Nationwide Prevalence of Video Head Impulse Test Abnormality and its Risk Factors in South Korea.

OBJECTIVE: To identify the prevalence of and relevant information for video head impulse test (vHIT) abnormality in a large population. STUDY DESIGN: A cross-sectional design. SETTING: Korean National Health and Nutrition Examination Survey, 2021. METHODS: The sample was representative of the Korean population, with 2237 participants aged ≥40 years. A vHIT was performed to evaluate vestibular function. The vestibulo-ocular reflex (VOR) gain and the presence of reproducible catch-up saccades was assessed in a vHIT. Participants also completed questionnaires for demographics, socioeconomic status, and basic information regarding systemic diseases and dizziness and underwent hearing tests with automated pure-tone audiometry. RESULTS: The prevalence of vHIT abnormality was 22.5%, with unilateral (14.3%) being more common than bilateral (8.2%). The prevalence of vHIT abnormality increased significantly with age, with the highest rate observed in individuals aged >70 years (42.5%). Both hearing and VOR gain deteriorated with age, but the patterns of age-related progression were different. While hearing loss (HL) deteriorated gradually and progressively throughout adulthood, VOR gain deterioration was markedly evident after 70 years of age. CONCLUSION: Considering the high prevalence of vHIT abnormality, appropriate social and medical policies are needed to prevent associated injuries and improve patients' quality of life. The distinct age-related changes in HL and objective findings of vestibular dysfunction indicate the need for different approaches to address these social problems in aging countries.

Rational Design of a Necklace-like ZIF-67/Poly(vinylidene fluoride) Electrospun Nanofiber Hybrid Membrane for Simultaneous Removal of PM0.3 and SO2.

Growing concerns over poor air quality, especially in urban and industrial regions, have led to increased global demands for advanced air-purification technologies. However, the stability and airborne pollutant control abilities of the available air-purification materials under diverse environmental conditions are limited. Thus, the advanced development of filtration materials that can effectively control different types of pollutants, such as particulate matter (PM) and gaseous pollutants, simultaneously has attracted attention. The zeolitic imidazolate framework (ZIF), a type of porous metal-organic framework (MOF), is a promising material for capturing weakly acidic toxic gases such as SO2 owing to its excellent adsorption performance and high thermal and chemical stability. In this study, we successfully developed an ultrastable necklace-like multifunctional hybrid membrane via the cetyltrimethylammonium bromide-assisted in situ growth of zeolitic imidazolate framework (ZIF)-67 crystals on electrospun Co2+-doped poly(vinylidene fluoride) nanofibers (70 nm) that can be used in different moisture environments to achieve sustainable air-filtration performance. The hybrid nanocomposite membrane demonstrated excellent performance for the simultaneous control of intractable fine PM0.3 (filtration efficiency, 99.461%) and SO2 (adsorption capacity, 1476.5 mg g-1) under different humidity conditions. This study contributes to the optimal synergistic integration of the advanced metal-organic framework (MOF)-nanofiber nanocomposite membranes and can guide the rational design and conceptualization of a facile and novel membrane for various applications in the environmental science and energy fields.

SERTAD1 initiates NLRP3-mediated inflammasome activation through restricting NLRP3 polyubiquitination.

We here demonstrate that SERTAD1 is an adaptor protein responsible for the regulation of lysine 63 (K63)-linked NLRP3 polyubiquitination by the Cullin1 E3 ubiquitin ligase upon inflammasome activation. SERTAD1 specifically binds to NLRP3 but not to other inflammasome sensors. This endogenous interaction increases after inflammasome activation, interfering with the interaction between NLRP3 and Cullin1. Interleukin (IL)-1ß and IL-18 secretion, as well as the cleavage of gasdermin D, are decreased in SERTAD1 knockout bone-marrow-derived macrophages, together with reduced formation of the NLRP3 inflammasome complex. Additionally, SERTAD1-deficient mice show attenuated severity of monosodium-uric-acid-induced peritonitis and experimental autoimmune encephalomyelitis. Analysis of public datasets indicates that expression of SERTAD1 mRNA is significantly increased in the patients of autoimmune diseases. Thus, our findings uncover a function of SERTAD1 that specifically reduces Cullin1-mediated NLRP3 polyubiquitination via direct binding to NLRP3, eventually acting as a crucial factor to regulate the initiation of NLRP3-mediated inflammasome activation.

Application of the Barany Society's Presbyvestibulopathy Criteria in Older Adults With Chronic Dizziness.

