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Petra D Cravens, Rehana Z Hussain, William A Miller-Little, Li-Hong Ben, Benjamin M Segal, Emily Herndon, Olaf Stüve
BACKGROUND: Interleukin (IL)-12 and IL-23 are heterodimers that share the p40 subunit, and both cytokines are critical in the differentiation of T helper (Th)1 and Th17 cells, respectively. Th1 and Th17 effector cells have been implicated in the pathogenesis of experimental autoimmune encephalitis (EAE), an animal model of the human central nervous system (CNS) autoimmune demyelinating disorder multiple sclerosis (MS). However, ustekinumab, a monoclonal antibody (mAb) against p40 failed to show efficacy over placebo in a phase II clinical trial in patients with MS...
2016: PloS One
Emma Otta, Eloisa de S Fernandes, Tiziana G Acquaviva, Tania K Lucci, Leda C Kiehl, Marco A C Varella, Nancy L Segal, Jaroslava V Valentova
The present study investigates the twinning rates in the city of São Paulo, Brazil, during the years 2003-2014. The data were drawn from the Brazilian Health Department database of Sistema de Informações de Nascidos Vivos de São Paulo-SINASC (Live Births Information System of São Paulo). In general, more information is available on the incidence of twinning in developed countries than in developing ones. A total of 24,589 twin deliveries and 736 multiple deliveries were registered in 140 hospitals of São Paulo out of a total of 2,056,016 deliveries during the studied time period...
October 25, 2016: Twin Research and Human Genetics: the Official Journal of the International Society for Twin Studies
J Bradley Segal
Certain genes and neurobiology ('neurogenetics') may predispose some people to violent behavior. Increasingly, defendants introduce neurogenetic evidence as a mitigating factor during criminal sentencing. Identifying the cause of a criminal act, biological or otherwise, does not necessarily preclude moral or legal liability. However, valid scientific evidence of an inherited proclivity sometimes should be considered when evaluating whether a defendant is less morally culpable for a crime and perhaps less deserving of punishment...
April 2016: Journal of Law and the Biosciences
Jingwen Tan, Shuiqing Liu, Jodi B Segal, G Caleb Alexander, Mara McAdams-DeMarco
BACKGROUND: Patients with end stage renal disease (ESRD), including stage 5 chronic kidney disease (CKD), hemodialysis (HD) and peritoneal dialysis (PD), are at high risk for stroke-related morbidity, mortality and bleeding. The overall risk/benefit balance of warfarin treatment among patients with ESRD and AF remains unclear. METHODS: We systematically reviewed the associations of warfarin use and stroke outcome, bleeding outcome or mortality in patients with ESRD and AF...
October 21, 2016: BMC Nephrology
Boris Redko, Helena Tuchinsky, Tamar Segal, Dror Tobi, Galia Luboshits, Osnat Ashur-Fabian, Albert Pinhasov, Gabi Gerlitz, Gary Gellerman
The newly discovered short (9 amino acid) non-RGD S-S bridged cyclic peptide ALOS-4 (H-cycl(Cys-Ser-Ser-Ala-Gly-Ser-Leu-Phe-Cys)-OH), which binds to integrin αvβ3 is investigated as peptide carrier for targeted drug delivery against human metastatic melanoma. ALOS4 binds specifically the αvβ3 overexpressing human metastatic melanoma WM-266-4 cell line both in vitro and in ex vivo assays. Coupling ALOS4 to the topoisomerase I inhibitor Camptothecin (ALOS4-CPT) increases the cytotoxicity of CPT against human metastatic melanoma cells while reduces dramatically the cytotoxicity against non-cancerous cells as measured by the levels of γH2A...
October 19, 2016: Oncotarget
Lauren Segal, Moshe Ben-Shoshan, Reza Alizadehfar, Marie-Noël Primeau, Yuka Asai, Katie R Killorn, Edmond Chan, Stephen Cheuk, Greg Shand, Yvan St-Pierre, Laurie Harada, Ann Clarke
No abstract text is available yet for this article.
October 17, 2016: Journal of Allergy and Clinical Immunology in Practice
Moran Frenkel-Pinter, Sharon Tal, Roni Scherzer-Attali, Malak Abu-Hussien, Idan Alyagor, Tal Eisenbaum, Ehud Gazit, Daniel Segal
Alzheimer's disease (AD) is the most abundant tauopathy and is characterized by Aβ-derived plaques and tau-derived tangles, resulting from the unfolding of the corresponding monomeric subunits into ordered β-sheet oligomers and fibrils. Intervening in the toxic aggregation process is a promising therapeutic approach, but, to date, a disease-modifying therapy is neither available for AD nor for other tauopathies. Along these lines, we have previously demonstrated that a small naphthoquinone-tryptophan hybrid, termed NQTrp, is an effective modulator of tauopathy in vitro and in vivo...
