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Robert Gorman

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https://www.readbyqxmd.com/read/29747965/mitral-annuloplasty-ring-flexibility-preferentially-reduces-posterior-suture-forces
#1
Eric L Pierce, Charles H Bloodworth, Akito Imai, Keitaro Okamoto, Yoshiaki Saito, Robert C Gorman, Joseph H Gorman, Ajit P Yoganathan
Annuloplasty ring repair is a common procedure for the correction of mitral valve regurgitation. Commercially available rings vary in dimensions and material properties. Annuloplasty ring suture dehiscence from the native annulus is a catastrophic yet poorly understood phenomenon that has been reported across ring types. Recognizing that sutures typically dehisce from the structurally weaker posterior annulus, our group is conducting a multi-part study in search of ring design parameters that influence forces acting on posterior annular sutures in the beating heart...
May 3, 2018: Journal of Biomechanics
https://www.readbyqxmd.com/read/29735722/mtdna-heteroplasmy-level-and-copy-number-indicate-disease-burden-in-m-3243a-g-mitochondrial-disease
#2
John P Grady, Sarah J Pickett, Yi Shiau Ng, Charlotte L Alston, Emma L Blakely, Steven A Hardy, Catherine L Feeney, Alexandra A Bright, Andrew M Schaefer, Gráinne S Gorman, Richard Jq McNally, Robert W Taylor, Doug M Turnbull, Robert McFarland
Mitochondrial disease associated with the pathogenic m.3243A>G variant is a common, clinically heterogeneous, neurogenetic disorder. Using multiple linear regression and linear mixed modelling, we evaluated which commonly assayed tissue (blood N  = 231, urine N  = 235, skeletal muscle N  = 77) represents the m.3243A>G mutation load and mitochondrial DNA (mtDNA) copy number most strongly associated with disease burden and progression. m.3243A>G levels are correlated in blood, muscle and urine ( R 2  = 0...
May 7, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29722051/liquid-chromatographic-tandem-mass-spectrometry-assay-for-the-quantification-of-mdt-637-in-human-nasal-wash
#3
Shane C Karnik, Robert Cook, Steve H Gorman, Ray Bakhtiar
MDT-637 is a new chemical entity (NCE) that shows potent and selective antiviral activity against Respiratory Syncytial Virus (RSV). As part of the new drug development program, a method for quantitating MDT-637 in nasal wash collected from human subjects was required. This article describes the method development, validation and application of a bioanalytical assay for MDT-637 in human nasal wash using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sample pretreatment utilized supported liquid extraction and final extracts were injected onto an Agilent Poroshell 120 EC-C18 column and eluted under isocratic conditions of 65/35 (v/v) 10 mM ammonium formate in water and acetonitrile Detection was performed on an API 5000 tandem mass spectrometer operating in negative electrospray ionization mode applying multiple reaction monitoring (MRM)...
May 2, 2018: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29709799/optimization-of-strong-base-anion-exchange-o-m-costs-for-hexavalent-chromium-treatment
#4
Sarah Plummer, Craig Gorman, Tarrah Henrie, Kyle Shimabuku, Robert Thompson, Chad Seidel
Hexavalent chromium [Cr(VI)] in drinking water is pending regulation in California and is being considered for regulation in other locations. While strong-base anion exchange (SBA-IX) can efficiently remove Cr(VI) to low-levels that may be required to comply with future MCLs, operational and maintenance (O&M) costs can be considerable if the spent brine is disposed of as hazardous waste. Through bench- and pilot-scale experiments and full-scale demonstrations, this study examined the ability of emerging and established brine treatment and reuse techniques as well as recently developed resins to decrease O&M costs...
