Publications by authors named "Woo-Hyung Lee"

56 Publications

Effect of robot-assisted gait training on gait automaticity in Parkinson disease: A prospective, open-label, single-arm, pilot study.

Medicine (Baltimore) 2021 Feb;100(5):e24348

Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Hospital.

Abstract: Gait automaticity is reduced in patients with Parkinson disease (PD) due to impaired habitual control. The aim of this study was to investigate the effect of robot-assisted gait training (RAGT) on gait automaticity as well as gait speed and balance in patients with PD.This study was a prospective, open-label, single-arm, pilot study. We planned to recruit 12 patients with idiopathic PD. Participants received 12 sessions of RAGT using exoskeleton-type robotic device. Sessions were 45-minute each, 3 days a week, for 4 consecutive weeks using an exoskeleton-type gait robot. The primary outcome was the percentage of dual-task interference measured by the 10-Meter Walk Test (10MWT) under single and dual-task (cognitive and physical) conditions. Secondary outcomes were the Berg Balance Scale and Korean version of the Falls Efficacy Scale-International. All measures were evaluated before treatment (T0), after treatment (T1), and 1-month post-treatment (T2).Twelve patients were enrolled and 1 dropped out. Finally, 11 patients with idiopathic PD were analyzed. The mean age of 11 patients (5 males) was 66.46 ± 5.66 years, and disease duration was 112.91 ± 50.19 months. The Hoehn and Yahr stages were 2.5 in 8 patients and 3 in 3 patients. Linear mixed-effect model analysis showed a significant change over time only in single-task gait speed of the 10MWT (P = .007), but not in dual-task gait speed, dual-task interferences, and Korean version of the Falls Efficacy Scale-International. Cognitive dual-task interference significantly increased (P = .026) at T1, but not at T2 (P = .203). No significant changes were observed for physical dual-task interference at T1 and T2. Single-task gait speed of the 10MWT was significantly increased at T1 (P = .041), but not at T2 (P = .445). There were no significant changes in the dual-task gait speed of 10MWT. A significant improvement was observed in Berg Balance Scale score at T1 and T2 (P = .004 and P = .024, respectively).In this pilot study, despite improvement in walking speed and balance, gait automaticity in patients with PD was not improved by RAGT using an exoskeleton-type robot. Additional therapeutic components may be needed to improve gait automaticity using RAGT in patients with PD.
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http://dx.doi.org/10.1097/MD.0000000000024348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870221PMC
February 2021

Hyoid kinematic features for poor swallowing prognosis in patients with post-stroke dysphagia.

Sci Rep 2021 01 14;11(1):1471. Epub 2021 Jan 14.

Department of Biomedical Engineering, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Identification of prognostic factors for swallowing recovery in patients with post-stroke dysphagia is crucial for determining therapeutic strategies. We aimed at exploring hyoid kinematic features of poor swallowing prognosis in patients with post-stroke dysphagia. Of 122 patients who experienced dysphagia following ischemic stroke, 18 with poor prognosis, and 18 age- and sex-matched patients with good prognosis were selected and retrospectively reviewed. Positional data of the hyoid bone during swallowing were obtained from the initial videofluoroscopic swallowing study after stroke onset. Normalized hyoid profiles of displacement/velocity and direction angle were analyzed using functional regression analysis, and maximal or mean values were compared between the good and poor prognosis patient groups. Kinematic analysis showed that maximal horizontal displacement (P = 0.031) and velocity (P = 0.034) in forward hyoid motions were significantly reduced in patients with poor prognosis compared to those with good prognosis. Mean direction angle for the initial swallowing phase was significantly lower in patients with poor prognosis than in those with good prognosis (P = 0.0498). Our study revealed that reduced horizontal forward and altered initial backward motions of the hyoid bone during swallowing can be novel kinematic features indicating poor swallowing prognosis in patients with post-stroke dysphagia.
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http://dx.doi.org/10.1038/s41598-020-80871-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809117PMC
January 2021

Development of a Novel Prognostic Model to Predict 6-Month Swallowing Recovery After Ischemic Stroke.

Stroke 2020 02 30;51(2):440-448. Epub 2019 Dec 30.

From the Department of Biomedical Engineering, Seoul National University College of Medicine, Republic of Korea (W.H.L., M.H.L., S.K.).

Background and Purpose- The aim of this study was to explore clinical and radiological prognostic factors for long-term swallowing recovery in patients with poststroke dysphagia and to develop and validate a prognostic model using a machine learning algorithm. Methods- Consecutive patients (N=137) with acute ischemic stroke referred for swallowing examinations were retrospectively reviewed. Dysphagia was monitored in the 6 months poststroke period and then analyzed using the Kaplan-Meier method and Cox regression model for clinical and radiological factors. Bayesian network models were developed using potential prognostic factors to classify patients into those with good (no need for tube feeding or diet modification for 6 months) and poor (tube feeding or diet modification for 6 months) recovery of swallowing function. Results- Twenty-four (17.5%) patients showed persistent dysphagia for the first 6 months with a mean duration of 65.6 days. The time duration of poststroke dysphagia significantly differed by tube feeding status, clinical dysphagia scale, sex, severe white matter hyperintensities, and bilateral lesions at the corona radiata, basal ganglia, or internal capsule (CR/BG/IC). Among these factors, tube feeding status (<0.001), bilateral lesions at CR/BG/IC (=0.001), and clinical dysphagia scale (=0.042) were significant prognostic factors in a multivariate analysis using Cox regression models. The tree-augmented network classifier, based on 10 factors (sex, lesions at CR, BG/IC, and insula, laterality, anterolateral territory of the brain stem, bilateral lesions at CR/BG/IC, severe white matter hyperintensities, clinical dysphagia scale, and tube feeding status), performed better than other benchmarking classifiers developed in this study. Conclusions- Initial dysphagia severity and bilateral lesions at CR/BG/IC are revealed to be significant prognostic factors for 6-month swallowing recovery. The prediction of 6-month swallowing recovery was feasible based on clinical and radiological factors using the Bayesian network model. We emphasize the importance of bilateral subcortical lesions as prognostic factors that can be utilized to develop prediction models for long-term swallowing recovery.
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http://dx.doi.org/10.1161/STROKEAHA.119.027439DOI Listing
February 2020

Target-oriented motor imagery for grasping action: different characteristics of brain activation between kinesthetic and visual imagery.

Sci Rep 2019 09 4;9(1):12770. Epub 2019 Sep 4.

