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1. Locating the evidence for children and young people social prescribing: Where to start? A scoping review protocol.

Author

Julie Feather, Shaun Liverpool, Eve Allen, Michael Owen, Nicola Relph, Lynsey Roocroft, Tasneem Patel, Hayley McKenzie, Ciaran Murphy, and Michelle Howarth

Subjects
Medicine, Science
Abstract

It is estimated that disruptions to life caused by the COVID-19 pandemic have led to an increase in the number of children and young people suffering from mental health issues globally. In England one in four children experienced poor mental health in 2022. Social prescribing is gaining traction as a systems-based approach, which builds upon person-centered methods, to refer children and young people with non-clinical mental health issues to appropriate community assets. Recognition of social prescribing benefits for children's mental health is increasing, yet evidence is limited. Inconsistent terminology and variation of terms used to describe social prescribing practices across the literature hinders understanding and assessment of social prescribing's impact on children's mental health. This scoping review thus aims to systematically identify and analyse the various terms, concepts and language used to describe social prescribing with children and young people across the wider health and social care literature base. The scoping review will be undertaken using a six-stage framework which includes: identifying the research question, identifying relevant studies, study selection, charting the data, collating, summarising and reporting the results, and consultation. Electronic databases (MEDLINE, Embase, Cumulative Index to Nursing and Allied Health, PsychInfo, Social Policy Practice, Scopus, Science Direct, Cochrane library and Joanna Briggs), alongside evidence from grey literature, hand search, citation tracking, and use of expert correspondence will be included in the review to ensure published and unpublished literature is captured. Data extraction will be carried out by two reviewers using a predefined form to capture study characteristics, intervention descriptions, outcomes, and key terms used to report social prescribing for children and young people. No formal quality appraisal or risk of bias evaluation will be performed, as this scoping review aims to map and describe the literature. Data will be stored and managed using the Rayaan.ai platform and a critical narrative of the common themes found will be included.

Published
2024
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2. Mental health and wellbeing of further and higher education students returning to face-to-face learning after Covid-19 restrictions.

Author

Shaun Liverpool, Mohammed Moinuddin, Supritha Aithal, Michael Owen, Katie Bracegirdle, Meggie Caravotta, Rachel Walker, Ciaran Murphy, and Vicky Karkou

Subjects
Medicine, Science
Abstract

AimThis study aimed to examine the mental health and wellbeing of further and higher education students and the associating factors after returning to face-to-face (in-person) learning after Covid-19 restrictions.MethodsA cross-sectional study informed by student consultations was conducted using a survey design. Mental health and wellbeing were assessed using self-report items on the Depression, Anxiety and Stress Scale (DASS-21) and the Short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS). Descriptive statistics and stepwise multiple linear regression analyses were conducted on data collected between December 2021 and June 2022.ResultsN = 1160 students participated; 69.6% between 16 and 25 years, 67.9% studying in the UK, 66.5% studying away from home, 60.2% identified as she/her, 59.8% studying at the undergraduate degree level, 42.5% belonging to non-White ethnic backgrounds, 29.6% identifying as having additional needs and 22.8% as sexual minority. Moderate anxiety (M = 13.67, SD = 9.92) and depression (M = 17.04, SD = 11.56) scores were mainly reported. Wellbeing scores (M = 20.31, SD = 3.93) were lower than the estimate for the pre-pandemic general population. Gender expression, sexuality, age, ethnicity, having additional needs, and level and location of study was associated with mental health or wellbeing. Individual coping styles, levels of self-efficacy and physical activity were also associated with mental health or wellbeing.ConclusionsMany students returning to further and higher education after Covid-19 restrictions experienced reduced mental health and wellbeing, and some students were at greater risk. Providing student-centred interventions focusing on self-efficacy, coping styles and physical activity may help improve the mental health and wellbeing of students.

Published
2023
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3. A genetically encoded fluorescent biosensor for extracellular l-lactate

Author

Yusuke Nasu, Ciaran Murphy-Royal, Yurong Wen, Jordan N. Haidey, Rosana S. Molina, Abhi Aggarwal, Shuce Zhang, Yuki Kamijo, Marie-Eve Paquet, Kaspar Podgorski, Mikhail Drobizhev, Jaideep S. Bains, M. Joanne Lemieux, Grant R. Gordon, and Robert E. Campbell

Subjects
Science
Abstract

l-lactate is an important intercellular energy currency. Here the authors report a genetically encoded biosensor eLACCO1.1 to monitor extracellular l-lactate; they use eLACCO1.1 to image extracellular l-lactate in cultured mammalian cells and brain tissue.

Published
2021
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4. Stress gates an astrocytic energy reservoir to impair synaptic plasticity

Author

Ciaran Murphy-Royal, April D. Johnston, Andrew K. J. Boyce, Blanca Diaz-Castro, Adam Institoris, Govind Peringod, Oliver Zhang, Randy F. Stout, David C. Spray, Roger J. Thompson, Baljit S. Khakh, Jaideep S. Bains, and Grant R. Gordon

Subjects
Science
Abstract

Enduring changes in synaptic efficacy are highly sensitive to stress. Here, the authors show that astrocytic delivery of metabolites has an important role in the stress-mediated impairment of synaptic plasticity.

Published
2020
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5. Author Correction: Stress gates an astrocytic energy reservoir to impair synaptic plasticity

Author

Ciaran Murphy-Royal, April D. Johnston, Andrew K. J. Boyce, Blanca Diaz-Castro, Adam Institoris, Govind Peringod, Oliver Zhang, Randy F. Stout, David C. Spray, Roger J. Thompson, Baljit S. Khakh, Jaideep S. Bains, and Grant R. Gordon

Subjects
Science
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020
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6. Circulating microparticles, protein C, free protein S and endothelial vascular markers in children with sickle cell anaemia

Author

Andrea Piccin, Ciaran Murphy, Elva Eakins, Jan Kunde, Daisy Corvetta, Angela Di Pierro, Giovanni Negri, Mazzoleni Guido, Laura Sainati, Corrina Mc Mahon, Owen Patrick Smith, and William Murphy

Subjects
sickle cell anaemia, microparticles, protein C, protein S, adrenomedullin, endothelin-1, nitric oxide, Cytology, QH573-671
Abstract

