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Amyloid precursor protein (APP) plays an important role in the pathogenesis of Alzheimer’s disease (AD), but the normal function of APP at synapses is poorly understood. We and others have found that APP interacts with Reelin and that each protein is individually important for dendritic spine formation, which is associated with learning and memory, in vitro. However, whether Reelin acts through APP to modulate dendritic spine formation or synaptic function remains unknown. In the present study, we found that Reelin treatment significantly increased dendritic spine density and PSD-95 puncta number in primary hippocampal neurons. An examination of the molecular mechanisms by which Reelin regulates dendritic spinogenesis revealed that Reelin enhanced hippocampal dendritic spine formation in a Ras/ERK/CREB signaling-dependent manner. Interestingly, Reelin did not increase dendritic spine number in primary hippocampal neurons when APP expression was reduced or in vivo in APP knockout (KO) mice. Taken together, our data are the first to demonstrate that Reelin acts cooperatively with APP to modulate dendritic spine formation and suggest that normal APP function is critical for Reelin-mediated dendritic spinogenesis at synapses.
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Objective@#To develop an integrated and comprehensive community-based mental healthcare model, opinions were collected on various issues from practitioners in mental health service institutions currently offering mental healthcare services in Seoul through a focus group interview, qualitative research method, and Delphi survey. @*Methods@#The focus group interview was conducted with six practitioners from mental health welfare centers and six hospital-based psychiatrists. A questionnaire of opinions on the mental healthcare model was filled by these practitioners and psychiatrists. A Delphi survey was additionally conducted with a panel of 20 experts from a community mental health welfare center and hospital-based psychiatrists. @*Results@#The focus group interview results showed the need for integrated community-based mental healthcare service and the need to establish a system for managing mental and physical health in an integrated manner. Based on the survey results, the current status of community-based mental healthcare services was investigated, and the direction of the revised model was established. The Delphi survey was then conducted to refine the revised model. @*Conclusion@#The present study presents the Seoul-type community-based mental healthcare model with integrated services between a psychiatric hospital with a mental health welfare center as well as combined mental and physical health services. This is ultimately expected to help people with mental illnesses live healthy lives by meeting their needs as community members.
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Background@#Short stature is defined as a height below the 3rd percentile or more than two standard deviations below the mean for a given age, sex, and population. There have been inconsistent results regarding craniofacial morphology in short-statured children. This study aimed to analyze the differences between short-statured children with growth hormone deficiency, idiopathic short-statured children, and normal children. @*Methods@#Thirty-one short-statured children with growth hormone deficiency, 32 idiopathic short-statured children, and 32 healthy children were enrolled in this study. The measurements of their craniofacial structures from lateral cephalograms were evaluated. @*Results@#There were statistically significant differences among the three groups seven variables (anterior cranial base length, posterior cranial base length, total cranial base length, upper posterior facial height, posterior total facial height, mandibular ramus length, and overall mandibular length) in the linear measurement and five variables (saddle angle, gonial angle, mandibular plane angle, position of mandible, and maxilla versus mandible) in the angular measurement. @*Conclusion@#Compared to the control group, many linear and angular measurements of the craniofacial structures were significantly different in the two short-statured groups (p<0.05). Treatment plans by orthodontists should include these craniofacial structure characteristics.
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To the Editor:The authors regret that there were errors in the text. This notice corrects the numbers in the result of the Abstract. We changed the percentages indicating the decrease in the number of patients (adults and children) who visited the emergency department (EDs) during the study period.Content of correction:Before:“ Fewer patients, particularly children visited the EDs during the study period in 2020 than those in the previous (2018/2019) year period: the number of adult patient decreased by 46.4% and children by 76.9%.”After:“ Fewer patients, particularly children visited the EDs during the study period in 2020 than those in the previous (2018/2019) year period: the number of adult patient decreased by 26.0% and children by 62.0%.”