April 10, 2018: Water Research
https://www.readbyqxmd.com/read/29683790/multicenter-phase-ib-trial-of-carboxyamidotriazole-orotate-and-temozolomide-for-recurrent-and-newly-diagnosed-glioblastoma-and-other-anaplastic-gliomas
#5
Antonio Omuro, Kathryn Beal, Katharine McNeill, Robert J Young, Alissa Thomas, Xuling Lin, Robert Terziev, Thomas J Kaley, Lisa M DeAngelis, Mariza Daras, Igor T Gavrilovic, Ingo Mellinghoff, Eli L Diamond, Andrew McKeown, Malbora Manne, Andrew Caterfino, Krishna Patel, Linda Bavisotto, Greg Gorman, Michael Lamson, Philip Gutin, Viviane Tabar, Debyani Chakravarty, Timothy A Chan, Cameron W Brennan, Elizabeth Garrett-Mayer, Rashida A Karmali, Elena Pentsova
Purpose Carboxyamidotriazole orotate (CTO) is a novel oral inhibitor of non-voltage-dependent calcium channels with modulatory effects in multiple cell-signaling pathways and synergistic effects with temozolomide (TMZ) in glioblastoma (GBM) models. We conducted a phase IB study combining CTO with two standard TMZ schedules in GBM. Methods In cohort 1, patients with recurrent anaplastic gliomas or GBM received escalating doses of CTO (219 to 812.5 mg/m2 once daily or 600 mg fixed once-daily dose) combined with TMZ (150 mg/m2 5 days during each 28-day cycle)...
April 23, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29629128/direct-sulfonylation-of-anilines-mediated-by-visible-light
#6
Tarn C Johnson, Bryony L Elbert, Alistair J M Farley, Timothy W Gorman, Christophe Genicot, Bénédicte Lallemand, Patrick Pasau, Jakub Flasz, José L Castro, Malcolm MacCoss, Darren J Dixon, Robert S Paton, Christopher J Schofield, Martin D Smith, Michael C Willis
Sulfones feature prominently in biologically active molecules and are key functional groups for organic synthesis. We report a mild, photoredox-catalyzed reaction for sulfonylation of aniline derivatives with sulfinate salts, and demonstrate the utility of the method by the late-stage functionalization of drugs. Key features of the method are the straightforward generation of sulfonyl radicals from bench-stable sulfinate salts and the use of simple aniline derivatives as convenient readily available coupling partners...
January 21, 2018: Chemical Science
https://www.readbyqxmd.com/read/29602790/retrospective-natural-history-of-thymidine-kinase-2-deficiency
#7
Caterina Garone, Robert W Taylor, Andrés Nascimento, Joanna Poulton, Carl Fratter, Cristina Domínguez-González, Julie C Evans, Mariana Loos, Pirjo Isohanni, Anu Suomalainen, Dipak Ram, M Imelda Hughes, Robert McFarland, Emanuele Barca, Carlos Lopez Gomez, Sandeep Jayawant, Neil D Thomas, Adnan Y Manzur, Karin Kleinsteuber, Miguel A Martin, Timothy Kerr, Grainne S Gorman, Ewen W Sommerville, Patrick F Chinnery, Monika Hofer, Christoph Karch, Jeffrey Ralph, Yolanda Cámara, Marcos Madruga-Garrido, Jana Domínguez-Carral, Carlos Ortez, Sonia Emperador, Julio Montoya, Anupam Chakrapani, Joshua F Kriger, Robert Schoenaker, Bruce Levin, John L P Thompson, Yuelin Long, Shamima Rahman, Maria Alice Donati, Salvatore DiMauro, Michio Hirano
BACKGROUND: Thymine kinase 2 (TK2) is a mitochondrial matrix protein encoded in nuclear DNA and phosphorylates the pyrimidine nucleosides: thymidine and deoxycytidine. Autosomal recessive TK2 mutations cause a spectrum of disease from infantile onset to adult onset manifesting primarily as myopathy. OBJECTIVE: To perform a retrospective natural history study of a large cohort of patients with TK2 deficiency. METHODS: The study was conducted by 42 investigators across 31 academic medical centres...
