Mesenchymal Stem Cell-Extracellular Vesicle Therapy for Stroke: Scalable Production and Imaging Biomarker Studies

A major clinical hurdle to translate MSC-derived extracellular vesicles (EVs) is the lack of a method to scale-up the production of EVs with customized therapeutic properties. In this study, we tested whether EV production by a scalable 3D-bioprocessing method is feasible and improves neuroplasticity in animal models of stroke using MRI study. MSCs were cultured in a 3D-spheroid using a micro-patterned well. The EVs were isolated with filter and tangential flow filtration and characterized using electron microscopy, nanoparticle tracking analysis, and small RNA sequencing. Compared to conventional 2D culture, the production-reproduction of EVs (the number/size of particles and EV purity) obtained from 3D platform were more consistent among different lots from the same donor and among different donors. Several microRNAs with molecular functions associated with neurogenesis were upregulated in EVs obtained from 3D platform. EVs induced both neurogenesis and neuritogenesis via microRNAs (especially, miR-27a-3p and miR-132-3p)-mediated actions. EV therapy improved functional recovery on behavioral tests and reduced infarct volume on MRI in stroke models. The dose of MSC-EVs of 1/30 cell dose had similar therapeutic effects. In addition, the EV group had better anatomical and functional connectivity on diffusion tensor imaging and resting-state functional MRI in a mouse stroke model. This study shows that clinical-scale MSC-EV therapeutics are feasible, cost-effective, and improve functional recovery following experimental stroke, with a likely contribution from enhanced neurogenesis and neuroplasticity

Triage results of children who visited the emergency department via emergency medical service providers: an observational study in a regional emergency medical center

Purpose We aimed to investigate the triage results and the degree of agreement between prehospital and hospital stages of pediatric patients who visited the emergency department (ED) via emergency medical service providers (EMSP) in comparison with adult patients. Methods We retrospectively reviewed 8,152 pediatric patients who visited a regional emergency medical center ED via EMSP from January 2015 to December 2015. Pediatric patients were defined as younger than 15 years according to the Korean Triage and Acuity Scale (KTAS). Given the difference of the triage tools of the prehospital (EMSP) and hospital (KTAS) stages, we performed the re-triage into “critical” and “non-critical”. Comparisons of characteristics between pediatric and adult patients were made using chi-square tests. The degree of agreement between the tools was analyzed using κanalysis. Results Of 8,152 patients, 654 (8.0%) were pediatric patients. Direct medical control was more frequently performed to adult patients (P < 0.001). Critical patients were more common among adults (12.2% by KTAS, 24.8% by EMSP) than children (3.5% by KTAS, 14.1% by EMSP). The κ value of pediatric patients was lower than that of adult patients (0.09 [poor]; 95% confidence interval [CI], 0.01-0.18 vs. 0.38 [fair]; 95% CI, 0.35-0.40). Conclusion Pediatric patients transferred by EMSP showed lower severity and degree of agreements of the triage results between prehospital and hospital stages than adult patients. It is necessary to pay particular attention to pediatric triage in a pre-hospital setting

Safe and cost-effective method for application of liquid ethyl formate (FumateTM) as a methyl bromide alternative for perishable commodities: Poster

The cylinderized liquid ethyl formate (EF) formulated with CO2 is one of the great potential fumigants to replace methyl bromide (MeBr) for fresh fruit. However, it is too expensive to adapt commercial practices, and also involves work place safety issue including handling of heavy cylinders as well as restrict emission of CO2, particularly for use in large scale commercial fumigationw. Therefore, it is urgently needed to develop environmental friendly, safe for workers and cost-effective alternative method for application of liquid ethyl formate as a MeBr alternative for perishable commodities. Recently, the environmentally friendly, cost-effective and practically safe use of liquid EF (FumateTM, registered name) with nitrogen gas has been developed and commercialized in Republic of Korea and Australia. The new technology for application of liquid EF is 100 times safer than MeBr in terms of threshold values (EF, TLV = 100 ppm). Ethyl formate is known as food additive and naturally occurred substances as well as a non-ozone depletion chemical. In this report, we demonstrate the liquid EF application technology that offers a clean environment (no ozone depletions and CO2 emissions), safe to fumigators and related workers and practically cost-effective technology to fumigation industry.The cylinderized liquid ethyl formate (EF) formulated with CO2 is one of the great potential fumigants to replace methyl bromide (MeBr) for fresh fruit. However, it is too expensive to adapt commercial practices, and also involves work place safety issue including handling of heavy cylinders as well as restrict emission of CO2, particularly for use in large scale commercial fumigationw. Therefore, it is urgently needed to develop environmental friendly, safe for workers and cost-effective alternative method for application of liquid ethyl formate as a MeBr alternative for perishable commodities. Recently, the environmentally friendly, cost-effective and practically safe use of liquid EF (FumateTM, registered name) with nitrogen gas has been developed and commercialized in Republic of Korea and Australia. The new technology for application of liquid EF is 100 times safer than MeBr in terms of threshold values (EF, TLV = 100 ppm). Ethyl formate is known as food additive and naturally occurred substances as well as a non-ozone depletion chemical. In this report, we demonstrate the liquid EF application technology that offers a clean environment (no ozone depletions and CO2 emissions), safe to fumigators and related workers and practically cost-effective technology to fumigation industry

Enhanced cardiac expression of two isoforms of matrix metalloproteinase-2 in experimental diabetes mellitus.

