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https://www.readbyqxmd.com/read/28106992/discovery-of-n-pyridin-4-yl-1-5-naphthyridin-2-amines-as-potential-tau-pathology-pet-tracers-for-alzheimer-s-disease
#1
Frederik J R Rombouts, José-Ignacio Andrés, Manuela Ariza, José Manuel Alonso, Nigel Austin, Astrid Bottelbergs, Lu Chen, Vladimir Chupakhin, Erna Cleiren, Katleen Fierens, Alberto Fontana, Xavier Langlois, Joseph E Leenaerts, Jonas Mariën, Carolina Martinez Lamenca, Rhys Salter, Mark E Schmidt, Paula Te Riele, Cindy Wintmolders, Andrés A Trabanco, Wei Zhang, Gregor J Macdonald, Diederik Moechars
A mini-HTS on 4000 compounds selected using 2D fragment-based similarity and 3D pharmacophoric and shape similarity to known selective tau aggregate binders identified N-(6-methylpyridin-2-yl)quinolin-2-amine 10 as a novel potent binder to human AD aggregated tau with modest selectivity versus aggregated β-amyloid (Aβ). Initial medicinal chemistry efforts identified key elements for potency and selectivity, as well as suitable positions for radiofluorination, leading to a first generation of fluoroalkyl-substituted quinoline tau binding ligands with sub-optimal physicochemical properties...
January 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28093026/out-of-sight-out-of-mind-racial-retrieval-cues-increase-the-accessibility-of-social-justice-concepts
#2
Phia S Salter, Nicholas J Kelley, Ludwin E Molina, Luyen T Thai
Photographs provide critical retrieval cues for personal remembering, but few studies have considered this phenomenon at the collective level. In this research, we examined the psychological consequences of visual attention to the presence (or absence) of racially charged retrieval cues within American racial segregation photographs. We hypothesised that attention to racial retrieval cues embedded in historical photographs would increase social justice concept accessibility. In Study 1, we recorded gaze patterns with an eye-tracker among participants viewing images that contained racial retrieval cues or were digitally manipulated to remove them...
January 16, 2017: Memory
https://www.readbyqxmd.com/read/28081210/mutations-in-hyal2-encoding-hyaluronidase-2-cause-a-syndrome-of-orofacial-clefting-and-cor-triatriatum-sinister-in-humans-and-mice
#3
Martina M A Muggenthaler, Biswajit Chowdhury, S Naimul Hasan, Harold E Cross, Brian Mark, Gaurav V Harlalka, Michael A Patton, Miho Ishida, Elijah R Behr, Sanjay Sharma, Kenneth Zahka, Eissa Faqeih, Brian Blakley, Mike Jackson, Melissa Lees, Vernon Dolinsky, Leroy Cross, Philip Stanier, Claire Salter, Emma L Baple, Fowzan S Alkuraya, Andrew H Crosby, Barbara Triggs-Raine, Barry A Chioza
Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate the complexities of the genetic etiology of this heterogeneous condition, this factor remains incompletely understood. Here, we describe mutations in the HYAL2 gene as a cause of syndromic orofacial clefting. HYAL2, encoding hyaluronidase 2, degrades extracellular hyaluronan, a critical component of the developing heart and palatal shelf matrix...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28076751/salter-harris-type-iv-fracture-of-the-proximal-phalanx-of-the-thumb-with-rotation-of-the-epiphysis-outcome-10-years-following-open-reduction-and-k-wire-fixation
#4
Mohammad M Al-Qattan
INTRODUCTION: Salter-Harris type IV fracture of the proximal phalanx with 90° rotation of the epiphysis is very rare. We report on a case of Salter-Harris type IV fracture of the proximal phalanx of the thumb with rotation of the epiphysis and document the outcome 10 years after surgery. PRESENTATION OF CASE: A 5-year old boy presented with Salter-Harris type IV fracture of the thumb with 90° rotation of the epiphysis. Open reduction and K-wire fixation was done...
December 27, 2016: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28074581/conflating-capacity-authority-why-we-re-asking-the-wrong-question-in-the-adolescent-decision-making-debate
#5
Erica K Salter
Whether adolescents should be allowed to make their own medical decisions has been a topic of discussion in bioethics for at least two decades now. Are adolescents sufficiently capacitated to make their own medical decisions? Is the mature-minor doctrine, an uncommon legal exception to the rule of parental decision-making authority, something we should expand or eliminate? Bioethicists have dealt with the curious liminality of adolescents-their being neither children nor adults-in a variety of ways. However, recently there has been a trend to rely heavily, and often exclusively, on emerging neuroscientific and psychological data to answer these questions...
