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Juliet Chhay Bishop, Karin Blakemore, Luca Vricella, Priya Sekar, Katelynn Sagaser, Jude Crino, Paul Ness, Benjamin K Kogutt, Joan Boyd, Susan Aucott, Angie C Jelin, Joanne Chiu, Eric Gehrie, Kristen Nelson McMillan
Compared to standard component therapy, fresh whole blood (FWB) offers potential benefits to neonates undergoing cardiopulmonary bypass (CPB) in the context of open cardiac surgery: decreased blood loss and subsequent risk of volume overload, improved coagulation status, higher platelet counts during and following CPB, circumvention of limited vascular access, and significantly reduced donor exposures. Obtaining FWB, however, entails 2-5 days of preparation, which often precludes its availability for neonates requiring CPB in the immediate newborn period...
March 14, 2018: Fetal Diagnosis and Therapy
R L Blakemore, M R Mac Askill, R Shoorangiz, T J Anderson
Recent animal studies have shown that stress can profoundly affect motor behaviour and worsen motor deficits associated with Parkinson's disease (PD) by acting on the dopaminergic system, possibly due to stress-associated emotional changes. However, systematic investigation of the influence of acute emotional stressors on motor function in PD is scarce. Here we examined the effect of repeated exposure to negative emotional stimuli on grip-force control in PD. Eighteen patients with idiopathic PD (tested off-medication) and 18 healthy controls produced an isometric precision grip contraction at 15% of maximum force while viewing a series of unpleasant, pleasant, or neutral emotional images (blocked presentation; without visual feedback of force output)...
March 6, 2018: Neuropsychologia
Nicholas J Wald, Joan K Morris, Colin Blakemore
The neural tube defects anencephaly and spina bifida are two of the most common serious congenital malformations. Most cases can be prevented by consuming sufficient folic acid immediately before pregnancy and in early pregnancy. Fortification of flour with folic acid to prevent these defects has been implemented in 81 countries without public objection or indication of harm. An obstacle to the wider adoption of fortification arises from the creation of a "tolerable upper intake level" for folate (which includes natural food folate as well as synthetic folic acid), and which has been set at 1 mg/day, thereby proscribing higher folate intakes...
2018: Public Health Reviews
So Young Lee, Kun Woo Kim, Jae-Ik Lee, Dong-Kyun Park, Kook-Yang Park, Chul-Hyun Park, Kuk-Hui Son
Early diagnosis followed by primary repair is the best treatment for spontaneous esophageal perforation. However, the appropriate management of esophageal leakage after surgical repair is still controversial. Recently, the successful adaptation of vacuum-assisted closure therapy, which is well established for the treatment of chronic surface wounds, has been demonstrated for esophageal perforation or leakage. Conservative treatment methods require long-term fasting with total parenteral nutrition or enteral feeding through invasive procedures, such as percutaneous endoscopic gastrostomy or a feeding jejunostomy...
February 2018: Korean Journal of Thoracic and Cardiovascular Surgery
Lucy Foulkes, Sarah-Jayne Blakemore
Adolescence is a period of social, psychological and biological development. During adolescence, relationships with others become more complex, peer relationships are paramount and social cognition develops substantially. These psychosocial changes are paralleled by structural and functional changes in the brain. Existing research in adolescent neurocognitive development has focused largely on averages, but this obscures meaningful individual variation in development. In this Perspective, we propose that the field should now move toward studying individual differences...
February 5, 2018: Nature Neuroscience
Cristobal L Miranda, Lance A Johnson, Oriane de Montgolfier, Valerie D Elias, Lea S Ullrich, Joshua J Hay, Ines L Paraiso, Jaewoo Choi, Ralph L Reed, Johana S Revel, Chrissa Kioussi, Gerd Bobe, Urszula T Iwaniec, Russell T Turner, Benita S Katzenellenbogen, John A Katzenellenbogen, Paul R Blakemore, Adrian F Gombart, Claudia S Maier, Jacob Raber, Jan F Stevens
Xanthohumol (XN), a prenylated flavonoid from hops, improves dysfunctional glucose and lipid metabolism in animal models of metabolic syndrome (MetS). However, its metabolic transformation into the estrogenic metabolite, 8-prenylnaringenin (8-PN), poses a potential health concern for its use in humans. To address this concern, we evaluated two hydrogenated derivatives, α,β-dihydro-XN (DXN) and tetrahydro-XN (TXN), which showed negligible affinity for estrogen receptors α and β, and which cannot be metabolically converted into 8-PN...