Introduction: Circulating microparticles (MP) have been described in sickle cell anaemia (SCA); however, their interaction with endothelial markers remains unclear. We investigated the relationship between MP, protein C (PC), free protein S (PS), nitric oxide (NO), endothelin-1 (ET-1) and adrenomedullin (ADM) in a large cohort of paediatric patients. Method: A total of 111 children of African ethnicity with SCA: 51 in steady state; 15 in crises; 30 on hydroxyurea (HU) therapy; 15 on transfusion; 17 controls (HbAA) of similar age/ethnicity. MP were analysed by flow cytometry using: Annexin V (AV), CD61, CD42a, CD62P, CD235a, CD14, CD142 (tissue factor), CD201 (endothelial PC receptor), CD62E, CD36 (TSP-1), CD47 (TSP-1 receptor), CD31 (PECAM), CD144 (VE-cadherin). Protein C, free PS, NO, pro-ADM and C-terminal ET-1 were also measured. Results: Total MP AV was lower in crisis (1.26×106 ml−1; 0.56–2.44×106) and steady state (1.35×106 ml−1; 0.71–3.0×106) compared to transfusion (4.33×106 ml−1; 1.6–9.2×106, p0.9, p

Published
2015
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7. Evidence of Pre-mortem Opioid Use among Fentanyl Overdose Decedents in a Safety Net Healthcare System

Author

Phillip O. Coffin, Vanessa M. McMahan, and Ciaran Murphy

Subjects
Analgesics, Opioid, Fentanyl, Urban Studies, Health (social science), Public Health, Environmental and Occupational Health, Humans, Drug Overdose, Opioid-Related Disorders, Delivery of Health Care
Abstract

The rapid increase in fentanyl overdose deaths, particularly those also attributed to stimulants, has led to concerns about unintentional fentanyl exposure. Utilizing vital and medical record data, we identified overdose decedents from 2018 to 2021 in San Francisco who received care in the safety net system in the 3 years preceding death. Among 506 decedents, medical record evidence of pre-mortem opioid use was present for 48% of stimulant-only, 56% of stimulant-fentanyl, 65% of fentanyl-only, and 82% of non-fentanyl opioid decedents (plt;0.001). Among stimulant-fentanyl decedents, an increase in 10 years of age (adjusted odds ratio (aOR) 0.74 [95% CI:0.59-0.94]) and race other than White or Black (aOR 0.36 [95% CI:0.15-0.87]) had lower odds of evidence of pre-mortem opioid use. While not conclusive, these findings raise the possibility that a significant proportion of fentanyl overdose decedents in San Francisco may have not intended to consume an opioid on the occasion of their death.

Published
2022
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10. Astrocyte glucocorticoid signaling mediates cognitive impairment induced by early-life stress

Author

Ifeoluwa I. Adedipe, Lewis R. Depaauw-Holt, Jade Latraverse-Arquilla, Juliette Vaugeois, Manon Duquenne, Benjamin Rogers, Sarah Peyrard, Anthony Bosson, and Ciaran Murphy-Royal

Abstract

Early-life stress can have lifelong consequences, enhancing stress susceptibility and resulting in behavioural and cognitive deficits. While the effects of early-life stress (ELS) on neuronal function have been well-described, we still know very little about the contribution of nonneuronal brain cells to the cellular and behavioural adaptations following ELS. Here, using a rodent model of ELS, we report that astrocytes play a key role in mediating the impact of stress on amygdala-dependent behaviour and synaptic plasticity during adolescence. We report that ELS induces generalisation of fear, associated with increased levels of circulating corticosterone and activation of glucocorticoid receptors in astrocytes. In addition, we identify astrocyte glucocorticoid receptors as targets, mediating ELS-induced cognitive and synaptic impairments. This work establishes astrocytes as key elements in amygdala-dependent memory, and as central mediators of the effects of stress on cognitive function via stress hormone signalling pathways.SummaryELS impairs lateral amygdala-dependent cognition and synaptic plasticity during adolescence.Stress-induced behavioural changes were associated with astrocyte dysfunction in the lateral amygdala.Genetic disruption of astrocyte function in the lateral amygdala replicated the cognitive and synaptic impairments induced by stress.ELS induced a latent increase in blood glucocorticoid levels during adolescence.Ablating glucocorticoid signalling in astrocytes rescued cognitive impairments induced by ELS.

Published
2022
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34. A genetically encoded fluorescent biosensor for extracellular L-lactate

Author

Abhi Aggarwal, Marie-Eve Paquet, Molina Mrs, Joanne Lemieux M, Jaideep S. Bains, Yurong Wen, Mikhail Drobizhev, Shuce Zhang, Jordan N. Haidey, Robert E. Campbell, Ciaran Murphy-Royal, Kaspar Podgorski, Kamijo Y, Yusuke Nasu, and Grant R. Gordon

Subjects
L lactate, Cellular resolution, Chemistry, Extracellular, Brain tissue, Biosensor, Fluorescence, Cell biology
Abstract

To enable investigations of the emerging roles of cell-to-cell shuttling of L-lactate, we have developed an intensiometric green fluorescent genetically encoded biosensor for extracellular L-lactate. We demonstrate that this biosensor, designated eLACCO1.1, enables minimally invasive cellular resolution imaging of extracellular L-lactate in cultured mammalian cells and brain tissue.

Published
2021
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37. Whole brain irradiation in mice causes long-term impairment in astrocytic calcium signaling but preserves astrocyte-astrocyte coupling

Author

Stefano Tarantini, Zoltan Ungvari, Jordan N. Haidey, Grant R. Gordon, Andriy Yabluchanskiy, Ciaran Murphy-Royal, Adam Institoris, and Anna Csiszar

Subjects
Aging, Stimulation, 03 medical and health sciences, Mice, 0302 clinical medicine, medicine, Premovement neuronal activity, Animals, Humans, Cognitive Dysfunction, Calcium Signaling, Cognitive decline, 030304 developmental biology, Calcium signaling, 0303 health sciences, Chemistry, Brain, Long-term potentiation, Cortex (botany), medicine.anatomical_structure, Cerebral blood flow, Astrocytes, Cerebrovascular Circulation, Original Article, Geriatrics and Gerontology, Neuroscience, 030217 neurology & neurosurgery, Astrocyte
Abstract

