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Gradenigo's syndrome, a rare but serious complication of otitis media, encompasses a triad of symptoms including otalgia, facial palsy, and abducens nerve palsy, pointing to the involvement of the petrous apex. This case report presents an 11-year-old boy with an atypical manifestation of Gradenigo's syndrome, characterized by the absence of classic features such as abducens nerve palsy and purulent otorrhea. MRI findings were significant for petrous apicitis extending to Meckel's cave and the cavernous sinus, along with abscess formation and clivus osteomyelitis. The report highlights the critical role of advanced neuroimaging, particularly MRI, in the diagnosis and management of this condition. It underscores the importance of recognizing atypical presentations of Gradenigo's syndrome and the effectiveness of imaging-guided conservative treatment strategies in pediatric otological cases.

A review of randomized controlled trials (RCTs) using electroacupuncture (EA) to treat patients with foot drop was performed to analyze the effectiveness of EA for this condition. Relevant studies (n = 183) from 7 databases (Cochrane Library, Excerpta Medica Database, PubMed, China National Knowledge Infrastructure, Korean Studies Information Service System, Research Information Sharing Service, and Oriental Medicine Advanced Searching Integrated System) were selected based on the inclusion and exclusion criteria, and 12 RCTs met the selection criteria. In all 12 studies, EA showed significantly positive changes. In most indicators, positive changes were observed in the EA group compared with that in the control group. Significant increases were confirmed in muscle strength-related indicators such as the Fugl–Meyer motor scale, surface electromyography, active range of motion, and gait-related indicators such as the Tinetti score, maximum walking speed, and Berg balance scale. No notable adverse events were reported. EA is suggested as an effective treatment for post-stroke foot drop; however, more RCTs are required.

The development of accurate and high-throughput tools for cancer biomarker detection is crucial for the diagnosis, monitoring, and treatment of diseases. In this study, we developed a simple and rapid fluorescence-linked immunosorbent assay (FLISA) using fluorescent dye-conjugated antibody fragments against programmed cell death ligand 1 (PDL1) and human epithelial growth factor receptor 2 (HER2). We optimized key steps in the FLISA process, including antigen immobilization, blocking, and antibody reaction, reading the assay time to 3 h—significantly faster compared to the 23 h duration of usual FLISA. The limit of detection for the rapid FLISA in detecting PDL1 was lower than that of FLISA, and the detection of HER2 was similar between the two methods, indicating that the rapid FLISA provides a fast and accurate approach for detecting PDL1 and HER2. This robust platform can be readily adapted for various fluoroimmunoassays targeting other antigens of interest.

Abstract Background This study aimed to develop a novel combined immune score (CIS)-based model assessing prognosis in triple-negative breast cancer (TNBC). Methods The expression of eight immune markers (PD-1, PD-L1, PD-L2, IDO, TIM3, OX40, OX40L, and H7-H2) was assessed with immunohistochemistry on the tumor cells (TCs) and immune cells (ICs) of 227 TNBC cases, respectively, and subsequently associated with selected clinicopathological parameters and survival. Data retrieved from The Cancer Genome Atlas (TCGA) were further examined to validate our findings. Results All immune markers were often expressed in TCs and ICs, except for PD-1 which was not expressed in TCs. In ICs, the expression of all immune markers was positively correlated between one another, except between PD-L1 and OX40, also TIM3 and OX40. In ICs, PD-1, PD-L1, and OX40L positive expression was associated with a longer progression-free survival (PFS; p = 0.040, p = 0.020, and p = 0.020, respectively). In TCs, OX40 positive expression was associated with a shorter PFS (p = 0.025). Subsequently, the TNBC patients were classified into high and low combined immune score groups (CIS-H and CIS-L), based on the expression levels of a selection of biomarkers in TCs (TCIS-H or TCIS-L) and ICs (ICIS-H or ICIS-L). The TCIS-H group was significantly associated with a longer PFS (p

To determine the effectiveness of acupuncture in treating restless legs syndrome (RLS), we conducted a literature review of randomized controlled trials (RCTs) that utilized acupuncture as an intervention for patients diagnosed with RLS. Relevant clinical studies (n = 158) from seven databases (the Cochrane Library, PubMed, Embase, CNKI, KISS, RISS, and OASIS) were included based on the inclusion and exclusion criteria and analyzed. Moreover, 6 RCTs were selected for review. In all six studies, it was indicated people who underwent acupuncture treatment showed significant improvements in their overall health. An increase in the treatment efficacy rate, sleep quality, and quality of life indicators after the acupuncture treatment was confirmed. The severity of pain as assessed using the visual analog scale (VAS) scores and International RLS Study Group Rating Scale (IRLSRS) scores and the severity of RLS symptoms were significantly reduced. Any significant side effects were not reported. Acupuncture is suggested as an effective and safe treatment method for RLS. However, further large-scale RCT studies are needed to confirm our findings.

Abstract Objectives Persistent postural‐perceptual dizziness (PPPD) is a chronic functional vestibular disorder for which the Bárány Society has established diagnostic criteria. This nationwide multicenter study aims to investigate the clinical features of individuals with definite PPPD and clinical variant PPPD who do not fully meet the diagnostic criteria, with a particular focus on visual exaggeration. Methods Between September 2020 and September 2021, a total of 76 individuals with definite PPPD and 109 individuals with clinical variant PPPD who did not meet all three exacerbating factors outlined in Criterion B were recruited from 18 medical centers in South Korea. The study gathered information on demographic factors, clinical manifestations, balance scales, and personality assessments. Results Comparative analysis between groups with definite PPPD and clinical variant with visual exacerbation revealed no significant differences in sociodemographic characteristics, clinical course, dizziness impact, and specific precipitants. Only disease duration was significantly longer in definite PPPD compared with variant with visual exacerbation. However, the variant without visual exacerbation displayed significantly reduced rates of panic disorder, diminished space‐motion discomfort, lesser impact of dizziness, and decreased prevalence of depression when compared with the definitive PPPD. Conclusion This is the first comprehensive nationwide study examining clinical features of both definite PPPD patients and its clinical variants, considering visual exacerbating factors. Differences in dizziness and personality traits emerged between definite PPPD and its potential variant without visual issues. Our results highlight the possibility of a distinct clinical variant of PPPD influenced by visual dependency.

