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https://www.readbyqxmd.com/read/28819026/therapeutic-targeting-of-the-cbp-p300-bromodomain-blocks%C3%A2-the-growth-of-castration-resistant-prostate-cancer
#1
Lingyan Jin, Jesse Garcia, Emily Chan, Cecile de la Cruz, Ehud Segal, Mark Merchant, Samir Kharbanda, Ryan Raisner, Peter M Haverty, Zora Modrusan, Justin Ly, Edna Choo, Susan Kaufman, Maureen H Beresini, F Anthony Romero, Steven Magnuson, Karen E Gascoigne
Resistance invariably develops to anti-androgen therapies used to treat newly diagnosed prostate cancers, but effective treatments for castration-resistant disease remain elusive. Here we report that the transcriptional co-activator CBP/p300 is required to maintain the growth of castration-resistant prostate cancer. To exploit this vulnerability, we developed a novel small-molecule inhibitor of the CBP/p300 bromodomain that blocks prostate cancer growth in vitro and in vivo. Molecular dissection of the consequences of drug treatment revealed a critical role for CBP/p300 in histone acetylation required for the transcriptional activity of the androgen receptor and its target gene expression...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28817835/history-of-thyroid-disease-and-survival-of-ovarian-cancer-patients-results-from-the-ovarian-cancer-association-consortium-a-brief-report
#2
Albina N Minlikeeva, Jo L Freudenheim, Rikki A Cannioto, Kevin H Eng, J Brian Szender, Paul Mayor, John L Etter, Daniel W Cramer, Brenda Diergaarde, Jennifer A Doherty, Thilo Dörk, Robert Edwards, Anna deFazio, Grace Friel, Marc T Goodman, Peter Hillemanns, Estrid Høgdall, Allan Jensen, Susan J Jordan, Beth Y Karlan, Susanne K Kjær, Rüdiger Klapdor, Keitaro Matsuo, Mika Mizuno, Christina M Nagle, Kunle Odunsi, Lisa Paddock, Mary Anne Rossing, Joellen M Schildkraut, Barbara Schmalfeldt, Brahm H Segal, Kristen Starbuck, Kathryn L Terry, Penelope M Webb, Emese Zsiros, Roberta B Ness, Francesmary Modugno, Elisa V Bandera, Jenny Chang-Claude, Kirsten B Moysich
BACKGROUND: Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited. METHODS: We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using multivariate Cox proportional hazards models, we estimated associations between hyper- and hypothyroidism and medications prescribed for these conditions with 5-year all-cause survival among women diagnosed with invasive ovarian cancer...
August 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28815147/triangulating-methodologies-from-software-medicine-and-human-factors-industries-to-measure-usability-and-clinical-efficacy-of-medication-data-visualization-in-an-electronic-health-record-system
#3
Bora Chang, Manoj Kanagaraj, Ben Neely, Noa Segall, Erich Huang
Within the last decade, use of Electronic Health Record (EHR) systems has become intimately integrated into healthcare practice in the United States. However, large gaps remain in the study of clinical usability and require rigorous and innovative approaches for testing usability principles. In this study, validated tools from the core functions that EHRs serve-software, medicine and human factors-were combined to holistically understand and objectively measure usability of medication data displays. The first phase of this study included 132 medical trainee participants who were randomized to one of two simulated EHR environments with either a medication list or a medication timeline visualization...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28807909/development-and-use-of-personalized-bacteriophage-based-therapeutic-cocktails-to-treat-a-patient-with-a-disseminated-resistant-acinetobacter-baumannii-infection
#4
