62 research outputs found
Targeting host cell proteases to prevent SARS-CoV-2 invasion
No full textSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread worldwide and caused widespread devastation. In the absence of definitive therapy, symptomatic management remains the standard of care. Repurposing of many existing drugs including several anti-viral drugs is being attempted to tackle the COVID-19 pandemic. However, most of them have failed to show significant benefit in clinical trials. An attractive approach may be to target host proteases involved in SARS-CoV-2 pathogenesis. The priming of the spike (S) protein of the virus by proteolytic cleavage by the trans-membrane serine protease-2 (TMPRSS2) is necessary for fusion of the virus to the host cell after it binds to its receptor angiotensin converting enzyme-2 (ACE2). There are other proteases with varying spatiotemporal locations that may be important for viral entry and subsequent replication inside the cells, and these include trypsin, furin and cathepsins. In this report, we discuss the tentative therapeutic role of inhibitors of TMPRSS2, cathepsin, trypsin, furin, plasmin, factor X and elastase in infection caused by SARS-CoV-2. Both available evidence as well as hypotheses are discussed, with emphasis on drugs which are approved for other indications such as bromhexine, ammonium chloride, nafamostat, camostat, tranexamic acid, epsilon amino-caproic acid, chloroquine, ulinastatin, aprotinin and anticoagulant drugs. Simultaneously, novel compounds being tested and problems with using these agents are also discussed
Oxidative stress, neuroinflammation, and NADPH oxidase: implications in the pathogenesis and treatment of Alzheimer's disease
No full textNADPH oxidase as an important source of intracellular reactive oxygen species (ROS) has gained enormous importance over the years, and the detailed structures of all the isoenzymes of the NADPH oxidase family and their regulation have been well explored. The enzyme has been implicated in a variety of diseases including neurodegenerative diseases. The present brief review examines the body of evidence that links NADPH oxidase with the genesis and progression of Alzheimer's disease (AD). In short, evidence suggests that microglial activation and inflammatory response in the AD brain is associated with increased production of ROS by microglial NADPH oxidase. Along with other inflammatory mediators, ROS take part in neuronal degeneration and enhance the microglial activation process. The review also evaluates the current state of NADPH oxidase inhibitors as potential disease-modifying agents for AD
Should ACE2 be given a chance in COVID-19 therapeutics: a semi-systematic review of strategies enhancing ACE2
No full textThe severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has resulted in almost 28 million cases of COVID-19 (Corona virus disease-2019) and more than 900000 deaths worldwide since December 2019. In the absence of effective antiviral therapy and vaccine, treatment of COVID-19 is largely symptomatic. By making use of its spike (S) protein, the virus binds to its primary human cell receptor, angiotensin converting enzyme 2 (ACE2) which is present in the pulmonary epithelial cells as well as other organs. SARS-CoV-2 may cause a downregulation of ACE2. ACE2 plays a protective role in the pulmonary system through its Mas-receptor and alamandine-MrgD-TGR7 pathways. Loss of this protective effect could be a major component of COVID-19 pathogenesis. An attractive strategy in SARS-CoV-2 therapeutics would be to augment ACE2 either directly by supplementation or indirectly through drugs which increase its levels or stimulate its downstream players. In this semi-systematic review, we have analysed the pathophysiological interplay between ACE and ACE2 in the cardiopulmonary system, the modulation of these two proteins by SARS-CoV-2, and potential therapeutic avenues targeting ACE-Ang II and ACE2-Ang (1-7) axes, that can be utilized against COVID-19 disease progression
“Risk Management Can Actually Be Fun”: Using the Serious Cards for Biosafety Game to Stimulate Proper Discussions About Biosafety
No full textAs part of a Dutch Science Foundation project called T-TRIPP, the authors developed the serious game Cards for Biosafety. The aim of Cards for Biosafety is to let young biotechnology researchers learn more about biosafety. Analyses of workshops with researchers from the biotechnology domain as well as results of interviews with several biosafety officers clearly indicated the need for such a serious game with a focus on educational learning. Cards for Biosafety is a physical (also playable online on Tabletopia) round-based card game and playable with up to eight players. The game itself consists of scenario, risk and measure cards, and the task of the players is to choose risk and measure cards that fit the scenario explained by the facilitator at the beginning of each round. To test the efficiency of Cards for Biosafety as a learning tool, the authors conducted two online-workshops with twelve participants. The results of these sessions have not only shown that Cards for Biosafety is a well-designed game, but also a successful game to achieve the intended learning goal. In addition, the authors recognized that ‘fun’ is an important element in the game which leads to ‘learning’ in a very effective way. Future research should focus on the role of such positive states in serious games and their influence on learning outcomes.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Policy AnalysisGame La