March 30, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29588995/the-adjunctive-application-of-transcranial-direct-current-stimulation-in-the-management-of-de-novo-refractory-epilepsia-partialis-continua-in-adolescent-onset-polg-related-mitochondrial-disease
#8
Yi Shiau Ng, Henriette van Ruiten, H Ming Lai, Rebecca Scott, Venkateswaran Ramesh, Karen Horridge, Robert W Taylor, Doug M Turnbull, Gráinne S Gorman, Robert McFarland, Mark R Baker
Focal status epilepticus in POLG -related mitochondrial disease is highly refractory to pharmacological agents, including general anesthesia. We report the challenges in managing a previously healthy teenager who presented with de novo epilepsia partialis continua and metabolic stroke resulting from the homozygous p.Ala467Thr POLG mutation, the most common pathogenic variant identified in the Caucasian population. We applied transcranial direct current stimulation (tDCS; 2 mA; 20 min) daily as an adjunctive therapy because her focal seizures failed to respond to five antiepileptic drugs at maximal doses...
March 2018: Epilepsia Open
https://www.readbyqxmd.com/read/29566124/sustained-release-of-endothelial-progenitor-cell-derived-extracellular-vesicles-from-shear-thinning-hydrogels-improves-angiogenesis-and-promotes-function-after-myocardial-infarction
#9
Carol W Chen, Leo L Wang, Samir Zaman, Jon Gordon, Maria F Arisi, Chantel M Venkataraman, Jennifer J Chung, George Hung, Ann C Gaffey, Lynn A Spruce, Hossein Fazelinia, Robert C Gorman, Steven H Seeholzer, Jason A Burdick, Pavan Atluri
Aims: Previous studies have demonstrated improved cardiac function following myocardial infarction (MI) after administration of endothelial progenitor cells (EPCs) into ischemic myocardium. A growing body of literature supports paracrine effectors, including extracellular vesicles (EVs), as the main mediators of the therapeutic benefits of EPCs. The use of paracrine factors is an attractive strategy that harnesses the effects of cell therapy without concerns of cell engraftment or viability...
March 16, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29560378/phenotypic-heterogeneity-in-m-3243a-g-mitochondrial-disease-the-role-of-nuclear-factors
#10
Sarah J Pickett, John P Grady, Yi Shiau Ng, Gráinne S Gorman, Andrew M Schaefer, Ian J Wilson, Heather J Cordell, Doug M Turnbull, Robert W Taylor, Robert McFarland
Objective: The pathogenic mitochondrial DNA m.3243A>G mutation is associated with a wide range of clinical features, making disease prognosis extremely difficult to predict. We aimed to understand the cause of this heterogeneity. Methods: We examined the phenotypic profile of 238 adult m.3243A>G carriers (patients and asymptomatic carriers) from the UK MRC Mitochondrial Disease Patient Cohort using the Newcastle Mitochondrial Disease Adult Scale. We modeled the role of risk factors for the development of specific phenotypes using proportional odds logistic regression...
March 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29529980/scientific-and-ethical-issues-in-mitochondrial-donation
#11
Lyndsey Craven, Julie Murphy, Doug M Turnbull, Robert W Taylor, Grainne S Gorman, Robert McFarland
The development of any novel reproductive technology involving manipulation of human embryos is almost inevitably going to be controversial and evoke sincerely held, but diametrically opposing views. The plethora of scientific, ethical and legal issues that surround the clinical use of such techniques fuels this divergence of opinion. During the policy change that was required to allow the use of mitochondrial donation in the UK, many of these issues were intensely scrutinised by a variety of people and in multiple contexts...
