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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/29342404/association-between-severity-of-liver-disease-frequency-of-helicobacter-pylori-infection-and-degree-of-gastric-lesion-in-egyptian-patients-with-hepatitis-b-virus-infection
#2
Amal A Mohamed, Amal A Elshimy, Abir O El Sadik, Elham Ezzat, Mona Nasar, Shereen S M Elshaer, Moataz M Sayed
The relationship between hepatitis B virus (HBV) infection, severity of liver disease, frequency of Helicobacter pylori infection, and degree of gastric lesions was not yet fully investigated in Egyptian patients. The present work was performed on 100 Egyptian patients with HBV from the National Hepatology and Tropical Medicine Institute and 70 healthy volunteers as control group. The participants were subjected to full medical history taking, clinical examination, and laboratory investigations. All patients were positive for HBV surface antigen (HBV sAg), HBV DNA, and negative for hepatitis C virus antibodies...
January 2018: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29342393/hyperthermic-intraperitoneal-chemotherapy-in-ovarian-cancer
#3
Willemien J van Driel, Simone N Koole, Karolina Sikorska, Jules H Schagen van Leeuwen, Henk W R Schreuder, Ralph H M Hermans, Ignace H J T de Hingh, Jacobus van der Velden, Henriëtte J Arts, Leon F A G Massuger, Arend G J Aalbers, Victor J Verwaal, Jacobien M Kieffer, Koen K Van de Vijver, Harm van Tinteren, Neil K Aaronson, Gabe S Sonke
Background Treatment of newly diagnosed advanced-stage ovarian cancer typically involves cytoreductive surgery and systemic chemotherapy. We conducted a trial to investigate whether the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery would improve outcomes among patients who were receiving neoadjuvant chemotherapy for stage III epithelial ovarian cancer. Methods In a multicenter, open-label, phase 3 trial, we randomly assigned 245 patients who had at least stable disease after three cycles of carboplatin (area under the curve of 5 to 6 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area) to undergo interval cytoreductive surgery either with or without administration of HIPEC with cisplatin (100 mg per square meter)...
January 18, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29342391/case-2-2018-a-41-year-old-woman-with-vision-disturbances-and-headache
#4
Dean M Cestari, Mary E Cunnane, Joseph F Rizzo, John H Stone
Presentation of Case. Dr. John H. Stone: A 41-year-old woman was evaluated in the rheumatology clinic of this hospital because of headaches and a 6-week history of intermittent, transient vision loss. Four years before the current presentation, a skin eruption on the right foot and a lesion on the..
January 18, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29342390/household-contact-investigation-for-detection-of-tuberculosis-in-vietnam
#5
Greg J Fox, Nguyen V Nhung, Dinh N Sy, Nghiem L P Hoa, Le T N Anh, Nguyen T Anh, Nguyen B Hoa, Nguyen H Dung, Tran N Buu, Nguyen T Loi, Le T Nhung, Nguyen V Hung, Phan T Lieu, Nguyen K Cuong, Pham D Cuong, Jessica Bestrashniy, Warwick J Britton, Guy B Marks
Background Active case finding is a top priority for the global control of tuberculosis, but robust evidence for its effectiveness in high-prevalence settings is lacking. We sought to evaluate the effectiveness of household-contact investigation, as compared with standard, passive measures alone, in Vietnam. Methods We performed a cluster-randomized, controlled trial at clinics in 70 districts (local government areas with an average population of approximately 500,000 in urban areas and 100,000 in rural areas) in eight provinces of Vietnam...
January 18, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29342370/fgf8-signaling-alters-the-osteogenic-cell-fate-in-the-hard-palate
#6
J Xu, Z Huang, W Wang, X Tan, H Li, Y Zhang, W Tian, T Hu, Y P Chen
Fibroblast growth factor (FGF) signaling has been implicated in the regulation of osteogenesis in both intramembranous and endochondral ossifications. In the developing palate, the anterior bony palate forms by direct differentiation of cranial neural crest (CNC)-derived mesenchymal cells, but the signals that regulate the osteogenic cell fate in the developing palate remain unclear. In the present study, we investigated the potential role of FGF signaling in osteogenic fate determination of the palatal mesenchymal cells...