L type CCBs and delirium, psychosis and extrapyramidal disturbances
No full textThis systematic review aims to analyse all cases of delirum, psychosis and extrapyramidal disturbances with L -type calcium channel blocker
Facilitated Tabletop Games in a Mediated Environment
No full textTabletop games that require the aid of a human facilitator are typically designed for a physical environment. However, during the COVID-19 pandemic, lockdown measures prevented people from gathering. Therefore, tabletop games were sometimes played and facilitated in a mediated environment using online communication tools instead. But this setting possibly deteriorates the players’ game experience. To understand the effect of playing facilitated tabletop games in a mediated environment we measured the player experience of the game Cue Kitchen in a mixed-method study comparing physical and mediated game sessions. Forty-four players played eleven game sessions, three in a physical environment and eight in a mediated environment. Of all seven dimensions of game experience measured, only one differed significantly between the two experimental conditions: players in a mediated environment became significantly more tired than players in a physical environment. The qualitative results explained why: players in a physical setting can wander off, while players in an online setting have to stay focused on their screen and, therefore, grow more tired. The research results suggest that facilitated tabletop games may be played in a mediated environment instead of a physical environment, without significant loss of player experience.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Policy AnalysisOrganisation & Governanc
Frame Game as Teaching Methodology in Higher Education: The Case of RElastiCity
No full textThe objective of the study is to illustrate the use of the frame game, RElastiCity as a framework to learn about the resilience of urban areas and the shocks and stresses in those areas. The question is if use of the frame game as a basis for game co-design is a useful approach to explore complex systems and its dynamics. This study covers the exploratory application of the approach in two university courses in the Netherlands. The results show divergent student experiences between the two courses. The main difference between the courses was the scope of the co-design assignment and the amount of time students had to complete the design process. It was found that using frame games as a framework for understanding complex systems is useful if students have sufficient time to investigate the topic, develop the game and playtest the game.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Organisation & GovernanceDesign Conceptualization and Communicatio
Favole Animate
No full textI cannot believe that this book is not already in the collection. Six simple pop-up spreads of two pages facing each other present Il Topo e l'Elefante; Le Due Capre'; FC; TH; L'Aquila e il Gufo; and La Volpe, la Scimia e gli Animali. The book is in good condition, and all the pop-ups work well. This book sets a record for the least bibliographical information. One learns little more than that it cost 1000 Lire.This is a hardbound book (hard cover)Language note: ItalianPop-upInder Mali
Comparison of changes in retentive force and wear pattern of two stud attachments for implant overdentures: An in vitro study
No full textContext: Edentulous patients often complain about the instability of mandibular denture. To overcome that, implant-supported overdentures (IODs) have been applied as a good prosthetic option. Aims: The current study compared the changes in retentive force and patterns of surface wear of nylon rings of two stud attachments (ball and locator) upon cyclic loading. Subjects and Methods: Two implant analogs were fixed parallel to each other, 22 mm apart, in custom-made rectangular blocks for each attachment system. Ten nylon inserts of each attachment system were tested. Universal testing machine was used to measure the retentive force, and a low-value fatigue testing machine was used for cyclic loading of 2500 insertion–removal cycles. Surface changes of the components were evaluated by scanning electron microscope (SEM). Statistical Analysis Used: Paired Student's t-test was used to determine groups that were statistically significant. Results: The greatest retention loss rate, i.e., the difference between the initial retentive force and final retentive force was observed in the ball attachment (6.20 N) followed by locator attachment (3.70 N). The results were found to be statistically significant (d ≤ 0.001**). Upon SEM analysis, the nylon inserts of ball attachment revealed more surface wear compared to that of locator attachment. Conclusions: For greater retention and longer function, locator overdenture attachment should be preferred for implant overdentures over ball attachment
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