April 2018: New Bioethics: a Multidisciplinary Journal of Biotechnology and the Body
https://www.readbyqxmd.com/read/29506874/mt-nd5-mutation-exhibits-highly-variable-neurological-manifestations-at-low-mutant-load
#12
Yi Shiau Ng, Nichola Z Lax, Paul Maddison, Charlotte L Alston, Emma L Blakely, Philippa D Hepplewhite, Gillian Riordan, Surita Meldau, Patrick F Chinnery, Germaine Pierre, Efstathia Chronopoulou, Ailian Du, Imelda Hughes, Andrew A Morris, Smaragda Kamakari, Georgia Chrousos, Richard J Rodenburg, Christiaan G J Saris, Catherine Feeney, Steven A Hardy, Takafumi Sakakibara, Akira Sudo, Yasushi Okazaki, Kei Murayama, Helen Mundy, Michael G Hanna, Akira Ohtake, Andrew M Schaefer, Mike P Champion, Doug M Turnbull, Robert W Taylor, Robert D S Pitceathly, Robert McFarland, Gráinne S Gorman
Mutations in the m.13094T>C MT-ND5 gene have been previously described in three cases of Leigh Syndrome (LS). In this retrospective, international cohort study we identified 20 clinically affected individuals (13 families) and four asymptomatic carriers. Ten patients were deceased at the time of analysis (median age of death was 10years (range: 5·4months-37years, IQR=17·9years). Nine patients manifested with LS, one with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), and one with Leber hereditary optic neuropathy...
April 2018: EBioMedicine
https://www.readbyqxmd.com/read/29290614/topoisomerase-3%C3%AE-is-required-for-decatenation-and-segregation-of-human-mtdna
#13
Thomas J Nicholls, Cristina A Nadalutti, Elisa Motori, Ewen W Sommerville, Gráinne S Gorman, Swaraj Basu, Emily Hoberg, Doug M Turnbull, Patrick F Chinnery, Nils-Göran Larsson, Erik Larsson, Maria Falkenberg, Robert W Taylor, Jack D Griffith, Claes M Gustafsson
How mtDNA replication is terminated and the newly formed genomes are separated remain unknown. We here demonstrate that the mitochondrial isoform of topoisomerase 3α (Top3α) fulfills this function, acting independently of its nuclear role as a component of the Holliday junction-resolving BLM-Top3α-RMI1-RMI2 (BTR) complex. Our data indicate that mtDNA replication termination occurs via a hemicatenane formed at the origin of H-strand replication and that Top3α is essential for resolving this structure. Decatenation is a prerequisite for separation of the segregating unit of mtDNA, the nucleoid, within the mitochondrial network...
January 4, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29285527/spatiotemporal-segmentation-and-modeling-of-the-mitral-valve-in-real-time-3d-echocardiographic-images
#14
Alison M Pouch, Ahmed H Aly, Eric K Lai, Natalie Yushkevich, Rutger H Stoffers, Joseph H Gorman, Albert T Cheung, Joseph H Gorman, Robert C Gorman, Paul A Yushkevich
Transesophageal echocardiography is the primary imaging modality for preoperative assessment of mitral valves with ischemic mitral regurgitation (IMR). While there are well known echocardiographic insights into the 3D morphology of mitral valves with IMR, such as annular dilation and leaflet tethering, less is understood about how quantification of valve dynamics can inform surgical treatment of IMR or predict short-term recurrence of the disease. As a step towards filling this knowledge gap, we present a novel framework for 4D segmentation and geometric modeling of the mitral valve in real-time 3D echocardiography (rt-3DE)...
September 2017: Medical Image Computing and Computer-assisted Intervention: MICCAI ..
https://www.readbyqxmd.com/read/29283441/pathological-mechanisms-underlying-single-large-scale-mitochondrial-dna-deletions
#15
Mariana C Rocha, Hannah S Rosa, John P Grady, Emma L Blakely, Langping He, Nadine Romain, Ronald G Haller, Jane Newman, Robert McFarland, Yi Shiau Ng, Grainne S Gorman, Andrew M Schaefer, Helen A Tuppen, Robert W Taylor, Doug M Turnbull
OBJECTIVE: Single, large-scale deletions in mitochondrial DNA (mtDNA) are a common cause of mitochondrial disease. This study aimed to investigate the relationship between the genetic defect and molecular phenotype to improve understanding of pathogenic mechanisms associated with single, large-scale mtDNA deletions in skeletal muscle. METHODS: We investigated 23 muscle biopsies taken from adult patients (6 males/17 females with a mean age of 43 years) with characterized single, large-scale mtDNA deletions...
