Anosmia, characterized by the loss of smell, is associated not only with dysfunction in the peripheral olfactory system but also with changes in several brain regions involved in olfactory processing. Specifically, the orbitofrontal cortex is recognized for its pivotal role in integrating olfactory information, engaging in bidirectional communication with the primary olfactory regions, including the olfactory cortex, amygdala, and entorhinal cortex. However, little is known about alterations in structural connections among these brain regions in patients with anosmia. In this study, highresolution T1-weighted images were obtained from participants. Utilizing the volumes of key brain regions implicated in olfactory function, we employed a structural covariance approach to investigate brain reorganization patterns in patients with anosmia (n=22) compared to healthy individuals (n=30). Our structural covariance analysis demonstrated diminished connectivity between the amygdala and entorhinal cortex, components of the primary olfactory network, in patients with anosmia compared to healthy individuals (z=-2.22, FDR-corrected p=0.039). Conversely, connectivity between the orbitofrontal cortex—a major region in the extended olfactory network—and amygdala was found to be enhanced in the anosmia group compared to healthy individuals (z=2.32, FDR-corrected p=0.039). However, the structural connections between the orbitofrontal cortex and entorhinal cortex did not differ significantly between the groups (z=0.04, FDR-corrected p=0.968). These findings suggest a potential structural reorganization, particularly of higher-order cortical regions, possibly as a compensatory effort to interpret the limited olfactory information available in individuals with olfactory loss.

Purpose: Triple-negative breast cancer (TNBC) does not have defined therapeutic targets and is currently treated with chemotherapy only. Kinase dysregulation triggers cancer cell proliferation and metastasis and is a crucial therapeutic target for cancer. In this study, targeted kinome sequencing of TNBC tumors was performed to assess the association between kinome gene alterations and disease outcomes in TNBC. Methods: A kinome gene panel consisting of 612 genes was used for the targeted sequencing of 166 TNBC samples and matched normal tissues. Analyses of the significantly mutated genes were performed. Genomic differences between Asian and non-Asian patients with TNBC were evaluated using two Asian TNBC datasets (from Seoul National University Hospital [SNUH] and Fudan University Shanghai Cancer Center [FUSCC]) and three nonAsian TNBC datasets (The Cancer Genome Atlas [TCGA], METABRIC, and Gustave Roussy).The prognostic value of kinome gene mutations was evaluated using tumor mutational burden (TMB) and oncogenic pathway analyses. Mutational profiles from the TCGA were used for validation. Results: The significantly mutated genes included TP53 (60% of patients), PIK3CA (21%), BRCA2 (8%), and ATM (8%). Compared with data from non-Asian public databases, the mutation rates of PIK3CA p.H1047R/Q were significantly higher in the SNUH cohort (p = 0.003, 0.048, and 0.032, respectively). This was verified using the FUSCC dataset (p = 0.003, 0.078, and 0.05, respectively). The TMB-high group showed a trend toward longer progression-free survival in our cohort and the TCGA TNBC cohort (p = 0.041 and 0.195, respectively). Kinome gene alterations in the Wnt pathway in patients with TNBC were associated with poor survival in both datasets (p = 0.002 and 0.003, respectively). Conclusion Comprehensive analyses of kinome gene alterations in TNBC revealed genomic alterations that offer therapeutic targets and should help identify high-risk patients more precisely in future studies.

Background/Aims: Multi-drug resistant pathogens are increasing among healthcare-associated infections. It is well known that copper and copper alloys have antimicrobial activity. We evaluated the activity of copper against bacteria in a hospital setting in Korea. Methods: This study was conducted in a laboratory and medical intensive care unit (ICU). Methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus faecium (VRE) were inoculated onto copper, copper alloy and stainless steel plates. After 24 hours of incubation, colony-forming units (CFU) were counted in the laboratory. Two similar rooms were chosen in the ICU; one room had copper-containing surface, and the other room contained items with a stainless steel surfaces. Items were sampled weekly for 8 weeks when the rooms were not crowded and when the rooms were busier with healthcare workers or visitors. Results: In vitro time-kill curves showed copper or, a copper alloy yielded a significant reduction in MRSA and VRE CFUs over 15 minutes. Upon exposure to stainless steel plates, CFUs were slowly reduced for 24 hours. In vivo, MRSA CFUs were lower in rooms with copper-containing surfaces compared with controls, both after cleaning and after patients had received visitors (p < 0.05). Analysis of VRE revealed similar results, but VRE CFUs from copper-containing surfaces of drug carts in the ICU did not decrease significantly. Conclusions Copper has antimicrobial activity and appears to reduce the number of multi-drug resistant microorganisms in a hospital environment. This finding suggests the potential of the use of copper fittings, instruments and surfaces in hospital.

