This retrospective clinical study was performed to evaluate whether a visual or quantitative method is more valuable for assessing painful temporomandibular disorder (TMD) using bone scintigraphy results.In total, 230 patients (172 women and 58 men) with TMD were enrolled. All patients were questioned about their temporomandibular joint (TMJ) pain. Bone scintigraphic data were acquired in all patients, and images were analyzed by visual and quantitative methods using the TMJ-to-skull uptake ratio. The diagnostic performances of both bone scintigraphic assessment methods for painful TMD were compared.In total, 241 of 460 TMJs (52.4%) were finally diagnosed with painful TMD. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the visual analysis for diagnosing painful TMD were 62.8%, 59.6%, 58.6%, 63.8%, and 61.1%, respectively. The quantitative assessment showed the ability to diagnose painful TMD with a sensitivity of 58.8% and specificity of 69.3%. The diagnostic ability of the visual analysis for diagnosing painful TMD was not significantly different from that of the quantitative analysis.Visual bone scintigraphic analysis showed a diagnostic utility similar to that of quantitative assessment for the diagnosis of painful TMD.

Stress induced premature senescence (SIPS) occurs after exposure to many different sublethal stresses including H(2)O(2), hyperoxia, or tert-butylhydroperoxide. Human mesenchymal stem cells (hMSCs) exhibit limited proliferative potential in vitro, the so-called Hayflick limit. According to the free-radical theory, reactive oxygen species (ROS) might be the candidates responsible for senescence and age-related diseases. H(2)O(2) may be responsible for the production of high levels of ROS, in which the redox balance is disturbed and the cells shift into a state of oxidative stress, which subsequently leads to premature senescence with shortening telomeres. H(2)O(2) has been the most commonly used inducer of SIPS, which shares features of replicative senescence (RS) including a similar morphology, senescence-associated β-galactosidase activity, cell cycle regulation, etc. Therefore, in this study, the senescence of hMSC during SIPS was confirmed using a range of different analytical methods. In addition, we determined five differentially expressed spots in the 2-DE map, which were identified as Annexin A2 (ANXA2), myosin light chain 2 (MLC2), peroxisomal enoyl-CoA hydratase 1 (ECH1), prosomal protein P30-33K (PSMA1) and mutant β-actin by ESI-Q-TOF MS/MS. Also, proton ((1)H) nuclear magnetic resonance spectroscopy (NMR) was used to elucidate the difference between metabolites in the control and hMSCs treated with H(2)O(2). Among these metabolites, choline and leucine were identified by (1)H-NMR as up-regulated metabolites and glycine and proline were identified as down-regulated metabolites.

Emergency nurses are expected to provide required nursing services by using their professional expertise to reduce the risk posed by disasters. Thus, emergency nurses' disaster nursing core competencies are essential for coping with disasters. The purpose of the study reported here was to identify factors influencing the disaster nursing core competencies of emergency nurses.

Hereditary spastic paraplegia (HSP) is characterized by progressive spasticity and weakness of the lower extremities. Additional findings include ataxia, extrapyramidal signs, and dementia. Pendular nystagmus (PN) has been reported in some subtypes of HSP caused by PLP1 (SPG2) or paraplegin (SPG7) mutation. To describe the patterns and modulation of PN in HSP, we performed eye movement recording using video-oculography in a Korean family with HSP and PN. The PN was convergent-divergent in the oblique plane with a frequency of 6 to 7Hz and maximum amplitude at about 1.5°. The nystagmus diminished briefly after blinks and horizontal saccades, and decreased during eccentric gaze and convergence. Horizontal saccades shifted the phase of the oscillations. During lateral gazes, the PN increased in the abducting eye, but decreased in the adducting eye. Vibratory stimuli decreased the nystagmus mostly in the left but not in the right eye. No pathogenic mutation was found in the genetic loci known for causing spastic paraplegia by whole-exome sequencing. The unusual features and modulation of PN in our patients with HSP emphasize the role of disconjugate and disjunctive capabilities of the brain in ocular motor control, and exemplify what can go wrong.

