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https://www.readbyqxmd.com/read/28651159/health-related-quality-of-life-results-from-the-phase-iii-checkmate-067-study
#1
Dirk Schadendorf, James Larkin, Jedd Wolchok, F Stephen Hodi, Vanna Chiarion-Sileni, Rene Gonzalez, Piotr Rutkowski, Jean-Jacques Grob, C Lance Cowey, Christopher Lao, John Wagstaff, Margaret K Callahan, Michael A Postow, Michael Smylie, Pier Francesco Ferrucci, Reinhard Dummer, Andrew Hill, Fiona Taylor, Javier Sabater, Dana Walker, Srividya Kotapati, Amy Abernethy, Georgina V Long
BACKGROUND: Nivolumab, a monoclonal antibody of immune checkpoint programmed death 1 on T cells (PD-1), combined with ipilimumab, an immune checkpoint cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, as combination therapy on the one hand and nivolumab as monotherapy on the other, have both demonstrated improved efficacy compared with ipilimumab alone in the CheckMate 067 study. However, the combination resulted in a higher frequency of grade 3/4 adverse events (AEs), which could result in diminished health-related quality of life (HRQoL)...
June 22, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28650638/identification-and-structure-activity-relationships-of-novel-compounds-that-potentiate-the-activities-of-antibiotics-in-escherichia-coli
#2
Keith M Haynes, Narges Abdali, Varsha Jhawar, Helen I Zgurskaya, Jerry M Parks, Adam T Green, Jerome Yves Baudry, Valentin V Rybenkov, Jeremy C Smith, John K Walker
In Gram-negative bacteria, efflux pumps are able to prevent effective cellular concentrations from being achieved for a number of antibiotics. Small molecule adjuvants that act as efflux pump inhibitors (EPIs) have the potential to reinvigorate existing antibiotics that are currently ineffective due to efflux mechanisms. Through a combination of rigorous experimental screening and in silico virtual screening we recently identified novel classes of EPIs that interact with the membrane fusion protein AcrA, a critical component of the AcrAB-TolC efflux pump in E...
June 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28649841/elucidating-the-mechanisms-driving-the-ageing-of-porous-hollow-ptni-c-nanoparticles-by-the-means-of-coads-stripping
#3
Tristan Asset, Raphael Chattot, Jakub Drnec, Pierre Bordet, Nathalie Job, Frédéric Maillard, Laetitia Dubau
The oxygen reduction reaction (ORR) activity of Pt-alloy electrocatalysts depends on (i) strain/ligand effects induced by the non-noble metal (3d transition metal or a rare-Earth ele-ment) alloyed to Pt, (ii) the orientation of the catalytic surfaces and (iii) the density of struc-tural defects (ex. vacancies, voids, interconnections). These structural defects influence the 'generalized' coordination number of Pt atoms, the Pt-alloy lattice parameter and thus the adsorption strength of the ORR intermediates (O*, OH*, OOH*)...
June 26, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28649780/therapeutic-efficacy-and-safety-of-oral-tranexamic-acid-and-that-of-tranexamic-acid-local-infiltration-with-microinjections-in-patients-with-melasma-a-comparative-study
#4
R Sharma, V K Mahajan, K S Mehta, P S Chauhan, R Rawat, T N Shiny
BACKGROUND: Tranexamic acid (TXA) has been used orally, intravenously, topically and intradermally (microinjection, microneedling) for treating melasma. However, the comparative efficacy of these different routes of administration remains underevaluated. AIM: To ascertain the comparative efficacy of different routes of administration of TXA. METHODS: In total, 100 consecutive patients with melasma (8 men, 92 women, age range 18-55 years) were randomly assigned to one of two groups comprising 50 patients each...
June 25, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28648953/synthesis-of-thiazole-linked-indolyl-3-glyoxylamide-derivatives-as-tubulin-polymerization-inhibitors
#5
Sravanthi Devi Guggilapu, Lalita Guntuku, T Srinivasa Reddy, Atulya Nagarsenkar, Dilep Kumar Sigalapalli, V G M Naidu, Suresh K Bhargava, Nagendra Babu Bathini
A series of thiazole linked indolyl-3-glyoxylamide derivatives were synthesized and evaluated for their in vitro cytotoxic activity against DU145 (prostate), PC-3 (prostate), A549 (lung) and HCT-15 (colon) cancer cell lines by employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized compounds, compound 13d displayed cytotoxicity of IC50 = 93 nM towards DU145 cancer cell line. The most active compound 13d was also tested on RWPE-1 cells and was found to be safe compared to the DU145 cells...
