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Robert Gorman

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https://www.readbyqxmd.com/read/29046338/regulation-of-valve-interstitial-cell-homeostasis-by-mechanical-deformation-implications-for-heart-valve-disease-and-surgical-repair
#1
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
#2
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
#3
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.
September 21, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28913697/developing-a-post-treatment-survivorship-care-plan-to-help-breast-cancer-survivors-understand-their-fertility
#4
Jessica R Gorman, Anne K Julian, Samantha A Roberts, Sally A D Romero, Jennifer L Ehren, Michael L Krychman, Sarah G Boles, Jun Mao, H Irene Su
PURPOSE: Reproductive-aged breast cancer survivors (BCS) who have completed initial cancer treatment frequently want to know about their future fertility potential. The purpose of this qualitative study was to assess if the fertility-related content presented in the survivorship care plan prototype met the informational needs of post-treatment BCS and to provide an opportunity for the target audience to review and react to the proposed content and design. METHODS: We conducted and analyzed transcripts from seven focus groups with BCS to evaluate their reactions to the survivorship care plan prototype...
September 14, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28888476/computational-sensitivity-investigation-of-hydrogel-injection-characteristics-for-myocardial-support
#5
Hua Wang, Christopher B Rodell, Madonna E Lee, Neville N Dusaj, Joseph H Gorman, Jason A Burdick, Robert C Gorman, Jonathan F Wenk
Biomaterial injection is a potential new therapy for augmenting ventricular mechanics after myocardial infarction (MI). Recent in vivo studies have demonstrated that hydrogel injections can mitigate the adverse remodeling due to MI. More importantly, the material properties of these injections influence the efficacy of the therapy. The goal of the current study is to explore the interrelated effects of injection stiffness and injection volume on diastolic ventricular wall stress and thickness. To achieve this, finite element models were constructed with different hydrogel injection volumes (150µL and 300 µL), where the modulus was assessed over a range of 0...
November 7, 2017: Journal of Biomechanics
https://www.readbyqxmd.com/read/28861630/an-integrated-inverse-model-experimental-approach-to-determine-soft-tissue-three-dimensional-constitutive-parameters-application-to-post-infarcted-myocardium
#6
Reza Avazmohammadi, David S Li, Thomas Leahy, Elizabeth Shih, João S Soares, Joseph H Gorman, Robert C Gorman, Michael S Sacks
Knowledge of the complete three-dimensional (3D) mechanical behavior of soft tissues is essential in understanding their pathophysiology and in developing novel therapies. Despite significant progress made in experimentation and modeling, a complete approach for the full characterization of soft tissue 3D behavior remains elusive. A major challenge is the complex architecture of soft tissues, such as myocardium, which endows them with strongly anisotropic and heterogeneous mechanical properties. Available experimental approaches for quantifying the 3D mechanical behavior of myocardium are limited to preselected planar biaxial and 3D cuboidal shear tests...
August 31, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28833674/c-h-cyanation-of-6-ring-n-containing-heteroaromatics
#7
Bryony L Elbert, Alistair J M Farley, Timothy W Gorman, Tarn C Johnson, Christophe Genicot, Bénédicte Lallemand, Patrick Pasau, Jakub Flasz, José L Castro, Malcolm MacCoss, Robert S Paton, Christopher J Schofield, Martin D Smith, Michael C Willis, Darren J Dixon
Heteroaromatic nitriles are important compounds in drug discovery, both for their prevalence in the clinic and due to the diverse range of transformations they can undergo. As such, efficient and reliable methods to access them have the potential for far-reaching impact across synthetic chemistry and the biomedical sciences. Herein, we report an approach to heteroaromatic C-H cyanation through triflic anhydride activation, nucleophilic addition of cyanide, followed by elimination of trifluoromethanesulfinate to regenerate the cyanated heteroaromatic ring...
August 23, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28821329/cardiac-progenitor-cell-recruitment-drives-fetal-cardiac-regeneration-by-enhanced-angiogenesis
#8
Carlos Zgheib, Maggie M Hodges, Myron W Allukian, Junwang Xu, Kara L Spiller, Joseph H Gorman, Robert C Gorman, Kenneth W Liechty
BACKGROUND: In contrast to adults, the fetal response to myocardial infarction (MI) is regenerative, requiring the recruitment of cardiac progenitor cells to replace infarcted myocardium. Macrophage contribution to tissue repair depends on their phenotype: M1 are proinflammatory and initiate angiogenesis; M2a are profibrotic and contribute to blood vessels maturation; and M2c are proremodeling and proangiogenesis. The goal of the present study was to expand on this work by examining cardiac progenitor cells recruitment, and the role of macrophages in promoting angiogenesis and cardiac regeneration in the fetal heart after MI...
August 16, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28812649/decreased-male-reproductive-success-in-association-with-mitochondrial-dysfunction
#9
Mika H Martikainen, John P Grady, Yi Shiau Ng, Charlotte L Alston, Grainne S Gorman, Robert W Taylor, Robert McFarland, Doug M Turnbull
The reproductive success of men with mitochondrial disease is to date unreported. We compared the age- and era-adjusted reproductive success of 94 British male patients with mitochondrial disease to that of the UK general male population. The reproductive success of men with mitochondrial disease was 65% of that in the general population (95% confidence interval: 53%; 79%), and the effect magnitude was related to the disease severity. This contrasts with the two previous studies finding that the reproductive success of women with mitochondrial DNA disease is not impaired...
