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0 (CC BY-NC).A novel, thin-film platform that preserves live viruses, bacteria, antibodies, and enzymes without refrigeration for extended periods of time is described. Studies with recombinant adenovirus in an optimized formulation that supports recovery of live virus through 16 freeze-thaw cycles revealed that production of an amorphous solid with a glass transition above room temperature and nitrogen-hydrogen bonding between virus and film components are critical determinants of stability. Administration of live influenza virus in the optimized film by the sublingual and buccal routes induced antibody-mediated immune responses as good as or better than those achieved by intramuscular injection. This work introduces the possibility of improving global access to a variety of medicines by offering a technology capable of reducing costs of production, distribution, and supply chain maintenance. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Introduction As the global burden of neurological disorders continues to rise, physicians' need for a solid understanding of neuroanatomy is becoming more important. Traditional neuroanatomy curricula offer a limited approach to educating a diverse profile of learning styles. In an attempt to incorporate recent literature addressing diverse learning formats, we developed and evaluated two new image-based resources for the neuroscience curriculum. Methods We created narrated videos demonstrating the brain dissections that students were to perform in the laboratory and quiz-style, postdissection review slides for later self-guided study. These were offered as optional study aids to two classes of preclerkship medical students at the Uniformed Services University of the Health Sciences F. Edward Hébert School of Medicine. Effectiveness was evaluated through examination questions, and a survey was administered to one of the classes to assess usage of and satisfaction with the materials. Results Mean scores on the practical examination questions were 83% and 89% for the two classes of students given the resources. Notably, 100% of respondents used the review slides after the laboratory, and more than 99% found them very helpful or extremely helpful for learning relevant concepts. Discussion Our results support the usefulness of these resources as learning tools for neuroanatomy. These resources were meant to augment various traditional resources (textbooks, lecture) to provide a broad range of study options in line with current research. Our experience suggests that similar tools could be developed for application in other visually based content areas of the preclerkship curriculum. Copyright © 2020 Welch et al.Tartrate-resistant acid phosphatase 5 (TRAP/ACP5) has been shown to involve the development and prognosis of multiple tumors in previous studies; however, the mechanism in lung cancer is still unclear, and thus this study investigated the role of ACP5 in the progression of lung adenocarcinoma. After a series of in vitro and in vivo experiments, we observed that ACP5 expression was increased in lung adenocarcinomas (40/69, 57.97%); importantly, an increased ACP5 level was associated with patient age (p = 0.044) and lymph node metastasis (p = 0.0385). ACP5 overexpression significantly enhanced A549 and NCI-H1975 cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) and reduced cell apoptosis. Knocking down the expression of ACP5 could rescue the above cell phenotypes. Furthermore, enhancing ACP5 expression promoted lung adenocarcinoma cell hyperplasia and intrapulmonary metastasis in a mouse model. Additionally, mechanistic studies revealed that ACP5 might regulate p53 phosphorylation at Ser392, thereby enhancing the ubiquitination of p53, which then underwent degradation. Reducing the levels of p53 intensified the transcription of SMAD3, which promotes EMT in lung adenocarcinoma cells. In summary, the present study provides a theoretical basis and important scientific evidence on the key role of ACP5 in lung adenocarcinoma progression by inducing EMT via the regulation of p53/SMAD3 signaling. selleck chemicals llc © 2020 The Authors.This study aimed to assess the effectiveness of inhibiting cholesterol acyltransferase 1 (ACAT-1) in chimeric antigen receptor T (CAR-T) cells on potentiating the antitumor response against mesothelin (MSLN)-expressing pancreatic carcinoma (PC) cells. We engineered ACAT-1-inhibited CAR-T cells (CAR-T-1847 and CAR-T-1848) using the targeting MSLN CAR lentiviral vector and small interfering RNA (siRNA) targeting the conserved region of the ACAT-1 gene, and characterized the efficacy of these modified CAR-T cells in terms of the cytotoxicity and cytokine release of both MSLN-positive and MSLN-negative PC cells using in vitro methods and in vivo mouse xenografts. The ACAT-1-inhibited CAR-T-1847 and CAR-T-1848 cells showed a higher cytotoxicity at effector-to-target cell (ET) ratios of 81 and 101, respectively, and induced a higher secretion of proinflammatory cytokines interleukin-2 (IL-2) and interferon-gamma (IFNγ) in vitro. In addition, bioluminescence imaging of tumor xenografts of ACAT-1-inhibited targeting MSLN CAR-T cells in MSLN-positive PC mice in vivo showed significant tumor regression, which is consistent with the in vitro observations. Our findings demonstrate a novel immunotherapeutic strategy involving the transplantation of ACAT-1-inhibited targeting MSLN CAR-T cells and the feasibility of enhancing the antitumor potency of CAR-T through the novel strategy. © 2020 The Author(s).Introduction Oscillatory positive expiratory pressure (OPEP) devices facilitate secretion clearance by generating positive end expiratory pressure. However, different device designs