Publications by authors named "Mi-Sun Choi"

50 Publications

Construction of a non-contact community treatment center for asymptomatic and mildly symptomatic COVID 19 patients during the COVID-19 pandemic.

Epidemiol Infect 2021 Apr 27:1-8. Epub 2021 Apr 27.

Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

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http://dx.doi.org/10.1017/S0950268821000996DOI Listing
April 2021

TNFα enhances trovafloxacin-induced in vitro hepatotoxicity by inhibiting protective autophagy.

Toxicol Lett 2021 May 17;342:73-84. Epub 2021 Feb 17.

Department of Predictive Toxicology, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea; Department of Human and Environmental Toxicology, University of Science & Technology, Daejeon, 34113, Republic of Korea. Electronic address:

Trovafloxacin (TVX) is associated with idiosyncratic drug-induced liver injury (iDILI) and inflammation-mediated hepatotoxicity. However, the inflammatory stress-regulated mechanisms in iDILI remain unclear. Herein, we elucidated the novel role of tumor-necrosis factor alpha (TNFα), an inflammatory stress factor, in TVX-induced in vitro hepatotoxicity and synergistic toxicity. TVX specifically induced synergistic toxicity in HepG2 cells with TNFα, which inhibits autophagy. TVX-treated HepG2 cells induced protective autophagy by inhibiting the expression of mTOR signaling proteins, while ATG5 knockdown in HepG2 cells, responsible for the impairment of autophagy, enhanced TVX-induced toxicity due to the increase in cytochrome C release and JNK pathway activation. Interestingly, the expression of mTOR signal proteins, which were suppressed by TVX, disrupted the negative feedback of the PI3K/AKT pathway and TNFα rebounded p70S6K phosphorylation. Co-treatment with TVX and TNFα inhibited protective autophagy by maintaining p70S6K activity, which enhanced TVX-induced cytotoxicity. Phosphorylation of p70S6K was inhibited by siRNA knockdown and rapamycin to restore TNFα-inhibited autophagy, which prevented the synergistic effect on TVX-induced cytotoxicity. These results indicate that TVX activates protective autophagy in HepG2 cells exposed to toxicity and an imbalance in negative feedback regulation of autophagy by TNFα synergistically enhanced the toxicity. The finding from this study may contribute to a better understanding of the mechanisms underlying iDILI associated with inflammatory stress.
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http://dx.doi.org/10.1016/j.toxlet.2021.02.009DOI Listing
May 2021

Competition Among Mental Health Organizations: Environmental Drivers and Strategic Responses.

Adm Policy Ment Health 2021 05;48(3):393-407

College of Social Work, Ohio State University, 1947 College Road, Columbus, OH, 43210, USA.

While mental health system reforms have sought to leverage competition in the private sector to improve service quality and costs, competition among mental health organizations is poorly understood. To inform future studies about the impact of policy and system reforms on mental health organizations and service delivery, this qualitative study explores (1) resources for which organizations compete most intensively, (2) drivers of competition, and (3) leaders' strategic organizational responses. Semi-structured phone interviews were conducted with 15 organizational leaders (CEO's, executive directors) representing about 22% of organizations in the regional mental health market. Interviews covered leaders' perceptions about competition, and their strategic responses. Porter's seminal framework on competition was used to interpret codes and themes. Intensive competition for personnel was driven by workforce shortages, new for-profit organizations, and alternative employment opportunities. In response, organizations have attended to wages/benefits, recruitment, and retention. However, strong community need, expanded insurance coverage, and a history of local strategic responses that created service niches appeared to have minimized competition for financial resources in the region. Competition for funding and clients was expected to intensify under systems reform, and in anticipation, organizations were expanding services. Leaders also feared for the viability of smaller organizations in highly competitive environments. Consistent with theory on competition, mental health organizations compete and respond in ways that might improve services. However, the goals of privatization may have been unrealized because of minimal competition for funding and clients, and intense competition may undermine quality.
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http://dx.doi.org/10.1007/s10488-020-01079-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038990PMC
May 2021

Preparing for long-term non-face-to-face outpatient care services during the COVID-19 pandemic.

J Infect 2021 Jan 7;82(1):e8-e10. Epub 2020 Aug 7.

Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, #56, Donsu-Ro, Bupyung-Gu, Incheon, Republic of Korea; Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

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http://dx.doi.org/10.1016/j.jinf.2020.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411425PMC
January 2021

Does Self-Efficacy and Team Leader Equity Matter for Older Workers' Mental Health?

Gerontologist 2020 08;60(6):996-1004

The Ohio State University College of Social Work, Columbus.

Background And Objectives: Prolonged working life is not necessarily associated with good mental health. Despite the importance of healthy working life in later years, little research has been conducted on predictors of mental health in the workplace among older workers. This study aimed to investigate how personal (self-efficacy) and team (leader equity) factors are associated with older workers' mental health through work engagement.

Research Design And Methods: We analyzed responses of 508 U.S. workers aged 50 years and older from the Age and Generations Study data using structural equation modeling.

Results: Results showed that perceived self-efficacy was a strong predictor of mental health. Also, work engagement was a powerful mechanism for promoting older adults' mental health; engagement partially mediated the relationship between perceived self-efficacy and mental health, and fully mediated the relationship between team leader equity and mental health.

Discussion And Implications: The findings highlight how important it is for employers to invest in human capital development, suggesting human resource programs should focus on strategies that target older adults' engagement through tailored self-efficacy programs and inclusive leadership training programs. Such attempts would contribute to enhancing the mental health of older workers.
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http://dx.doi.org/10.1093/geront/gnz191DOI Listing
August 2020

Chronic encapsulated expanding hematoma after stereotactic radiosurgery of cerebral arteriovenous malformation.

J Cerebrovasc Endovasc Neurosurg 2019 Sep 30;21(3):152-157. Epub 2019 Sep 30.

