1.Validation of the Korean Version of the Anosognosia Questionnaire for Dementia
Gi Hwan BYEON ; Woo Jin KIM ; Min Soo BYUN ; Jun Ho LEE ; So Yeon JEON ; Kang KO ; Kiyoung SUNG ; Dongkyun HAN ; Haejung JOUNG ; Younghwa LEE ; Gijung JUNG ; Han Na LEE ; Dahyun YI ; Dong Young LEE ;
Psychiatry Investigation 2021;18(4):324-331
Objective:
Anosognosia is a common phenomenon in individuals with dementia. Anosognosia Questionnaire for dementia (AQ-D) is a well-known scale for evaluating anosognosia. This study aimed to establish a Korean version of the AQ-D (AQ-D-K) and to evaluate the reliability and validity of the AQ-D-K in patients with Alzheimer’s disease (AD) dementia.
Methods:
We translated the original English version of AQ-D into Korean (AQ-D-K). Eighty-four subjects with very mild or mild AD dementia and their caregivers participated. Reliability of AQ-D-K was assessed by internal consistency and one-month test-retest reliability. Construct validity and concurrent validity were also evaluated.
Results:
Internal consistencies of the AQ-D-K patient form and caregiver form were high (Cronbach alpha 0.95 and 0.93, respectively). The test-retest reliability of AQ-D-K measured by intra-class correlation coefficient was 0.84. Three factors were identified: 1) anosognosia of instrumental activity of daily living; 2) anosognosia basic activity of daily living; and 3) anosognosia of depression and disinhibition. AQ-D-K score was significantly correlated with the clinician-rated anosognosia rating scale (ARS), center for epidemiological studies-depression scale (CES-D) and state-trait anxiety inventory (STAI).
Conclusion
The findings suggest that the AQ-D-K is a reliable and valid scale for evaluating anosognosia for AD dementia patients using Korean language.
2.Normative Study of the Block Design Test for Adults Aged 55 Years and Older in Korean Aging Population
Haejung JOUNG ; Dahyun YI ; Hyejin AHN ; Younghwa LEE ; Min Soo BYUN ; Kiyoung SUNG ; Dongkyun HAN ; Dong Young LEE ;
Psychiatry Investigation 2021;18(6):539-544
Objective:
The Block Design Test (BDT) is known to be an effective measure in diagnosing age-related cognitive decline of visuospatial function. The goal of this study is to investigate the effects of age, education years, and gender on the performance of the BDT and to provide normative data in Korean community-dwelling participants who are 55 to 90 years old.
Methods:
The participants were 432 non-demented adults aging from 55 to 90 years old. The BDT was administered to participants according to its manual. Multiple linear regressions and analyses of variance were conducted, including age, gender, and educations were used as covariates.
Results:
Age, educational years, and gender were found to be significantly associated with performance on the BDT. As age increased, BDT performance decreased. Educational years were associated with BDT performance. Men showed higher performance (29.9±10.3) compare to women (26.1±8.7). The BDT is influenced by age, educational years, and gender.
Conclusion
Unlike the previous study, the current study shows that gender has a significant influence in visuospatial ability in the old population. Present normative data will be useful for clinicians in evaluating aging participants with cognitive impairment.
3.Generation of Hepatic Progenitor Cells from the Primary Hepatocytes of Nonhuman Primates Using Small Molecules
Da Hee HONG ; Changhee LEE ; Yohan KIM ; Seung BUM ; Su-Cheol HAN ; Sung Joo KIM ; Heung-Mo YANG ; Dongho CHOI ; Jaemin JEONG ; Kiyoung RYU
Tissue Engineering and Regenerative Medicine 2021;18(2):305-313
BACKGROUND:
Since primates have more biological similarities to humans than do other animals, they are a valuable resource in various field of research, including biomedicine, regenerative medicine, and drug discovery. However, there remain limitations to maintenance and expansion of primary hepatocytes derived from nonhuman primates. To overcome these limitations, we developed a novel culture system for primate cells.
METHODS:
Primary hepatocytes from Macaca fascicularis (mf-PHs) were isolated from hepatectomized liver. To generate chemically derived hepatic progenitor cells (mf-CdHs), mf-PHs were cultured with reprogramming medium containing A83-01, CHIR99021, and hepatocyte growth factor (HGF). The bi-potent differentiation capacity of mf-CdHs into hepatocytes and biliary epithelial cells was confirmed by treatment with hepatic differentiation medium (HDM) and cholangiocytic differentiation medium (CDM), respectively.
RESULTS:
mf-PHs cultured with reprogramming medium showed rapid proliferation capacity in vitro and expressed progenitor-specific markers. Moreover, when cultured in HDM, these progenitor cells stably differentiated into hepatocytelike cells expressing the mature hepatic markers. On the other hand, when cultured in CDM, the differentiated biliary epithelial cells expressed mature cholangiocyte characteristics.
