fraction, did not show an inhibitory effect. Thus, the antioxidant capacity of the coffee silverskin extract may be attributable to some compounds that exhibit a high antioxidant capacity even at low concentrations or the total antioxidant capacity of various constituent phenolic compounds., Conclusion: Our findings indicate that coffee silverskin has the potential for application as a natural functional material in multifunctional cosmetics., Competing Interests: Not applicable.The author consents for publication.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Most people use cosmetics to protect their skin. Preservatives are often used to prevent their contamination upon use. There has been a great demand for natural preservatives due to recent reports on the side effects of parabens. Therefore, we evaluated the antimicrobial activities of Lonicera japonica and Magnolia obovata extracts and determined their potential as natural preservatives. We found that the 50% ethanol extract from L. japonica had antibacterial activity only against S. aureus and P. aeruginosa , while the ethyl acetate fraction showed antimicrobial activity against all six microbial strains tested. On the other hand, the 70% ethanol extract and the ethyl acetate fraction from M. obovata showed antimicrobial activity against all six strains. A synergistic effect against S. aureus , B. subtilis , and C. albicans was confirmed when two ethyl acetate fractions having antimicrobial activity against all six strains were used in combination. Synergistic activity against B. subtilis was also confirmed through kill-time analysis. High-performance liquid chromatography was performed to identify the components of each extract. Based on the minimum inhibitory concentration and the results of a disc diffusion assay, we confirmed that caffeic acid and luteolin influenced the antimicrobial activity of L. japonica and that the antimicrobial activity of M. obovata was influenced by the interaction of magnolol and honokiol with other components. Therefore, this study suggests that the combination of L. japonica and M. obovata extracts may be used as a plant-derived natural preservative.

Objectives: The aim of this multicenter registry study was to investigate the effectiveness of ventilation tube insertion and the microbiology of otitis media with effusion (OME) in children. This part I study was conducted to evaluate the microbiological profile of children with OME who needed ventilation tube insertion., Methods: Patients <15 years old who were diagnosed as having OME and received ventilation tube insertion were prospectively enrolled in 16 tertiary hospitals from June 2014 to December 2016. After excluding patients with missing data, the data of 397 patients were analyzed among a total of 433 enrolled patients. The clinical symptoms, findings of the tympanic membrane, hearing level, and microbiological findings were collected., Results: In 103 patients (25.9%), antibiotics were used within 3 weeks before surgery. Ventilation tube insertion was performed in a total of 710 ears (626 in both ears in 313 patients, 55 in the left ear only, and 29 in the right ear only). Culture of middle ear effusion was done in at least one ear in 221 patients (55.7%), and in a total of 346 ears. Only 46 ears (13.3%) showed positive results in middle ear effusion culture. Haemophilus influenzae (17.3%, followed by coagulase-negative Staphylococcus and Staphylococcus auricularis ) was the most common bacteria detected., Conclusion: H. influenzae was the most commonly found bacteria in middle ear effusion. Relatively low rates of culture positivity were noted in middle ear effusion of patients with OME in Korea.

Objectives: The classical overlay tympanoplasty is technically difficult with some disadvantages and thus less popular. However, it is particularly useful for large, anterior perforations. In this study, we describe the technique of a modified overlay graft in the tympanoplasty coined as the swing-door overlay tympanoplasty and report its outcomes., Methods: Retrospective review of patients undergoing the swing-door overlay tympanoplasty at a tertiary referral center between 2003 and 2016 was performed. Patient who had ossicular abnormality, previous tympanoplasty, and profound hearing loss were excluded. The surgical technique is described in detail. The outcomes were evaluated by the graft success rate, complication rate, and hearing results. The hearing level was determined by four pure-tone average at 0.5, 1, 2, and 4 kHz. Air-bone gap closure was mainly assessed., Results: A total of 306 patients (110 males and 196 females) were included. The mean age was 49.1±16.6 years. Follow-up periods ranged from 6 to 108 months with an average of 18.4 months. The overall graft success rate reached 98.4%. Five graft failures occurred with reperforation in three cases and lateralization in two cases. Postoperative complications occurred in 12 cases (3.9%). Air-bone gap changes (closures) were 7.8±12.8, 5.2±12.2, 5.7±10.2, and 6.0± 12.8 dB at 0.5, 1, 2, and 4 kHz, respectively (all P <0.001) with an average improvement of 6.2 dB. Postoperative airbone gap was closed to ≤20 dB in 86.9%., Conclusion: The swing-door overlay tympanoplasty is a highly successful surgical technique suitable for all types of tympanic membrane perforations. This approach is technically easier than classical overlay tympanoplasty and affords an excellent graft success rate with satisfying hearing results.