January 12, 2018: Scientific Reports
Maria Panagioti, Suzanne M Skevington, Mark Hann, Kelly Howells, Amy Blakemore, David Reeves, Peter Bower
PURPOSE: The levels of health literacy in patients with long-term conditions (LTCs) are critical for better disease management and quality of life (QoL). However, the impact of health literacy on QoL in older adults with LTCs is unclear. This study examined the association between health literacy and domains of QoL in older people with LTCs, investigating key socio-demographic and clinical variables, as confounders. METHODS: A prospective cohort study was conducted on older adults (n = 4278; aged 65 years and over) with at least one LTC, registered in general practices in Salford, UK...
January 10, 2018: Quality of Life Research
Davide Lionetti, Victor W Day, Benedikt Lassalle-Kaiser, James D Blakemore
The ligand 2,2'-bipyridine (bpy) can support metal centers in low formal oxidation states by delocalization of electron density into its π-system. We show that, in a model rhodium complex supported by the pentamethylcyclopentadienyl ligand (Cp*), the analogous dimethyldipyridylmethane ligand (Me2dpma) enforces a bpy-like coordination environment but disrupts the inter-ring conjugation responsible for charge delocalization upon metal reduction. As a result, reduction proceeds in discrete one-electron steps (Rh(iii) to Rh(ii) to Rh(i)), contrasting with the 2e- chemistry engendered by bpy...
January 5, 2018: Chemical Communications: Chem Comm
David Reeves, Kelly Howells, Mark Sidaway, Amy Blakemore, Mark Hann, Maria Panagioti, Peter Bower
OBJECTIVE: The 'cohort multiple randomized controlled trial' (cmRCT) is a recent innovation by which novel interventions are trialled within large longitudinal cohorts of patients to take gain efficiencies and align trials more closely to standard clinical practice. The use of cmRCTs is outpacing methodological understanding of them and more appropriate methods for designing and analysing such trials are urgently needed. STUDY DESIGN AND SETTING: We established the UK CLASSIC cohort of 4,377 patients with long-term conditions within which we are conducting a cmRCT ("PROTECTS") of telephone-based health coaching...
December 19, 2017: Journal of Clinical Epidemiology
Hotaka Nonaka, Hiroshi Onishi, Masatoki Ozaki, Kengo Kuriyama, Takafumi Komiyama, Ryo Saito
BACKGROUND: In recent reports, re-irradiation with stereotactic body radiotherapy for lung tumors in patients previously treated with thoracic radiation therapy resulted in several serious toxicities. Serious non-lung toxicities were observed mostly in patients with central tumors, but we experienced a case of fatal gastric perforation after a second stereotactic body radiotherapy in a patient with a peripheral lung tumor. CASE PRESENTATION: An 83-year-old Asian man was diagnosed with T2N0M0 lung cancer in the form of squamous cell carcinoma in the lower lobe of his left lung...
December 10, 2017: Journal of Medical Case Reports
Danping Wang, Xie Zhang, Xuesong Zhang, Zhigang Huang, Yufei Song
BACKGROUND: Irritable bowel syndrome (IBS) is a common functional disease of the gastrointestinal tract. The current study aimed to examine the association between visceral hypersensitivity in IBS and cortical activation using functional magnetic resonance imaging (fMRI), and to elucidate the role of psychological factors in the pathogenesis of IBS. METHODS: The present study included 31 patients with IBS and 20 healthy controls. Cerebral function was assessed using fMRI...
