1.Alterations in Brain Morphometric Networks and Their Relationship with Memory Dysfunction in Patients with Type 2 Diabetes Mellitus
Rye Young KIM ; Yoonji JOO ; Eunji HA ; Haejin HONG ; Chaewon SUH ; Youngeun SHIM ; Hyeonji LEE ; Yejin KIM ; Jae-Hyoung CHO ; Sujung YOON ; In Kyoon LYOO
Experimental Neurobiology 2024;33(2):107-117
Cognitive dysfunction, a significant complication of type 2 diabetes mellitus (T2DM), can potentially manifest even from the early stages of the disease. Despite evidence of global brain atrophy and related cognitive dysfunction in early-stage T2DM patients, specific regions vulnerable to these changes have not yet been identified. The study enrolled patients with T2DM of less than five years’ duration and without chronic complications (T2DM group, n=100) and demographically similar healthy controls (control group, n=50). High-resolution T1-weighted magnetic resonance imaging data were subjected to independent component analysis to identify structurally significant components indicative of morphometric networks. Within these networks, the groups’ gray matter volumes were compared, and distinctions in memory performance were assessed. In the T2DM group, the relationship between changes in gray matter volume within these networks and declines in memory performance was examined. Among the identified morphometric networks, the T2DM group exhibited reduced gray matter volumes in both the precuneus (Bonferronicorrected p=0.003) and insular-opercular (Bonferroni-corrected p=0.024) networks relative to the control group. Patients with T2DM demonstrated significantly lower memory performance than the control group (p=0.001). In the T2DM group, reductions in gray matter volume in both the precuneus (r=0.316, p=0.001) and insular-opercular (r=0.199, p=0.047) networks were correlated with diminished memory performance. Our findings indicate that structural alterations in the precuneus and insular-opercular networks, along with memory dysfunction, can manifest within the first 5 years following a diagnosis of T2DM.
2.Characterization of Glycosyl Inositol Phosphoceramides from Panax ginseng using Nanospray Tandem Mass Spectrometry
So-Hyun KIM ; Ye-Been LEE ; Yoonho JEONG ; Jae-Yeon CHO ; Hyung-Kyoon CHOI
Natural Product Sciences 2024;30(2):103-116
Korean ginseng (Panax ginseng C. A. Meyer) is one of the most popular medicinal herbs in the world. This plant is known to have many health benefits and contain a wide variety of bioactive components. However, the knowledge on its lipid compound is still far from being fully explored. Although glycosyl inositol phosphoceramides (GIPCs) are the main sphingolipids in plant tissues, GIPCs of P. ginseng are unknown. The present study employed nanoESI-MS n , which generated characteristic fragmentation pattern that were used for the structural identification of P. ginseng GIPCs. In addition to detecting a typical mass fragmentation pattern for GIPC in positive ion mode, novel fragmentation correlating with cleavage of the last carbohydrate and fatty acyl chain of the ceramide moiety was identified. In total, 42 GIPC species were detected in P. ginseng. The major P. ginseng GIPC structure was hexose (R 1 )-hexuronic acid-inositol phosphoceramide, with three types of R 1 (amine, N-acetylamine, or hydroxyl). The most intense peak was found at m/z 1136.3 ([M+H] + ion), corresponding to a GIPC (d18:0/h16:0, R 1 = OH). Only three GIPC subtypes showed significantly different levels in five- and six-year-old P. ginseng tap roots.
3.Full-Term Baby with Cerebellar Hemorrhage Referred for Severe Jaundice Occurring within the First 3 Days of Life
In Wook LEE ; Jae Kyoon HWANG ; Ja-Hye AHN ; Hyun Ju LEE ; Chang-Ryul KIM
Neonatal Medicine 2024;31(1):9-15
Cerebellar hemorrhage in full-term infants is a rare condition recently recognized in high-risk newborns requiring intensive care with the availability of advanced neuroimaging techniques. Several aspects such as the incidence, pathophysiology, clinical features, and prognosis of cerebellar hemorrhage in full-term infants remain unknown. We present a case of cerebellar hemorrhage with subdural hemorrhage in a patient hospitalized for jaundice after birth without a history of traumatic delivery, such as breech presentation, prolonged labor or forceps delivery. A full-term female infant weighing 3,100 g at birth, with no complications during delivery, developed jaundice within 48 hours of birth and was admitted for intensive phototherapy in the first 3 days of life with a transcutaneous total bilirubin level of 18.1 mg/dL. Magnetic resonance imaging revealed cerebellar brain lesions with a subdural hemorrhage. At the age of 3 months, the infant exhibited leg rigidity and was referred for rehabilitation. The patient showed signs of improvement during treatment and was generally catching up well with her peers at the age of 9 months. Long-term follow-ups are required to evaluate the consequences on cognitive development, behavior, and motor performance subsequently in life.