January 2017: Hastings Center Report
https://www.readbyqxmd.com/read/28068139/do-acceptance-and-mindfulness-moderate-the-relationship-between-maladaptive-beliefs-and-posttraumatic-distress
#6
Jillian C Shipherd, Kristalyn Salters-Pedneault
OBJECTIVE: Maladaptive pre- and posttraumatic beliefs are reliable predictors of distress in the wake of trauma. Acceptance and mindfulness skills may be associated with less distress in the presence of these beliefs, but few studies have explored these relationships. This study examined whether individual differences in acceptance and mindfulness moderate the relationship between maladaptive thoughts and distress in postdeployment soldiers. METHOD: We explored the relationships between posttraumatic maladaptive beliefs, acceptance, mindfulness, and posttraumatic distress (posttraumatic stress disorder [PTSD] and general psychological symptoms) in a sample of recently postdeployed active duty U...
January 9, 2017: Psychological Trauma: Theory, Research, Practice and Policy
https://www.readbyqxmd.com/read/28062402/the-ras-effector-interaction-as-a-drug-target
#7
REVIEW
Adam B Keeton, E Alan Salter, Gary A Piazza
About a third of all human cancers harbor mutations in one of the K-, N-, or HRAS genes that encode an abnormal RAS protein locked in a constitutively activated state to drive malignant transformation and tumor growth. Despite more than three decades of intensive research aimed at the discovery of RAS-directed therapeutics, there are no FDA-approved drugs that are broadly effective against RAS-driven cancers. Although RAS proteins are often said to be "undruggable," there is mounting evidence suggesting it may be feasible to develop direct inhibitors of RAS proteins...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28056721/controlling-new-knowledge-genomic-science-governance-and-the-politics-of-bioinformatics
#8
Brian Salter, Charlotte Salter
The rise of bioinformatics is a direct response to the political difficulties faced by genomics in its quest to be a new biomedical innovation, and the value of bioinformatics lies in its role as the bridge between the promise of genomics and its realization in the form of health benefits. Western scientific elites are able to use their close relationship with the state to control and facilitate the emergence of new domains compatible with the existing distribution of epistemic power - all within the embrace of public trust...
January 1, 2017: Social Studies of Science
https://www.readbyqxmd.com/read/28052917/a-mutation-of-ept1-selenoi-underlies-a-new-disorder-of-kennedy-pathway-phospholipid-biosynthesis
#9
Mustafa Y Ahmed, Aisha Al-Khayat, Fathiya Al-Murshedi, Amna Al-Futaisi, Barry A Chioza, J Pedro Fernandez-Murray, Jay E Self, Claire G Salter, Gaurav V Harlalka, Lettie E Rawlins, Sana Al-Zuhaibi, Faisal Al-Azri, Fatma Al-Rashdi, Amaury Cazenave-Gassiot, Markus R Wenk, Fatema Al-Salmi, Michael A Patton, David L Silver, Emma L Baple, Christopher R McMaster, Andrew H Crosby
Mutations in genes involved in lipid metabolism have increasingly been associated with various subtypes of hereditary spastic paraplegia, a highly heterogeneous group of neurodegenerative motor neuron disorders characterized by spastic paraparesis. Here, we report an unusual autosomal recessive neurodegenerative condition, best classified as a complicated form of hereditary spastic paraplegia, associated with mutation in the ethanolaminephosphotransferase 1 (EPT1) gene (now known as SELENOI), responsible for the final step in Kennedy pathway forming phosphatidylethanolamine from CDP-ethanolamine...