December 8, 2017: BMC Gastroenterology
Jan Pringle, Kathryn L Mills, John McAteer, Ruth Jepson, Emma Hogg, Neil Anand, Sarah-Jayne Blakemore
Objectives : To examine physiological influences of adolescent sexual behaviour, including associated psychosocial factors. Methods : Systematic review. Results : Thirteen studies met the inclusion criteria relating to adolescents, physiology and sexual behaviour. We excluded studies relating to abnormal development. Findings highlighted hormonal and gender differences. Females appear to be more influenced by psychosocial aspects, including the effects of peers, than males. Males may be more inclined to engage in unprotected sex with a greater number of partners...
January 2017: Cogent Social Sciences
Thomas Lissek, Michelle Adams, John Adelman, Ehud Ahissar, Mohammed Akaaboune, Huda Akil, Mustafa al'Absi, Fazal Arain, Juan Carlos Arango-Lasprilla, Deniz Atasoy, Jesus Avila, Ashraf Badawi, Hilmar Bading, Abdul Mannan Baig, Jimena Baleriola, Carlos Belmonte, Ilaria Bertocchi, Heinrich Betz, Colin Blakemore, Olaf Blanke, Philipp Boehm-Sturm, Tobias Bonhoeffer, Paolo Bonifazi, Nils Brose, Patrizia Campolongo, Tansu Celikel, Cathy C Chang, Ta-Yuan Chang, Ami Citri, Hollis T Cline, Jesus M Cortes, Kathleen Cullen, Kellie Dean, José M Delgado-Garcia, Mathieu Desroches, John F Disterhoft, John E Dowling, Andreas Draguhn, Sherif F El-Khamisy, Abdeljabbar El Manira, S Ather Enam, Juan M Encinas, Asier Erramuzpe, José A Esteban, Isabel Fariñas, Edmond Fischer, Izumi Fukunaga, Iñigo Gabilondo, Detlev Ganten, Albert Gidon, Juan Carlos Gomez-Esteban, Paul Greengard, Valery Grinevich, Agnés Gruart, Roger Guillemin, Ahmad R Hariri, Bassem Hassan, Michael Häusser, Yasunori Hayashi, Natasha K Hussain, Adnan Abdul Jabbar, Mohamed Jaber, Reinhardt Jahn, Essam Mohammed Janahi, Mohamed Kabbaj, Helmut Kettenmann, Merel Kindt, Shira Knafo, Georg Köhr, Shoji Komai, Harm Krugers, Bernd Kuhn, Nouria Lakhdar Ghazal, Matthew E Larkum, Mickey London, Beat Lutz, Carlos Matute, Luis Martinez-Millan, Mouna Maroun, James McGaugh, Ahmed A Moustafa, Anwar Nasim, Klaus-Armin Nave, Erwin Neher, Karoly Nikolich, Tiago Outeiro, Lucy M Palmer, Olga Penagarikano, Isabel Perez-Otano, Donald W Pfaff, Bruno Poucet, Atta-Ur Rahman, Pedro Ramos-Cabrer, Ali Rashidy-Pour, Richard J Roberts, Serafim Rodrigues, Joshua R Sanes, Andreas T Schaefer, Menahem Segal, Idan Segev, Saad Shafqat, Nikhat Ahmed Siddiqui, Hermona Soreq, Eduardo Soriano-García, Rainer Spanagel, Rolf Sprengel, Greg Stuart, Thomas C Südhof, Jan Tønnesen, Mario Treviño, Basim M Uthman, J Craig Venter, Alexei Verkhratsky, Craig Weiss, Torsten N Wiesel, Emre Yaksi, Ofer Yizhar, Larry J Young, Paul Young, Nasser H Zawia, José L Zugaza, Mazahir T Hasan
Science is ideally suited to connect people from different cultures and thereby foster mutual understanding. To promote international life science collaboration, we have launched "The Science Bridge" initiative. Our current project focuses on partnership between Western and Middle Eastern neuroscience communities.
