Osteoclasts (OCs) are clinically important cells that resorb bone matrix. Accelerated bone destruction by OCs is closely linked to the development of metabolic bone diseases. In this study, we screened novel chemical inhibitors targeting OC differentiation to identify drug candidates for metabolic bone diseases. We identified that 1,3-dibenzyl-5-fluorouracil, also named OCI-101, is a novel inhibitor of osteoclastogenesis. The formation of multinucleated OCs is reduced by treatment with OCI-101 in a dose-dependent manner. OCI-101 inhibited the expression of OC markers via downregulation of receptor activator of NF-κB ligand and M-CSF signaling pathways. Finally, we showed that OCI-101 prevents ovariectomy-induced bone loss by suppressing OC differentiation in mice. Hence, these results demonstrated that OCI-101 is a good drug candidate for treating metabolic bone diseases.

Background: Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully.We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis. Methods: We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants. Results: No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. Klebsiella increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions. Conclusion We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including Klebsiella, in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer.

Background: Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully.We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis. Methods: We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants. Results: No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. Klebsiella increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions. Conclusion We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including Klebsiella, in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer.

Purpose: To assess patient radiation doses during diagnostic and therapeutic neurointerventional procedures from multiple centers and propose dose reference level (RL). Materials and Methods: Consecutive neurointerventional procedures, performed in 22 hospitals from December 2020 to June 2021, were retrospectively studied. We collected data from a sample of 429 diagnostic and 731 therapeutic procedures. Parameters including dose-area product (DAP), cumulative air kerma (CAK), fluoroscopic time (FT), and total number of image frames (NI) were obtained. RL were calculated as the 3rd quartiles of the distribution. Results: Analysis of 1160 procedures from 22 hospitals confirmed the large variability in patient dose for similar procedures. RLs in terms of DAP, CAK, FT, and NI were 101.6 Gy·cm2, 711.3 mGy, 13.3 minutes, and 637 frames for cerebral angiography, 199.9 Gy·cm2, 3,458.7 mGy, 57.3 minutes, and 1,000 frames for aneurysm coiling, 225.1 Gy·cm2, 1,590 mGy, 44.7 minutes, and 800 frames for stroke thrombolysis, 412.3 Gy·cm2, 4,447.8 mGy, 99.3 minutes, and 1,621.3 frames for arteriovenous malformation (AVM) embolization, respectively. For all procedures, the results were comparable to most of those already published. Statistical analysis showed male and presence of procedural complications were significant factors in aneurysmal coiling. Male, number of passages, and procedural combined technique were significant factors in stroke thrombolysis. In AVM embolization, a significantly higher radiation dose was found in the definitive endovascular cure group. Conclusion Various RLs introduced in this study promote the optimization of patient doses in diagnostic and therapeutic interventional neuroradiology procedures. Proposed 3rd quartile DAP (Gy·cm2) values were 101.6 for diagnostic cerebral angiography, 199.9 for aneurysm coiling, 225.1 for stroke thrombolysis, and 412.3 for AVM embolization. Continual evolution of practices and technologies requires regular updates of RLs.

Purpose: The purpose of the study was to identify the health anxiety issues of middleaged women, their health-promoting behavior, and quality of life as well as to examine the relationship between these variables. Methods: The participants were 334 women in Jeonbuk area. Demographic characteristics, the status of health anxiety, health-promoting behavior, and life quality was assessed using a self-administered questionnaire. The data were analyzed using a t-test, analysis of variance, Duncan test, and hierarchical regression analysis with SPSS ver. 24.0. Results: The score for health anxiety was 37.64 points out of a possible score of 60, and the score for health-promoting behavior was 79.18 points out of a possible score of 115.The score for the quality of life was 101.18 points out of a possible score of 150. The health anxiety scores showed significant differences, varying as per body mass index (BMI) (p < 0.05), income (p < 0.05), occupation (p < 0.05), disease (p < 0.05), satisfaction with weight (p < 0.05), and interest in weight control (p < 0.05). The health-promoting behavior showed significant differences according to age (p < 0.01), BMI (p < 0.01), income (p < 0.05), menses (p < 0.05), intake of dietary supplements (p < 0.05), perception of body image (p < 0.05), and satisfaction with weight (p < 0.05). The quality of life showed significant differences according to BMI (p < 0.05), income (p < 0.01), education level (p < 0.05), occupation (p < 0.05), disease (p < 0.05), and satisfaction with weight (p < 0.05). Regression analysis showed that health-promoting behavior was the most influential variable on the quality of life, followed by disease and health anxiety. Conclusion Based on these results, we conclude that it is necessary to consider educational programs on improving the quality of life of middle-aged women according to the health anxiety levels and health-promoting behavior.