Department of Neurosurgery, Ilsan Paik Hospital, College of Medicine, Inje University, Korea.

Stereotactic radiosurgery has become excellent alternative treatment for cerebral arteriovenous malformations (AVM). This technique has expanded to treatment of larger AVM which is not amenable to surgical management. However, its variable adverse effects should be also taken into considerations sincerely because of radiobiological characteristics such as delayed onset and progressive neurological deteriorations. Herein, we report a case in which progressively expanding hemorrhagic cyst with repeated bleedings so called chronic encapsulated expanding hematoma was developed on several years after radiosurgery treatment. Neurological and radiological findings were improved by surgical removal.
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http://dx.doi.org/10.7461/jcen.2019.21.3.152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911927PMC
September 2019

Dysregulation of the miRNA biogenesis components DICER1, DROSHA, DGCR8 and AGO2 in clear cell renal cell carcinoma in both a Korean cohort and the cancer genome atlas kidney clear cell carcinoma cohort.

Oncol Lett 2019 Oct 16;18(4):4337-4345. Epub 2019 Aug 16.

Department of Immunology, School of Medicine, Keimyung University, Dalseo-gu, Daegu 42601, Republic of Korea.

Impairment of microRNA (miRNA) biogenesis may be involved in clear cell renal cell carcinoma (ccRCC). The objective of the present study was to investigate the mRNA levels of important miRNA machinery components, , DiGeroge syndrome critical region gene 8 (), and Argonaute 2 (), and their correlations with clinicopathological characteristics of ccRCC using mRNA expression data from The Cancer Genome Atlas kidney clear cell carcinoma (TCGA KIRC) cohort and a Korean ccRCC cohort. mRNA levels of , and were significantly decreased in both cohorts. However, was significantly downregulated only in the Korean ccRCC cohort. Additionally, positive correlations were observed between the altered mRNA levels of and as well as and in both cohorts. In the TCGA KIRC cohort, alterations in the mRNA levels of were significantly correlated with histological grade. Furthermore, the altered mRNA levels of showed significant associations with sex and histologic grades. However, in the Korean ccRCC cohort, no factors were significantly associated with any clinicopathological parameters, including sex, age, T stage, Fuhrman grade/The International Society of Urological Pathology grade, lymphovascular invasion, and peri-renal fat invasion. Taken together, these findings indicate that and are significantly dysregulated in ccRCC, suggesting that they are important in the pathophysiology of this malignancy.
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http://dx.doi.org/10.3892/ol.2019.10759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732956PMC
October 2019

Identification of clinical characteristics and factors predicting favorable treatment outcomes in elderly patients with traumatic brain injury.

J Clin Neurosci 2019 Nov 23;69:61-66. Epub 2019 Aug 23.

Department of Neurosurgery, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea. Electronic address:

Age is an important prognostic factor for patients with traumatic brain injury (TBI), and worse treatment outcomes have been reported in elderly patients. Therefore, proper treatment is needed for the increasing number of elderly patients with TBI. We aimed to analyze predictive factors of favorable treatment outcomes (FTO) in elderly patients. Clinical and radiological data from 493 patients with TBI who visited a single institute were retrospectively collected from January 2014 to December 2015. We compared the characteristics of the elderly group (individuals above 65 years) and younger group (16-65 years). We analyzed the characteristics and outcomes in both groups and the factors related to the Glasgow outcome scale-extended score at 6 months after injury in 170 elderly patients. The treatment outcomes were dichotomized into favorable and unfavorable groups. In the elderly group, the proportion of female patients and the incidence of subdural hemorrhage (SDH) were higher than in the younger group. Among the 170 elderly patients, 62 had pure SDH, and 21 of the 62 with pure SDH had undergone surgical treatment. Compared with other types of intracranial hemorrhage, FTO was as high as 85.5%, and mortality was as low as 11.3% in patients with pure SDH. High initial Glasgow coma scale score, low injury severity score, and normal pupillary reflex were significantly related to FTO in multivariate analysis. Therefore, active therapeutic strategies, including surgery should be considered for elderly patients with pure SDH without intra-parenchymal injury.
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http://dx.doi.org/10.1016/j.jocn.2019.08.035DOI Listing
November 2019

Age-friendly communities and perceived disconnectedness: the role of built environment and social engagement.

J Aging Health 2020 10 26;32(9):937-948. Epub 2019 Jul 26.

The Ohio State University, Columbus, OH, USA.

To examine the effect of access to outdoor space and buildings and social or community events on elders' perceived disconnectedness. Data were from a representative survey conducted as part of an age-friendly community initiative in a large midwestern city in the United States. Hierarchical logistic regression was employed to examine the relationships between environment, engagement, and connection. Having access to ramps to enter buildings reduced the odds of perceived disconnectedness by 79%, participation in social or community events reduced the odds of perceived disconnectedness by 83%. The odds of perceived disconnectedness for elders "not sure" of their access to public buildings were around 6 times that of those without access, holding all else constant. Ensuring access to ramps to enter buildings, disseminating information about the accessibility of parks and buildings, and social or community events may reduce elders' perceived disconnectedness.
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http://dx.doi.org/10.1177/0898264319865421DOI Listing
October 2020

Intimate Partner Violence in India: Abuse in India's Empowered Action Group States.

Violence Against Women 2020 07 10;26(9):972-986. Epub 2019 Jun 10.

The Ohio State University, Columbus, USA.

Married women in India experience intimate partner violence (IPV) at alarming rates. This study explores regional differences in Indian women's physical IPV experiences by looking at the effect of living in eight Empowered Action Group (EAG) states. It is hypothesized that women in EAG states will be more likely to have experienced physical IPV than women living outside EAG states. A sample of 65,587 women was selected from the 2005-2006 India National Family Health Survey (NFHS-3). Counter to our hypothesis, logistic regression results show that living in an EAG state decreases likelihood of physical IPV in the past 12 months.
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http://dx.doi.org/10.1177/1077801219848500DOI Listing
July 2020

Comparative omics analyses of hepatotoxicity induced by oral azole drugs in mice liver and primary hepatocytes.