Robert T Schooley, Biswajit Biswas, Jason J Gill, Adriana Hernandez-Morales, Jacob Lancaster, Lauren Lessor, Jeremy J Barr, Sharon L Reed, Forest Rohwer, Sean Benler, Anca M Segall, Randy Taplitz, Davey M Smith, Kim Kerr, Monika Kumaraswamy, Victor Nizet, Leo Lin, Melanie D McCauley, Steffanie A Strathdee, Constance A Benson, Robert K Pope, Brian M Leroux, Andrew C Picel, Alfred J Mateczun, Katherine E Cilwa, James M Regeimbal, Luis A Estrella, David M Wolfe, Matthew S Henry, Javier Quinones, Scott Salka, Kimberly A Bishop-Lilly, Ry Young, Theron Hamilton
Widespread antibiotic use in clinical medicine and the livestock industry has contributed to the global spread of multidrug-resistant (MDR) bacterial pathogens, including Acinetobacter baumannii We report on a method used to produce a personalized bacteriophage-based therapeutic treatment for a 68-year old diabetic patient with necrotizing pancreatitis complicated by a MDR A. baumannii infection. Despite multiple antibiotic courses and efforts at percutaneous drainage of a pancreatic pseudocyst, the patient deteriorated over a four-month period...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28805874/microfluidic-modeling-of-the-biophysical-microenvironment-in-tumor-cell-invasion
#5
Yu Ling Huang, Jeffrey E Segall, Mingming Wu
Tumor cell invasion, whether penetrating through the extracellular matrix (ECM) or crossing a vascular endothelium, is a critical step in the cancer metastatic cascade. Along the way from a primary tumor to a distant metastatic site, tumor cells interact actively with the microenvironment either via biomechanical (e. g. ECM stiffness) or biochemical (e.g. secreted cytokines) signals. Increasingly, it is recognized that the tumor microenvironment (TME) is a critical player in tumor cell invasion. A main challenge for the mechanistic understanding of tumor cell-TME interactions comes from the complexity of the TME, which consists of extracellular matrices, fluid flows, cytokine gradients and other cell types...
August 14, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28804763/effects-of-chest-physical-therapy-in-patients-with-non-tuberculous-mycobacteria
#6
Ashwin Basavaraj, Leopoldo Segal, Jonathan Samuels, Jeremy Feintuch, Joshua Feintuch, Kevin Alter, Daniella Moffson, Adrienne Scott, Doreen Addrizzo-Harris, Mengling Liu, David Kamelhar
Antibiotic therapy against non-tuberculous mycobacteria (NTM) is prolonged and can be associated with toxicity. We sought to evaluate whether chest physical therapy (PT) was associated with clinical improvement in patients with NTM not receiving anti-mycobacterial pharmacotherapy. A retrospective review of 77 subjects that were followed from June 2006 to September 2014 was performed. Baseline time point was defined as the first positive sputum culture for NTM; symptoms, pulmonary function, and radiology reports were studied...
2017: International Journal of Respiratory and Pulmonary Medicine
https://www.readbyqxmd.com/read/28800887/evaluation-of-the-boussignac-cardiac-arrest-device-b-card-during-cardiopulmonary-resuscitation-in-an-animal-model
#7
Johanna C Moore, Lionel Lamhaut, Alice Hutin, Kenneth W Dodd, Aaron E Robinson, Michael C Lick, Bayert J Salverda, Mason B Hinke, Jose Larabere, Guillaume Debaty, Nicolas Segal
AIM OF THE STUDY: The purpose of this study was to examine continuous oxygen insufflation (COI) in a swine model of cardiac arrest. The primary hypothesis was COI during standard CPR (S-CPR) should result in higher intrathoracic pressure (ITP) during chest compression and lower ITP during decompression versus S-CPR alone. These changes with COI were hypothesized to improve hemodynamics. The second hypothesis was that changes in ITP with S-CPR+COI would result in superior hemodynamics compared with active compression decompression (ACD) + impedance threshold device (ITD) CPR, as this method primarily lowers ITP during chest decompression...
