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https://www.readbyqxmd.com/read/29342447/design-synthesis-and-anticancer-studies-of-novel-aminobenzazolyl-pyrimidines-as-tyrosine-kinase-inhibitors
#1
Rupesh Chikhale, Sonali Thorat, Rajan Kumar Choudhary, Nikhil Gadewal, Pramod Khedekar
Abnormal signalling from the Protein tyrosine kinases (PTKs) like receptor tyrosine kinases and intracellular tyrosine kinases can lead to diseases such as cancer especially non-small cell lung cancer, chronic myeloid leukaemia and gastrointestinal stromal tumours. Various Protein tyrosine kinase inhibitors are available but face poor bioavailability, severe toxicities and recent cases of drug-resistant cancers prompts for development of better drug molecules. In this study we report the design and development of a novel Protein Tyrosine Kinase (PTK) inhibitor on the basis of pharmacophore modelling...
January 4, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29342443/test-retest-reliability-of-transcranial-magnetic-stimulation-eeg-evoked-potentials
#2
Lewis J Kerwin, Corey J Keller, Wei Wu, Manjari Narayan, Amit Etkin
BACKGROUND: Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs), recorded using electroencephalography (TMS-EEG), offer a powerful tool for measuring causal interactions in the human brain. However, the test-retest reliability of TEPs, critical to their use in clinical biomarker and interventional studies, remains poorly understood. OBJECTIVE/HYPOTHESIS: We quantified TEP reliability to: (i) determine the minimal TEP amplitude change which significantly exceeds that associated with simply re-testing, (ii) locate the most reliable scalp regions of interest (ROIs) and TEP peaks, and (iii) determine the minimal number of TEP pulses for achieving reliability...
December 29, 2017: Brain Stimulation
https://www.readbyqxmd.com/read/29342432/pharmacists-scope-of-practice-in-travel-health-a-review-of-state-laws-and-regulations
#3
Keri Hurley-Kim, Rebecca Snead, Karl M Hess
OBJECTIVES: The primary objective of this study was to assess pharmacists' authority to provide travel health services in each state and Washington, DC. Secondary objectives were to determine the need for collaborative practice agreements (CPAs), protocols, or prescriptions for this type of pharmacy practice and to identify jurisdictions where pharmacists are able to practice as travel health providers independent of CPAs or individual physician protocols. METHODS: An online survey was developed to assess pharmacists' authority to administer travel immunizations, furnish travel-related medications, and order travel-related laboratory tests...
January 13, 2018: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/29342421/the-relation-between-plasma-%C3%AE-synuclein-level-and-clinical-symptoms-or-signs-of-parkinson-s-disease
#4
Michalina Malec-Litwinowicz, Andrzej Plewka, Danuta Plewka, Edyta Bogunia, Michał Morek, Andrzej Szczudlik, Michał Szubiga, Monika Rudzińska-Bar
INTRODUCTION: Parkinson disease (PD) is the common neurodegenerative disease. α-Synuclein (ASN), main aggregating protein in neural cells of CNS in PD, was found in peripheral fluids. Testing ASN in plasma is potential test for diagnose PD, but previous studies are controversial. The aim of this study was to investigate if plasma ASN level may be a valuable biomarker, is the level of plasma ASN concentration different in various motor subtypes of diseases, is there a relation between the level of plasma ASN and the severity of motor symptoms...
November 21, 2017: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/29342415/lysosomes-targeting-imaging-and-anticancer-properties-of-novel-bis-naphthalimide-derivatives
#5
Rui-Xue Rong, Shan-Shan Wang, Xuan Liu, Ren-Feng Li, Ke-Rang Wang, Zhi-Ran Cao, Xiao-Liu Li
A series of novel N,N-bis(3-aminopropyl)methylamine bridged bis-naphthalimide derivatives NI1-NI8 containing saturated nitrogenous heterocycles were designed and synthesized, their cytotoxic activities against Hela, MCF-7, A549 and MGC-803 cells were investigated, Compounds NI1-NI4 modified with piperidine and piperazine exhibited good and selective cytotoxic activity, for instance, compounds NI1 and NI4 showed potent cytotoxic activity against Hela cells and MGC-803 cells with the IC50 values of 2.89, 060, 2...