Toxicol Mech Methods 2019 Sep 11;29(7):531-541. Epub 2019 Jun 11.

a Department of Predictive Toxicology , Korea Institute of Toxicology (KIT) , Daejeon , Republic of Korea.

Ketoconazole (KTZ) and itraconazole (ITZ) are antifungal agents that have a broad spectrum of activity against fungal pathogens. However, the therapeutic indications of many antifungal drugs, including those of the azole group, are restricted due to possible hepatotoxicity. We performed toxicogenomic analyses using and models to investigate the molecular mechanisms underlying the hepatotoxicity of two azole antifungal drugs. C57BL/6 male mice were treated daily with KTZ or ITZ, sacrificed at days 1 or 7, and the serum biochemistry and histopathology results showed that the KTZ-treated mice exhibited hepatotoxicity. Primary hepatocytes from C57BL/6 mice also exposed to KTZ or ITZ, and the cytotoxic effects of KTZ and ITZ were evaluated; KTZ exerted a greater cytotoxic effect than ITZ. The gene expression profiles in the livers of the 7-day-treated group and primary hepatocytes of the 24-h-treated group for both KTZ and ITZ were comparatively analyzed. Differentially expressed genes were selected based on the fold-changes and statistical significance, and the biological functions were analyzed using ingenuity pathways analysis. The results revealed that genes related to cholesterol synthesis were overexpressed in the liver in the KTZ-treated group, whereas expression of those related to acute phase injury was significantly altered in the ITZ-treated group. Causal gene analyses suggested that sterol regulatory element-binding transcription factors are key regulators that activate the transcription of target genes associated with the hepatotoxicity induced by oral KTZ. These findings enhance our understanding of the molecular mechanisms underlying the hepatotoxicity of azole drugs.
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http://dx.doi.org/10.1080/15376516.2019.1619214DOI Listing
September 2019

Access to Employment, Volunteer Activities, and Community Events and Perceptions of Age-Friendliness: The Role of Social Connectedness.

J Appl Gerontol 2020 09 5;39(9):1016-1024. Epub 2019 May 5.

The Ohio State University, Columbus, USA.

The aim of this study was to investigate the direct and indirect effects of access to employment, volunteer opportunities, and community events on older adults' perception of age-friendliness and feelings of connectedness. Data were from an age-friendly community survey conducted in a Midwestern city in the United States. We analyzed the responses of 264 older adult residents (50 years and older) using path analysis. Results showed that access to community events, job resources, and connectedness were predictors of older adults' perceptions of age-friendliness of their community, and that connectedness mediated the relationship between access to community events and perceived age-friendliness. The findings help to refine the concept of an age-friendly community from older adults' perspectives and emphasize the importance of fostering interactions through community events to enhance older adults' feelings of connectedness.
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http://dx.doi.org/10.1177/0733464819847588DOI Listing
September 2020

Gene networking in colistin-induced nephrotoxicity reveals an adverse outcome pathway triggered by proteotoxic stress.

Int J Mol Med 2019 Mar 8;43(3):1343-1355. Epub 2019 Jan 8.

Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea.

Colistin has been widely used for the treatment of infections of multidrug‑resistant Gram‑negative bacteria, despite the fact that it induces serious kidney injury as a side effect. To investigate the mechanism underlying its nephrotoxicity, colistin methanesulfonate sodium (CMS; 25 or 50 mg/kg) was administered via intraperitoneal injection to Sprague‑Dawley rats daily over 7 days. Serum biochemistry and histopathology indicated that nephrotoxicity occurred in the rats administered with CMS. Whole‑genome microarrays indicated 894 differentially expressed genes in the group treated with CMS (analysis of variance, false discovery rate <0.05, fold‑change ≥1.3). Gene pathway and networking analyses revealed that genes associated with proteotoxic stress, including ribosome synthesis, protein translation, and protein folding, were significantly associated with the nephrotoxicity induced by CMS. It was found that colistin inhibited the expression of the target genes heat shock factor 1 and nuclear factor erythroid‑2‑related factor‑2, which are associated with proteostasis, and that nephrotoxicity of CMS may be initiated by proteotoxic stress due to heat shock response inhibition, leading to oxidative stress, endoplasmic reticulum stress, cell cycle arrest and apoptosis, eventually leading to cell death. A putative adverse outcome pathway was constructed based on the integrated gene networking data, which may clarify the mode of action of colistin‑induced nephrotoxicity.
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http://dx.doi.org/10.3892/ijmm.2019.4052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365082PMC
March 2019

Identifying candidates for gamma knife radiosurgery among elderly patients with brain metastases.

J Neurooncol 2018 May 11;137(3):559-565. Epub 2018 Jan 11.

Gamma Knife Center, Department of Neurosurgery, Ajou University School of Medicine, 164 World Cup-ro, Yeongtong-Gu, Suwon, 16499, South Korea.

