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https://www.readbyqxmd.com/read/29454290/ligand-based-computer-aided-drug-design-reveals-new-tropomycin-receptor-kinase-a-trka-inhibitors
#1
Rand Shahin, Iman Mansi, Lubna Swellmeen, Tahani Alwidyan, Nabil Al-Hashimi, Yaser Al-Qarar'h, Omar Shaheen
Targeting tropomycin kinase A (TrkA) by small molecule inhibitors is considered as a promising strategy for treating several human cancers. To achieve this goal, a ligand based QSAR model was applied using the Discovery studio 4.5 (DS 4.5). Hence, a total list of 161 TrkA inhibitors was investigated. The TrkA inhibitors were extensively explored to detect their optimal physicochemical properties and pharmacophoric binding modes, which were converted into numeric descriptors and allowed to compete within the context of the Genetic Function Algorithm (GFA) approximations to find the subset of terms that correlates best with the activity...
January 13, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29454256/five-month-old-infants-have-expectations-for-the-accumulation-of-nonsolid-substances
#2
Erin M Anderson, Susan J Hespos, Lance J Rips
Infants fail to represent quantities of non-cohesive substances in paradigms where they succeed with solid objects. Some investigators have interpreted these results as evidence that infants do not yet have representations for substances. More recent research, however, shows that 5-month-old infants expect objects and substances to behave and interact in different ways. In the present experiments, we test whether infants have expectations for substances when the outcomes are not simply the opposite of those for objects...
February 14, 2018: Cognition
https://www.readbyqxmd.com/read/29454247/tolerance-and-growth-kinetics-of-bacteria-isolated-from-gold-and-gemstone-mining-sites-in-response-to-heavy-metal-concentrations
#3
Oluwatosin Gbemisola Oladipo, Obinna Tobechukwu Ezeokoli, Mark Steve Maboeta, Jacobus Johannes Bezuidenhout, Louwrens R Tiedt, Anine Jordaan, Cornelius Carlos Bezuidenhout
Response and growth kinetics of microbes in contaminated medium are useful indices for the screening and selection of tolerant species for eco-friendly bio-augmentative remediation of polluted environments. In this study, the heavy metal (HM) tolerance, bioaccumulation and growth kinetics of seven bacterial strains isolated from mining sites to 10 HMs (Cd, Hg, Ni, Al, Cr, Pb, Cu, Fe, Mn and Zn) at varied concentrations (25-600 mgL -1 ) were investigated. The isolates were phylogenetically (16S rRNA gene) related to Lysinibacillus macroides, Achromobacter spanius, Bacillus kochii, B...
February 14, 2018: Journal of Environmental Management
https://www.readbyqxmd.com/read/29454221/-13-c-phenylalanine-breath-test-and-serum-biopterin-in-schizophrenia-bipolar-disorder-and-major-depressive-disorder
#4
Toshiya Teraishi, Masahiro Kajiwara, Hiroaki Hori, Daimei Sasayama, Shinsuke Hidese, Junko Matsuo, Ikki Ishida, Yasuhiro Kajiwara, Yuji Ozeki, Miho Ota, Kotaro Hattori, Teruhiko Higuchi, Hiroshi Kunugi
Phenylalanine is required for the synthesis of the neurotransmitters dopamine, noradrenaline, and adrenaline. The rate-limiting step for phenylalanine metabolism is catalyzed by phenylalanine hydroxylase (PAH) and its cofactor tetrahydrobiopterin. We aimed to detect altered phenylalanine metabolism in major psychiatric disorders using the l-[1- 13 C]phenylalanine breath test ( 13 C-PBT) and serum biopterin levels. We also investigated association of PAH mutations with schizophrenia and phenylalanine metabolism...
February 3, 2018: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/29454079/a-novel-metric-that-quantifies-risk-stratification-for-evaluating-diagnostic-tests-the-example-of-evaluating-cervical-cancer-screening-tests-across-populations
#5
Hormuzd A Katki, Mark Schiffman
Our work involves assessing whether new biomarkers might be useful for cervical-cancer screening across populations with different disease prevalences and biomarker distributions. When comparing across populations, we show that standard diagnostic accuracy statistics (predictive values, risk-differences, Youden's index and Area Under the Curve (AUC)) can easily be misinterpreted. We introduce an intuitively simple statistic for a 2 × 2 table, Mean Risk Stratification (MRS): the average change in risk (pre-test vs...