Department of Rehabilitation Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Motor imagery (MI) for target-oriented movements, which is a basis for functional activities of daily living, can be more appropriate than non-target-oriented MI as tasks to promote motor recovery or brain-computer interface (BCI) applications. This study aimed to explore different characteristics of brain activation among target-oriented kinesthetic imagery (KI) and visual imagery (VI) in the first-person (VI-1) and third-person (VI-3) perspectives. Eighteen healthy volunteers were evaluated for MI ability, trained for the three types of target-oriented MIs, and scanned using 3 T functional magnetic resonance imaging (fMRI) under MI and perceptual control conditions, presented in a block design. Post-experimental questionnaires were administered after fMRI. Common brain regions activated during the three types of MI were the left premotor area and inferior parietal lobule, irrespective of the MI modalities or perspectives. Contrast analyses showed significantly increased brain activation only in the contrast of KI versus VI-1 and KI versus VI-3 for considerably extensive brain regions, including the supplementary motor area and insula. Neural activity in the orbitofrontal cortex and cerebellum during VI-1 and KI was significantly correlated with MI ability measured by mental chronometry and a self-reported questionnaire, respectively. These results can provide a basis in developing MI-based protocols for neurorehabilitation to improve motor recovery and BCI training in severely paralyzed individuals.
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http://dx.doi.org/10.1038/s41598-019-49254-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726765PMC
September 2019

Differential kinematic features of the hyoid bone during swallowing in patients with Parkinson's disease.

J Electromyogr Kinesiol 2019 Aug 16;47:57-64. Epub 2019 May 16.

Department of Biomedical Engineering, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea; Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. Electronic address:

This study aimed to investigate spatiotemporal characteristics of the hyoid bone during swallowing in patients with Parkinson's disease (PD) and dysphagia. Spatiotemporal data of the hyoid bone was obtained from videofluoroscopic images of 69 subjects (23 patients with PD, 23 age- and sex-matched healthy elderly controls, and 23 healthy young controls). Normalized profiles of displacement/velocity were analyzed during different periods (percentile) of swallowing using functional regression analysis, and the maximal values were compared between the groups. Maximal horizontal displacement and velocity were significantly decreased during the initial backward (P = 0.006 and P < 0.001, respectively) and forward (P = 0.008 and P < 0.001, respectively) motions in PD patients compared to elderly controls. Maximal vertical velocity was significantly lower in PD patients than in elderly controls (P = 0.001). No significant difference was observed in maximal displacement and velocity in both horizontal and vertical planes between the healthy elderly and young controls, although horizontal displacement was significantly decreased during the forward motion (51st-57th percentiles) in the elderly controls. In conclusion, reduced horizontal displacement and velocity of the hyoid bone during the forward motion would be due to combined effects of disease and aging, whereas those over the initial backward motion may be considered specific to patients with PD.
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http://dx.doi.org/10.1016/j.jelekin.2019.05.011DOI Listing
August 2019

Inertial Measurement Unit Based Upper Extremity Motion Characterization for Action Research Arm Test and Activities of Daily Living.

Sensors (Basel) 2019 Apr 14;19(8). Epub 2019 Apr 14.

Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 03080, Korea.

In practical rehabilitation robot development, it is imperative to pre-specify the critical workspace to prevent redundant structure. This study aimed to characterize the upper extremity motion during essential activities in daily living. An IMU-based wearable motion capture system was used to access arm movements. Ten healthy subjects performed the Action Research Arm Test (ARAT) and six pre-selected essential daily activities. The Euler angles of the major joints, and acceleration from wrist and hand sensors were acquired and analyzed. The size of the workspace for the ARAT was 0.53 (left-right) × 0.92 (front-back) × 0.89 (up-down) m for the dominant hand. For the daily activities, the workspace size was 0.71 × 0.70 × 0.86 m for the dominant hand, significantly larger than the non-dominant hand ( ≤ 0.011). The average range of motion (RoM) during ARAT was 109.15 ± 18.82° for elbow flexion/extension, 105.23 ± 5.38° for forearm supination/pronation, 91.99 ± 0.98° for shoulder internal/external rotation, and 82.90 ± 22.52° for wrist dorsiflexion/volarflexion, whereas the corresponding range for daily activities were 120.61 ± 23.64°, 128.09 ± 22.04°, 111.56 ± 31.88°, and 113.70 ± 18.26°. The shoulder joint was more abducted and extended during pinching compared to grasping posture ( < 0.001). Reaching from a grasping posture required approximately 70° elbow extension and 36° forearm supination from the initial position. The study results provide an important database for the workspace and RoM for essential arm movements.
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http://dx.doi.org/10.3390/s19081782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514920PMC
April 2019

Vision-aided brain-machine interface training system for robotic arm control and clinical application on two patients with cervical spinal cord injury.

Biomed Eng Online 2019 Feb 11;18(1):14. Epub 2019 Feb 11.

Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, 03080, South Korea.

Background: While spontaneous robotic arm control using motor imagery has been reported, most previous successful cases have used invasive approaches with advantages in spatial resolution. However, still many researchers continue to investigate methods for robotic arm control with noninvasive neural signal. Most of noninvasive control of robotic arm utilizes P300, steady state visually evoked potential, N2pc, and mental tasks differentiation. Even though these approaches demonstrated successful accuracy, they are limited in time efficiency and user intuition, and mostly require visual stimulation. Ultimately, velocity vector construction using electroencephalography activated by motion-related motor imagery can be considered as a substitution. In this study, a vision-aided brain-machine interface training system for robotic arm control is proposed and developed.

Methods: The proposed system uses a Microsoft Kinect to detect and estimates the 3D positions of the possible target objects. The predicted velocity vector for robot arm input is compensated using the artificial potential to follow an intended one among the possible targets. Two participants with cervical spinal cord injury trained with the system to explore its possible effects.

Results: In a situation with four possible targets, the proposed system significantly improved the distance error to the intended target compared to the unintended ones (p < 0.0001). Functional magnetic resonance imaging after five sessions of observation-based training with the developed system showed brain activation patterns with tendency of focusing to ipsilateral primary motor and sensory cortex, posterior parietal cortex, and contralateral cerebellum. However, shared control with blending parameter α less than 1 was not successful and success rate for touching an instructed target was less than the chance level (= 50%).

Conclusions: The pilot clinical study utilizing the training system suggested potential beneficial effects in characterizing the brain activation patterns.
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http://dx.doi.org/10.1186/s12938-019-0633-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371594PMC
February 2019

Effect of Dexmedetomidine Combined Anesthesia on Motor evoked Potentials During Brain Tumor Surgery.

World Neurosurg 2019 Mar 26;123:e280-e287. Epub 2018 Nov 26.

Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Dexmedetomidine (DEX) is used as an adjunct to total intravenous anesthesia. However, its effect on intraoperative neurophysiologic monitoring (IOM) during brain tumor surgery remains controversial. The aim of this study was to explore the effect of DEX on IOM during brain tumor surgery.