Whole brain irradiation (WBI) therapy is an important treatment for brain metastases and potential microscopic malignancies. WBI promotes progressive cognitive dysfunction in over half of surviving patients, yet, the underlying mechanisms remain obscure. Astrocytes play critical roles in the regulation of neuronal activity, brain metabolism, and cerebral blood flow, and while neurons are considered radioresistant, astrocytes are sensitive to γ-irradiation. Hallmarks of astrocyte function are the ability to generate stimulus-induced intercellular Ca(2+) signals and to move metabolic substrates through the connected astrocyte network. We tested the hypothesis that WBI-induced cognitive impairment associates with persistent impairment of astrocytic Ca(2+) signaling and/or gap junctional coupling. Mice were subjected to a clinically relevant protocol of fractionated WBI, and 12 to 15 months after irradiation, we confirmed persistent cognitive impairment compared to controls. To test the integrity of astrocyte-to-astrocyte gap junctional coupling postWBI, astrocytes were loaded with Alexa-488-hydrazide by patch-based dye infusion, and the increase of fluorescence signal in neighboring astrocyte cell bodies was assessed with 2-photon microscopy in acute slices of the sensory-motor cortex. We found that WBI did not affect astrocyte-to-astrocyte gap junctional coupling. Astrocytic Ca(2+) responses induced by bath administration of phenylephrine (detected with Rhod-2/AM) were also unaltered by WBI. However, an electrical stimulation protocol used in long-term potentiation (theta burst), revealed attenuated astrocyte Ca(2+) responses in the astrocyte arbor and soma in WBI. Our data show that WBI causes a long-lasting decrement in synaptic-evoked astrocyte Ca(2+) signals 12–15 months postirradiation, which may be an important contributor to cognitive decline seen after WBI.

Published
2020

42. Obesity-induced astrocyte dysfunction impairs heterosynaptic plasticity in the orbitofrontal cortex

Author

Jaideep S. Bains, Grant R. Gordon, Stephanie L. Borgland, Ciaran Murphy-Royal, Manpreet Kaur, Benjamin K. Lau, and Min Qiao

Subjects
Male, Heterosynaptic plasticity, Glutamic Acid, Prefrontal Cortex, Neurotransmission, Biology, Inhibitory postsynaptic potential, Synaptic Transmission, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Glutamate homeostasis, 0502 economics and business, medicine, Animals, Homeostasis, Rats, Long-Evans, Obesity, GABAergic Neurons, 050207 economics, 030304 developmental biology, 0303 health sciences, Neuronal Plasticity, 050208 finance, Metabotropic glutamate receptor 5, 05 social sciences, Glutamate receptor, Biological Transport, Neural Inhibition, Hypertrophy, medicine.disease, Endocannabinoid system, Acetylcysteine, Diet, medicine.anatomical_structure, nervous system, Metabotropic glutamate receptor, Astrocytes, Synapses, Synaptic plasticity, Excitatory postsynaptic potential, Orbitofrontal cortex, Neuroscience, psychological phenomena and processes, 030217 neurology & neurosurgery, Endocannabinoids, Astrocyte
Abstract

SummaryOverconsumption of highly palatable, energy dense food is considered a key driver of the obesity pandemic. The orbitofrontal cortex (OFC) is critical for reward valuation of gustatory signals, yet how the OFC adapts to obesogenic diets is poorly understood. Here we show that extended access to a cafeteria diet impairs astrocyte glutamate clearance, which leads to a heterosynaptic depression of GABA transmission onto pyramidal neurons of the OFC. This decrease in GABA tone is due to an increase in extrasynaptic glutamate, which acts via metabotropic glutamate receptors to liberate endocannabinoids. This impaired the induction of endocannabinoid-mediated long-term plasticity. In obese rats, this cascade of synaptic impairments was rescued by restoring astrocyte glutamate transport with the nutritional supplement, N-acetylcysteine. Together, our findings indicate that obesity targets astrocytes to disrupt the delicate balance between excitatory and inhibitory transmission in the OFC.HighlightsDiet-induced obesity induces hypertrophy of astrocytes and impairs their ability to transport glutamate.Failure of astrocytes to clear extrasynaptic glutamate drives endocannabinoid-mediated inhibitory long-term depression of principal output neurons in the OFC.Astrocytic glutamate transporter function is restored with NAC, which rescues the synaptic deficits.

Published
2021
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43. Steady-State Free Ca2+ in Astrocytes Is Decreased by Experience and Impacts Arteriole Tone

Author

Grant R. Gordon, Eslam M.F. Mehina, and Ciaran Murphy-Royal

Subjects
0301 basic medicine, Neocortex, General Neuroscience, Glutamate receptor, Biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Arteriole, Metabotropic glutamate receptor, medicine.artery, medicine, NMDA receptor, Synaptic signaling, Neuroscience, 030217 neurology & neurosurgery, Astrocyte, Ionotropic effect
Abstract

Astrocytes can control basal synaptic strength and arteriole tone via their resting Ca2+ activity. However, whether resting astrocyte Ca2+ can adjust to a new steady-state level, with an impact on surrounding brain cells, remains unknown. Using two-photon Ca2+ imaging in male rat acute brain slices of the somatosensory neocortex, we found that theta burst neural activity produced an unexpected long-lasting reduction in astrocyte free Ca2+ in the soma and endfeet. The drop in intracellular Ca2+ was attenuated by antagonists targeting multiple ionotropic and metabotropic glutamate receptors, and intracellular cascades involved Ca2+ stores and nitric oxide. The reduction in astrocyte endfoot Ca2+ was coincident with an increase in arteriole tone, and both the Ca2+ drop and the tone change were prevented by an NMDA receptor antagonist. Astrocyte patch-clamp experiments verified that the glutamate receptors in question were located on astrocytes and that Ca2+ changes within astrocytes were responsible for the long-lasting change in arteriole diameter caused by theta burst neural activity. In astrocytes from animals that lived in an enriched environment, we measured a relatively lower resting Ca2+ level that occluded any further drop in Ca2+ in response to theta burst activity. These data suggest that electrically evoked patterns of neural activity or natural experience can adjust steady-state resting astrocyte Ca2+ and that the effect has an impact on basal arteriole diameter.SIGNIFICANCE STATEMENT The field of astrocyte-neuron and astrocyte-arteriole interactions is currently in a state of refinement. Experimental evidence ex vivo suggests that direct manipulation of astrocyte-free Ca2+ regulates synaptic signaling and local blood flow control; however, in vivo experiments fail to link synaptically evoked astrocyte Ca2+ transients and immediate changes to various astrocyte-mediated processes. To clarify this discrepancy, we examined a different aspect of astrocyte Ca2+: the resting, steady-state free Ca2+ of astrocytes, its modulation, and its potential role in the tonic regulation of surrounding brain cells. We found that ex vivo or in vivo neural activity induced a long-lasting reduction in resting free astrocyte Ca2+ and that this phenomenon changed arteriole tone.

