Objective: Tic disorders can affect the quality of life in both childhood and adolescence. Many factors are involved in the etiology of tic disorders, and the genetic and epigenetic factors of tic disorders are considered complex and heterogeneous. Methods: In this study, the differentially methylated regions (DMRs) between normal controls (n = 24; aged 6−15; 7 females) and patients with tic disorders (n = 16; aged 6−15; 5 females) were analyzed. We performed an epigenome-wide association study of tic disorders in Korean children. The tics were assessed using Yale Global Tic Severity Scale. The DNA methylation data consisted of 726,945 cytosine phosphate guanine (CpG) sites, assessed using the Illumina Infinium MethylationEPIC (850k) BeadChip. The DNA methylation data of the 40 participants were retrieved, and DMRs between the four groups based on sex and tic disorder were identified. From 28 male and 16 female samples, 37 and 38 DMRs were identified, respectively. We analyzed the enriched terms and visualized the network, heatmap, and upset plot. Results: In male, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed hypomethylated patterns in the ligand, receptor, and second signal transductors of the PI3K-Akt and MAPK signaling pathway (most cells were indicated as green color), and in female, the opposite patterns were revealed (most cells were indicated as red color). Five mental disorder-related enriched terms were identified in the network analysis. Conclusion Here, we provide insights into the epigenetic mechanisms of tic disorders. Abnormal DNA methylation patterns are associated with mental disorder-related symptoms.

Loeys-Dietz syndrome is a hereditary connective-tissue disorder first reported in 2005. It is caused by genetic defects in the transforming growth factor-beta (TGF-β) signaling pathway. TGF-β signaling plays an important role in connective-tissue development, differentiation, and homeostasis. Dysregulation of TGF-β signaling causes various defects in the skull, face, skeletal system, skin, and blood vessels. Symptoms of Loeys-Dietz syndrome include scoliosis, spider finger, joint laxity, club foot, hypertelorism, and cleft palate. In addition, aortic aneurysm, aortic dissection, bleeding tendency, delayed wound healing, allergic disease, and autoimmune disease have been reported. Here, we describe an 11-year-old male with type 1 diabetes mellitus who had frequent epistaxis and easy bruising from an early age, along with skin and joint hyperextension, atrophic scars, and long limbs. He was suspected of having a hereditary connective-tissue disorder and was diagnosed with Loeys-Dietz syndrome type 1 by next-generation sequencing. Similar to Marfan syndrome and Ehlers-Danlos syndrome, this disease has a high risk of aortic aneurysm and aortic dissection. In addition, because aortic dissection can occur at a young age, early diagnosis and periodic examination and treatment for cardiovascular diseases are necessary.

Objective: Recent studies have detailed the genomic landscape of endometrial cancer (EC); however, no study has focused on genetic alterations in advanced EC. We performed genomic profiling of patients with advanced EC using targeted next-generation sequencing (NGS). Methods: Archival tissue samples from 21 patients diagnosed with stage III and IV EC were obtained and subjected to NGS. Our data and the cancer genome atlas dataset were combined, and somatic mutation patterns were analyzed and compared according to the stage and histological type. Additionally, survival effects of specific mutated genes were analyzed. Results: Somatic mutation patterns of 38 genes were identified in 263 EC samples, and the most commonly mutated genes were PTEN and PIK3CA. PTEN was the most common in endometrioid histology, while PPP2R1A was the most commonly mutated gene in serous histology. The mutation rates of PPP2R1A and TP53 were significantly higher in advanced EC sample than in stage I samples (22.5% vs. 4.3% [p<0.001] and 8.4% vs. 1.4% [p=0.021], respectively). Survival analysis of the total population and endometrioid subgroup revealed that patients with PPP2R1A mutations had significantly shorter survival than did those without mutations (p=0.005 and p<0.001, respectively). Conclusion PPP2R1A mutations might have a role in dismal prognosis of advanced EC.