Objectives. Endoscopic tympanoplasty (ET) provides minimally invasive transcanal access to the middle ear and improves middle ear visibility for the treatment of tympanic membrane (TM) perforations. However, the literature on surgical outcomes for large TM perforations is lacking and limited to small series. This study aimed to evaluate the clinical benefits of ET for large TM perforations. Methods. This retrospective cohort study was conducted at nine tertiary referral hospitals in South Korea, where 252 patients who underwent ET as primary surgery from September 2019 to August 2021 were included. The outcome measures included the graft success rate and pre- and postoperative audiometric data. Results. In 239 patients, the graft success rate of ET for large or subtotal perforations was 86.2% (206 patients), while the graft failure rate was 13.8% (33 patients). The graft failure rate was directly correlated with surgical techniques, including overlay and medial or lateral underlay tympanoplasty (P=0.027). Lateral underlay tympanoplasty showed the most favorable results. Sex, laterality, etiology, site and size of perforation, operation time, and graft materials did not vary significantly between the graft success and failure groups (P>0.05). The mean air-bone gap (ABG) improved significantly in both groups (graft success group: 10.0±0.6 dB and graft failure group: 7.7±0.3 dB; P

Abstract Background High mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) molecule that plays a central role in innate immunity. HMGB1 acts as a late mediator of inflammation when actively secreted in response to inflammatory stimuli. Several post-translational modifications (PTMs), including acetylation, phosphorylation, and oxidation, are involved in HMGB1 secretion. However, the E3 ligases of HMGB1 and the mechanism by which DUBs regulate HMGB1 deubiquitination are not well known. Methods LC–MS/MS, proximity ligation assay, immunoprecipitation were used to identify ubiquitin-specific protease 13 (USP13) as a binding partner of HMGB1 and to investigate ubiquitination of HMGB1. USP13 domain mutant was constructed for domain study and Spautin-1 was treated for inhibition of USP13. Confocal microscopy image showed localization of HMGB1 by USP13 overexpression. The data were analyzed using one-way analysis of variance with Tukey’s honestly significant difference post-hoc test for multiple comparisons or a two-tailed Student’s t-test. Results We identified ubiquitin-specific protease 13 (USP13) as a novel binding partner of HMGB1 and demonstrated that USP13 plays a role in stabilizing HMGB1 from ubiquitin-mediated degradation. USP13 overexpression increased nucleocytoplasmic translocation of HMGB1 and promoted its secretion, which was inhibited by treatment with Spautin-1, a selective inhibitor of USP13. Conclusion Taken together, we suggest that USP13 is a novel deubiquitinase of HMGB1 that regulates the stability and secretion of HMGB1.

Abstract Background Phase I of the Korean Undiagnosed Diseases Program (KUDP), performed for 3 years, has been completed. The Phase I program aimed to solve the problem of undiagnosed patients throughout the country and develop infrastructure, including a data management system and functional core laboratory, for long-term translational research. Herein, we share the clinical experiences of the Phase I program and introduce the activities of the functional core laboratory and data management system. Results During the program (2018–2020), 458 patients were enrolled and classified into 3 groups according to the following criteria: (I) those with a specific clinical assessment which can be verified by direct testing (32 patients); (II) those with a disease group with genetic and phenotypic heterogeneity (353 patients); and (III) those with atypical presentations or diseases unknown to date (73 patients). All patients underwent individualized diagnostic processes based on the decision of an expert consortium. Confirmative diagnoses were obtained for 242 patients (52.8%). The diagnostic yield was different for each group: 81.3% for Group I, 53.3% for Group II, and 38.4% for Group III. Diagnoses were made by next-generation sequencing for 204 patients (84.3%) and other genetic testing for 35 patients (14.5%). Three patients (1.2%) were diagnosed with nongenetic disorders. The KUDP functional core laboratory, with a group of experts, organized a streamlined research pipeline covering various resources, including animal models, stem cells, structural modeling and metabolic and biochemical approaches. Regular data review was performed to screen for candidate genes among undiagnosed patients, and six different genes were identified for functional research. We also developed a web-based database system that supports clinical cohort management and provides a matchmaker exchange protocol based on a matchbox, likely to reinforce the nationwide clinical network and further international collaboration. Conclusions The KUDP evaluated the unmet needs of undiagnosed patients and established infrastructure for a data-sharing system and future functional research. The advancement of the KUDP may lead to sustainable bench-to-bedside research in Korea and contribute to ongoing international collaboration.

Tumor budding (TB) is classified, based on location, into peritumoral budding (PTB) or intratumoral budding (ITB). This study aimed to evaluate the relationship between PTB and ITB in colorectal cancers (CRCs). PTB and ITB were investigated and subsequently divided into high and low groups. CRCs were divided into three groups: (1) high PTB/ITB, (2) high PTB or ITB, and (3) low PTB/ITB. The clinicopathological and prognostic significances were evaluated according to the three tumor budding (TB) groups. High PTB/ITB and low PTB/ITB were identified in 32 (12.0%) and 135 (50.8%) patients, respectively. A total of 99 patients (37.2%) were found to have high PTB or ITB. TB was significantly correlated with lymphatic and perineural invasion, lymph node metastasis, metastatic lymph node ratio, distant metastasis, and a higher pTNM stage. A significant correlation was found between high PTB and high ITB (p = 0.010). The amount of PTB was found to increase significantly with the amount of ITB (p < 0.001) in a linear regression test. Patients with high PTB/ITB had worse overall and recurrence-free survival than those with high PTB or ITB. Conversely, patients with low PTB/ITB had better overall and recurrence-free survival rates than those with high PTB or ITB. However, there was no significant difference in overall and recurrence-free survival between patients with high PTB/low ITB and high ITB/low PTB (p = 0.336 and p = 0.623, respectively). In summary, the presence of TB, regardless of PTB or ITB, was significantly correlated with aggressive tumor behavior and a worse prognosis than the absence of TB. Additionally, the present study demonstrated that it is feasible to stratify the prognosis of patients based on whether they have both PTB and ITB or only one of the two.

