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https://www.readbyqxmd.com/read/28221861/inhibiting-histone-deacetylase-as-a-means-to-reverse-resistance-to-angiogenesis-inhibitors-phase-i-study-of-abexinostat-plus-pazopanib-in-advanced-solid-tumor-malignancies
#1
Rahul Aggarwal, Scott Thomas, Nela Pawlowska, Imke Bartelink, Jennifer Grabowsky, Thierry Jahan, Amy Cripps, Armand Harb, Jim Leng, Anne Reinert, Ilaria Mastroserio, Thach-Giao Truong, Charles J Ryan, Pamela N Munster
Purpose This phase I trial evaluated epigenetic modulation of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor by using a histone deacetylase abexinostat in combination with pazopanib to enhance response and reverse resistance. Patients and Methods Pazopanib was administered once a day on days 1 to 28 and abexinostat was administered orally twice a day on days 1 to 5, 8 to 12, and 15 to 19 (schedule A) or on days 1 to 4, 8 to 11, and 15 to 18 (schedule B). Dose escalation (3 + 3 design) in all solid tumors was followed by dose expansion in renal cell carcinoma (RCC)...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28221285/genome-wide-methylation-analysis-of-a-large-population-sample-shows-neurological-pathways-involvement-in-chronic-widespread-musculoskeletal-pain-cwp
#2
Gregory Livshits, Ida Malkin, Maxim B Freidin, Yudong Xia, Fei Gao, Jun Wang, Timothy D Spector, Alex MacGregor, Jordana T Bell, Frances Mk Williams
Chronic widespread musculoskeletal pain (CWP), has a considerable heritable component, which remains to be explained. Epigenetic factors may contribute to and account for some of the heritability estimate. We analysed epigenome-wide methylation using MeDIPseq in whole blood DNA from 1708 monozygotic (MZ) and dizygotic (DZ) Caucasian twins having CWP prevalence of 19.9%. Longitudinally stable methylation bins (lsBINs), were established by testing repeated measurements conducted ≥3 years apart, n=292. DNA methylation variation at lsBINs was tested for association with CWP in a discovery set of 50 MZ twin pairs discordant for CWP, and in an independent dataset (n=1608 twins), and the results from the two samples were combined using Fisher's method...
February 15, 2017: Pain
https://www.readbyqxmd.com/read/28220684/living-donor-liver-transplantation-during-the-first-three-months-of-life
#3
Mureo Kasahara, Seisuke Sakamoto, Kengo Sasaki, Hajime Uchida, Toshihiro Kitajima, Takanobu Shigeta, Soichi Narumoto, Yoshihiro Hirata, Akinari Fukuda
BACKGROUND: Living donor liver transplantation is now an established technique for treating children with end-stage liver disease. Few data exist about liver transplantation for exclusively young infants, especially infants of <3 months of age. We report our single-center experience with 12 cases in which living donor liver transplantation (LT) was performed during the first 3 months of life and compare the results with those of older infants who underwent LT. All of the patients were treated at the National Center of Child Health and Development, Tokyo, Japan...
February 21, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28220578/renal-damage-following-alloxan-induced-diabetes-is-associated-with-generation-of-reactive-oxygen-species-alterations-of-p53-tgf-%C3%AE-1-and-extracellular-matrix-metalloproteinases-in-rats
#4
Mohamed A Abdel Aziz, Dalia M Badary, Mahmoud Rezk Abdelwahed Hussein
: Renal damage is a common problem in diabetes. Alloxan , a potent hyperglycemic and diabetogenic molecule, can induce diabetes through oxidative stress-related mechanisms. Here, we hypothesize that "Alloxan-induced renal damage is associated with alterations of p53, TGF-β1 and extracellular matrix metalloproteinases". To test our hypothesis, we established an animal model (male abino rats) and induced diabetes by intraperitoneal injection of Alloxan monohydrate. Rats with fasting blood glucose level ≥ 200 mg/dl were considered diabetic and were sacrificed after 14, 28, and 42 day intervals...
February 21, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28220499/three-year-follow-up-of-implementation-of-evidence-based-transfusion-practice-in-a-tertiary-hospital
#5
A Norgaard, J Stensballe, T H de Lichtenberg, J O White, A Perner, M Wanscher, J Hillingsø, M L Holm, M Mau-Sørensen, H Sillesen, L Kjeldsen, C Bäck, J Nielsen, J Seeberg, M B Hansen, P I Johansson
BACKGROUND AND OBJECTIVES: Traditionally, Denmark has had a high rate of allogeneic red blood cell transfusion caused by a liberal transfusion practice despite the existence of restrictive guidelines. We established a Patient Blood Management programme in a tertiary hospital and report the results of the implementation of evidence-based transfusion practice. MATERIALS AND METHODS: Red blood cell transfusion quality indicators were compared with the evidence-based guideline at hospital and department level...
