A 'circadian rhythm' is a self-sustained biological rhythm (cycle) that repeats itself approximately every 24 hours. Circadian rhythms are generated by an internal clock, or pacemaker, and persist even in the absence of environmental time cues, collectively termed 'zeitgebers.' Although organisms generate circadian rhythms internally, they are entrained by environmental stimuli, particularly the light-dark cycle. Measurement of the endogenous melatonin rhythm provides relatively reliable surrogate way of assessing the timing of the internal circadian clock. Also, core body temperature and cortisol can be used as markers of circadian rhythms. The sleep-wake cycle, body temperature, and melatonin rhythm have a stable internal phase relationship in humans and other diurnal species. They play an important role in controlling daily behavioral rhythms including task performance, blood pressure, and synthesis and secretion of several hormones. In this review, we address not only the properties, methods of measurement, and markers of circadian rhythms, but also the physiological and psychological importance of human circadian rhythms.
Blood Pressure ; Body Temperature ; Circadian Clocks ; Circadian Rhythm* ; Cues ; Humans ; Hydrocortisone ; Melatonin ; Photoperiod ; Task Performance and Analysis

PURPOSE: Parenteral nutrition (PN) is known to provide therapeutic beneficial improvements in malnourished patients for whom enteral nutrition is not feasible. The objective of this study was to investigate the current clinical characteristics and utilization of PN in Korea. METHODS: We analyzed the Health Insurance Review Agency National Inpatients Sample database from 2014 to 2016, which included 13% of all hospitalized patients in Korea. Adult patients aged 20 years or older and receiving premixed multi-chamber bag containing PN were included for this study. Patient characteristics, admission type, primary diagnosis, and hospital demographics were evaluated. SAS version 9.4 was used for data analysis. RESULTS: From 2014 to 2016, 149,504 patients received premixed PN, with 226,281 PN prescriptions being written. The mean patient age was 65.0 years, and 81,876 patients (54.8%) were male. Premixed 3-chamber bag and 2-chamber bag PN solutions were utilized in 131,808 (88.2%) and 32,033 (21.4%) patients, respectively. The number of patients hospitalized through the emergency department were 70,693 (47.3%), whereas 43,125 patients (28.8%) were administered PN in intensive care units. In the adult PN patients, the highest primary diagnosis was malignant neoplasm of the stomach (8,911, 6.0%), followed by organism unspecified pneumonia (7,008, 4.7%), and gastroenteritis and colitis of unspecified origin (6,381, 4.3%). Overall, 34% of adult PN patients were diagnosed with malignancies, the most common being neoplasm of the stomach (17.7%), neoplasm of bronchus/lung (11.2%), neoplasm of colon (11.1%), and neoplasm of liver/intrahepatic bile ducts (10.0%). PN solutions were most frequently administered in the metropolitan area (55.0%) and in hospitals with more than 1,000 beds (23.6%). CONCLUSION: PN was commonly administered in older patients, with primary diagnosis of malignancy in a significant number of cases. This study is the first large-scale description of PN-prescribing patterns in real-world clinical practice in South Korea.
Adult* ; Bile Ducts ; Colitis ; Colon ; Demography ; Diagnosis ; Emergency Service, Hospital ; Enteral Nutrition ; Gastroenteritis ; Humans ; Inpatients ; Insurance, Health ; Intensive Care Units ; Korea* ; Male ; Nutritional Support ; Parenteral Nutrition* ; Pneumonia ; Prescriptions ; Statistics as Topic ; Stomach

PURPOSE: To evaluate the clinical manifestations of adverse drug reactions (ADRs) of parenteral nutrition (PN) use in Korea. METHODS: The Korean Adverse Event Reporting System (KAERS) database records in 2015 on PN-treated patients were used. ADRs classified as “certain,”“probable,” and “possible” based on the WHO-Uppsala Monitoring Centre criteria were analyzed. RESULTS: In total, 21,436 ADRs from 2,346 patients were included for analysis. The mean patient age was 57.1 years and the mean number of ADRs per patient was 9.1. ADRs were reported frequently with amino acids solutions (682 events, 40.8%), followed by combinations products (519 events, 31.1%), and fat emulsions (363 events, 21.7%). The frequent ADRs were gastrointestinal (507 events, 30.3%), skin (343 events, 20.5%), general disorders (239 events, 14.3%), and central/peripheral nervous system disorders (165 events, 9.9%). The common clinical symptoms were nausea (321 events, 19.2%), vomiting (105 events, 6.3%), and vein pain (102 events, 6.1%). Serious ADRs accounted for 220 patients (9.4%) and dyspnea was the most frequent clinical manifestation. CONCLUSION: This study analyzed the KAERS data in 2015 from patients treated with PN and revealed gastrointestinal and skin disorders to be the leading ADRs.
Amino Acids ; Drug-Related Side Effects and Adverse Reactions ; Dyspnea ; Emulsions ; Humans ; Korea* ; Nausea ; Nervous System Diseases ; Parenteral Nutrition* ; Skin ; Veins ; Vomiting

BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) effectively reduce serum levels of low-density lipoprotein (LDL) and total cholesterol. High-intensity statins are recommended for all patients aged ≤75 with clinical atherosclerotic cardiovascular disease (ASCVD), diabetes mellitus aged 40–75 with ≥7.5% estimated 10-year ASCVD risk and LDL-C ≥190 mg/ dL. High-intensity statins associated with more frequent adverse events (AEs) compared to moderate- to low-intensity statins. The aim of this study was to compare AEs between high-intensity and moderate- to low-intensity statin group using the Korea Adverse Event Reporting System (KAERS) database. METHODS: Adults (≥18 years) with statin-associated AEs from July 2009-June 2014 were included. Only AEs classified as “certain”, “probable” and “possible” based on the WHO-Uppsala Monitoring Center criteria were analyzed. RESULTS: In total, 247 AEs from 196 patients [high-intensity statin group (HG), n = 25 (13%); moderate- to lowintensity statin group (MLG), n = 171 (87%)] were included. Mean age was higher in HG compared with MLG (67 ± 14 vs 62 ± 12). The HG showed a significant higher frequency of liver/biliary system disorders (37% vs 14%, p = 0.001). Hepatic function abnormal was reported more frequently in HG compared to MLG (26% vs 9%, p = 0.006). CONCLUSION: According to KAERS data, liver/biliary system disorders were more frequently reported in HG compared to MLG.
Adult ; Cardiovascular Diseases ; Cholesterol ; Coenzyme A ; Diabetes Mellitus ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors* ; Korea ; Lipoproteins ; Oxidoreductases

BACKGROUND: Previous studies have noted that the simultaneous use of sulfonylureas and antimicrobials, which is common, could increase the risk of hypoglycemia. In particular, an age of 65 years or older is a known risk factor for sulfonylurea-related hypoglycemia in hospitalized patients. Therefore, we performed this study to determine the potential risk of hypoglycemia from the concurrent use of antimicrobials and sulfonylureas. METHODS: We performed a cross-sectional study on the National Health Insurance Service-National Sample Cohort from 2013. The eligibility criteria included patients of 65 years of age or older taking a sulfonylurea with 25 different antimicrobials. Different risk ratings of severity in drug-drug interactions (potential DDIs), level X, D, or C in Lexi-Interact™online, and contraindicated, major, or moderate severity level in Micromedex® were included. SAS version 9.4 was used for data analysis. RESULTS: A total of 6,006 elderly patients with 25,613 prescriptions were included. The largest age group was 70 to 74 (32.7%), and 39.7% of patients were men. The mean number of prescriptions was 4.3 per patient. The most frequently used antimicrobials were levofloxacin (6,583, 25.7%), ofloxacin (6,549, 25.6%), fluconazole (4,678, 18.0%), and ciprofloxacin (2,551, 9.8%). Among sulfonylureas, glimepiride was prescribed most frequently, followed by gliclazide, glibenclamide, and glipizide. CONCLUSION: Of the antimicrobials with a high potential of hypoglycemia, levofloxacin, ofloxacin, fluconazole, and ciprofloxacin were used frequently. Thus, the monitoring of clinically relevant interactions is required for patients concurrently administered sulfonylureas and antimicrobials.
Aged* ; Anti-Infective Agents ; Ciprofloxacin ; Cohort Studies ; Cross-Sectional Studies ; Drug Interactions ; Fluconazole ; Gliclazide ; Glipizide ; Glyburide ; Humans ; Hypoglycemia* ; Korea* ; Levofloxacin ; Male ; National Health Programs ; Ofloxacin ; Prescriptions ; Risk Factors ; Statistics as Topic ; Sulfonylurea Compounds