Noise exposure can destroy the synaptic connections between hair cells and auditory nerve fibers without damaging the hair cells, and this synaptic loss could contribute to difficult hearing in noisy environments. In this study, we investigated whether delivering lithium chloride to the round-window can regenerate synaptic loss of cochlea after acoustic overexposure. Our rat animal model of noise-induced cochlear synaptopathy caused about 50% loss of synapses in the cochlear basal region without damaging hair cells. We locally delivered a single treatment of poloxamer 407 (vehicle) containing lithium chloride (either 1 mM or 2 mM) to the round-window niche 24 hours after noise exposure. Controls included animals exposed to noise who received only the vehicle. Auditory brainstem responses were measured 3 days, 1 week, and 2 weeks post-exposure treatment, and cochleas were harvested 1 week and 2 weeks post-exposure treatment for histological analysis. As documented by confocal microscopy of immunostained ribbon synapses, local delivery of 2 mM lithium chloride produced synaptic regeneration coupled with corresponding functional recovery, as seen in the suprathreshold amplitude of auditory brainstem response wave 1. Western blot analyses revealed that 2 mM lithium chloride suppressed N-methyl-D-aspartate (NMDA) receptor expression 7 days after noise-exposure. Thus, round-window delivery of lithium chloride using poloxamer 407 reduces cochlear synaptic loss after acoustic overexposure by inhibiting NMDA receptor activity in rat model.

Background: FAM83H has been implicated in cancer progression, and PD1 is an important target for anti-cancer immune checkpoint therapy. Recent studies suggest an association between FAM83H expression and immune infiltration. However, studies on the roles of FAM83H and its relationship with PD1 in breast carcinomas have been limited. Methods: Immunohistochemical expression of FAM83H and PD1 and their prognostic significance were evaluated in 198 breast carcinomas. Results: The expression of FAM83H in cancer cells was significantly associated with the presence of PD1-positive lymphoid cells within breast carcinoma tissue. Individual and co-expression patterns of nuclear FAM83H and PD1 were significantly associated with shorter survival of breast carcinomas in univariate analysis. In multivariate analysis, the expression of nuclear FAM83H (overall survival, p < 0.001; relapse-free survival, p = 0.003), PD1 (overall survival, p < 0.001; relapse-free survival, p = 0.003), and co-expression patterns of nuclear FAM83H and PD1 (overall survival, p < 0.001; relapse-free survival, p < 0.001) were the independent indicators of overall survival and relapse-free survival of breast carcinoma patients. Conclusions: This study suggests a close association between FAM83H expression and the infiltration of PD1-positive lymphoid cells in breast carcinomas and their expression as the prognostic indicators for breast carcinoma patients, and further studies are needed to clarify this relationship.

Abstract Background C1q has been reported to reveal complement-independent roles in immune and non-immune cells. C1q binds to its specific receptors to regulate distinct functions that rely on the environment and cell types. Discoidin domain receptor 2 (DDR2) is activated by collagen and functions in wound healing by controlling matrix metalloproteinase (MMP) expression. Since C1q exhibits a collagen-like structure, we hypothesized that C1q might engage DDR2 to regulate wound healing and extracellular matrix (ECM) remodeling. Methods Cell-based assay, proximity ligation assay, ELISA, and surface plasmon analysis were utilized to investigate DDR2 and C1q binding. We also investigate the C1q-mediated in vitro wound healing ability using the human fibrosarcoma cell line, HT1080. Results C1q induced the phosphorylation of DDR2, p38 kinase, and ERK1/2. C1q and DDR2 binding improved cell migration and induced MMP2 and MMP9 expression. DDR2-specific shRNA reduced C1q-mediated cell migration for wound healing. Conclusions C1q is a new DDR2 ligand that promotes wound healing. These findings have therapeutic implications in wound healing-related diseases.

Background: Fecal microbiota transplantation against gut colonization using a multidrugresistant organism is a technique used to treat infections through normalizing the gut microbiota via fecal microbiota transplantation in patients with confirmed colonization by carbapenem-resistant Enterobacteriaceae (CRE) or vancomycin-resistant enterococci (VRE) based on a fecal culture test within the past one week. In this study, we aimed to determine the safety and effectiveness of this technique. Methods: The safety and effectiveness were assessed via a systematic review. A literature search was conducted using five Korean databases, such as KoreaMed, and international databases, including Ovid-MEDLINE, Ovid-EMBASE, and Cochrane Library. Results: Main results are described here. From the studies retrieved using the aforementioned search strategy, the remaining 581 studies were screened using the inclusion and exclusion criteria, resulting in the selection of nine studies for further consideration. In terms of safety, many studies reported deaths and adverse reactions associated with different causes. Fewer studies reported the rate of colonization; however, the effect of colony rate was inconsistent when compared to no treatment group. Additionally, none of the studies assessed the recurrence rate, a decrease in the prevalence of diseases related to infection by multidrugresistant bacteria, and the quality of life. Conclusion: Fecal bacterial colonization for the decolonization of intestinal multidrugresistant bacteria was evaluated using a technique that requires further research as there is insufficient literature evidence to validate its safety and efficacy in treating infections through normalizing the intestinal flora of patients with confirmed colonization by CRE or VRE.

Caffeine, a methylxanthine derivative, affects various physiological conditions such as cell growth, proliferation, and energy metabolism. A genome-wide screening for genes required for caffeine resistance in Schizosaccharomyces pombe revealed several candidates, including Pap1 and downstream target genes involved in caffeine efflux. We found that Yap1, a budding yeast AP-1 homolog required for oxidative stress response, has a caffeine tolerance function. Although the Yap1 mutant is not sensitive to caffeine, overexpression of Yap1 renders cells resistant to high concentrations of caffeine. Caffeine sensitivity of mutants lacking two multidrug transporters, Pdr5 or Snq2, is completely recovered by Yap1 overexpression. Among Yap1-dependent target genes, FLR1, a fluconazole-resistant gene, is necessary but not sufficient for caffeine tolerance. Low concentrations of hydrogen peroxide induce Yap1 activation, which restores cell viability against caffeine toxicity. Intriguingly, oxidative stress-mediated cellular adaptation to caffeine toxicity requires Yap1, but not Flr1. Moreover, caffeine is involved in reduction of intracellular reactive oxygen species (ROS), as well as mutation rate and Rad52 foci formation. Altogether, we identified novel reciprocal crosstalk between ROS signaling and caffeine resistance.