January 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29214652/pharmacology-in-translation-the-preclinical-and-early-clinical-profile-of-the-novel-%C3%AE-2-3-functionally-selective-gaba-a-receptor-positive-allosteric-modulator-pf-06372865
#16
Sarah A Nickolls, Rachel Gurrell, Guido van Amerongen, Juha Kammonen, Lishuang Cao, Adam R Brown, Clara Stead, Andy Mead, Christine Watson, Cathleen Hsu, Robert M Owen, Andy Pike, Rebecca L Fish, Laigao Chen, Ruolun Qiu, Evan D Morris, Gang Feng, Mark Whitlock, Donal Gorman, Joop van Gerven, David S Reynolds, Pinky Dua, Richard P Butt
BACKGROUND AND PURPOSE: Benzodiazepines, non-selective positive allosteric modulators (PAMs) of GABAA receptors, have significant side effects that limit their clinical utility. As many of these side effects are mediated by the α1 subunit, there has been a concerted effort to develop α2/3 subtype-selective PAMs. EXPERIMENTAL APPROACH: In vitro screening assays were used to identify molecules with functional selectivity for receptors containing α2/3 subunits over those containing α1 subunits...
February 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29161071/risk-of-concussion-during-sports-versus-physical-education-among-new-mexico-middle-and-high-school-students
#17
Richard A Campbell, Stephanie A Gorman, Robert J Thoma, Robert D Annett, Christopher A McGrew, Ronald A Yeo, Andrew R Mayer, John H King, Andrew S Rowland
OBJECTIVES: To measure the risk of concussion among New Mexico middle and high school students during both sports and physical education. METHODS: Athletic directors or athletic trainers in 147 schools were asked to report the number of concussions occurring during sports and physical education in the 2013 to 2014 school year. We calculated 1-year cumulative incidence rates. RESULTS: Of the 147 schools, 99 responded (67%). During the school year, 598 students were removed from athletics because of a concussion, a 1-year cumulative incidence of 3...
January 2018: American Journal of Public Health
https://www.readbyqxmd.com/read/29046338/regulation-of-valve-interstitial-cell-homeostasis-by-mechanical-deformation-implications-for-heart-valve-disease-and-surgical-repair
#18
Salma Ayoub, Chung-Hao Lee, Kathryn H Driesbaugh, Wanda Anselmo, Connor T Hughes, Giovanni Ferrari, Robert C Gorman, Joseph H Gorman, Michael S Sacks
Mechanical stress is one of the major aetiological factors underlying soft-tissue remodelling, especially for the mitral valve (MV). It has been hypothesized that altered MV tissue stress states lead to deviations from cellular homeostasis, resulting in subsequent cellular activation and extracellular matrix (ECM) remodelling. However, a quantitative link between alterations in the organ-level in vivo state and in vitro- based mechanobiology studies has yet to be made. We thus developed an integrated experimental-computational approach to elucidate MV tissue and interstitial cell responses to varying tissue strain levels...
October 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28983742/multi-resolution-geometric-modeling-of-the-mitral-heart-valve-leaflets
#19
Amir H Khalighi, Andrew Drach, Robert C Gorman, Joseph H Gorman, Michael S Sacks
An essential element of cardiac function, the mitral valve (MV) ensures proper directional blood flow between the left heart chambers. Over the past two decades, computational simulations have made marked advancements toward providing powerful predictive tools to better understand valvular function and improve treatments for MV disease. However, challenges remain in the development of robust means for the quantification and representation of MV leaflet geometry. In this study, we present a novel modeling pipeline to quantitatively characterize and represent MV leaflet surface geometry...
October 5, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28942898/the-need-for-pediatric-drug-development
#20
Robert M Ward, Daniel K Benjamin, Jonathan M Davis, Richard L Gorman, Ralph Kauffman, Gregory L Kearns, Mary Dianne Murphy, Catherine M T Sherwin
No abstract text is available yet for this article.
January 2018: Journal of Pediatrics
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