We aimed to review the current data composition of the Korean Tuberculosis and Post-Tuberculosis Cohort, which was constructed by linking the Korean Tuberculosis Surveillance System (KNTSS; established and operated by the Korean Disease Control and Prevention Agency since 2000) and the National Health Information Database (NHID; established by the National Health Insurance Service in 2012). The following data were linked: KNTSS data pertaining to patients diagnosed with tuberculosis between 2011 and 2018, NHID data of patients with a history of tuberculosis and related diseases between 2006 and 2018, and data (obtained from the Statistics Korea database) on causes of death. Data from 300 117 tuberculosis patients (177 206 men and 122 911 women) were linked. The rate of treatment success for new cases was highest in 2015 (86.7%), with a gradual decrease thereafter. The treatment success rate for previously treated cases showed an increasing trend until 2014 (79.0%) and decreased thereafter. In total, 53 906 deaths were confirmed among tuberculosis patients included in the cohort. The Korean Tuberculosis and Post-Tuberculosis Cohort can be used to analyze different measurement variables in an integrated manner depending on the data source. Therefore, these cohort data can be used in future epidemiological studies and research on policy-effect analysis, treatment outcome analysis, and health-related behaviors such as treatment discontinuation.

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

The National Evidence-based Healthcare Collaborating Agency (NECA), an institution for health technology assessment in Korea, has used public solicitation of research topics since its establishment in 2009. This creates a necessity for examining whether a given research topic was selected to be considered when prioritizing healthcare technology assessment and distributing healthcare resources. This study aimed to investigate the relationship between the research topics suggested to NECA and the disease burden in Korea. To find the correlation between disease burden and 1,112 suggested topics and 91 performed topics that were classified by Human Research Classification System a linear auxiliary trend line and scatter plot were constructed using disability-adjusted life years (DALYs), and Pearson's correlation coefficients were calculated. The results suggested that cancer was most common, followed by cardiovascular diseases, among suggested research topics and research topics performed by NECA, as well as in terms of the ratio of performed to suggested topics. The correlation between research topic and disease burden index indicated a strong correlation with DALYs and years of life lost (YLLs). However, years lived with disability and research topic had no relationship. Suggested topics showed a greater correlation with YLLs than DALYs, whereas performed topics showed a greater correlation with DALYs than YLLs, showing that despite the fact that the diseases with a high burden from morbidity were appropriately considered with respect to selecting research topics, a statistically significant difference was not found. As the first Korean study to assess the correlation between research topics and disease burden, our results will be used as base data for prioritizing the allocation of healthcare resources in the future.
Adenosine-5'-(N-ethylcarboxamide) ; Biomedical Technology* ; Cardiovascular Diseases ; Classification ; Cost of Illness ; Delivery of Health Care ; Evidence-Based Practice ; Humans ; Korea ; Technology Assessment, Biomedical*

OBJECTIVES: The aim of this study was to investigate the relationship between social exclusion and paranoid ideation, and to explore moderating and mediating effects of depression and self-esteem in that relationship. METHODS: Ninety seven neurosis patients receiving treatment in a psychiatric outpatient setting were selected. Social Exclusion Scale, Beck Depression Inventory, paranoia scale of Symptom Checklist-90-Revised, and Rosenberg Self-Esteem Scale were used for evaluation. RESULTS: Social exclusion showed highly positive correlation with paranoid ideation, and had significant influence. Among three types of social exclusion, contempt, bullying, and isolation, only isolation showed significant influence on paranoid ideation. Depression showed a partial mediating effect on that relationship indicating that social exclusion affects paranoid ideation not only directly, but also indirectly. On the other hand, self-esteem showed no moderating or mediating effects on that relationship. CONCLUSION: Depression mediates the influence of social exclusion on paranoid ideation. This finding provides an opportunity to decrease paranoid ideation of neurosis patients by not only prescription of antipsychotic agents but also therapeutic approach to social exclusion and depression. An experimental study to verify these findings seems to be needed.
Antipsychotic Agents ; Bullying ; Depression* ; Hand ; Humans ; Negotiating* ; Outpatients ; Paranoid Disorders ; Prescriptions ; Social Isolation