Published
2017
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44. Students' participation in collaborative research should be recognised

Author

Aditya Borakati, Kenneth McLean, Thomas M. Drake, Ewen M. Harrison, Sivesh K. Kamarajah, Chetan Khatri, Dmitri Nepogodiev, Minaam Abbas, Muhammad Abdalkoddus, Areej Abdel-Fattah, Reem Abdelgalil, Haweya Abdikadir, Ryan Adams, Sarah Adams, Inioluwa Adelaja, Abiola Adeogun, Helena Adjei, Amirul Adlan, Hussamuddin Adwan, Sara Aeyad, Raiyyan Aftab, Amir Afzul, Vani Agarwal, Hosam Aglan, Medha Agrawal, Rishi Agrawal, Fiza Ahmed, Sobia Akhtar, Onyinye Akpenyi, Maithem Al-Attar, Muhammed Al-Ausi, Waleed Al-Khyatt, Alia Al-Mousawi, Zainab Al-Nasser, Anand Alagappan, Justin Alberts, Maryam Alfa-Wali, Abdulmajid Ali, Adnan Ali, Tamara Ali, Bilal Alkhaffaf, Rachael Allen, Kassem Alubaidi, Edemanwan Andah, Richard Anderson, Kirstine Andrew, Andrew Ang, Eshen Ang, Theophilus Anyomih, James Archer, Matt Archer, Steven Arnell, Matthew Arnold, Esha Arora, Nadeem Ashraf, Raees Ashraf, Jordan Ashwood, Usama Asif, Andrew Atayi, Sameera Auckburally, Ralph Austin, Sultana Azam, Aishah Azri Yahaya, Fiyin Babatunde, Simon Bach, Roudi Bachar, Abdul Badran, Caroline Baillie, Edward Balai, Alexander Baldwin, Vartan Balian, Danielle Banfield, Jonathan Bannard-Smith, Connor Barker, Behrad Barmayehvar, Jane Barnfield, David Bartlett, Richard Bartlett, Kwaku Baryeh, Siddharth Basetti, Kellie Bateman, Michael Bath, Andrew Beamish, William Beasley, Simon Beecroft, Ardit Begaj, Gurpreet Beghal, Jessica Belchos, Katarzyna Bera, Tara Bergara, Anna Betts, Aneel Bhangu, Gayathri Bhaskaran, Amina Bhatti, Mihai Bica, Caitlin Billyard, Emily Birkin, Jane Blazeby, Harry Blege, Natalie Blencowe, Christopher Blore, Alex Boddy, Matthew Boissaud-Cooke, Anita Bolina, William Bolton, David Bosanquet, Doug Bowley, Kathryn Boyce, Graham Branagan, Jessica Brayley, Joanna Brecher, Kristina Bresges, Emily Briggs, Ryan Broll, Damien Brown, Elliot Brown, Leo Brown, Robin Brown, Rory Brown, Connor Bruce, Pepa Bruce, Rory Buckle, Emily Budd, Richard Buka, Dermot Burke, Joshua Burke, Alisha Burman, Laura Burney, Amy Burrows, Mohammed Bux, Ronan Cahill, Clementina Calabria, Julian Camilleri-Brennan, Amy Campbell, Bill Campbell, Matthew Cant, Yun Cao, Sophie Carlson, Grace Carr, Luke Carr, Rebecca Carr, Richard Carr, Eleanor Cartwright, Alice Castle, Kirsty Cattle, Daniel Cave, Stephen Chapman, Alexandros Charalabopoulos, Sanjay Chaudhri, Ahmad Chaudhry, Paresh Chauhan, Priyesh Chauhan, Ryad Chebbout, Yunzi Chen, Louisa Chenciner, Jingjie Cheng, Natalie Cheng, Lin Chew, Zenab China, Abhishek Chitnis, Praminthra Chitsabesan, Paul Choi, Sarah Choi, Mariam Choudhry, Chern Choy, Claudia Ciurleo, Henry Claireaux, Peter Coe, Simon Cole, Katy Concannon, Edward Cope, Olivia Corbridge, Jessica Court, Louise Cox, Anna Craig-Mcquaide, Ben Cresswell, Lauren Crozier, Neil Cruickshank, Lucy Cuckow, Helen Cui, Elspeth Cumber, Sarah Cumming, Olivia Cundy, Melissa Cunha, Pedro Cunha, Laura Cunliffe, Jazleen Dada, Prita Daliya, Jeffrey Dalli, Ian Daniels, James Daniels, Ahmed Daoub, Sabeera Dar, Emma Das, Kaustuv Das, Emily Davies, Gareth Davies, Kirsty Davies, Kristen Davies, Rachel Davies, Victoria Dawe, Joshua Lucas de Carvalho, Katie De Jong, Katherine Deasy, Praveena Deekonda, Sahil Deepak, Henal Desai, Karishma Desai, Ryan Devlin, Nishat Dewan, Akashdeep Dhillon, Priya Dhillon, Tanya Dhir, Salomone Di Saverio, Julia Diamond, Peter Dib, Panagiotis A. Dimitriadis, Shiva Dindyal, Matthew Doe, Ciaran Doehrty, Tara Dogra, Arpan Doshi, Alison Downey, Joseph Doyle, Ashleigh Draper, Sarah Duff, Joseph Duncumb, Sophie Dupre, Justine Durno, Michal Dzieweczynski, Nicola Eardley, Sarah Easby, Sam Easdon, Hamdi Ebdewi, Lydon Eccles, Jacob Edwards, Padma Eedarapalli, Mohamed Elbuzidi, Patrick Elder, Lucy Elliott, Malaz Elsaddig, Ysabelle Embury-Young, Sophie Emesih, Alec Engledow, William English, Christos Episkopos, Jonathan Epstein, Rahim Esmail, Taher Fatayer, Nicolò Favero, Nicola Fearnhead, Maxine Feldman, Evelyn Fennelly, Stephen Fenwick, Lucie Ferguson, Stuart Fergusson, Petros Fessas, Isabel FitzGerald, J. Edward Fitzgerald, Harry Fitzpatrick, Daniel Fletcher, Tonia Forjoe, Beniamino Forte, Alex Fowler, Benjamin France, Abraham Francis, Niroshan Francis, Sunil Francis, Sam Freeman, Vicky Fretwell, Teresa Fung, Hugh Furness, Michael Gallagher, Stuart Gallagher, Chuanyu Gao, Lothaire Garard, Shona Gardner, Andrew Gaukroger, Daniel George, Simi George, Jamal Ghaddar, Ali Ghaffar, Shamira Ghouse, Amanda Gilbert, Ashveen Gill, Francesco Giovinazzo, Carey Girling, Lolade Giwa, James Glasbey, Paul Glen, Mary Goble, Jenna Godfrey, Shreya Goel, Wenn Goh, Kajal Gohil, Shyam