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Background@#Limited data exist on children's utilization of the emergency department (ED) in the ongoing coronavirus disease 2019 (COVID-19) pandemic. Thus, we aimed to examine ED utilization among pediatric patients and the impact of COVID-19 in one large city affected by the outbreak. @*Methods@#This retrospective study included data from six EDs in Daegu, Korea. We compared the demographic and clinical data of patients presenting to the ED during the COVID-19 pandemic (February 1st–June 30th 2020) with those of patients who visited the ED in this period during 2018 and 2019. @*Results@#Fewer patients, particularly children visited the EDs during the study period in 2020 than those in the previous (2018/2019) year period: the number of adult patient decreased by 46.4% and children by 76.9%. Although the number of patients increased from the lowest point of the decrease in March 2020, the number of pediatric patients visiting the ED remained less than half (45.2%) in June 2020 compared with that of previous years. The proportion of patients with severe conditions increased in adults, infants, and school-aged children, and consequently resulted in increased ambulance use and higher hospitalization rates. Fewer infants and young children but more school-aged children visited the ED with febrile illnesses in 2020 than in 2018/2019. @*Conclusion@#The COVID-19 pandemic has led to a substantial decrease in pediatric ED utilization. These findings can help reallocate human and material resources in the EDs during infectious disease outbreaks.
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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.
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Objective@#Repetitive transcranial magnetic stimulation (rTMS) has contributed to increase in the remission rate for patients with major depressive disorder (MDD). However, current rTMS treatment is practically inconvenient because it requires daily treatment sessions for several weeks. Accelerated rTMS treatment is as efficient and safe for MDD patients as conventional rTMS. @*Methods@#Fifty-one patients with MDD participated in this study; they were randomized into accelerated rTMS (n = 21), conventional rTMS (n = 22), and sham-treatment (n = 8) groups. The accelerated and conventional rTMS groups received 15 sessions for 3 days and 3 weeks, respectively. The sham-treatment group received 15 sham rTMS sessions for 3 days. Primary outcome was assessed using self-report and clinician-rated Korean Quick Inventory of Depressive Symptomatology (KQIDS-SR and KQIDS-C, respectively). Adverse effects were monitored using the Frequency, Intensity, and Burden of Side Effects Rating scale. Changes in depressive symptoms were compared among the three groups using mixed model analyses. @*Results@#For the KQIDS-SR score, there was a significant main effect of “time” (F3,47 = 11.05, p < 0.001), but no effect of “group” (F2,47 = 2.04, p = 0.142), and a trend-level interaction effect of “group × time” (F6,47 = 2.26, p = 0.053). Improvement in depressive symptoms, based on the KQIDS-SR score 3 weeks after treatment, was more prominent in the accelerated rTMS group than in the sham-treatment group (p = 0.011). Tolerability was comparable among the three groups. @*Conclusion@#The accelerated rTMS treatment group showed rapid improvement of depressive symptoms compared with the sham-treatment and conventional rTMS treatment groups. Therefore, accelerated rTMS treatment could be a viable option for MDD, with improved accessibility.
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Merkel cell carcinoma is an extremely rare neuroendocrine neoplasm of the external auditory canal (EAC) skin, which requires wide excision and adjuvant radiation due to a high recurrence rate. In this report, we describe a case of Merkel cell carcinoma arising from the EAC which was successfully treated with endoscopic excision. A 32-years-old female patient with a history of papillary thyroid cancer was diagnosed with an EAC tumor incidentally. There was a erythematous papular lesion on the posterior EAC without any evidence of locoregional metastasis. The patient underwent endoscopic tumor resection under general anesthesia, and the final pathologic report confirmed the diagnosis of Merkel cell carcinoma. There was no clinical or radiographic evidence of recurrence or metastasis of Merkel cell tumor for 41 months after surgical resection alone.
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Background@#The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases. @*Methods@#This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016. @*Results@#Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53%) and infection (44%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels. @*Conclusions@#Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.