Purpose In Alzheimer disease (AD), brain regions such as the cortex and the hippocampus show abundant amyloid load which correlates with cognitive function decline. Prior to the significant development of AD pathophysiology, patients report the manifestation of neuropsychiatric symptoms, indicating a functional interplay between basal ganglia structures and hippocampal regions. Zinc finger and BTB domain-containing protein 16 (ZBTB16) is a transcription factor that controls the expression of downstream genes and the involvement of ZBTB16 in the striatum undergoing pathological aging in AD and the resulting behavioral phenotypes has not yet been explored. Methods To study molecular alterations in AD pathogenesis, we analyzed the brain from amyloid precursor protein (APP)/ presenilin 1 (PS1) transgenic mice. The molecular changes in the striatal region of the brain were analyzed via the immunoblotting, and the quantitative RNA sequencing. The cognitive impairments of APP/PS1 mice were assessed via 3 behavioral tests: 3-chamber test, Y-maze test, and noble object recognition test. And multielectrode array experiments for the analysis of the neuronal activity of the striatum in APP/PS1 mice was performed. Results We found that the alteration in ZBTB16 levels that occurred in the early ages of the pathologically aging striatum coalesces with the disruption of transcriptional dysregulation while causing social memory deficits, anxiety-like behavior. The early ZBTB16 knockdown treatment in the striatum of APP/PS1 mice rescued cognition that continued into later age. Conclusions This study demonstrates that perturbation of transcriptional regulation of ZBTB16 during pathological aging may influence cognitive impairments and reveals a potent approach to targeting the transcriptional regulation of the striatum for the treatment of AD.

Purpose Vigabatrin has proven efficacy in the treatment of infantile spasms, but it carries the risk of irreversible visual field constriction. The incidence of vigabatrin-induced visual field constriction seems to depend on the extent of vigabatrin exposure. The aim of this study was to evaluate whether the therapeutic effect of vigabatrin is maintained in patients with infantile spasms receiving a short vigabatrin course followed by switching to another antiepileptic drug. Methods Patients with infantile spasms responsive to initial vigabatrin treatment were divided into a vigabatrin switch group (n=25) and a vigabatrin maintenance group (n=41). In the former group, vigabatrin was switched to other drugs within 6 months of spasm remission. The rate of seizure recurrence at 6 and 12 months from spasm remission was compared between the two groups. Results No statistically significant differences were found between the vigabatrin switch and maintenance groups in the age of onset, presence of concomitant seizures, time from spasm onset to vigabatrin treatment, time from vigabatrin treatment initiation to spasm remission, or vigabatrin dose at spasm remission. The number of patients with seizure recurrence at 12 months after spasm remission was 3 (3/25, 12%) in the vigabatrin switch group and 10 (10/41, 24.4%) in the vigabatrin maintenance group. The seizure recurrence rate at 12 months from spasm remission was not significantly different between groups. Conclusion A short course of vigabatrin could be considered in patients with infantile spasms who are responsive to initial vigabatrin treatment, since spasm remission was maintained after switching to other drugs.

Purpose Rituximab is increasingly used as a second-line treatment of neuroinflammatory disorders to improve clinical outcomes in cases refractory to conventional immunotherapy and to reduce relapses. This study aimed to demonstrate the efficacy and safety of rituximab used for pediatric autoimmune neuroinflammatory disorders. Methods We retrospectively reviewed the medical records of 32 patients (median age, 8.5 years; range, 1.1 to 17.1; 23 girls) who received rituximab treatment at Seoul National University Children’s Hospital. The disease subgroups were anti-N-methyl-D-aspartate (NMDA) receptor (anti-NMDAR) encephalitis (n=11), opsoclonus-myoclonus ataxia syndrome (OMAS) (n=10), other suspected autoimmune encephalitis (n=5), neuromyelitis optica spectrum disorder (n=4), and chronic inflammatory demyelinating polyneuropathy (n=2). Efficacy was measured by modified Rankin Scale (mRS) scores at the initiation of rituximab administration, at 2 months after initiation, and at the last follow-up. A favorable clinical outcome was defined as an improvement of ≥2 in the mRS score or achievement of an mRS score ≤2. Safety was assessed by reviewing infusion-related adverse events and infectious complications, including progressive multifocal leukoencephalopathy. Results Two months after the initiation of rituximab therapy, 21patients (65.6%) had a favorable response, while 26 (82.1%) had a favorable response at the last follow-up. Among the disease subgroups, anti-NMDAR encephalitis and OMAS showed especially good responses. Rituximab infusion-related adverse events were identified in nine patients (28.1%). All complications recovered spontaneously or with only symptomatic treatment. Conclusion Rituximab can be used safely for various pediatric autoimmune neuroinflammatory diseases. Rituximab is expected to improve clinical outcomes in pediatric patients with anti-NMDAR encephalitis and OMAS.