Methods: Seventy-eight consecutive patients (DEX group, n = 40; control group, n = 38), who underwent brain tumor surgery with IOM, were retrospectively reviewed. The outcomes included the predictability, laterality of alterations, and stimulation parameters of transcranial motor evoked potentials (tcMEPs) and somatosensory evoked potentials (SSEPs).

Results: The predictability of tcMEPs for postoperative motor outcomes showed a higher false-positive rate in the DEX group than in the control group (27.5% vs. 5.3%, P = 0.047). Bilateral alterations were observed only in the DEX group (31.3%; P = 0.053). Compared with the control group, the DEX group required significantly higher intensity (377.5 ± 48.0 vs. 347.1 ± 30.0 mV; P = 0.001) and repetition rate (6.0 ± 0.2 vs. 5.7 ± 0.5 pulse/train; P = 0.001) of transcranial electric stimulation to evoke adequate tcMEPs. The SSEP results were comparable between both groups. In the DEX group, false-positive tcMEPs changes occurred 222.2 ± 70.5 minutes (range, 95-342 minutes) after the induction of anesthesia. In addition, the patients who were administered DEX under bispectral index monitoring (n = 12) showed a significantly higher false-positive rate than shown by the control group (50.5% vs. 5.3%; P = 0.003).

Conclusions: This study showed that DEX had significant effects on tcMEPs during IOM in brain tumor surgery. Because the high false-positive rate could decrease the accuracy of IOM, outcomes after using DEX should be cautiously interpreted.
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http://dx.doi.org/10.1016/j.wneu.2018.11.152DOI Listing
March 2019

Unravelling interrelations between chemical composition and refractive index dispersion of infrared-transmitting chalcogenide glasses.

Sci Rep 2018 Oct 19;8(1):15482. Epub 2018 Oct 19.

Department of Materials Science and Engineering, Korea Aerospace University, Gyeonggi, 10540, Republic of Korea.

A facile procedure for compositional screening of chalcogenide glass (CG) is proposed to manage its infrared transmission edge (ω) as well as refractive index dispersion (ν) in the long-wavelength infrared (LWIR) range. Both ω and ν of CG turn out to be interpretable simply in connection with its chemical composition based on a postulation that CG behaves as a single average harmonic oscillator (SAHO). In this SAHO model, ω is expressed as a function of molar mass and average bond energy, both of which are easily accessible for a given CG composition. Two prototypical CG-forming systems in Ge-Sb-Se and Ge-Sb-S compositions exemplify the empirical compositional dependence of ω, which further plays a decisive role in determining ν. Following the present approach, a set of highly dispersive CG compositions in the Ge-Sb-S system is newly unveiled together with low-dispersion Ge-Sb-Se glasses. It is then experimentally demonstrated that a doublet lens configuration consisting of convex and concave lenses with low and high ν values, respectively, is able to reduce the optical aberrations. This finding presents an opportunity that ν can be envisaged just based on the compositional ratio of CG, thus facilitating completion of the LWIR Abbe diagram.
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http://dx.doi.org/10.1038/s41598-018-33824-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195534PMC
October 2018

Changes in Hyolaryngeal Movement During Swallowing in the Lateral Decubitus Posture.

Ann Rehabil Med 2018 Jun 27;42(3):416-424. Epub 2018 Jun 27.

Department of Physical Medicine and Rehabilitation, Kosin University College of Medicine, Busan, Korea.

Objective: To investigate the differences in hyolaryngeal kinematics at rest and during swallowing in the upright sitting (UP) and the lateral decubitus (LD) postures in healthy adults, and delineating any potential advantages of swallowing while in the LD posture.

Methods: Swallowing was videofluoroscopically evaluated in 20 healthy volunteers in UP and LD postures, based on the movements of hyoid bone, vocal folds, and the bolus head. Parameters included the Penetration-Aspiration Scale (PAS), horizontal and vertical displacement, horizontal and vertical initial position, horizontal and vertical peak position, time to peak position of the hyoid bone and vocal folds, and pharyngeal transit time (PTT).

Results: Nine participants were rated PAS 2 in the UP and 1 was rated PAS 2 in the LD (p=0.003) at least 1 out of 3 swallows each posture. The hyoid and vocal folds showed more anterior and superior peak and initial positions in the LD. In addition, swallowing resulted in greater vertical and smaller horizontal displacement of the hyoid in LD posture compared with UP. Time to peak position of the hyoid was shorter in LD. The maximal vertical and horizontal displacement of the vocal folds, and PTT were comparable between postures.

Conclusion: The results showed that the peak and initial positions of the hyoid and larynx and the pattern of hyoid movement varied significantly depending on the body postures. This study suggests that the LD posture was one of the safe feeding postures without any increased risk compared with UP posture.
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http://dx.doi.org/10.5535/arm.2018.42.3.416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058586PMC
June 2018

Impaired facial expression recognition in patients with social anxiety disorder: a case-control study.

Cogn Neuropsychiatry 2018 07 10;23(4):218-228. Epub 2018 Apr 10.

a Department of Psychiatry , Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine , Seoul , Korea.

Introduction: The aim of this study was to investigate whether social anxiety disorder (SAD) patients have low emotion recognition accuracy, take longer for emotion recognition and tended to interpret a stimulus more negatively than controls.

Methods: Fifty-six SAD patients and 56 healthy controls were participated in this study. We evaluated facial emotion recognition using a computer program in which participants chose one of seven emotions as displayed in each of 55 photographs of faces. We compared the accuracy and reaction times of the patients and controls. We further analysed which emotions were selected in the incorrect answers.

Results: SAD patients showed delayed reaction times for all emotions except anger and lower accuracy for fear, surprise, neutrality and happiness compared to controls. After applying Bonferroni correction, only delayed reaction time for surprise and happiness were remain significant. Neutrality was not mistaken for a negative emotion at a higher rate by SAD patients than by controls.

Conclusion: This result suggests that the alterations of reaction time and accuracy of emotion recognition of SAD patients, especially in emotions with positive valence, play a more important role than negative bias in the cognitive aspects of SAD.
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http://dx.doi.org/10.1080/13546805.2018.1462695DOI Listing
July 2018

Characteristics of Early Oropharyngeal Dysphagia in Patients with Multiple System Atrophy.

Neurodegener Dis 2018 5;18(2-3):84-90. Epub 2018 Apr 5.

Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Jongno-Gu, Seoul, Republic of Korea.

Background/aims: Dysphagia, a symptom of multiple system atrophy (MSA), is a major clinical concern. In this study, we investigate the characteristics of early oropharyngeal dysphagia (OD) in patients with MSA, and the differences between MSA subtypes.

Methods: Patients enrolled in the study had previously been diagnosed with MSA at the clinic of the Department of Neurology, and had been referred for a videofluoroscopic swallowing study (VFSS), between 2005 and 2014, to check for dysphagia. The clinical characteristics and VFSS findings were analyzed and compared between the MSA subtypes.