January 9, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29342413/rapid-detection-of-blakpc-directly-from-surveillance-rectal-swabs-by-easyq-kpc
#6
Ana Carolina Ramos, Lygia Schandert, Cecilia G Carvalhaes, Rafael Affini Martins, Paola Cappellano, Flávia Ribeiro Machado, Ana Cristina Gales
The performance of EasyQ KPC assay was evaluated for the first time for blaKPC detection directly from surveillance rectal swabs without broth enrichment. Using conventional polymerase chain reaction as gold standard method, EasyQ KPC and culture-based molecular tests demonstrated a sensitivity/specificity of 100%/87.3% and 83.3%/98.2%, respectively.
December 16, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29342396/cross-domain-metric-and-multiple-kernel-learning-based-on-information-theory
#7
Wei Wang, Hao Wang, Chen Zhang, Yang Gao
Learning an appropriate distance metric plays a substantial role in the success of many learning machines. Conventional metric learning algorithms have limited utility when the training and test samples are drawn from related but different domains (i.e., source domain and target domain). In this letter, we propose two novel metric learning algorithms for domain adaptation in an information-theoretic setting, allowing for discriminating power transfer and standard learning machine propagation across two domains...
January 17, 2018: Neural Computation
https://www.readbyqxmd.com/read/29342369/added-sugar-consumption-and-chronic-oral-disease-burden-among-adolescents-in-brazil
#8
C D S Carmo, M R C Ribeiro, J X P Teixeira, C M C Alves, M M Franco, A K T C França, B B Benatti, J Cunha-Cruz, C C C Ribeiro
Chronic oral diseases are rarely studied together, especially with an emphasis on their common risk factors. This study examined the association of added sugar consumption on "chronic oral disease burden" among adolescents, with consideration of obesity and systemic inflammation pathways through structural equation modeling. A cross-sectional study was conducted of a complex random sample of adolescent students enrolled at public schools in São Luís, Brazil ( n = 405). The outcome was chronic oral disease burden, a latent variable based on the presence of probing depth ≥4 mm, bleeding on probing, caries, and clinical consequences of untreated caries...
January 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29342366/evaluation-of-the-get-active-questionnaire-in-community-dwelling-older-adults
#9
Andrea F M Petrella, Dawn P Gill, Robert J Petrella
BACKGROUND: Physical activity screening prior to starting a physical activity program is important to identify if there are any underlying health conditions. However, many older adults do not complete such assessments prior to beginning their physical activity program. This project compared the Canadian Society for Exercise Physiology's newly developed Get Active Questionnaire (GAQ) to a standardized exercise stress test in terms of screening out versus screening in false positive GAQ tests...
January 17, 2018: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29342326/mixed-fluorotryptophan-substitutions-at-the-same-residue-expand-the-versatility-of-%C3%A2-%C3%A2-f-protein-nmr-spectroscopy
#10
Calem Kenward, Kyungsoo Shin, Jan Rainey
The strategy of applying fluorine NMR to characterize ligand binding to a membrane protein prepared with mixtures of tryptophans substituted with F at different positions on the indole ring was tested. The ¹⁹F NMR behavior of 4-, 5-, 6-, and 7-fluorotryptophan were directly compared as a function of both micellar environment and fragment size for two overlapping apelin receptor (AR/APJ) segments - one with a single transmembrane (TM) helix and two tryptophan residues, the other with three TM helices and two additional tryptophan residues...
