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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

Purpose: Single-sided deafness (SSD) presents significant challenges for patients, including compromised sound localization, reduced speech recognition, and often, tinnitus. These issues are typically addressed using interventions such as cochlear implantation (CI) and bone conduction implant (BCI). However, evidence regarding the efficacy of BCI in reducing tinnitus in SSD patients remains limited. This study explored the ability of a novel active transcutaneous BCI (Bonebridge BCI602) to alleviate tinnitus in SSD patients., Study Design: Prospective cohort multicenter study., Setting: Tertiary referral hospitals., Methods: A prospective multicenter study of 30 SSD patients was conducted. The patients were divided into two groups: those with (n = 19) and without (n = 11) tinnitus. Audiometric assessments, subjective questionnaires including the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Bern Benefit in Single-Sided Deafness (BBSS), and tinnitus evaluations with the Tinnitus Handicap Inventory (THI) and tinnitogram were conducted before and after BCI surgery., Results: THI scores after surgery were significantly reduced in SSD patients with tinnitus. Subjective satisfaction improved in both the tinnitus and non-tinnitus groups; however, the former group exhibited a significantly greater improvement in the APHAB questionnaire score. According to tinnitograms, the loudness of tinnitus decreased, particularly in patients with ipsilateral tinnitus. Patients with residual hearing had greater reductions in their THI scores. However, three patients without residual hearing had a relative worsening of tinnitus after surgery., Conclusion: The Bonebridge BCI602 effectively reduced tinnitus in SSD patients, particularly in those with residual hearing. Subjective satisfaction improved in both the tinnitus and non-tinnitus groups. These findings demonstrate the therapeutic potential of BCI for managing SSD and associated tinnitus., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Vitamin D deficiency as a risk factor of tinnitus has not been well known. We tried to evaluate the association between the serum 25-(OH) vitamin D levels and tinnitus among the Korean population to propose the possible role of serum vitamin D in patients with tinnitus., Methods: This cross-sectional study investigated the potential risk factors of tinnitus in relation to serum 25(OH)D levels within the Korean population. It encompassed a health interview, nutrition assessment, and a health examination. Data was sourced from the KNHANES V (2010-2012), conducted by the Division of Health and Nutritional Survey under the Korean Centers for Disease Control and Prevention (KCDCP). Participants were chosen from various sampling units categorized by geography, gender, and age group. The selection was facilitated through household registries using a stratified, multistage, clustered probability sampling approach., Results: Data of 16 408 subjects were collected in this study. There were significant differences in gender, economic status, educational level, and sun exposure duration between the tinnitus and non-tinnitus groups. Serum 25(OH) vitamin D level between hearing loss and normal hearing was also significantly different. The logistic regression models with serum 25(OH) vitamin D quartile and tinnitus as the dependent variable, which were controlled for age, sex, smoking status, BMI, diabetes, hypertension, sun exposure, regular exercise, income, and education, eventually demonstrated that serum vitamin D deficiency and low sun exposure duration significantly increased the risk of tinnitus development., Conclusion: This study demonstrated a significant association between serum vitamin D levels and tinnitus, driven by large epidemiological data. The results of our study provide baseline data for further research to investigate the role of vitamin D in the pathogenesis and management of tinnitus., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: While mastoid obliteration techniques have received much attention in decreasing the disadvantages associated with the resultant mastoid cavity from canal wall down procedures, techniques for an anatomically normal looking ear canal reconstruction to increase the feasibility of hearing aid fitting are less commonly discussed as an alternative., Methods: Our mastoidoplasty technique basically utilises an inferiorly based periosteal flap with or without temporalis muscles and fascia to obliterate the epitympanum and reconstruct the external auditory canal (EAC). Stay sutures are used to keep them in place. For larger cavities, demineralized bone matrix (DBM) is used to obliterate the mastoid cavity and support the neo-EAC., Conclusions: The concept of our mastoidoplasty potentially provides a very useful alternative in recreating a near normal ear canal anatomy avoiding cavity problems as well as facilitating hearing aid fitting with canal type hearing aids after canal wall down mastoidectomy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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).)

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.)