October 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28731789/age-and-cancer-treatment-are-related-to-receiving-treatment-summaries-and-survivorship-care-plans-in-female-young-adult-cancer-survivors
#10
Ksenya Shliakhtsitsava, Sally A D Romero, Brian W Whitcomb, Jessica R Gorman, Samantha Roberts, H Irene Su
The study determined factors associated with patient-reported receipt of survivorship care plans and/or treatment summaries (SCP/TS). Two hundred forty female young adult cancer survivors ages 18-44 completed a web-based survey that included self-report on receiving SCP/TS. Mean age was 32.8 (standard deviation 5.8) years; 20% were diagnosed with cancer at age <21. Only 47% reported receipt of SCP/TS. Age <21 at diagnosis (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.0-3.9), chemotherapy (OR 2...
July 21, 2017: Journal of Adolescent and Young Adult Oncology
https://www.readbyqxmd.com/read/28728784/mitral-annuloplasty-ring-suture-forces-impact-of-surgeon-ring-and-use-conditions
#11
Eric L Pierce, Charles H Bloodworth, Andrew W Siefert, Thomas F Easley, Tetsushi Takayama, Tomonori Kawamura, Robert C Gorman, Joseph H Gorman, Ajit P Yoganathan
OBJECTIVE: The study objective was to quantify the effect of ring type, ring-annulus sizing, suture position, and surgeon on the forces required to tie down and constrain a mitral annuloplasty ring to a beating heart. METHODS: Physio (Edwards Lifesciences, Irvine, Calif) or Profile 3D (Medtronic, Dublin, Ireland) annuloplasty rings were instrumented with suture force transducers and implanted in ovine subjects (N = 23). Tie-down forces and cyclic contractile forces were recorded and analyzed at 10 suture positions and at 3 levels of increasing peak left ventricular pressure...
June 21, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28666979/predicting-the-response-to-ctla-4-blockade-by-longitudinal-noninvasive-monitoring-of-cd8-t-cells
#12
Mohammad Rashidian, Jessica R Ingram, Michael Dougan, Anushka Dongre, Katherine A Whang, Camille LeGall, Juan J Cragnolini, Brian Bierie, Monica Gostissa, James Gorman, Gijsbert M Grotenbreg, Atul Bhan, Robert A Weinberg, Hidde L Ploegh
Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non-small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno-positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy. We used (89)Zr-labeled PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratumoral CD8(+) T cells in the immunotherapy-susceptible B16 melanoma model in response to checkpoint blockade...
August 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28514685/virus-like-particles-identify-an-hiv-v1v2-apex-binding-neutralizing-antibody-that-lacks-a-protruding-loop
#13
Evan M Cale, Jason Gorman, Nathan A Radakovich, Ema T Crooks, Keiko Osawa, Tommy Tong, Jiaqi Li, Raju Nagarajan, Gabriel Ozorowski, David R Ambrozak, Mangai Asokan, Robert T Bailer, Anthony K Bennici, Xuejun Chen, Nicole A Doria-Rose, Aliaksandr Druz, Yu Feng, M Gordon Joyce, Mark K Louder, Sijy O'Dell, Courtney Oliver, Marie Pancera, Mark Connors, Thomas J Hope, Thomas B Kepler, Richard T Wyatt, Andrew B Ward, Ivelin S Georgiev, Peter D Kwong, John R Mascola, James M Binley
Most HIV-1-specific neutralizing antibodies isolated to date exhibit unusual characteristics that complicate their elicitation. Neutralizing antibodies that target the V1V2 apex of the HIV-1 envelope (Env) trimer feature unusually long protruding loops, which enable them to penetrate the HIV-1 glycan shield. As antibodies with loops of requisite length are created through uncommon recombination events, an alternative mode of apex binding has been sought. Here, we isolated a lineage of Env apex-directed neutralizing antibodies, N90-VRC38...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28429161/on-the-in-vivo-function-of-the-mitral-heart-valve-leaflet-insights-into-tissue-interstitial-cell-biomechanical-coupling
#14
Chung-Hao Lee, Will Zhang, Kristen Feaver, Robert C Gorman, Joseph H Gorman, Michael S Sacks
There continues to be a critical need for developing data-informed computational modeling techniques that enable systematic evaluations of mitral valve (MV) function. This is important for a better understanding of MV organ-level biomechanical performance, in vivo functional tissue stresses, and the biosynthetic responses of MV interstitial cells (MVICs) in the normal, pathophysiological, and surgically repaired states. In the present study, we utilized extant ovine MV population-averaged 3D fiducial marker data to quantify the MV anterior leaflet (MVAL) deformations in various kinematic states...