June 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28648855/decreasing-incidence-of-foot-ulcer-among-patients-with-type-1-and-type-2-diabetes-in-the-period-2001-2014
#6
A Rasmussen, T Almdal, A Anker Nielsen, K E Nielsen, M E Jørgensen, S Hangaard, V Siersma, P E Holstein
AIM: Diabetic foot ulcer (DFU) is a serious complication to diabetes. The aim was to study the incidence of first DFU among patients with type 1 (T1DM) and type 2 diabetes (T2DM), stratified according to etiology: neuropathic, neuro-ischemic or ischemic, over a period of 14years (2001-2014). METHODS: DFU incidence rates were calculated from electronic patient record data from patients with T1DM and complicated T2DM from a large specialized diabetes hospital with a multidisciplinary foot clinic in Denmark...
June 13, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28648699/prognostic-factors-and-outcomes-in-metastatic-uveal-melanoma-treated-with-programmed-cell-death-1-or-combined-pd-1-cytotoxic-t-lymphocyte-antigen-4-inhibition
#7
Markus V Heppt, Lucie Heinzerling, Katharina C Kähler, Andrea Forschner, Michael C Kirchberger, Carmen Loquai, Markus Meissner, Friedegund Meier, Patrick Terheyden, Beatrice Schell, Rudolf Herbst, Daniela Göppner, Felix Kiecker, David Rafei-Shamsabadi, Sebastian Haferkamp, Margit A Huber, Jochen Utikal, Mirjana Ziemer, Irmgard Bumeder, Christiane Pfeiffer, Susanne G Schäd, Christoph Schmid-Tannwald, Julia K Tietze, Thomas K Eigentler, Carola Berking
BACKGROUND: Uveal melanoma (UM) is an ocular malignancy with high potential for metastatic spread. In contrast to cutaneous melanoma, immunotherapy has not yet shown convincing efficacy in patients with UM. Combined immune checkpoint blockade with checkpoint programmed cell death-1 (PD-1) and checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibition has not been systematically assessed for UM to date. PATIENTS AND METHODS: Patients with metastatic UM treated with either PD-1 inhibitor monotherapy or combined PD-1 inhibitor and ipilimumab (an anti-CTLA-4 monoclonal antibody) were included from 20 German skin cancer centres...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28647593/features-of-emotional-and-social-behavioral-phenotypes-of-calsyntenin2-knockout-mice
#8
S V Ranneva, K S Pavlov, A V Gromova, T G Amstislavskaya, T V Lipina
Calsyntenin-2 (Clstn2) is the synaptic protein that belongs to the super family of cadherins, playing an important role in learning and memory. We recently reported that Clstn2 knockout mice (Clstn2-KO) have a deficit of GABAergic interneurons coupled with hyperactivity and deficient spatial memory. Given, that impaired functioning of GABA receptors is linked to several psychopathologies, including anxiety and autism, we sought to further characterize Clstn2-KO mice with respect to emotional and social behavior...
June 21, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28644774/cd33-splicing-polymorphism-determines-gemtuzumab-ozogamicin-response-in-de-novo-acute-myeloid-leukemia-report-from-randomized-phase-iii-children-s-oncology-group-trial-aaml0531
#9
Jatinder K Lamba, Lata Chauhan, Miyoung Shin, Michael R Loken, Jessica A Pollard, Yi-Cheng Wang, Rhonda E Ries, Richard Aplenc, Betsy A Hirsch, Susana C Raimondi, Roland B Walter, Irwin D Bernstein, Alan S Gamis, Todd A Alonzo, Soheil Meshinchi
Purpose Gemtuzumab ozogamicin (GO), a CD33-targeted immunoconjugate, is a re-emerging therapy for acute myeloid leukemia (AML). CD33 single nucleotide polymorphism rs12459419 C>T in the splice enhancer region regulates the expression of an alternatively spliced CD33 isoform lacking exon2 (D2-CD33), thus eliminating the CD33 IgV domain, which is the antibody-binding site for GO, as well as diagnostic immunophenotypic panels. We aimed to determine the impact of the genotype of this splicing polymorphism in patients with AML treated with GO-containing chemotherapy...