CONCLUSION
The results of the present study demonstrate that we successfully induced the formation of hepatic progenitor cells from mf-PHs by culturing them with a combination of small molecules, including growth factors. These results offer a means of expanding nonhuman primate hepatocytes without genetic manipulation for cellular resource, preclinical applications and regenerative medicine for the liver.
4.Validation of the Korean Version of the Anosognosia Questionnaire for Dementia
Gi Hwan BYEON ; Woo Jin KIM ; Min Soo BYUN ; Jun Ho LEE ; So Yeon JEON ; Kang KO ; Kiyoung SUNG ; Dongkyun HAN ; Haejung JOUNG ; Younghwa LEE ; Gijung JUNG ; Han Na LEE ; Dahyun YI ; Dong Young LEE ;
Psychiatry Investigation 2021;18(4):324-331
Objective:
Anosognosia is a common phenomenon in individuals with dementia. Anosognosia Questionnaire for dementia (AQ-D) is a well-known scale for evaluating anosognosia. This study aimed to establish a Korean version of the AQ-D (AQ-D-K) and to evaluate the reliability and validity of the AQ-D-K in patients with Alzheimer’s disease (AD) dementia.
Methods:
We translated the original English version of AQ-D into Korean (AQ-D-K). Eighty-four subjects with very mild or mild AD dementia and their caregivers participated. Reliability of AQ-D-K was assessed by internal consistency and one-month test-retest reliability. Construct validity and concurrent validity were also evaluated.
Results:
Internal consistencies of the AQ-D-K patient form and caregiver form were high (Cronbach alpha 0.95 and 0.93, respectively). The test-retest reliability of AQ-D-K measured by intra-class correlation coefficient was 0.84. Three factors were identified: 1) anosognosia of instrumental activity of daily living; 2) anosognosia basic activity of daily living; and 3) anosognosia of depression and disinhibition. AQ-D-K score was significantly correlated with the clinician-rated anosognosia rating scale (ARS), center for epidemiological studies-depression scale (CES-D) and state-trait anxiety inventory (STAI).
Conclusion
The findings suggest that the AQ-D-K is a reliable and valid scale for evaluating anosognosia for AD dementia patients using Korean language.
5.Normative Study of the Block Design Test for Adults Aged 55 Years and Older in Korean Aging Population
Haejung JOUNG ; Dahyun YI ; Hyejin AHN ; Younghwa LEE ; Min Soo BYUN ; Kiyoung SUNG ; Dongkyun HAN ; Dong Young LEE ;
Psychiatry Investigation 2021;18(6):539-544
Objective:
The Block Design Test (BDT) is known to be an effective measure in diagnosing age-related cognitive decline of visuospatial function. The goal of this study is to investigate the effects of age, education years, and gender on the performance of the BDT and to provide normative data in Korean community-dwelling participants who are 55 to 90 years old.
Methods:
The participants were 432 non-demented adults aging from 55 to 90 years old. The BDT was administered to participants according to its manual. Multiple linear regressions and analyses of variance were conducted, including age, gender, and educations were used as covariates.
Results:
Age, educational years, and gender were found to be significantly associated with performance on the BDT. As age increased, BDT performance decreased. Educational years were associated with BDT performance. Men showed higher performance (29.9±10.3) compare to women (26.1±8.7). The BDT is influenced by age, educational years, and gender.
Conclusion
Unlike the previous study, the current study shows that gender has a significant influence in visuospatial ability in the old population. Present normative data will be useful for clinicians in evaluating aging participants with cognitive impairment.
6.Generation of Hepatic Progenitor Cells from the Primary Hepatocytes of Nonhuman Primates Using Small Molecules
Da Hee HONG ; Changhee LEE ; Yohan KIM ; Seung BUM ; Su-Cheol HAN ; Sung Joo KIM ; Heung-Mo YANG ; Dongho CHOI ; Jaemin JEONG ; Kiyoung RYU
Tissue Engineering and Regenerative Medicine 2021;18(2):305-313
BACKGROUND:
Since primates have more biological similarities to humans than do other animals, they are a valuable resource in various field of research, including biomedicine, regenerative medicine, and drug discovery. However, there remain limitations to maintenance and expansion of primary hepatocytes derived from nonhuman primates. To overcome these limitations, we developed a novel culture system for primate cells.
METHODS:
Primary hepatocytes from Macaca fascicularis (mf-PHs) were isolated from hepatectomized liver. To generate chemically derived hepatic progenitor cells (mf-CdHs), mf-PHs were cultured with reprogramming medium containing A83-01, CHIR99021, and hepatocyte growth factor (HGF). The bi-potent differentiation capacity of mf-CdHs into hepatocytes and biliary epithelial cells was confirmed by treatment with hepatic differentiation medium (HDM) and cholangiocytic differentiation medium (CDM), respectively.
RESULTS:
mf-PHs cultured with reprogramming medium showed rapid proliferation capacity in vitro and expressed progenitor-specific markers. Moreover, when cultured in HDM, these progenitor cells stably differentiated into hepatocytelike cells expressing the mature hepatic markers. On the other hand, when cultured in CDM, the differentiated biliary epithelial cells expressed mature cholangiocyte characteristics.