Gokani, David Gold, David Golding, Andrea Gonzalez-Ciscar, Ross Goodson, Melissa Gough, Shubhangi Govil, Thomas Gower, Christopher Graham, Sam Gray, Patrick Green, Samuel Greenhalgh, Kyriacos Gregoriou, Rhiannon Gribbell, Mary Catherine Gribbon, Charlotte Grieco, Emma Griffiths, Ewen Griffiths, Nathan Griffiths, Sara Griffiths, Cathleen Grossart, Daniel Guerero, Christianne Guillotte, Rishi Gupta, Claire Guy, Adam Gwozdz, James Haddow, Shazia Hafiz, Constantine Halkias, Elisabeth Hall, Hasseb Hamid, Emma Hamilton, Gurvinder Singh Harbhajan Singh, John Hardman, Rhiannon Harries, Rhydian Harris, Suzanne Harrogate, Megan Harty, Jessica Harvey, Rahima Hashemi, Ahmed Hassane, Helen Hawkins, Thomas Hawthorne, John Hayes, Phoebe Hazenberg, Harry Heath, Madhusoodhana Hebbar, R. Heer, Roisin Hegarty O'Dowd, David Henshall, Philip Herrod, Elizabeth Hester, Emily Heywood, Nick Heywood, Frances Hill, James Hill, Kirsty Hill, May Ho, Marianne Hollyman, David Holroyd, Joseph Home, Steve Hornby, Laura Horne, Charlotte Horseman, Huma Hosamuddin, Amy Hough, George Hourston, Nathan Hudson-Peacock, Belinda Hughes, Katie Hughes, Isabel Huppatz, Penelope Hurst, Mahrukh Hussain, Shoaib Fahad Hussain, Syeda Hussain, Imogen Hutchings, Bilal Ibrahim, Lema Imam, Rory Ingham, Rose Ingleton, Rizwan Iqbal, Jenny Isherwood, Abdurrahman Islim, Omar Ismail, Shashank Iyer, Toby Jackman, Prashant Jain, Nadeem Jamal, Sabine Jamal, Ellen James, Nirmitha Jayaratne, Nathan Jeffreys, Hiral Jhala, Courtney Johnson, Zoe Johnston, Conor Jones, Emma-Jane Jones, Keaton Jones, Victor Jones, Roshan Joseph, Dilan Joshi, Holly Joyce, Claire Joyner, Aditya Kale, Sagar Kanabar, Lina Kanapeckaite, Hadyn Kankam, Sarantos Kaptanis, Edward Karam, Dimitrios Karponis, Anne Karunatilleke, Veeru Kasivisvanathan, Geeta Kaur, Samina Kauser, Nigel Keelty, Denise Kelly, Jessica Kennett, Molly Kerr, Ahmed Kerwan, Apoorva Khajuria, Mostafa Khalil, Mehnoor Khaliq, Ayushah Khan, Hamzah Khan, Haroon Khan, Maaz Khan, Maria Khan, Shahab Khan, Kaywaan Khan, Rachel Khaw, Ashni Kheterpal, Parisa Khonsari, Miraen Kiandee, Samuel Kim, Suji Kim, Sung-Hee Kim, Harry King, Anna Kinsella, Ajit Kishore, Stefan Klimach, Angelos G. Kolias, Anna Kolodziejczyk, Chia Yew Kong, Tseun Han James Kong, Omar Kouli, Sebi Kukran, Sevi Kukran, Geev Kumaran, Vladislav Kutuzov, Chris Laing, Georgina Laing, Kulvinder Lal, Peter Lalor, Joel Lambert, Sai Geethan Lambotharan, Eve Lancaster, Jasmine Latter, Michelle Latter, Kenny Lau, Alexa Lazarou, Madeline Leadon, Gabriel Lee, Jeyoung Lee, Kathryn Lee, Matthew Lee, Samuel Lee, Zong Lee, Edward Leung, Thomas Lewis, Hansen Li, Mimi Li, Wan Jane Liew, Yao Ren Liew, Alexander Light, Lydia Lilis, Diana Lim, Hui Lim, Joseph Lim, Zhi Lim, Siyin Liu, James Lloyd, Andrew Logan, Priya Loganathan, M. Long, Lydia Longstaff, Luisa Lopez Rojas, Richard Lovegrove, Jack Lowe-Zinola, Byron Lu Morrell, Joshua Luck, Andreas Luhmann, Surabhika Lunawat, Jon Lund, Cong Luo, Lorna Luo, Iona Lyell, Panagis Lykoudis, Jonathan Macdonald, Aliya Mackenzie, Conor Magee, Pooja Mahankali-Rao, Kamal Mahawar, Mehreen Mahfooz, Faisal Mahmood, Samir Makwana, Tom Malik, Sohaib Mallick, Jyothis Manalayil, Tinaye Mandishona, Sudhakar Mangam, Maniragav Manimaran, Natarajan Manimaran, Chris Manson, Sufyan Mansoor, Fatima Mansour, Alejandro Marcos Rodrigo, Nicholas Markham, Maria Marks, Paul Marriott, Hannah Marsden, Laura Martin, Tiago Martins, John Mason, Luke Mason, Mariam Masood, Nikhil Math, Ginimol Mathew, Jacob Matthews, Jonathan Mayes, Ursula Mc Gee, Ross Mcallister, Sandra Mcallister, Scott Mccain, Conor Mccann, Emmet Mccann, Cathal McCarthy, Gillian Mccoll, Greg Mcconaghie, Ace Mcdermott, Frank McDermott, Rachel Mcdougall, Mark McDowell, Gordon McFarlane, Richard McGregor, Doug McKechnie, Jillian McKenna, Scott McKinstry, Georgia Mclachlan, E. Mclean, Elizabeth McLennan, Angus McNair, Kenneth Mealy, Lauren Mecia, Alexander Mehta, Aidan Mellan, Arathi Menon, Donald Menzies, Zhubene Mesbah, David Messenger, George Miller, Aseem Mishra, Sona Mistry, Tahira Mohamed, Nisha Mohamed Mushaini, Midhun Mohan, Ameerah Mohd Azmilssss, Ajay Mohite, Krishna Moorthy, Jalal Moradzadeh, Richard Morgan, Gabriella Morley, Alice Mortimer, Hannah Mownah, Paul Moxey, Gagira Mudalige, Umarah Muhammad, Samuel Munday, Ben Murphy, Ciaran Murphy, Caoimhe Murray, Hannah Murray, Michael Murray, Mohammed Ibrar Murtaza, Jameel Mushtaq, Ameer Mustafa, Shams Mustafa, Laura Myers, Sam Myers, Adeeb Naasan, Kiran Nadeem, Hanzla Naeem, Prashant Naik, Arun Nair, Keshav K. Nambiar, Muhammad Naqi, Zehra Naqvi, Yan Ning Neo, Georgia Irene Neophytou, Jonathan Neville, Tom Newman, Benjamin Ng, Guat Ng, Jing Qi Ng, Vincent Ng, Zhan Herr Ng, Maire