November 15, 2017: Neuron
Lorène Nathalie Sabine Crespin, Andreas Greb, David C Blakemore, Steven V Ley
A visible-light mediated annulation of N-sulfonylallylamines and olefins is reported. Rapid access to highly functionalized chloromethylated pyrrolidines can be achieved using mild conditions for the generation of nitrogen-centered radicals. Both a transition metal based catalyst and an organic dye can be used as photosensitizers, with 0.5 mol% loading. The reaction was found to be applicable to a large variety of electron-rich olefins.
November 9, 2017: Journal of Organic Chemistry
Ja Yun Choi, Yun Won Jo, Sang Soo Lee, Wan Soo Kim, Hye Won Oh, Cha Young Kim, Eun Young Yun, Jin Joo Kim, Jae Min Lee, Hong Jun Kim, Hyun Jin Kim, Tae Hyo Kim, Woon Tae Jung, Ok Jae Lee, Rock Bum Kim
Background/Aims: The aim of this study was to investigate the mortality, bleeding control rate, and their associated predictors in patients treated with Sengstaken-Blakemore (SB) tube for uncontrolled variceal hemorrhage associated with hemodynamic instability or failure of endoscopic treatment. Methods: The clinical data of 66 consecutive patients with uncontrolled variceal hemorrhage treated with SB tube at Gyeongsang National University Hospital from October 2010 to October 2015 were retrospectively analyzed...
November 10, 2017: Korean Journal of Internal Medicine
Tim Markovic, Benjamin N Rocke, David C Blakemore, Vincent Mascitti, Michael C Willis
A range of 5- and 6-membered heterocycle-derived sulfinates are shown to be effective nucleophilic coupling partners with aryl chlorides and bromides using Pd(0) catalysis. The use of optimal reaction conditions, specifically incorporating a P(t-Bu)2Me-derived Pd catalyst, allowed reactions to be performed at moderate temperatures and enabled the inclusion of a variety of sensitive functional groups. Challenging heterocyclic sulfinates, including pyrazine, pyridazine, pyrimidine, pyrazole, and imidazole, were all shown to perform well...
November 17, 2017: Organic Letters
Laura J Blakemore, Paul Q Trombley
The olfactory bulb (OB) is central to the sense of smell, as it is the site of the first synaptic relay involved in the processing of odor information. Odor sensations are first transduced by olfactory sensory neurons (OSNs) before being transmitted, by way of the OB, to higher olfactory centers that mediate olfactory discrimination and perception. Zinc is a common trace element, and it is highly concentrated in the synaptic vesicles of subsets of glutamatergic neurons in some brain regions including the hippocampus and OB...
2017: Frontiers in Cellular Neuroscience
Beth L Parkin, Vincent Walsh
BACKGROUND: Having investigated the influence of acute physical exhaustion on decision-making in world-class elite athletes in Parkin et al. (2017), here a similar method is applied to subelite athletes. These subelite athletes were enrolled on a Team GB talent development program and were undergoing training for possible Olympic competition in 4-8 years. They differ from elite athletes examined previously according to expertise and age. While considered elite (Swann et al., 2015), the subelite athletes had approximately 8 years fewer sporting experience and were yet to obtain sustained success on the international stage...