Chemotherapy is used for childhood cancer but may lead to infertility in patients. Spermatogonia stem cells are present in the testes of prepubertal boys, although they do not produce sperm at this age. Herein, we evaluated the toxicity of cisplatin, a known medicine for cancer treatment, in neonatal mouse testes using in vitro organ culture. Mouse testicular fragments (MTFs) derived from 5.5-d postpartum mouse testes were exposed to 1-10 μg/mL cisplatin. The results showed that cisplatin significantly downregulated the expression of germ cell marker genes, including differentiated and undifferentiated, in a dose-dependent manner. In particular, a high dose of cisplatin (10 μg/mL) led to germ cell depletion. In addition, the expression levels of the Sertoli cell marker gene, the number of SOX9+ Sertoli cells, and the levels of SOX9 protein were markedly decreased in cisplatin-treated MTFs compared to controls. The mRNA expression of steroidogenic enzyme-related genes significantly increased in cisplatin-treated MTFs, except for estrogen receptor 1 (Esr1). Consistently, 3β-hydroxysteroid dehydrogenase protein was also observed in the interstitial regions of cisplatin-treated MTFs. Altogether, our findings showed a significant impairment in germ cell development, Sertoli cell survival, and steroidogenesis in the MTFs of cisplatin-treated mice.

Objectives: The aim of this study was to delineate the clinical and laboratory features suggestive of intralabyrinthine schwannoma (ILS). Methods: We compared the clinical features of 16 patients with ILS, who had been diagnosed at the Seoul National University Bundang Hospital from 2003 to 2018, with those of 18 patients with symptomatic unilateral intracanalicular schwannoma and randomly selected 20 patients with definite or probable unilateral Meniere's disease (MD). Results: Patients with ILS presented with either recurrent spontaneous dizziness/vertigo combined with auditory symptoms (n = 8), isolated auditory symptoms without dizziness/vertigo (n = 7), or recurrent spontaneous dizziness/vertigo without auditory symptoms (n = 1). Most patients reported no improvement (n = 11) or worsening (n = 1) of the symptoms despite medical treatments including intratympanic (n = 5) or intravenous steroids (n = 2). Conventional brain MRIs failed to detect ILS in about a half of the patients (7/16, 44%). However, ILS showed a filling defect on 3-dimensional (3D) heavily T2-weighted MRIs (n = 12), and nodular enhancement on 3D contrast-enhanced T1 (n = 15) or FLAIR MRIs (n = 13) targeted for the inner ear. Compared to MD or intracanalicular schwannoma, ILS showed mostly abnormal head-impulse tests (HITs, p = 0.001). In contrast, the incidence of canal paresis did not differ among the groups (p = 0.513). Conclusion: ILS may mimic MD by presenting recurrent dizziness/vertigo and auditory symptoms. ILS should be suspected in patients with recurrent audiovestibulopathy especially when (1) the duration of the dizziness is not typical for MD, (2) the patients do not respond to medical treatments, or (3) HITs are abnormal.

Colostrum, which contains various immune and growth factors, aids wound healing by promoting keratinocyte proliferation. Aquaporins (AQPs) are small, hydrophobic membrane proteins that regulate cellular water retention. However, few studies have examined the effect of processed colostrum whey on AQP-3 expression in human skin cells. Here, we investigated the effect of milk, colostrum, fermented milk, and fermented colostrum whey on AQP-3 expression in keratinocyte HaCaT cells. Concentrations of 100-400 μg/mL of fermented colostrum whey were found to induce HaCaT cell proliferation. AQP-3 was found to be expressed exclusively in HaCaT cells. AQP-3 expression was significantly increased in 100 μg/mL fermented colostrum whey-treated cells compared with that in controls. Moreover, fermented colostrum increased p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation, but not ERK1/2 phosphorylation. Thus, our results suggest that fermented colostrum whey increased AQP-3 expression in, and the proliferation of, keratinocytes via JNK and p38 MAPK activation.

The use of unmodified starch in frozen foods can cause extremely undesirable textural changes after the freeze-thaw process. In this study, using cyclodextrin glucanotransferase (CGTase) and branching enzymes, an amylopectin cluster with high freeze-thaw stability was produced, and was named CBAC. It was found to have a water solubility seven times higher, and a molecular weight 77 times lower, than corn starch. According to the results of a differential scanning calorimetry (DSC) analysis, dough containing 5% CBAC lost 19% less water than a control dough after three freeze-thaw cycles. During storage for 7 days at 4 °C, bread produced using CBAC-treated dough exhibited a 14% smaller retrogradation peak and 37% less hardness than a control dough, suggesting that CBAC could be a potential candidate for clean label starch, providing high-level food stability under repeated freeze-thaw conditions.

As the efficacy of current diagnostic methods for myasthenia gravis (MG) remains suboptimal, there is ongoing interest in developing more effective diagnostic models. As oculomotor fatigability is one of the most common and diagnostic symptoms in MG, we aimed to investigate whether quantitative saccadic and smooth-pursuit fatigability analyses with video-oculography (VOG) are useful for diagnosis of MG.