BackgroundDiabetic cardiomyopathy (DM CMP) is defined as cardiomyocyte damage and ventricular dysfunction directly associated with diabetes independent of concomitant coronary artery disease or hypertension. Matrix metalloproteinases (MMPs), especially MMP-2, have been reported to underlie the pathogenesis of DM CMP by increasing extracellular collagen content.PurposeWe hypothesized that two discrete MMP-2 isoforms (full length MMP-2, FL-MMP-2; N-terminal truncated MMP-2, NTT-MMP-2) are induced by high glucose stimulation in vitro and in an experimental diabetic heart model.MethodsRat cardiomyoblasts (H9C2 cells) were examined to determine whether high glucose can induce the expression of the two isoforms of MMP-2. For the in vivo study, we used the streptozotocin-induced DM mouse heart model and age-matched controls. The changes of each MMP-2 isoform expression in the diabetic mice hearts were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical stains were conducted to identify the location and patterns of MMP-2 isoform expression. Echocardiography was performed to compare and analyze the changes in cardiac function induced by diabetes.ResultsQuantitative RT-PCR and immunofluorescence staining showed that the two MMP-2 isoforms were strongly induced by high glucose stimulation in H9C2 cells. Although no definite histologic features of diabetic cardiomyopathy were observed in diabetic mice hearts, left ventricular systolic dysfunction was determined by echocardiography. Quantitative RT-PCR and IHC staining showed this abnormal cardiac function was accompanied with the increases in the mRNA levels of the two isoforms of MMP-2 and related to intracellular localization.ConclusionTwo isoforms of MMP-2 were induced by high glucose stimulation in vitro and in a Type 1 DM mouse heart model. Further study is required to examine the role of these isoforms in DM CMP

Comparison of infarct-related artery vs multivessel revascularization in ST-segment elevation myocardial infarction with multivessel disease: Analysis from Korea Acute Myocardial Infarction Registry

Background: Many ST-segment elevation myocardial infarction (STEMI) patients have multivessel disease. There is still controversy in treatment strategy in STEMI patients with multivessel disease. We compared clinical outcomes of multivessel revascularization with infarct- related artery (IRA) revascularization in STEMI patients. Methods: The 1,644 STEMI patients with multivessel disease (1,106 in IRA group, 538 in multivessel group) who were received primary percutaneous coronary intervention (PCI) were analyzed from a nationwide Korea Acute Myocardial Infarction Registry. Primary endpoint was 12-month major adverse cardiac events (MACE, defined as death, myocardial infarction, and repeated revascularization). Secondary endpoints were 1-month MACE and each component, stent thrombosis during 12 month follow-up, and each components of the 12-month MACE. Results: There were more patients with unfavorable baseline conditions in IRA group. 12-month MACE occurred in 165 (14.9%) patients in IRA group, 81 (15.1%) patients in multivessel group (p = 0.953). There were no statistical significance in the rate of 1-month MACE, each components of 1-month MACE, and stent thrombosis during 12 month follow-up. Each components of 12-month MACE were occurred similarly in both groups except for target lesion revascularization (2.4% in IRA group vs 5.9% in multivessel group, p < 0.0001). After adjusting for confounding factors, multivessel revascularization was not associated with reduced 12-month MACE (OR 1.096, 95% CI 0.676&#8211;1.775, p = 0.711). Conclusions: There were no significant differences in clinical outcomes between both groups except for high risk of target lesion revascularization in multivessel revascularization group

Mesothelial Cyst of the Round Ligament Mimicking a Metastasis: a Case Report

A mesothelial cyst of the round ligament is a rare cause of an inguinal mass. Clinically, it is frequently misdiagnosed as one of commoner diseases such as an inguinal hernia, femoral hernia, lipoma, and lymphadenopathy upon physical examination. Some previous reports elaborated the sonographic features of a mesothelial cyst of the round ligament. However, to our knowledge, few reports have described the CT features of a mesothelial cyst. We illustrated here the sonographic and multidetector CT features of a case of a mesothelial cyst of the round ligament that presented as an inguinal palpable mass and mimicked a metastasis in a patient with a Sertoli-Leydig cell tumor of the ovary