| 1. |
- Lilja, Gisela, et al.
(författare)
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Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest A Predefined Analysis of the TTM2 Randomized Clinical Trial
- 2023
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Ingår i: Jama Neurology. - 2168-6149 .- 2168-6157. ; 80:10, s. 1070-1079
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. OBJECTIVES To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. DESIGN, SETTING, AND PARTICIPANTS This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. INTERVENTIONS Randomization 1:1 to temperature control with targeted hypothermia at 33 degrees C or targeted normothermia and early treatment of fever (37.8 degrees C or higher). MAIN OUTCOMES AND MEASURES Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. RESULTS At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P =.46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P =.37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P =.62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). CONCLUSIONS In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common.
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| 2. |
- Fawzy, Iten M., et al.
(författare)
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Design, synthesis and biological evaluation of Novel Curcumin Analogs with anticipated anticancer activity
- 2015
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Ingår i: FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES. - : ELSEVIER SCIENCE BV. - 2314-7245. ; 1:1, s. 22-31
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Tidskriftsartikel (refereegranskat)abstract
- Context: Extensive research conducted within past years revealed that curcumin is a highly pleiotropic molecule that interacts with a diverse range of molecular targets and hence it possess anti-proliferative activities against tumor cells.The great similarities between curcumin analogs and chalcones inspired their testing against tubulin enzyme activity as recent research revealed that chalcones possess cytotoxic activity associated with tubulin inhibition and interference with microtubule formation, which is essential in mitosis and cell replication. Objective: Novel Curcumin analogs were designed, synthesized and tested for their antitumor activities. Also in silico and in vitro studies has been performed to predict the binding affinity of the target compounds and to test their ability to inhibit tubulin assembly and act as microtubule destabilizing agents. Methods: Six novel curcumin analogs were designed & synthesized with 3,5-dibenzylidenepiperidin-4-one core moiety. Results: Compounds showed interaction energy comparable to or within the range of podophyllotoxin itself when docked into the colchicine binding site of tubulin using the podophyllotoxin-tubulin complex (PDB 1SA1). Conclusion: Compounds showed moderate anticancer activity and moderate ability to destabilize microtubules and thus inhibiting tubulin polymerization, as a result; these compounds could be used for further future development to obtain more potent analogs. (C) 2015 Future University. Production and hosting by Elsevier B.V.
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| 3. |
- Fawzy, Iten M., et al.
(författare)
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Newly Designed and Synthesized Curcumin Analogs with in vitro Cytotoxicity and Tubulin Polymerization Activity
- 2015
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Ingår i: Chemical Biology and Drug Design. - : Wiley. - 1747-0277 .- 1747-0285. ; 86:1, s. 860-870
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Tidskriftsartikel (refereegranskat)abstract
- Novel curcumin analogs with 4-piperidone ring were designed, synthesized, and evaluated for their cytotoxic activities against five different cancer cell lines. 3,5-bis(4-Hydroxy-3-methoxybenzylidene)-4-oxo-N-phenylpiperidine-1-carbothioamide (XIIe) exhibited considerable cytotoxic activity with IC50 values in 1-2.5m range. In silico and in vitro, studies were also performed to predict the binding affinity of the target compounds to the -chain of tubulin receptor (PDB code 1SA1) and their abilities to affect microtubules polymerization cycle. 3,5-bis(3-Iodo-5-methoxy-4-propoxybenzylidene)-N-acetylpiperidin-4-one (VIIa) was found to exert 93.3% inhibition of tubulin and destabilization of microtubules in vitro compared to vincristine while, 3,5-bis(3,4,5-trimethoxybenzylidene)-N-benzoylpiperidin-4-one (XIIc) showed high potency in a differentway where it exerted 94.8% stabilization of microtubules in vitro compared to positive control paclitaxel.
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| 4. |
- Askarinejad, Amin, et al.
(författare)
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Physical modelling of rainfall induced landslides undercontrolled climatic conditions
- 2012
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Konferensbidrag (refereegranskat)abstract
- A series of small scale physical modelling tests are performed in a geotechnical drumcentrifuge in order to investigate the triggering mechanisms of landslides due to rainfall. They areconducted under controlled conditions of rainfall intensity and duration, ambient relative humidity, wind,and temperature. These tests have been designed to study the possible failure mechanisms proposed for afull scale landslide experiment. Accordingly, different shapes and hydraulic properties of the bedrock, interms of drainage and exfiltration, are provided for the model. A three dimensional close rangephotogrammetric technique is used to track the movements and monitor the volumetric changes of theground during the cycles of wetting and drying. The slope elevation is filmed during and following therainfall events using a high speed camera and the deformation vectors and strains are elaborated using thePIV method. Details of the design of the climate chamber are discussed in this paper.
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| 5. |
- Laue, J., et al.
(författare)
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15 years of experience using a physical model exercise in a Masters' course
- 2014
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Ingår i: Physical modelling in geotechnics. - Leiden : CRC Press/Balkema. - 9781138022218 ; , s. 445-450
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Konferensbidrag (refereegranskat)abstract
- Modelling in Geotechnics' has been taught for two hours over 14 weeks in the 2nd, and later 3rd, semester of the Masters' studies at ETH Zurich. In addition to a series of frontal lectures on modelling techniques, as well as for their application to various boundary value problems, this course contains an exercise that compares 3 ways of modelling a practical case. Students are invited to investigate a common boundary value problem through complementary analytical, physical and numerical (finite element) modelling. A suitable boundary value problem, such as for shallow foundations or slopes, is selected to ensure that the exercise can be conducted in the limited time available for the students, and that the physical model takes only a finite amount of time so that all students can witness a test from start to finish. A comparison allows the assumptions made for the various models or calculations to be discussed and trains the students to put the different results into perspective. Practical aspects such as feasibility and timing, as well as applicability to reaching the learning goal of the class, will be reviewed. © 2010 Taylor & Francis Group, London.
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