February 20, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28220320/a-novel-method-for-non-invasively-detecting-the-severity-and-location-of-aortic-aneurysms
#6
Igor Sazonov, Ashraf W Khir, Wisam S Hacham, Etienne Boileau, Jason M Carson, Raoul van Loon, Colin Ferguson, Perumal Nithiarasu
The influence of an aortic aneurysm on blood flow waveforms is well established, but how to exploit this link for diagnostic purposes still remains challenging. This work uses a combination of experimental and computational modelling to study how aneurysms of various size affect the waveforms. Experimental studies are carried out on fusiform-type aneurysm models, and a comparison of results with those from a one-dimensional fluid-structure interaction model shows close agreement. Further mathematical analysis of these results allows the definition of several indicators that characterize the impact of an aneurysm on waveforms...
February 21, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28219980/activation-of-neuronal-endothelin-b-receptors-mediates-pressor-response-through-alpha-1-adrenergic-receptors
#7
Bryan K Becker, Joshua S Speed, Mackenzie Powell, David M Pollock
Abnormalities in activity of the endothelin (ET) system have been widely reported in a number of cardiovascular disease states such as hypertension and heart failure. Although the vascular responses to ET are well established, the interaction between ET and other important modulators of blood pressure, such as the sympathetic nervous system, are less understood. Previous reports implicate ET signaling through ET type B (ETB) receptors in increasing neuronal activity. Therefore, we hypothesized that activation of ETB receptors on sympathetic nerves would increase blood pressure through an adrenergic-mediated mechanism...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28219818/ultrasonic-versus-electrosurgical-device-for-laparoscopic-cholecystectomy-a-systematic-review-with-meta-analysis-and-trial-sequential-analysis
#8
REVIEW
Hong-Peng Jiang, Ya-Dong Liu, Yan-Sen Li, Zhan-Long Shen, Ying-Jiang Ye
BACKGROUND: Ultrasonic and electrosurgical energy dissectors are main dissecting devices widely used for the laparoscopic cholecystectomy. Trial sequential analyses can establish whether firm evidence favoring a specific device has been reached from accumulated literature. To explore this, we performed a meta-analysis and trial sequential analyses. METHODS: PubMed, Embase, and the Cochrane Library were searched from inception to October 2016. The primary outcome was operative time...
February 17, 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/28219768/copper-therapy-reduces-intravascular-hemolysis-and-derepresses-ferroportin-in-mice-with-mosaic-mutation-atp7a-mo-ms-an-implication-for-copper-mediated-regulation-of-the-slc40a1-gene-expression
#9
Małgorzata Lenartowicz, Rafał R Starzyński, Aneta Jończy, Robert Staroń, Justyna Antoniuk, Wojciech Krzeptowski, Paweł Grzmil, Aleksandra Bednarz, Olga Pierzchała, Mateusz Ogórek, Zenon Rajfur, Zbigniew Baster, Paweł Lipiński
Mosaic mutant mice displaying functional dysfunction of Atp7a copper transporter (the Menkes ATPase) are an established animal model of Menkes disease and constitute a convenient tool for investigating connections between copper and iron metabolisms. This model allows to explore changes in iron metabolism in suckling mutant mice suffering from systemic copper deficiency as well as in young and adult ones undergone copper therapy, which reduces lethal effect of the Atp7a gene mutation. Our recent study demonstrated that 14-day-old mosaic mutant males display blood cell abnormalities associated with intravascular hemolysis, and show disturbances in the functioning of the hepcidin-ferroportin regulatory axis, which controls systemic iron homeostasis...
February 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28219652/influence-of-age-sex-and-hcmv-serostatus-on-blood-lymphocyte-subpopulations-in-healthy-adults
#10
P A Apoil, B Puissant-Lubrano, N Congy-Jolivet, M Peres, J Tkaczuk, F Roubinet, A Blancher
Using a standardized immunophenotyping procedure we studied thirty-eight distinct subpopulations of T, B and NK lymphocytes in 253 healthy blood donors aged from 19 to 67. We analysed the influence of age, sex and HCMV seropositivity on each lymphocyte subpopulations and established reference ranges. We observed that aging influences the largest number of lymphocyte subpopulations with a slow increase of CD8+ EMRA T lymphocytes and of the numbers of circulating Tregs. The proportion of HLA-DR+ cells among Tregs increased with age and was correlated to the proportion of HLA-DR+ cells among effector T CD4+ lymphocytes...
