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RISS 인기검색어
- 검색키워드
- 저자 : Flood, Amar H. (검색결과 4 건)
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Alex Mortimer,David Evans,Richard Flood,Owain Davies,James Wareham 대한신경중재치료의학회 2021 Neurointervention Vol.16 No.2
Purpose Aspirin has beneficial effects on coiling, even in acute subarachnoid hemorrhage, but there is also a perceived risk of increased bleeding and, importantly, a concern regarding ventriculostomy-associated hemorrhage (VAH) in those with complicating hydrocephalus. We aimed to assess the rate and extent of VAH in patients specifically treated with procedural intravenous aspirin during endovascular coiling of ruptured intracranial aneurysms. Materials and Methods This was a single neurovascular center retrospective observational study of consecutive patients treated over a three-year period. The rate of VAH assessed using computed tomography and clinical outcomes were compared in patients receiving intraprocedural intravenous aspirin loading (n=90) versus those that did not receive the drug (n=40). Results There was a significantly elevated rate of VAH in patients receiving intravenous aspirin (30% vs. 2.5%, odds ratio 16.7 [95% confidence interval: 2.2–128.0], P<0.0001). The majority of VAH was <10 mm in size (70%) with the largest bleed measuring 20 mm. No hematoma required surgical evacuation. No difference in favorable outcome at discharge was demonstrated. There was no difference in mortality between the 2 groups. Conclusion Loading with intravenous aspirin during endovascular treatment of ruptured intracranial aneurysms significantly increases the risk of VAH, but most are small with minimal impact on clinical outcome at discharge. Intravenous aspirin should probably be reserved for selected cases but should not be withheld based on risk of VAH.
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DISC1–ATF4 transcriptional repression complex: dual regulation of the cAMP-PDE4 cascade by DISC1
Soda, T,Frank, C,Ishizuka, K,Baccarella, A,Park, Y-U,Flood, Z,Park, S K,Sawa, A,Tsai, L-H Nature Publishing Group 2013 Molecular psychiatry Vol.18 No.8
<P>Disrupted-In-Schizophrenia 1 (<I>DISC1</I>), a risk factor for major mental illnesses, has been studied extensively in the context of neurodevelopment. However, the role of DISC1 in neuronal signaling, particularly in conjunction with intracellular cascades that occur in response to dopamine, a neurotransmitter implicated in numerous psychiatric disorders, remains elusive. Previous data suggest that DISC1 interacts with numerous proteins that impact neuronal function, including activating transcription factor 4 (ATF4). In this study, we identify a novel DISC1 and ATF4 binding region in the genomic locus of <I>phosphodiesterase 4D</I> (<I>PDE4D</I>), a gene implicated in psychiatric disorders. We found that the loss of function of either DISC1 or ATF4 increases <I>PDE4D9</I> transcription, and that the association of DISC1 with the <I>PDE4D9</I> locus requires ATF4. We also show that <I>PDE4D9</I> is increased by D1-type dopamine receptor dopaminergic stimulation. We demonstrate that the mechanism for this increase is due to DISC1 dissociation from the <I>PDE4D</I> locus in mouse brain. We further characterize the interaction of DISC1 with ATF4 to show that it is regulated via protein kinase A-mediated phosphorylation of DISC1 serine-58. Our results suggest that the release of DISC1-mediated transcriptional repression of <I>PDE4D9</I> acts as feedback inhibition to regulate dopaminergic signaling. Furthermore, as DISC1 loss-of-function leads to a specific increase in <I>PDE4D9</I>, <I>PDE4D9</I> itself may represent an attractive target for therapeutic approaches in psychiatric disorders.</P>
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High hopes: can molecular electronics realise its potential?
Coskun, Ali,Spruell, Jason M.,Barin, Gokhan,Dichtel, William R.,Flood, Amar H.,Botros, Youssry Y.,Stoddart, J. Fraser The Royal Society of Chemistry 2012 Chemical Society reviews Vol.41 No.14
<P>Manipulating and controlling the self-organisation of small collections of molecules, as an alternative to investigating individual molecules, has motivated researchers bent on processing and storing information in molecular electronic devices (MEDs). Although numerous ingenious examples of single-molecule devices have provided fundamental insights into their molecular electronic properties, MEDs incorporating hundreds to thousands of molecules trapped between wires in two-dimensional arrays within crossbar architectures offer a glimmer of hope for molecular memory applications. In this critical review, we focus attention on the collective behaviour of switchable mechanically interlocked molecules (MIMs)—specifically, bistable rotaxanes and catenanes—which exhibit reset lifetimes between their ON and OFF states ranging from seconds in solution to hours in crossbar devices. When these switchable MIMs are introduced into high viscosity polymer matrices, or self-assembled as monolayers onto metal surfaces, both in the form of nanoparticles and flat electrodes, or organised as tightly packed islands of hundreds and thousands of molecules sandwiched between two electrodes, the thermodynamics which characterise their switching remain approximately constant while the kinetics associated with their reset follow an intuitively predictable trend—that is, fast when they are free in solution and sluggish when they are constrained within closely packed monolayers. The importance of seamless interactions and constant feedback between the makers, the measurers and the modellers in establishing the structure-property relationships in these integrated functioning systems cannot be stressed enough as rationalising the many different factors that impact device performance becomes more and more demanding. The choice of electrodes, as well as the self-organised superstructures of the monolayers of switchable MIMs employed in the molecular switch tunnel junctions (MSTJs) associated with the crossbars of these MEDs, have a profound influence on device operation and performance. It is now clear, after much investigation, that a distinction should be drawn between two types of switching that can be elicited from MSTJs. One affords small ON/OFF ratios and is a direct consequence of the switching in bistable MIMs that leads to a relatively small remnant molecular signature—an activated chemical process. The other leads to a very much larger signature and ON/OFF ratios resulting from physical or chemical changes in the electrodes themselves. Control experiments with various compounds, including degenerate catenanes and free dumbbells, which cannot and do not switch, are crucial in establishing the authenticity of the small ON/OFF ratios and remnant molecular signatures produced by bistable MIMs. Moreover, experiments conducted on monolayers in MSTJs of molecules designed to switch and molecules designed not to switch have been probed directly by spectroscopic and other means in support of MEDs that store information through switching collections of bistable MIMs contained in arrays of MSTJs. In the quest for the next generation of MEDs, it is likely that monolayers of bistable MIMs will be replaced by robust crystalline extended structures wherein the switchable components, derived from bistable MIMs, are organised precisely in a periodic manner.</P> <P>Graphic Abstract</P><P>There is a world of difference between a molecular electronic device which switches at high (blue) rather than at low (red) bias. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c2cs35053j'> </P>
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