Ischemia of the inner ear may damage the otoconia. However, no study has explored any changes in the configuration of otoconia after transient ischemia of the labyrinth.

Episodic ataxia (EA) is a rare neurological condition characterized by recurrent spells of truncal ataxia and incoordination. Five genes (KCNA1, CACNA1A, CACNB4, SLC1A3, and UBR4) have been linked to EA. Despite extensive efforts to genetically diagnose EA, many patients remain still undiagnosed. Whole-exome sequencing was carried out in 39 Korean patients with EA to identify pathogenic mutations of the five known EA genes. We also evaluated 40 candidate genes that cause EA as a secondary phenotype or cerebellar ataxia. Eighteen patients (46%) revealed genetic information useful for establishing a molecular diagnosis of EA. In 11 patients, 16 pathogenic mutations were detected in three EA genes. These included nine mutations in CACNA1A, three in SLC1A3, and four in UBR4. Three patients had mutations in two genes, either CACNA1A and SLC1A3 or CACNA1A and UBR4, suggesting that SLC1A3 and UBR4 may act as genetic modifiers with synergic effects on the abnormal presynaptic activity caused by CACNA1A mutations. In seven patients with negative results for screening of EA genes, potential pathogenic mutations were identified in the candidate genes ATP1A2, SCN1A, TTBK2, TGM6, FGF14, and KCND3. This study demonstrates the genetic heterogeneity of Korean EA, and indicates that whole-exome sequencing may be useful for molecular genetic diagnosis of EA.

Patients with vestibular migraine are susceptible to motion sickness. This study aimed to determine whether the severity of posture instability is related to the susceptibility to motion sickness. We used a visual motion paradigm with two conditions of the stimulated retinal field and the head posture to quantify postural stability while maintaining a static stance in 18 patients with vestibular migraine and in 13 age-matched healthy subjects. Three parameters of postural stability showed differences between VM patients and controls: RMS velocity (0.34 ± 0.02 cm/s vs. 0.28 ± 0.02 cm/s), RMS acceleration (8.94 ± 0.74 cm/s2 vs. 6.69 ± 0.87 cm/s2), and sway area (1.77 ± 0.22 cm2 vs. 1.04 ± 0.25 cm2). Patients with vestibular migraine showed marked postural instability of the head and neck when visual stimuli were presented in the retinal periphery. The pseudo-Coriolis effect induced by head roll tilt was not responsible for the main differences in postural instability between patients and controls. Patients with vestibular migraine showed a higher visual dependency and low stability of the postural control system when maintaining quiet standing, which may be related to susceptibility to motion sickness.

JIB-04, a pan-histone lysine demethylase (KDM) inhibitor, targets drug-resistant cells, along with colorectal cancer stem cells (CSCs), which are crucial for cancer recurrence and metastasis. Despite the advances in CSC biology, the effect of JIB-04 on liver CSCs (LCSCs) and the malignancy of hepatocellular carcinoma (HCC) has not been elucidated yet. Here, we showed that JIB-04 targeted KDMs, leading to the growth inhibition and cell cycle arrest of HCC, and abolished the viability of LCSCs. JIB-04 significantly attenuated CSC tumorsphere formation, growth, relapse, migration, and invasion in vitro. Among KDMs, the deficiency of KDM4B, KDM4D, and KDM6B reduced the viability of the tumorspheres, suggesting their roles in the function of LCSCs. RNA sequencing revealed that JIB-04 affected various cancer-related pathways, especially the PI3K/AKT pathway, which is crucial for HCC malignancy and the maintenance of LCSCs. Our results revealed KDM6B-dependent AKT2 expression and the downregulation of E2F-regulated genes via JIB-04-induced inhibition of the AKT2/FOXO3a/p21/RB axis. A ChIP assay demonstrated JIB-04-induced reduction in H3K27me3 at the AKT2 promoter and the enrichment of KDM6B within this promoter. Overall, our results strongly suggest that the inhibitory effect of JIB-04 on HCC malignancy and the maintenance of LCSCs is mediated via targeting the KDM6B-AKT2 pathway, indicating the therapeutic potential of JIB-04.