Background: Sarcopenia is commonly found in the elderly due to a decline in muscle mass.Many researchers have performed genome-wide association studies (GWAS) to find genetic risk factors of sarcopenia. Although many studies have discovered sarcopenia associated single nucleotide polymorphisms (SNPs), most of them are studies targeting Caucasians. The purpose of this study was to evaluate genetic correlation according to muscle mass in middle aged Koreans using data of the Korean Genome and Epidemiology Study (KOGES), a large population-based genomic cohort study. Methods: Baseline participants were 10,030 subjects aged 40 to 69 years who were from Ansan or Anseong in Gyeonggi-do, South Korea. Among them, 9,351 subjects with laboratory data available were included in this study. To identify sarcopenia associated variants, those in the top 30% and bottom 30% of muscle mass index (MMI) were compared. A total of 7,452 people with an MMI of 30-70% were excluded. A total of 1,004 people were also excluded due to missing data. Finally, 895 people were selected for this study. The Korea Biobank Array generated 500,568 SNPs for this dataset. Results: When subjects were divided into top 30% and bottom 30% of MMI, the top 30% had 169 men and 308 women and the bottom 30% had 220 men and 198 women. In men, age, body mass index (BMI), waist and hip were significantly (P < 0.005) different between top 30% and bottom 30% MMI groups. In women, age, BMI, waist, hip, and hypertension history were significantly different between the two MMI groups. There were 13 significant SNPs in men and 14 significant SNPs in women. Genes associated with variants in men based on the single-nucleotide polymorphism database (dbSNP) were LRP1B containing rs11679458 and RGS6 containing rs11848300. A gene associated with variants in women was Pi4K2A, which contained rs1189312 as a variant. In addition, rs11189312 was associated with expression quantitative trait loci (eQTL) of ZFYVE27 in skeletal muscles and other SNPs of ZFYVE27 (rs10882883, rs17108378, rs35077384) known to be associated with spastic paraplegia. The eQTL analysis revealed that rs11189312 was a variant associated with SNPs of ZFYVE27. Conclusions In the demographic study, significant results were found in BMI, waist, hip, history of hyperlipidemia, and sedentary life status in male group, and significant results were found in BMI, waist, hip, and hypertension history in female group. Variant rs11189312 was found to be a novel variant affecting ZFYVE27 expressed in skeletal muscles, suggesting that rs11189312 might be related to sarcopenia as a novel discovery of this study. Further study is needed to determine the association between sarcopenia and ZFYVE27 known to be associated with spastic paraplegia.

The purpose of this study was to redesign a problem-based learning (PBL) curriculum and compare the differences between the previous and redesigned PBL based on the results of course satisfaction and student assessments. The PBL was redesigned using curriculum design guidelines (including revisions of curriculum objectives, learning components, learning environments, and assessment methods) that were developed based on previous studies and evaluation results. A comparative study was employed using course satisfaction surveys from the previous and redesigned curricula, and a total of 45 students participated. We also compared student assessment results from concept mapping, learning issue reports, modified essay questions, and reflection journals. We identified four key findings. First, we explored the possibility that the redesigned PBL could be implemented by student facilitators without professors as tutors. Second, the redesigned PBL fostered group dynamics that facilitated developing communication skills and collaborative learning through small-group discussions. Third, the new learning elements added in the redesigned PBL made a meaningful contribution to enhancing students’ clinical reasoning based on hypothetico-deductive reasoning. Fourth, concept maps in redesigned PBL contained more complex and various nodes and connections, and the levels of the nodes were more appropriate. The implications of this study can provide meaningful preliminary information for redesigning PBL curricula for medical students to develop their essential competencies through PBL.

Invasive fungal sinusitis is common in immunodeficiency patients and can spread into the orbit or intracranial cavity. The Onodi cell, which is one of the anatomical variations of the ethmoid sinus, refers to the space that has been pneumatized superolateral to the sphenoid sinus. We experienced a case of invasive fungal sinusitis that caused vision loss by invading the Onodi cells. Endoscopic sinus surgery and antifungal treatment successfully recovered the patient’s vision and we herein report on the case with a review of the literature.

Semisulcospira libertina, a species of freshwater snail, is widespread in East Asia. It is important as a food source. Additionally, it is a vector of clonorchiasis, paragonimiasis, metagonimiasis, and other parasites. Although S. libertina has ecological, commercial, and clinical importance, its whole-genome has not been reported yet. Here, we revealed the genome of S. libertina through de novo assembly. We assembled the whole-genome of S. libertina and determined its transcriptome for the first time using Illumina NovaSeq 6000 platform. According to the k-mer analysis, the genome size of S. libertina was estimated to be 3.04 Gb. Using RepeatMasker, a total of 53.68% of repeats were identified in the genome assembly. Genome data of S. libertina reported in this study will be useful for identification and conservation of S. libertina in East Asia.