We investigated the outcomes of gamma knife radiosurgery (GKRS) for elderly patients (≥ 65 years) with brain metastases, and identified survival-associated factors. We retrospectively analyzed data from 115 patients treated with GKRS for 1-15 brain metastases. The median patient age was 72 years; most primary tumors were pulmonary (n = 83). The mean lesion volume was 2.1 ± 4.8 mL. A mean dose of 19.3 Gy was delivered to the mean 63.9% isodose line. The median overall survival (OS) was 5.3 months (95% confidence interval [CI] 3.5-7.1). During follow-up (median, 5.1 months), 91 patients died of primary cancer progression while 1 died of unknown causes. The 6- and 12-month local control rates were 94.9 and 88.1%, respectively. On multivariate analysis, female sex (p = 0.005, hazard ratio [HR] 0.533, 95% CI 0.343-0.827) and a controlled primary tumor (p < 0.001, HR 0.328, 95% CI 0.180-0.596) were significantly favorable prognostic factors. Of non-small cell lung cancer patients with EGFR mutations, 76.5% were women (p = 0.005). The median OS of EGFR-mutant and EGFR-wildtype patients were 19.1 and 4.7 months, respectively (p = 0.080). Brain metastases < 3 mL showed better local control rates after GKRS (p = 0.005). GKRS produces favorable outcomes in women with brain metastases who are ≥ 65 years and have controlled primary tumors. Such patients are therefore suitable candidates for GKRS.
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http://dx.doi.org/10.1007/s11060-018-2745-4DOI Listing
May 2018

Severe Facial Fracture is Related to Severe Traumatic Brain Injury.

World Neurosurg 2018 Mar 7;111:e47-e52. Epub 2017 Dec 7.

Department of Neurosurgery, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address:

Background: Facial fractures frequently occur with traumatic brain injury (TBI). The relationship between facial fractures and brain trauma remains controversial. The objective of this study was to analyze the correlation between facial fracture and TBI.

Methods: Clinical and radiologic data of a total of 206 patients were retrospectively collected from May 2011 to December 2015 in a single institute. Facial fracture was classified by the Facial Injury Severity Scale (FISS). TBI was grouped according to the Glasgow Coma Scale. Outcome was measured with the Glasgow Outcome Scale Extended 3, 6, and 12 months after trauma.

Results: There were 206 TBI patients with concomitant facial fracture including 166 (78.1%) males and 40 (19.4%) females. Mean age of all patients was 46 ± 19 years. Contusion and brain swelling were more frequent in higher FISS patients. Cranial surgery was done in 63 cases while facial fracture surgery was performed in 89 cases. There were 33 expired cases, including 6 cases due to multi-organ failure. High FISS was significantly associated with severe TBI and less favorable outcome 3 months after trauma. Concomitant surgical treatment for TBI and facial fracture was done in 21 cases without achieving more improved outcome compared with staged operations for 41 cases.

Conclusion: Severity of facial fracture might be correlated with severity of TBI. Surgical timing of facial fracture with TBI patients does not affect the outcome of TBI.
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http://dx.doi.org/10.1016/j.wneu.2017.11.166DOI Listing
March 2018

Concurrent Surgery of Craniectomy and Splenectomy as Initial Treatment in Severe Traumatic Head Injury: A Case Report.

Korean J Neurotrauma 2017 Oct 31;13(2):141-143. Epub 2017 Oct 31.

Department of Neurosurgery, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea.

It is not a common case for neurosurgery department and the other departments to perform joint operation at the same time. Patients with severe head injury are a condition in which vital signs are unstable due to severe brain swelling and increased intracranial pressure, and emergency surgery is required. A 44-year-old man visited the trauma center with a motorcycle accident. The Glasgow Coma Scale score at the time of emergency department was 3 points, and the pupil was fixed at 6 mm on both sides. His medical history was unknown. His vital signs including blood pressure (BP), heart rate, respiratory rate and oxygen saturation were stable. Associated injuries included multiple fractures of whole body. Brain computed tomography revealed subarachnoid hemorrhage, intraventricular hemorrhage and severe cerebral edema. During the preparation of the craniectomy, abdominal ultrasonography performed because of decreased BP resulted in a large amount of hemoperitoneum. The bi-coronal craniectomy and splenectomy were performed simultaneously for about 4 hours. After fifty days of treatment, he was discharged with Glasgow Outcome Scale-extended 4 points and is undergoing rehabilitation. In severe polytrauma patients, active concurrent surgery is a good method to save their lives.
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http://dx.doi.org/10.13004/kjnt.2017.13.2.141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702750PMC
October 2017

Reappraisal of Neonatal Greenstick Skull Fractures Caused by Birth Injuries: Comparison of 3-Dimensional Reconstructed Computed Tomography and Simple Skull Radiographs.

World Neurosurg 2018 Jan 5;109:e305-e312. Epub 2017 Oct 5.

Department of Neurosurgery, Ajou University School of Medicine, Suwon, South Korea.

Objective: The most common birth-associated head injuries during vaginal delivery are cephalhematomas and subgaleal hematomas. Cranial injuries are rarely encountered. The neonate cranium is soft and pliable, and greenstick skull fractures (GSFs) are expected to be more frequent than linear or depressed fractures, but they are extremely difficult to detect with simple skull radiography. As a result, no reports have been issued on this topic to date. Recent reports suggest that technological advances in 3-dimensional (3D) computed tomography (CT) have successfully enhanced the diagnostic accuracy for cranial fractures. The authors researched the types and characteristics of GSFs and the diagnostic accuracy of 3D CT for cranial fractures in neonates.

Methods: The simple skull radiographs and 3D CT images of 101 neonates were retrospectively evaluated and compared with respect to diagnosis of cranial fractures, and skull GSFs were classified on the basis of 3D CT findings into 5 types depending on multiplicity and location.

Results: 3D CT detected 88 cases of cranial fractures, that is, 89 GSFs, 4 combined GSFs and linear fractures, and 3 combined GSFs and depressed fractures. The diagnostic rate of 3DCT was 91% and this was significantly higher than the 13% rate of simple skull radiographs (P < 0.001).

Conclusions: GSFs rather than linear fractures were found to account for most cranial injuries among neonates. The diagnostic accuracy of 3D CT was considerably superior than simple skull radiography, but the high radiation exposure levels of 3D CT warrant the need for development of a modality with lower radiation exposure.
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http://dx.doi.org/10.1016/j.wneu.2017.09.168DOI Listing
January 2018

Reappraisal of Pediatric Diastatic Skull Fractures in the 3-Dimensional CT Era: Clinical Characteristics and Comparison of Diagnostic Accuracy of Simple Skull X-Ray, 2-Dimensional CT, and 3-Dimensional CT.

