1.Coronary Artery Calcium Score as a Sensitive Indicator of Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus: A Long-Term Cohort Study
Dae-Jeong KOO ; Mi Yeon LEE ; Sun Joon MOON ; Hyemi KWON ; Sang Min LEE ; Se Eun PARK ; Cheol-Young PARK ; Won-Young LEE ; Ki Won OH ; Sung Rae CHO ; Young-Hoon JEONG ; Eun-Jung RHEE
Endocrinology and Metabolism 2023;38(5):568-577
Background:
Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden.
Methods:
We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease.
Results:
The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS <100, 100≤ CACS <400, and CACS ≥400, respectively. During the 12-year follow-up period, the difference in event-free survival more than doubled as the category increased. Patients with CACS below 10 had very low CVD incidence throughout the follow-up. The receiver operating characteristic analysis showed better area under curve when the CACS cutoff was 10 than 100.
Conclusion
CACS can be a sensitive marker of CVD risk. Specifically, CACS above 10 is an indicator of CVD high-risk requiring more intensive medical treatment in Koreans with T2DM.
2.The Effect of Vanishing Twin on Firstand Second-Trimester Maternal Serum Markers and Nuchal Translucency: A Multicenter Prospective Cohort Study
Se Jin LEE ; You Jung HAN ; Minhyoung KIM ; Jae-Yoon SHIM ; Mi-Young LEE ; Soo-young OH ; JoonHo LEE ; Soo Hyun KIM ; Dong Hyun CHA ; Geum Joon CHO ; Han-Sung KWON ; Byoung Jae KIM ; Mi Hye PARK ; Hee Young CHO ; Hyun Sun KO ; Ji Hye BAE ; Chan-Wook PARK ; Joong Shin PARK ; Jong Kwan JUN ; Sohee OH ; Da Rae LEE ; Hyun Mee RYU ; Seung Mi LEE
Journal of Korean Medical Science 2023;38(38):e300-
Background:
The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT).
Methods:
This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation.
Results:
Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment,AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group.
Conclusion
VT can be considered as an adjustment factor for risk assessment in the secondtrimester serum screening test.
3.Effect of hemp seed oil on lipid metabolism in rats fed a highcholesterol diet
Jin A LEE ; Seong-Soo ROH ; Woo Rak LEE ; Mi-Rae SHIN
Journal of Nutrition and Health 2023;56(4):361-376
Purpose:
This study evaluates the potential protective effects of hemp (Cannabis sativa L.) seed oil supplementation in rats fed a high-cholesterol diet.
Methods:
Rats were fed a 1.25% cholesterol diet for 8 weeks, followed by oral administration of either of the two doses of hemp seed oil (HO) (0.5 mL/kg (HOL group) or 1 mL/kg (HOH group) body weight/day) or simvastatin at 10 mg/kg body weight/day. Oxidative stress, lipids, liver enzymes, and renal markers were measured in the serum. Western blot analysis was applied for evaluating the expressions of inflammatory makers.
Results:
Except for HDL-cholesterol, the altered levels of lipoproteins, aminotransferases, urea, and creatine kinases in hypercholesterolemic rats were significantly corrected by HO administration. Especially, compared to the HOH group, HOL treatment further reduced AST, ALT, creatinine, TC, and LDL-cholesterol levels. Moreover, both the atherogenic index and cardiac risk factor (CRF) in the HOL group were more restrained compared to the HOH group. Increased levels of p-AMPK coincided with the inhibition of SREBP-2 activation which subsequently suppressed the expression of HMGCR. Nuclear factor (NF)-κB activation coincided with the PI3K/Akt pathway activation and the increased phosphorylation of p38;these levels were significantly suppressed by HO treatment. In addition, HO treatment markedly reversed the changes in chemokines such as ICAM-1, VCAM-1, and MCP-1.Histological alterations induced by cholesterol overload in cardiac and hepatic tissues were ameliorated by HO supplementation.
Conclusion
Taken together, our results indicate a low concentration of HO demonstrates improved dysfunctions caused by a high-cholesterol diet via inhibition of the PI3K/Akt/NF-κB signaling pathway.
4.The Role of De novo Serine Biosynthesis from Glucose in Papillary Thyroid Cancer
Seong Eun LEE ; Na Rae CHOI ; Jin-Man KIM ; Mi Ae LIM ; Bon Seok KOO ; Yea Eun KANG
International Journal of Thyroidology 2023;16(2):175-183
Background and Objectives:
The de novo serine biosynthetic pathway from glucose has emerged as one of cancer metabolism; however, it is not explored the interplay between papillary thyroid cancer and metabolic flux of de novo serine synthesis. In this study, we explored the interplay between glucose utilization via GLUT1 expression and phosphoglycerate dehydrogenase (PHGDH).