Non-invasive skin penetration of a drug is increased by an edge activator, which enhances the nanoliposome deformability. The objective of this study was to investigate the role of the alkyl chain number of sucrose surfactants as an edge activator in elastic nanoliposomes. In addition, the physicochemical properties of the elastic nanoliposomes were characterized and an in vitro human skin permeation study was performed. Elastic nanoliposomes that were composed of sucrose monostearate (MELQ), sucrose distearate (DELQ), and sucrose tristearte (TELQ) were prepared using a thin-film hydration method. Particle size and entrapment efficiency of elastic nanoliposomes increased proportionally with an increase in the amounts and the numbers of the stearate in sucrose surfactant. Deformability of elastic nanoliposomes was indicated as DELQ > MELQ > TELQ and the same pattern was revealed through the in vitro human skin permeability tests. These results suggest that the number of alkyl chains of sucrose surfactant as edge activator affects the physicochemical property, stability, and skin permeability in elastic nanoliposome. Our findings give a valuable platform for the development of elastic nanoliposomes as skin drug delivery systems., Competing Interests: The authors declare no conflict of interest

Objective: To analyze the clinical characteristics and evaluate the surgical outcomes of carcinoma of the external auditory canal (CEAC)., Materials and Methods: Overall, 31 patients from four multicenter hospitals, who were diagnosed and surgically treated for CEAC in 2009-2014, were enrolled for this retrospective study. Medical records were reviewed to determine cancer stage according to the Pittsburgh classification. Clinical data of age, sex, site, initial symptoms, surgery extent, postoperative complications including recurrence, follow-up period, and current patient status were collected for analysis. Five-year cumulative survival rate was obtained using Kaplan-Meier method., Results: At initial diagnosis, 22 patients were in the early stages (stage I: 15; stage II: 7) and 9 patients were in the advanced stages (stage III: 1; stage IV: 8). Lymph node metastasis was present in 5 patients and distant metastasis in 2. Of the 31 patients, 4 patients died (stage II: 1, stage IV: 3) during the follow-up period. Early-stage patients showed 100% 5-year estimated cumulative survival rate, whereas the advanced-stage patients showed 5-year estimated survival rate of 53.6% (p=.006). The overall survival rate of all enrolled patients was 90.3%. Although 5-year estimated disease-free survival rate of stage I was 100.0%, that for stage II was low at 30.0% because of considerable recurrences., Conclusion: The results of this multicenter study suggest that more aggressive treatment modality, including adjuvant therapy, is necessary for patients with CEAC with Pittsburgh stage II or more.

Purpose: The purpose of this study was to identify parental coping strategies in the face of early infant and toddler injury, and to provide basic data for a parental education program and the most desirable directions it should take., Methods: A Q-methodology to analyze the subjectivity of each item was used. Thirty-four Q-statements were derived from a literature review and interviews. Forty-seven parents were classified into a shape of normal distribution using a 9-point scale. Collected data were analyzed by the pc-QUANL program., Results: Five types of parental coping in early infant and toddler injury were identified. Type I was "hospital treatment focused", type II was "Improving the safety of the child's environment", type III was "expression of negative emotion", type IV was "taking the lead in problem solving", and type V was "Interrogating the person in charge of the situation in which the injury occurred"., Conclusion: The results of this study indicate that different approaches to educational programs can be used for parents in early childhood injury., Competing Interests: The authors declared no conflict of interest., (© 2018 Korean Society of Nursing Science.)

Lespedeza cuneata G. Don is a traditional herb that has been associated with multiple biological activities. In this study, we investigated the antioxidative/antiaging activities and performed an active component analysis of the non-fermented and fermented (using Lactobacillus pentosus ) extracts of Lespedeza cuneata G. Don. The antioxidative activities of the fermented extract were higher than those of non-fermented extracts. The elastase inhibitory activity, inhibitory effects on UV-induced MMP-1 expression, and ability to promote type I procollagen synthesis were investigated in Hs68 human fibroblasts cells. These tests also revealed that the fermented extract had increased antiaging activities compared with the non-fermented extract. A component analysis of the ethyl acetate fractions of non-fermented and fermented extracts was performed using TLC, HPLC, and LC/ESI-MS/MS to observe changes in the components before and after fermentation. Six components that were different before and after fermentation were investigated. It was thought that kaempferol and quercetin were converted from kaempferol glucosides and quercetin glucosides, respectively, via bioconversion with the fermentation strain. These results indicate that the fermented extract of L. cuneata G. Don has potential for use as a natural cosmetic material with antioxidative and antiaging effects.