Ni Bhoirne, James Nicholas, Gary Nicholson, George Ninkovic-Hall, Gemma Nixon, Mike Norwood, Toby Noton, Romman Nourzaie, Richard Novell, Donald Nyanhongo, James O'Brien, Rory O'Kane, Stephen O'Neill, Hugh O'Sullivan, Thomas Oakley, Chinomso Ogbuokiri, Oluwafunto Ogunleye, Su Oh, Emezie Okorocha, James Olivier, Rele Ologunde, Sharif Omara, Alice Ormrod, Caroline Osborne, Joanna Osmanska, Raisah Owasil, Sebastian Owczarek, Ezgi Ozcan, Sri Palaniappan, Francesco Palazzo, Abbas Palkhi, Gargi Pandey, James Park, Jennifer Parker, Anna Parry, James Parsonage, Lauren Passby, Bhavi Patel, Bhavik Patel, Chantal Patel, Dinisha Patel, Kirtan Patel, Panna Patel, Pratiksha Patel, Trupesh Patel, Mariasoosai Pathmarajah, Amogh Patil, Pradeep Patil, Yusuf Patrick, Jessica Pearce, Lyndsay Pearce, Colin Peirce, Bryony Peiris, Amy Pendrill, Sreelata Periketi, Michael Perry, George Petrov, Charlotte Phillips, Grace Pike, Ana Catarina Pinho-Gomes, Parhana Polly, Arachchige Ponweera, Yanish Poolovadoo, Raunak Poonawala, Petya Popova, Dimitri Pournaras, Brooke Powell, Praveena Prabakaran, Esha Prakash, Tapani Pratumsuwan, Anusha Prem Kumar, Helen Puddy, Michael Pullinger, Nikita Punjabi, Oliver Charles Putt, Omar Qadir, Mubasher Qamar, Patrick Quinn, Arham Qureshi, Mohamed Rabie, Angus Radford, Anand Radhakrishnan, Ansh Radotra, Nasir Rafiq, Aria Rahem, Nahim Rahman, Syed Rahman, Ramesh Rajagopal, Nick Rajan, Nikitha Rajaraman, Sumetha Rajendran, Liandra Ramachenderam, Divya Ramakrishnan, Denisha Ramjas, James Rammell, Ritika Rampal, George Ramsay, Ratan Randhawa, Ellis Rea, Stephanie Rees, Saad Rehman, Salwah Rehman, Nabila Rehnnuma, Melina Rejayee, Zakaria Rob, Charlotte Roberts, Grace Roberts, Ben Roberts, Harry Robinson, Stephen Robinson, Ailin Rogers, Alex Rogers, William Rook, Talisa Ross, Chloe Roy, Azelea Rushd, Duncan Rutherford, Michael Saat, Kaushik Sadanand, Rebecca Sagar, Harkiran Sagoo, Arin Saha, Kapil Sahnan, Mohammed Salik Sait, Saif Sait, Damien Salekin, Mostafa Salem, Nadia Salloum, Emma Sanders, Jasmesh Sandhu, N. Sandhu, Lorna Sandison, Laura Sandland-Taylor, Ron Sangal, Chandan Sanghera, Josephine Saramunda, Lauren Satterthwaite, Moritz Schramm, Rupert Scott, Chloe Searle, Harkiran Seehra, Juan Jose Segura-Sampedro, Harpreet Kaur Sekhon Inderjit Singh, Shaikh Sanjid Seraj, Ishani Seth, Rajiv Sethi, Apar Shah, Mario Shaid, Shafaque Shaikh, Awad Shamali, Elizabeth Sharkey, Abhi Sharma, Neil Sharma, Sachin Sharma, Aniruddh Shenoy, Maleasha Shergill, Shahram Shirazi, Imran Siddiqui, Raykal Sim, Lucy Simmonds, Andrew Simon, William Simpson, Bharpoor Singh, J. Singh, Prashant Singh, Anant Sinha, Sidhartha Sinha, Robert Sinnerton, Chaamanti Sivakumar, Brendan Skelly, Richard Slater, Samuel Small, Neil Smart, Yat Wing Smart, Alexander Smith, Charlotte Smith, Jason Smith, Rebecca Smith, Scott Smith, Peter Sodde, Zhi Min Soh, Aniket Sonsale, Ahmed Soualhi, John Spearman, Robert Spencer, Harry Spiers, Philip Stather, Michael Stoddart, Bradley Storey, Howard Stringer, Thomas Stringfellow, Ben Stubbs, Niv Sukir, Nivian Sukirthan, Yasir Suleman, Aparnah Sureshkumar, Ashwin Suri, Timen Swartbol, Hyder Tahir, E. Tian Tan, Huai Ling Tan, Laura Tan, Alethea Tang, Priyal Taribagil, Yao Zong Tay, Beth Taylor, Zara Taylor, Alexandra Thatcher, Rachel Thavayogan, Michael Thomaa, Daniah Thomas, Jenny Thomas, Paul Thomas, Thomas Pinkney, Chris Thompson, Mag Ting, Ethan Toner, Godwin Tong, Jared Torkington, Molly Traish, Miles Triniman, John Trotter, Kwong Tsang, Sanchit Turaga, Hannah Turley, James Turner, Tomas Urbonas, Alexandra Urquhart, Nimai Vadgama, Aashay Vaidya, Gijs van Boxel, Swati Vara, Massimo Varcada, Rebecca Varley, Dee Varma, Martinique Vella-Baldacchino, Sara Venturini, Naina Verma, Saurabh Verma, Gabrielle Vernet, Mark Vipond, Alex von Roon, Qasim Wadood, Kathryn Waite, Lewis Walker, Nathan Walker, Jonathan C.M. Wan, Liyang Wang, Xue Wang, Alex Ward, Thomas Ward, Nienke Warnaar, Lloyd Warren, Oliver Warren, Sam Waters, Angus Watson, Laura Jayne Watson, Dominic Waugh, Daniel Weinberg, Malcolm West, Carla White, Tim White, Katharine Whitehurst, Robert Whitham, Tharindri Wijekoon, Manuk Wijeyaratne, Richard Wilkin, Alex Wilkins, Adam Williams, Gethin Williams, Luke Williams, Robert Williams, Andrew Williamson, Jacinthe Willson, Andrew Wilson, Holly Wilson, James Wilson, Lizzie Wilson, Megan Wilson, Michael Wilson, Rebekah Wilson, Tim Wilson, Evelina Woin, Esther Wright, Jenny Wright, Nicholas Wroe, Joanne Wylie, Yiwang Xu, Satheesh Yalamarthi, Angela Yan, Narisu Yang, Eda Yardimci, Ibrahim Yasin, Ismael Yasin, Noor Yasin, Joseph Yates, Jih Dar Yau, Tricia Yeoh, Joshua Yip, Cissy Yong, Vasudev Zaver, Tatiana Zhelezniakova, and Adreana Zulkifli