January 3, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28051139/biosynthesis-of-magnetic-nanoparticles-by-human-mesenchymal-stem-cells-following-transfection-with-the-magnetotactic-bacterial-gene-mms6
#10
Alistair Elfick, Grigore Rischitor, Rabah Mouras, Asim Azfer, Lisa Lungaro, Marc Uhlarz, Thomas Herrmannsdörfer, John Lucocq, Wesam Gamal, Pierre Bagnaninchi, Scott Semple, Donald M Salter
The use of stem cells to support tissue repair is facilitated by loading of the therapeutic cells with magnetic nanoparticles (MNPs) enabling magnetic tracking and targeting. Current methods for magnetizing cells use artificial MNPs and have disadvantages of variable uptake, cellular cytotoxicity and loss of nanoparticles on cell division. Here we demonstrate a transgenic approach to magnetize human mesenchymal stem cells (MSCs). MSCs are genetically modified by transfection with the mms6 gene derived from Magnetospirillum magneticum AMB-1, a magnetotactic bacterium that synthesises single-magnetic domain crystals which are incorporated into magnetosomes...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28048736/su-f-j-55-feasibility-of-supraclavicular-field-treatment-by-investigating-variation-of-junction-position-between-breast-tangential-and-supraclavicular-fields-for-deep-inspiration-breath-hold-dibh-left-breast-radiation
#11
H Zhao, V Sarkar, A Paxton, P Rassiah-Szegedi, Y Huang, M Szegedi, L Huang, F Su, B Salter
PURPOSE: To explore the feasibility of supraclavicular field treatment by investigating the variation of junction position between tangential and supraclavicular fields during left breast radiation using DIBH technique. METHODS: Six patients with left breast cancer treated using DIBH technique were included in this study. AlignRT system was used to track patient's breast surface. During daily treatment, when the patient's DIBH reached preset AlignRT tolerance of ±3mm for all principle directions (vertical, longitudinal, and lateral), the remaining longitudinal offset was recorded...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047441/mo-e-brb-03-panel-member
#12
B Salter
: In this interactive session, lung SBRT patient cases will be presented to highlight real-world considerations for ensuring safe and accurate treatment delivery. An expert panel of speakers will discuss challenges specific to lung SBRT including patient selection, patient immobilization techniques, 4D CT simulation and respiratory motion management, target delineation for treatment planning, online treatment alignment, and established prescription regimens and OAR dose limits. Practical examples of cases, including the patient flow thought the clinical process are presented and audience participation will be encouraged...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28042255/a-comparison-of-statistical-emulation-methodologies-for-multi-wave-calibration-of-environmental-models
#13
James M Salter, Daniel Williamson
Expensive computer codes, particularly those used for simulating environmental or geological processes, such as climate models, require calibration (sometimes called tuning). When calibrating expensive simulators using uncertainty quantification methods, it is usually necessary to use a statistical model called an emulator in place of the computer code when running the calibration algorithm. Though emulators based on Gaussian processes are typically many orders of magnitude faster to evaluate than the simulator they mimic, many applications have sought to speed up the computations by using regression-only emulators within the calculations instead, arguing that the extra sophistication brought using the Gaussian process is not worth the extra computational power...
December 2016: Environmetrics
https://www.readbyqxmd.com/read/28035846/employment-and-absenteeism-in-working-age-persons-with-multiple-sclerosis
#14
Amber Salter, Nina Thomas, Tuula Tyry, Gary Cutter, Ruth Ann Marrie
AIMS: To better understand the impact of the clinical course of multiple sclerosis (MS) and disability on employment, absenteeism, and related factors. MATERIALS AND METHODS: We included respondents to the North American Research Committee on Multiple Sclerosis Registry spring 2015 update survey who were United States or Canadian residents, aged 18-65 years and reported having relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or primary progressive MS (PPMS)...
December 30, 2016: Journal of Medical Economics
https://www.readbyqxmd.com/read/28002964/asymmetric-hydroboration-approach-to-the-scalable-synthesis-of-1r-3s-1-amino-3-r-6-hexyl-5-6-7-8-tetrahydronaphthalen-2-yl-cyclopentyl-methanol-bms-986104-as-a-potent-s1p1-receptor-modulator
#15
Michael G Yang, Zili Xiao, T G Murali Dhar, Hai-Yun Xiao, John L Gilmore, David Marcoux, Jenny H Xie, Kim W McIntyre, Tracy L Taylor, Virna Borowski, Elizabeth Heimrich, Yu-Wen Li, Jianlin Feng, Alda Fernandes, Zheng Yang, Praveen Balimane, Anthony M Marino, Georgia Cornelius, Bethanne M Warrack, Arvind Mathur, Dauh-Rurng Wu, Peng Li, Anuradha Gupta, Bala Pragalathan, Ding Ren Shen, Mary Ellen Cvijic, Lois D Lehman-McKeeman, Luisa Salter-Cid, Joel C Barrish, Percy H Carter, Alaric J Dyckman
We describe a highly efficient route for the synthesis of 4a (BMS-986104). A key step in the synthesis is the asymmetric hydroboration of trisubstituted alkene 6. Particularly given the known difficulties involved in this type of transformation (6 → 7), the current methodology provides an efficient approach to prepare this class of compounds. In addition, we disclose the efficacy of 4a in a mouse EAE model, which is comparable to 4c (FTY720). Mechanistically, 4a exhibited excellent remyelinating effects on lysophosphatidylcholine (LPC) induced demyelination in a three-dimensional brain cell culture assay...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27990179/analysis-of-urine-oral-fluid-and-fingerprints-by-liquid-extraction-surface-analysis-coupled-to-high-resolution-ms-and-ms-ms-opportunities-for-forensic-and-biomedical-science
#16
Melanie Bailey, Elizabeth C Randall, Catia Costa, Tara L Salter, Alan M Race, Marcel de Puit, Mattijs Koeberg, Mark Baumert, Josephine Bunch
Liquid Extraction Surface Analysis (LESA) is a new, high throughput tool for ambient mass spectrometry. A solvent droplet is deposited from a pipette tip onto a surface and maintains contact with both the surface and the pipette tip for a few seconds before being re-aspirated. The technique is particularly suited to the analysis of trace materials on surfaces due to its high sensitivity and low volume of sample removal. In this work, we assess the suitability of LESA for obtaining detailed chemical profiles of fingerprints, oral fluid and urine, which may be used in future for rapid medical diagnostics or metabolomics studies...
