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https://www.readbyqxmd.com/read/28431428/computational-and-in-vitro-experimental-investigation-of-intrathecal-drug-distribution-parametric-study-of-the-effect-of-injection-volume-cerebrospinal-fluid-pulsatility-and-drug-uptake
#1
Kevin M Tangen, Roxanne Leval, Ankit I Mehta, Andreas A Linninger
BACKGROUND: Intrathecal drug delivery is an attractive option to circumvent the blood-brain barrier for pain management through its increased efficacy of pain relief, reduction in adverse side effects, and cost-effectiveness. Unfortunately, there are limited guidelines for physicians to choose infusion or drug pump settings to administer therapeutic doses to specific regions of the spine or the brain. Although empiric trialing of intrathecal drugs is critical to determine the sustained side effects, currently there is no inexpensive in vitro method to guide the selection of spinal drug delivery parameters...
May 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28431395/correlation-of-genomic-alterations-assessed-by-next-generation-sequencing-ngs-of-tumor-tissue-dna-and-circulating-tumor-dna-ctdna-in-metastatic-renal-cell-carcinoma-mrcc-potential-clinical-implications
#2
Andrew W Hahn, David M Gill, Benjamin Maughan, Archana Agarwal, Lubina Arjyal, Sumati Gupta, Jessica Streeter, Erin Bailey, Sumanta K Pal, Neeraj Agarwal
INTRODUCTION: Tumor tissue and circulating tumor DNA (ctDNA) next-generation sequencing (NGS) testing are frequently performed to detect genomic alterations (GAs) to help guide treatment in metastatic renal cell carcinoma (mRCC), especially after progression on standard systemic therapy. Our objective was to assess if GAs detected by ctDNA NGS are different from those detected by tumor tissue NGS, specifically in patients with mRCC, and if these platforms are interchangeable or complimentary...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431353/discovery-of-potential-anticancer-multi-targeted-ligustrazine-based-cyclohexanone-and-oxime-analogs-overcoming-the-cancer-multidrug-resistance
#3
Gao-Feng Zha, Hua-Li Qin, Bahaa G M Youssif, Muhammad Wahab Amjad, Maria Abdul Ghafoor Raja, Ahmed H Abdelazeem, Syed Nasir Abbas Bukhari
The drug research and development nowadays is focusing on multi-target drugs. In the treatment of cancer, therapies using drugs inhibiting one numerous targets signify a novel viewpoint. In comparison with traditional therapy, multi-targeted drugs directly aim cell subpopulations which are involved in progression of tumor. The current study comprises the synthesis of 34 novel ligustrazine-containing α, β-unsaturated carbonyl-based compounds and oximes. The growth of 5 various cancer cell types was strongly inhibited by ligustrazine-containing oximes as revealed by biological evaluation...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28431322/xanthohumol-and-8-prenylnaringenin-ameliorate-diabetic-related-metabolic-dysfunctions-in-mice
#4
Raquel Costa, Ilda Rodrigues, Luísa Guardão, Sílvia Rocha-Rodrigues, Carolina Silva, José Magalhães, Manuel Ferreira-de-Almeida, Rita Negrão, Raquel Soares
Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by metabolic disturbances in specific tissues. The present work aimed to analyze the effects of xanthohumol (XN) and 8-prenylnaringenin (8PN), two beer-derived polyphenols, in liver and skeletal muscle lipid and glycolytic metabolism in T2DM mice model. Thirty C57Bl/6 mice were randomly divided into five groups: standard diet (control), high-fat diet (DM), high-fat diet plus ethanol (DM-Ethanol), high-fat diet plus 10 mg/L XN (DM-XN) and high-fat diet plus 10 mg/L 8PN (DM-8PN) during 20 weeks...
April 6, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28431280/interleukin-1-receptor-associated-kinase-1-is-a-potential-therapeutic-target-of-anti-inflammatory-therapy-for-systemic-lupus-erythematosus
#5
Mingfang Li, Datang Yu, Bing Ni, Fei Hao
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease and currently has no effective therapy. The genome-wide analyses indicate that interleukin-1 receptor associated kinase 1 (IRAK1) is associated with the susceptibility of SLE in humans. In the present study, we identified that IRAK1 was overexpressed and hyper-activated in splenic mononuclear cells from B6.MRL-Fas(lpr)/Nju (B6.lpr) mice and peripheral blood mononuclear cells (PBMCs) from SLE patients. Intraperitoneal treatment with a small molecular inhibitor of IRAK1 (IRAK1/4 inhibitor or IRAK-Inh) significantly mitigated inflammatory responses and renal injury in B6...
