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Stephen May

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https://www.readbyqxmd.com/read/29775428/the-involvement-of-human-monogenic-cardiomyopathy-genes-in-experimental-polygenic-cardiac-hypertrophy
#1
Priscilla R Prestes, Francine Z Marques, Guillermo Lopez-Campos, Paul Lewandowski, Lea M D Delbridge, Fadi J Charchar, Stephen B Harrap
Hypertrophic cardiomyopathy thickens heart muscles reducing functionality and increasing risk of cardiac disease and morbidity. Genetic factors are involved, but their contribution is poorly understood. We used the hypertrophic heart rat (HHR), a unique normotensive polygenic model of cardiac hypertrophy and heart failure to investigate the role of genes associated with monogenic human cardiomyopathy. We selected 42 genes involved in monogenic human cardiomyopathies to study: 1) DNA variants, by sequencing the whole-genome of 13-week old HHR and age-matched normal heart rat (NHR), its genetic control strain; 2) mRNA expression, by targeted RNA-sequencing in left ventricles of HHR and NHR at five ages (2-days old, 4-, 13-, 33- and 50-weeks old) compared to human idiopathic dilated data; and 3) microRNA expression, with rat microRNA microarrays in left ventricles of 2-days old HHR and age-matched NHR...
May 18, 2018: Physiological Genomics
https://www.readbyqxmd.com/read/29775132/evaluation-of-lateral-atlantodental-interval-asymmetry-in-the-pediatric-age-group-normative-values
#2
Stephen K Mendenhall, Andrew Huh, Janit Pandya, Vincent Alentado, Karl Balsara, Chang Ho, Andrew Jea
OBJECTIVE The revelation of normative radiographic measurements for the developing pediatric spine is incomplete. The purpose of this analysis was to determine the normal range of asymmetry of the lateral atlantodental interval (LADI) and define age- and sex-related differences. METHODS A total of 3072 children aged 0-18 years who underwent CT scanning of the cervical spine were identified at Riley Hospital for Children between 2005 and 2017. Patients were stratified by sex and age (in years) into 36 cohorts...
May 18, 2018: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/29774305/multi-slice-mri-reveals-heterogeneity-in-disease-distribution-along-the-length-of-muscle-in-duchenne-muscular-dystrophy
#3
Stephen M Chrzanowski, Celine Baligand, Rebecca J Willcocks, Jasjit Deol, Ilona Schmalfuss, Donovan J Lott, Michael J Daniels, Claudia Senesac, Glenn A Walter, Krista Vandenborne
Background: Duchenne muscular dystrophy (DMD) causes progressive pathologic changes to muscle secondary to a cascade of inflammation, lipid deposition, and fibrosis. Clinically, this manifests as progressive weakness, functional loss, and premature mortality. Though insult to whole muscle groups is well established, less is known about the relationship between intramuscular pathology and function. Objective: Differences of intramuscular heterogeneity across muscle length were assessed using an ordinal MRI grading scale in lower leg muscles of boys with DMD and correlated to patient's functional status...
September 2017: Acta Myologica: Myopathies and Cardiomyopathies: Official Journal of the Mediterranean Society of Myology
https://www.readbyqxmd.com/read/29774245/evaluation-of-phylogenetic-reconstruction-methods-using-bacterial-whole-genomes-a-simulation-based-study
#4
John A Lees, Michelle Kendall, Julian Parkhill, Caroline Colijn, Stephen D Bentley, Simon R Harris
Background : Phylogenetic reconstruction is a necessary first step in many analyses which use whole genome sequence data from bacterial populations. There are many available methods to infer phylogenies, and these have various advantages and disadvantages, but few unbiased comparisons of the range of approaches have been made. Methods : We simulated data from a defined "true tree" using a realistic evolutionary model. We built phylogenies from this data using a range of methods, and compared reconstructed trees to the true tree using two measures, noting the computational time needed for different phylogenetic reconstructions...
2018: Wellcome Open Research
https://www.readbyqxmd.com/read/29773582/activation-of-large-conductance-calcium-activated-k-channels-by-nitric-oxide-mediates-apelin-induced-relaxation-of-coronary-arteries
#5
Amreen Mughal, Chengwen Sun, Stephen T O'Rourke
Apelin increases coronary blood flow, cardiac contractility and cardiac output. Based on these favorable hemodynamic effects, apelin and apelin-like analogs are being developed for treating heart failure and related disorders; however, the molecular mechanisms underlying apelin-induced coronary vasodilation are unknown. This study aimed to elucidate the signaling pathways by which apelin causes smooth muscle relaxation in coronary arteries. Receptors for apelin (APJ receptors) were expressed in coronary arteries, as determined by Western blot and PCR analyses...