Background/Aims: Multi-drug resistant pathogens are increasing among healthcare-associated infections. It is well known that copper and copper alloys have antimicrobial activity. We evaluated the activity of copper against bacteria in a hospital setting in Korea. Methods: This study was conducted in a laboratory and medical intensive care unit (ICU). Methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus faecium (VRE) were inoculated onto copper, copper alloy and stainless steel plates. After 24 hours of incubation, colony-forming units (CFU) were counted in the laboratory. Two similar rooms were chosen in the ICU; one room had copper-containing surface, and the other room contained items with a stainless steel surfaces. Items were sampled weekly for 8 weeks when the rooms were not crowded and when the rooms were busier with healthcare workers or visitors. Results: In vitro time-kill curves showed copper or, a copper alloy yielded a significant reduction in MRSA and VRE CFUs over 15 minutes. Upon exposure to stainless steel plates, CFUs were slowly reduced for 24 hours. In vivo, MRSA CFUs were lower in rooms with copper-containing surfaces compared with controls, both after cleaning and after patients had received visitors (p < 0.05). Analysis of VRE revealed similar results, but VRE CFUs from copper-containing surfaces of drug carts in the ICU did not decrease significantly. Conclusions Copper has antimicrobial activity and appears to reduce the number of multi-drug resistant microorganisms in a hospital environment. This finding suggests the potential of the use of copper fittings, instruments and surfaces in hospital.

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (PNET) included several significant changes. We aim to evaluate this staging system compared to the 7th edition AJCC staging system and European Neuroendocrine Tumors Society (ENETS) system. MATERIALS AND METHODS: We used Korean nationwide surgery database (2000-2014). Of 972 patients who had undergone surgery for PNET, excluding patients diagnosed with ENETS/World Health Organization 2010 grade 3 (G3), only 472 patients with accurate stage were included. RESULTS: Poor discrimination in overall survival rate (OSR) was noted between AJCC 8th stage III and IV (p=0.180). The disease-free survival (DFS) curves of 8th AJCC classification were well separated between all stages. Compared with stage I, the hazard ratio of II, III, and IV was 3.808, 13.928, and 30.618, respectively (p=0.007, p < 0.001, and p < 0.001). The curves of OSR and DFS of certain prognostic group in AJCC 7th and ENETS overlapped. In ENETS staging system, no significant difference in DFS between stage IIB versus IIIA (p=0.909) and IIIA versus IIIB (p=0.291). In multivariable analysis, lymphovascular invasion (p=0.002), perineural invasion (p=0.003), and grade (p < 0.001) were identified as independent prognostic factors for DFS. CONCLUSION: This is the first large-scale validation of the AJCC 8th edition staging system for PNET. The revised 8th system provides better discrimination compared to that of the 7th edition and ENETS TNM system. This supports the clinical use of the system.
Classification ; Discrimination (Psychology) ; Disease-Free Survival ; Humans ; Joints ; Neoplasm Staging ; Neuroectodermal Tumors, Primitive ; Neuroendocrine Tumors ; Pancreas ; Survival Rate

