Mesenchymal Stem Cell-Derived Extracellular Vesicle Therapy for Stroke: Challenges and Progress

Stroke is the leading cause of physical disability among adults. Stem cells such as mesenchymal stem cells (MSCs) secrete a variety of bioactive substances, including trophic factors and extracellular vesicles (EVs), into the injured brain, which may be associated with enhanced neurogenesis, angiogenesis, and neuroprotection. EVs are circular membrane fragments (30 nm−1 μm) that are shed from the cell surface and harbor proteins, microRNAs, etc. Since 2013 when it was first reported that intravenous application of MSC-derived EVs in a stroke rat model improved neurological outcomes and increased angiogenesis and neurogenesis, many preclinical studies have shown that stem cell-derived EVs can be used in stroke therapy, as an alternative approach to stem cell infusion. Although scientific research regarding MSC-derived EV therapeutics is still at an early stage, research is rapidly increasing and is demonstrating a promising approach for patients with severe stroke. MSC therapies have already been tested in preclinical studies and clinical trials, and EV-mediated therapy has unique advantages over cell therapies in stroke patients, in terms of biodistribution (overcoming the first pass effect and crossing the blood-brain-barrier), cell-free paradigm (avoidance of cell-related problems such as tumor formation and infarcts caused by vascular occlusion), whilst offering an off-the-shelf approach for acute ischemic stroke. Recently, advances have been made in the understanding of the function and biogenesis of EVs and EVs therapeutics for various diseases. This review presents the most recent advances in MSC-derived EV therapy for stroke, focusing on the application of this strategy for stroke patients

The Influence Of Job Insecurity On Career Commitment And Attitude In Multinational Corporations

As the perception of lifelong work shifts into lifelong career in the job insecurity market, the career development of employees through professional and competitive career management has become more important than being loyal to a lifelong work. Furthermore, in the case of multinational corporations, such as differentiation from the head office policy, cultural differences in labor relations, and the liquidity of business withdrawal, such a feature has a higher possibility of job insecurity than general companies. Therefore, the purpose of this study is to verify empirically how job insecurity influences career commitment and career attitude through individual, job and career characteristics as intermediation with the members of multinational corporations as objectives. For this purpose, a total of 366 questionnaire data that targeted 27 multinational corporations were collected and analyzed. The result shows that the job insecurity of multinational corporations affects individual characteristic rather than job or career characteristic, and it is confirmed that individual characteristic has an effect on career commitment and career attitude. In the end, multinational corporations, unlike ordinary domestic companies, need active organizational career development program that corresponds to an open corporate culture as well as innovative and open systems and policies that balance both internal and external networking activities in terms of human resource management of corporations

Upper Gastrointestinal Tract Foreign Bodies

Foreign body ingestion, a common emergency encountered in clinical practice, is a potentially serious condition. Most foreign bodies in the gastrointestinal tract pass spontaneously. However, objects that are relatively long or large may lodge in the upper gastrointestinal tract, potentially causing perforation, bleeding, and obstruction. This literature review summarizes the natural history and clinical aspects of these types of foreign bodies in adults as well as the various methods for their removal. Endoscopic removal is a relatively safe and effective procedure for removing these types of foreign bodies. The development of endoscopic techniques and devices has resulted in their widespread use, with good results, as the primary treatment

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

An Efficient Building Evacuation Algorithm in Congested Networks

This paper proposes a new network model for the building evacuation problem considering congestion levels and provides a mixed integer linear programming (MILP) model and an efficient heuristic algorithm solving the problem. Constructing an optimization model with several congestion levels, we introduce a new network called the multi-class time-expanded (MCTE) network having several exclusive arcs connecting the same tail and head nodes. The MCTE networks make both the MILP model and the heuristic algorithm reflect a realistic situation in congested networks. Considering MCTE networks makes the problem difficult to solve, which motivates us to develop an efficient heuristic algorithm. We test our heuristic algorithm using several real-world networks such as a multiplex cinema, a subway station, and a large-size complex shopping mall in addition to an artificial network for clear comparison between the proposed algorithm and the MILP approaches. The results indicate that the proposed algorithm runs fast and produces a near-optimal solution compared with those from MILP models with a commercial solver.11Ysciescopu

Association of neuromuscular reversal by sugammadex and neostigmine with 90-day mortality after non-cardiac surgery

Abstract Background Reversing a neuromuscular blockade agent with sugammadex is known to lessen postoperative complications by reducing postoperative residual curarization. However, its effects on 90-day mortality are unknown. Therefore, this study aimed to compare the effects of sugammadex and neostigmine in terms of 90-day mortality after non-cardiac surgery. Methods This retrospective cohort study analyzed the medical records of adult patients aged 18 years or older who underwent non-cardiac surgery at a single tertiary care hospital between 2011 and 2016. Propensity score matching and Cox regression analysis were used to investigate the effectiveness of sugammadex and neostigmine in lowering 90-day mortality after non-cardiac surgery. Results A total of 65,702 patients were included in the analysis (mean age: 52.3 years, standard deviation: 15.7), and 23,532 of these patients (35.8%) received general surgery. After propensity score matching, 14,179 patients (3906 patients from the sugammadex group and 10,273 patients from the neostigmine group) were included in the final analysis. Cox regression analysis in the propensity score-matched cohort showed that the risk of 90-day mortality was 40% lower in the sugammadex group than in the neostigmine group (hazard ratio: 0.60, 95% confidence interval: 0.37, 0.98; P = 0.042). These results were similar in the multivariable Cox regression analysis of the entire cohort (hazard ratio: 0.62, 95% confidence interval: 0.39, 0.96; P = 0.036). Conclusions This retrospective cohort study suggested that reversing rocuronium with sugammadex might be associated with lower 90-day mortality after non-cardiac surgery compared to neostigmine. However, since this study did not evaluate quantitative neuromuscular function in the postoperative period due to its retrospective design, the results should be interpreted carefully. Future prospective studies with quantitative neuromuscular monitoring in the postoperative period should be performed to confirm these results