August 9, 2017: Resuscitation
https://www.readbyqxmd.com/read/28797687/the-role-of-nitric-oxide-in-spectral-information-processing-in-the-distal-turtle-retina
#8
Elena Segal, Ido Perlman
Chromaticity type horizontal cells (C-type HCs) are the first retinal neurons exhibiting spectral information processing in cold-blooded vertebrates. The simple input of hyperpolarizing responses of cone photoreceptors is transformed in the C-type HCs into spectral opponent output. Nitric oxide (NO), a known background neuromodulator in the distal retina, was tested here for its effects upon spectral information processing by C-type HCs in the retina of turtle. Photoresponses were intracellularly recorded from C-type HCs, using light stimuli of different wavelength, applied over backgrounds of different wavelengths, and changing retinal NO level...
August 7, 2017: Vision Research
https://www.readbyqxmd.com/read/28790113/neurotensin-receptor-1-antagonist-sr48692-improves-response-to-carboplatin-by-enhancing-apoptosis-and-inhibiting-drug-efflux-in-ovarian-cancer
#9
Jin Liu, Mikael Agopiantz, Joel Poupon, Zherui Wu, Pierre-Alexandre Just, Bruno Borghese, Evelyne Ségal-Bendirdjian, Guillaume Gauchotte, Anne Gompel, Patricia Forgez
PURPOSE: The high affinity receptor 1 (NTSR1) and its agonist, neurotensin (NTS), is correlated with tumor cell aggressiveness in most solid tumors. As chemo-resistance and tumor aggressiveness are often related; we decided to study the role of the NTSR1 complex within platinum-based chemotherapy responses. In an ovarian model, we studied carboplatin because it is the main standard of care for ovarian cancer (OC). EXPERIMENTAL DESIGN: Experimental tumors and in vitro studied were performed using SKOV3 and A2780 cells treated with carboplatin, with or without a very specific NTSR1 antagonist, SR48692...
August 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28789991/potential-impact-of-a-prehospital-redirection-system-for-refractory-cardiac-arrest
#10
Alexis Cournoyer, Éric Notebaert, Luc de Montigny, Sylvie Cossette, Luc Londei-Leduc, Massimiliano Iseppon, Yoan Lamarche, Catalina Sokoloff, Judy Morris, Éric Piette, Raoul Daoust, Jean-Marc Chauny, Dave Ross, Dominique Lafrance, Eli Segal, Yiorgos Alexandros Cavayas, Jean Paquet, André Denault
AIM: A change in prehospital redirection practice could potentially increase the proportion of E-CPR eligible patients with out-of-hospital cardiac arrest (OHCA) transported to extracorporeal cardiopulmonary resuscitation (E-CPR) capable centers. The objective of this study was to quantify this potential increase of E-CPR candidates transported to E-CPR capable centers. METHODS: Adults with non-traumatic OHCA refractory to 15min of resuscitation were selected from a registry of adult OHCA collected between 2010 and 2015 in Montreal, Canada...
August 5, 2017: Resuscitation
https://www.readbyqxmd.com/read/28789550/the-anderson-impurity-model-out-of-equilibrium-assessing-the-accuracy-of-simulation-techniques-with-an-exact-current-occupation-relation
#11
Bijay Kumar Agarwalla, Dvira Segal
We study the interacting, symmetrically coupled single impurity Anderson model. By employing the nonequilibrium Green's function formalism, we reach an exact relationship between the steady-state charge current flowing through the impurity (dot) and its occupation. We argue that the steady-state current-occupation relation can be used to assess the consistency of simulation techniques and identify spurious transport phenomena. We test this relation in two different model variants: First, we study the Anderson-Holstein model in the strong electron-vibration coupling limit using the polaronic quantum master equation method...