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard procedure to evaluate suspicious lymph node involvement of lung cancer because computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography-CT (PET-CT) have limitations in their sensitivity and specificity. There are a number of benign causes of false positive lymph node such as anthracosis or anthracofibrosis, pneumoconiosis, old or active tuberculosis, interstitial lung disease, and other infectious conditions including pneumonia. The purpose of this study was to evaluate possible causes of false positive lymph node detected in chest CT or PET-CT. METHODS: Two hundred forty-seven patients who were initially diagnosed with lung cancer between May 2009 and December 2012, and underwent EBUS-TBNA to confirm suspicious lymph node involvement by chest CT or PET-CT were analyzed for the study. RESULTS: Of 247 cases, EBUS-TBNA confirmed malignancy in at least one lymph node in 189. The remaining 58 patients whose EBUS-TBNA results were negative were analyzed. Age ≥65, squamous cell carcinoma as the histologic type, and pneumoconiosis were related with false-positive lymph node involvement on imaging studies such as chest CT and PET-CT. CONCLUSION: These findings suggest that lung cancer staging should be done more carefully when a patient has clinically benign lymph node characteristics including older age, squamous cell carcinoma, and benign lung conditions.
Anthracosis ; Carcinoma, Squamous Cell ; Electrons ; Humans ; Lung Diseases, Interstitial ; Lung Neoplasms* ; Lung* ; Lymph Nodes* ; Needles* ; Pneumoconiosis ; Pneumonia ; Sensitivity and Specificity ; Thorax* ; Tomography, X-Ray Computed* ; Tuberculosis

OBJECTIVE: This study determined whether cognitive behavioral therapy for insomnia (CBT-i) decreased the need for sleep medications and produced better treatment outcomes than pharmacotherapy alone. METHODS: We reviewed data from patients with insomnia in the outpatient clinic of a general hospital between 2009 and 2015. We compared 41 patients who received five sessions of CBT-i with 100 age- and sex-matched patients who received pharmacotherapy only. We evaluated the change in prescription for sleep (i.e., antidepressants, hypnotics, and others) between the first and last visits using repeated measures analysis of variance (ANOVA). Clinical global impressions and completion status at the last visit were assessed using the chisquare test. RESULTS: We found a significant decrease in the prescription rate and the dosage of hypnotics among patients who received CBT-i when compared with control patients. There was no significant change in the dosage of antidepressants between the two groups. Achievement of case closure was better in the CBT-i group at the trend level. Clinical global impression at the last visit was not significantly different. CONCLUSION: These results show that CBT-i reduces the need for hypnotics among insomnia patients. Our results indicate that CBT-i offers additional benefits beyond improving sleep characteristics and thus provides another reason for recommending CBT-i as a first-line treatment for insomnia.
Ambulatory Care Facilities ; Antidepressive Agents ; Cognitive Therapy* ; Drug Therapy ; Hospitals, General ; Humans ; Hypnotics and Sedatives ; Prescriptions* ; Sleep Initiation and Maintenance Disorders*

OBJECTIVES: Sleep disturbance is a very rapidly growing disease with aging. The purpose of this study was to investigate the prevalence of sleep disturbances and its predictive factors in a three-year cohort study of people aged 60 years and over in Korea. METHODS: In 2012 and 2014, we obtained data from a survey of the Korean Social Life, Health, and Aging Project. We asked participants if they had been diagnosed with stroke, myocardial infarction, angina pectoris, arthritis, pulmonary tuberculosis, asthma, cataract, glaucoma, hepatitis B, urinary incontinence, prostate hypertrophy, cancer, osteoporosis, hypertension, diabetes, hyperlipidemia, or metabolic syndrome. Cognitive function was assessed using the Mini-Mental State Examination for dementia screening in 2012, and depression was assessed using the Center for Epidemiologic Studies Depression Scale in 2012 and 2014. In 2015, a structured clinical interview for Axis I psychiatric disorders was administered to 235 people, and sleep disturbance was assessed using the Pittsburgh Sleep Quality Index. The perceived stress scale and the State-trait Anger Expression Inventory were also administered. Logistic regression analysis was used to predict sleep disturbance by gender, age, education, depression score, number of coexisting diseases in 2012 and 2014, current anger score, and perceived stress score. RESULTS: Twenty-seven percent of the participants had sleep disturbances. Logistic regression analysis showed that the number of medical diseases three years ago, the depression score one year ago, and the current perceived stress significantly predicted sleep disturbances. CONCLUSION: Comorbid medical disease three years previous and depressive symptoms evaluated one year previous were predictive of current sleep disturbances. Further studies are needed to determine whether treatment of medical disease and depressive symptoms can improve sleep disturbances.
Aged* ; Aging ; Anger ; Angina Pectoris ; Arthritis ; Asthma ; Cataract ; Cognition ; Cohort Studies ; Comorbidity ; Dementia ; Depression ; Education ; Epidemiologic Studies ; Follow-Up Studies* ; Glaucoma ; Hepatitis B ; Humans ; Hyperlipidemias ; Hypertension ; Hypertrophy ; Korea ; Logistic Models ; Mass Screening ; Myocardial Infarction ; Osteoporosis ; Prevalence ; Prostate ; Sleep Initiation and Maintenance Disorders ; Stroke ; Tuberculosis, Pulmonary ; Urinary Incontinence