June 23, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28644674/constraints-on-oscillation-parameters-from-%C3%AE-_-e-appearance-and-%C3%AE-_-%C3%AE-disappearance-in-nova
#10
P Adamson, L Aliaga, D Ambrose, N Anfimov, A Antoshkin, E Arrieta-Diaz, K Augsten, A Aurisano, C Backhouse, M Baird, B A Bambah, K Bays, B Behera, S Bending, R Bernstein, V Bhatnagar, B Bhuyan, J Bian, T Blackburn, A Bolshakova, C Bromberg, J Brown, G Brunetti, N Buchanan, A Butkevich, V Bychkov, M Campbell, E Catano-Mur, S Childress, B C Choudhary, B Chowdhury, T E Coan, J A B Coelho, M Colo, J Cooper, L Corwin, L Cremonesi, D Cronin-Hennessy, G S Davies, J P Davies, P F Derwent, R Dharmapalan, P Ding, Z Djurcic, E C Dukes, H Duyang, S Edayath, R Ehrlich, G J Feldman, M J Frank, M Gabrielyan, H R Gallagher, S Germani, T Ghosh, A Giri, R A Gomes, M C Goodman, V Grichine, R Group, D Grover, B Guo, A Habig, J Hartnell, R Hatcher, A Hatzikoutelis, K Heller, A Himmel, A Holin, J Hylen, F Jediny, M Judah, G K Kafka, D Kalra, S M S Kasahara, S Kasetti, R Keloth, L Kolupaeva, S Kotelnikov, I Kourbanis, A Kreymer, A Kumar, S Kurbanov, K Lang, W M Lee, S Lin, J Liu, M Lokajicek, J Lozier, S Luchuk, K Maan, S Magill, W A Mann, M L Marshak, K Matera, V Matveev, D P Méndez, M D Messier, H Meyer, T Miao, W H Miller, S R Mishra, R Mohanta, A Moren, L Mualem, M Muether, S Mufson, R Murphy, J Musser, J K Nelson, R Nichol, E Niner, A Norman, T Nosek, Y Oksuzian, A Olshevskiy, T Olson, J Paley, P Pandey, R B Patterson, G Pawloski, D Pershey, O Petrova, R Petti, S Phan-Budd, R K Plunkett, R Poling, B Potukuchi, C Principato, F Psihas, A Radovic, R A Rameika, B Rebel, B Reed, D Rocco, P Rojas, V Ryabov, K Sachdev, P Sail, O Samoylov, M C Sanchez, R Schroeter, J Sepulveda-Quiroz, P Shanahan, A Sheshukov, J Singh, J Singh, P Singh, V Singh, J Smolik, N Solomey, E Song, A Sousa, K Soustruznik, M Strait, L Suter, R L Talaga, M C Tamsett, P Tas, R B Thayyullathil, J Thomas, X Tian, S C Tognini, J Tripathi, A Tsaris, J Urheim, P Vahle, J Vasel, L Vinton, A Vold, T Vrba, B Wang, M Wetstein, D Whittington, S G Wojcicki, J Wolcott, N Yadav, S Yang, J Zalesak, B Zamorano, R Zwaska
Results are reported from an improved measurement of ν_{μ}→ν_{e} transitions by the NOvA experiment. Using an exposure equivalent to 6.05×10^{20} protons on target, 33 ν_{e} candidates are observed with a background of 8.2±0.8 (syst.). Combined with the latest NOvA ν_{μ} disappearance data and external constraints from reactor experiments on sin^{2}2θ_{13}, the hypothesis of inverted mass hierarchy with θ_{23} in the lower octant is disfavored at greater than 93% C.L. for all values of δ_{CP}.