April 28, 2016: Analytical Methods: Advancing Methods and Applications
https://www.readbyqxmd.com/read/27984688/-ankle-fracture-in-adolescents-triplanar-injury-associated-to-fracture-of-leg
#17
D Cuzmar-Grimalt, M Escudero-Heldt, J T Aldunate-González, N Plaza-Guzmán
the vast mayority of epiphyseal children fractures could be classified according to Salter Harris. There are other types of patterns such as triplanar and Tillaux fractures. The former is a complex type with fracture lines in sagital, axial and frontal planes. These fractures have main complications such as early epiphyseal closure, mechanical axis malalignment and gait disturbances. A clinical case is pictured which had a tibial shaft and ipsilateral triplanar fracture, this complex scenario of rare ocurrence was treated with reduction and osteosynthesis of both fractures...
May 2016: Acta Ortopédica Mexicana
https://www.readbyqxmd.com/read/27928844/glucagon-like-peptide-1-receptor-expression-on-human-eosinophils-and-its-regulation-of-eosinophil-activation
#18
Patrick D Mitchell, Brittany M Salter, John Paul Oliveria, Amani El-Gammal, Damian Tworek, Steve G Smith, Roma Sehmi, Gail M Gauvreau, Marcus Butler, Paul M O'Byrne
BACKGROUND: Glucagon Like Peptide-1 (GLP-1) and its receptor are part of the incretin family of hormones the regulate glucose metabolism. GLP-1 also has immune modulatory roles. OBJECTIVES: To measure the expression of the GLP-1 receptor (GLP-1R) on eosinophils and neutrophils in normal and asthmatic subjects and evaluate effects of a GLP-1 analog on eosinophil function. METHODS: Peripheral blood samples were taken from 10 normal and 10 allergic asthmatic subjects...
December 8, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27926876/potentiation-of-synaptic-glun2b-nmdar-currents-by-fyn-kinase-is-gated-through-bdnf-mediated-disinhibition-in-spinal-pain-processing
#19
Michael E Hildebrand, Jian Xu, Annemarie Dedek, Yi Li, Ameet S Sengar, Simon Beggs, Paul J Lombroso, Michael W Salter
In chronic pain states, the neurotrophin brain-derived neurotrophic factor (BDNF) transforms the output of lamina I spinal neurons by decreasing synaptic inhibition. Pain hypersensitivity also depends on N-methyl-D-aspartate receptors (NMDARs) and Src-family kinases, but the locus of NMDAR dysregulation remains unknown. Here, we show that NMDAR-mediated currents at lamina I synapses are potentiated in a peripheral nerve injury model of neuropathic pain. We find that BDNF mediates NMDAR potentiation through activation of TrkB and phosphorylation of the GluN2B subunit by the Src-family kinase Fyn...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27925240/closed-reduction-and-fluoroscopic-assisted-percutaneous-pinning-of-42-physeal-fractures-in-37-dogs-and-4-cats
#20
Christina L Boekhout-Ta, Stanley E Kim, Alan R Cross, Richard Evans, Antonio Pozzi
OBJECTIVE: To report complications and clinical outcome of dogs and cats that underwent fluoroscopic-assisted percutaneous pinning (FAPP) of physeal fractures. STUDY DESIGN: Retrospective study. ANIMALS: Client-owned dogs (n = 37) and cats (n = 4). MATERIALS AND METHODS: Records (August 2007-August 2014) of physeal fractures treated with FAPP in 3 hospitals were evaluated. Data collected included signalment, fracture characteristics (etiology, location, duration, Salter-Harris classification, preoperative and postoperative displacement), surgical information (implant size, surgical duration), and outcome assessment information (functional outcome, radiographic outcome, and complications)...
December 7, 2016: Veterinary Surgery: VS
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