October 20, 2016: Neuro-degenerative Diseases
András Kotschy, Zoltán Szlavik, James Murray, James Davidson, Ana Leticia Maragno, Gaëtane Le Toumelin-Braizat, Maïa Chanrion, Gemma L Kelly, Jia-Nan Gong, Donia M Moujalled, Alain Bruno, Márton Csekei, Attila Paczal, Zoltán B Szabo, Szabolcs Sipos, Gábor Radics, Agnes Proszenyak, Balázs Balint, Levente Ondi, Gábor Blasko, Alan Robertson, Allan Surgenor, Pawel Dokurno, Ijen Chen, Natalia Matassova, Julia Smith, Christopher Pedder, Christopher Graham, Aurélie Studeny, Gaëlle Lysiak-Auvity, Anne-Marie Girard, Fabienne Gravé, David Segal, Chris D Riffkin, Giovanna Pomilio, Laura C A Galbraith, Brandon J Aubrey, Margs S Brennan, Marco J Herold, Catherine Chang, Ghislaine Guasconi, Nicolas Cauquil, Fabien Melchiore, Nolwen Guigal-Stephan, Brian Lockhart, Frédéric Colland, John A Hickman, Andrew W Roberts, David C S Huang, Andrew H Wei, Andreas Strasser, Guillaume Lessene, Olivier Geneste
Avoidance of apoptosis is critical for the development and sustained growth of tumours. The pro-survival protein myeloid cell leukemia 1 (MCL1) is overexpressed in many cancers, but the development of small molecules targeting this protein that are amenable for clinical testing has been challenging. Here we describe S63845, a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. Our mechanistic studies demonstrate that S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway...
October 19, 2016: Nature
Leonie Segal, Claire Marsh, Rob Heyes
OBJECTIVES: We explored the real cost of training the workforce in a range of primary health care professions in Australia with a focus on the impact of retention to contribute to the debate on how best to achieve the optimal health workforce mix. METHODS: The cost to train an entry-level health professional across 12 disciplines was derived from university fees, payment for clinical placements and, where relevant, cost of internship, adjusted for student drop-out...
October 6, 2016: Journal of Health Services Research & Policy
Neil H Segal, Theodore F Logan, F Stephen Hodi, David F McDermott, Ignacio Melero, Omid Hamid, Henrik Schmidt, Caroline Robert, Vanna Chiarion-Sileni, Paolo A Ascierto, Michele Maio, Walter J Urba, Tara C Gangadhar, Satyendra Suryawanshi, Jaclyn Neely, Maria Jure-Kunkel, Suba Krishnan, Holbrook E Kohrt, Mario Sznol, Ronald Levy
PURPOSE: Urelumab is an agonist antibody to CD137 with potential application as an immuno-oncology therapeutic. Data were analyzed to assess safety, tolerability, and pharmacodynamic activity of urelumab, including the dose selected for ongoing development in patients with advanced solid tumors and lymphoma. PATIENTS AND METHODS: Three hundred and forty-six patients with advanced cancers who had progressed after standard treatment received at least one dose of urelumab in one of three dose-escalation, monotherapy studies...
October 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Jonathan David Tyzack, Peter A Hunt, Matthew D Segall
We describe methods for predicting Cytochrome P450 (CYP) metabolism incorporating both pathway-specific reactivity and isoform-specific accessibility considerations. Semi-empirical quantum mechanical (QM) simulations, parameterized using experimental data and ab initio calculations, estimate the reactivity of each potential site of metabolism in the context of the whole molecule. Ligand-based models, trained using high quality regioselectivity data, correct for orientation and steric effects of the different CYP isoform binding pockets...
October 18, 2016: Journal of Chemical Information and Modeling
Andrea G Segal, Dominic A Sisti
Several forms of mandated community treatment exist in the United States. One mechanism, assisted outpatient treatment (AOT), has become both more common and more controversial in recent years. The status of individuals committed to AOT remains unclear within regulatory guidelines aimed at protecting research participants. Should individuals on AOT be considered psychiatric inpatients, prisoners, community members, or something else? The authors argue that persons on AOT inhabit a gray area wherein they should be given some of the ethical protections afforded to involuntary inpatients and prisoners, but they should also enjoy freedoms as members of the community...