Objective: To investigate the safety and efficacy of a novel active transcutaneous bone conduction implant (BCI) device for patients with single-sided deafness (SSD)., Study Design: Prospective cohort study., Setting: Tertiary referral hospitals., Methods: This prospective multicenter study was conducted at 15 institutions nationwide. Thirty adult (aged ≥19 years) SSD patients were recruited. They underwent implantation of an active transcutaneous BCI device (Bonebridge BCI602). Objective outcomes included aided pure-tone thresholds, aided speech discrimination scores (SDSs), and the Hearing in Noise Test (HINT) and sound localization test results. The Bern Benefit in Single-Sided Deafness (BBSS) questionnaire, the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire, and the Tinnitus Handicap Inventory (THI) were used to measure subjective benefits., Results: The mean aided pure-tone threshold was 34.2 (11.3), mean (SD), dB HL at 500 to 4000 Hz. The mean total BBSS score was 27.5 (13.8). All APHAB questionnaire domain scores showed significant improvements: ease of communication, 33.6 (23.2) versus 22.6 (21.3), P = .025; reverberation, 44.8 (16.6) versus 32.8 (15.9), P = .002; background noise, 55.5 (23.6) versus 35.2 (18.1), P < .001; and aversiveness, 36.7 (22.8) versus 25.8 (21.4), P = .028. Moreover, the THI scores were significantly reduced [47.4 (30.1) versus 31.1 (27.0), P = .003]. Congenital SSD was a significant factor of subjective benefit (-11.643; 95% confidence interval: -21.946 to -1.340)., Conclusion: The BCI602 active transcutaneous BCI device can provide functional hearing gain without any adverse effects and is a feasible option for acquired SSD patients with long-term deafness., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: The upright head roll test (UHRT) is a recently introduced diagnostic maneuver for lateral semicircular canal benign paroxysmal positional vertigo (LSC-BPPV)., Objective: This study aimed to evaluate the reliability and validity of the UHRT., Methods: Two separate studies were conducted. Study 1 analyzed 827 results of videonystagmography (VNG) to assess UHRT reliability, and Study 2 analyzed 130 LSC-BPPV cases to evaluate UHRT validity., Results: The inter-test reliability between UHRT and the supine head roll test (SHRT) showed substantial agreement (Cohen's kappa = 0.753) in direction-changing positional nystagmus (DCPN) and almost perfect agreement (Cohen's kappa = 0.836) in distinguishing the direction of DCPN. The validity assessment of UHRT showed high accuracy in diagnosing LSC-BPPV (80.0%) and in differentiating the variant types (74.6%). UHRT was highly accurate in diagnosing the canalolithiasis type in LSC-BPPV patients (Cohen's kappa = 0.835); however, it showed only moderate accuracy in diagnosing the cupulolithiasis type (Cohen's kappa = 0.415). The intensity of nystagmus in UHRT was relatively weaker than that in SHRT (P < 0.05)., Conclusion: UHRT is a reliable test for diagnosing LSC-BPPV and distinguishing subtypes. However, UHRT has a limitation in discriminating the affected side owing to a weaker intensity of nystagmus than SHRT.

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.)

Objective: Middle ear myoclonic tinnitus (MEMT) is a disease caused by myoclonus or abnormal contractive movement of middle ear muscles (MEMs). This translational study was conducted to propose intratympanic botulinum toxin (IT-BTX) injection as a new therapeutic modality to treat MEMT., Study Design: Animal experiment and nonrandomized controlled clinical trial., Setting: Laboratory and medical center of an academic tertiary medical institution., Methods: For the animal study, male Sprague-Dawley rats were divided into 4 subgroups according to the sacrificing day after IT-BTX injection. After initial hearing tests, randomly assigned experimental ears were intratympanically injected with 1 unit/100 μL of BTX-A, whereas control ears were injected with normal saline. Changes in the hearing thresholds, morphometry of the cochleae, electron microscopy study, and immunofluorescence analysis of MEMs were evaluated. For the human study, 10 intractable MEMT patients were enrolled. The hearing thresholds and the degree of tinnitus distress were observed for changes after IT-BTX injection. All patients were followed up for 3 months., Results: As for the animal study, there were no significant changes in hearing thresholds and cochlear morphologies in all 4 subgroups of the rats. Significant MEM degenerations and immuno-detection of cleaved synaptosome-associated protein of 25 kDa (cSNAP-25) indicated the efficacy of IT-BTX. MEMT patients enrolled for the pilot clinical trial showed statistically significant improvement in tinnitus after IT-BTX injection. No major complications were noted., Conclusion: The new therapeutic modality of IT-BTX injection for the treatment of MEMT seems highly promising with an excellent result., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

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”.

Competing Interests: The authors disclose no conflicts of interest.

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.