Results: This study enrolled 59 patients with MSA (24 men; 31 with MSA-P, 21 with MSA-C, and 7 with MSA-PC). Dysphagia symptoms were mostly limited to aspiration symptoms (90.48%) in patients with MSA-C, while difficulty in swallowing, increased mealtime, and drooling were frequent in those with MSA-P. The most common VFSS finding amongst patients was vallecular residue (n = 53, 89.8%), followed by penetration/aspiration (n = 40, 67.8%), and coating of the pharyngeal wall (n = 39, 66.1%). Comparison analysis between subtypes showed that apraxia and vallecular residue were more frequent and severe in MSA-P than in MSA-C (p = 0.033 and p = 0.010, respectively).

Conclusion: Understanding early OD characteristics in patients with MSA and the differences between MSA subtypes could be helpful in managing dysphagia in patients with MSA. Several dysphagia symptoms similar to those of Parkinson disease were frequently observed in MSA-P, but not in MSA-C. A follow-up study is needed to elucidate the natural course of OD in MSA patients and the difference between MSA subtypes.
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http://dx.doi.org/10.1159/000487800DOI Listing
January 2019

SYSTEMATIC REVIEW WITH NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS OF ROTATOR CUFF TEAR TREATMENT.

Int J Technol Assess Health Care 2018 22;34(1):78-86. Epub 2018 Feb 22.

National Evidence-Based Healthcare Collaborating

Objectives: Rotator cuff tear is the leading cause of the decline in quality of life for older adults, but comparative evidence on treatment effectiveness is lacking. This study systematically reviewed the effects of various rotator cuff tear treatments through a Bayesian meta-analysis of the related randomized clinical trials (RCTs).Methods: We searched nine electronic databases for RCTs evaluating rotator cuff tear treatments from their inception through June 2017. A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the National Institute for Health and Care Excellence-Decision Support Unit guidelines (Supplementary Table 1). Outcomes included functional improvement, pain one year after surgical treatment, and tendon structural integrity. The Bayesian network meta-analysis was applied for functional improvement and pain, based on an assumption of consistency and similarity. Tendon integrity was reported descriptively.Results: Fifteen RCTs were selected. Patients undergoing physiotherapy after open surgery showed statistically significant functional improvements compared with those undergoing physiotherapy only (mean differences, 9.1 [credible interval, 0.9-17.4]). Open surgery with physiotherapy was associated with a decrease in pain 1 year after treatment compared with when physiotherapy was combined with arthroscopic rotator cuff surgery, mini open surgery, platelet-rich plasma therapy, or physiotherapy alone (absolute value of mean difference 1.2 to 1.4). The tendon integrity results were inconsistent.Conclusions: Some surgical treatments were associated with significant improvement in function and pain, but evidence regarding their comparative effectiveness is still lacking. A well-designed RCT discussing functional and structural treatment outcomes is needed in future.
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http://dx.doi.org/10.1017/S0266462317004500DOI Listing
February 2018

Diagnostic Accuracy of Clinical Measures Considering Segmental Tissue Composition and Volume Changes of Breast Cancer-Related Lymphedema.

Lymphat Res Biol 2018 08 17;16(4):368-376. Epub 2018 Jan 17.

2 Department of Rehabilitation Medicine, Seoul National University Hospital , Jongno-gu, Korea.

Background: If we use only volumetry for measuring lymphedema, we could underdiagnose lymphedema with characteristics of biomechanical changes without definite volume change, especially in the medial forearm.

Methods And Results: In total, 158 breast cancer patients participated in this study. Arm volume was measured by water displacement volumetry, and segmental volumes were calculated from circumferences by using the truncated cone method. Subcutaneous ultrasound echogenicities were assessed on the medial side of the upper arm and forearm of both arms and graded by subcutaneous echogenicity grade (SEG) and revised SEG (rSEG). The standards for diagnosing secondary lymphedema were according to the volume change and clinical stage. Sensitivity, specificity, receiver-operating characteristic (ROC) curve, and area under the curve (AUC) were used. Analysis of ROC curves yielded AUCs of 0.875-0.933 (p < 0.001). Volume differences in each segment were significantly different among the grades by SEG. The highest AUC was found for volume difference (AUC = 0.919, 95% confidence interval [CI] = 0.860-0.978) in the upper arm near the elbow; however, in the medial forearm, the highest AUC was found for rSEG (AUC = 0.948, 95% CI = 0.923-0.965 in the proximal forearm; AUC = 0.940, 95% CI = 0.923-0.965 in the distal forearm).

Conclusions: Our findings support the use of SEG by ultrasound in the assessment of lymphedema, especially in the medial region of the forearm. Subcutaneous ultrasound echogenicities may improve the accuracy of diagnosis of lymphedema in the forearm.
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http://dx.doi.org/10.1089/lrb.2017.0047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104249PMC
August 2018

STAMPS: development and verification of swallowing kinematic analysis software.

Biomed Eng Online 2017 Oct 17;16(1):120. Epub 2017 Oct 17.

Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Background: Swallowing impairment is a common complication in various geriatric and neurodegenerative diseases. Swallowing kinematic analysis is essential to quantitatively evaluate the swallowing motion of the oropharyngeal structures. This study aims to develop a novel swallowing kinematic analysis software, called spatio-temporal analyzer for motion and physiologic study (STAMPS), and verify its validity and reliability.

Methods: STAMPS was developed in MATLAB, which is one of the most popular platforms for biomedical analysis. This software was constructed to acquire, process, and analyze the data of swallowing motion. The target of swallowing structures includes bony structures (hyoid bone, mandible, maxilla, and cervical vertebral bodies), cartilages (epiglottis and arytenoid), soft tissues (larynx and upper esophageal sphincter), and food bolus. Numerous functions are available for the spatiotemporal parameters of the swallowing structures. Testing for validity and reliability was performed in 10 dysphagia patients with diverse etiologies and using the instrumental swallowing model which was designed to mimic the motion of the hyoid bone and the epiglottis.

Results: The intra- and inter-rater reliability tests showed excellent agreement for displacement and moderate to excellent agreement for velocity. The Pearson correlation coefficients between the measured and instrumental reference values were nearly 1.00 (P < 0.001) for displacement and velocity. The Bland-Altman plots showed good agreement between the measurements and the reference values.

Conclusions: STAMPS provides precise and reliable kinematic measurements and multiple practical functionalities for spatiotemporal analysis. The software is expected to be useful for researchers who are interested in the swallowing motion analysis.
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http://dx.doi.org/10.1186/s12938-017-0412-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645924PMC
October 2017

Robotic-assisted gait training combined with transcranial direct current stimulation in chronic stroke patients: A pilot double-blind, randomized controlled trial.