January 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29342357/diffusion-controlled-epitaxy-of-large-area-coalesced-wse2-monolayers-on-sapphire
#7
Xiaotian Zhang, Tanushree H Choudhury, Mikhail Chubarov, Yu Xiang, Bhakti Jariwala, Fu Zhang, Nasim Alem, Gwo-Ching Wang, Joshua A Robinson, Joan M Redwing
A multi-step diffusion-mediated process was developed to control the nucleation density, size and lateral growth rate of WSe2 domains on c-plane sapphire for the epitaxial growth of large area monolayer films by gas source chemical vapor deposition (CVD). The process consists of an initial nucleation step followed by an annealing period in H2Se to promote surface diffusion of tungsten-containing species to form oriented WSe2 islands with uniform size and controlled density. The growth conditions were then adjusted to suppress further nucleation and laterally grow the WSe2 islands to form a fully coalesced monolayer film in less than one hour...
January 17, 2018: Nano Letters
https://www.readbyqxmd.com/read/29342353/synthesis-and-computational-studies-demonstrate-the-utility-of-an-intramolecular-styryl-diels-alder-reaction-and-bht-assisted-1-3-shift-to-construct-anticancer-dl-deoxypodophyllotoxin
#8
Diana I Saavedra, Benjamin D Rencher, Doo-Hyun Kwon, Stacey J Smith, Daniel H Ess, Merritt B Andrus
Deoxypodophyllotoxin is a secondary metabolite lignan possessing potent anticancer activity with potential as a precursor for known anticancer drugs, but its use is limited by scarcity from natural sources. We here report the total synthesis of racemic deoxypodophyllotoxin (DPT) in seven steps using an intramolecular styryl Diels-Alder reaction (ISDA) strategy uniquely suited to assemble the deoxypodophyllotoxin core. Computational studies are also reported for this reaction that demonstrate the ability to overcome the limitations of slow reactivity and electronic mismatch of the diene and dieneophile...
January 17, 2018: Journal of Organic Chemistry
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
#9
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/29342291/portuguese-study-of-mean-glandular-dose-in-mammography-and-comparison-with-european-references
#10
Cláudia Sá Dos Reis, Mário João Fartaria, João H Garcia Alves, Ana Pascoal
To characterise the mean glandular dose (MGD) in a sample of healthcare providers for digital mammography in Portugal. To compare the achieved values with European references. The MGD was measured on a poly-methyl-methacrylate phantom (45 mm) for each system using dosimeters. In addition, MGD was estimated using exposure settings collected from mammography exams in clinical context. Data were collected from 25 computed-radiography systems (CR) and 13 integrated digital (DR). For both measurements (phantom and clinical exposures), the average MGD for CR was higher compared to the DR...
January 12, 2018: Radiation Protection Dosimetry
https://www.readbyqxmd.com/read/29342275/hot-spot-kif5a-mutations-cause-familial-als
#11
David Brenner, Rüstem Yilmaz, Kathrin Müller, Torsten Grehl, Susanne Petri, Thomas Meyer, Julian Grosskreutz, Patrick Weydt, Wolfgang Ruf, Christoph Neuwirth, Markus Weber, Susana Pinto, Kristl G Claeys, Berthold Schrank, Berit Jordan, Antje Knehr, Kornelia Günther, Annemarie Hübers, Daniel Zeller, Christian Kubisch, Sibylle Jablonka, Michael Sendtner, Thomas Klopstock, Mamede de Carvalho, Anne Sperfeld, Guntram Borck, Alexander E Volk, Johannes Dorst, Joachim Weis, Markus Otto, Joachim Schuster, Kelly Del Tredici, Heiko Braak, Karin M Danzer, Axel Freischmidt, Thomas Meitinger, Tim M Strom, Albert C Ludolph, Peter M Andersen, Jochen H Weishaupt
Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de novo frame-shift mutations in the C-terminal domain of KIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings, together with the observation that many of the disease genes associated with amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular transport, led us to hypothesize that mutations in KIF5A are also a cause of amyotrophic lateral sclerosis...