Idiopathic hypereosinophilia (IHE)/idiopathic hypereosinophilic syndrome (IHES) has been defined by a persistent elevation of the blood eosinophil count exceeding 1.5×103/μL, without evidence of reactive or clonal causes. While T-cell clonality assessment has been recommended for unexplained hypereosinophilia, this approach is not often applied to routine practice in the clinic. We hypothesized that the clonality would exist in a subset of IHE/IHES patients. We aimed to investigate the candidate mutations and T-cell clonality in IHE/IHES and to explore the role of mutations in eosinophil proliferation. We performed targeted capture sequencing for 88 genes using next-generation sequencing, T-cell receptor (TCR) gene rearrangement assays, and pathway network analysis in relation to eosinophil proliferation. By targeted sequencing, 140 variants in 59 genes were identified. Sixteen out of 30 patients (53.3%) harbored at least one candidate mutation. The most frequently affected genes were NOTCH1 (26.7%), SCRIB and STAG2 (16.7%), and SH2B3 (13.3%). Network analysis revealed that our 21 candidate genes (BIRC3, BRD4, CSF3R, DNMT3A, EGR2, EZH2, FAT4, FLT3, GATA2, IKZF, JAK2, MAPK1, MPL, NF1, NOTCH1, PTEN, RB1, RUNX1, TET2, TP53 and WT1) are functionally linked to the eosinophilopoietic pathway. Among the 21 candidate genes, five genes (MAPK1, RUNX1, GATA2, NOTCH1 and TP53) with the highest number of linkages were considered major genes. A TCR assay revealed that four patients (13.3%) had a clonal TCR rearrangement. NOTCH1 was the most frequently mutated gene and was shown to be a common node for eosinophilopoiesis in our network analysis, while the possibility of hidden T cell malignancy was indwelling in the presence of NOTCH1 mutation, though not revealed by aberrant T cell study. Collectively, these results provide new evidence that mutations affecting eosinophilopoiesis underlie a subset of IHE/IHES, and the candidate genes are inferred to act their potential roles in the eosinophilopoietic pathway.

Objectives: Baso-apical gradients exist in various cochlear structures including medial olivocochlear (MOC) efferent system. This study investigated the cochlear regional differentials in the function and morphology of the MOC system, and addressed the functional implications of regional MOC efferent terminals (ETs) in the mouse cochlea., Methods: In CBA/J mice, MOC reflex (MOCR) was assessed based on the distortion product otoacoustic emission in the absence and presence of contralateral acoustic stimulation. High, middle, and low frequencies were grouped according to a mouse place-frequency map. Cochlear whole mounts were immunostained for ETs with anti-α-synuclein and examined using confocal laser scanning microscopy. The diameters of ETs and the number of ETs per outer hair cell were measured from the z-stack images of the basal, middle and apical regions, respectively., Results: The middle cochlear region expressed large, clustered MOC ETs with strong MOCR, the base expressed small, less clustered ETs with strong MOCR, and the apex expressed large, but less clustered ETs with weak MOCR., Conclusion: The mouse cochlea demonstrated regional differentials in the function and morphology of the MOC system. Strong MOCR along with superior MOC morphology in the middle region may contribute to 'signal detection in noise,' the primary efferent function, in the best hearing frequencies. Strong MOCR in spite of inferior MOC morphology in the base may reflect the importance of 'protection from noise trauma' in the high frequencies.

Background: Telomere shortening is thought to be involved in the pathophysiology of myeloid malignancies, but telomere lengths (TL) during interphase and metaphase in hematopoietic malignancies have not been analyzed. We aimed to assess the TLs of interphase and metaphase cells of MDS and telomerase activity (TA) and to find out prognostic significances of TL and TA., Methods: The prognostic significance of TA by quantitative PCR and TL by quantitative fluorescence in situ hybridization (QFISH) of interphase nuclei and metaphase chromosome arms of bone marrow cells from patients with MDS were evaluated., Results: MDS patients had shorter interphase TL than normal healthy donors (P<0.001). Average interphase and metaphase TL were inversely correlated (P=0.013, p arm; P=0.029, q arm), but there was no statistically significant correlation between TA and TL (P=0.258). The progression free survival was significantly shorter in patients with high TA, but the overall survival was not different according to average TA or interphase TL groups. Multivariable Cox analysis showed that old age, higher International Prognostic Scoring System (IPSS) subtypes, transformation to AML, no history of hematopoietic stem cell transplantation and short average interphase TL (<433 TL) as independent prognostic factors for poorer survival (P=0.003, 0.001, 0.005, 0.005, and 0.013, respectively)., Conclusions: The lack of correlation between age and TL, TA, and TL, and the inverse relationship between TL and TA in MDS patients reflect the dysregulation of telomere status and proliferation. As a prognostic marker for leukemia progression, TA may be considered, and since interphase TL has the advantage of automated measurement by QFISH, it may be used as a prognostic marker for survival in MDS., (© The Korean Society for Laboratory Medicine)