OBJECTIVE: To evaluate the older adults with chronic dizziness using the Barany Society's presbyvestibulopathy (PVP) diagnostic criteria and to assess the clinical usability of the criteria. STUDY DESIGN: Retrospective study. SETTING: Single tertiary medical center. METHODS: Among a total of 1964 patients aged 60 years or older, 55 patients who had symptoms suitable for the PVP criteria and who underwent all 3 vestibular function tests were analyzed. Of these 55 patients, 13 patients were diagnosed with PVP based on the peripheral vestibular hypofunction criteria; the remaining 42 patients were categorized as patients without PVP. RESULTS: In both patients with PVP and patients without PVP, postural imbalance or unsteadiness was the most frequently reported vestibular symptom. The rotatory chair test contributed the most to the quantitative diagnosis of PVP (6 of 13), followed by the caloric response test (3 of 13) and video head impulse test (vHIT; 2 of 13). When we included the presence of catch-up saccades in addition to the vHIT gain in the diagnostic criteria, 5 patients without PVP were additionally diagnosed with PVP. Furthermore, when accounting for the inclusion of catch-up saccades, patients who experienced recurrent falls demonstrated a significantly higher rate of impairments in the lateral and posterior semicircular canals according to the multivariate analysis. CONCLUSION: Considering the catch-up saccades in addition to vHIT gain seemed to contribute to the diagnosis of PVP and prediction of recurrent fall risks in older adults. Further studies are needed to solidify the diagnostic criteria for PVP.

Treatment Efficacy of Various Maneuvers for Lateral Canal Benign Paroxysmal Positional Vertigo With Apogeotropic Nystagmus: A Randomized Controlled Trial.

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.

A Comparative Study Using Vestibular Mapping in Sudden Sensorineural Hearing Loss With and Without Vertigo.

OBJECTIVE: To investigate the impairment patterns in peripheral vestibular organs in sudden sensorineural hearing loss (SSNHL) with and without vertigo. STUDY DESIGN: Retrospective study. SETTING: Single tertiary medical center. METHODS: Data from 165 SSNHL patients in a tertiary referral center from January 2017 to December 2022 were retrospectively analyzed. All patients underwent a video head impulse test, vestibular evoked myogenic potential test, and pure-tone audiometry. Hierarchical cluster analysis was performed to investigate vestibular impairment patterns. The prognosis of the hearing was determined using American Academy of Otolaryngology-Head and Neck Surgery recommendations. RESULTS: After excluding patients with vestibular schwannoma and Meniere's disease, 152 patients were included in this study. A total of 73 of 152 patients were categorized as SSNHL with vertigo (SSNHL_V) and showed an independent merge of the posterior semicircular canal (PSCC) in cluster analysis. A total of 79 of 152 patients were categorized as SSNHL without vertigo (SSNHL_N) and showed an independent merge of saccule in cluster analysis. The PSCC (56.2%) and saccule (20.3%) were the most frequently impaired vestibular organs in SSNHL_V and SSNHL_N, respectively. In terms of prognosis, 106 of 152 patients had partial/no recovery and showed an independent merge of the PSCC in cluster analysis. A total of 46 of 152 patients had a complete recovery and showed an independent merge of the saccule in cluster analysis. CONCLUSION: A tendency of isolated PSCC dysfunction was seen in SSNHL_V and partial/no recovery. A tendency of isolated saccular dysfunction was seen in SSNHL_N and complete recovery. Different treatments might be needed in SSNHL depending on the presence of vertigo.

Peli3 ablation ameliorates acetaminophen-induced liver injury through inhibition of GSK3ß phosphorylation and mitochondrial translocation.

The signaling pathways governing acetaminophen (APAP)-induced liver injury have been extensively studied. However, little is known about the ubiquitin-modifying enzymes needed for the regulation of APAP-induced liver injury. Here, we examined whether the Pellino3 protein, which has E3 ligase activity, is needed for APAP-induced liver injury and subsequently explored its molecular mechanism. Whole-body Peli3-/- knockout (KO) and adenovirus-mediated Peli3 knockdown (KD) mice showed reduced levels of centrilobular cell death, infiltration of immune cells, and biomarkers of liver injury, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), upon APAP treatment compared to wild-type (WT) mice. Peli3 deficiency in primary hepatocytes decreased mitochondrial and lysosomal damage and reduced the mitochondrial reactive oxygen species (ROS) levels. In addition, the levels of phosphorylation at serine 9 in the cytoplasm and mitochondrial translocation of GSK3ß were decreased in primary hepatocytes obtained from Peli3-/- KO mice, and these reductions were accompanied by decreases in JNK phosphorylation and mitochondrial translocation. Pellino3 bound more strongly to GSK3ß compared with JNK1 and JNK2 and induced the lysine 63 (K63)-mediated polyubiquitination of GSK3ß. In rescue experiments, the ectopic expression of wild-type Pellino3 in Peli3-/- KO hepatocytes restored the mitochondrial translocation of GSK3ß, but this restoration was not obtained with expression of a catalytically inactive mutant of Pellino3. These findings are the first to suggest a mechanistic link between Pellino3 and APAP-induced liver injury through the modulation of GSK3ß polyubiquitination.