April 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28431270/clinicians-conflicting-emotional-responses-to-high-suicide-risk-patients-association-with-short-term-suicide-behaviors-a-prospective-pilot-study
#6
Zimri S Yaseen, Igor I Galynker, Lisa J Cohen, Jessica Briggs
BACKGROUND: Clinician's emotional responses to patients have been recognized as potentially relating to treatment outcome, however they have received little attention in the literature on suicide risk. We examine the relationship between a novel targeted measure of clinicians' emotional responses to high-risk psychiatric inpatients and their short-term post-discharge suicide behavior. METHODS: First-year psychiatry residents' emotional responses to their patients were assessed anonymously with the novel self-report 'Therapist Response Questionnaire-Suicide Form' (TRQ-SF)...
April 6, 2017: Comprehensive Psychiatry
https://www.readbyqxmd.com/read/28431267/mir-19-targeting-of-gsk3%C3%AE-mediates-sulforaphane-suppression-of-lung-cancer-stem-cells
#7
Jianyun Zhu, Shijia Wang, Yue Chen, Xiaoting Li, Ye Jiang, Xue Yang, Yuan Li, Xiaoqian Wang, Yu Meng, Mingming Zhu, Xiao Ma, Cong Huang, Rui Wu, Chunfeng Xie, Shanshan Geng, Jieshu Wu, Caiyun Zhong, Hongyu Han
Cancer stem cells (CSCs) play a central role in the development of cancer. The canonical Wnt/β-catenin pathway is critical for maintaining stemness of CSCs. Phytochemicals from dietary compounds possess anti-CSCs properties and have been characterized as promising therapeutic agents for the prevention and treatment of many cancers. To date, the involvement and function of miR-19, a key oncogenic miRNA, in regulating Wnt/β-catenin pathway and lung CSCs has not been defined. Meanwhile, the effect of sulforaphane (SFN) on lung CSCs also remains to be elucidated...
April 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28431262/immunologic-approaches-for-the-treatment-of-multiple-myeloma
#8
REVIEW
Leo Rasche, Niels Weinhold, Gareth J Morgan, Frits van Rhee, Faith E Davies
The FDA approval of two monoclonal antibodies in 2015has heralded a new era of targeted immunotherapies for multiple myeloma (MM). In this review we discuss the recent approaches using different immunological components to treat MM. In particular, we review current monoclonal antibody based therapies, engineered T- and NK cell products, 'off-target' immunomodulation, and strategies utilizing allogeneic cell transplantation in MM. We discuss how an immunologic approach offers promise for the treatment of this genetically heterogeneous disease, and how patients with acquired drug resistance may particularly benefit from these therapies...
April 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28431122/the-sense-study-treatment-mechanisms-of-a-cognitive-behavioral-and-mindfulness-based-group-sleep-improvement-intervention-for-at-risk-adolescents
#9
Matthew Blake, Orli Schwartz, Joanna M Waloszek, Monika Raniti, Julian G Simmons, Greg Murray, Laura Blake, Ronald E Dahl, Richard Bootzin, Dana L McMakin, Paul Dudgeon, John Trinder, Nicholas B Allen
Objective: The aim of this study was to test whether a cognitive-behavioral and mindfulness-based sleep intervention could improve sleep and anxiety on school nights in a group of at-risk adolescents. We also examined whether benefits to sleep and anxiety would be mediated by improvements in sleep hygiene awareness and pre-sleep hyperarousal. Method: Secondary analysis of a randomized controlled trial conducted with 123 adolescent participants (Female=60%; Mean Age=14...
April 18, 2017: Sleep
https://www.readbyqxmd.com/read/28431115/spatial-distribution-of-falciparum-malaria-infections-in-zanzibar-implications-for-focal-drug-administration-strategies-targeting-asymptomatic-parasite-carriers
#10
Anders Björkman, Jackie Cook, Hugh Sturrock, Mwinyi Msellem, Abdullah Ali, Weiping Xu, Fabrizio Molteni, Roly Gosling, Chris Drakeley, Andreas Mårtensson
Background.: Optimal use of mass/targeted screen-and-treat or mass or focal drug administration as malaria elimination strategies remains unclear. We therefore studied spatial distribution of Plasmodium falciparum infections to compare simulated effects of these strategies on reducing the parasite reservoir in a pre-elimination setting. Methods.: P. falciparum rapid diagnostic tests (RDTs) and molecular (polymerase chain reaction [PCR]) and serological (enzyme-linked immunosorbent assay) analyses were performed on finger-prick blood samples from a population-based survey in 3 adjacent communities...