Introduction: Despite recent advancement in the prediction of cochlear implant outcome, the benefit of bilateral procedures compared to bimodal stimulation and how we predict speech perception outcomes of sequential bilateral cochlear implant based on bimodal auditory performance in children remain unclear. Objectives: This investigation was performed: (1) to determine the benefit of sequential bilateral cochlear implant and (2) to identify the associated factors for the outcome of sequential bilateral cochlear implant. Methods: Observational and retrospective study. We retrospectively analyzed 29 patients with sequential cochlear implant following bimodal-fitting condition. Audiological evaluations were performed; the categories of auditory performance scores, speech perception with monosyllable and disyllables words, and the Korean version of Ling. Audiological evaluations were performed before sequential cochlear implant with the bimodal fitting condition (CI1 + HA) and one year after the sequential cochlear implant with bilateral cochlear implant condition (CI1 + CI2). The good performance group (GP) was defined as follows; 90% or higher in monosyllable and bisyllable tests with auditory-only condition or 20% or higher improvement of the scores with CI1 + CI2. Age at first implantation, inter-implant interval, categories of auditory performance score, and various comorbidities were analyzed by logistic regression analysis. Results: Compared to the CI1 + HA, CI1 + CI2 provided significant benefit in categories of auditory performance, speech perception, and Korean version of Ling results. Preoperative categories of auditory performance scores were the only associated factor for being GP (odds ratio = 4.38, 95% confidence interval – 95% = 1.07–17.93, p = 0.04). Conclusions: The children with limited language development in bimodal condition should be considered as the sequential bilateral cochlear implant and preoperative categories of auditory performance score could be used as the predictor in speech perception after sequential cochlear implant. Resumo: Introdução: Apesar dos avanços recentes na predição do resultado do implante coclear, ainda não está claro o benefício do procedimento bilateral em comparação com a estimulação bimodal e como podemos prever resultados de percepção da fala com implante coclear bilateral sequencial com base no desempenho auditivo bimodal em crianças. Objetivos: Este estudo foi realizado para: 1) Determinar o benefício do implante coclear bilateral sequencial e 2) Identificar os fatores associados com o resultado do implante bilateral sequencial. Método: Estudo observacional e retrospectivo. Analisamos retrospectivamente 29 pacientes com implantes sequenciais após a adaptação bimodal. Avaliações audiológicas foram realizadas; os escores das categorias de desempenho auditivo, a percepção da fala com palavras monossílabas e dissílabas e a versão coreana de Ling. As avaliações audiológicas foram realizadas antes do implante sequencial com o ajuste bimodal (IC1 + AH) e um ano após o implante coclear sequencial com implante bilateral (IC1 + IC2). O grupo com bom desempenho (BD) foi definido da seguinte forma: 90% ou mais em testes com monossílabos e dissílabos com condição apenas auditiva ou melhoria de 20% ou mais dos escores com IC1 + IC2. A idade no primeiro implante, o intervalo interimplante, o escore categorias de desempenho auditivo e as diversas comorbidades foram analisadas através de análise de regressão logística. Resultados: Em comparação com o IC1 + AA, IC1 + IC2 demonstraram benefícios significativos nos escores categorias de desempenho auditivo, percepção da fala e a versão coreana de Ling. Os escores de categorias de desempenho auditivo pré-operatórios foram o único fator associado para ser do grupo BD (odds ratio - OR = 4,38, intervalo de confiança de 95% - IC 95% = 1,07-17,93, p = 0,04). Conclusões: As crianças com desenvolvimento limitado de linguagem em condição bimodal devem ser consideradas, pois o implante coclear bilateral sequencial e o escore pré-operatório das categorias de desempenho auditivo poderiam ser usados como preditores na percepção da fala após implante sequencial. Keywords: Bilateral cochlear implant, Pediatric, Predictive factors, Speech perception, Palavras-chave: Implante coclear bilateral, Pediátrico, Fatores preditivos, Percepção da fala

Abstract Background The Korean Undiagnosed Diseases Program (KUDP) was launched in January 2017 as a one-year pilot project to address the increasing global interest in patients with undiagnosed rare diseases. The purpose of this paper is to summarize the project results and emphasize the unmet research needs among patients with undiagnosed rare diseases in Korea. Results Patient enrollment, assessment, and diagnostic processes were determined by the KUDP clinical expert consortium. Patients followed a diagnostic workflow after being categorized into one of four groups: I) insufficient clinical information or lack of standard diagnostic processes; II) undiagnosed due to low disease awareness; III) clinically diagnosed but unconfirmed genetically due to genetic heterogeneities; or IV) unknown disease due to complex, atypical clinical presentations. After excluding two patients from group I, 97 patients were enrolled, including 10 in group II, 67 in group III, and 20 in group IV. Most of them (92 of 97, 94.8%) were pediatric patients (

IntroductionA defect in the cochlear afferent synapse between the inner hair cells and spiral ganglion neurons, after noise exposure, without changes in the hearing threshold has been reported. Animal studies on auditory evoked potentials demonstrated changes in the auditory brainstem response (ABR) measurements of peak I amplitude and the loss of synapses, which affect the temporal resolution of complex sounds. Human studies of auditory evoked potential have reported ambiguous results regarding the relationship between peak I amplitude and noise exposure. Paired click stimuli have been used to investigate the temporal processing abilities of humans and animals. In this study, we investigated the utility of measuring auditory evoked potentials in response to paired click stimuli to assess the temporal processing function of ribbon synapses in noise-induced cochlear synaptopathy.Materials and MethodsTwenty-two Sprague Dawley rats were used in this study, and synaptopathy was induced by narrow-band noise exposure (16 kHz with 1 kHz bandwidth, 105 dB sound pressure level for 2 h). ABRs to tone and paired click stimuli were measured before and 1, 3, 7, and 14 days after noise exposure. For histological analyses, hair cells and ribbon synapses were immunostained and the synapses quantified. The relationships among ABR peak I amplitude, number of synapses, and ABR to paired click stimuli were examined.ResultsOur results showed that ABR thresholds increase 1 day after noise exposure but fully recover to baseline levels after 14 days. Further, we demonstrated test frequency-dependent decreases in peak I amplitude and the number of synapses after noise exposure. These decreases were statistically significant at frequencies of 16 and 32 kHz. However, the ABR recovery threshold to paired click stimuli increased, which represent deterioration in the ability of temporal auditory processing. Our results indicate that the ABR recovery threshold is highly correlated with ABR peak I amplitude after noise exposure. We also established a direct correlation between the ABR recovery threshold and histological findings.ConclusionThe result from this study suggests that in animal studies, the ABR to paired click stimuli along with peak I amplitude has potential as an assessment tool for hidden hearing loss.