Subjects
Medical education, Manchester Cancer Research Centre, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, MEDLINE, General Medicine, 030230 surgery, Collaborative research, 03 medical and health sciences, 0302 clinical medicine, Foundation Programme, Medicine, Surgery, 030212 general & internal medicine, business
Published
2017
Full Text
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45. Astroglial glutamate transporters in the brain: Regulating neurotransmitter homeostasis and synaptic transmission

Author

Julien P. Dupuis, Laurent Groc, Stéphane H. R. Oliet, and Ciaran Murphy-Royal

Subjects
0301 basic medicine, Synaptic cleft, Central nervous system, Glutamate receptor, Excitotoxicity, Biology, Neurotransmission, medicine.disease_cause, 03 medical and health sciences, Cellular and Molecular Neuroscience, Glutamatergic, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, chemistry, Synaptic plasticity, medicine, Neurotransmitter, Neuroscience, 030217 neurology & neurosurgery
Abstract

Astrocytes, the major glial cell type in the central nervous system (CNS), are critical for brain function and have been implicated in various disorders of the central nervous system. These cells are involved in a wide range of cerebral processes including brain metabolism, control of central blood flow, ionic homeostasis, fine-tuning synaptic transmission, and neurotransmitter clearance. Such varied roles can be efficiently carried out due to the intimate interactions astrocytes maintain with neurons, the vasculature, as well as with other glial cells. Arguably, one of the most important functions of astrocytes in the brain is their control of neurotransmitter clearance. This is particularly true for glutamate whose timecourse in the synaptic cleft needs to be controlled tightly under physiological conditions to maintain point-to-point excitatory transmission, thereby limiting spillover and activation of more receptors. Most importantly, accumulation of glutamate in the extracellular space can trigger excessive activation of glutamatergic receptors and lead to excitotoxicity, a trademark of many neurodegenerative diseases. It is thus of utmost importance for both physiological and pathophysiological reasons to understand the processes that control glutamate time course within the synaptic cleft and regulate its concentrations in the extracellular space. © 2017 Wiley Periodicals, Inc.

Published
2017
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47. Stress-induced structural and functional modifications of astrocytes-Further implicating glia in the central response to stress

Author

Ciaran Murphy-Royal, Grant R. Gordon, and Jaideep S. Bains

Subjects
0301 basic medicine, Human studies, Stress induced, Brain, Neurotransmission, Biology, Stress (mechanics), 03 medical and health sciences, Cellular and Molecular Neuroscience, 030104 developmental biology, 0302 clinical medicine, Neurology, Astrocytes, Stress disorders, Animals, Humans, Neuroscience, 030217 neurology & neurosurgery, Stress, Psychological
Abstract

An organism's response to stress requires activation of multiple brain regions. This can have long-lasting effects on synaptic transmission and plasticity that likely provide adaptive benefits. Recent evidence implicates not only neurones, but also glial cells in the regulation of the central response to stress. Intense, repeated or uncontrolled stress has been implicated in the emergence of multiple neuropsychiatric conditions. Human studies have consistently observed glial dysfunction in mood and stress disorders such as major depression. Interestingly animal models of stress have recapitulated glial abnormalities that are comparable to the human condition, validating the use of rodent models for the study of stress disorders. In this review we will focus upon one family of glia, the astrocytes, and describe the evidence to date that links astrocytes to possible stress-related disorders.