2017: Progress in Brain Research
Aldi T Kraja, James P Cook, Helen R Warren, Praveen Surendran, Chunyu Liu, Evangelos Evangelou, Alisa K Manning, Niels Grarup, Fotios Drenos, Xueling Sim, Albert Vernon Smith, Najaf Amin, Alexandra I F Blakemore, Jette Bork-Jensen, Ivan Brandslund, Aliki-Eleni Farmaki, Cristiano Fava, Teresa Ferreira, Karl-Heinz Herzig, Ayush Giri, Franco Giulianini, Megan L Grove, Xiuqing Guo, Sarah E Harris, Christian T Have, Aki S Havulinna, He Zhang, Marit E Jørgensen, AnneMari Käräjämäki, Charles Kooperberg, Allan Linneberg, Louis Little, Yongmei Liu, Lori L Bonnycastle, Yingchang Lu, Reedik Mägi, Anubha Mahajan, Giovanni Malerba, Riccardo E Marioni, Hao Mei, Cristina Menni, Alanna C Morrison, Sandosh Padmanabhan, Walter Palmas, Alaitz Poveda, Rainer Rauramaa, Nigel William Rayner, Muhammad Riaz, Ken Rice, Melissa A Richard, Jennifer A Smith, Lorraine Southam, Alena Stančáková, Kathleen E Stirrups, Vinicius Tragante, Tiinamaija Tuomi, Ioanna Tzoulaki, Tibor V Varga, Stefan Weiss, Andrianos M Yiorkas, Robin Young, Weihua Zhang, Michael R Barnes, Claudia P Cabrera, He Gao, Michael Boehnke, Eric Boerwinkle, John C Chambers, John M Connell, Cramer K Christensen, Rudolf A de Boer, Ian J Deary, George Dedoussis, Panos Deloukas, Anna F Dominiczak, Marcus Dörr, Roby Joehanes, Todd L Edwards, Tõnu Esko, Myriam Fornage, Nora Franceschini, Paul W Franks, Giovanni Gambaro, Leif Groop, Göran Hallmans, Torben Hansen, Caroline Hayward, Oksa Heikki, Erik Ingelsson, Jaakko Tuomilehto, Marjo-Riitta Jarvelin, Sharon L R Kardia, Fredrik Karpe, Jaspal S Kooner, Timo A Lakka, Claudia Langenberg, Lars Lind, Ruth J F Loos, Markku Laakso, Mark I McCarthy, Olle Melander, Karen L Mohlke, Andrew P Morris, Colin N A Palmer, Oluf Pedersen, Ozren Polasek, Neil R Poulter, Michael A Province, Bruce M Psaty, Paul M Ridker, Jerome I Rotter, Igor Rudan, Veikko Salomaa, Nilesh J Samani, Peter J Sever, Tea Skaaby, Jeanette M Stafford, John M Starr, Pim van der Harst, Peter van der Meer, Cornelia M van Duijn, Anne-Claire Vergnaud, Vilmundur Gudnason, Nicholas J Wareham, James G Wilson, Cristen J Willer, Daniel R Witte, Eleftheria Zeggini, Danish Saleheen, Adam S Butterworth, John Danesh, Folkert W Asselbergs, Louise V Wain, Georg B Ehret, Daniel I Chasman, Mark J Caulfield, Paul Elliott, Cecilia M Lindgren, Daniel Levy, Christopher Newton-Cheh, Patricia B Munroe, Joanna M M Howson
BACKGROUND: Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association. METHODS AND RESULTS: Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure...
October 2017: Circulation. Cardiovascular Genetics
R Ian Storer, Andy Pike, Nigel A Swain, Aristos J Alexandrou, Bruce M Bechle, David C Blakemore, Alan D Brown, Neil A Castle, Matthew S Corbett, Neil J Flanagan, David Fengas, M Scott Johnson, Lyn H Jones, Brian E Marron, C Elizabeth Payne, David Printzenhoff, David J Rawson, Colin R Rose, Thomas Ryckmans, Jianmin Sun, Jonathan W Theile, Rubben Torella, Elaine Tseng, Joseph S Warmus
The discovery and selection of a highly potent and selective NaV 1.7 inhibitor PF-06456384, designed specifically for intravenous infusion, is disclosed. Extensive in vitro pharmacology and ADME profiling followed by in vivo preclinical PK and efficacy model data are discussed. A proposed protein-ligand binding mode for this compound is also provided to rationalise the high levels of potency and selectivity over inhibition of related sodium channels. To further support the proposed binding mode, potent conjugates are described which illustrate the potential for development of chemical probes to enable further target evaluation...
November 1, 2017: Bioorganic & Medicinal Chemistry Letters
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