Vestibular mapping in Ramsay-Hunt syndrome and idiopathic sudden sensorineural hearing loss.

PURPOSE: To observe vestibular impairment patterns in patients with Ramsay Hunt syndrome with dizziness (RHS_D) and sudden sensorineural hearing loss with dizziness (SSNHL_D) using hierarchical cluster analysis (HCA) to interpret results with possible mechanisms. METHODS: The data of 30 RHS_D and 81 SSNHL_D patients from January 2017 to August 2022 in a single tertiary referral center were retrospectively analyzed. Video head impulse test (vHIT) and vestibular evoked myogenic potential (VEMP) were used for vestibular analysis of peripheral vestibular organs, and the results of vHIT and VEMP were analyzed. HCA was used to analyze vestibular impairment patterns. RESULTS: In RHS_D patients, the lateral semicircular canal (LSCC) was the most impaired semicircular canal (SCC), followed by the anterior semicircular canal (ASCC) and the posterior semicircular canal (PSCC), and the utricle was more impaired than the saccule. In SSNHL_D patients, the PSCC was the most impaired SCC, followed by the LSCC and the ASCC, and the utricle was more impaired than the saccule. In HCA of RHS_D patients, the ASCC and utricle were initially clustered, followed by the LSCC, PSCC and saccule in order. In the HCA of SSNHL_D patients, the PSCC was solely merged and independently clustered. CONCLUSION: There were different patterns of vestibular impairments between RHS_D and SSNHL_D patients. The vestibular analysis and HCA results of SSNHL_D showed tendency of skip lesion, which could be explained by vascular pathophysiology.

Symmetric Bilateral Congenital Middle Ear Cholesteatoma: A Case Report.

Congenital middle ear cholesteatoma (CMEC) accounts for 2%-5% of all cases of middle ear cholesteatoma. CMEC is rare and diagnostically challenging; therefore, only a few cases are reported in the literature, and the pathophysiology of this condition remains largely unclear. Currently, epidermoid formation, amniotic fluid contamination, lack of the tympanic ring, and squamous metaplasia are among the mechanisms implicated in the pathogenesis of CMEC; however, no single theory satisfactorily explains the pathophysiology of this disorder. We report a case of CMEC in a young male patient, who showed a symmetric, binaural whitish mass posterior to the anterosuperior quadrant of the tympanic membrane. A few reports have described bilateral CMEC; however, no study has reported symmetrical CMEC as observed in this case. Bilateral tympanoplasty concomitant with cholesteatoma removal was performed, and histopathological evaluation of the resected specimen showed closed-type cholesteatoma. In this report, we describe a rare case of symmetric CMEC, which supports the epidermoid formation theory associated with CMEC, together with a literature review.

Action-driven contrastive representation for reinforcement learning.

In reinforcement learning, reward-driven feature learning directly from high-dimensional images faces two challenges: sample-efficiency for solving control tasks and generalization to unseen observations. In prior works, these issues have been addressed through learning representation from pixel inputs. However, their representation faced the limitations of being vulnerable to the high diversity inherent in environments or not taking the characteristics for solving control tasks. To attenuate these phenomena, we propose the novel contrastive representation method, Action-Driven Auxiliary Task (ADAT), which forces a representation to concentrate on essential features for deciding actions and ignore control-irrelevant details. In the augmented state-action dictionary of ADAT, the agent learns representation to maximize agreement between observations sharing the same actions. The proposed method significantly outperforms model-free and model-based algorithms in the Atari and OpenAI ProcGen, widely used benchmarks for sample-efficiency and generalization.

Crataegus pinnatifida Bunge Inhibits RANKL-Induced Osteoclast Differentiation in RAW 264.7 Cells and Prevents Bone Loss in an Ovariectomized Rat Model.