August 7, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28770702/prevalence-of-anti-dfs70-antibodies-in-patients-with-and-without-systemic-autoimmune-rheumatic-diseases
#12
Ora Shovman, Boris Gilburd, Chen Chayat, Howard Amital, Pnina Langevitz, Abdulla Watad, Adi Guy, Dolores Perez, Danielle Azoulay, Miri Blank, Yael Segal, Chelsea Bentow, Michael Mahler, Yehuda Shoenfeld
OBJECTIVES: Autoantibodies to the dense fine speckled 70 (DFS70) antigen are common among antinuclear antibodies (ANA) positive healthy individuals (HI). We assessed the prevalence of anti-DFS70 antibodies in patients with and without ANA-associated rheumatic diseases (AARDs) by two methods: chemiluminescent immunoassay (CIA) and an indirect immunofluorescence (IIF) assay based on immunoadsorption for DFS70. METHODS: Fifty-one ANA-positive sera samples from patients with confirmed clinical diagnosis of AARD, 92 samples from HI and 85 samples submitted to a reference laboratory for routine ANA testing were evaluated for the presence of anti-DFS70 antibodies...
July 27, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28768804/synergistic-action-of-the-mcl-1-inhibitor-s63845-with-current-therapies-in-preclinical-models-of-triple-negative-and-her2-amplified-breast-cancer
#13
Delphine Merino, James R Whittle, François Vaillant, Antonin Serrano, Jia-Nan Gong, Goknur Giner, Ana Leticia Maragno, Maïa Chanrion, Emilie Schneider, Bhupinder Pal, Xiang Li, Grant Dewson, Julius Gräsel, Kevin Liu, Najoua Lalaoui, David Segal, Marco J Herold, David C S Huang, Gordon K Smyth, Olivier Geneste, Guillaume Lessene, Jane E Visvader, Geoffrey J Lindeman
The development of BH3 mimetics, which antagonize prosurvival proteins of the BCL-2 family, represents a potential breakthrough in cancer therapy. Targeting the prosurvival member MCL-1 has been an area of intense interest because it is frequently deregulated in cancer. In breast cancer, MCL-1 is often amplified, and high expression predicts poor patient outcome. We tested the MCL-1 inhibitor S63845 in breast cancer cell lines and patient-derived xenografts with high expression of MCL-1. S63845 displayed synergistic activity with docetaxel in triple-negative breast cancer and with trastuzumab or lapatinib in HER2-amplified breast cancer...
August 2, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28766077/nancy-segal-twin-mythconceptions-false-beliefs-fables-and-facts-about-twins-academic-press-2017-334-pages-ebook-isbn-9780128039953-paperback-isbn-9780128039946
#14
https://www.readbyqxmd.com/read/28765125/sepsis-and-critical-illness-research-center-investigators-protocols-and-standard-operating-procedures-for-a-prospective-cohort-study-of-sepsis-in-critically-ill-surgical-patients
#15
Tyler J Loftus, Juan C Mira, Tezcan Ozrazgat-Baslanti, Gabriella L Ghita, Zhongkai Wang, Julie A Stortz, Babette A Brumback, Azra Bihorac, Mark S Segal, Stephen D Anton, Christiaan Leeuwenburgh, Alicia M Mohr, Philip A Efron, Lyle L Moldawer, Frederick A Moore, Scott C Brakenridge
INTRODUCTION: Sepsis is a common, costly and morbid cause of critical illness in trauma and surgical patients. Ongoing advances in sepsis resuscitation and critical care support strategies have led to improved in-hospital mortality. However, these patients now survive to enter state of chronic critical illness (CCI), persistent low-grade organ dysfunction and poor long-term outcomes driven by the persistent inflammation, immunosuppression and catabolism syndrome (PICS). The Sepsis and Critical Illness Research Center (SCIRC) was created to provide a platform by which the prevalence and pathogenesis of CCI and PICS may be understood at a mechanistic level across multiple medical disciplines, leading to the development of novel management strategies and targeted therapies...