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Purpose@#The purpose of this study is to identify the educational needs of a severe trauma treatment simulation program based on mixed reality which combines element of both virtual reality and augmented reality. @*Methods@#Focus group interviews were conducted with ten military hospital nurses on February 4 and 5, 2021. The collected data were analyzed using a qualitative content analysis. As a framework for data analysis, the educational needs were clustered into the following four categories: teaching contents, teaching methods, teaching evaluation, and teaching environment. @*Results@#The educational needs for each category that emerged were as follows: three subcategories including “realistic education reflecting actual clinical practice” and “motivating education” for teaching contents; five subcategories including “team-based education,” “repeated education that acts as embodied learning,” and “stepwise education” for teaching methods; six subcategories including “debriefing through video conferences,” “team evaluation and evaluator in charge of the team,” “combination of knowledge and practice evaluation” for teaching evaluation; six subcategories including “securing safety,” “similar settings to real clinical environments,” “securing of convenience and accessibility for learners,” and “operating as continuing education” for teaching environment. @*Conclusion@#The findings of this study can provide a guide for the development and operation of a severe trauma treatment simulation program based on mixed reality. Moreover, it suggests that research to identify the educational needs of various learners should be conducted.
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Genome-wide association studies (GWASs) facilitated the discovery of countless disease-associated variants. However, GWASs have mostly been conducted in European ancestry samples. Recent studies have reported that these European-based association results may reduce disease prediction accuracy when applied in non-Europeans. Therefore, previously reported variants should be validated in non-European populations to establish reliable scientific evidence for precision medicine. In this study, we validated known associations with type 2 diabetes (T2D) and related metabolic traits in 125,850 samples from a Korean population genotyped by the Korea Biobank Array (KBA). At the end of December 2020, there were 8,823 variants associated with glycemic traits, lipids, liver enzymes, and T2D in the GWAS catalog. Considering the availability of imputed datasets in the KBA genome data, publicly available East-Asian T2D summary statistics, and the linkage disequilibrium among the variants (r2 < 0.2), 2,900 independent variants were selected for further analysis. Among these, 1,837 variants (63.3%) were statistically significant (p < 0.05). Most of the non-replicated variants (n = 1,063) showed insufficient statistical power and decreased minor allele frequencies compared with the replicated variants. Moreover, known variants showed <10% genetic heritability. These results could provide valuable scientific evidence for future study designs, the current power of GWASs, and future applications in precision medicine in the Korean population.
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Purpose@#Sphingosine kinase is a lipid kinase that phosphorylates sphingosine to generate sphingosine 1-phosphate (S1P). S1P regulates pancreatic islet β-cell endoplasmic reticulum stress and proliferation. Type 1 and type 2 diabetes share some key pathogenic processes. In this study, we investigated whether secretion of insulin and production of S1P is altered in alloxan and glucose-treated cells from the rat pancreatic β-cell line RIN-5F. @*Methods@#RIN-5F cells were treated with 2 mM alloxan and 20 mM glucose for 6 hours or 24 hours before being evaluated by enzyme linked immunosorbent assay (ELISA) and Western blotting. @*Results@#Insulin secretion and expression was higher in RIN-5F cells treated with glucose compared to control cells. In contrast, alloxan treatment did not affect insulin secretion and expression in RIN-5F cells. Interestingly, compared with normal control levels, S1P/EDG-5 was increased in both alloxan and glucose-treated pancreatic β cell than normal control. Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) inhibition strongly decreased the expression of insulin and S1P in glucose- or alloxan-treated RIN-5F cells. @*Conclusion@#We observe that production of S1P is increased in both diabetic cell models. In addition, MAPK/ERK signaling regulates secretion of insulin and S1P expression in pancreatic β-cells. Based on the literature and our findings, S1P may be a promising agent for the treatment of insulin-related disorders.
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Hepatocellular carcinoma (HCC) is heterogeneous in pathogenesis, phenotype and biological behavior. Various histopathological features of HCC had been sporadically described, and with the identification of common molecular alterations of HCC and its genomic landscape over the last decade, morpho-molecular correlation of HCC has become possible. As a result, up to 35% of HCCs can now be classified into histopathological variants, many of which have unique molecular characteristics. This review will provide an introduction to the variously described histopathological variants of HCC in the updated WHO Classification of Digestive System Tumors.