Abstract Background Healthcare professionals who experience trauma due to patient safety incidents can be considered second victims, and they also suffer from various difficulties. In order to support second victims, it is necessary to determine the circumstances of the incidents in question, along with the symptoms that the victims are experiencing and the support they require. A qualitative study on healthcare professionals of various occupations, such as physicians and nurses working in Korea, was conducted, and the experiences and response methods and processes of second victims were examined. Methods In-depth interviews were conducted with 16 healthcare professionals (six physicians, eight nurses, and two pharmacists) who had experienced a patient safety incident. All interviews were recorded and transcribed, and the data analysis was conducted in accordance with Strauss and Corbin’s grounded theory. Both open coding and axial coding were performed. Consolidated criteria for reporting qualitative research (COREQ) were applied in this study. Results The results of the open coding demonstrated that the experiences of second victims can be categorized into “the reactions of the first victim and surrounding people after the incident,” “Influence of factors aside from the incident,” “the initial complex responses of the participants to the incident,” “open discussion of the incident,” “the culture in medical institutions regarding early-stage incident response,” “the coping responses of the participants after incidents,” and “living with the incident.” Then, the seven categories in the open coding stage were rearranged according to the paradigm model, and the reaction process of the second victims was analyzed through process analysis, being divided into the “entanglement stage,” “agitating stage,” “struggling stage,” “managing stage,” and “indurating stage.” Conclusions This research is significant because it provides a comprehensive understanding of second victims’ experiences in the eastern region of Korea, by obtaining data using a qualitative research method. The findings of the study also highlight the five stages of the second victim response process, and can be used to design a specialized second victim support program in Korea.

Purpose: To compare the diagnostic performance of magnetic resonance (MR) sequences for the evaluation of cerebral venous sinus thrombosis (CVST) during followup examinations. Materials and Methods: Thirteen cases that were confirmed to be CVST between January 2006 and March 2016 were included in this study. Two neuroradiologists independently examined each initial and follow-up MR sequence image in random order. Results: Gadolinium-enhanced T1-weighted imaging (Gd-enhanced T1WI) was the most sensitive sequence for the detection of CVST in the initial and follow-up MR examinations (82% and 55.3%, respectively). Among the non-enhanced MR sequences of the initial examination, gradient-recalled echo was the most sensitive (77.4%), fluid-attenuated inversion recovery (FLAIR) had low sensitivity (34.4%). The overall diagnostic performances of all MR sequences except for FLAIR decreased during the follow-up. FLAIR was the most sensitive during follow-up, and was also the only sequence with increased sensitivity during follow-up (from 34.4% to 55.6%). Conclusion: Gd-enhanced T1WI had the best diagnostic performance for CVST in both initial and follow-up MR examinations. Therefore, it is reasonable to use Gdenhanced T1WI to evaluate CVST during follow-up examinations. However, for patients who cannot tolerate MR contrast agents, the use of FLAIR to assess the remaining CVST during the follow-up may be helpful.

Abstract The yeast strain Metschnikowia persimmonesis Kang and Choi et al., sp. nov. [type strain KIOM_G15050 = Korean Collection for Type Cultures (KCTC) 12991BP] was isolated from the stalk of native persimmon cultivars (Diospyros kaki Thumb) obtained from different regions of South Korea and was characterized phenotypically, genetically, and physiologically. The isolate grew between 4 and 40 °C (optimum temperature: 24–28 °C), pH 3–8 (pH optimum = 6.0), and in 0–4% NaCl solution (with optimal growth in absence of NaCl). It also exhibited strong antibiotic and antimicrobial activities. Morphologically, cells were characterized by the presence of long, needle-shaped ascospores. Based on 18S ribosomal DNA gene sequence analysis, the new species was found to belong to the genus Metschnikowia as a sister clade of Metschnikowia fructicola. We therefore conclude that this yeast isolate from D. kaki is a new member of the genus Metschnikowia and propose the name M. persimmonesis sp. nov. This strain has been deposited in the KCTC for future reference. This discovery provides a basis for future research on M. persimmonesis sp. nov., including its possible contribution to the medicinal properties of the host persimmon plant.

Objectives This study aimed to compare the outcome of endoscopic and microscopic tympanoplasty. Methods This was a retrospective comparative study of 73 patients (35 males and 38 females) who underwent type I tympanoplasty at Samsung Medical Center from April to December 2014. The subjects were classified into two groups; endoscopic tympanoplasty (ET, n=25), microscopic tympanoplasty (MT, n=48). Demographic data, perforation size of tympanic membrane at preoperative state, pure tone audiometric results preoperatively and 3 months postoperatively, operation time, sequential postoperative pain scale (NRS-11), and graft success rate were evaluated. Results The perforation size of the tympanic membrane in ET and MT group was 25.3%±11.7% and 20.1%±11.9%, respectively (P=0.074). Mean operation time of MT (88.9±28.5 minutes) was longer than that of the ET (68.2±22.1 minutes) with a statistical significance (P=0.002). External auditory canal (EAC) width was shorter in the ET group than in the MT group (P=0.011). However, EAC widening was not necessary in the ET group and was performed in 33.3% of patients in the MT group. Graft success rate in the ET and MT group were 100% and 95.8%, respectively; the values were not significantly different (P=0.304). Pre- and postoperative audiometric results including bone and air conduction thresholds and air-bone gap were not significantly different between the groups. In all groups, the postoperative air-bone gap was significantly improved compared to the preoperative air-bone gap. Immediate postoperative pain was similar between the groups. However, pain of 1 day after surgery was significantly less in the ET group. Conclusion With endoscopic system, minimal invasive tympanoplasty can be possible with similar graft success rate and less pain.