January 12, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29342260/interaction-between-staphylococcus-aureus-and-pseudomonas-aeruginosa-is-beneficial-for-colonisation-and-pathogenicity-in-a-mixed-biofilm
#12
Patrícia M Alves, Eide Al-Badi, Cathryn Withycombe, Paul M Jones, Kevin J Purdy, Sarah E Maddocks
Debate regarding the co-existence of Staphylococcus aureus and Pseudomonas aeruginosa in wounds remains contentious, with the dominant hypothesis describing a situation akin to niche partitioning, whereby both microorganisms are present but occupy distinct regions of the wound without interacting. In contrast, we hypothesised that these microorganisms do interact during early co-colonisation in a manner beneficial to both bacteria. We assessed competitive interaction between S. aureus and P. aeruginosa in biofilm cultured for 24-72 h and bacterial aggregates analogous to those observed in early ( < 24h) biofilm formation, and interaction with human keratinocytes...
January 12, 2018: Pathogens and Disease
https://www.readbyqxmd.com/read/29342258/insulin-and-estrogen-independently-and-differentially-reduce-macronutrient-intake-in-healthy-men
#13
Rosemarie Krug, Linda Mohwinkel, Bernhard Drotleff, Jan Born, Manfred Hallschmid
Context: Insulin administration to the central nervous system inhibits food intake, but this effect has been found to be less pronounced in female compared to male organisms. This sex-specific pattern has been suggested to arise from a modulating influence of estrogen signaling on the insulin effect. Objective: We assessed in healthy young men whether pre-treatment with transdermal estradiol interacts with the hypophagic effect of central nervous insulin administration via the intranasal pathway...
January 12, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29342256/comparison-of-pregnancy-outcomes-between-maternity-waiting-home-users-and-non-users-at-hospitals-with-and-without-a-maternity-waiting-home-retrospective-cohort-study
#14
Floris Braat, Tienke Vermeiden, Gashaw Getnet, Rita Schiffer, Thomas van den Akker, Jelle Stekelenburg
Objective: To examine the impact of a maternity waiting home (MWH) by comparing pregnancy outcomes between users and non-users at hospitals with and without an MWH. Methods: We conducted a retrospective cohort study in Ethiopia comparing one hospital with an MWH (Attat) to a second hospital without one (Butajira). A structured questionnaire among sampled women in 2014 and hospital records from 2011 to 2014 were used to compare sociodemographic characteristics and pregnancy outcomes between Attat MWH users and non-MWH users, Attat MWH users and Butajira, and Attat non-MWH users and Butajira...
January 12, 2018: International Health
https://www.readbyqxmd.com/read/29342252/triglyceride-rich-lipoprotein-cholesterol-trl-c-the-ugly-stepsister-of-ldl-c
#15
Michael H Davidson
No abstract text is available yet for this article.
January 12, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29342250/pneumococcal-community-acquired-pneumonia-detected-by-serotype-specific-urinary-antigen-detection-assays
#16
Richard G Wunderink, Wesley H Self, Evan J Anderson, Robert Balk, Sherene Fakhran, Daniel Mark Courtney, Chao Qi, Derek J Williams, Yuwei Zhu, Cynthia G Whitney, Matthew R Moore, Anna Bramley, Seema Jain, Kathryn M Edwards, Carlos G Grijalva
Background: Streptococcus pneumoniae is considered the leading bacterial cause of pneumonia in adults. Yet, it was not commonly detected by traditional culture-based and conventional urinary testing in a recent multicenter etiology study of adults hospitalized with community-acquired pneumonia (CAP). We used novel serotype-specific urinary antigen detection (SSUAD) assays to determine whether pneumococcal cases were missed by traditional testing. Methods: We studied adult patients hospitalized with CAP at 5 hospitals in Chicago and Nashville (2010-2012) and enrolled in the Etiology of Pneumonia in the Community (EPIC) study...