PURPOSE: The severity and mortality of motorcycle accidents are higher than those of other traffic accidents. The majority of risk factors for injury severity identified in previous studies are difficult to apply. This study attempted to identify the clinically useful risk factors for predicting severely injured patients presenting to the emergency department after a motorcycle accident. METHODS: Motorcycle accident patients who visited a Level I trauma center from October 2015 to March 2017 were analyzed. The patients were classified as the severely injured group (Injury Severity Score, ISS≥16) and non-severely injured group (ISS<16). RESULTS: A total of 271 patients were analyzed; 135 (49.8%) patients were included in the severely injured group. Multiple logistic regression analysis was performed with the statistically significant factors between the two groups, including age, systolic blood pressure, heart rate, Glasgow coma scale, alcohol ingestion, and site of injury. The final risk factors predicting severely injured patients were as follows: age (adjusted odds ratio [aOR], 1.023; 95% confidence interval [CI], 1.005– 1.041; p=0.011), systolic blood pressure (aOR, 0.981; 95% CI, 0.970–0.993; p=0.002) and site of injury including abdomen (aOR, 5.785; 95% CI, 2.513–13.316; p<0.001), chest (aOR, 4.567; 95% CI, 2.274–9.173; p<0.001), head and neck (aOR, 5.762; 95% CI, 2.656–12.504; p<0.001), and face (aOR, 2.465; 95% CI, 1.229–4.943; p=0.011). CONCLUSION: Motorcycle accident patients should be assessed promptly for injury to the chest or abdomen by a careful physical examination and focused assessment with sonography for trauma.
Abdomen ; Accidents, Traffic ; Blood Pressure ; Critical Care ; Eating ; Emergency Service, Hospital ; Glasgow Coma Scale ; Head ; Heart Rate ; Humans ; Injury Severity Score ; Logistic Models ; Mortality ; Motorcycles* ; Neck ; Odds Ratio ; Physical Examination ; Risk Factors ; Thorax ; Trauma Centers

A hypoxic microenvironment leads to cancer progression and increases the metastatic potential of cancer cells within tumors via epithelial-mesenchymal transition (EMT) and cancer stemness acquisition. The hypoxic response pathway can occur under oxygen tensions of < 40 mmHg through hypoxia-inducible factors (HIFs), which are considered key mediators in the adaptation to hypoxia. Previous studies have shown that cellular responses to hypoxia are required for EMT and cancer stemness maintenance through HIF-1α and HIF-2α. The principal transcription factors of EMT include Twist, Snail, Slug, Sip1 (Smad interacting protein 1), and ZEB1 (zinc finger E-box-binding homeobox 1). HIFs bind to hypoxia response elements within the promoter region of these genes and also target cancer stem cell-associated genes and mediate transcriptional responses to hypoxia during stem cell differentiation. Acquisition of stemness characteristics in epithelial cells can be induced by activation of the EMT process. The mechanism of these phenotypic changes includes epigenetic alterations, such as DNA methylation, histone modification, chromatin remodeling, and microRNAs. Increased expression of EMT and pluripotent genes also play a role through demethylation of their promoters. In this review, we summarize the role of hypoxia on the acquisition of EMT and cancer stemness and the possible association with epigenetic regulation, as well as their therapeutic applications.
Anoxia* ; Chromatin Assembly and Disassembly ; DNA Methylation ; Epigenomics* ; Epithelial Cells ; Epithelial-Mesenchymal Transition* ; Fingers ; Gastropoda ; Genes, Homeobox ; Histones ; MicroRNAs ; Oxygen ; Promoter Regions, Genetic ; Response Elements ; Snails ; Stem Cells ; Transcription Factors