Objective: Review of a sigmoid sinus diverticuli (SSDi) variants surgically managed with a novel technique using an inferior periosteal flap., Study Design: Case series., Setting: Tertiary referral center., Patients: Patients presenting with pulsatile tinnitus to a tertiary referral center between January 1, 2015, and June 31, 2021, who were diagnosed with SSDi variants on CT temporal bone and who received surgical management for these SSDi variants., Interventions: Obliteration of SSDi variants using a novel technique with an inferiorly based periosteal flap., Main Outcome Measures: Pure-tone audiometry, Tinnitus Handicap Inventory score, and visual analogue scale score for tinnitus severity (loudness, awareness, annoyance, and effect on life)., Results: Include statistical measures as appropriate., Conclusions: We would like to propose the use of an inferiorly based periosteal flap as an option for obliteration and concomitant hemostasis of more sizeable or complex (e.g., bifid) SSDi. Further study of this technique with a long-term follow-up will be needed to evaluate its long-term safety and efficacy., Competing Interests: Conflict of interest statement: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

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.)

Objectives: This study was performed to evaluate the effectiveness of our novel group vestibular rehabilitation therapy (G-VRT) and to analyze the factors affecting outcomes., Study Design: Retrospective case series., Setting: Tertiary referral center., Patients: Patients with chronic dizziness who received G-VRT between December 2019 and July 2020., Intervention: The G-VRT program consisted of a 1-hour physical therapy session by an otologist in a small group setting., Main Outcome Measures: Dizziness Handicap Inventory, visual analog scale, functional level scales, and video head impulse test, as well as the compliance to the program, were evaluated., Results: All scores of dizziness questionnaires were significantly improved after G-VRT ( p < 0.001). The overall vestibule-ocular reflex gain calculated by video head impulse test increased compared to the initial scores, whereas the average PR scores of all three semicircular canals significantly decreased from the initial scores, indicating enhanced vestibular compensation ( p < 0.05). Enrolled patients showed high compliance to the program., Conclusion: G-VRT program is a cost-effective and efficient way to provide relief for chronic dizzy patients. Further case-control studies in a larger group, as well as comparative studies with generic or customized vestibular exercise, will be needed to validate the clinical value of G-VRT., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

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.

In this study, we investigated the effect of the stacking order of metal precursors on the formation of volume defects, such as blisters and nanopores, in CZTSSe thin-film solar cells. We fabricated CZTSSe thin films using three types of metal-precursor combinations, namely, Zn/Cu/Sn/Mo, Cu/Zn/Sn/Mo, and Sn/Cu/Zn/Mo, and studied the blister formation. The blister-formation mechanism was based on the delamination model, taking into consideration the compressive stress and adhesion properties. A compressive stress could be induced during the preferential formation of a ZnSSe shell. Under this stress, the adhesion between the ZnSSe film and the Mo substrate could be maintained by the surface tension of a metallic liquid phase with good wettability, or by the functioning of ZnSSe pillars as anchors, depending on the type of metal precursor used. Additionally, the nanopore formation near the back-contact side was found to be induced by the columnar microstructure of the metal precursor with the Cu/Zn/Mo stacking order and its dezincification. Based on the two volume-defect-formation mechanisms proposed herein, further development of volume-defect-formation suppression technology is expected to be made.

This study compared the accuracy of a new MALDI-TOF mass spectrometry system, ASTA MicroIDSys system, with that of MALDI Biotyper system for the identification of reference and clinical bacterial and yeast strains. The identification accuracy of the 2 systems was compared using a total of 406 strains comprising 142 aerobic and 180 anaerobic bacterial strains and 84 yeast strains. The genus and species identification rates were 98.0% and 89.4% using MicroIDSys and 96.1% and 89.4% using Biotyper, respectively. The species identification rates of MicroIDSys and Biotyper for aerobic bacteria were 93.0% and 97.2%, respectively, and those for anaerobic bacteria were 85.6% and 81.7%, respectively. The accuracy of yeast identification at the species level was 91.7% using MicroIDSys and 92.9% using Biotyper. These findings indicate that MicroIDSys could be useful for the accurate identification of bacteria and yeast in clinical microbiology laboratories., (Copyright © 2022. Published by Elsevier Inc.)

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.