Various digital healthcare devices and apps, such as blood glucose meters, blood pressure monitors, and step-trackers are commonly used by patients; however, digital healthcare devices have not been widely accepted in the medical market as of yet. Despite the various legal and privacy issues involved in their use, the main reason for its poor acceptance is that users do not use such devices voluntarily and continuously. Digital healthcare devices generally do not provide valuable information to users except for tracking self-checked glucose or walking. To increase the use of these devices, users must first understand the health data produced in the context of their personal health, and the devices must be easy to use and integrated into everyday life. Thus, users need to know how to manage their own data. Medical staff must teach and encourage users to analyze and manage their patient-generated healthcare data, and users should be able to find medical values from these digital devices. Eventually, a single customized service that can comprehensively analyze various medical data to provide valuable customized services to users, and which can be linked to various heterogeneous digital healthcare devices based on the integration of various health data should be developed. Digital healthcare professionals should have detailed knowledge about a variety of digital healthcare devices and fully understand the advantages and disadvantages of digital healthcare to help patients understand and embrace the use of such devices.

Various digital healthcare devices and apps, such as blood glucose meters, blood pressure monitors, and step-trackers are commonly used by patients; however, digital healthcare devices have not been widely accepted in the medical market as of yet. Despite the various legal and privacy issues involved in their use, the main reason for its poor acceptance is that users do not use such devices voluntarily and continuously. Digital healthcare devices generally do not provide valuable information to users except for tracking self-checked glucose or walking. To increase the use of these devices, users must first understand the health data produced in the context of their personal health, and the devices must be easy to use and integrated into everyday life. Thus, users need to know how to manage their own data. Medical staff must teach and encourage users to analyze and manage their patient-generated healthcare data, and users should be able to find medical values from these digital devices. Eventually, a single customized service that can comprehensively analyze various medical data to provide valuable customized services to users, and which can be linked to various heterogeneous digital healthcare devices based on the integration of various health data should be developed. Digital healthcare professionals should have detailed knowledge about a variety of digital healthcare devices and fully understand the advantages and disadvantages of digital healthcare to help patients understand and embrace the use of such devices.

BACKGROUND: Dendritic cell (DC)-based cancer immunotherapy is studied for several years. However, it is mainly derived from autologous PBMC or leukapheresis from patient, which has limitations about yield and ability of DC production according to individual status. In order to solve these problems, inquiries about allogeneic DCs are performed but there are no preclinical trial answers for effect or toxicity of allogeneic DC to use for clinical trial. In this study, we compared the anti-tumor effect of allogeneic and autologous DCs from mouse bone marrow stem cells in mouse metastatic melanoma model. METHODS: B16F10 melanoma cells (5 x 10(4)/mouse) were injected intravenously into the C57BL/6 mouse. Therapeutic DCs were differentiated from autologous (C57BL/6: CDC) or allogeneic (B6C3F1: BDC) bone marrow stem cells with GM-CSF, SCF and IL-4 for 13days and pulsed with B16F10 tumor cell lysate (Blys) for 18hrs. DC intra-peritoneal injections began on the 8th day after the tumor cell injection by twice with one week interval. RESULTS: Anti-tumor response was observed by DC treatment without any toxicity especially in allogeneic DC treated mice (tumor burden score: 2.667+/-0.184, 2.500+/-0.463, 2.000+/-0.286, 1.500+/-0.286, 1.667+/-0.297 for saline, CDC/unpulsed-DC: U-DC, CDC/Blys-DC, BDC/U-DC and BDC/Blys-DC, respectively). IFN-gamma secretion was significantly increased in allogeneic DC group stimulated with B16F10 cell lysate (2,643.3+/-5,89.7, 8,561.5+/-2,204.9. 6,901.2+/-141.1 pg/1 x 10(6) cells for saline, BDC/U-DC and BDC/Blys-DC, respectively) with increased NK cell activity. CONCLUSION: Conclusively, promising data was obtained that allogeneic DC can be used for DC-based cancer immunotherapy.
Animals ; Bone Marrow ; Dendritic Cells ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Immunotherapy ; Interleukin-4 ; Killer Cells, Natural ; Leukapheresis ; Melanoma* ; Mice ; Neoplasm Metastasis* ; Stem Cells