January 17, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29342319/validation-of-the-individualized-neuromuscular-quality-of-life-in-japanese-patients-with-myotonic-dystrophy
#11
Haruo Fujino, Toshio Saito, Masanori P Takahashi, Hiroto Takada, Takahiro Nakayama, Katsuhisa Ogata, Michael R Rose, Osamu Imura, Tsuyoshi Matsumura
INTRODUCTION: The Individualized Neuromuscular Quality of Life (INQoL) is used to measure the quality of life (QoL) of patients with neuromuscular disease. We conducted this study to translate and validate the Japanese version of the INQoL in patients with myotonic dystrophy. METHODS: Forward and backward translation, patient testing, and psychometric validation were performed. We used the SF-36 Health Survey and the modified Rankin scale for concurrent validation...
January 17, 2018: Muscle & Nerve
https://www.readbyqxmd.com/read/29342317/osteoblast-like-mc3t3-e1-cells-prefer-glycolysis-for-atp-production-but-adipocyte-like-3t3-l1-cells-prefer-oxidative-phosphorylation
#12
Anyonya R Guntur, Akos A Gerencser, Phuong T Le, Victoria E DeMambro, Sheila A Bornstein, Shona A Mookerjee, David E Maridas, David E Clemmons, Martin D Brand, Clifford J Rosen
Mesenchymal stromal cells (MSCs) are early progenitors that can differentiate into osteoblasts, chondrocytes and adipocytes. We hypothesized that osteoblasts and adipocytes utilize distinct bioenergetic pathways during MSC differentiation. To test this hypothesis, we compared the bioenergetic profiles of pre-osteoblast MC3T3-E1 cells and calvarial osteoblasts with pre-adipocyte 3T3L1 cells, before and after differentiation. Differentiated MC3T3-E1 osteoblasts met ATP demand mainly by glycolysis with minimal reserve glycolytic capacity, whereas non-differentiated cells generated ATP through oxidative phosphorylation...
January 17, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29342309/prognostic-power-of-a-tumor-differentiation-gene-signature-for-bladder-urothelial-carcinomas
#13
Qianxing Mo, Fotis Nikolos, Fengju Chen, Zoe Tramel, Yu-Cheng Lee, Kazukuni Hayashi, Jing Xiao, Jianjun Shen, Keith Syson Chan
Background: Muscle-invasive bladder cancers (MIBCs) cause approximately 150 000 deaths per year worldwide. Survival for MIBC patients is heterogeneous, with no clinically validated molecular markers that predict clinical outcome. Non-MIBCs (NMIBCs) generally have favorable outcome; however, a portion progress to MIBC. Hence, development of a prognostic tool that can guide decision-making is crucial for improving clinical management of bladder urothelial carcinomas. Methods: Tumor grade is defined by pathologic evaluation of tumor cell differentiation, and it often associates with clinical outcome...
January 12, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29342307/using-phylogenomic-data-to-explore-the-effects-of-relaxed-clocks-and-calibration-strategies-on-divergence-time-estimation-primates-as-a-test-case
#14
Mario Dos Reis, Gregg F Gunnell, José Barba-Montoya, Alex Wilkins, Ziheng Yang, Anne D Yoder
Primates have long been a test case for the development of phylogenetic methods for divergence time estimation. Despite a large number of studies, however, the timing of origination of crown Primates relative to the K-Pg boundary and the timing of diversification of the main crown groups remain controversial. Here we analysed a dataset of 372 taxa (367 Primates and 5 outgroups, 3.4 million aligned base pairs) that includes nine primate genomes. We systematically explore the effect of different interpretations of fossil calibrations and molecular clock models on primate divergence time estimates...
January 12, 2018: Systematic Biology
https://www.readbyqxmd.com/read/29342298/periodontal-disease-assessed-using-clinical-dental-measurements-and-cancer-risk-in-the-aric-study
#15
Dominique S Michaud, Jiayun Lu, Alexandra Y Peacock-Villada, John R Barber, Corinne E Joshu, Anna E Prizment, James D Beck, Steven Offenbacher, Elizabeth A Platz
Background: While evidence is increasingly consistent with a positive association between periodontitis and cancer risk, most studies have relied on self-reported periodontitis. In this study, we prospectively evaluated the association of periodontal disease severity with cancer risk in black and white older adults in a cohort study that included a dental examination. Methods: Included were 7466 participants in the Atherosclerosis Risk in Communities study cohort who at visit 4 (1996-1998) reported being edentulous or underwent the dental examination...