Objectives: To investigate the deficits of spatial memory and navigation from unilateral vestibular deafferentation (UVD) and to determine the efficacy of galvanic vestibular stimulation (GVS) for recovery from these deficits using a mouse model of unilateral labyrinthectomy (UL). Methods: Thirty-six male C57BL/6 mice were allocated into three groups that comprise a control group and two experimental groups, UVD with (GVS group) and without GVS intervention (non-GVS group). In the experimental groups, we assessed the locomotor and cognitive behavioral function before (baseline) and 3, 7, and 14 days after surgical UL, using the open field (OF), Y maze, and Morris water maze (MWM) tests. In the GVS group, the stimulations were applied for 30 min daily from postoperative day (POD) 0-4 via the electrodes inserted subcutaneously close to both bony labyrinths. Results: Locomotion and spatial cognition were significantly impaired in the mice with UVD non-GVS group compared to the control group. GVS significantly accelerated recovery of locomotion compared to the control and non-GVS groups on PODs 3 (p < 0.001) and 7 (p < 0.05, Kruskal-Wallis and Mann-Whitney U tests) in the OF and Y maze tests. The mice in the GVS group were better in spatial working memory assessed with spontaneous alternation performance and spatial reference memory assessed with place recognition during the Y maze test than those in the non-GVS group on POD 3 (p < 0.001). In addition, the recovery of long-term spatial navigation deficits during the MWM, as indicated by the escape latency and the probe trial, was significantly better in the GVS group than in the non-GVS group 2 weeks after UVD (p < 0.01). Conclusions: UVD impairs spatial memory, navigation, and motor coordination. GVS accelerated recoveries in short- and long-term spatial memory and navigation, as well as locomotor function in mice with UVD, and may be applied to the patients with acute unilateral vestibular failure.

Objectives: To elucidate the mechanism of paroxysmal central positional nystagmus (CPN) by determining the effects of head rotation velocity on the intensity of paroxysmal downbeat nystagmus induced during straight head hanging (SHH). Methods: We recruited 21 patients with paroxysmal downbeat CPN induced during SHH at the Dizziness Center of Seoul National University Bundang Hospital from September 2018 to July 2019. Twenty-one patients had manual SHH at two different lying velocities, the fast (routine) and slow, and they also underwent SHH at different rotation velocities of 10, 20, 30, and 40 °/s using a motorized rotation chair. Induced nystagmus was recorded using video-oculography and the maximum slow phase velocity (SPV) and time constant (TC) of the induced paroxysmal nystagmus were analyzed. Results: During manual SHH, paroxysmal downbeat nystagmus was invariably induced during routine SHH (fast lying down), but absent or minimal during slow positioning. During motorized SHH, the median of maximum intensity of downbeat nystagmus increased from 7.6 °/s (0-16.9) to 14.0 °/s (0-32.5), 16.5 °/s (0-44.6), and 19.1 °/s (0-55.2) as the rotation velocity increased from 10 to 20, 30, and 40°/s (P < 0.001, P < 0.001, P = 0.004; linear mixed models). In contrast, the TCs of paroxysmal downbeat CPN remained unchanged (P = 0.558, P = 0.881, P = 0.384, linear mixed models). Conclusions: The dependence of nystagmus intensity on head rotation velocity supports a disinhibited and exaggerated inhibitory rebound of the canal signals as the mechanism of paroxysmal CPN.

We present a novel approach for computing link-based similarities among objects accurately by utilizing the link information pertaining to the objects involved. We discuss the problems with previous link-based similarity measures and propose a novel approach for computing link based similarities that does not suffer from these problems. In the proposed approach each target object is represented by a vector. Each element of the vector corresponds to all the objects in the given data, and the value of each element denotes the weight for the corresponding object. As for this weight value, we propose to utilize the probability of reaching from the target object to the specific object, computed using the "Random Walk with Restart" strategy. Then, we define the similarity between two objects as the cosine similarity of the two vectors. In this paper, we provide examples to show that our approach does not suffer from the aforementioned problems. We also evaluate the performance of the proposed methods in comparison with existing link-based measures, qualitatively and quantitatively, with respect to two kinds of data sets, scientific papers and Web documents. Our experimental results indicate that the proposed methods significantly outperform the existing measures.

Abnormal autophagy is frequently observed during dopaminergic neurodegeneration in Parkinson's disease (PD). However, it is not yet firmly established whether active autophagy is beneficial or pathogenic with respect to dopaminergic cell loss. Staurosporine, a common inducer of apoptosis, is often used in mechanistic studies of dopaminergic cell death. Here we report that staurosporine activates both autophagy and mitophagy simultaneously during dopaminergic neuronal cell death, and evaluate the physiological significance of these processes during cell death. First, staurosporine treatment resulted in induction of autophagy in more than 75% of apoptotic cells. Pharmacological inhibition of autophagy by bafilomycin A1 decreased significantly cell viability. In addition, staurosporine treatment resulted in activation of the PINK1-Parkin mitophagy pathway, of which deficit underlies some familial cases of PD, in the dopaminergic neuronal cell line, SN4741. The genetic blockade of this pathway by PINK1 null mutation also dramatically increased staurosporine-induced cell death. Taken together, our data suggest that staurosporine induces both mitophagy and autophagy, and that these pathways exert a significant neuroprotective effect, rather than a contribution to autophagic cell death. This model system may therefore be useful for elucidating the mechanisms underlying crosstalk between autophagy, mitophagy, and cell death in dopaminergic neurons.