February 9, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28219589/estimation-of-right-lobe-graft-weight-from-computed-tomographic-volumetry-for-living-donor-liver-transplantation
#11
X Yang, C W Chu, J D Yang, K H Yang, H C Yu, B H Cho, H You
BACKGROUND: The objective of the study was to establish a right-lobe graft weight (GW) estimation formula for living donor liver transplantation (LDLT) from right-lobe graft volume without veins (GVw/o_veins), including portal vein and hepatic vein measured by computed tomographic (CT) volumetry, and to compare its estimation accuracy with those of existing formulas. Right-lobe GW estimation formulas established with the use of graft volume with veins (GVw_veins) sacrifice accuracy because GW measured intra-operatively excludes the weight of blood in the veins...
March 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28218758/variant-aware-saturating-mutagenesis-using-multiple-cas9-nucleases-identifies-regulatory-elements-at-trait-associated-loci
#12
Matthew C Canver, Samuel Lessard, Luca Pinello, Yuxuan Wu, Yann Ilboudo, Emily N Stern, Austen J Needleman, Frédéric Galactéros, Carlo Brugnara, Abdullah Kutlar, Colin McKenzie, Marvin Reid, Diane D Chen, Partha Pratim Das, Mitchel A Cole, Jing Zeng, Ryo Kurita, Yukio Nakamura, Guo-Cheng Yuan, Guillaume Lettre, Daniel E Bauer, Stuart H Orkin
Cas9-mediated, high-throughput, saturating in situ mutagenesis permits fine-mapping of function across genomic segments. Disease- and trait-associated variants identified in genome-wide association studies largely cluster at regulatory loci. Here we demonstrate the use of multiple designer nucleases and variant-aware library design to interrogate trait-associated regulatory DNA at high resolution. We developed a computational tool for the creation of saturating-mutagenesis libraries with single or multiple nucleases with incorporation of variants...
February 20, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28218221/gene-expressions-underlying-mishandled-calcium-clearance-and-elevated-generation-of-reactive-oxygen-species-in-the-coronary-artery-smooth-muscle-cells-of-chronic-heart-failure-rats
#13
Liang Ding, Xian-Xiu Su, Wen-Hui Zhang, Yu-Xiang Xu, Xue-Feng Pan
BACKGROUND: The calcium clearance and reactive oxygen species (ROS) generations in the coronary artery smooth muscle cells in chronic heart failure (HF) have not been fully investigated. Therefore, we attempted to understand the gene expressions underlying the mishandling of calcium clearance and the accumulations of ROS. METHODS: We initially established an animal model of chronic HF by making the left anterior descending coronary artery ligation (CAL) in rats, and then isolated the coronary artery vascular smooth muscle cells from the ischemic and the nonischemic parts of the coronary artery vessels in 12 weeks after CAL operation...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28218220/establishment-of-a-rabbit-model-of-chronic-obstructive-sleep-apnea-and-application-in-cardiovascular-consequences
#14
Li-Fang Xu, Xiu-Fang Zhou, Ke Hu, Si Tang, Yu-Chuan Luo, Wen Lu
BACKGROUND: Although obstructive sleep apnea (OSA) has been recognized as a major risk factor for cardiovascular complications and its clinical features are well characterized, it is difficult to replicate the OSA hypoxic model in humans. We aimed to establish an experimental rabbit model for chronic OSA and to explore its application to measure blood pressure (BP), myocardial systolic function, and oxidative stress. METHODS: The rabbit model for OSA was established by repeatedly closing the airway and then reopening it...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28217890/cerebellar-hemangioblastoma-with-perivascular-pseudorosette-formation-and-glial-differentiation-a-case-report
#15
Jian Wang, Xu-Yong Lin, Xue-Shan Qiu, En-Hua Wang, Lian-He Yang, Juan-Han Yu
Hemangioblastoma is a well-circumscribed, highly vascular, lipid-rich and low-grade tumor of uncertain histogenesis. Its histopathological features have been well established. Herein, we present a case of cerebellar hemangioblastoma in a 43-year-old woman. Histologically, the tumor was predominantly composed of cellular areas showing eosinophilic or vacuolated stromal cells arranged in nests and sheets. Focally, conventional reticular areas could be seen. Additionally, in some areas, the stromal cells were arranged radially around blood vessels, exhibiting perivascular pseudorosette structures, which were similar mostly to those of ependymomas...