BACKGROUND: To perform the successful dendritic cell-based cancer immunotherapy one of the main issues to be solved is the source of antigen for DC pulsing. Limitations occur by using auto-tumor lysate due to the difficulties obtaining enough tumor tissue(s) quantitatively as well as qualitatively. In this study the possibility of allogeneic tumor cell lysate as a DC pulsing antigen has been tested in mouse melanoma pulmonary metastasis model. METHODS: B16F10 melanoma cells (1x10(5)/mouse) were inoculated intravenously into the C57BL/6 mouse. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 (1,000 U/ml each) for 7 days and pulsed with lysate of either autologous B16F10 (B-DC), allogeneic K1735 (C3H/He origin; K-DC) or CloneM3 (DBA2 origin; C-DC) melanoma cells for 18 hrs. Pulsed-DCs (1x10(6)/mouse)[CGP1] were injected i.p. twice with one week interval starting from the day 1 after tumor cell inoculation. RESULTS: Without observable toxicity, allogeneic tumor cell lysate pulsed-DC induced the significantly better anti-tumor response (tumor scale: 2.7+/-0.3, 0.7+/-0.3 and 0.3+/-0.2 for saline, B-DC and C-DC treated group, respectively). Along with increased tumor specific lymphocyte proliferations, induction of IFN-gamma secretion against both auto- and allo-tumor cell lysates was observed from the DC treated mice. (w/B16F10-lysate: 44.97+/-10.31, 1787.94+/-131.18, 1257.15+/-48.27, w/CloneM3 lysate: 0, 1591.13+/-1.83, 1460.47+/-86.05 pg/ml for saline, B-DC and C-DC treated group, respectively) Natural killer cell activity was also increased in the mice treated with tumor cell lysate pulsed-DC (8.9+/-[CGP2]0.1, 11.6+/-0.8 and 12.6+/-0.7% specific NK activity for saline, B-DC and C-DC treated group, respectively). CONCLUSION: Conclusively, promising data were obtained that allogeneic-tumor cell lysate can be used as a tumor antigen for DC-based cancer immunotherapy.
Animals ; Bone Marrow ; Dendritic Cells* ; Granulocyte-Macrophage Colony-Stimulating Factor ; Immunotherapy ; Interleukin-4 ; Killer Cells, Natural ; Lymphocytes ; Melanoma* ; Mice ; Neoplasm Metastasis*

BACKGROUND: Tumor cell lysate has been considered as a preferential antigen source for the therapeutic dendritic cell pulsing. Our experiences with in vivo study with animal tumor model indicate the tumor cell lysate dependent differential effect of DC therapy. Our previous data show that MC38 lysate pulsed-DC induced stronger ag-specific immunity than CT26 lysate pulsed-DC in vitro. In this study we tried to reveal the mechanism for differential induction of ag-specific immunity of different colon cancer cell lysate pulsed-DCs. METHODS: MC38 and CT26 cell lines were prepared as lysate by freezing-thawing procedure. Tumor cell antigenicity was confirmed by detecting the surface expression of MHC I/II & B7.1/2 molecules. IL-10, IL-12 and TGF-beta in the tumor cell lysate were detected by ELISA and the presence of heat shock proteins were analysed by western blotting. RESULTS: The secretion of IL-10, a immune-inhibitory cytokine was about 470% higher in CT26 lysate than in MC38. Hsp 70 was detected only in the MC38 lysate but not in the CT26. On the other hand, Hsp 60 and 90 expression were not different in two colon cancer cell lysates. CONCLUSION: In two different colon caner cell lysate, immune inhibitory IL-10 (higher in CT26) and Hsp70 (MC38 superiority) were differentially expressed. These data indicate that higher ag- specific immunity induction by MC38 lysate pulsed-DC may due to the expression of hsp70 and lower secretion of IL-10, a immune-inhibitory cytokine than CT26 lysate. The significance of other cytokine and the surface marker expression will be discussed.
Animals ; Blotting, Western ; Cell Line ; Colon ; Colonic Neoplasms ; Dendritic Cells ; Enzyme-Linked Immunosorbent Assay ; Hand ; Heat-Shock Proteins ; Interleukin-10 ; Interleukin-12 ; Transforming Growth Factor beta