February 14, 2018: Preventive Medicine
https://www.readbyqxmd.com/read/29454059/towards-a-regulatory-use-of-alternative-developmental-neurotoxicity-testing-dnt
#6
Andrea Terron, Susanne Hougaard Bennekou
There is a need for a more effective Developmental Neurotoxicity (DNT) screening which is scientifically driven by the fact that the developing nervous system might be more sensitive to exposures to some hazardous chemical. Additional concern comes from the recent societal concerns that toxic chemicals can contribute to the prevalence of neurodevelopment disabilities. Consequently, hazard identification and actions to reduce exposure to these chemicals is a priority in chemical risk assessment. To reach this goal a cost-efficient testing strategy based on a reliable in-vitro testing battery should be developed...
February 14, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29454049/emergence-of-vancomycin-intermediate-and-resistant-staphylococcus-aureus-among-methicillin-resistant-s-aureus-isolated-from-clinical-specimens-in-the-northwest-of-iran
#7
Maryam Ghahremani, Nima Hosseini Jazani, Yaeghob Sharifi
OBJECTIVES: This study aimed to evaluate the frequency, the, phenotypic and molecular characteristics of methicillin- resistant, Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA), from clinical specimens at three university teaching hospitals in Urmia-North West of Iran (2012- 2015). METHODS: After identification of the isolates, the antibiotic, susceptibility, the presence of mecA, vanA, pvl genes and staphylococcal, cassette chromosome mec (SCCmec) typing were evaluated...
February 14, 2018: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29453934/distinct-domains-of-the-avrpm3-a2-f2-avirulence-protein-from-wheat-powdery-mildew-are-involved-in-immune-receptor-recognition-and-putative-effector-function
#8
Kaitlin Elyse McNally, Fabrizio Menardo, Linda Lüthi, Coraline Rosalie Praz, Marion Claudia Müller, Lukas Kunz, Roi Ben-David, Kottakota Chandrasekhar, Amos Dinoor, Christina Cowger, Emily Meyers, Mingfeng Xue, Fangsong Zeng, Shuangjun Gong, Dazhao Yu, Salim Bourras, Beat Keller
Recognition of the AVRPM3 A2/F2 avirulence protein from powdery mildew by the wheat PM3A/F immune receptor induces a hypersensitive response after co-expression in Nicotiana benthamiana. The molecular determinants of this interaction and how they shape natural AvrPm3 a2/f2 allelic diversity are unknown. We sequenced the AvrPm3 a2/f2 gene in a worldwide collection of 272 mildew isolates. Using the natural polymorphisms of AvrPm3 a2/f2 as well as sequence information from related gene family members, we tested 85 single-residue-altered AVRPM3 A2/F2 variants with PM3A, PM3F and PM3F L 456P/Y458H (modified for improved signaling) in Nicotiana benthamiana for effects on recognition...
February 17, 2018: New Phytologist
https://www.readbyqxmd.com/read/29453853/role-of-bi-weekly-serum-galactomannan-screening-for-the-diagnosis-of-invasive-aspergillosis-in-hematologic-cancer-patients
#9
Jade Couchepin, Anne-Sophie Brunel, Katia Jaton, Pascal Meylan, Pierre-Yves Bochud, Frédéric Lamoth
Invasive aspergillosis (IA) is a life-threatening infection affecting hematologic cancer patients with chemotherapy-induced neutropenia. The diagnosis of IA often relies on the detection of galactomannan (GM) in serum or bronchoalveolar lavage fluid (BAL). Bi-weekly serum GM screening has been proposed for a preemptive therapeutic approach of IA in patients not receiving mold-active prophylaxis. We have analyzed all IA cases among patients with hematologic malignancies and prolonged chemotherapy-induced neutropenia (>14 days) in our institution over a 10-year period (2007-2017)...
February 17, 2018: Mycoses
https://www.readbyqxmd.com/read/29453831/evaluation-of-a-recombinant-multiepitope-antigen-for-diagnosis-of-hepatitis-c-virus-a-lower-cost-alternative-for-antigen-production
#10
Ronaldo Luis Thomasini, Hortencia Gisele Amaro Souza, Oscar Bruna-Romero, Antonio Helvecio Totola, Neiva Sellan Lopes Gonçales, Cristiano Xavier Lima, Mauro Martins Teixeira
BACKGROUND: The most of the hepatitis C-infected patients remain undiagnosed until they develop severe liver damage or submitted for serological screening. OBJECTIVE: To evaluate a recombinant multiepitope protein for detection of IgG anti-hepatitis C virus. METHOD: A synthetic gene was cloned, expressed in Escherichia coli, and the recombinant protein was purified. Human serum panel consisted of 88 positives (20 HCV genotyped) and 376 negatives for hepatitis C, 6 positives for human acquired immunodeficiency virus, 6 syphilis positives, 6 hepatitis B positives were tested by IgG antihepatitis C virus using the protein by enzyme-linked immunosorbent assay...