4.Peripheral Markers of Suicidal Behavior: Current Findings and Clinical Implications
Hee-Ju KANG ; Ju-Wan KIM ; Sung-Wan KIM ; Jung-Soo HAN ; In Kyoon LYOO ; Jae-Min KIM
Clinical Psychopharmacology and Neuroscience 2023;21(4):650-664
Biomarkers of suicidal behavior (SB), particularly peripheral biomarkers, may aid in the development of preventive and intervention strategies. The peripheral biomarkers of SB should be easily accessible, cost-effective, and minimally invasive. To identify peripheral biomarkers of SB, we summarized the current knowledge related to SB biomarkers with a focus on suicidal outcomes (suicidal ideation [SI], suicide risk [SR], suicide attempt [SA], and suicide death [SD]), measured site (center or periphery), and study design (cross-sectional or longitudinal). We also evaluated the central findings to validate the findings of peripheral biomarkers of SB. We found reduced peripheral interleukin (IL)-2 levels in individuals with a recent SA, higher cerebrospinal fluid (CSF) IL-6 levels in patients with a current SR and future SD, higher CSF tumor necrosis factor-α levels for current and future SRs, higher high-sensitivity C-reactive protein levels and lower peripheral total cholesterol levels for recent SAs, lower peripheral 5-HT levels for present SR, and a lower folate level for future SR and SA within 1 year. Previous studies have shown inconsistent associations of low peripheral leptin levels with SR and recent SA; therefore, further study is required. Given the multiple determinants of SB and weak associations with single biological markers, combinations of potential biological markers rather than single markers may improve the screening, diagnosis, and prediction of SB.
5.Effects of Ponderal Index on Neonatal Mortality and Morbidities in Extremely Premature Infants
Jae Kyoon HWANG ; Ha-Na KANG ; Ja-Hye AHN ; Hyun Ju LEE ; Hyun-Kyung PARK ; Chang-Ryul KIM
Journal of Korean Medical Science 2022;37(24):e198-
Background:
To evaluate how intrauterine stress affects extremely premature infants in terms of intrauterine growth restriction. We hypothesized that extremely premature infants with mildly-low ponderal index (MPI) would have better neonatal outcomes.
Methods:
We selected 2,721 subjects of 23 to 28 weeks of gestation between 2013 and 2015 from Korean Neonatal Network database. They were divided into 4 groups based on ponderal index (PI) percentile; PI ≤ 3rd as severely-low PI (SPI, n = 82), 3rd < PI ≤ 10th as MPI (n = 190), 10th < PI ≤ 90th as adequate PI (API, n = 2,179), and PI > 90th as high PI (HPI, n = 270).
Results:
The mortality in MPI and API groups was comparable (16.3% vs. 16.9%). It was significantly lower than that in the SPI and HPI groups (30.5% and 24.9%, respectively;P = 0.001). The MPI and API groups had better neonatal morbidities compared with the SPI and/or HPI groups, while the MPI group (8.2%) showed a lower incidence of severe intraventricular hemorrhage (IVH) than the other groups (SPI, 21.3%; API, 15.0%; HPI, 19.7%, respectively; P = 0.004). The MPI group had a trend of a bottom in neonatal mortality and morbidities in extremely premature infants.
Conclusion
The MPI and API groups had lower mortality, massive pulmonary hemorrhage, severe bronchopulmonary dysplasia or death, pulmonary hypertension and neonatal seizure rates than the SPI and/or HPI groups, while the MPI group showed a lower incidence of severe IVH than the other groups. We speculate that the lower incidence of neonatal morbidities and mortality in the MPI group indicating mild intrauterine stress might accelerate fetal maturation resulting in better outcomes in extremely premature infants.