Materials and Methods:
The Cancer Genome Atlas (TCGA) database was used to determine the association between glucose importation and the serine metabolic pathway. The effects of glucose on serine biosynthesis and the role of PHGDH were investigated in papillary thyroid cancer cell lines. PHGDH and GLUT1 expression in 230 patients with papillary thyroid cancer (PTC) was explored using immunohistochemistry to explore the impact of the de novo serine biosynthetic pathway from glucose.
Results:
Glucose importation was significantly correlated with the serine biosynthetic and L-serine metabolic processes. Glucose uptake and serine synthesis were significantly increased and mitochondrial complex expression was upregulated in PTC cell lines grown in high-glucose media. Knockdown and inhibition of PHGDH decreased cell migration associated with glucose utilization. High PHGDH expression is significantly related with tumor aggressiveness and GLUT1 expression in patients with PTC.
Conclusion
In this study, we demonstrated that de novo serine biosynthesis from glucose is highly expressed in papillary thyroid cancer and associated with cancer cell metastasis through glucose utility. Our findings suggest the link between glucose utilization PHGDH to regulate tumor aggressiveness in PTC.
5.Differential Gene Expression in the Hippocampi of Nonhuman Primates Chronically Exposed to Methamphetamine, Cocaine, or Heroin
Mi Ran CHOI ; Yeung-Bae JIN ; Han-Na KIM ; Heejin LEE ; Young Gyu CHAI ; Sang-Rae LEE ; Dai-Jin KIM
Psychiatry Investigation 2022;19(7):538-550
Objective:
Methamphetamine (MA), cocaine, and heroin cause severe public health problems as well as impairments in neural plasticity and cognitive function in the hippocampus. This study aimed to identify the genes differentially expressed in the hippocampi of cynomolgus monkeys in response to these drugs.
Methods:
After the monkeys were chronically exposed to MA, cocaine, and heroin, we performed large-scale gene expression profiling of the hippocampus using RNA-Seq technology and functional annotation of genes differentially expressed. Some genes selected from RNA-Seq analysis data were validated with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). And the expression changes of ADAM10 protein were assessed using immunohistochemistry.
Results:
The changes in genes related to axonal guidance (PTPRP and KAL1), the cell cycle (TLK2), and the regulation of potassium ions (DPP10) in the drug-treated groups compared to the control group were confirmed using RT-qPCR. Comparative analysis of all groups showed that among genes related to synaptic long-term potentiation, CREBBP and GRIN3A were downregulated in both the MA- and heroin-treated groups compared to the control group. In particular, the mRNA and protein expression levels of ADAM10 were decreased in the MA-treated group but increased in the cocaine-treated group compared to the control group.
Conclusion
These results provide insights into the genes that are upregulated and downregulated in the hippocampus by the chronic administration of MA, cocaine, or heroin and basic information for developing novel drugs for the treatment of hippocampal impairments caused by drug abuse.
6.Clostridioides Infection in Patients with Inflammatory Bowel Disease
The Korean Journal of Gastroenterology 2022;80(2):66-71
Inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, is a chronic inflammatory condition of the gastrointestinal tract, which is often accompanied by altered gut microbial composition. Gut dysbiosis in IBD is considered to be the reason for the high risk of Clostridioides difficile infection (CDI) in patients with IBD. Therefore, CDI should be evaluated in IBD patients with a symptom flare. Medical treatment of non-severe CDI in IBD is similar to that in non-IBD patients and includes oral vancomycin or fidaxomicin. The risk of recurrent CDI in IBD is higher than in non-IBD patients and this could be mitigated by fecal microbiota transplantation. As CDI may worsen the clinical outcomes of IBD, patients should be carefully monitored and an escalation of IBD therapy needs to be considered when there is no improvement seen with the antimicrobial treatment of CDI. This review discusses the risk, pathophysiology, diagnosis, and management of CDI in IBD.
7.Risk Factors for Coronavirus Disease 2019 (COVID-19)-Associated Pulmonary Aspergillosis in Critically Ill Patients: A Nationwide, Multicenter, Retrospective Cohort Study
Si-Ho KIM ; Jin Yeong HONG ; Seongman BAE ; Hojin LEE ; Yu Mi WI ; Jae-Hoon KO ; Bomi KIM ; Eun-Jeong JOO ; Hyeri SEOK ; Hye Jin SHI ; Jeong Rae YOO ; Miri HYUN ; Hyun ah KIM ; Sukbin JANG ; Seok Jun MUN ; Jungok KIM ; Min-Chul KIM ; Dong-Sik JUNG ; Sung-Han KIM ; Kyong Ran PECK
Journal of Korean Medical Science 2022;37(18):e134-
Background:
Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated.