Osteoporosis is characterized by a decrease in bone microarchitecture with an increased risk of fracture. Long-term use of primary treatments, such as bisphosphonates and selective estrogen receptor modulators, results in various side effects. Therefore, it is necessary to develop alternative therapeutics derived from natural products. Crataegus pinnatifida Bunge (CPB) is a dried fruit used to treat diet-induced indigestion, loss of appetite, and diarrhea. However, research into the effects of CPB on osteoclast differentiation and osteoporosis is still limited. In vitro experiments were conducted to examine the effects of CPB on RANKL-induced osteoclast differentiation in RAW 264.7 cells. Moreover, we investigated the effects of CPB on bone loss in the femoral head in an ovariectomized rat model using microcomputed tomography. In vitro, tartrate-resistant acid phosphatase (TRAP) staining results showed the number of TRAP-positive cells, and TRAP activity significantly decreased following CPB treatment. CPB also significantly decreased pit formation. Furthermore, CPB inhibited osteoclast differentiation by suppressing NFATc1, and c-Fos expression. Moreover, CPB treatment inhibited osteoclast-related genes, such as Nfatc1, Ca2, Acp5, mmp9, CtsK, Oscar, and Atp6v0d2. In vivo, bone mineral density and structure model index were improved by administration of CPB. In conclusion, CPB prevented osteoclast differentiation in vitro and prevented bone loss in vivo. Therefore, CPB could be a potential alternative medicine for bone diseases, such as osteoporosis.

Microplastics with adsorbed contaminants: Mechanisms and Treatment.

Plastic pollution has been a significant and widespread global issue, and the recent COVID-19 pandemic has been attributed to its worsening effect as plastics have been contaminated with the deadly infectious virus. Microplastics (MPs) may have played a role as a vector that carries hazardous microbes such as emerging bacterial threats (i.e. antibiotic resistant bacteria) and deadly viruses (e.g., coronavirus); this causes great concern over microplastics contaminated with emerging contaminants. Mitigation and treatment of MPs are challenging because of a range of factors including but not limited to physicochemical properties and composition of MPs and pH and salinity of the solution. Despite the heterogeneous nature of aquatic systems, research has overlooked interactions between contaminants and MPs under environmental conditions, degradation pathways of MPs with adsorbed contaminants, and, especially, the role of adsorbed contaminants in the efficiency of MP treatment through membrane filtration, in comparison with other treatment methods. This review aims to (1) analyze an assortment of factors that could influence the removal of MPs and mechanisms of contaminant adsorption on MPs, (2) identify mechanisms influencing membrane filtration of MPs, (3) examine the fate and transport of MPs with adsorbed contaminants, (4) evaluate membrane filtration of contaminant-adsorbing MPs in comparison to other treatment methods, and (5) draw conclusions and the future outlook based on a literature analysis.

Effect of Aging and Direction of Impulse in Suppression Head Impulse Test.

OBJECTIVE: To identify differences in the vestibulo-ocular reflex (VOR) gain value and the peak saccade velocity in the suppression video head impulse test paradigms according to the age of the subject and the direction of the impulse. STUDY DESIGN: Retrospective chart analysis. SETTING: Tertiary referral hospital. PATIENTS/INTERVENTIONS: Between October 2017 and May 2019, we enrolled subjects who had previous histories of dizziness but no dizziness over the last 1 month. MAIN OUTCOME MEASURE: We conducted cervical vestibular-evoked myogenic potential and caloric tests, as well as video head impulse tests. We excluded the subjects who had abnormal cervical vestibular-evoked myogenic potential results (asymmetry ratio of greater than 30%) and abnormal caloric test results (caloric paresis of greater than 25%). RESULTS: We included 647 subjects aged 10 to 87 years. The mean VOR gain and peak saccade velocity were maintained in subjects less than 70 years old (VOR gain, 0.991 ±â€Š0.08, peak saccade velocity, 348.47 ±â€Š142.32). However, the decreases in VOR gain and peak saccade velocity were significant in subjects over 70 years old (VOR gain, 0.928 ±â€Š0.09, peak saccade velocity, 315.51 ±â€Š0.09; p < 0.001). The mean VOR gain of the rightward impulse (1.00 ±â€Š0.09) was higher than the leftward impulse (0.96 ±â€Š0.08, p < 0.001). CONCLUSIONS: Both the VOR gain and peak saccade velocity of suppression video head impulse test paradigms declined with increasing age over 70 years. In addition, the VOR gain of the rightward impulse was higher than the leftward impulse in the right-eye recordings.