6.Rapidly Progressive Pericardial Effusion and Cardiac Tamponade in a Term Infant with an Umbilical Venous Catheter: A Case Report
Min-Jung PARK ; Ja-Hye AHN ; Hyun Ju LEE ; Hyun-Kyung PARK ; Jae-Kyoon HWANG ; Chang-Ryul KIM ; Jae Yoon NA
Neonatal Medicine 2022;29(4):135-140
Pericardial effusion (PCE) in neonates has various clinical presentations depending on the amount and speed of fluid accumulation and can cause cardiac tamponade (CT). We report a case of rapidly accumulating PCE and near-fatal CT with an umbilical venous catheter successfully resolved by emergent echo-guided pericardiocentesis in a term infant who had been hospitalized with meconium aspiration syndrome and persistent pulmonary hypertension. This case report suggests that if a patient with an intracardiac umbilical catheter shows sudden cardiopulmonary instability, the possibility of PCE and CT should be considered. Furthermore, if necessary, emergency drainage of the PCE and removal of the umbilical catheter should be immediately performed.
7.Phosphodiesterase-5 Inhibitor Attenuates Anxious Phenotypes and Movement Disorder Induced by Mild Ischemic Stroke in Rats
Yeon Hee YU ; Seong-Wook KIM ; Juhyeon KANG ; Yejin SONG ; Hyuna IM ; Seo Jeong KIM ; Dae Young YOO ; Man-Ryul LEE ; Dae-Kyoon PARK ; Jae Sang OH ; Duk-Soo KIM
Journal of Korean Neurosurgical Society 2022;65(5):665-679
Objective:
: Patients with mild ischemic stroke experience various sequela and residual symptoms, such as anxious behavior and deficits in movement. Few approaches have been proved to be effective and safe therapeutic approaches for patients with mild ischemic stroke by acute stroke. Sildenafil (SIL), a phosphodiesterase-5 inhibitor (PDE5i), is a known remedy for neurodegenerative disorders and vascular dementia through its angiogenesis and neurogenesis effects. In this study, we investigated the efficacy of PDE5i in the emotional and behavioral abnormalities in rats with mild ischemic stroke.
Methods:
: We divided the rats into four groups as follows (n=20, respectively) : group 1, naïve; group 2, middle cerebral artery occlusion (MCAo30); group 3, MCAo30+SIL-pre; and group 4, MCAo30+SIL-post. In the case of drug administration groups, single dose of PDE5i (sildenafil citrate, 20 mg/kg) was given at 30-minute before and after reperfusion of MCAo in rats. After surgery, we investigated and confirmed the therapeutic effect of sildenafil on histology, immunofluorescence, behavioral assays and neural oscillations.
Results:
: Sildenafil alleviated a neuronal loss and reduced the infarction volume. And results of behavior task and immunofluorescence shown possibility that anti-inflammation process and improve motor deficits sildenafil treatment after mild ischemic stroke. Furthermore, sildenafil treatment attenuated the alteration of theta-frequency rhythm in the CA1 region of the hippocampus, a known neural oscillatory marker for anxiety disorder in rodents, induced by mild ischemic stroke.
Conclusion
: PDE5i as effective therapeutic agents for anxiety and movement disorders and provide robust preclinical evidence to support the development and use of PDE5i for the treatment of mild ischemic stroke residual disorders.
8.A Randomized Controlled Trial for Doing vs. Omitting Intraoperative Frozen Section Biopsy for Resection Margin Status in Selected Patients Undergoing Breast-Conserving Surgery (OFF-MAP Trial)
Tae-Kyung YOO ; Young-Joon KANG ; Joon JEONG ; Jeong-Yoon SONG ; Sun Hee KANG ; Hye Yoon LEE ; Eui Tae KIM ; Onvox YI ; Han-Byoel LEE ; Soojeong CHOI ; Hyung Seok PARK ; Geumhee GWAK ; Jae Il KIM ; Min Kyoon KIM ; Jeeyeon LEE ; Hee Joon KANG ; Byung Joo CHAE
Journal of Breast Cancer 2021;24(6):569-577
Purpose:
Intraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate.
Methods
This study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the “frozen section biopsy” or “frozen section biopsy omission” group after lumpectomy. Patients with clinical stage T1–T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness.Discussion: This is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy.We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety.