June 9, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28644650/nature-of-the-spin-liquid-ground-state-in-a-breathing-kagome-compound-studied-by-nmr-and-series-expansion
#11
J-C Orain, B Bernu, P Mendels, L Clark, F H Aidoudi, P Lightfoot, R E Morris, F Bert
In the vanadium oxyfluoride compound (NH_{4})_{2}[C_{7}H_{14}N][V_{7}O_{6}F_{18}] (DQVOF), the V^{4+} (3d^{1}, S=1/2) ions realize a unique, highly frustrated breathing kagome lattice composed of alternately sized, corner-sharing equilateral triangles. Here we present an ^{17}O NMR study of DQVOF, which isolates the local susceptibility of the breathing kagome network. By a fit to series expansion, we extract the ratio of the interactions within the breathing kagome plane, J_{∇}/J_{Δ}=0.55(4), and the mean antiferromagnetic interaction J[over ¯]=60(7)  K...
June 9, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28644119/damage-control-plating-in-open-tibial-shaft-fractures-a-cheaper-and-equally-effective-alternative-to-spanning-external-fixation
#12
Paul S Whiting, Phillip M Mitchell, Aaron M Perdue, Arnold J Silverberg, Sarah E Greenberg, Rachel V Thakore, Vasanth Sathiyakumar, Hassan R Mir, William T Obremskey, Manish K Sethi
The purpose of this study was to evaluate damage control plating (DCP) as an alternative to external fixation (EF) in the provisional stabilization of open tibial shaft fractures. Through retrospective analysis, the study found 445 patients who underwent operative fixation for tibial shaft fractures from 2008 to 2012. Twenty patients received DCP or EF before intramedullary nailing with a minimum follow-up of 3 months. Charts and radiographs were reviewed for postoperative complications. Hospital charges were reviewed for implant costs...
2017: Journal of Surgical Orthopaedic Advances
https://www.readbyqxmd.com/read/28643938/oral-application-of-a-periodontal-pathogen-impacts-serpine1-expression-and-pancreatic-islet-architecture-in-prediabetes
#13
V Ilievski, U G Bhat, S Suleiman-Ata, B A Bauer, P T Toth, S T Olson, T G Unterman, K Watanabe
BACKGROUND AND OBJECTIVES: Epidemiological studies suggest a close association between periodontitis and prediabetes/insulin resistance (IR) but whether periodontitis causes prediabetes in humans is not known. Using various animal models, we have recently established that periodontitis can be an initiator of prediabetes, which is characterized by glucose intolerance, hyperinsulinemia and IR. In addition, our in vitro studies indicated that Porphyromonas gingivalis (Pg) induced insulin secretion in MIN6 β cells and this induction was in part SerpinE1 (plasminogen activator inhibitor 1, PAI1) dependent...
June 23, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28643900/exploring-perspectives-of-young-onset-dementia-caregivers-with-high-versus-low-unmet-needs
#14
Joany K Millenaar, Christian Bakker, Deliane van Vliet, Raymond T C M Koopmans, Alexander Kurz, Frans R J Verhey, Marjolein E de Vugt
BACKGROUND: This study is part of the Research to Assess Policies and Strategies for Dementia in the Young project. Information about specific needs in young onset dementia (YOD) will provide the basis for the development of an e-health intervention to assist caregivers in coping with YOD in several European countries. OBJECTIVE: The aim was to investigate the issues caregivers of people with YOD face. METHODS: A qualitative content analysis method was used to analyse interviews with YOD caregivers...
June 23, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28643840/synchronization-of-excitable-cardiac-cultures-of-different-origin
#15
N N Agladze, O V Halaidych, V A Tsvelaya, T Bruegmann, C Kilgus, P Sasse, K I Agladze
In the present work, we investigated the synchronization of electrical activity in cultured cardiac cells of different origin put in direct contact. In the first set of experiments synchronization was studied in the primary culture cells of neonatal rats taken at different developmental ages, and in the second - in the neonatal rat cardiomyocytes and HL-1 cells. The electrical excitation of cells was recorded using the calcium transient marker Fluor-4. In the confluent cell layers created with the aid of a specially devised mask, the excitation waves and their propagation between areas occupied by cells of different origin were observed...