May 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28431070/emerging-molecular-therapies-targeting-myocardial-infarction-related-arrhythmias
#11
Helen E Driessen, Toon A B van Veen, Gerard J J Boink
Cardiac disease is the leading cause of death in the developed world. Ventricular arrhythmias associated with myocardial ischaemia and/or infarction are a major contributor to cardiovascular mortality, and require improved prevention and treatment. Drugs, devices, and radiofrequency catheter ablation have made important inroads, but have significant limitations ranging from incomplete success to undesired toxicities and major side effects. These limitations derive from the nature of the intervention. Drugs are frequently ineffective, target the entire heart, and often do not deal with the specific arrhythmia trigger or substrate...
April 1, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28431011/the-relationship-between-pain-characteristics-peer-difficulties-and-emotional-functioning-among-adolescents-seeking-treatment-for-chronic-pain-a-test-of-mediational-models
#12
Sherilynn F Chan, Mark Connelly, Dustin P Wallace
To evaluate patterns of relationships between pain characteristics, peer difficulties, and emotional functioning in a sample of adolescents seeking treatment for chronic pain. Participants were 172 adolescents (age M  = 14.88 years; 76% female, 88% White) with heterogeneous chronic pain disorders who completed measures of pain characteristics, peer difficulties, and emotional functioning before their new patient appointment in a pain management clinic. Direct and indirect relationships between variables were tested using path analysis...
April 19, 2017: Journal of Pediatric Psychology
https://www.readbyqxmd.com/read/28430999/repurposing-quantiferon-for-detection-of-neutralizing-ifn-%C3%AE-autoantibodies-in-patients-with-nontuberculous-mycobacterial-infections
#13
Isabelle Suárez, Clara Lehmann, Henning Gruell, Jessica Graeb, Matthias Kochanek, Gerd Fätkenheuer, Georg Plum, Annelies van Wengen, Esther van de Vosse, Pia Hartmann, Leif G Hanitsch, Jan Rybniker
Nontuberculous mycobacterial (NTM) infections due to autoantibodies targeting IFN-γ are an emerging medical problem. However, case finding is hampered due to highly complex diagnostic procedures not available in routine laboratories. We show that QuantiFERON assays can be exploited as a simple screening tool that may facilitate adequate and timely treatment.
April 20, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28430956/achieving-high-reliability-in-histology-%C3%A2-an-improvement-series-to-reduce-errors
#14
Yael K Heher, Yigu Chen, Sergey Pyatibrat, Edward Yoon, Jeffrey D Goldsmith, Kenneth E Sands
Objectives: Despite sweeping medical advances in other fields, histology processes have by and large remained constant over the past 175 years. Patient label identification errors are a known liability in the laboratory and can be devastating, resulting in incorrect diagnoses and inappropriate treatment. The objective of this study was to identify vulnerable steps in the histology workflow and reduce the frequency of labeling errors (LEs). Methods: In this 36-month study period, a numerical step key (SK) was developed to capture LEs...
November 1, 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28430919/non-coding-rnas-in-cardiovascular-diseases-diagnostic-and-therapeutic-perspectives
#15
Wolfgang Poller, Stefanie Dimmeler, Stephane Heymans, Tanja Zeller, Jan Haas, Mahir Karakas, David-Manuel Leistner, Philipp Jakob, Shinichi Nakagawa, Stefan Blankenberg, Stefan Engelhardt, Thomas Thum, Christian Weber, Benjamin Meder, Roger Hajjar, Ulf Landmesser
Recent research has demonstrated that the non-coding genome plays a key role in genetic programming and gene regulation during development as well as in health and cardiovascular disease. About 99% of the human genome do not encode proteins, but are transcriptionally active representing a broad spectrum of non-coding RNAs (ncRNAs) with important regulatory and structural functions. Non-coding RNAs have been identified as critical novel regulators of cardiovascular risk factors and cell functions and are thus important candidates to improve diagnostics and prognosis assessment...