May 17, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29772447/one-to-one-specialling-and-sitters-in-acute-care-hospitals-a-scoping-review
#6
REVIEW
Victoria J Wood, Cecilia Vindrola-Padros, Nick Swart, Michelle McIntosh, Sonya Crowe, Stephen Morris, Naomi J Fulop
BACKGROUND: One to one specialling is a type of care which is provided to ensure the safety of patients who may be suffering from cognitive impairment, exhibit challenging behaviour, or may be at risk of falls or of causing harm to themselves or others. Care such as this, often referred to as 'specialling' or 'sitting' is common practice in most hospitals around the world, but there is a lack of evidence regarding its cost effectiveness and the quality of care provided. AIM: The aim of this scoping review was to explore the breadth and scope of literature on one to one specialling, sitters and similar types of care in acute secondary care settings, in order to identify the challenges and concerns relating to the quality of care (process and outcomes) and cost effectiveness emerging from the literature, and determine the implications of this for policy, practice and future research...
April 30, 2018: International Journal of Nursing Studies
https://www.readbyqxmd.com/read/29772353/cardiac-profile-of-chimeric-antigen-receptor-car-t-cell-therapy-in-children-a-single-institution-experience
#7
Danielle Burstein, Shannon Maude, Stephen Grupp, Heather Griffis, Joseph Rossano, Kimberly Lin
BACKGROUND: Immunotherapy with chimeric antigen receptor (CAR)-modified T-cells targeting CD19 for pediatric acute lymphoblastic leukemia (ALL) has demonstrated significant efficacy. The principle toxicity is cytokine release syndrome with resultant hypotension. However, the spectrum of cardiovascular effects associated with CAR T-cell therapy has not been systematically evaluated. METHODS: We reviewed all patients who received CD19-directed CAR T-cells at the Children's Hospital of Philadelphia between April 2012 and September 2016...
May 14, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29772020/so-many-genes-so-little-time-a-practical-approach-to-divergence-time-estimation-in-the-genomic-era
#8
Stephen A Smith, Joseph W Brown, Joseph F Walker
Phylogenomic datasets have been successfully used to address questions involving evolutionary relationships, patterns of genome structure, signatures of selection, and gene and genome duplications. However, despite the recent explosion in genomic and transcriptomic data, the utility of these data sources for efficient divergence-time inference remains unexamined. Phylogenomic datasets pose two distinct problems for divergence-time estimation: (i) the volume of data makes inference of the entire dataset intractable, and (ii) the extent of underlying topological and rate heterogeneity across genes makes model mis-specification a real concern...
2018: PloS One
https://www.readbyqxmd.com/read/29771928/chip-exo-interrogation-of-crp-dna-and-rnap-holoenzyme-interactions
#9
Haythem Latif, Stephen Federowicz, Ali Ebrahim, Janna Tarasova, Richard Szubin, Jose Utrilla, Karsten Zengler, Bernhard O Palsson
Numerous in vitro studies have yielded a refined picture of the structural and molecular associations between Cyclic-AMP receptor protein (Crp), the DNA motif, and RNA polymerase (RNAP) holoenzyme. In this study, high-resolution ChIP-exonuclease (ChIP-exo) was applied to study Crp binding in vivo and at genome-scale. Surprisingly, Crp was found to provide little to no protection of the DNA motif under activating conditions. Instead, Crp demonstrated binding patterns that closely resembled those generated by σ70...
2018: PloS One
https://www.readbyqxmd.com/read/29771796/a-population-based-cohort-analysis-of-chemoradiation-versus-radiation-alone-for-definitive-treatment-of-stage-i-anal-cancer-in-older-patients
#10
Michael Buckstein, Yotam Arens, Juan Wisnivesky, Michael Gaisa, Stephen Goldstone, Keith Sigel
BACKGROUND: Although the benefit of chemoradiation over radiation therapy alone has been shown in randomized trials for stage II to III squamous cell of the anus, this benefit is not clear for patients with stage I cancer. Nevertheless, most societal recommendations endorse chemoradiation for patients with stage I squamous cell carcinoma of the anus despite the lack of proven benefit and potential increase in toxicity. OBJECTIVE: The purpose of this study was to determine whether outcomes are improved with the addition of chemotherapy versus radiation alone for stage I squamous cell carcinoma of the anus...