Published
2018

48. Cholecystokinin Switches the Plasticity of GABA Synapses in the Dorsomedial Hypothalamus via Astrocytic ATP Release

Author

Jaideep S. Bains, Quentin J. Pittman, Karen M. Crosby, Grant R. Gordon, Sarah A. Wilson, and Ciaran Murphy-Royal

Subjects
0301 basic medicine, Male, Gliotransmitter, Receptor, Metabotropic Glutamate 5, Long-Term Potentiation, Dorsomedial Hypothalamic Nucleus, Inhibitory postsynaptic potential, Cholecystokinin receptor, Synaptic Transmission, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Adenosine Triphosphate, Animals, Research Articles, gamma-Aminobutyric Acid, Cholecystokinin, Chemistry, General Neuroscience, Long-Term Synaptic Depression, digestive, oral, and skin physiology, Glutamate receptor, Long-term potentiation, 030104 developmental biology, Metabotropic glutamate receptor, Receptors, Purinergic P2X, Astrocytes, Synaptic plasticity, Receptors, Cholecystokinin, Neuroscience, 030217 neurology & neurosurgery, hormones, hormone substitutes, and hormone antagonists
Abstract

Whether synapses in appetite-regulatory brain regions undergo long-term changes in strength in response to satiety peptides is poorly understood. Here we show that following bursts of afferent activity, the neuromodulator and satiety peptide cholecystokinin (CCK) shifts the plasticity of GABA synapses in the dorsomedial nucleus of the hypothalamus of male Sprague Dawley rats from long-term depression to long-term potentiation (LTP). This LTP requires the activation of both type 2 CCK receptors and group 5 metabotropic glutamate receptors, resulting in a rise in astrocytic intracellular calcium and subsequent ATP release. ATP then acts on presynaptic P2X receptors to trigger a prolonged increase in GABA release. Our observations demonstrate a novel form of CCK-mediated plasticity that requires astrocytic ATP release, and could serve as a mechanism for appetite regulation.SIGNIFICANCE STATEMENTSatiety peptides, like cholecystokinin, play an important role in the central regulation of appetite, but their effect on synaptic plasticity is not well understood. The current data provide novel evidence that cholecystokinin shifts the plasticity from long-term depression to long-term potentiation at GABA synapses in the rat dorsomedial nucleus of the hypothalamus. We also demonstrate that this plasticity requires the concerted action of cholecystokinin and glutamate on astrocytes, triggering the release of the gliotransmitter ATP, which subsequently increases GABA release from neighboring inhibitory terminals. This research reveals a novel neuropeptide-induced switch in the direction of synaptic plasticity that requires astrocytes, and could represent a new mechanism by which cholecystokinin regulates appetite.

Published
2018

49. Insight into the complex pathophysiology of sickle cell anaemia and possible treatment

Author

Owen P Smith, Elva Eakins, Maria Beatrice Rondinelli, Dominik Wolf, Cinzia Vecchiato, Corrina Mc Mahon, Ciaran Murphy, Andrea Piccin, and Massimo Daves

Subjects
Genotype, Cell, Hemoglobin, Sickle, Erythrocytes, Abnormal, Anemia, Sickle Cell, beta-Globins, Nitric Oxide, Hemolysis, Protein S, Nitric oxide, Pathogenesis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Antisickling Agents, Cell-Derived Microparticles, Medicine, Animals, Humans, Hydroxyurea, Blood Coagulation, Clinical Trials as Topic, biology, business.industry, Erythrocyte Membrane, Hematology, General Medicine, Haemolysis, Intermediate-Conductance Calcium-Activated Potassium Channels, Pathophysiology, Disease Models, Animal, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, Immunology, Mutation, biology.protein, business, Cell Adhesion Molecules, Protein C, Intracellular, Biomarkers, 030215 immunology, medicine.drug
Abstract

Sickle cell anaemia (SCA) is the consequence of abnormal haemoglobin production due to an inherited point mutation in the β-globin gene. The resulting haemoglobin tetramer is poorly soluble when deoxygenated, and when this is prolonged, intracellular gelation of sickle haemoglobin occurs, followed by haemoglobin polymerisation. If many cycles of sickling and unsickling occur, the red cell membrane will be disrupted leading to haemolysis and vaso-occlusive events. Recent studies have also shown that leucocyte adhesion molecules and nitric oxide (NO) depletion are involved in endothelial damage. New insights in SCA pathophysiology and vascular biology have shown that cell-derived microparticle (MP) generation is also involved in the vaso-occlusion. Endothelial damage is perpetuated by impaired production or increased consumption of protective modulators such as protein C, protein S and NO. New therapeutic interventions should address these aspects of SCA pathogenesis. To date, the only US-FDA-approved therapy to prevent painful vaso-occulsive episodes is hydroxyurea that reduces haemoglobin polymerisation in sickle cells by increasing the production of foetal haemoglobin and L-glutamine. However, several new drugs have been tested in the last years in randomised clinical trials. We here report an update on the current status of knowledge on SCA.

Published
2018

50. Circulating microparticles, protein C, free protein S and endothelial vascular markers in children with sickle cell anaemia

Author

Daisy Corvetta, Laura Sainati, Corrina Mc Mahon, Angela Maria Di Pierro, Elva Eakins, William G. Murphy, Andrea Piccin, Ciaran Murphy, Mazzoleni Guido, Jan Kunde, Owen P. Smith, and Giovanni Negri

Subjects
medicine.medical_specialty, Histology, CD36, sickle cell anaemia, protein C, Protein S, nitric oxide, Internal medicine, medicine, Platelet, Platelet activation, Original Research Article, lcsh:QH573-671, microparticles, Sickle Cell Anaemia, microparticles, protein C, protein S, adrenomedullin, endothelin-1 , nitric oxide, Red Cell, biology, business.industry, lcsh:Cytology, Cell Biology, Endothelin 1, Adrenomedullin, Endocrinology, Immunology, adrenomedullin, endothelin-1, biology.protein, business, protein S, Protein C, medicine.drug
Abstract

Introduction: Circulating microparticles (MP) have been described in sickle cell anaemia (SCA); however, their interaction with endothelial markers remains unclear. We investigated the relationship between MP, protein C (PC), free protein S (PS), nitric oxide (NO), endothelin-1 (ET-1) and adrenomedullin (ADM) in a large cohort of paediatric patients.Method: A total of 111 children of African ethnicity with SCA: 51 in steady state; 15 in crises; 30 on hydroxyurea (HU) therapy; 15 on transfusion; 17 controls (HbAA) of similar age/ethnicity. MP were analysed by flow cytometry using: Annexin V (AV), CD61, CD42a, CD62P, CD235a, CD14, CD142 (tissue factor), CD201 (endothelial PC receptor), CD62E, CD36 (TSP-1), CD47 (TSP-1 receptor), CD31 (PECAM), CD144 (VE-cadherin). Protein C, free PS, NO, pro-ADM and C-terminal ET-1 were also measured.Results: Total MP AV was lower in crisis (1.26×106 ml−1; 0.56–2.44×106) and steady state (1.35×106 ml−1; 0.71–3.0×106) compared to transfusion (4.33×106 ml−1; 1.6–9.2×106, p0.9, p

Published
2015

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