Restor Neurol Neurosci 2017 ;35(5):527-536

Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea.

Background: Although robotic-assisted gait training (RAGT) is becoming a standard method in stroke rehabilitation, its effect on chronic stroke patients is uncertain.

Objective: This study aimed to investigate whether anodal transcranial direct current stimulation (tDCS) enhances the effect of RAGT on functional ambulation in chronic stroke patients.

Methods: Chronic hemiplegic stroke patients with a Functional Ambulatory Category (FAC) score≤4 were randomly assigned to either the RAGT with anodal tDCS (Anodal) group the sham tDCS (Sham) group. The patients were provided with RAGT for 45 min after allocated tDCS on the leg motor cortex in the impaired hemisphere for 20 min every weekday for 2 weeks. The primary outcome measure was the FAC, and the secondary outcome measures included 10-m walking test, 6-min walking test, Berg Balance Scale, Fugl-Meyer assessment of the lower extremity, Medical Research Council Scale, and motor-evoked potential (MEP) parameters. They were evaluated before treatment (T0), immediately after treatment (T1), and 4 weeks after the end of treatment (T2).

Results: Twenty-one patients were finally included. The percentage of participants who achieved improvement in the FAC score was greater in the Anodal group than in the Sham group, and the difference was significant at T2 (66.7% vs. 12.5%, p = 0.024). In secondary outcome measures, the Anodal group showed greater improvement in the 6-min walking test than the Sham group at T2 (56.49±38.87 vs. 23.59±17.00, p = 0.038). The changes in the MEP parameters were not significantly different between the two groups.

Conclusion: This pilot study suggested that anodal tDCS on the leg motor cortex in the impaired hemisphere may facilitate the effect of RAGT on functional ambulation in chronic stroke patients. Larger clinical trials will be needed to confirm the effect of RAGT combined with tDCS in chronic stroke patients based on the present study.
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http://dx.doi.org/10.3233/RNN-170745DOI Listing
June 2018

Biomechanical Reactions of Exoskeleton Neurorehabilitation Robots in Spastic Elbows and Wrists.

IEEE Trans Neural Syst Rehabil Eng 2017 11 9;25(11):2196-2203. Epub 2017 Jun 9.

Spasticity is an important factor in designing wearable and lightweight exoskeleton neurorehabilitation robots. The proposed study evaluates biomechanical reactions of an exoskeleton robot to spasticity and establishes relevant guidelines for robot design. A two-axis exoskeleton robot is used to evaluate a group of 20 patients post-stroke with spastic elbow and/or wrist joints. All subjects are given isokinetic movements at various angular velocities within the capable range of motion for both joints. The resistance torque and corresponding angular position at each joint are recorded continuously. Maximal resistance torques caused by low (modified Ashworth scale (MAS) 0, 1), intermediate (MAS 1+), and high (MAS 2 and 3) grade spasticity were 3.68 ± 2.42, 5.94 ± 2.55, and 8.25 ± 3.35 Nm for the elbow flexor ( , between each grades) and 4.23 ± 1.75, 5.68 ± 1.96, and 5.44 ± 2.02 Nm for the wrist flexor ( , for low versus intermediate, low versus high grade spasticity). The angular velocity did not significantly influence maximal resistance torque in either joint. The catch occurred more quickly at higher velocities for low and intermediate elbow flexor spasticity ( ). Spasticity caused considerable resistance to the robots during mechanically actuated movements. The resistance range according to the degree of spasticity should be considered when designing practical neurorehabilitation robots.
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http://dx.doi.org/10.1109/TNSRE.2017.2714203DOI Listing
November 2017

Synthesis and Characterization of a Soluble A-D-A Molecule Containing a 2D Conjugated Selenophene-Based Side Group for Organic Solar Cells.

Macromol Rapid Commun 2017 Jun 21;38(11). Epub 2017 Mar 21.

Department of Chemistry, The Catholic University of Korea, Bucheon-si, Gyeonggido, 420-743, Republic of Korea.

A new acceptor-donor-acceptor (A-D-A) small molecule based on benzodithiophene (BDT) and diketopyrrolopyrrole (DPP) is synthesized via a Stille cross-coupling reaction. A highly conjugated selenophene-based side group is incorporated into each BDT unit to generate a 2D soluble small molecule (SeBDT-DPP). SeBDT-DPP thin films produce two distinct absorption peaks. The shorter wavelength absorption (400 nm) is attributed to the BDT units containing conjugated selenophene-based side groups, and the longer wavelength band is due to the intramolecular charge transfer between the BDT donor and the DPP acceptor. SeBDT-DPP thin films can harvest a broad solar spectrum covering the range 350-750 nm and have a low bandgap energy of 1.63 eV. Solution-processed field-effect transistors fabricated with this small molecule exhibit p-type organic thin film transistor characteristics, and the field-effect mobility of a SeBDT-DPP device is measured to be 2.3 × 10 cm V s . A small molecule solar cell device is prepared by using SeBDT-DPP as the active layer is found to exhibit a power conversion efficiency of 5.04% under AM 1.5 G (100 mW cm ) conditions.
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http://dx.doi.org/10.1002/marc.201700016DOI Listing
June 2017

Swallowing Function and Kinematics in Stroke Patients with Tracheostomies.

Dysphagia 2017 06 24;32(3):393-400. Epub 2016 Dec 24.

Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Republic of Korea.

The purpose of this study was to compare the swallowing function and kinematics in stroke patients with and without tracheostomies. In this retrospective matched case-control study, we compared stroke patients with (TRACH group, n = 24) and without (NO-TRACH group, n = 24) tracheostomies. Patients were matched for age, sex, and stroke-type. Swallowing function was evaluated using the videofluoroscopic dysphagia scale (VDS) and functional oral intake scale (FOIS) obtained from videofluoroscopic swallow study (VFSS) images. Swallowing kinematics were evaluated using a two-dimensional kinematic analysis of the VFSS images. Mean duration of tracheostomy was 132.38 ± 150.46 days in the TRACH group. There was no significant difference in the total VDS score between the TRACH (35.17 ± 15.30) and NO-TRACH groups (29.25 ± 16.66, p = 0.247). FOIS was significantly lower in the TRACH group (2.33 ± 1.40) than in the NO-TRACH group (4.33 ± 1.79, p = 0.001). The TRACH group had a significantly lower maximum vertical displacement (15.23 ± 7.39 mm, p = 0.011) and velocity (54.99 ± 29.59 mm/s, p = 0.011), and two-dimensional velocity (61.07 ± 24.89 mm/s, p = 0.013) of the larynx than the NO-TRACH group (20.18 ± 5.70 mm, 82.23 ± 37.30 mm/s, and 84.40 ± 36.05 mm/s, respectively). Maximum horizontal velocity of the hyoid bone in the TRACH group (36.77 ± 16.97 mm/s) was also significantly lower than that in the NO-TRACH group (47.49 ± 15.73 mm/s, p = 0.032). This study demonstrated that stroke patients with tracheostomies had inferior swallowing function and kinematics than those without tracheostomies. A prospective longitudinal study is needed to elucidate the effect of a tracheostomy on swallowing recovery in stroke patients.
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http://dx.doi.org/10.1007/s00455-016-9767-xDOI Listing
June 2017

Computer-assisted detection of swallowing difficulty.