February 17, 2018: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29453822/full-genome-sequencing-of-porcine-circovirus-3-field-strains-from-denmark-italy-and-spain-demonstrates-a-high-within-europe-genetic-heterogeneity
#11
G Franzo, M Legnardi, C K Hjulsager, F Klaumann, L E Larsen, J Segales, M Drigo
Porcine circovirus 3 (PCV3) is a new species of the Circovirus genus, which has recently been associated with different clinical syndromes. Its presence has been reported in different countries of North and South America, Asia and recently also Europe (Poland). However, different from the other continents, no European PCV3 sequence is currently available in public databases. There is a strong need of epidemiological data and full-genome sequences from Europe because of its relevance in the understanding of PCV3 molecular epidemiology and control...
February 16, 2018: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/29453636/assessment-of-oximetry-based-statistical-classifiers-as-simplified-screening-tools-in-the-management-of-childhood-obstructive-sleep-apnea
#12
Andrea Crespo, Daniel Álvarez, Leila Kheirandish-Gozal, Gonzalo C Gutiérrez-Tobal, Ana Cerezo-Hernández, David Gozal, Roberto Hornero, Félix Del Campo
PURPOSE: A variety of statistical models based on overnight oximetry has been proposed to simplify the detection of children with suspected obstructive sleep apnea syndrome (OSAS). Despite the usefulness reported, additional thorough comparative analyses are required. This study was aimed at assessing common binary classification models from oximetry for the detection of childhood OSAS. METHODS: Overnight oximetry recordings from 176 children referred for clinical suspicion of OSAS were acquired during in-lab polysomnography...
February 16, 2018: Sleep & Breathing, Schlaf & Atmung
https://www.readbyqxmd.com/read/29453630/somatic-brca1-mutations-in-clinically-sporadic-breast-cancer-with-medullary-histological-features
#13
Markus Rechsteiner, Konstantin Dedes, Daniel Fink, Bernhard Pestalozzi, Bettina Sobottka, Holger Moch, Peter Wild, Zsuzsanna Varga
BACKGROUND: The role of somatic BRCA1/2 gene mutations in breast cancer is getting increasing attention in view of hereditary disease. The medullary phenotype and triple negative intrinsic subtypes are often, but not exclusively encountered in BRCA1 germline mutated breast cancer, whilst for BRCA2, no association to specific histological features are known. In this study, we addressed the relationship between morphological medullary phenotype and BRCA1/2 somatic mutations in breast cancer without known positive family anamnesis...
February 17, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29453510/next-generation-metabolic-screening-targeted-and-untargeted-metabolomics-for-the-diagnosis-of-inborn-errors-of-metabolism-in-individual-patients
#14
Karlien L M Coene, Leo A J Kluijtmans, Ed van der Heeft, Udo F H Engelke, Siebolt de Boer, Brechtje Hoegen, Hanneke J T Kwast, Maartje van de Vorst, Marleen C D G Huigen, Irene M L W Keularts, Michiel F Schreuder, Clara D M van Karnebeek, Saskia B Wortmann, Maaike C de Vries, Mirian C H Janssen, Christian Gilissen, Jasper Engel, Ron A Wevers
The implementation of whole-exome sequencing in clinical diagnostics has generated a need for functional evaluation of genetic variants. In the field of inborn errors of metabolism (IEM), a diverse spectrum of targeted biochemical assays is employed to analyze a limited amount of metabolites. We now present a single-platform, high-resolution liquid chromatography quadrupole time of flight (LC-QTOF) method that can be applied for holistic metabolic profiling in plasma of individual IEM-suspected patients. This method, which we termed "next-generation metabolic screening" (NGMS), can detect >10,000 features in each sample...
February 16, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29453499/screening-for-gene-environment-g%C3%A3-e-interaction-using-omics-data-from-exposed-individuals-an-application-to-gene-arsenic-interaction
#15
Maria Argos, Lin Tong, Shantanu Roy, Mekala Sabarinathan, Alauddin Ahmed, Md Tariqul Islam, Tariqul Islam, Muhammad Rakibuz-Zaman, Golam Sarwar, Hasan Shahriar, Mahfuzar Rahman, Md Yunus, Joseph H Graziano, Farzana Jasmine, Muhammad G Kibriya, Xiang Zhou, Habibul Ahsan, Brandon L Pierce
Identifying gene-environment interactions is a central challenge in the quest to understand susceptibility to complex, multi-factorial diseases. Developing an understanding of how inter-individual variability in inherited genetic variation alters the effects of environmental exposures will enhance our knowledge of disease mechanisms and improve our ability to predict disease and target interventions to high-risk sub-populations. Limited progress has been made identifying gene-environment interactions in the epidemiological setting using existing statistical approaches for genome-wide searches for interaction...
