ABSTRACT
We analyzed age-/sex-specific morbidity and mortality data from the SARS-CoV-2 pandemic in China and Republic of Korea (ROK). Data from China exhibit a Gaussian distribution with peak morbidity in the 50-59-year cohort, while the ROK data have a bimodal distribution with the highest morbidity in the 20-29-year cohort.
Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Adult , Betacoronavirus/pathogenicity , COVID-19 , China/epidemiology , Coronavirus Infections/virology , Female , Humans , Male , Middle Aged , Morbidity , Pandemics , Pneumonia, Viral/virology , Republic of Korea/epidemiology , SARS-CoV-2 , Young AdultABSTRACT
Diagnosis of scrub typhus is challenging due to its more than twenty serotypes and the similar clinical symptoms with other acute febrile illnesses including leptospirosis, murine typhus and hemorrhagic fever with renal syndrome. Accuracy and rapidity of a diagnostic test to Orientia tsutsugamushi is an important step to diagnose this disease. To discriminate scrub typhus from other diseases, the improved ImmuneMed Scrub Typhus Rapid Diagnostic Test (RDT) was evaluated in Korea and Sri Lanka. The sensitivity at the base of each IgM and IgG indirect immunofluorescent assay (IFA) in Korean patients was 98.6% and 97.1%, and the specificity was 98.2% and 97.7% respectively. The sensitivity and specificity for retrospective diagnosis at the base of IFA in Sri Lanka was 92.1% and 96.1%. ImmuneMed RDT was not reactive to any serum from seventeen diseases including hemorrhagic fever with renal syndrome (n = 48), leptospirosis (n = 23), and murine typhus (n = 48). ImmuneMed RDT shows superior sensitivity (98.6% and 97.1%) compared with SD Bioline RDT (84.4% at IgM and 83.3% at IgG) in Korea. The retrospective diagnosis of ImmuneMed RDT exhibits 94.0% identity with enzyme-linked Immunosorbent assay (ELISA) using South India patient serum samples. These results suggest that this RDT can replace other diagnostic tests and is applicable for global diagnosis of scrub typhus. This rapid and accurate diagnosis will be beneficial for diagnosing and managing scrub typhus.
Subject(s)
Scrub Typhus/diagnosis , Antibodies, Bacterial/blood , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique, Indirect , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Orientia tsutsugamushi/immunology , Reagent Kits, Diagnostic , Retrospective Studies , Scrub Typhus/microbiology , Sensitivity and SpecificityABSTRACT
Thiazolidinediones, synthetic ligands of peroxisomal proliferator-activated receptor-gamma (PPAR-gamma), improve peripheral insulin sensitivity and glucose-stimulated insulin secretion in pancreatic beta-cells. To explore the role of PPAR-gamma in glucose sensing of beta-cells, we have dissected the beta-cell-specific glucokinase (betaGK) promoter, which constitutes glucose-sensing apparatus in pancreatic beta-cells, and identified a peroxisomal proliferator response element (PPRE) in the promoter. The betaGK-PPRE is located in the region between +47 and +68 bp. PPAR-gamma/retinoid X receptor-alpha heterodimer binds to the element and activates the betaGK promoter. The betaGK promoter lacking or having mutations in PPRE cannot be activated by PPAR-gamma. PPAR-gamma activates the betaGK promoter in beta-cells as well as non-beta-cells. Furthermore, troglitazone increases endogenous GK expression and its enzyme activity in beta-cell lines. These results indicate that PPAR-gamma can regulate GK expression in beta-cells. Taking these results together with our previous work, we conclude that PPAR-gamma regulates gene expression of glucose-sensing apparatus and thereby improves glucose-sensing ability of beta-cells, contributing to the restoration of beta-cell function in type 2 diabetic subjects by troglitazone.
Subject(s)
Glucokinase/genetics , Islets of Langerhans/enzymology , Receptors, Cytoplasmic and Nuclear/physiology , Thiazolidinediones , Transcription Factors/physiology , Animals , Cell Line , Chromans/pharmacology , DNA/metabolism , Dimerization , Enzyme Activation/drug effects , Gene Expression/drug effects , Hypoglycemic Agents/pharmacology , Mice , Mutagenesis, Site-Directed , Promoter Regions, Genetic , Rats , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Retinoic Acid/metabolism , Response Elements , Retinoid X Receptors , Thiazoles/pharmacology , Transcription Factors/metabolism , Transcription Factors/pharmacology , Transcriptional Activation , Transfection , TroglitazoneABSTRACT
Discoidin domain receptors belong to the cell surface receptor tyrosine kinase family and recognize collagens for their activating ligands. They have been implicated for cell growth and migration and their elevated expressions were observed in various human cancers. When we expressed human Discoidin domain receptor 2 (DDR2) in insect cells, the protein was targeted properly into the cell membrane and this could enforce the cells to adhere on culture plate coated with type I collagen. By taking advantage of this, we established a novel insect cell based screening protocol to identify chemicals which inhibit the interaction between DDR2 and collagen. We screened a drug-compound library to select an anti-cancer drug, actinomycin D, as the inhibitory compound. Actinomycin D prevented the activation of DDR2 by type I collagen in human embryonic kidney 293 cells with an IC(50) value of 9 microM, while it did not interfere with the activation of other receptor tyrosine kinases by their ligands. In conclusion we identified a new biological function of actinomycin D and the insect cell based method provides a useful protocol for screening inhibitors against the association of DDR2 with collagen.