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Purpose@#This study is a content analysis to understand the nursing informatics competence of clinical nurses. @*Methods@#Focus group interviews were used to collect data. Two focus group interviews were held with a total of nine clinical nurses. All interviews were recorded and transcribed. Content analysis was used to analyze data. @*Results@#The five main categories of nursing informatics competence that emerged are 1) software program use, 2) use of nursing information, 3) use of information communication technology in nursing, 4) professional responsibilities and ethics, and 5) active attitudes and recognition. Next, there are three strategies to improve nursing informatics competence: 1) organizational approach, 2) opportunity of continuous education, 3) presentation of standards in nursing informatics competence. @*Conclusion@#Further studies such as educational program development and evaluation tool development are necessary. Moreover, there is a need to enhance clinical nurses' nursing informatics competence by using the proposed strategies.
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Maturity-onset diabetes of the young (MODY) is a clinically heterogeneous group of monogenic disorders characterized by ß-cell dysfunction. MODY accounts for between 2% and 5% of all diabetes cases, and distinguishing it from type 1 or type 2 diabetes is a diagnostic challenge. Recently, MODY-causing mutations have been identified in 14 different genes. Sanger DNA sequencing is the gold standard for identifying the mutations in MODY-related genes, and may facilitate the diagnosis. Despite the lower frequency among diabetes mellitus cases, a correct genetic diagnosis of MODY is important for optimizing treatment strategies. There is a discrepancy in the disease-causing locus between the Asian and Caucasian patients with MODY. Furthermore, the prevalence of the disease in Asian populations remains to be studied. In this review, the current understanding of MODY is summarized and the Asian studies of MODY are discussed in detail.
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OBJECTIVE: To evaluate the performance of predicting early recurrence using preoperative factors only in comparison with using both pre-/postoperative factors.MATERIALS AND METHODS: We retrospectively reviewed 549 patients who had undergone curative resection for single hepatcellular carcinoma (HCC) within Milan criteria. Multivariable analysis was performed to identify pre-/postoperative high-risk factors of early recurrence after hepatic resection for HCC. Two prediction models for early HCC recurrence determined by stepwise variable selection methods based on Akaike information criterion were built, either based on preoperative factors alone or both pre-/postoperative factors. Area under the curve (AUC) for each receiver operating characteristic curve of the two models was calculated, and the two curves were compared for non-inferiority testing. The predictive models of early HCC recurrence were internally validated by bootstrap resampling method.RESULTS: Multivariable analysis on preoperative factors alone identified aspartate aminotransferase/platelet ratio index (OR, 1.632; 95% CI, 1.056–2.522; p = 0.027), tumor size (OR, 1.025; 95% CI, 0.002–1.049; p = 0.031), arterial rim enhancement of the tumor (OR, 2.350; 95% CI, 1.297–4.260; p = 0.005), and presence of nonhypervascular hepatobiliary hypointense nodules (OR, 1.983; 95% CI, 1.049–3.750; p = 0.035) on gadoxetic acid-enhanced magnetic resonance imaging as significant factors. After adding postoperative histopathologic factors, presence of microvascular invasion (OR, 1.868; 95% CI, 1.155–3.022; p = 0.011) became an additional significant factor, while tumor size became insignificant (p = 0.119). Comparison of the AUCs of the two models showed that the prediction model built on preoperative factors alone was not inferior to that including both pre-/postoperative factors {AUC for preoperative factors only, 0.673 (95% confidence interval [CI], 0.623–0.723) vs. AUC after adding postoperative factors, 0.691 (95% CI, 0.639–0.744); p = 0.0013}. Bootstrap resampling method showed that both the models were valid.CONCLUSION: Risk stratification solely based on preoperative imaging and laboratory factors was not inferior to that based on postoperative histopathologic risk factors in predicting early recurrence after curative resection in within Milan criteria single HCC patients.