The cerebellopontine angle (CPA) is a triangular-shaped space that lies at the junction of the pons and cerebellum. It contains cranial nerves and the anterior inferior cerebellar artery (AICA). The anatomical shape and location of the AICA is variable within the CPA and internal auditory canal (IAC). A possible etiology of idiopathic sudden sensorineural hearing loss (ISSNHL) is ischemia of the labyrinthine artery, which is a branch of the AICA. As such, the position of the AICA within the CPA and IAC may be related to the clinical development of ISSNHL. We adopted two methods to classify the anatomic position of the AICA, then analyzed whether these classifications affected the clinical features and prognosis of ISSNHL. We retrospectively reviewed patient data from January 2015 to March 2018. Two established classification methods designed by Cahvada and Gorrie et al. were used. Pure tone threshold at four different frequencies (0.5, 1, 4, and 8 kHz), at two different time points (at initial presentation and three months after treatment), were analyzed. We compared the affected and unaffected ears, and investigated whether there were any differences in hearing recovery and symptoms between the two classification types. There was no difference in AICA types between ears with and without ISSNHL. Patients who had combined symptoms such as tinnitus and vertigo did not show a different AICA distribution compared with patients who did not. There were differences in quantitative hearing improvement between AICA types, although without statistic significance (p = 0.09–0.13). At two frequencies, 1 and 4 kHz, there were differences in Chavda types between hearing improvement and no improvement (p

Background: Extraction conditions greatly affect composition, as well as biological activity. Therefore, optimization is essential for maximum efficacy. Methods: Korean Red Ginseng (KRG) was extracted under different conditions and antioxidant activity, extraction yield, and ginsenoside Rg1 and phenolic content evaluated. Optimized extraction conditions were suggested using response surface methodology for maximum antioxidant activity and extraction yield. Results: Analysis of KRG extraction conditions using response surface methodology showed a good fit of experimental data as demonstrated by regression analysis. Among extraction factors, such as extraction solvent and extraction time and temperature, ethanol concentration greatly affected antioxidant activity, extraction yield, and ginsenoside Rg1 and phenolic content. The optimal conditions for maximum antioxidant activity and extraction yield were an ethanol concentration of 48.8%, an extraction time 73.3 min, and an extraction temperature of 90°C. The antioxidant activity and extraction yield under optimal conditions were 43.7% and 23.2% of dried KRG, respectively. Conclusion: Ethanol concentration is an important extraction factor for KRG antioxidant activity and extraction yield. Optimized extraction conditions provide useful economic advantages in KRG development for functional products.

This study directly compared the performance of a contralateral routing of signal (CROS)/bilateral routing of signal (BiCROS) and a soft-band bone-anchored hearing aid (BAHA) in patients with unilateral sensorineural hearing loss (SNHL) and assessed the relationship between hearing aid benefits and personal factors. Participants with unilateral SNHL were prospectively enrolled in the study and were tested under the following three conditions: unaided, with CROS/BiCROS, and with soft-band BAHA. Sound localization, consonant, hearing in noise, and psychoacoustic tests were performed. Pseudobinaural benefits (e.g., squelch, summation, and head shadow effect) were obtained in both the CROS/BiCROS and soft-band BAHA conditions and compared to the unaided condition. Sound localization ability was not improved in either the CROS/BiCROS condition or soft-band BAHA condition. Rather, sound localization ability was significantly decreased in the CROS/BiCROS setting. A CROS/BiCROS hearing aid and a soft-band BAHA provided additional benefit for speech-in-noise perception when target speech was directed to the impaired ear side. The CROS/BiCROS hearing aid was superior to the soft-band BAHA one in decreasing the head shadow effect, but it appeared to have a negative effect when the noise was delivered to the better ear. The positive and negative effects of CROS/BiCROS for localization and speech perception were significantly correlated with personal factors such as age, hearing threshold in the better ear, and unaided psychoacoustic performances. Despite the lack of device acclimatization, we believe that this study provides counseling information for hearing aid clinics to use in the context of patients with unilateral SNHL.

In our previous study, we found that horizontal ocular deviation (OD) was significantly increased in patients with unilateral vestibular neuritis (VN). This study is aimed to compare the measurements of horizontal OD in various diseases which can present as acute vertigo in the emergency department. We retrospectively reviewed patients who visited the emergency department and underwent brain MRI due to acute vertigo. We compared them to healthy controls who underwent brain MRI for a regular health examination. Among the study participants, 149 patients who were diagnosed with benign paroxysmal positional vertigo (BPPV), unilateral Ménière's disease (MD), vestibular migraine (VM), unilateral vestibular neuritis (VN), or posterior inferior cerebellar artery (PICA) infarction were enrolled. Absolute angles of horizontal OD were larger in the definite MD (19.1 ± 12.7°), possible and probable MD (15.5 ± 11.7°), and VN (22.2 ± 11.7°) groups compared to the control group (4.3 ± 3.7°). Most VN patients (83.3%) had horizontal OD toward the direction of the lesion. About half of the MD patients (46.2%) and half of the patients with PICA infarction (50.0%) had horizontal OD toward the opposite direction of the lesion. Regarding PICA infarction, horizontal OD was observed only in patients who immediately underwent an MRI after developing the PICA territory vestibulocerebellar infarction. Although the exact mechanism of horizontal OD is unclear, this study suggests that horizontal OD reflects a static vestibular imbalance, and that the eyeball is deviated to the weaker of the two vestibular nuclei during neural resting activity. Therefore, horizontal OD could be helpful in assessing for a prior vestibular imbalance.

High-mobility group box 1 (HMGB1), a well-known danger-associated molecular pattern molecule, acts as a pro-inflammatory molecule when secreted by activated immune cells or released after necrotic cell damage. HMGB1 binds to immunogenic bacterial components and augments septic inflammation. In this study, we show how HMGB1 mediates complement activation, promoting sterile inflammation. We show that HMGB1 activates the classical pathway of complement system in an antibody-independent manner after binding to C1q. The C3a complement activation product in human plasma and C5b-9 membrane attack complexes on cell membrane surface are detected after the addition of HMGB1. In an acetaminophen (APAP)-induced hepatotoxicity model, APAP injection reduced HMGB1 levels and elevated C3 levels in C1q-deficient mouse serum samples, compared to that in wild-type (WT) mice. APAP-induced C3 consumption was inhibited by sRAGE treatment in WT mice. Moreover, in a mouse model of brain ischemia–reperfusion injury based on middle cerebral arterial occlusion, C5b-9 complexes were deposited on vessels where HMGB1 was accumulated, an effect that was suppressed upon HMGB1 neutralization. We propose that the HMGB1 released after cell necrosis and in ischemic condition can trigger the classical pathway of complement activation to exacerbate sterile inflammation.