World Neurosurg 2017 Dec 24;108:399-406. Epub 2017 Aug 24.

Department of Neurosurgery, Inje University Seoul Paik Hospital, Seoul, Korea.

Background: Diastatic skull fractures (DSFs) in children are difficult to detect in skull radiographs before they develop into growing skull fractures; therefore, little information is available on this topic. However, recent advances in 3-dimensional (3D) computed tomography (CT) imaging technology have enabled more accurate diagnoses of almost all forms of skull fracture. The present study was undertaken to document the clinical characteristics of DSFs in children and to determine whether 3D CT enhances diagnostic accuracy.

Methods: Two hundred and ninety-two children younger than 12 years with skull fractures underwent simple skull radiography, 2-dimensional (2D) CT, and 3DCT. Results were compared with respect to fracture type, location, associated lesions, and accuracy of diagnosis.

Results: DSFs were diagnosed in 44 (15.7%) of children with skull fractures. Twenty-two patients had DSFs only, and the other 22 had DSFs combined with compound or mixed skull fractures. The most common fracture locations were the occipitomastoid (25%) and lambdoid (15.9%). Accompanying lesions consisted of subgaleal hemorrhages (42/44), epidural hemorrhages (32/44), pneumocephalus (17/44), and subdural hemorrhages (3/44). A total of 17 surgical procedures were performed on 15 of the 44 patients. Fourteen and 19 patients were confirmed to have DSFs by skull radiography and 2D CT, respectively, but 3D CT detected DSFs in 43 of the 44 children (P < 0.001).

Conclusion: 3D CT was found to be markedly superior to skull radiography or 2D CT for detecting DSFs. This finding indicates that 3D CT should be used routinely rather than 2D CT for the assessment of pediatric head trauma.
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http://dx.doi.org/10.1016/j.wneu.2017.08.107DOI Listing
December 2017

Role of semi-quantitative dynamic contrast-enhanced MR imaging in characterization and grading of prostate cancer.

Eur J Radiol 2017 Sep 6;94:154-159. Epub 2017 Jul 6.

Kyungbook National University Hospital, Department of Radiology, Republic of Korea.

Objective: The study retrospectively assessed the diagnostic value of semi-quantitative dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in characterization and grading of prostate cancer, with correlation to histopathological analysis.

Materials And Methods: 161 consecutive patients with prostate cancer underwent DCE MRI. 430 lesions, including 200 cancers with Gleason grade (GG) of 6 (n=25), 7 (n=112) and 8 or higher (n=63); 80 benign hyperplasia; and 150 healthy tissues were assessed using a histology-MRI correlation. Time-intensity curve types between two radiologists and kinetic parameters (C, time to peak, wash-in and wash-out) were compared in the different tissue types and GGs. Receiver operating characteristic curve analysis was performed to assess for each parameter to differentiate cancer from benign hyperplasia or healthy tissue, and GG 8 or higher from GG 6 or 7.

Results: Type 2 was the prevalent assigned curve type. Inter-radiologist agreement for the curve types was excellent. Cancer and GG 8 or higher significantly showed a higher C and faster wash-in compared to healthy tissue and GG 6. Only wash-in significantly differentiated cancer from healthy tissue, and GG 8 or higher from GG 6, having an area under the curve (AUC) of 0.755 and 0.815 respectively. Wash-in for the combined parameters revealed AUCs of 0.791 and 0.839 in two (C) parameters, and AUCs of 0.862 and 0.891 in three (C and wash-out) parameters.

Conclusion: Semi-quantitative parameters can differentiate cancer from benign hyperplasia and healthy tissue. Wash-in is the most accurate differentiation parameter of cancer foci and GG 8 or higher.
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http://dx.doi.org/10.1016/j.ejrad.2017.06.021DOI Listing
September 2017

Validation of Prostate Imaging Reporting and Data System Version 2 Using an MRI-Ultrasound Fusion Biopsy in Prostate Cancer Diagnosis.

AJR Am J Roentgenol 2017 Oct 13;209(4):800-805. Epub 2017 Jul 13.

1 Department of Radiology, Dongsan Hospital, Keimyung University, 56 Dalsungro, Jung-gu, Daegu 41932, Korea.

Objective: The purpose of our study was to prospectively assess Prostate Imaging Reporting and Data System (PI-RADS) version 2 using an MRI-ultrasound fusion biopsy.

Subjects And Methods: This study included 295 consecutive patients with 478 lesions who underwent multiparametric MRI and subsequent MRI-ultrasound fusion biopsy between December 2014 and September 2016. Lesions were assessed by using an overall score of PI-RADS version 2. One radiologist assessed the presence or absence of clinically significant prostate cancer in the whole gland and in subgroups of the peripheral zone and transition zone by using cutoff values of ≥ 4 and ≥ 3. Histologic examination of MRI-ultrasound fusion biopsy specimens was used as the reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated to assess the utility of PI-RADS version 2 for the diagnosis of clinically significant prostate cancer.

Results: The overall PI-RADS version 2 scores showed an accuracy of 82.2% (393/478) for the whole gland, with a cutoff value of ≥ 4 granting sensitivity of 90.0% (90/100), specificity of 80.1% (303/378), PPV of 83.3% (90/108), and NPV of 81.8% (303/370). The overall scores showed accuracies of 84.7% (301/355) in the peripheral zone and 74.7% (92/123) in the transition zone. When we applied an arbitrary overall score of ≥ 3, accuracy was 68.6% (328/478), sensitivity was 94.6% (124/131), specificity was 58.7% (204/347), PPV was 51.6% (124/240), and NPV was 85.7% (204/238).