April 20, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28395030/clinical-features-molecular-heterogeneity-and-prognostic-implications-in-yars2-related-mitochondrial-myopathy
#15
Ewen W Sommerville, Yi Shiau Ng, Charlotte L Alston, Cristina Dallabona, Micol Gilberti, Langping He, Charlotte Knowles, Sophie L Chin, Andrew M Schaefer, Gavin Falkous, David Murdoch, Cheryl Longman, Marianne de Visser, Laurence A Bindoff, John M Rawles, John C S Dean, Richard K Petty, Maria E Farrugia, Tobias B Haack, Holger Prokisch, Robert McFarland, Douglass M Turnbull, Claudia Donnini, Robert W Taylor, Gráinne S Gorman
Importance: YARS2 mutations have been associated with a clinical triad of myopathy, lactic acidosis, and sideroblastic anemia in predominantly Middle Eastern populations. However, the identification of new patients expands the clinical and molecular spectrum of mitochondrial disorders. Objectives: To review the clinical, molecular, and genetic features of YARS2-related mitochondrial disease and to demonstrate a new Scottish founder variant. Design, Setting, and Participants: An observational case series study was conducted at a national diagnostic center for mitochondrial disease in Newcastle upon Tyne, England, and review of cases published in the literature...
June 1, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28347308/erratum-to-assessment-of-myocardial-injury-after-reperfused-infarction-by-t1%C3%AF-cardiovascular-magnetic-resonance
#16
Rutger H Stoffers, Marie Madden, Mohammed Shahid, Francisco Contijoch, Joseph Solomon, James J Pilla, Joseph H Gorman, Robert C Gorman, Walter R T Witschey
No abstract text is available yet for this article.
March 27, 2017: Journal of Cardiovascular Magnetic Resonance
https://www.readbyqxmd.com/read/28290481/identification-of-elongated-primary-cilia-with-impaired-mechanotransduction-in-idiopathic-scoliosis-patients
#17
Niaz Oliazadeh, Kristen F Gorman, Robert Eveleigh, Guillaume Bourque, Alain Moreau
The primary cilium is an outward projecting antenna-like organelle with an important role in bone mechanotransduction. The capacity to sense mechanical stimuli can affect important cellular and molecular aspects of bone tissue. Idiopathic scoliosis (IS) is a complex pediatric disease of unknown cause, defined by abnormal spinal curvatures. We demonstrate significant elongation of primary cilia in IS patient bone cells. In response to mechanical stimulation, these IS cells differentially express osteogenic factors, mechanosensitive genes, and signaling genes...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28274519/regional-heterogeneity-in-the-mitral-valve%C3%A2-apparatus-in-patients-with-ischemic%C3%A2-mitral-regurgitation
#18
Feroze Mahmood, Ziyad O Knio, Lu Yeh, Rabia Amir, Robina Matyal, Azad Mashari, Robert C Gorman, Joseph H Gorman, Kamal R Khabbaz
BACKGROUND: Apical displacement of the coaptation point of the mitral valve (MV) in response to ischemic mitral regurgitation (IMR) represents remodeling of the MV apparatus. Whereas it implies chronicity, it lacks specificity in discriminating normal from a significantly remodeled MV apparatus. Regional aspects of MV remodeling have shown superior value over global remodeling in predicting recurrence after MV repair for IMR. Quite possibly, presence of specific regional changes in MV geometry that are unique to chronic IMR patients could also be used to diagnose the presence and track progression of remodeling...
April 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28265843/validity-of-self-reported-fertility-threatening-cancer-treatments-in-female-young-adult-cancer-survivors
#19
Samantha C Roberts, Amber Knight, Brian W Whitcomb, Jessica R Gorman, Andrew C Dietz, H Irene Su
PURPOSE: Detailed cancer treatment information is important to fertility and pregnancy care of female young adult cancer survivors. Accuracy of self-report of treatments that impact fertility and pregnancy is unknown. This study assessed agreement between self-report and medical records on receipt of fertility-threatening treatments. METHODS: A national cohort study of female young adult cancer survivors reported cancer treatments via Web-based questionnaires. Primary cancer treatment records were abstracted...
August 2017: Journal of Cancer Survivorship: Research and Practice
https://www.readbyqxmd.com/read/28196494/assessment-of-myocardial-injury-after-reperfused-infarction-by-t1%C3%AF-cardiovascular-magnetic-resonance
#20
Rutger H Stoffers, Marie Madden, Mohammed Shahid, Francisco Contijoch, Joseph Solomon, James J Pilla, Joseph H Gorman, Robert C Gorman, Walter R T Witschey
BACKGROUND: The evolution of T1ρ and of other endogenous contrast methods (T2, T1) in the first month after reperfused myocardial infarction (MI) is uncertain. We conducted a study of reperfused MI in pigs to serially monitor T1ρ, T2 and T1 relaxation, scar size and transmurality at 1 and 4 weeks post-MI. METHODS: Ten Yorkshire swine underwent 90 min of occlusion of the circumflex artery and reperfusion. T1ρ, T2 and native T1 maps and late gadolinium enhanced (LGE) cardiovascular magnetic resonance (CMR) data were collected at 1 week (n = 10) and 4 weeks (n = 5)...
February 15, 2017: Journal of Cardiovascular Magnetic Resonance
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