August 1, 2017: BMJ Open
https://www.readbyqxmd.com/read/28764876/determinants-of-potentially-inappropriate-medication-use-in-long-term-and-acute-care-settings-a-systematic-review
#16
REVIEW
Stephanie K Nothelle, Ritu Sharma, Allison H Oakes, Madeline Jackson, Jodi B Segal
BACKGROUND: Potentially inappropriate medications (PIMs) are widely used in institutionalized older adults, yet the key determinants that drive their use are incompletely characterized. METHODS: We systematically searched published literature within MEDLINE and Embase from January 1998 to March 2017. We searched for studies conducted in the United States that described determinants of PIM use in adults ≥60 years of age in a nursing home or residential care facility, in the emergency department (ED), or in the hospital...
July 29, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/28760100/the-utility-of-outpatient-commitment-i-a-need-for-treatment-and-a-least-restrictive-alternative-to-psychiatric-hospitalization
#17
Steven P Segal, Stephania L Hayes, Lachlan Rimes
OBJECTIVES: This study examined whether psychiatric patients assigned to community treatment orders (CTOs), outpatient commitment in Victoria, Australia, have a greater need for treatment to protect their health and safety than patients not assigned to CTOs. It also considered whether such treatment is provided in a least restrictive manner-that is, in a way that contributes to reduced use of psychiatric hospitalization. METHODS: The sample included 11,424 patients first placed on a CTO between 2000 and 2010, and 16,161 patients not placed on a CTO...
August 1, 2017: Psychiatric Services: a Journal of the American Psychiatric Association
https://www.readbyqxmd.com/read/28760099/the-utility-of-outpatient-commitment-ii-mortality-risk-and-protecting-health-safety-and-quality-of-life
#18
Steven P Segal, Stephania L Hayes, Lachlan Rimes
OBJECTIVE: This study assessed the contribution of a form of outpatient commitment-community treatment orders (CTOs)-to mortality risk and quality of life of patients with severe mental illness. METHODS: Data (2000--2012) were obtained from the Australian National Death Index, Victoria Department of Health, Victoria police records, and National Outcomes and CaseMix Collection quality-of-life records for patients in the Victorian Psychiatric Case Register/RAPID with a history of psychiatric hospitalization: CTO cohort, N=11,424; non-CTO cohort, N=16,161...
August 1, 2017: Psychiatric Services: a Journal of the American Psychiatric Association
https://www.readbyqxmd.com/read/28752539/disparities-in-treatment-of-older-adults-with-suicide-risk-in-the-emergency-department
#19
Sarah A Arias, Edwin D Boudreaux, Daniel L Segal, Ivan Miller, Carlos A Camargo, Marian E Betz
BACKGROUND/OBJECTIVE: We described characteristics and treatment received for older (≥60 years) vs younger (<60 years) adult emergency department (ED) patients with suicide risk. DESIGN: Retrospective chart review. SETTING: An ED with universal screening for suicide risk. PARTICIPANTS: Eligible charts included a random sample of adults (≥18 years) who screened positive for suicidal ideation (SI) in past 2 weeks and/or a suicide attempt (SA) within the past 6 months...
July 28, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28751770/enhancing-venetoclax-activity-in-acute-myeloid-leukemia-by-co-targeting-mcl1
#20
T-C Teh, N-Yn Nguyen, D M Moujalled, D Segal, G Pomilio, S Rijal, A Jabbour, K Cummins, K Lackovic, P Blombery, E Thompson, P G Ekert, G Lessene, S P Glaser, D C S Huang, A W Roberts, M A Guthridge, A H Wei
Targeted therapies are frequently combined with standard cytotoxic drugs to enhance clinical response. Targeting the BCL-2 family of proteins is an attractive option to combat chemoresistance in leukemia. Pre-clinical and clinical studies indicate modest single-agent activity with selective BCL-2 inhibitors (e.g. venetoclax). We show that venetoclax synergizes with cytarabine and idarubicin to increase anti-leukemic efficacy in a TP53 dependent manner. Although TP53 deficiency impaired sensitivity to combined venetoclax and chemotherapy, higher-dose idarubicin was able to suppress MCL1 and induce cell death independently of TP53...
July 28, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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