Importance of Video Head Impulse Test Parameters for Recovery of Symptoms in Acute Vestibular Neuritis.

OBJECTIVE: To examine the importance of video head impulse test parameter for recovery of symptoms in acute vestibular neuritis (AVN). STUDY DESIGN: Prospective study. SETTING: Tertiary referral hospital. PATIENTS/INTERVENTIONS: Twenty-seven patients with AVN were enrolled. We divided patients into two groups according to both dizziness handicap inventory (DHI) score and visual analog scale (VAS) at 6 months: Group F (symptoms free), DHI = 0 and VAS = 0; Group R (symptoms residual), DHI more than zero or VAS more than zero. MAIN OUTCOME MEASURE: All patients underwent video head impulse test paradigm (HIMP), and suppression head impulse test paradigm (SHIMP) initially and at 1 month. Patients were also asked to complete DHI and VAS initially, at 1 month and 6 months. We compared measured parameters between Group F and R. RESULTS: In HIMP, Group F showed higher vestibular-ocular reflex (VOR) gain, higher occurrence of covert corrective saccade (CS), lower occurrence and peak velocity of overt CS, and lower PR score than Group R at 1 month. In SHIMP, Group F showed higher VOR gain, higher occurrence and peak velocity of anti-CS, and higher PR score than Group R at 1 month. CONCLUSIONS: Above parameters of both HIMP and SHIMP at 1 month would be important factors to predict the residual symptoms in chronic phase of AVN.

Vestibular function analysis of sudden sensorineural hearing loss with dizziness.

BACKGROUND: A considerable number of patients with sudden sensorineural hearing loss (SSNHL) have been reported to have dizziness. OBJECTIVE: To analyze vestibular functions and identify the clinical characteristics of SSNHL with dizzinessMETHODS:71 patients with SSNHL who complained of dizziness were investigated retrospectively. The patients underwent vestibular function tests consisting of video-nystagmography, video head impulse test and vestibular evoked myogenic potentials. RESULTS: Among 35 patients with spontaneous nystagmus (SN), 21 showed ipsilesional posterior canal gain deficit, 11 showed a gain deficit in the posterior canal only and 9 showed both horizontal and posterior canal gain deficit in video head impulse test. In only one subject with bilateral horizontal canal gain deficit with contralesional SN, AICA infarction was observed.Among 36 patients without SN, 10 were diagnosed as benign paroxysmal positional vertigo and 5 had ipsilesional canal paresis in caloric test. Other 21 patients showed no abnormal signs in vestibular function tests. CONCLUSIONS: In VFT analysis of SSNHL with dizziness, diverse patterns were identified. In the absence of SN, no definite vestibular organ involvement was the most frequent. But in the case with SN, posterior canal deficit was most common and cerebellar ischemic stroke was rare.

The Deubiquitinating Enzyme USP20 Regulates the TNFα-Induced NF-κB Signaling Pathway through Stabilization of p62.

p62/sequestosome-1 is a scaffolding protein involved in diverse cellular processes such as autophagy, oxidative stress, cell survival and death. It has been identified to interact with atypical protein kinase Cs (aPKCs), linking these kinases to NF-κB activation by tumor necrosis factor α (TNFα). The diverse functions of p62 are regulated through post-translational modifications of several domains within p62. Among the enzymes that mediate these post-translational modifications, little is known about the deubiquitinating enzymes (DUBs) that remove ubiquitin chains from p62, compared to the E3 ligases involved in p62 ubiquitination. In this study, we first demonstrate a role of ubiquitin-specific protease USP20 in regulating p62 stability in TNFα-mediated NF-κB activation. USP20 specifically binds to p62 and acts as a positive regulator for NF-κB activation by TNFα through deubiquitinating lysine 48 (K48)-linked polyubiquitination, eventually contributing to cell survival. Furthermore, depletion of USP20 disrupts formation of the atypical PKCζ-RIPK1-p62 complex required for TNFα-mediated NF-κB activation and significantly increases the apoptosis induced by TNFα plus cycloheximide or TNFα plus TAK1 inhibitor. These findings strongly suggest that the USP20-p62 axis plays an essential role in NF-κB-mediated cell survival induced by the TNFα-atypical PKCζ signaling pathway.

Change of VOR gain and pure-tone threshold after single low-dose intratympanic gentamicin injection in Meniere's disease.