Conclusion: PI-RADS version 2 has an overall good performance for the diagnosis of clinically significant prostate cancer.
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http://dx.doi.org/10.2214/AJR.16.17629DOI Listing
October 2017

HSV-1 ICP27 represses NF-κB activity by regulating Daxx sumoylation.

BMB Rep 2017 May;50(5):275-280

Department of Microbiology & Molecular Biology, College of Biological Science and Biotechnology, Chungnam National University, Daejeon 34134, Korea.

Herpes simplex virus type 1 ICP27 is a multifunctional protein responsible for viral replication, late gene expression, and reactivation from latency. ICP27 interacts with various cellular proteins, including Daxx. However, the role of interaction between ICP27 and Daxx is largely unknown. Since Daxx is known to repress NF-κB activity, there is a possibility that ICP27 may influence the inhibitory effect of Daxx on NF-κB activity. In this study, we tested whether ICP27 affects the NF-κB activity through its interaction with Daxx. Interestingly, ICP27 enhanced the Daxx-mediated repression of NF-κB activity. In addition, we found that sumoylation of Daxx regulates its interaction with p65. ICP27 binds to Daxx, inhibits Daxx sumoylation, and enhances p65 deacetylation induced by Daxx. Consequently, ICP27 represses the NF-B activity, by elevating the inhibitory effect of Daxx on NF-κB activity through desumoylation of Daxx. [BMB Reports 2017; 50(5): 275-280].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458678PMC
http://dx.doi.org/10.5483/bmbrep.2017.50.5.010DOI Listing
May 2017

Immunogenomics reveal molecular circuits of diclofenac induced liver injury in mice.

Oncotarget 2016 Mar;7(12):14983-5017

Centre for Pharmacology and Toxicology, Hannover Medical School, 30625 Hannover, Germany.

Diclofenac is a non-steroidal anti-inflammatory drug and its use can be associated with severe adverse reactions, notably myocardial infarction, stroke and drug-induced liver injury (DILI). In pursue of immune-mediated DILI mechanisms an immunogenomic study was carried out. Diclofenac treatment of mice at 30 mg/kg for 3 days caused significant serum ALT and AST elevations, hepatomegaly and degenerative changes including hepatic glycogen depletion, hydropic swelling, cholesterolosis and eosinophilic hepatocytes with one animal presenting subsegmental infarction due to portal vein thrombosis. Furthermore, portal/periportal induction of the rate limiting enzyme in ammonia detoxification, i.e. carbamoyl phosphate synthetase 1 was observed. The performed microarray studies informed on > 600 differential expressed genes of which 35, 37 and 50 coded for inflammation, 51, 44 and 61 for immune and 116, 129 and 169 for stress response, respectively after single and repeated dosing for 3 and 14 days. Bioinformatic analysis defined molecular circuits of hepatic inflammation with the growth hormone (Ghr)- and leptin receptor, the protein-tyrosine-phosphatase, selectin and the suppressor-of-cytokine-signaling (Socs) to function as key nodes in gene regulatory networks. Western blotting confirmed induction of fibronectin and M-CSF to hallmark tissue repair and differentiation of monocytes and macrophages. Transcript expression of the macrophage receptor with collagenous structure increased > 7-fold and immunohistochemistry of CD68 evidenced activation of tissue-resident macrophages. Importantly, diclofenac treatment prompted strong expression of phosphorylated Stat3 amongst individual animals and the associated 8- and 4-fold Soc3 and Il-6 induction reinforced Ghr degradation as evidenced by immunoblotting. Moreover, immunohistochemistry confirmed regulation of master regulatory proteins of diclofenac treated mice to suggest complex pro-and anti-inflammatory reactions in immune-mediated hepatic injury. The findings encourage translational research.
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http://dx.doi.org/10.18632/oncotarget.7698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924767PMC
March 2016

Frequency of MED12 mutations in phyllodes tumors: Inverse correlation with histologic grade.

Genes Chromosomes Cancer 2016 06 3;55(6):495-504. Epub 2016 Mar 3.

Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Phyllodes tumor (PT) is a rare breast biphasic tumor with a potential risk of recurrence and metastasis. In this study, the frequency of MED12 mutations in 176 PTs (49 benign, 49 borderline, and 78 malignant) was determined and the prognostic effect of these mutations in malignant type PT was evaluated. Analysis of MED12 mutations was performed by Sanger sequencing targeting the hotspot mutation region (exon 2) of MED12. Immunohistochemistry was also applied for evaluation of MED12 protein expression on tissue microarray blocks for 133 PTs including 50 benign, 50 borderline, and 33 malignant cases. A notable difference in the frequency of MED12 mutations was found according to histologic grade (71.4% of benign PTs, 51% of borderline PTs, 26.9% of malignant PTs; P < 0.001). MED12 protein expression was not correlated with MED12 mutation status. Patients with malignant PTs that harbored MED12 mutations demonstrated improved disease-free survival (DFS) compared with those without MED12 mutation (P = 0.07). MED12 mutation was a common molecular alteration in PT and the frequency of MED12 mutation decreased with increasing histologic grade. In malignant PT, MED12 exon 2 mutations showed improved DFS but without significance. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/gcc.22351DOI Listing
June 2016

Integrative analysis of genes and miRNA alterations in human embryonic stem cells-derived neural cells after exposure to silver nanoparticles.

Toxicol Appl Pharmacol 2016 May 6;299:8-23. Epub 2015 Nov 6.

Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea; Department of human and environmental toxicology, University of Science & Technology, Daejeon 34113, Republic of Korea. Electronic address:

Given the rapid growth of engineered and customer products made of silver nanoparticles (Ag NPs), understanding their biological and toxicological effects on humans is critically important. The molecular developmental neurotoxic effects associated with exposure to Ag NPs were analyzed at the physiological and molecular levels, using an alternative cell model: human embryonic stem cell (hESC)-derived neural stem/progenitor cells (NPCs). In this study, the cytotoxic effects of Ag NPs (10-200μg/ml) were examined in these hESC-derived NPCs, which have a capacity for neurogenesis in vitro, at 6 and 24h. The results showed that Ag NPs evoked significant toxicity in hESC-derived NPCs at 24h in a dose-dependent manner. In addition, Ag NPs induced cell cycle arrest and apoptosis following a significant increase in oxidative stress in these cells. To further clarify the molecular mechanisms of the toxicological effects of Ag NPs at the transcriptional and post-transcriptional levels, the global expression profiles of genes and miRNAs were analyzed in hESC-derived NPCs after Ag NP exposure. The results showed that Ag NPs induced oxidative stress and dysfunctional neurogenesis at the molecular level in hESC-derived NPCs. Based on this hESC-derived neural cell model, these findings have increased our understanding of the molecular events underlying developmental neurotoxicity induced by Ag NPs in humans.
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http://dx.doi.org/10.1016/j.taap.2015.11.004DOI Listing
May 2016

Photoprotective Potential of Penta-O-Galloyl-β-DGlucose by Targeting NF-κB and MAPK Signaling in UVB Radiation-Induced Human Dermal Fibroblasts and Mouse Skin.

Mol Cells 2015 Nov 4;38(11):982-90. Epub 2015 Nov 4.

Department of Pharmacology, Seoul National University College of Medicine, Seoul 110-799, Korea.

Exposure of the skin to ultraviolet radiation can cause skin damage with various pathological changes including inflammation. In the present study, we identified the skin-protective activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (pentagalloyl glucose, PGG) in ultraviolet B (UVB) radiation-induced human dermal fibroblasts and mouse skin. PGG exhibited antioxidant activity with regard to intracellular reactive oxygen species (ROS) generation as well as ROS and reactive nitrogen species (RNS) scavenging. Furthermore, PGG exhibited anti-inflammatory activity, inhibiting the activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, resulting in inhibition of the expression of pro-inflammatory mediators. Topical application of PGG followed by chronic exposure to UVB radiation in the dorsal skin of hairless mice resulted in a significant decrease in the progression of inflammatory skin damages, leading to inhibited activation of NF-κB signaling and expression of pro-inflammatory mediators. The present study demonstrated that PGG protected from skin damage induced by UVB radiation, and thus, may be a potential candidate for the prevention of environmental stimuli-induced inflammatory skin damage.
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http://dx.doi.org/10.14348/molcells.2015.0169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673413PMC
November 2015

Hemorrhagic hemangioma in the liver: A case report.

World J Gastroenterol 2015 Jun;21(23):7326-30

Jeong Min Kim, Woo Jin Chung, Byoung Kuk Jang, Jae Seok Hwang, Department of Internal Medicine, Keimyung University School of Medicine, Daegu 700-712, South Korea.

Hemangioma is the most common type of benign tumor that arises in the liver. Although rupture and hemorrhage of hepatic hemangioma are rare complications, they can be the cause of mortality. The authors report a case of hemorrhagic hepatic hemangioma: in a 54-year-old woman who was admitted with epigastric pain. She had taken oral contraceptives several weeks prior. The results of a blood examination were normal. An abdominal computed tomography scan revealed a tumor in hepatic segment 4, and a hemorrhage inside the cystic mass was suspected. The mass was removed laparoscopically to confirm the tumor properties and control the hemorrhage. The pathologic findings of the resected mass were consistent with hepatic hemangioma with intratumoral hemorrhage. The patient was discharged 8 d after the surgery, without further complications or complaints, and the patient's condition was found to have improved during follow-up.
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http://dx.doi.org/10.3748/wjg.v21.i23.7326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476897PMC
June 2015

Lipoma causing glossopharyngeal neuralgia: a case report and review of literature.

J Korean Neurosurg Soc 2014 Aug 31;56(2):149-51. Epub 2014 Aug 31.

Department of Neurosurgery, Ajou University School of Medicine, Suwon, Korea.

The cerebello-pontine angle lipomas causing trigeminal neuralgia or hemifacial spasm are rare. A lipoma causing glossopharyngel neuralgia is also very rare. A 46-year-old woman complained of 2-year history of severe right throat pain, with ipsilateral episodic otalgic pain. The throat pain was described as an episodic lancinating character confined to the throat. Computed tomography and magnetic resonance imaging revealed a suspicious offending posterior inferior cerebellar artery (PICA) compressing lower cranial nerves including glossopharyngeal nerve. At surgery, a soft, yellowish mass (2×3×3 mm in size) was found incorporating the lateral aspect of proximal portion of 9th and 10th cranial nerves. Only microvascular decompression of the offending PICA was performed. Additional procedure was not performed. Her severe lancinating pain remained unchanged, immediate postoperatively. The neuralgic pain disappeared over a period of several weeks. In this particular patient with a fatty neurovascular lump causing glossopharyngeal neuralgia, microvascular decompression of offending vessel alone was enough to control the neuralgic pain.
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http://dx.doi.org/10.3340/jkns.2014.56.2.149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200364PMC
August 2014

Incidence of post-traumatic stress disorder after a mild traumatic brain injury: preliminary investigation using the brief neuropsychological screening test.

J Korean Neurosurg Soc 2014 Apr 30;55(4):190-4. Epub 2014 Apr 30.

Department of Neurosurgery, Ajou University College of Medicine, Suwon, Korea.

Objective: Post-traumatic stress disorder (PTSD) is a group of diseases that are observed in patients who had experienced a serious trauma or accident. However, some experienced it even after only a mild traumatic brain injury (TBI), and they are easily ignored due to the relatively favorable course of mild TBI. Herein, the authors investigated the incidence of PTSD in mild TBI using brief neuropsychological screening test (PTSD checklist, PCL).