January 12, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29342240/presence-of-myocardial-damage-predicts-future-development-of-hypertension-in-a-normotensive-japanese-general-population-the-yamagata-takahata-study
#17
Yuki Honda, Tetsu Watanabe, Harutoshi Tamura, Satoshi Nishiyama, Hiroki Takahashi, Takanori Arimoto, Tetsuro Shishido, Takuya Miyamoto, Yoko Shibata, Tsuneo Konta, Takamasa Kayama, Isao Kubota
Background: A modest rise in blood pressure (BP) reportedly increases cardiovascular mortality despite not reaching obvious hypertension, suggesting that target organ damages are latently induced by slight BP rising. The goal of this study was to determine whether presence of subclinical myocardial damage can predict the future development of hypertension in the normotensive general population. Methods and results: The cohort study was conducted with subjects who participated in a community-based annual health check...
January 12, 2018: American Journal of Hypertension
https://www.readbyqxmd.com/read/29342223/development-of-a-job-exposure-matrix-for-noise-in-the-swedish-soft-tissue-paper-industry
#18
Richard Lee Neitzel, Marianne Andersson, Helena Eriksson, Kjell Torén, Eva Andersson
Objectives: Noise exposure is a common occupational hazard, but has not been sufficiently characterized in paper mills. We developed a job-exposure matrix (JEM) for noise exposure for use in estimating exposures among Swedish soft tissue paper mill workers. Methods: We used a combination of area and personal dosimetry noise exposure measurements made at four soft tissue paper mills by industry and research staff between 1977 and 2013 to estimate noise exposures by department, location, and job title...
December 16, 2017: Annals of Work Exposures and Health
https://www.readbyqxmd.com/read/29342213/circulating-neutrophil-transcriptome-may-reveal-intracranial-aneurysm-signature
#19
Vincent M Tutino, Kerry E Poppenberg, Kaiyu Jiang, James N Jarvis, Yijun Sun, Ashish Sonig, Adnan H Siddiqui, Kenneth V Snyder, Elad I Levy, John Kolega, Hui Meng
BACKGROUND: Unruptured intracranial aneurysms (IAs) are typically asymptomatic and undetected except for incidental discovery on imaging. Blood-based diagnostic biomarkers could lead to improvements in IA management. This exploratory study examined circulating neutrophils to determine whether they carry RNA expression signatures of IAs. METHODS: Blood samples were collected from patients receiving cerebral angiography. Eleven samples were collected from patients with IAs and 11 from patients without IAs as controls...
2018: PloS One
https://www.readbyqxmd.com/read/29342199/a-non-linear-pharmacokinetic-pharmacodynamic-relationship-of-metformin-in-healthy-volunteers-an-open-label-parallel-group-randomized-clinical-study
#20
Hyewon Chung, Jaeseong Oh, Seo Hyun Yoon, Kyung-Sang Yu, Joo-Youn Cho, Jae-Yong Chung
BACKGROUND: The aim of this study was to explore the pharmacokinetic-pharmacodynamic (PK-PD) relationship of metformin on glucose levels after the administration of 250 mg and 1000 mg of metformin in healthy volunteers. METHODS: A total of 20 healthy male volunteers were randomized to receive two doses of either a low dose (375 mg followed by 250 mg) or a high dose (1000 mg followed by 1000 mg) of metformin at 12-h intervals. The pharmacodynamics of metformin was assessed using oral glucose tolerance tests before and after metformin administration...
2018: PloS One
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