Methods:
This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model.
Results:
Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03–13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26–14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P= 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089).
Conclusion
Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.
8.Organized Hematoma of the Maxillary Sinus: Surgical Excision by Midfacial Degloving Approach
Seul Ki LEE ; Mi Ri MOON ; Sang Rae PARK ; Hye Hyeon JO ; Yong Bin LEE
Journal of Korean Dental Science 2022;15(1):68-74
Organized hematoma of maxillary sinus is a rare pathologically benign mass in which pressure in the hematoma increases as it undergoes a process of organization, causing the deformation of the surrounding tissue, mimicking malignancies. The midfacial degloving approach can be used when extensive exposure is required in the treatment of lesions or traumas in the midfacial area with intranasal and intraoral incisions. We report a surgical excision case of organized hematoma of maxillary sinus using midfacial degloving approach without major complications and recurrence after one-year follow up.
9.Diabetes Fact Sheets in Korea, 2020: An Appraisal of Current Status
Chan-Hee JUNG ; Jang Won SON ; Shinae KANG ; Won Jun KIM ; Hun-Sung KIM ; Hae Soon KIM ; Mihae SEO ; Hye-Jung SHIN ; Seong-Su LEE ; Su Jin JEONG ; Yongin CHO ; Seung Jin HAN ; Hyang Mi JANG ; Mira RHO ; Shinbi LEE ; Mihyun KOO ; Been YOO ; Jung-Wha MOON ; Hye Young LEE ; Jae-Seung YUN ; Sun Young KIM ; Sung Rae KIM ; In-Kyung JEONG ; Ji-Oh MOK ; Kun Ho YOON
Diabetes & Metabolism Journal 2021;45(1):1-10
Background:
This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data.
Methods:
This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated.
Results:
In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of <6.5%. Moreover, only 11.5% of subjects with diabetes met all three targets of glycosylated hemoglobin, blood pressure, and LDL-C. The percentage of energy intake from carbohydrates was higher in diabetes patients than in those without diabetes, while that from protein and fat was lower in subjects with diabetes.
Conclusion
The high prevalence and low control rate of diabetes and its comorbidities in Korean adults were confirmed. More stringent efforts are needed to improve the comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.
10.Evaluation of sleep quality and stress response in patients requiring dental prosthetic treatment
Hye-Mi JEON ; Kyoung-Hwa JUNG ; Na-Rae CHOI ; Jae-Min SONG ; So-Hyoun LEE ; So-Yeun KIM
The Journal of Korean Academy of Prosthodontics 2021;59(2):181-189
Purpose:
The purpose of this study is to investigate the stress response and sleep state of the new patients who visit the hospital for prosthodontic treatment due to tooth loss to make reference to further treatment direction.
Materials and methods:
Examinations, consultations, and surveys were conducted on 236 patients (94 males, 142 females, and 24-86 years old), who newly registered at the department of prosthodontics at Pusan national university hospital, for 2 years from 2018. The number of remaining teeth, edentulous arch, possibility of mastication, and future prosthetic treatment directions were recorded. The visual analogue scale (VAS), stress response inventory (SRI) and Insomnia severity index (ISI) were used as tools to measure patient’s subjective discomfort, stress response, and sleep status.
Results:
Among the entire prosthodontic patient group, the average value of ‘fatigue’ was significantly higher among the 7 items of SRI, and the value of ‘aggression’ was significantly lower (P<.001). There are a significant difference between the edentulous and full dentition in the oral discomfort value measured by VAS (P=.004). In cases where less than 20 teeth remain, mastication is impossible, and patients who are planning treatment with removable prostheses, VAS value and ‘depression’ and ‘fatigue’ values in SRI were higher than those in the reverse case (P<.05).The patients showed severe level in VAS value have high value of ‘tension’, ‘somatization’, ‘depression’, ‘fatigue’and ‘frustration’in SRI than non-serious patients (P<.05). Clinical insomnia occurred in 11.4% of all patients, and women had significantly lower sleep quality than men (P=.044). Patients with insomnia showed significantly higher scores on the VAS value and all 7 SRI items than those of normal sleepers (P<.05).
Conclusion
The new prosthetics had high ‘fatigue’ value among the 7 items of SRI. The oral condition, number of residual teeth and mastication function and clinical insomnia affected oral discomfort and the stress response.

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