OBJECTIVE: After spinal cord injury (SCI), functional and structural reorganization occurs at multiple levels of brain including motor cortex. However, the underlying mechanism still remains unclear. The current study was performed to investigate the alterations in the expression of the main regulators of neuronal development, survival and death, in the brain following thoracic contusive SCI in a mouse model. METHODS: Eight-week-old female imprinting control region mice (n=60; 30-35 g) were used in this study. We analyzed the expression levels of regulators such as brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF) and histone deacetylase (HDAC) 1 in the brain following thoracic contusive SCI. RESULTS: The expression of BDNF levels were elevated significantly compared with control group at 2 weeks after injury (p<0.05). The expression of NGF levels were elevated at 2, 4 weeks compared with control group, but these difference were not significant (p>0.05). The GDNF levels were elevated at 2 week compared with control group, but these differences were not significant (p>0.05). The difference of HDAC1 levels were not significant at 2, 4 and 8 weeks compared with control group (p>0.05). CONCLUSION: These results demonstrate that the upregulation of BDNF may play on important role in brain reorganization after SCI.
Animals ; Brain ; Brain-Derived Neurotrophic Factor ; Epigenomics ; Female ; Glial Cell Line-Derived Neurotrophic Factor ; Histone Deacetylases ; Humans ; Mice ; Motor Cortex ; Nerve Growth Factor ; Neurons ; Spinal Cord ; Spinal Cord Injuries ; Up-Regulation

OBJECTIVE: Alcoholic neuropathy is characterized by allodynia (a discomfort evoked by normally innocuous stimuli), hyperalgesia (an exaggerated pain in response to painful stimuli) and spontaneous burning pain. The aim of the present study is to investigate the effect of rolipram, a phosphodiesterase 4 inhibitor, against alcohol-induced neuropathy in rats. METHODS: Allodynia was induced by administering 35% v/v ethanol (10 g/kg; oral gavage) to Spraue-Dawley rats for 8 weeks. Rolipram and saline (vehicle) were administered intraperitoneally. Mechanical allodynia was measured by using von Frey filaments. Somatosensory evoked potential (SEP) was proposed as complementary measure to assess the integrity of nerve pathway. RESULTS: The ethanol-induced mechanical allodynia began to manifest from 3 week, and then peaked within 1 week. Beginning from 3 week, latency significantly started to increased in control group. In rolipram treated rats, the shorter latency was sustained until 8 weeks (p<0.05). The mechanical allodynia, which began to manifest on the 3 weeks, intraperitoneal injections of rolipram sustained statistical difference until 8 weeks, the final week of the study (p<0.05). CONCLUSION: This study suggests that rolipram might alleviate mechanical allodynia induced by alcohol in rats, which clearly has clinical implication.
Alcoholic Neuropathy ; Alcoholics ; Animals ; Burns ; Cyclic Nucleotide Phosphodiesterases, Type 4 ; Ethanol ; Evoked Potentials, Somatosensory ; Humans ; Hyperalgesia ; Injections, Intraperitoneal ; Rats ; Rolipram

OBJECTIVE: Peripheral neuropathy is characterized by hyperalgesia, spontaneous burning pain, and allodynia. The purpose of this study was to investigate the effect of rolipram, a phosphodiesterase-4-specific inhibitor, in a segmental spinal nerve ligation model in rats. METHODS: Both the L5 and L6 spinal nerves of the left side of the rats were ligated. Phosphodiesterase-4 inhibitor (rolipram) and saline (vehicle) were administered intraperitoneally. We measured mechanical allodynia using von Frey filaments and a nerve conduction study. RESULTS: The mechanical allodynia, which began to manifest on the first day, peaked within 2 days. Multiple intraperitoneal injections of rolipram ameliorated the mechanical allodynia. Furthermore, an intraperitoneal administration of rolipram improved the development of pain behavior and nerve conduction velocity. CONCLUSION: This study suggests that the phosphodiesterase-4 inhibitor, rolipram, alleviates mechanical allodynia induced by segmental spinal nerve ligation in rats. This finding may have clinical implications.
Animals ; Burns ; Cyclic Nucleotide Phosphodiesterases, Type 4 ; Hyperalgesia ; Injections, Intraperitoneal ; Ligation ; Neural Conduction ; Peripheral Nerve Injuries ; Peripheral Nervous System Diseases ; Rats ; Rolipram ; Spinal Nerves