May 15, 2018: Diseases of the Colon and Rectum
https://www.readbyqxmd.com/read/29771740/closing-the-referral-loop-improving-ambulatory-referral-management-electronic-health-record-connectivity-and-care-coordination-processes
#11
Stephen L Davidow, Jignesh Sheth, Constance S Sixta, Linda Thomas-Hemak
More than 105 million referrals of Medicare beneficiaries to specialists occur annually. Different settings and electronic health records have made care coordination complex. PCPI (formerly American Medical Association-convened Physicians Consortium for Performance Improvement) and The Wright Center for Graduate Medical Education sponsored the Closing the Referral Loop pilot project. Twelve dyads of primary care and specialist physicians sought to improve ambulatory referrals by mapping the referral process, and using care compacts, metrics, and electronic health records...
May 15, 2018: Journal of Ambulatory Care Management
https://www.readbyqxmd.com/read/29771715/whole-blood-for-resuscitation-in-adult-civilian-trauma-in-2017-a-narrative-review
#12
Evan G Pivalizza, Christopher T Stephens, Srikanth Sridhar, Sam D Gumbert, Susan Rossmann, Marsha F Bertholf, Yu Bai, Bryan A Cotton
After a hiatus of several decades, the concept of cold whole blood (WB) is being reintroduced into acute clinical trauma care in the United States. Initial implementation experience and data grew from military medical applications, followed by more recent development and data acquisition in civilian institutions. Anesthesiologists, especially those who work in acute trauma facilities, are likely to be presented with patients either receiving WB from the emergency department or may have WB as a therapeutic option in massive transfusion situations...
May 15, 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29770905/congenital-grouped-albinotic-spots-of-the-retinal-pigment-epithelium-in-a-patient-with-hemihypertrophy-and-caf%C3%A3-au-lait-spots
#13
Eugenia C White, Jesse D Sengillo, Galaxy Y Cho, Mathieu F Bakhoum, Stephen H Tsang
PURPOSE: To describe the finding of circularly grouped hypomelanotic spots in the central macula of a patient with syndromic characteristics. METHODS: Case report of a patient with albinotic spots grouped within the macula, café au lait spots, and left-sided hemihypertrophy. RESULTS: A 15-year-old boy presented with hypomelanotic spots which were hyperautofluorescent on fundus autofluorescence imaging with no disruption of the retinal laminae or photoreceptor inner and outer segment (IS/OS) junction on spectral domain optical coherence tomography...
May 16, 2018: Documenta Ophthalmologica. Advances in Ophthalmology
https://www.readbyqxmd.com/read/29769666/an-unexpected-and-persistent-increase-in-global-emissions-of-ozone-depleting-cfc-11
#14
Stephen A Montzka, Geoff S Dutton, Pengfei Yu, Eric Ray, Robert W Portmann, John S Daniel, Lambert Kuijpers, Brad D Hall, Debra Mondeel, Carolina Siso, J David Nance, Matt Rigby, Alistair J Manning, Lei Hu, Fred Moore, Ben R Miller, James W Elkins
The Montreal Protocol was designed to protect the stratospheric ozone layer by enabling reductions in the abundance of ozone-depleting substances such as chlorofluorocarbons (CFCs) in the atmosphere1-3 . The reduction in the atmospheric concentration of trichlorofluoromethane (CFC-11) has made the second-largest contribution to the decline in the total atmospheric concentration of ozone-depleting chlorine since the 1990s 1 . However, CFC-11 still contributes one-quarter of all chlorine reaching the stratosphere, and a timely recovery of the stratospheric ozone layer depends on a sustained decline in CFC-11 concentrations 1 ...
May 2018: Nature
https://www.readbyqxmd.com/read/29769538/organic-matter-loading-by-hippopotami-causes-subsidy-overload-resulting-in-downstream-hypoxia-and-fish-kills
#15
Christopher L Dutton, Amanda L Subalusky, Stephen K Hamilton, Emma J Rosi, David M Post
Organic matter and nutrient loading into aquatic ecosystems affects ecosystem structure and function and can result in eutrophication and hypoxia. Hypoxia is often attributed to anthropogenic pollution and is not common in unpolluted rivers. Here we show that organic matter loading from hippopotami causes the repeated occurrence of hypoxia in the Mara River, East Africa. We documented 49 high flow events over 3 years that caused dissolved oxygen decreases, including 13 events resulting in hypoxia, and 9 fish kills over 5 years...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29769307/orally-bioavailable-and-blood-brain-barrier-penetrating-atm-inhibitor-az32-radiosensitizes-intracranial-gliomas-in-mice
#16
Jeremy Karlin, Jasmine Allen, Syed F Ahmad, Gareth Hughes, Victoria Sheridan, Rajesh Odedra, Paul Farrington, Elaine B Cadogan, Lucy C Riches, Antonio Garcia-Trinidad, Andrew G Thomason, Bhavika Patel, Jennifer Vincent, Alan Lau, Kurt G Pike, Thomas A Hunt, Amrita Sule, Nicholas C K Valerie, Laura Biddlestone-Thorpe, Jenna Kahn, Jason M Beckta, Nitai Mukhopadhyay, Bernard Barlaam, Sebastien L Degorce, Jason Kettle, Nicola Colclough, Joanne Wilson, Aaron Smith, Ian P Barrett, Li Zheng, Tianwei Zhang, Yingchun Wang, Kan Chen, Martin Pass, Stephen T Durant, Kristoffer Valerie
Inhibition of ataxia-telangiectasia mutated (ATM) during radiotherapy of glioblastoma multiforme (GBM) may improve tumor control by short-circuiting the response to radiation-induced DNA damage. A major impediment for clinical implementation is that current inhibitors have limited CNS bioavailability, thus, the goal was to identify ATM inhibitors (ATMi) with improved CNS penetration. Drug screens and refinement of lead compounds identified AZ31 and AZ32. The compounds were then tested in vivo for efficacy and impact on tumor and healthy brain...