OBJECTIVE: Endometriosis is a common and recurring gynecologic disease which have afflicting females of reproductive age. We investigated the efficacy of long-term, post-operative use of dienogest for ovarian endometrioma. METHODS: We studied 203 patients who had undergone laparoscopic or robotic surgery for ovarian endometrioma, and were administrated dienogest 2 mg/day beginning in July of 2013, and continuing. We evaluated side effects of dienogest and ultrasonography was performed every 6 months to detect potential recurrence of endometrioma (2 cm) in these post-surgical patients. RESULTS: The follow-up observation periods were 30.2±20.9 months from surgery. The mean age was 34.1±7.2 years old. The mean diameter of pre-operative endometrioma was 5.6±3.0 cm2. One hundred eighty-two (89.7%) women received dienogest continuously for 12.0±7.1 months. Of the subjects, 21 (10.3%) patients discontinued dienogest at 2.4±1.0 months. The most common side effect when dienogest was discontinued was abnormal uterine bleeding. The occurrence rate of vaginal bleeding was 15.8%, a number which did not differ significantly in patients with/without post-operative gonadotropin releasing hormone agonist administration. The other side effects were gastrointestinal trouble including constipation, acne, headache, depression, hot flush, weight gain, and edema. However, no serious adverse events or side effects were documented and recurrent endometriomas were diagnosed in 3 patients (1.5%). CONCLUSION: The data indicates that dienogest was both tolerable and safe for long-term use as prophylaxis in an effort to obviate the recurrence of ovarian endometrioma post-operatively, as well as potential need for surgical re-intervention.
Acne Vulgaris ; Constipation ; Depression ; Edema ; Endometriosis ; Female ; Follow-Up Studies ; Genital Diseases, Female ; Gonadotropin-Releasing Hormone ; Headache ; Humans ; Recurrence ; Ultrasonography ; Uterine Hemorrhage ; Weight Gain

The Korean Society of Nephrology participated in the task force team consisting of government authorities and civilian experts to prevent and control the spread of Middle East respiratory syndrome (MERS) in 2015. The Korean Society of Nephrology MERS Task Force Team took an immediate action and drafted ‘the clinical recommendation for hemodialysis facilities’ to follow when the first and the only confirmed case was reported in the hemodialysis unit. Owing to the dedicated support from medical doctors, dialysis nurses, and related medical companies, we could prevent further transmission of MERS infection successfully in hemodialysis units. This special report describes the experience of infection control during MERS outbreak in 2015 and summarizes the contents of ‘the clinical practice guideline for hemodialysis facilities dealing with MERS patients’ built upon our previous experience.
Advisory Committees ; Coronavirus Infections* ; Dialysis ; Infection Control ; Middle East Respiratory Syndrome Coronavirus ; Middle East* ; Nephrology ; Quarantine ; Renal Dialysis*

Lynch syndrome is the most common inherited colon cancer syndrome. Patients with Lynch syndrome develop a range of cancers including colorectal cancer (CRC) and carry a mutation on one of the mismatched repair (MMR) genes. Although CRC usually occurs after the fourth decade in patients with Lynch syndrome harboring a heterozygous MMR gene mutation, it can occur in children with Lynch syndrome who have a compound heterozygous or homozygous MMR gene mutation. We report a case of CRC in a 13-year-old patient with Lynch syndrome and congenital heart disease. This patient had a heterozygous mutation in MLH1 (an MMR gene), but no compound MMR gene defects, and a K-RAS somatic mutation in the cancer cells.
Adolescent* ; Child ; Colonic Neoplasms ; Colorectal Neoplasms* ; Colorectal Neoplasms, Hereditary Nonpolyposis* ; Female* ; Heart Defects, Congenital ; Humans

T-cell acute lymphoblastic leukemia (T-ALL) accounts for approximately 10-15% of entire ALL in children. The outcome of T-ALL has been improved through the intensified therapeutic strategy, however, it is still a more aggressive disease. In T-ALL a couple of transcription factor oncogenes are known to be relocated to the juxtaposition of T-cell receptor genes, potent promoter, by chromosome translocation. However the incidence of each chimeric gene formation in T-ALL is less than 5% and their clinical significance as a prognostic marker is lacking. A decade ago it was identified that activating mutations in NOTCH1 in about 60% of T-ALL. After then, activating NOTCH1 mutations present in T-ALL have been extensively investigated with regard to understanding its molecular pathogenesis, its prognostic significance, and developing molecularly tailored novel agents. Small molecule gamma-secretase inhibitor, blocking a proteolytic step required for creation of a fragment of NOTCH intracellular domain which actually act as a controller of its target gene expression, was tried as a target therapeutic drug for T-ALL. Although outcome of this drug was not satisfactory, challenges have been launched to develop new drugs which specifically act on the aberrant behavior of mutated NOTCH1 in T-ALL.
Amyloid Precursor Protein Secretases ; Child ; Gene Expression ; Genes, T-Cell Receptor ; Humans ; Incidence ; Oncogenes ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; T-Lymphocytes ; Transcription Factors

The name "Sung Min Kim" should be "Seong Min Kim" and "Yoon Mi Kim" should be "Yun Mi Kim".