Direct visualization of glucagon‐like peptide‐1 secretion by fluorescent fusion proteins

Live‐cell imaging with fluorescent proteins (FPs) is a powerful tool for investigating the exocytosis processes of hormones. However, the secretion process of glucagon‐like peptide‐1 (GLP‐1) has not been visualized by FPs, which might be because tagging FPs inhibits GLP‐1 synthesis through the post‐translational processing from proglucagon. Here, we have developed FP‐tagged GLP‐1 by inserting FPs into the middle of GLP‐1 and adding the proglucagon signal peptide. Confocal imaging confirmed that GLP‐1 fused to FPs with high folding efficiency showed granular structure, in which secretory vesicle markers colocalized. The fluorescence intensity of FP in the culture supernatant from cells treated with KCl or forskolin was significantly increased compared with those from untreated cells. Furthermore, FP‐tagged GLP‐1 enables direct visualization of stimulation‐dependent exocytosis of GLP‐1 at a single granule resolution with total internal reflection fluorescence microscopy. FP‐tagged GLP‐1 might facilitate the screening of GLP‐1 secretagogues and the discovery of new antidiabetic drugs.     

Myiasis in Kuwait: nosocomial infections caused by lucilia sericata and Megaselia scalaris

Myiasis, the invasion of live human tissue by larvae of Diptera, is reported in the nasopharynx and a leg wound in two patients who were hospitalized for more than 72 hours in Mubarak Al-Kabeer Teaching Hospital in Kuwait City, Kuwait. On the fourth and fifth days after a 10-year-old Kuwaiti boy was admitted to the hospital intensive care unit in a bloodied and comatose state following a traffic accident, 'worms' that came out of his nostrils were fixed, cleared, and identified as second and third instar of Lucilia sericata (Diptera: Calliphoridae). After 14 days, 'worms' were seen in the original dressing of a 35-year-old Iranian man admitted to the Orthopedic Unit of the hospital with multiple lacerations and fractures. The larvae, in various stages of development, were identified as those of Megaselia scalaris (Diptera: Phoridae). Since the presence of larvae in both patients was recorded after a stay of at least 3-4 days in the hospital, by definition, these infestations are considered nosocomial.     

Clinical impact of complete atrioventricular block in patients with ST‐segment elevation myocardial infarction

Complete atrioventricular block (CAVB) is a common complication of ST‐segment elevation myocardial infarction (STEMI). Although STEMI patients complicated with CAVB had a higher mortality in the thrombolytic era, little is known about the impact of CAVB on STEMI patients who underwent primary percutaneous coronary intervention (PCI). The study aimed at evaluating the clinical impact of CAVB on STEMI patients in the primary PCI era. We consecutively enrolled 1295 STEMI patients undergoing primary PCI within 24 hours from onset. Patients were divided into two groups according to the infarct location: anterior STEMI (n = 640) and nonanterior STEMI (n = 655). The outcomes were all‐cause death and major adverse cardiocerebrovascular events (MACCE) with a median follow‐up period of 3.8 (1.7–6.6) years. Eighty‐one patients (6.3%) developed CAVB. The incidence of CAVB was lower in anterior STEMI patients than in nonanterior STEMI (1.7% vs 10.7%, p < .05). Anterior STEMI patients with CAVB had a higher incidence of all‐cause deaths (82% vs 20%, p < .05) and MACCE (82% vs 25%, p < .05) than those without CAVB. Although higher incidence of all‐cause deaths was found more in nonanterior STEMI patients with CAVB compared with those without CAVB (30% vs 18%, p < .05), there was no significant difference in the incidence of MACCE (24% vs 19%). Multivariate analysis showed that CAVB was an independent predictor for all‐cause mortality and MACCE in anterior STEMI patients, but not in nonanterior STEMI. CAVB is rare in anterior STEMI patients, but remains a poor prognostic complication even in the primary PCI era.     

Shape-controlled synthesis of magnetic Fe3O4 nanoparticles with different iron precursors and capping agents

This paper describes a modified method to prepare monodisperse Fe₃O₄ magnetic nanoparticles with different shapes (cube, octahedron, and sphere). The shape of the magnetic nanoparticles could be conveniently controlled by changing the types of precursor/capping agent and concentration of capping agent. The prepared samples were characterized using scanning electron microscopy, X-ray diffraction and vibrating sample magnetometry. Cubes and octahedra were formed using ferrous sulfate heptahydrate as an iron source, ethylene glycol as a solvent and potassium hydroxide (KOH) as a capping agent while spheres were formed by using ferric chloride hexahydrate as an iron source, ethylene glycol as a solvent and ammonium acetate as a capping agent. By varying KOH concentration (0.5 M, 1 M, 1.5 M, and 5 M), the shape was transformed from cubes to octahedra because octahedra are developed dominantly at higher concentration of KOH within the reaction mixture. The magnetic studies show superparamagnetic behavior for all samples at room temperature. The Fe₃O₄ nanoparticles show the magnetic saturation values of 87 emu g⁻¹, 85 emu g⁻¹, and 82 emu g⁻¹ for spheres, cubes, and octahedrons, respectively.

This paper describes a modified method to prepare monodisperse Fe₃O₄ magnetic nanoparticles with different shapes (cube, octahedron, and sphere).     

Liver-related events after direct-acting antiviral therapy in patients with hepatitis C virus-associated cirrhosis

Journal of Gastroenterology - Direct-acting antiviral (DAA) therapy enables a high rate of sustained virologic response (SVR) in patients with hepatitis C virus associated cirrhosis. However, the...     

Risk of hepatocellular carcinoma after hepatitis C virus cure

Hepatitis C virus(HCV)is a significant cause of hepatocellular carcinoma(HCC).The direct-acting antivirals marked a new era of HCV therapy and are associated with greater than 95%cure rate.Successful treatment of chronic hepatitis C greatly reduces the risk of HCC.A proportion of patients,especially those with pre-existing cirrhosis,remain at risk for HCC despite sustained virologic response(SVR).Diabetes mellitus,hepatic steatosis,alcohol consumption and lack of fibrosis regression are associated with risks of HCC after HCV cure.Noninvasive modalities such as aspartate aminotransferase to platelet ratio index and fibrosis-4 index and transient elastography have been used to monitor hepatic fibrosis.More recently,various fibrosis scores have been combined with clinical parameters and other novel biomarkers to predict risks of HCC for patients who achieved SVR.These models still need to be validated and standardized prior to applying to routine clinical care.     

Comparison of the effects of predilution and postdilution hemodiafiltration on neutrophils, lymphocytes and platelets

Numerous studies have been carried out to investigate the solute removal efficiency of hemodiafiltration (HDF). However, the effect of the dilution mode on blood cell damage during HDF has not yet been examined in detail. Here, we compared predilution and postdilution HDF with respect to their effects on blood cells. Five patients were allocated to one session each of predilution HDF and postdilution HDF. Concentrations of interleukin (IL)-6, intercellular adhesion molecule (ICAM)-1, and platelet-derived microparticles (PDMP), and the phagocytotic and sterilizing functions of neutrophils before and after the HDF sessions were evaluated. Lymphocyte blastoid transformation induced by mitogens was also evaluated by measurement of the [³H]-thymidine uptake. The IL-6 and ICAM-1 concentrations decreased after predilution HDF, and increased after postdilution HDF. Lymphocyte blastoid transformation was more pronounced after predilution HDF than after postdilution HDF. There was no significant difference in PDMP between the dilution modes. We conclude that predilution HDF could be more favorable for dialysis patients than postdilution HDF from the point of view of the effects on the blood cells, especially neutrophils and lymphocytes.