May 16, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29769147/association-of-pulmonary-cardiovascular-and-hematologic-metrics-with-carbon-nanotube-and-nanofiber-exposure-among-u-s-workers-a-cross-sectional-study
#17
Mary K Schubauer-Berigan, Matthew M Dahm, Aaron Erdely, John D Beard, M Eileen Birch, Douglas E Evans, Joseph E Fernback, Robert R Mercer, Stephen J Bertke, Tracy Eye, Marie A de Perio
BACKGROUND: Commercial use of carbon nanotubes and nanofibers (CNT/F) in composites and electronics is increasing; however, little is known about health effects among workers. We conducted a cross-sectional study among 108 workers at 12 U.S. CNT/F facilities. We evaluated chest symptoms or respiratory allergies since starting work with CNT/F, lung function, resting blood pressure (BP), resting heart rate (RHR), and complete blood count (CBC) components. METHODS: We conducted multi-day, full-shift sampling to measure background-corrected elemental carbon (EC) and CNT/F structure count concentrations, and collected induced sputum to measure CNT/F in the respiratory tract...
May 16, 2018: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/29769070/serum-magnesium-levels-and-risk-of-coronary-artery-disease-mendelian-randomisation-study
#18
Susanna C Larsson, Stephen Burgess, Karl Michaëlsson
BACKGROUND: Observational studies have shown that serum magnesium levels are inversely associated with risk of cardiovascular disease, but whether this association is causal is unknown. We conducted a Mendelian randomisation study to investigate whether serum magnesium levels may be causally associated with coronary artery disease (CAD). METHODS: This Mendelian randomisation analysis is based on summary-level data from the CARDIoGRAMplusC4D consortium's 1000 Genomes-based genome-wide association meta-analysis of 48 studies with a total of 60,801 CAD cases and 123,504 non-cases...
May 17, 2018: BMC Medicine
https://www.readbyqxmd.com/read/29769041/cortical-atrophy-and-hypofibrinogenemia-due-to-fgg-and-tbcd-mutations-in-a-single-family-a-case-report
#19
Joshi Stephen, Sheela Nampoothiri, K P Vinayan, Dhanya Yesodharan, Preetha Remesh, William A Gahl, May Christine V Malicdan
BACKGROUND: Blended phenotypes or co-occurrence of independent phenotypically distinct conditions are extremely rare and are due to coincidence of multiple pathogenic mutations, especially due to consanguinity. Hereditary fibrinogen deficiencies result from mutations in the genes FGA, FGB, and FGG, encoding the three different polypeptide chains that comprise fibrinogen. Neurodevelopmental abnormalities have not been associated with fibrinogen deficiencies. In this study, we report an unusual patient with a combination of two independently inherited genetic conditions; fibrinogen deficiency and early onset cortical atrophy...
May 16, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29769016/whole-genome-sequencing-data-of-1110-mycobacterium-tuberculosis-isolates-identifies-insertions-and-deletions-associated-with-drug-resistance
#20
Xi Zeng, Jamie Sui-Lam Kwok, Kevin Yi Yang, Kenneth Siu-Sing Leung, Mai Shi, Zhiyuan Yang, Wing-Cheong Yam, Stephen Kwok-Wing Tsui
BACKGROUND: Drug resistance in Mycobacterium tuberculosis (MTB) is one of the major challenges in tuberculosis (TB) treatment. However, known mutations cannot explain all of the cases of resistance and little research has focused on the relationship between insertions / deletions (indels) and drug resistance. RESULTS: Here, we retrieved whole genome sequencing data of 743 drug-resistant MTB strains and 367 pan-susceptible strains from TB patients from the public domain to identify novel genomic markers of drug resistance...
May 16, 2018: BMC Genomics
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