may produce different levels of expiratory pressure with the same expiratory flow rate. We bench tested four devices to determine the relationship between expiratory flow and expiratory pressure in each. Methods A bench model was created to test the gas flow rates required by different OPEP devices to generate target expiratory pressure. Four different devices were tested Acapella® (DH Green, Smiths Medical), AerobiKa® (Monaghan Medical Corporation), VibraPEP® (Curaplex), and vPEP™ (D R Burton Healthcare). Each OPEP device was tested to determine the expiratory flow needed to generate expiratory pressure thresholds considered appropriate for OPEP therapy. Results The expiratory flow required to generate the same expiratory pressure thresholds varied considerably among devices. Valved OPEP devices such as the VibraPEP required less flow than mechanical devices such as the vPEP, Aerobika, and Acapella. Discussion In this bench test of OPEP devices, we found considerable variability in expiratory flow requirements needed to generate an expiratory pressure of >10 cm H2O. Our finding suggests that smaller patients or those with limited expiratory airflow due to diseases such as COPD, obesity, chronic congestive heart failure, and restrictive lung disease may have better results when matched to OPEP devices requiring less expiratory airflow.Aims Although the bacterial virulent factor of cytotoxin-associated gene-A (CagA)-seropositivity and the host genetic factors of interleukin (IL)-1 polymorphisms have been suggested to influence Helicobacter pylori (HP) -related diseases, the underlying mechanisms of the association between HP infection and acute coronary syndrome (ACS) remain unknown. Methods and results Among 341 consecutive ACS patients, the clinical outcomes after ACS included composite cardiovascular events within the 2-year follow-up period.A significantly higher probability of primary outcomes was observed in HP positive patients than in HP negative patients. There were no significant differences in the rate of cardiovascular events between HP positive and HP negative patients in the absence of an IL-polymorphism, while there were significant differences in the presence of an IL-polymorphism. There were significant differences in the rate of cardiovascular events among CagA positive, CagA negative/ HP positive and CagA negative/HP negative patients. Moreover, via immunohistochemical staining, aortic CagA positive cells were confirmed in the vasa vasorum in CagA positive patients, whereas they could not be identified in CagA negative patients. Conclusions The bacterial virulence factor CagA and host genetic IL-1 polymorphisms influence the incidence of adverse cardiovascular events, possibly through infection of atherosclerotic lesions.Registration University Hospital Medical Information Network (UMIN)-CTR (http//www.umin.ac.jp/ctr/).Identifier UMIN000035696. © 2020 The Authors.Background In the era of High-sensitive troponin (hs-Tn), up to 50% of patients with a mild increase of hs-Tn will finally have a normal invasive coronary angiogram. Fractional Flow Reserve (FFR) derived from coronary computed tomographic angiography (FFR-CT) has never been used as a non-invasive tool for the diagnosis of coronary artery disease in patients with high-risk acute coronary syndrome without ST segment elevation (NSTE-ACS). Aims The study aims to determine the role of coronary CT angiography and FFR-CT in the setting of high-risk NSTE-ACS. Methodology We will conduct a prospective trial, enrolling 250 patients admitted with high-risk NSTE-ACS who will rapidly undergo a coronary CT angiography and then a coronary angiography with FFR measurements. Results of coronary CT, FFR-CT and coronary angiography (± FFR) will be compared. Potential significance In conclusion, non-invasive identification of patients with high-risk NSTE-ACS who could avoid coronary angiography would reduce procedure related risks and medical costs. © 2020 The Authors. Published by Elsevier B.V.Aims The impact of anatomical versus functional testing in patients with prior coronary artery bypass surgery (CABG) is poorly defined. We therefore sought to determine the rates of downstream investigations and the attendant healthcare costs in CABG patients undergoing CCTA versus SPECT. Methods and results 2754 consecutive CABG patients were imaged by SPECT (2163) or CCTA (591). 425 patients (15.4%) underwent downstream testing which was more common in those imaged with CCTA versus SPECT (23.18% vs 13.31% respectively, p less then 0.01). When a propensity score adjustment was made for differences in baseline characteristics, the findings in downstream testing persisted (p less then 0.01). When patients who subsequently underwent repeat revascularization (arguably the highest risk patients) were removed from the analysis, downstream testing remained more frequent in CCTA (12.7%) versus SPECT imaged patients (8.8%) (p = 0.01). Costs of downstream tests per patient were two-fold greater in the CCTA group in comparison to the SPECT group ($366.79 ± 29.59 vs $167.35 ± 10.12 respectively, p less then 0.01). Conversely, total costs which included the index costs were less in the CCTA group, $764.66 ± 29.59 versus $1396.73 ± 1012 for the SPECT cohort, p less then 0.0001). Conclusions Index imaging with SPECT versus CCTA in CABG patients was associated with fewer downstream tests, less ICA, less repeat revascularization but greater expense. Cost however is only part of the decision making process that determines an optimal index test. Until CCTA demonstrates improved risk stratification over SPECT in CABG patients it is likely SPECT will remain the preferred first imaging test. © 2020 The Authors.
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