9.Effects of Lipopolysaccharide on Oligodendrocyte Differentiation at Different Developmental Stages: an In Vitro Study
Ja-Hye AHN ; Hyun Ju LEE ; Kyeongmi LEE ; Jean LIM ; Jae Kyoon HWANG ; Chang-Ryul KIM ; Hyun A KIM ; Han-Suk KIM ; Hyun-Kyung PARK
Journal of Korean Medical Science 2021;36(49):e332-
Background:
Lipopolysaccharide (LPS) exerts cytotoxic effects on brain cells, especially on those belonging to the oligodendrocyte lineage, in preterm infants. The susceptibility of oligodendrocyte lineage cells to LPS-induced inflammation is dependent on the developmental stage. This study aimed to investigate the effect of LPS on oligodendrocyte lineage cells at different developmental stages in a microglial cell and oligodendrocyte coculture model.
Methods:
The primary cultures of oligodendrocytes and microglia cells were prepared from the forebrains of 2-day-old Sprague–Dawley rats. The oligodendrocyte progenitor cells (OPCs) co-cultured with microglial cells were treated with 0 (control), 0.01, 0.1, and 1 µg/mL LPS at the D3 stage to determine the dose of LPS that impairs oligodendrocyte differentiation. The co-culture was treated with 0.01 µg/mL LPS, which was the lowest dose that did not impair oligodendrocyte differentiation, at the developmental stages D1 (early LPS group), D3 (late LPS group), or D1 and D3 (double LPS group). On day 7 of differentiation, oligodendrocytes were subjected to neural glial antigen 2 (NG2) and myelin basic protein (MBP) immunostaining to examine the number of OPCs and mature oligodendrocytes, respectively.
Results:
LPS dose-dependently decreased the proportion of mature oligodendrocytes (MBP+ cells) relative to the total number of cells. The number of MBP+ cells in the early LPS group was significantly lower than that in the late LPS group. Compared with those in the control group, the MBP+ cell numbers were significantly lower and the NG2+ cell numbers were significantly higher in the double LPS group, which exhibited impaired oligodendrocyte lineage cell development, on day 7 of differentiation.
Conclusion
Repetitive LPS stimulation during development significantly inhibited brain cell development by impairing oligodendrocyte differentiation. In contrast, brain cell development was not affected in the late LPS group. These findings suggest that inflammation at the early developmental stage of oligodendrocytes increases the susceptibility of the preterm brain to inflammation-induced injury.
10.Effect of Childhood Trauma on the Association Between Stress-Related Psychological Factors and Hair Cortisol Level in Young Adults
Won Jae KIM ; Kyung Mee PARK ; Jung Tak PARK ; Eunchong SEO ; Minji BANG ; Suk Kyoon AN ; Hye Yoon PARK ; Eun LEE
Psychiatry Investigation 2021;18(11):1131-1136
Objective:
Relationship between hair cortisol concentration (HCC) and stress-related psychological measures are inconclusive, possibly due to overlooked heterogeneity regarding childhood trauma and a lack of comprehensive research on stress-related psychological factors. This study aims to compare young adults without history of childhood trauma to young adults who experienced childhood trauma using HCC and various stress-related psychological factors, as well as investigate the impacts of childhood trauma on the association between HCC and stress-related psychological measures.
Methods:
A total of 206 young, healthy adults were recruited. We divided participants into two groups depending on whether or not they had suffered moderate-to-severe childhood trauma (CT+ and CT-) and compared HCC and various stress-related psychological measures between groups. Using multiple linear regression analyses, we assessed the associations between HCC and stress-related psychological measures for each group.
Results:
We found no difference between the groups in HCC or the reported number of stressful life events in the past year; however, CT+ individuals reported higher stress perception, more depressive and anxiety-related symptoms, and more difficulties in emotion regulation than CT- individuals. HCC was associated with emotion dysregulation among the CT- individuals, but not among the CT+ individuals.
Conclusion
These findings suggest that history of childhood trauma should be considered in studies using HCC as a biomarker for stress in young adults. Furthermore, HCC might be a useful biomarker of stress and stress-related emotion dysregulation in individuals without moderate-to-severe childhood trauma.

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