June 23, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28643785/dnmt3a-mutant-transcript-levels-persist-in-remission-and-do-not-predict-outcome-in-patients-with-acute-myeloid-leukemia
#16
V I Gaidzik, D Weber, P Paschka, A Kaumanns, S Krieger, A Corbacioglu, J Krönke, S Kapp-Schwoerer, D Krämer, H-A Horst, I Schmidt-Wolf, G Held, A Kündgen, M Ringhoffer, K Götze, T Kindler, W Fiedler, M Wattad, R F Schlenk, L Bullinger, V Teleanu, B Schlegelberger, F Thol, M Heuser, A Ganser, H Döhner, K Döhner
We investigated the prognostic impact of minimal residual disease (MRD) monitoring in acute myeloid leukemia (AML) patients harboring DNA methyltransferase 3A-R882H/-R882C mutations (DNMT3A(mut)). MRD was determined by real-time quantitative polymerase chain reaction (RQ-PCR) in 1,494 samples of 181 DNMT3A(mut) patients. At the time of diagnosis, DNMT3A(mut) transcript levels did not correlate with presenting clinical characteristics, concurrent gene mutations as well as the survival endpoints. In Cox regression analyses, bone marrow DNMT3A(mut) transcript levels (log 10 transformed continuous variable) were not associated with the rate of relapse or death...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28643716/prevalence-of-ocular-morbidity-in-school-going-children-in-west-uttar-pradesh
#17
Veer Singh, K P S Malik, V K Malik, Kirti Jain
AIM OF THE STUDY: This study aims to evaluate the prevalence and to make a comparison between the ocular morbidity pattern in school going children of urban and rural areas of West Uttar Pradesh. MATERIALS AND METHODS: A school-based cross-sectional study design was adopted to examine children aged 5-15 years in randomly selected urban and rural schools of West Uttar Pradesh from June 2012 to August 2014. An optometrist did the vision and refraction, and a detailed ophthalmic examination was done by an ophthalmologist...
June 2017: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/28643328/drug-repurposing-by-simulating-flow-through-protein-protein-interaction-networks
#18
M Manczinger, V Bodnár, B T Papp, B Sz Bolla, K Szabó, B Balázs, E Csányi, E Szél, G Erős, L Kemény
As drug development is extremely expensive, the identification of novel indications for in-market drugs is financially attractive. Multiple algorithms are used to support such drug repurposing, but highly reliable methods combining simulation of intracellular networks and machine learning are currently not available. We developed an algorithm that simulates drug effects on the flow of information through protein-protein interaction networks, and uses Support Vector Machine to identify potentially effective drugs in our model disease, psoriasis...
June 23, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28643121/a-study-on-the-expression-of-genes-involved-in-carotenoids-and-anthocyanins-during-ripening-in-fruit-peel-of-green-yellow-and-red-colored-mango-cultivars
#19
G R Karanjalker, K V Ravishankar, K S Shivashankara, M R Dinesh, T K Roy, D V Sudhakar Rao
Mango (Mangiferaindica L.) fruits are generally classified based on peel color into green, yellow, and red types. Mango peel turns from green to yellow or red or retain green colors during ripening. The carotenoids and anthocyanins are the important pigments responsible for the colors of fruits. In the present study, peels of different colored cultivars at three ripening stages were characterized for pigments, colors, and gene expression analysis. The yellow colored cultivar "Arka Anmol" showed higher carotenoid content, wherein β-carotene followed by violaxanthin were the major carotenoid compounds that increased during ripening...
June 22, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28642330/effects-of-intensive-bp-control-in-ckd
#20
Alfred K Cheung, Mahboob Rahman, David M Reboussin, Timothy E Craven, Tom Greene, Paul L Kimmel, William C Cushman, Amret T Hawfield, Karen C Johnson, Cora E Lewis, Suzanne Oparil, Michael V Rocco, Kaycee M Sink, Paul K Whelton, Jackson T Wright, Jan Basile, Srinivasan Beddhu, Udayan Bhatt, Tara I Chang, Glenn M Chertow, Michel Chonchol, Barry I Freedman, William Haley, Joachim H Ix, Lois A Katz, Anthony A Killeen, Vasilios Papademetriou, Ana C Ricardo, Karen Servilla, Barry Wall, Dawn Wolfgram, Jerry Yee
The appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of <120 mm Hg (intensive group; n=1330) or <140 mm Hg (standard group; n=1316). After a median follow-up of 3.3 years, the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants (hazard ratio [HR], 0...
June 22, 2017: Journal of the American Society of Nephrology: JASN
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