February 16, 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/29453471/significance-of-non-invasive-markers-as-predictor-of-esophageal-varices-in-liver-cirrhosis
#16
Dipendra Khadka, Sushil Prajapati, Sudhamshu Kc, Jeetendra Kaji Shrestha, Niyanta Karki, Bikash Jaishi, Kiran Regmi, Sandip Khadka
INTRODUCTION: Upper gastro-intestinal endoscopy remains the gold standard for screening for esophageal varices but it has its own limitations. It is an invasive, expensive and uncomfortable procedure and needs clinical expertise. Accordingly, this study was conducted to establish the role of non-invasive markers for prediction of esophageal varices in liver cirrhosis. METHODS: A hospital based descriptive cross-sectional study was carried out in Liver unit of National Academy of Medical Sciences, Bir Hospital, from October 2016 to September 2017...
October 2017: JNMA; Journal of the Nepal Medical Association
https://www.readbyqxmd.com/read/29453190/testing-behavior-change-techniques-to-encourage-primary-care-physicians-to-access-cancer-screening-audit-and-feedback-reports-protocol-for-a-factorial-randomized-experiment-of-email-content
#17
Gratianne Vaisson, Holly O Witteman, Zachary Bouck, Caroline A Bravo, Laura Desveaux, Diego Llovet, Justin Presseau, Marianne Saragosa, Monica Taljaard, Shama Umar, Jeremy M Grimshaw, Jill Tinmouth, Noah M Ivers
BACKGROUND: Cancer Care Ontario's Screening Activity Report (SAR) is an online audit and feedback tool designed to help primary care physicians in Ontario, Canada, identify patients who are overdue for cancer screening or have abnormal results requiring follow-up. Use of the SAR is associated with increased screening rates. To encourage SAR use, Cancer Care Ontario sends monthly emails to registered primary care physicians announcing that updated data are available. However, analytics reveal that 50% of email recipients do not open the email and less than 7% click the embedded link to log in to their report...
February 16, 2018: JMIR Research Protocols
https://www.readbyqxmd.com/read/29453188/web-based-alcohol-smoking-and-substance-involvement-screening-test-results-for-the-general-spanish-population-cross-sectional-study
#18
Juan A Lopez-Rodriguez, Gabriel Rubio Valladolid
BACKGROUND: Information technology in health sciences could be a screening tool of great potential and has been shown to be effective in identifying single-drug users at risk. Although there are many published tests for single-drug screening, there is a gap for concomitant drug use screening in general population. The ASSIST (Alcohol, Smoking and Substance Involvement Screening Test) website was launched on February 2015 in Madrid, Spain, as a tool to identify those at risk. OBJECTIVE: The aim of this study was to describe the use of a tool and to analyze profiles of drug users, their consumption patterns, and associated factors...
February 16, 2018: Journal of Medical Internet Research
https://www.readbyqxmd.com/read/29453154/unique-pharmacology-of-a-novel-allosteric-agonist-sensitizer-insulin-receptor-monoclonal-antibody
#19
Simon A Hinke, Anne M Cieniewicz, Thomas Kirchner, Katharine D'Aquino, Rupesh Nanjunda, Jason Aligo, Robert Perkinson, Philip Cooper, Ken Boayke, Mark L Chiu, Steve Jarantow, Eilyn R Lacy, Yin Liang, Dana L Johnson, Jean M Whaley, Russell B Lingham, Anthony J Kihm
OBJECTIVE: Insulin resistance is a key feature of Type 2 Diabetes (T2D), and improving insulin sensitivity is important for disease management. Allosteric modulation of the insulin receptor (IR) with monoclonal antibodies (mAbs) can enhance insulin sensitivity and restore glycemic control in animal models of T2D. METHODS: A novel human mAb, IRAB-A, was identified by phage screening using competition binding and surface plasmon resonance assays with the IR extracellular domain...
February 3, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29452988/expert-consensus-recommendations-on-the-cardiogenetic-care-for-patients-with-thoracic-aortic-disease-and-their-first-degree-relatives
#20
Judith M A Verhagen, Marlies Kempers, Luc Cozijnsen, Berto J Bouma, Anthonie L Duijnhouwer, Jan G Post, Yvonne Hilhorst-Hofstee, Sebastiaan C A M Bekkers, Wilhelmina S Kerstjens-Frederikse, Thomas J van Brakel, Eric Lambermon, Marja W Wessels, Bart L Loeys, Jolien W Roos-Hesselink, Ingrid M B H van de Laar
BACKGROUND: Thoracic aortic aneurysm (TAA) is a potentially life-threatening disorder with a strong genetic component. The number of genes implicated in TAA has increased exponentially over the last decade. Approximately 20% of patients with TAA have a positive family history. As most TAA remain asymptomatic for a long time, screening of at risk relatives is warranted to prevent complications. Existing international guidelines lack detailed instructions regarding genetic evaluation and family screening of TAA patients...
February 7, 2018: International Journal of Cardiology
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