Background: Intratympanic gentamicin injection (ITG) is a well-accepted means to treat intractable Meniere's disease (MD).Aims/Objectives: To investigate change of vestibule-ocular reflex (VOR) gain and pure-tone threshold after low-dose ITG for MD.Methods: Sixteen patients with definite MD who were treated by low-dose ITG were retrospectively reviewed. We defined VOR gain difference as an amount of decreased gain in video head impulse test one month after ITG. Patients were classified into two groups: single injection vs. multiple injections. Multiple injections group was composed of patients with poor vertigo control after initial ITG who required second or third ITG later in follow up period.Results: VOR gain differences of both horizontal and posterior canal plane were higher than those of anterior canal plane. Between two groups, mean VOR gain difference of horizontal canal plane in multiple injections group was lower than that in single injection group. Only two patients showed increased pure-tone threshold more than 10 dB.Conclusion and significance: Our results suggest that ITG appears to cause a differential loss of function across three semicircular canals. Furthermore, if VOR gain difference of horizontal canal is relatively low after initial ITG, patient might have poor vertigo control and be required another ITG.

Comparing the Suppression Head Impulse Paradigm and the Head Impulse Paradigm in Vestibular Neuritis.

OBJECTIVE: To compare the results of suppression head impulse paradigm (SHIMP) and head impulse paradigm (HIMP) in acute vestibular neuritis (AVN). STUDY DESIGN: Retrospective study. SETTING: Tertiary otology clinic. PATIENTS AND INTERVENTIONS: We tested 21 patients with AVN with the HIMP, SHIMP, and caloric tests, and we analyzed the relationships between the tests' results. MAIN OUTCOME MEASURES: For this study, we adopted vestibulo-ocular reflex (VOR) gains in the SHIMP and HIMP, peak saccade velocity (PSV) of SHIMP which is another indicator of residual vestibular function, and canal paresis of caloric test. RESULTS: VOR gains showed significant correlation (R = 0.926, p < 0.001) between the SHIMP and HIMP, but VOR gains were slightly lower in the SHIMP than in the HIMP (mean difference 0.07 ±â€Š0.09, p < 0.001). The difference between the HIMP and SHIMP gains was slightly larger on the affected side (0.10 ±â€Š0.09) than on the healthy side (0.03 ±â€Š0.09). The PSV of SHIMP had significant correlation with HIMP gain and canal paresis. Sixteen of 21 patients showed 100% ipsilesional caloric canal paresis, and eight (50%) of them showed no anti-compensatory saccade (direction toward head rotation) in the SHIMP. However, they showed not extremely low VOR gain but variable VOR gain. CONCLUSION: The new parameters of SHIMP might be used as complement for evaluating vestibular function in AVN. However, the clinical impact of the saccades of SHIMP in AVN has not been revealed clearly yet. This question should be investigated in further studies.

The deubiquitinating enzyme PSMD14 facilitates tumor growth and chemoresistance through stabilizing the ALK2 receptor in the initiation of BMP6 signaling pathway.

BACKGROUND: Although bone morphogenetic protein 6 (BMP6) signaling pathway has been implicated in many types of cancer, its role of tumorigenesis seems to be controversial and its ubiquitin-modifying mechanisms have not been fully addressed. Our study was designed to investigate how BMP6 signaling pathway is regulated by ubiquitin-modifying systems and to address molecular and clinical significance in colorectal cancers. METHODS: Human deubiquitnase (DUB) siRNA library was used to screen the specific DUB, named PSMD14, involved in BMP6 signaling pathway. Immunoblot, immunoprecipitation and ubiquitination assays were used to analyze targets of the PSMD14. A role of PSMD14-mediated BMP6 signaling pathway for malignant cancer progression was investigated using in vitro and in vivo model of colorectal cancers as well as clinical samples of colorectal cancer patients. FINDINGS: The deubiquitinase PSMD14 acts as a positive regulator for the initiation of the BMP6 signaling pathway through deubiquitinating K48-linked ALK2 type I receptor ubiquitination mediated by Smurf1 E3 ligase, resulting in increased stability of the ALK2. This role of PSMD14 is independent of its intrinsic role in the 26S proteasome system. Furthermore, either PSMD14 or ALK2 depletion significantly decreases tumorigenesis of HCT116 colorectal cancer cells in a xenograft model as well as cancer stemness/chemoresistance, and expression of the PSMD14 and ALK2 gene are correlated with malignant progression and the survival of colorectal cancer patients. INTERPRETATION: These findings suggest that the PSMD14-ALK2 axis plays an essential role in initiation of the BMP6 signaling pathway and contributes to tumorigenesis and chemoresistance of colorectal cancers.