Comput Methods Programs Biomed 2016 Oct 5;134:79-88. Epub 2016 Jul 5.

Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. Electronic address:

To evaluate classification performance of a support vector machine (SVM) classifier for diagnosing swallowing difficulty based on the hyoid movement data attained from videofluoroscopic swallowing study, the hyoid kinematics during the swallowing of 2 mL of liquid barium solution were analyzed for 90 healthy volunteers and 116 dysphagic stroke patients. SVM was used to classify the kinematic results as normal or dysfunctional swallowing. Various kernel functions and kernel parameters were used for optimization. Features were selected to find an optimal feature subset and to minimize redundancy. Accuracy, sensitivity, specificity, and area under a receiving operating characteristic curve (AUC) were used to assess the discrimination performance. In 19 out of 26 features, mean comparison revealed a significant difference between healthy subjects and dysphagic patients. By reducing the number of features to 10, an AUC of 0.9269 could be reached. Common features showing the best classification in both kernel functions included forward maximum excursion time, upward maximum excursion time, maximum excursion length, upward maximum velocity time, upward maximum acceleration time, maximum acceleration, maximum acceleration time, and mean acceleration. SVM-based classification method with the use of kernel functions showed an outstanding (AUC of 0.9269) discrimination performance for either healthy or dysphagic hyoid movement during swallowing. We expect that this classification method will be useful as an adjunct diagnostic tool by providing automatic detection of swallowing dysfunction as well as a research tool providing deeper understanding of pathophysiology.
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http://dx.doi.org/10.1016/j.cmpb.2016.07.010DOI Listing
October 2016

Characteristics of Dysphagia in Severe Traumatic Brain Injury Patients: A Comparison With Stroke Patients.

Ann Rehabil Med 2016 Jun 29;40(3):432-9. Epub 2016 Jun 29.

Department of Rehabilitation Medicine, Gangwon-Do Rehabilitation Hospital, Chuncheon, Korea.

Objective: To compare the swallowing characteristics of dysphagic patients with traumatic brain injury (TBI) with those of dysphagic stroke patients.

Methods: Forty-one patients with TBI were selected from medical records (between December 2004 to March 2013) and matched to patients with stroke (n=41) based on age, sex, and disease duration. Patients' swallowing characteristics were analyzed retrospectively using a videofluoroscopic swallowing study (VFSS) and compared between both groups. Following thorough review of medical records, patients who had a history of diseases that could affect swallowing function at the time of the study were excluded. Dysphagia characteristics and severity were evaluated using the American Speech-Language-Hearing Association National Outcome Measurement System swallowing scale, clinical dysphagia scale, and the videofluoroscopic dysphagia scale.

Results: There was a significant difference in radiological lesion location (p=0.024) between the two groups. The most common VFSS finding was aspiration or penetration, followed by decreased laryngeal elevation and reduced epiglottis inversion. Swallowing function, VFSS findings, or quantified dysphagia severity showed no significant differences between the groups. In a subgroup analysis of TBI patients, the incidence of tube feeding was higher in patients with surgical intervention than in those without (p=0.011).

Conclusion: The swallowing characteristics of dysphagic patients after TBI were comparable to those of dysphagic stroke patients. Common VFSS findings comprised aspiration or penetration, decreased laryngeal elevation, and reduced epiglottis inversion. Patients who underwent surgical intervention after TBI were at high risk of tube feeding requirement.
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http://dx.doi.org/10.5535/arm.2016.40.3.432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951361PMC
June 2016

Clinical Outcomes of Conservative Treatment and Arthroscopic Repair of Rotator Cuff Tears: A Retrospective Observational Study.

Ann Rehabil Med 2016 Apr 25;40(2):252-62. Epub 2016 Apr 25.

National Evidence-Based Healthcare Collaborating Agency, Seoul, Korea.; Department of Rehabilitation Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Objective: To compare the clinical outcomes following conservative treatment and arthroscopic repair in patients with a rotator cuff tear.

Methods: In this retrospective study, patients aged >50 years with a symptomatic rotator cuff tear were reviewed. The rotator cuff tendons were evaluated using ultrasonography, shoulder magnetic resonance imaging or MR arthrography, and the patients with either a high-grade partial-thickness or small-to-medium-sized (≤3 cm) full-thickness tear were included in this study. The primary outcome measures were a pain assessment score and range of motion (ROM) at 1-year follow-up. The secondary outcomes were the rate of tear progression or retear along with the rate of symptom aggravation after the treatments.

Results: A total of 357 patients were enrolled, including 183 patients that received conservative treatment and 174 patients who received an arthroscopic repair. The pain assessment score (p<0.001) and the ROM in forward flexion (p<0.001) were significantly improved in both groups. The ROM in internal rotation did not significantly change after conservative treatment and arthroscopic repair. The pain assessment score and ROM were not significantly different between the two groups. Retear was observed in 9.6% of patients who had an arthroscopic repair and tear progression was found in 6.7% of those who underwent conservative treatment. The proportion of aggravation for pain and ROM did not significantly differ between the two groups.

Conclusion: The effectiveness of conservative treatment is not inferior to arthroscopic repair for patients >50 years old with a less than medium-sized rotator cuff tear in a 1-year follow-up period. Further study is warranted to find the optimal combination of conservative treatment for a symptomatic rotator cuff tear.
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http://dx.doi.org/10.5535/arm.2016.40.2.252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855119PMC
April 2016

Crystallization of Local Anesthetics When Mixed With Corticosteroid Solutions.

Ann Rehabil Med 2016 Feb 26;40(1):21-7. Epub 2016 Feb 26.

Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Objective: To evaluate at which pH level various local anesthetics precipitate, and to confirm which combination of corticosteroid and local anesthetic crystallizes.

Methods: Each of ropivacaine-HCl, bupivacaine-HCl, and lidocaine-HCl was mixed with 4 different concentrations of NaOH solutions. Also, each of the three local anesthetics was mixed with the same volume of 3 corticosteroid solutions (triamcinolone acetonide, dexamethasone sodium phosphate, and betamethasone sodium phosphate). Precipitation of the local anesthetics (or not) was observed, by the naked eye and by microscope. The pH of each solution and the size of the precipitated crystal were measured.