Acrylic pressure-sensitive adhesives (PSAs) are used as fixatives between layers of a display. PSAs' function is an important factor that determines the performance of the display. Of the various display types available, the touch screen panel (TSP) of smart devices is firmly related to the relative permittivity of the elementals. Therefore, adjusting the relative permittivity of the PSA is indispensable for driving the TSP. Accordingly, selected acrylic pre-polymers were polymerized and the pre-polymer was blended and cross-linked with monomers with different chemical structure to adjust the relative permittivity. The monomers were hexametyldisiloxane (HMDS), N-vinylcaprolactam (NVC), tert-butyl acrylate (TBA), and isooctadecyl acrylate (ISTA). The gel fraction and transmittance as a function of the monomers show a similar result to the pure acrylic PSA. However, the gel fraction value decreased to about 90% and the transmittance decreased to about 85%, due to the immiscibility between nonpolar HMDS and acrylic PSA. On the other hand, the adhesion properties were improved when NVC was added because of the polarity of the nitrogen group. In addition, the relative permittivity of the PSA decreased regardless of the monomer chosen. There was, however, a difference in the optimal content of each monomer, and NVC decreased from 4 phr content to about 3.4 in reducing relative permittivity. Through the above results, it was confirmed that NVC having a nitrogen group is most advantageous in lowering adhesion properties and relative permittivity, and necessitates further research based on the findings.

Objectives: To reveal the neural basis of Wernicke's encephalopathy (WE) with impaired vestibulo-ocular reflex (VOR), we evaluated resting-state functional connectivity (rs-fc) in the vestibular processing brain regions. Methods: Rs-fc between the vestibular regions and the rest of the brain were compared with neurotological features including the head-impulse tests (vHIT) and caloric responses in patients with WE (n = 5, mean age 53.4 ± 10 years) and healthy controls (n = 20, mean age 55.0 ± 9.2 years). Rs-fc analyses employed a region of interest (ROI)-based approach using regions selected a priori that participate in vestibular processing including the cerebellar vermis, insula, parietal operculum, and calcarine cortex. Results: The main neurologic findings for patients with WE were mental changes; gait ataxia; spontaneous and gaze-evoked nystagmus (GEN); and bilaterally positive HIT for the horizontal canals. Video HIT documented bilateral horizontal canal dysfunction with decreased gain and corrective saccades. Caloric irrigation and rotation chair testing revealed prominent bilateral horizontal canal paresis. Patients with WE also had decreased spatial memory, which substantially recovered after treatments. Functional connections at the predefined seed regions, including the insular cortex and parietal operculum, were attenuated in the WE group compared to healthy controls. Conclusions: WE is related to impaired VOR and visuospatial dysfunction, and fMRI documented changes in the rs-fc of multisensory vestibular processing regions including the insula, parietal operculum, and superior temporal gyrus, which participate in integration of vestibular perception.

Purpose: Patients with benign paroxysmal positional vertigo (BPPV) experience gait unsteadiness not only during the attacks but also between the spells. This study aimed to measure gait changes in BPPV and determine whether these changes are associated with the involved canal or lesion side. Methods: We recruited 33 patients with a diagnosis of unilateral BPPV. Patients with other vestibular or central nervous system disorders were excluded. Gait was assessed using the GAITRite™ system before and after canalith repositioning treatment (CRT). Results: After CRT, improvements were observed in various gait parameters including velocity (p < 0.001), cadence (p < 0.001), functional ambulation profile (p = 0.011), and the coefficient of variation of stride time (p = 0.004). Exploration of the center of pressure (COP) distribution also revealed improved stabilization during locomotion after CRT. The spatiotemporal gait variables did not differ between the patients with horizontal- and posterior-canal BPPV, or between the ipsilesional and contralesional sides before CRT. Conclusions: The gait parameters reflecting velocity and rhythmicity along with stability of COP distribution improved after the resolution of BPPV. Episodic overexcitation of semicircular canal may impair the vestibular information that is integrated with the other reference afferent systems and lead to impaired gait performance.