Introduction: Subjective cognitive decline (SCD) is a self-reported cognitive decline without objective cognitive impairment. The relationship between audiometric hearing loss (HL) and cognitive function has not been reported in SCD. The purpose of this study was to investigate whether HL affects cognition-related indexes in SCD individuals., Methods: This is a cross-sectional study that used the baseline data of a multicenter cohort study that monitors clinical progression from SCD to dementia. Individuals aged ≥60 years who reported cognitive decline but had no objective cognitive impairment on comprehensive neuropsychological tests were recruited. Participants were grouped into the normal-hearing (NH) and bilateral HL groups. The demographics, clinical characteristics, dementia biomarkers, global cognition, questionnaire scores, neuropsychological test scores, and segmental brain volumes from MRI were compared between the groups., Results: Of a total of 120 participants, one hundred and two had NH (n = 57) or bilateral HL (n = 45). There were no group differences in the demographic and clinical data except the age. The biomarkers, global cognition, and questionnaire scores were not different between the groups. The HL group performed worse (the z-score of -0.06) in the Stroop Color Word Test than the NH group (0.27) (p = 0.025). Brain volumetric analysis revealed that the HL group had reduced gray matter volumes in four brain subregions: left temporal pole, left caudal middle frontal gyrus, left hippocampus, and right isthmus of the cingulate gyrus., Conclusion: In SCD, HL exerted an adverse effect on cognitive function, primarily frontal executive function tested in the Stroop task. HL was also related to gray matter volume reductions in brain subregions, although causality needs further investigation. This study may provide evidence for a potential link between hearing and cognition in SCD, an emerging clinical entity., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Objectives/hypothesis: Tinnitus can develop due to, or be aggravated by, stress in a rat model. To investigate stress as a possible causal factor in the development of tinnitus, we designed an animal study that included tinnitus behavior and excitatory/inhibitory neurotransmitter expression after noise exposure as well as restraint stress., Study Design: An experimental animal study., Methods: Wistar rats were grouped according to single or double exposure to noise and restraint stress. The noise exposure (NE) group was subjected to 110 dB sound pressure level (SPL) of 16 kHz narrow-band noise (NBN) for 1 hour, and the restraint stress (RS) group was restrained for 1 hour with or without noise exposure. Gap prepulse inhibition of the acoustic startle (GPIAS) reflex was measured at an NBN of 16 kHz to investigate tinnitus development. Various immunohistopathologic and molecular biologic studies were undertaken to evaluate possible mechanisms of tinnitus development after noise and/or restraint stress., Results: The RS-only group showed a reduced GPIAS response, which is a reliable sign of tinnitus development. In the double-stimulus groups, more tinnitus-development signs of reduced GPIAS responses were observed. The expression of γ-aminobutyric acid A receptor α1 (GABAAR α1) in the hippocampus decreased in the NE│RS group. Increased N-methyl-d-aspartate receptor1 intensities in the NE│RS group and decreased GABAAR α1 intensities in the RS and NE│RS groups were observed in the CA3 region of the hippocampus., Conclusions: Tinnitus appeared to develop after stress alone in this animal study. An imbalance in excitatory and inhibitory neurotransmitters in the hippocampus may be related to the development of tinnitus after acute NE and/or stress., Level of Evidence: NA Laryngoscope, 131:2332-2340, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc..)

Objective: Despite the efforts to treat patients with patulous Eustachian tube (PET), intractable symptoms of PET may require surgical intervention. In this study, we introduce our surgical technique of "transtympanic tripod-shaped angiocatheter" (TTA) insertion and evaluate the safety and efficacy of the procedure in patients with intractable PET., Study Design: Retrospective chart review., Setting: Tertiary referral center., Patients: Thirty-two cases (26 patients) diagnosed with intractable PET between the years 2011 and 2019 were included in this study., Intervention: All cases were surgically treated with TTA insertion., Main Outcome Measures: The clinical characteristics, surgical results, complication rates, and the level of satisfaction by questionnaires were analyzed for evaluation., Results: The mean age of enrolled patients was 40.9 ± 19.5 years, with slight male gender predominance (59.4% vs. 40.6%). Both ears were operated in six patients, simultaneously in three. All patients successfully received the insertion of TTA, with no immediate complication. Eleven cases were re-inserted after the first insertion due to the recurrence of symptoms or spontaneous extrusion of TTA. No major complications were observed during the follow-up period of 1 to 115 months (mean 37.7 mo). The average Visual Analogue Scale score of PET symptoms was significantly decreased (p < 0.05), along with 92% of patients with relief from autophony symptoms., Conclusions: TTA insertion is a relatively simple procedure that can be performed in a short period under local anesthesia. Surgical intervention of TTA insertion for patients with intractable PET symptoms seems promising with a high success rate., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021, Otology & Neurotology, Inc.)