Results: Alkalinized with NaOH to a certain value of pH, local anesthetics precipitated (ropivacaine pH 6.9, bupivacaine pH 7.7, and lidocaine pH 12.9). Precipitation was observed as a cloudy appearance by the naked eye and as the aggregation of small particles (<10 µm) by microscope. The amount of particles and aggregation increased with increased pH. Mixed with betamethasone sodium phosphate, ropivacaine was precipitated in the form of numerous large crystals (>300 µm, pH 7.5). Ropivacaine with dexamethasone sodium phosphate also precipitated, but it was only observable by microscope (a few crystals of 10-100 µm, pH 7.0). Bupivacaine with betamethasone sodium phosphate formed precipitates of non-aggregated smaller particles (<10 µm, pH 7.7). Lidocaine mixed with corticosteroids did not precipitate.

Conclusion: Ropivacaine and bupivacaine can precipitate by alkalinization at a physiological pH, and therefore also produce crystals at a physiological pH when they are mixed with betamethasone sodium phosphate. Thus, the potential risk should be noted for their use in interventions, such as epidural steroid injections.
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http://dx.doi.org/10.5535/arm.2016.40.1.21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775754PMC
February 2016

Ischemic Cervical Myelopathy Caused by Vertebral Artery Dissection: The Clinical Utility of a Motor-evoked Potential Study.

Neurologist 2016 Jan;21(1):8-10

*Department of Rehabilitation Medicine, Seoul National University Hospital ‡Department of Rehabilitation Medicine, Seoul National University Boramae Medical Center †Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, Republic of Korea.

Introduction: Vertebral artery dissection (VAD) has been increasingly recognized as one of the important causes of ischemic stroke especially in young and middle-aged population. Rarely, VAD can involve the spinal cord, causing ischemic cervical myelopathy.

Case Report: A 51-year-old man presented with sudden onset of weakness and hypesthesia involving right upper extremity, accompanied by posterior neck pain and headache. He also complained nonwhirling type of dizziness and nausea and he exhibited ataxic gait. Brain magnetic resonance imaging showed acute infarction at the right cerebellar hemisphere and temporo-occipital lobe. Right VAD was identified by MR angiography and confirmed by transfemoral cerebral angiography. Because the selective proximal weakness of the right upper extremity and hypesthesia at C5 and C6 dermatomes was not be fully explained by the brain lesion, electrophysiological studies were performed. The motor-evoked potential studies revealed that the latency and central motor conduction time was prolonged in the right cervical and lumbosacral roots. These studies implied cervical myelopathy involving the right anterior column. Magnetic resonance imaging of the cervical spine demonstrated high signal intensity of the right anterior column at C3-C4 level, which confirmed cervical ischemic myelopathy.

Conclusions: When there is diagnostic ambiguity between the upper and lower motor neuron lesions in VAD, motor-evoked potential study can be helpful to diagnose peripheral neurological complication of VAD.
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http://dx.doi.org/10.1097/NRL.0000000000000066DOI Listing
January 2016

One-year outcome of postoperative swallowing impairment in pediatric patients with posterior fossa brain tumor.

J Neurooncol 2016 Mar 30;127(1):73-81. Epub 2015 Nov 30.

Department of Rehabilitation Medicine, Gangwon-Do Rehabilitation Hospital, Chuncheon, Republic of Korea.

Impaired swallowing in children who underwent posterior fossa brain tumor (PFBT) resection disrupts development and quality of life, yet its downstream consequences remain unclear. This study explored the risk factors and functional prognosis of postoperative swallowing impairment in pediatric patients (<19 years old) with PFBT. Among 183 patients with PFBT who underwent surgical resection, 39 patients with postoperative swallowing difficulty were analyzed using the videofluoroscopic swallowing study (VFSS). The association between clinical features, swallowing characteristics, and swallowing impairment was explored during the early postoperative phase and 1-year following surgical resection. Duration of tube feeding was investigated using Kaplan-Meier analysis. Twenty-seven (14.8 %) patients needed tube feeding in the early postoperative phase and 11 (6.01 %) at 1-year after surgical resection. Mean duration of tube feeding was 240.2 days and differed by tumor pathologies (P = 0.001), delayed triggering of pharyngeal swallow (DTP) (P = 0.002) and pharyngeal wall coating (P = 0.033). Tumor pathology was associated significantly with the referral for swallowing evaluation (P < 0.001) and 1-year tube feeding (P = 0.019). Tube feeding at 1-year was significantly associated with the tumor's brainstem involvement (P = 0.039), and swallowing abnormalities at early phase including DTP (P = 0.030) and pharyngeal wall coating (P = 0.004). Our results suggest that tumor pathology, brainstem involvement, and specific swallowing abnormalities at early phase are important risk factors for sustained 1-year swallowing impairment following surgical resection. These results can be applied to determine the plan of evaluation, nutrition, and intervention in clinical practice.
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http://dx.doi.org/10.1007/s11060-015-2010-zDOI Listing
March 2016

Specific oligopeptides in fermented soybean extract inhibit NF-κB-dependent iNOS and cytokine induction by toll-like receptor ligands.

J Med Food 2014 Nov 3;17(11):1239-46. Epub 2014 Sep 3.

1 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul, Korea.

The ethanol extract of fermented soybean from Glycine max (chungkookjang, CHU) has been claimed to have chemopreventive and cytoprotective effects. In the present study, we examined the inhibitory effect of CHU on inducible nitric oxide synthase (iNOS) and cytokine induction by toll-like receptor (TLR) ligands treatment and attempted to identify the responsible active components. Nitric oxide (NO) content and iNOS levels in the media or RAW264.7 cells were measured using the Griess reagent and real-time polymerase chain reaction assays. CHU treatment inhibited NO production and iNOS induction elicited by lipopolysaccharide (LPS, TLR4L) in a concentration-dependent manner. Tumor necrosis factor-α and interleukin-6 productions were also diminished. Peptidoglycans (TLR2/6L) and CpG-oligodeoxynucleotides (TLR9L) from CHU inhibited iNOS induction, but not poly I:C (TLR3L) or loxoribine (TLF7L). The anti-inflammatory effect resulted from the inhibition of nuclear factor-kappa B (NF-κB) through the inhibition of inhibitory-κB degradation. Of the representative components in CHU, specific oligopeptides (AFPG and GVAWWMY) had the ability to inhibit iNOS induction by LPS, whereas others failed to do so. Daidzein, an isoflavone used for comparative purposes, was active at a relatively higher concentration. In an animal model, oral administration of CHU to rats significantly diminished carrageenan-induced paw edema and iNOS induction. Our results demonstrate that CHU has anti-inflammatory effects against TLR ligands by inhibiting NF-κB activation, which may result from specific oligopeptide components in CHU. Since CHU is orally effective, dietary applications of CHU and/or the identified oligopeptides may be of use in the prevention of inflammatory diseases.
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http://dx.doi.org/10.1089/jmf.2013.3070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224054PMC
November 2014

Discovery of an integrative network of microRNAs and transcriptomics changes for acute kidney injury.