April 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28430910/low-density-lipoprotein-cholesterol-targeting-with-pitavastatin-ezetimibe-for-patients-with-acute-coronary-syndrome-and-dyslipidaemia-the-hij-proper-study-a-prospective-open-label-randomized-trial
#16
Nobuhisa Hagiwara, Erisa Kawada-Watanabe, Ryo Koyanagi, Hiroyuki Arashi, Junichi Yamaguchi, Koichi Nakao, Tetsuya Tobaru, Hiroyuki Tanaka, Toshiaki Oka, Yasuhiro Endoh, Katsumi Saito, Tatsuro Uchida, Kunihiko Matsui, Hiroshi Ogawa
Aims: To elucidate the effects of intensive LDL-C lowering treatment with a standard dose of statin and ezetimibe in patients with dyslipidaemia and high risk of coronary events, targeting LDL-C less than 70 mg/dL (1.8 mmol/L), compared with standard LDL-C lowering lipid monotherapy targeting less than 100 mg/dL (2.6 mmol/L). Methods and Results: The HIJ-PROPER study is a prospective, randomized, open-label trial to assess whether intensive LDL-C lowering with standard-dose pitavastatin plus ezetimibe reduces cardiovascular events more than standard LDL-C lowering with pitavastatin monotherapy in patients with acute coronary syndrome (ACS) and dyslipidaemia...
April 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28430892/anti-arrhythmic-potential-of-the-late-sodium-current-inhibitor-gs-458967-in-murine-scn5a-1798insd-and-human-scn5a-1795insd-ipsc-derived-cardiomyocytes
#17
Vincent Portero, Simona Casini, Maaike Hoekstra, Arie O Verkerk, Isabella Mengarelli, Luiz Belardinelli, Sridharan Rajamani, Arthur A M Wilde, Connie R Bezzina, Marieke W Veldkamp, Carol Ann Remme
AIM: Selective inhibition of cardiac late sodium current (INaL) is an emerging target in the treatment of ventricular arrhythmias. We investigated the electrophysiological effects of GS-458967 (GS967), a potent, selective inhibitor of INaL, in an overlap syndrome model of both gain and loss of sodium channel function, comprising cardiomyocytes derived from both human SCN5A-1795insD+/- induced pluripotent stem cells (hiPSC-CMs) and mice carrying the homologous mutation Scn5a-1798insD+/-...
April 18, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28430857/repurposed-drugs-targeting-eif2%C3%AE-p-mediated-translational-repression-prevent-neurodegeneration-in-mice
#18
Mark Halliday, Helois Radford, Karlijn A M Zents, Collin Molloy, Julie A Moreno, Nicholas C Verity, Ewan Smith, Catharine A Ortori, David A Barrett, Martin Bushell, Giovanna R Mallucci
Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer's disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss...
April 19, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28430840/checkpoint-dependent-phosphorylation-of-med1-trap220-in-response-to-dna-damage
#19
Hyun-Ju Kim, Jeanho Yun
Mediator complex subunit 1 (Med1)/Thyroid hormone receptor-associated protein 220 (TRAP220), an essential component of thyroid hormone receptor-associated proteins (TRAP)/mediator, plays important roles in hormone responses and tumorigenesis. However, the role of Med1 in the DNA damage response has not been studied. In this study, we found that DNA damage, resulted from γ-irradiation, ultraviolet (UV)-irradiation, or hydroxyurea, induced phosphorylation of Med1 in vivo. Phosphorylation of Med1 was abrogated by either caffeine or wortmannin treatment, suggesting that Med1 is phosphorylated through the DNA damage checkpoint pathway...
April 19, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28430714/ultrasound-molecular-imaging-of-inflammation-in-mouse-abdominal-aorta
#20
Shiying Wang, Sunil Unnikrishnan, Elizabeth B Herbst, Alexander L Klibanov, Frank William Mauldin, John A Hossack
OBJECTIVES: The aim of this study was to demonstrate a new clinically translatable ultrasound molecular imaging approach, modulated acoustic radiation force-based imaging, which is capable of rapid and reliable detection of inflammation as validated in mouse abdominal aorta. MATERIALS AND METHODS: Animal studies were approved by the Institutional Animal Care and Use Committee at the University of Virginia. C57BL/6 mice stimulated with tumor necrosis factor α, or fed with a high-fat diet, were used as inflammation (MInflammation) and diet-induced obesity (DIO) (MDIO) models, respectively...
April 20, 2017: Investigative Radiology
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