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: This prospective randomized case-control study was performed to compare the surgical outcomes of our swing-door overlay tympanoplasty with or without absorbable gelatine sponge (AGS, gelfoam) packing in the middle ear cavity, according to the surgical procedure., Methods: Fifty-seven patients who underwent swing-door overlay tympanoplasty by a single surgeon were enrolled in the study. The data of 30 patients of the gelfoam-packing group (GPG) and 27 patients of the non-gelfoam-packing group (NGPG) were prospectively collected and compared., Results: Closure of the tympanic membrane was found to be successful in all patients at postoperative 3 months evaluation. NGPG showed a statistically better healing process compared to GPG; earlier epithelialization and less fascia edema in NGPG than in GPG (P < 0.05). The air-bone gap (ABG) measured at postoperative 1 and 2 months was smaller in NGPG than GPG, although there were no statistical differences., Conclusion: This study revealed earlier healing process and faster recovery of ABG in NGPG, thereby indicating that the gelfoam in the middle ear may interfere with both hearing recovery and the healing process of neodrum., (Copyright © 2020 Elsevier Inc. All rights reserved.)

As for hypertension, chronic pain, epilepsy and other disorders with particular symptoms, a commonly accepted and unambiguous definition provides a common ground for researchers and clinicians to study and treat the problem. The WHO's ICD11 definition only mentions tinnitus as a nonspecific symptom of a hearing disorder, but not as a clinical entity in its own right, and the American Psychiatric Association's DSM-V doesn't mention tinnitus at all. Here we propose that the tinnitus without and with associated suffering should be differentiated by distinct terms: "Tinnitus" for the former and "Tinnitus Disorder" for the latter. The proposed definition then becomes "Tinnitus is the conscious awareness of a tonal or composite noise for which there is no identifiable corresponding external acoustic source, which becomes Tinnitus Disorder "when associated with emotional distress, cognitive dysfunction, and/or autonomic arousal, leading to behavioural changes and functional disability.". In other words "Tinnitus" describes the auditory or sensory component, whereas "Tinnitus Disorder" reflects the auditory component and the associated suffering. Whereas acute tinnitus may be a symptom secondary to a trauma or disease, chronic tinnitus may be considered a primary disorder in its own right. If adopted, this will advance the recognition of tinnitus disorder as a primary health condition in its own right. The capacity to measure the incidence, prevalence, and impact will help in identification of human, financial, and educational needs required to address acute tinnitus as a symptom but chronic tinnitus as a disorder., (© 2021 Elsevier B.V. All rights reserved.)

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.)

In this study, we investigated the antimicrobial, antioxidant, and cytoprotective activities of ethanol extract and the ethyl acetate (EtOAc) fraction of P. kleiniana Wight & Arn. The EtOAc fraction exhibited antimicrobial effects against most of the microorganisms that were tested, including Staphylococcus aureus, Candida albicans , Pseudomonas aeruginosa , and, Escherichia coli , but not Aspergillus niger . In addition to its excellent antioxidant activity, the EtOAc fraction attenuated the UVB-induced cell death via upregulation of caspase-3 expression in human keratinocytes. The HPLC/ESI-MS/MS analysis allowed identification of the components in the EtOAc fraction. Overall, our results suggest that P. kleiniana is a valuable source of bioactive compounds for the development of pharmaceuticals and cosmetics.

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.

Objectives: Due to its rarity and similar sound, typewriter tinnitus (TT) can be misdiagnosed as middle ear myoclonic tinnitus (MEMT). We aim to clarify the characteristics of TT compared to MEMT, and the long-term therapeutic response to carbamazepine., Methods: Fourteen patients with TT and 28 patients with MEMT were enrolled., Results: TT patients were older than MEMT patients, and their tinnitus symptoms were mostly unilateral. Tinnitus symptoms, which is associated with dizziness, facial spasm, and head motion, were more common in TT, whereas MEMT were more related to noise. Acoustic reflex decay perturbation and low loudness discomfort level were diagnostic signs in MEMT patients, while decreased level of wave II in ABR was the most reliable sign in TT patients. All TT patients exhibited partial or complete response to carbamazepine, but there was a relapse rate after withdrawal of the drug was 60%. Increase in age and longer duration of symptoms were the risk factors of relapse of TT., Conclusion: The different characteristics observed in this study will be helpful to diagnose TT and MENT. Duration of tinnitus was the most important long-term prognostic factor of the carbamazepine trial, which indicates the importance of its earlier diagnosis., Competing Interests: Declaration of Competing Interest There is no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)