Kidney Int 2014 Nov 23;86(5):943-53. Epub 2014 Apr 23.

Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.

The contribution of miRNA to the pathogenesis of acute kidney injury (AKI) is not well understood. Here we evaluated an integrative network of miRNAs and mRNA data to discover a possible master regulator of AKI. Microarray analyses of the kidneys of mice treated with cisplatin were used to extract putative miRNAs that cause renal injury. Of them, miR-122 was mostly downregulated by cisplatin, whereas miR-34a was upregulated. A network integrating dysregulated miRNAs and altered mRNA expression along with target prediction enabled us to identify Foxo3 as a core protein to activate p53. The miR-122 inhibited Foxo3 translation as assessed using an miR mimic, an inhibitor, and a Foxo3 3'-UTR reporter. In a mouse model, Foxo3 levels paralleled the degree of tubular injury. The role of decreased miR-122 in inducing Foxo3 during AKI was strengthened by the ability of the miR-122 mimic or inhibitor to replicate results. Increase in miR-34a also promoted the acetylation of Foxo3 by repressing Sirt1. Consistently, cisplatin facilitated the binding of Foxo3 and p53 for activation, which depended not only on decreased miR-122 but also on increased miR-34a. Other nephrotoxicants had similar effects. Among targets of p53, Phlda3 was robustly induced by cisplatin, causing tubular injury. Consistently, treatment with miR mimics and/or inhibitors, or with Foxo3 and Phlda3 siRNAs, modulated apoptosis. Thus, our results uncovered an miR integrative network regulating toxicant-induced AKI and identified Foxo3 as a bridge molecule to the p53 pathway.
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http://dx.doi.org/10.1038/ki.2014.117DOI Listing
November 2014

Thermally cross-linkable hole transport polymers for solution-based organic light-emitting diodes.

Macromol Rapid Commun 2014 Apr 13;35(8):807-12. Epub 2014 Feb 13.

Department of Information Display and Advanced Display Research Center, Kyung Hee University, Seoul, 130-701, Republic of Korea.

Two thermally cross-linkable hole transport polymers that contain phenoxazine and triphenylamine moieties, X-P1 and X-P2, are developed for use in solution-processed multi-stack organic light-emitting diodes (OLEDs). Both X-P1 and X-P2 exhibit satisfactory cross-linking and optoelectronic properties. The highest occupied molecular orbital (HOMO) levels of X-P1 and X-P2 are -5.24 and -5.16 eV, respectively. Solution-processed super yellow polymer devices (ITO/X-P1 or X-P2/PDY-132/LiF/Al) with X-P1 or X-P2 hole transport layers of various thicknesses are fabricated with the aim of optimizing the device characteristics. The fabricated multi-stack yellow devices containing the newly synthesized hole transport polymers exhibit satisfactory currents and power efficiencies. The optimized X-P2 device exhibits a device efficiency that is dramatically improved by more than 66% over that of a reference device without an HTL.
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http://dx.doi.org/10.1002/marc.201400002DOI Listing
April 2014

Structural requirements within protoporphyrin IX in the inhibition of heat shock protein 90.

Chem Biol Interact 2013 Jun 24;204(1):49-57. Epub 2013 Apr 24.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, South Korea.

Porphyrins are used for photodynamic therapy for their light-absorbing properties, and some of them were approved for the treatment of certain types of cancers. Porphyrins prevent activation of hypoxia inducible factor-1α (HIF-1α) by inhibiting heat shock protein 90 (HSP90). This study investigated the structural requirements within protoporphyrin IX (PPIX) for the inhibition of HSP90 activity. In HCT116, HT29 and DLD-1 cells, PPIX treatment directly hindered the binding between HSP90 and HIF-1α; PPIX treatment inhibited the chaperone activity of HSP90, accelerating protein degradation of HIF-1α. In addition, PPIX treatment suppressed cancer cell migration, endothelial cell tube formation, and aortic ring sprouting, being consistent with its anti-tumor and anti-angiogenic activities. In silico analysis, molecular docking model indicated that a tetrapyrrole macrocycle and two propionate chains within PPIX are necessary for the binding to the adenosine triphosphate (ATP)-binding pocket of HSP90. The predicted structural requirement was verified by the differential inhibitory effects of PPIX analogs, or the precursor of PPIX, on HIF-1α; compounds lacking either the tetrapyrrole macrocycle or the propionate chains were inactive. Our results show that a tetrapyrrole macrocycle and two attached propionate chains in PPIX coordinately interact with the ATP-binding pocket of HSP90, offering structural information on the inhibitory effect of porphyrins on angiogenesis.
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http://dx.doi.org/10.1016/j.cbi.2013.04.006DOI Listing
June 2013

An easily accessible donor-π-acceptor-conjugated small molecule from a 4,8-dialkoxybenzo[1,2-b:4,5-b']dithiophene unit for efficient solution-processed organic solar cells.

ACS Appl Mater Interfaces 2012 Dec 26;4(12):6669-75. Epub 2012 Nov 26.

School of Semiconductor and Chemical Engineering, Chonbuk National University, Duckjin-dong 664-14, Jeonju 561-756, Republic of Korea.

A new donor-acceptor-conjugated organic small molecule, BDT(TBT)(2), comprised of benzo[1,2-b:4,5-b']dithiophene and 2,1,3-benzothiadiazole units was designed and synthesized. The small molecule BDT(TBT)(2) in its thin film showed an absorption band in the range of 300-700 nm with an absorption edge at 650 nm and an optical band gap of 1.90 eV. As estimated from the cyclic voltammetry measurements, the HOMO and LUMO energy levels of BDT(TBT)(2) were -5.44 and -3.37 eV, respectively. The spin-coated thin film of BDT(TBT)(2) exhibited p-channel output characteristics with a hole mobility of 2.7 × 10(-6). BDT(TBT)(2), when explored as an electron-donor material in solution-processed bulk-heterojunction organic solar cells in conjunction with a PC(71)BM acceptor with an active layer thickness of 50-55 nm, generated a power conversion efficiency (PCE) of 1.18%. A more impressive PCE of ~2.9% with a short-circuit current density (J(sc)) of 7.94 mA cm(-2) and an open-circuit voltage (V(oc)) of 0.89 V was achieved when the active layer of the cell was annealed at higher temperature (~180 °C).
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http://dx.doi.org/10.1021/am301841pDOI Listing
December 2012
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