Background and Objectives: PET/CT is widely used to determine whether metastasis or recurrence will occur following initial treatment of thyroid cancer. However, there are not much research on diagnostic usefulness of preoperative PET/CT imaging for papillary thyroid cancer (PTC). We analyzed the correlation between the preoperative maximum standard uptake value (SUVmax) of PET/CT and prognostic factors of PTC to evaluate the diagnostic usefulness of PET/CT. Materials and Methods: Of the 133 patients who underwent surgery for PTC, 88 patients who had an increased uptake in thyroid mass in preoperative PET/CT were enrolled. They were divided into two groups according to B-RAF gene mutation, extrathyroidal extension (ETE), lymph node metastasis, and recurrence. The average of the SUVmax for each group was analyzed through multiple regression analysis. Correlation analysis were performed on changes in SUVmax according to the size of the thyroid tumor. Statistical analysis was performed to determine whether there were stage differences between the 47 patients who had no increased uptake in PET/CT and the others who had. Results: There were no statistical correlation between recurrence, the presence of central/lateral lymph node metastasis, ETE, stage and the SUVmax in PET/CT (p=0.513, p=0.8, p=0.73, p=0.01, p=0.9). There were statistical correlations between the size of tumor (p=0.001), the presence of the B-RAF mutation (p=0.024) and SUVmax. Statistical correlations between the presence of the hypermetabolic uptake and high stage were found by the chi-square test (p=0.012). Conclusion The size of tumor, B-RAF are major factors in determining prognosis of PTC. There is a possibility that there is a correlation between preoperative SUVmax and prognosis of PTC.

Background: Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA. Methods: We collected the data of a newly diagnosed pediatric HHA cohort (2007–2016) and compared this cohort's characteristics with those of a previously surveyed pediatric HHA cohort (1997–2006) in Korea. Each participant's information was retrospectively collected by a questionnaire survey. Results: A total of 369 children with HHA from 38 hospitals distributed in 16 of 17 districts of Korea were investigated. RBC membranopathies, hemoglobinopathies, RBC enzymopathies, and unknown etiologies accounted for 263 (71.3%), 59 (16.0%), 23 (6.2%), and 24 (6.5%) of the cases, respectively. Compared to the cohort from the previous decade, the proportions of hemoglobinopathies and RBC enzymopathies significantly increased (P < 0.001 and P = 0.008, respectively). Twenty-three of the 59 hemoglobinopathy patients had immigrant mothers, mostly from South-East Asia. Conclusion In Korea, thalassemia traits have increased over the past 10 years, reflecting both increased awareness of this disease and increased international marriages. The enhanced recognition of RBC enzymopathies is due to advances in diagnostic technique; however, 6.5% of HHA patients still do not have a clear diagnosis. It is necessary to improve accessibility of diagnosing HHA.

BACKGROUND AND OBJECTIVES: Cancer of the oral cavity is a disease of the head and neck that is difficult to treat. Periodic observation and biopsy are important for its early diagnosis once a premalignant lesion in the oral cavity is confirmed. The purpose of this study was to determine the importance of early excisional biopsy by investigating the histological features of oral leukoplakia and the rate of malignant change in the oral cavity. SUBJECTS AND METHOD: A total of 327 patients who underwent punch biopsy of oral cavity from January 2011 to December 2017 were reviewed retrospectively for the presence of initial gross lesions and for their biopsy results. The histological findings of 6 initial gross lesion groups were compared. Additional excisional biopsies were performed in the seven oral cavity subsites. RESULTS: There were 33 cases of oral leukoplakia. The punch biopsies of 3 of these cases (9.1%) showed malignancy. Additional excisional biopsies were performed in 6 cases, 4 of which were malignant (66.7%). Additional excisional biopsies of the tongue were performed in 14 cases (9.0%), 5 of which (35.7%) were malignant. The rate of atypia in leukoplakia (9.1%) was higher than in other atypia groups. Additional excisional biopsies were performed in 3 cases (100%) of atypia of leukoplakia, all of which were assessed to be malignant. CONCLUSION: For tongue leukoplakia, performing an early excisional biopsy rather than an incisional biopsy is recommendable. Moreover, additional excisional biopsies are needed when the initial biopsy is suggestive of hyperkeratosis, parakeratosis, or atypia.
Biopsy ; Early Diagnosis ; Head ; Humans ; Leukoplakia ; Leukoplakia, Oral ; Methods ; Mouth ; Neck ; Parakeratosis ; Retrospective Studies ; Tongue