Methods: This study was conducted on patients with mild TBI (Glasgow coma scale ≥13) who were admitted from January 2012 to December 2012. As for PCL, it was done on patients who showed no difficulties in communication upon admission and agreed to participate in this study. By using sum of PCL, the patients were divided into high-risk group and low-risk group. PTSD was diagnosed as the three major symptoms of PTSD according to the Diagnostic and Statistical Manual of Mental Disorders, fourth-edifion.

Results: A total of 314 TBI patients were admitted and 71 of them met the criteria and were included in this study. The mean age was 52.9 years-old (range: 15-94). The mean PCL score was 28.8 (range: 17-68), and 10 patients were classified as high-risk group. During follow-up, 2 patients (2.7%) of high risk group, were confirmed as PTSD and there was no patient who was suspected of PTSD in the low-risk group (p=0.017).

Conclusion: PTSD is observed 2.8% in mild TBI. Although PTSD after mild TBI is rare, PCL could be considered as a useful tool for screening of PTSD after mild TBI.
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http://dx.doi.org/10.3340/jkns.2014.55.4.190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094742PMC
April 2014

Low-risk prostate cancer: the accuracy of multiparametric MR imaging for detection.

Radiology 2014 May 23;271(2):435-44. Epub 2014 Jan 23.

From the Departments of Radiology (J.Y.K., S.H.K., Y.H.K., H.J.L., M.J.K.) and Pathology (M.S.C.), Keimyung University, Dongsan Hospital, 216 Dalsung-ro, Jung-gu, Daegu 700-714, Korea.

Purpose: To retrospectively determine diagnostic performance with multiparametric magnetic resonance (MR) imaging for detection of cancer of different tumor volumes and Gleason grades in patients with clinically low-risk prostate cancer.

Materials And Methods: The local ethical committee and institutional review board approved this study. Consecutive patients with clinically determined low-risk cancer (n = 100) were examined with multiparametric MR imaging (T2 weighted, diffusion weighted, and dynamic contrast material enhanced) by using a 3.0-T imager before prostatectomy. Two radiologists independently assessed the likelihood of cancer per sextant. Cancers with a volume of 0.5 cm(3) or more identified at histopathologic examination were compared with multiparametric MR images. Cancer detection with multiparametric MR imaging was assessed for tumors of different volumes and Gleason grades by using a logistic generalized estimating equation model with 95% confidence intervals (CIs) with two optimal dichotomized cutoff scores.

Results: For cancers greater than or equal to 0.5 cm(3), with respect to cancer volume and Gleason grade, multiparametric MR imaging showed high diagnostic performance for the detection of cancer. Diagnostic accuracy with multiparametric MR imaging was significantly higher for cancers with a volume greater than 1 cm(3) than for those with a volume of 0.5-1 cm(3) (87.7%; 95% CI: 82.4%, 94.3% vs 82.6%; 95% CI: 79.0%, 88.7%; P = .02) and for cancers with Gleason grades of 7 or more than for those with grades of 6 or less (89.2%; 95% CI: 85.4%, 93.8% vs 80.6%; 95% CI: 71.2%, 89.8%; P = .01). Detection rates for cancers with a volume more than 1 cm(3) and a Gleason grade of 7 or more were significantly higher than for those with a volume of 0.5-1 cm(3) and a Gleason grade of 6 or less(87.8%; 95% CI: 85.3%, 93.7% vs 82.0%; 95% CI: 75.6%, 86.1%; P = .01).

Conclusion: Detection of prostate cancer in patients with clinically low-risk cancer with multiparametric MR imaging is highly accurate, and larger cancer volume and higher Gleason grade are associated with higher detection accuracy.
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http://dx.doi.org/10.1148/radiol.13130801DOI Listing
May 2014

Effect of overexpression of glucose-regulated protein 78 and bcl-2 on recurrence and survival in patients with ureter tumors.

Korean J Urol 2013 Oct 15;54(10):671-6. Epub 2013 Oct 15.

Department of Urology, Keimyung University School of Medicine, Daegu, Korea.

Purpose: The utility of the expression of glucose-regulated protein 78 (GRP78) in the evaluation of prognosis depends on the type of tumor. Hence, we aimed to examine the impact of expression of GRP78 and Bcl-2, which are used in the existing prognostic evaluation of ureter tumors, in the evaluation of recurrence and survival rates of ureter tumors.

Materials And Methods: In 53 patients who had undergone radical nephroureterectomy for a ureter tumor from March 2002 to March 2012, age, sex, T stage, nuclear grade, bladder recurrence, and survival rate were analyzed at the time of the patient's surgery depending on the extent of immunohistochemical expression of GRP78 and Bcl-2.

Results: GRP78 was overexpressed in 25 patients (47.2%). When GRP78 was overexpressed, there was a high T stage (p=0.001) and nuclear grade (p=0.007) and a lot of bladder recurrence (40.0%, p=0.034). Bcl-2 was overexpressed in 16 patients (30.1%), and there were no significant associations with any risk factors (p>0.05, respectively). In the multivariate analysis regarding bladder recurrence, the recurrence rate was higher with higher pT stage (p=0.048) and when GRP78 (p=0.033) was overexpressed. In the Kaplan-Meier survival analysis, although the survival rate was significantly lower in the group in which GRP78 was overexpressed (p=0.03), there was no correlation between Bcl-2 overexpression and survival rate (p=0.07).

Conclusions: Patients with ureter tumors who had overexpression of GRP78 had a high T stage and nuclear grade, a lot of bladder recurrence, and a low survival rate. Therefore, if GRP78 is overexpressed in ureter tumor patients, active postoperative follow-up should be carried out.
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http://dx.doi.org/10.4111/kju.2013.54.10.671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3806990PMC
October 2013