October 17, 2016: Psychiatric Services: a Journal of the American Psychiatric Association
David K Packham, Ian R Fraser, Peter G Kerr, Karen R Segal
BACKGROUND: Diabetic nephropathy is the most common cause of end stage renal failure. We assessed the safety, tolerability, and explored therapeutic effects of adult allogeneic bone-marrow derived mesenchymal precursor cells (MPC) in patients with moderate to severe diabetic nephropathy. METHODS: Multicenter, randomized, double-blind, dose-escalating, sequential, placebo-controlled trial assessing a single intravenous (IV) infusion of allogeneic MPC (United States adopted name: rexlemestrocel-L) 150×10(6) (n=10), 300×10(6) (n=10) or placebo (n=10) in adults with diabetic nephropathy with an estimated glomerular filtration rate (eGFR) 20-50ml/min/1...
September 17, 2016: EBioMedicine
Ana L Fernandez-Cruz, Ola Mohamed Ali, Gifty Asare, Morgan S Whyte, Ishan Walpola, Julia Segal, J Bruno Debruille
Some personal drives correspond to extraordinary social roles. Given that behavioral strategies associated with such drives may conflict with those associated with ordinary roles, they could cause behavioral disorganization. To test whether they do so independent of the factors responsible for full-blown schizotypy and schizophrenia, these drives were assessed in the general population. Two hundred and nine healthy volunteers were individually presented with hundreds of names of social roles in experimental psychology conditions...
2016: NPJ Schizophrenia
Eduard Korkotian, Menahem Segal
No abstract text is available yet for this article.
October 13, 2016: Channels
Mathilde Labbé, Katerina Nikolitch, Romeo Penheiro, Marilyn Segal, Karl J Looper, Nathan Herrmann, Steven Selchen, Soham Rej
No abstract text is available yet for this article.
September 2016: Canadian Geriatrics Journal: CGJ
Eric Segal, Helio Pedro, Karen Valdez-Gonzalez, Sarah Parisotto, Felicia Gliksman, Stephen Thompson, Jomard Sabri, Evan Fertig
BACKGROUND: When no chromosomal variations are identified, patients with suspected genetic etiologies can be tested using next-generation sequencing utilizing epilepsy panels. The primary objective of this study was to analyze the diagnostic yield of next-generation sequencing epilepsy panels in medication-resistant epilepsy subjects with non-clinically significant comparative genomic hybridization microarray results. METHODS: We completed a single-center retrospective review of the diagnostic yield of next-generation sequencing epilepsy panels in medication-resistant epilepsy subjects aged 18 years or less who had non-clinically significant comparative genomic hybridization microarray results from January 2011 to December 2014...
July 1, 2016: Pediatric Neurology
Adam P Levine, Anthony W Segal
This review is devoted to a consideration of the way in which the NADPH oxidase of neutrophils, NOX2, functions to enable the efficient killing of bacteria and fungi. It includes a critical examination of the current dogma that its primary purpose is the generation of hydrogen peroxide as substrate for myeloperoxidase-catalyzed generation of hypochlorite. Instead, it is demonstrated that NADPH oxidase functions to optimize the ionic and pH conditions within the vacuole for the solubilization and optimal activity of the proteins released into this compartment from the cytoplasmic granules, which kill and digest the microbes...
August 2016: Microbiology Spectrum
Kevin M Fain, Carlos Castillo-Salgado, David D Dore, Jodi B Segal, Andrew R Zullo, G Caleb Alexander
OBJECTIVE: We quantified transdermal fentanyl prescribing in elderly nursing home residents without prior opioid use or persistent pain, and the association of individual and facility traits with opioid-naïve prescribing. DESIGN: Cross-sectional study. SETTING: Linked Minimum Data Set (MDS) assessments; Online Survey, Certification and Reporting (OSCAR) records; and Medicare Part D claims. PARTICIPANTS: From a cross-section of all long-stay US nursing home residents in 2008 with an MDS assessment and Medicare Part D enrollment, we identified individuals (≥65 years old) who initiated transdermal fentanyl, excluding those with Alzheimer disease, severe cognitive impairment, cancer, or receipt of hospice care...
October 6, 2016: Journal of the American Medical Directors Association
Zindel V Segal, Le-Anh Dinh-Williams
No abstract text is available yet for this article.
October 2016: World Psychiatry: Official Journal of the World Psychiatric Association (WPA)
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