CONCLUSION
The results of the present study demonstrate that we successfully induced the formation of hepatic progenitor cells from mf-PHs by culturing them with a combination of small molecules, including growth factors. These results offer a means of expanding nonhuman primate hepatocytes without genetic manipulation for cellular resource, preclinical applications and regenerative medicine for the liver.
7.Tumor Spheroids of an Aggressive Form of Central Neurocytoma Have Transit-Amplifying Progenitor Characteristics with Enhanced EGFR and Tumor Stem Cell Signaling
Hye Young SHIN ; Kyung-Seok HAN ; Hyung Woo PARK ; Yun Hwa HONG ; Yona KIM ; Hyo Eun MOON ; Kwang Woo PARK ; Hye Ran PARK ; C. Justin LEE ; Kiyoung LEE ; Sang Jeong KIM ; Man Seung HEO ; Sung-Hye PARK ; Dong Gyu KIM ; Sun Ha PAEK
Experimental Neurobiology 2021;30(2):120-143
Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.
8.Fever in Trauma Patients without Brain Injury
Boyoon CHOI ; Kiyoung SUNG ; Jinbeom CHO
Journal of Acute Care Surgery 2021;11(1):6-13
Purpose:
Distinguishing a fever caused by infection from the necessary febrile response in injured patients is difficult, because trauma patients often have concomitant obvious infectious origins. In traumatic brain injury, early fever might be associated with worse clinical outcomes; however, few reports on trauma patients without brain injury are available.
Methods:
In this retrospective observational study, consecutive trauma patients without brain injury who were admitted to the surgical intensive care unit during a 3 year period were included. The surgical and clinical outcomes were compared according to body temperature. Locally weighted scatterplot smoothing was used to identify the relationship between body temperature and injury severity.
Results:
A total of 111 patients were included. Body temperature increased as the injury severity score increased up to 47.717, above which it decreased. Mortality was high in hypothermic patients (72.7%; p < 0.001); however, few differences were observed between normothermic and hyperthermic patients (3.5% and 2.4%, respectively). The nonsurvivors had lower body temperatures on the 1st and 2nd days after admission (36 ˚C and 36.9 ˚C) compared with the survivors (37.3 ˚C and 37.7 ˚C; p < 0.001 and p = 0.006). In severely injured patients, low levels of inflammatory biomarkers and low body temperature were correlated with mortality.
Conclusions
Fever in trauma patients without brain injury is correlated with injury severity but not with prognosis. Hypothermia on the 1st and 2nd days after admission was significantly correlated with mortality. In severely injured patients, a decreased inflammatory response might play a certain role in promoting a high mortality rate.
9.Tumor Spheroids of an Aggressive Form of Central Neurocytoma Have Transit-Amplifying Progenitor Characteristics with Enhanced EGFR and Tumor Stem Cell Signaling
Hye Young SHIN ; Kyung-Seok HAN ; Hyung Woo PARK ; Yun Hwa HONG ; Yona KIM ; Hyo Eun MOON ; Kwang Woo PARK ; Hye Ran PARK ; C. Justin LEE ; Kiyoung LEE ; Sang Jeong KIM ; Man Seung HEO ; Sung-Hye PARK ; Dong Gyu KIM ; Sun Ha PAEK
Experimental Neurobiology 2021;30(2):120-143
Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.
10.Fever in Trauma Patients without Brain Injury
Boyoon CHOI ; Kiyoung SUNG ; Jinbeom CHO
Journal of Acute Care Surgery 2021;11(1):6-13
Purpose:
Distinguishing a fever caused by infection from the necessary febrile response in injured patients is difficult, because trauma patients often have concomitant obvious infectious origins. In traumatic brain injury, early fever might be associated with worse clinical outcomes; however, few reports on trauma patients without brain injury are available.
Methods:
In this retrospective observational study, consecutive trauma patients without brain injury who were admitted to the surgical intensive care unit during a 3 year period were included. The surgical and clinical outcomes were compared according to body temperature. Locally weighted scatterplot smoothing was used to identify the relationship between body temperature and injury severity.
Results:
A total of 111 patients were included. Body temperature increased as the injury severity score increased up to 47.717, above which it decreased. Mortality was high in hypothermic patients (72.7%; p < 0.001); however, few differences were observed between normothermic and hyperthermic patients (3.5% and 2.4%, respectively). The nonsurvivors had lower body temperatures on the 1st and 2nd days after admission (36 ˚C and 36.9 ˚C) compared with the survivors (37.3 ˚C and 37.7 ˚C; p < 0.001 and p = 0.006). In severely injured patients, low levels of inflammatory biomarkers and low body temperature were correlated with mortality.
Conclusions
Fever in trauma patients without brain injury is correlated with injury severity but not with prognosis. Hypothermia on the 1st and 2nd days after admission was significantly correlated with mortality. In severely injured patients, a decreased inflammatory response might play a certain role in promoting a high mortality rate.

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