January 12, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29342297/an-exact-goodness-of-fit-test-based-on-the-occupancy-problems-to-study-zero-inflation-and-zero-deflation-in-biological-dosimetry-data
#16
Amanda Fernández-Fontelo, Pedro Puig, Elizabeth A Ainsbury, Manuel Higueras
The goal in biological dosimetry is to estimate the dose of radiation that a suspected irradiated individual has received. For that, the analysis of aberrations (most commonly dicentric chromosome aberrations) in scored cells is performed and dose response calibration curves are built. In whole body irradiation (WBI) with X- and gamma-rays, the number of aberrations in samples is properly described by the Poisson distribution, although in partial body irradiation (PBI) the excess of zeros provided by the non-irradiated cells leads, for instance, to the Zero-Inflated Poisson distribution...
January 12, 2018: Radiation Protection Dosimetry
https://www.readbyqxmd.com/read/29342288/association-between-abcg2-rs2231142-and-poor-response-to-allopurinol-replication-and-meta-analysis
#17
Mary C Wallace, Rebecca L Roberts, Payal Nanavati, Jeffrey N Miner, Nicola Dalbeth, Ruth Topless, Tony R Merriman, Lisa K Stamp
Objective: ABCG2 rs2231142 (Q141K) has been reported to be associated with poor response to allopurinol, while there are conflicting data on the association between the genetically independent ABCG2 rs10011796 variant and allopurinol response. The aim of this study was to replicate the association of ABCG2 rs2231142 and rs10011796 with allopurinol response and perform a meta-analysis. Methods: Participants in the Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) (n = 299) were studied...
January 12, 2018: Rheumatology
https://www.readbyqxmd.com/read/29342286/the-ethics-of-general-population-preventive-genomic-sequencing-rights-and-social-justice
#18
Clair Morrissey, Rebecca L Walker
Advances in DNA sequencing technology open new possibilities for public health genomics, especially in the form of general population preventive genomic sequencing (PGS). Such screening programs would sit at the intersection of public health and preventive health care, and thereby at once invite and resist the use of clinical ethics and public health ethics frameworks. Despite their differences, these ethics frameworks traditionally share a central concern for individual rights. We examine two putative individual rights-the right not to know, and the child's right to an open future-frequently invoked in discussions of predictive genetic testing, in order to explore their potential contribution to evaluating this new practice...
January 12, 2018: Journal of Medicine and Philosophy
https://www.readbyqxmd.com/read/29342285/serial-participation-and-the-ethics-of-phase-1-healthy-volunteer-research
#19
Rebecca L Walker, Marci D Cottingham, Jill A Fisher
Phase 1 healthy volunteer clinical trials-which financially compensate subjects in tests of drug toxicity levels and side effects-appear to place pressure on each joint of the moral framework justifying research. In this article, we review concerns about phase 1 trials as they have been framed in the bioethics literature, including undue inducement and coercion, unjust exploitation, and worries about compromised data validity. We then revisit these concerns in light of the lived experiences of serial participants who are income-dependent on phase 1 trials...
January 12, 2018: Journal of Medicine and Philosophy
https://www.readbyqxmd.com/read/29342276/a-predictive-quantitative-model-of-spiking-activity-and-stimulus-secretion-coupling-in-oxytocin-neurons
#20
Jorge Maícas-Royo, Gareth Leng, Duncan J MacGregor
Oxytocin neurons of the rat hypothalamus project to the posterior pituitary where they secrete their products into the bloodstream. The pattern and quantity of that release depends on the afferent inputs to the neurons, on their intrinsic membrane properties, and on non-linear interactions between spiking activity and exocytosis: a given number of spikes will trigger more secretion when they arrive close together. Here we present a quantitative computational model of oxytocin neurons that can replicate the results of a wide variety of published experiments...
January 12, 2018: Endocrinology
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