Magnetic resonance imaging (MRI) of six Yukatan minipig brains was performed. The animals were placed in stereotaxic conditions currently used in experiments. To allow for correctpositioning of the animal in the MRI instrument, landmarks were previously traced on the snout of the pig. To avoid movements, animal were anesthetized. The animals were placed in a prone position in a Siemens Magnetom Avanto 1.5 System with a head coil. Axial T2-weighted and sagittal T1-weighted MRI images were obtained from each pig. Afterwards, the brains of the pigs were fixed and cut into axial sections. Histologic and MR images were compared. The usefulness of this technique is discussed.
Animals ; Brain ; Head ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Magnetics ; Magnets ; Nervous System Diseases ; Prone Position ; Swine ; Swine, Miniature

PURPOSE: The objective of this study is to evaluate the effects of heat and massage application on autonomic nervous system. MATERIALS AND METHODS: One hundred thirty-nine subjects volunteered and completed this study. Heat and massage was daily applied for 40 minutes, 5 days a week for 2 weeks. Primary-dependent measures included heart rate variability, sympathetic skin response, and serum cortisol and norepinephrine levels. RESULTS: Serum cortisol levels were significantly decreased at 2 weeks compared to baseline (p=0.003). Plasma norepinephrine levels at 4 weeks were significantly decreased compared to baseline (p=0.010). Heart rate, using the power spectra, increased significantly after 2 weeks compared to baseline. Of autonomic nerve conduction measures, latency was significantly increased at 2 and 4 weeks compared to baseline (p=0.023, 0.012), and amplitude was significantly decreased at 4 weeks compared to baseline (p=0.008). There were no serious adverse events such as burns or other major complications. CONCLUSION: The results of this study suggest that heat and massage applications provide relaxation to the autonomic nervous system without serious adverse events.
Autonomic Nervous System/*physiopathology ; Female ; Heart Rate/*physiology ; Hot Temperature/adverse effects/*therapeutic use ; Humans ; Hydrocortisone/blood ; Male ; Massage/adverse effects/*methods ; Norepinephrine/blood

OBJECTIVE: Several important roles of 1,25(OH)2D3 have been recognized in the immune system. The availability of 1,25(OH)2D3 at the cellular level is significantly influenced by the relative abundance of enzymes to synthesize (CYP27B1) and catabolize (CYP24) 1,25(OH)2D3. In this study, we examined the effect of 1,25(OH)2D3 on the expression of the CYP24 gene and the role of MAPK for the induction of CYP24 by 1,25(OH)2D3 in activated human macrophages. METHODS: For obtaining human activated macrophages, we treated U937 cells with PMA and we cultured these cells for 24 hours to adhere. After 24 hours treatment with PMA, the differentiated cells were washed with phosphate buffered saline (PBS), and then they were used for examining the effect of 1,25(OH)2D3 on the expression of the CYP24 gene. The mRNA expressions of the vitamin-D3 inducible genes were measured by real-time PCR, and the change of the protein expression by 1,25(OH)2D3 was measured by immunoblotting. RESULTS: 1,25(OH)2D3 significantly induced the expression of CYP24 in the U937 cells and the 1,25(OH)2D3-induced expression of CYP24 was strongly augmented in the PMA-differentiated U937 cells. The 1,25(OH)2D3-induced expression of CYP24 was mediated by Erk1/2 and p38 MAPKs. Parallel to the induced expression of CYP24, 1,25(OH)2D3 induced the expression and phosphorylation of the CCAAT enhancer-binding protein (C/EBPbeta). CONCLUSION: In this study, we found that 1,25(OH)2D3 inducedthe expression of CYP24 via activation of MAPKs. These results suggest that MAPK inhibitors may be useful for the treatment of inflammatory conditions, in which active vitamin D3 can be used as the therapeutic molecule, by increasing the availability of 1,25(OH)2D3.
Cholecalciferol ; Humans ; Immune System ; Immunoblotting ; Macrophages ; p38 Mitogen-Activated Protein Kinases ; Phosphorylation ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Steroid Hydroxylases ; U937 Cells