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Longitudinal bone growth is primarily mediated by the growth plate, which is a specialized cartilaginous structure. Aggrecan, encoded by ACAN, is a primary proteoglycan component of the extracellular matrix in both the growth plate and articular cartilage. Aggrecanopathies have emerged as a phenotype of genetic skeletal disease in humans. A heterozygous ACAN mutation causes short stature, premature growth cessation, and accelerated bone age maturation. We report the case of a 15-year-old boy with familial short stature, with height of 149 cm (Korean standard deviation score [SDS] of -3.6) and weight of 50.5 kg (-1.48 SDS). He presented with mild midfacial hypoplasia, frontal bossing, a broad chest, and a short neck. The father's and mother's heights were 150 cm (-4.8 SDS) and 153 cm (-1.69 SDS), respectively. The patient's bone age was 2–3 years more advanced than his chronological age, and no endocrine abnormalities were detected. Wholeexome sequencing followed by Sanger sequencing revealed a heterozygous ACAN mutation, c.512C>T (p.Ala171Val), in both the proband and his father. Short stature is generally associated with a delayed bone age, and this case suggests that ACAN mutations may be the most likely etiology among patients with short stature and an advanced bone age and should warrant early treatment.
ABSTRACT
Longitudinal bone growth is primarily mediated by the growth plate, which is a specialized cartilaginous structure. Aggrecan, encoded by ACAN, is a primary proteoglycan component of the extracellular matrix in both the growth plate and articular cartilage. Aggrecanopathies have emerged as a phenotype of genetic skeletal disease in humans. A heterozygous ACAN mutation causes short stature, premature growth cessation, and accelerated bone age maturation. We report the case of a 15-year-old boy with familial short stature, with height of 149 cm (Korean standard deviation score [SDS] of -3.6) and weight of 50.5 kg (-1.48 SDS). He presented with mild midfacial hypoplasia, frontal bossing, a broad chest, and a short neck. The father's and mother's heights were 150 cm (-4.8 SDS) and 153 cm (-1.69 SDS), respectively. The patient's bone age was 2–3 years more advanced than his chronological age, and no endocrine abnormalities were detected. Wholeexome sequencing followed by Sanger sequencing revealed a heterozygous ACAN mutation, c.512C>T (p.Ala171Val), in both the proband and his father. Short stature is generally associated with a delayed bone age, and this case suggests that ACAN mutations may be the most likely etiology among patients with short stature and an advanced bone age and should warrant early treatment.
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Over the last decade, genome-wide association studies (GWASs) have provided an unprecedented amount of genetic variations that are associated with various phenotypes. However, previous GWAS were mostly conducted in European populations, and these biased results for non-Europeans may result in a significant reduction in risk prediction for non-Europeans. An issue with the early GWAS was the winner's curse problem, which led to misleading results when constructing the polygenic risk scores (PRS). Therefore, more non-European population-based studies are needed to validate reported variants and improve genetic risk assessment across diverse populations. In this study, we validated 422 variants independently associated with glycemic indexes, liver enzymes, and type 2 diabetes in 125,872 samples from a Korean population, and further validated the results by assessing publicly available summary statistics from European GWAS (n = 898,130). Among the 422 independently associated variants, 284, 320, and 361 variants were replicated in Koreans, Europeans, and either one of the two populations. In addition, the effect sizes for Koreans and Europeans were moderately correlated (r = 0.33–0.68). However, 61 variants were not replicated in both Koreans and Europeans. Our findings provide valuable information on effect sizes and statistical significance, which is essential to improve the assessment of disease risk using PRS analysis.
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Klinefelter syndrome (KS) is characterized by small testes, gynecomastia, tall stature, and hypergonadotropic hypogonadism. This condition is associated with extra X chromosomes. It is well known that these aneuploidies predispose individuals to the development of several cancers. Moreover, there are many case reports that show KS patients to have a higher relative risk for the development of malignancy. However, incracranial germ cell tumor (ICGCT) associated with KS is very uncommon. Herein, we report delayed diagnosis of KS in a 15-year-old boy with ICGCT, embryonal carcinoma of the pineal gland, after multimodality treatment in Korea.