ObjectivesThe aims of this study were to find and compare the effect of directional (DIR) processing of two different hearing aids via both subjective and objective methods, to determine the association between the results of the subjective and objective evaluations, and to find out individual predictive factors influencing the DIR benefit.MethodsTwenty-six hearing aid users fitted unilaterally with each two different experimental hearing aid performed modified Korean Hearing in Noise Test (K-HINT) in three DIR conditions; omnidirectional (OMNI) mode, OMNI plus noise reduction feature, fixed DIR mode. In order to determine benefits from DIR benefit within a hearing aid and compare performance of the DIR processing between hearing aids, a subjective questionnaire was administrated on speech quality (SQ) and discomfort in noise (DN) domain. Correlation analysis of factors influencing DIR benefit was accomplished.ResultsBenefits from switching OMNI mode to DIR mode within both hearing aids in K-HINT were about 2.8 (standard deviation, 3.5) and 2.1 dB SNR (signal to ratio; SD, 2.5), but significant difference in K-HINT results between OMNI and OMNI plus noise reduction algorithm was not shown. The subjective evaluation resulted in the better SQ and DN scores in DIR mode than those in OMNI mode. However, the difference of scores on both SQ and DN between the two hearing aids with DIR mode was not statistically significant. Any individual factors did not significantly affect subjective and objective DIR benefits.ConclusionDIR benefit was found not only in the objective measurement performed in the laboratory but also in the subjective questionnaires, but the subjective results was failed to have significant correlation with the DIR benefit obtained in the K-HINT. Factors influencing individual variation in perceptual DIR benefit were still hard to explain.

This study evaluated the prevalence of minimal hearing loss (MHL) in South Korea based on the 2010 to 2012 Korea National Health and Nutrition Examination Survey. A total of 16,630 representative individuals (older than 12 years) who completed ear examinations and structured questionnaires were analyzed. Only participants who had normal tympanic membranes were included. MHL was categorized into the following three groups: 1) unilateral sensorineural hearing loss (USHL, pure-tone average (PTA) ≥ 15 dB in the affected ear), 2) bilateral sensorineural hearing loss (BSHL, 15 dB ≤ PTA < 40 dB in both ears), and 3) high-frequency sensorineural hearing loss (HFSHL, two or more high-frequency thresholds > 25 dB in either ear). To evaluate clinical symptoms, subjective hearing status, tinnitus, and quality of life of each MHL group were compared to those of normal-hearing listeners. The use of hearing aids (HAs) was also investigated in the MHL population. The prevalence of normal hearing and MHL were 58.4% and 37.4%, respectively. In univariate analyses, the prevalence of MHL increased with age. It was significantly increased in males. Regarding clinical symptoms, 13.0% and 92.1% of participants with MHL reported difficulties with hearing and annoying tinnitus, respectively. In multivariate analyses, these proportions were significantly higher in the MHL groups than in normal-hearing listeners. Participants with MHL also showed significantly lower Euro Qol-5D index scores than did normal-hearing listeners. Regarding hearing rehabilitation, among minimally hearing impaired participants with subjective hearing loss, only 0.47% of individuals used HAs. Our results reveal that MHL is common in South Korea. It is associated with significant subjective hearing loss, tinnitus, and poor quality of life. Therefore, clinicians need to pay attention to this special group and provide proper counselling and rehabilitative management.

The purpose of this study was to prove the hypothesis that caloric response in Ménière's disease (MD) is reduced by hydropic expansion of the vestibular labyrinth, not by vestibular hypofunction, by evaluating the correlation morphologically using an intravenous Gadolinium (IV-Gd) inner ear MRI. In study I, the prevalence of abnormal video Head Impulse Test (vHIT) results among the patients with definite unilateral MD (n = 24) and vestibular neuritis (VN) (n = 22) were investigated. All patients showed abnormal canal paresis (CP) (> 26%) on caloric tests. The prevalence of abnormal vHIT in patients with abnormal CP was significantly lower in MD patients (12.5%) than that in VN patients (81.8%) (p < 0.001). In study II, morphological correlation between caloric tests and vestibular hydrops level was evaluated in unilateral MD patients (n = 16) who had normal vHIT results. Eleven patients (61%) had abnormal CP. After taking the images of IV-Gd inner ear MRI, the vestibular hydrops ratio (endolymph volume/total lymph volume = %VH) was measured. In addition, the relative vestibular hydrops ratio (%RVH = (%VHaffected ear-%VHunaffected ear) / (%VHaffected ear + %VHunaffected ear)) was calculated. Each ratio (%VH and %RVH) was compared with average peak slow phase velocity (PSPV) and CP, respectively. In the MD patients, %VH of the affected ear correlated significantly with mean PSPV on the same side (rs = -0.569, p = 0.024), while %RVH correlated significantly with CP (rs = 0.602, p = 0.014). In most MD patients (87.5%) compared to VN patients, vHIT results were normal even though the caloric function was reduced. In addition, the reduced caloric function with normal vHIT was related to the severity of the vestibular hydrops measured by the IV-Gd inner ear MRI. These findings concluded that the abnormal caloric tests with normal vHIT in MD indicated severe endolymphatic hydrops rather than vestibular hypofunction.

Purpose: Hospice and palliative care is a multidisciplinary approach to treatment and care designed to meet the needs of patients and their families at the end of life. Social workers are essential members of the hospice team, but their role is not well understood. The purpose of this study was to explore achievements and barriers in hospice social work practice and to suggest strategies for enhancing the role of social workers. Methods: The participants were 10 social workers who had worked in hospice institutions for over 5 years and were recruited based on reputational case sampling. Data were collected through two focus group interviews, and were qualitatively analyzed using thematic analysis. Results: Through the data analysis, two topics (achievements in hospice social work practice, barriers to achievements in hospice social work practice), five categories, 17 subcategories, and 182 concepts were derived. Conclusion: Based on an in-depth discussion of our key findings, we propose several types of institutional support, including expanding the hospice social work workforce, improving competence through education and supervision, developing professional programs and community resources, and refining methods for measuring achievements. [ABSTRACT FROM AUTHOR]