August 24, 2016: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28217808/-lipid-lowering-effect-of-seven-traditional-chinese-medicine-monomers-in-zebrafish-system
#16
Kan Chen, Chang-Qian Wang, Yu-Qi Fan, Zhi-Hua Han, Yue Wang, Lin Gao, Hua-Su Zeng
The present study aimed to study lipid-lowering effect of seven traditional Chinese medicine monomers in zebrafish system. Zebrafish were fed with high fat diet to establish a hyperlipemia model, then fasted and bathed with seven traditional Chinese medicine monomers stigmasterol, triacontanol, chrysophanol, vanillic acid, shikimic acid, polydatin and oleanolic acid respectively. The oil red O staining was used to detect the blood lipids of zebrafish. Serum total cholesterol and triglyceride levels were detected to validate the lipid-lowering effect...
February 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28217776/iron-acquisition-in-fungal-pathogens-of-humans
#17
Gaurav Bairwa, Won Hee Jung, James W Kronstad
The devastating infections that fungal pathogens cause in humans are underappreciated relative to viral, bacterial and parasitic diseases. In recent years, the contributions to virulence of reductive iron uptake, siderophore-mediated uptake and heme acquisition have been identified in the best studied and most life-threatening fungal pathogens: Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. In particular, exciting new work illustrates the importance of iron acquisition from heme and hemoglobin in the virulence of pathogenic yeasts...
February 20, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28217523/safe-and-pragmatic-use-of-sodium-glucose-co-transporter-2-inhibitors-in-type-2-diabetes-mellitus-south-asian-federation-of-endocrine-societies-consensus-statement
#18
REVIEW
Sanjay Kalra, Sujoy Ghosh, A H Aamir, Md Tofail Ahmed, Mohammod Feroz Amin, Sarita Bajaj, Manash P Baruah, Uditha Bulugahapitiya, A K Das, Mimi Giri, Sonali Gunatilake, Saeed A Mahar, Md Faruque Pathan, Nazmul Kabir Qureshi, S Abbas Raza, Rakesh Sahay, Santosh Shakya, Dina Shreshta, Noel Somasundaram, Manilka Sumanatilleke, A G Unnikrishnan, Achini Madushani Wijesinghe
Diabetes prevalence shows a continuous increasing trend in South Asia. Although well-established treatment modalities exist for type 2 diabetes mellitus (T2DM) management, they are limited by their side effect profile. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) with their novel insulin-independent renal action provide improved glycemic control, supplemented by reduction in weight and blood pressure, and cardiovascular safety. Based on the clinical outcomes with SGLT2i in patients with T2DM, treatment strategies that make a "good clinical sense" are desirable...
January 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28217401/presence-of-arachidonoyl-carnitine-is-associated-with-adverse-cardiometabolic-responses-in-hypertensive-patients-treated-with-atenolol
#19
Liming Weng, Yan Gong, Jeffrey Culver, Stephen J Gardell, Christopher Petucci, Alison M Morse, Reginald F Frye, Stephen T Turner, Arlene Chapman, Eric Boerwinkle, John Gums, Amber L Beitelshees, Peggy R Borum, Julie A Johnson, Timothy J Garrett, Lauren M McIntyre, Rhonda M Cooper-DeHoff
INTRODUCTION: Atenolol, a commonly prescribed β blocker for hypertension, is also associated with adverse cardiometabolic effects such as hyperglycemia and dyslipidemia. Knowledge of the mechanistic underpinnings of these adverse effects of atenolol is incomplete. OBJECTIVE: We sought to identify biomarkers associated with risk for these untoward effects of atenolol. We measured baseline blood serum levels of acylcarnitines (ACs) that are involved in a host of different metabolic pathways, to establish associations with adverse cardiometabolic responses after atenolol treatment...
October 2016: Metabolomics: Open Access
https://www.readbyqxmd.com/read/28217314/potential-role-for-clinical-calibration-to-increase-engagement-with-and-application-of-home-telemonitoring-a-report-from-the-heartcycle-programme
#20
Paloma Gastelurrutia, Josep Lupón, Mar Domingo, Wim Stut, Silviu Dovancescu, John Cleland, Lutz Frankenstein, Antoni Bayes-Genis
AIMS: There is a need for alternative strategies that might avoid recurrent admissions in patients with heart failure. home telemonitoring (HTM) to monitor patient's symptoms from a distance may be useful. This study attempts to assess changes in HTM vital signs in response to daily life activities (variations in medication, salt intake, exercise, and stress) and to establish which variations affect weight, blood pressure, and heart rate. METHODS AND RESULTS: We assessed 76 patients with heart failure (mean age 76 ± 10...
February 2017: ESC Heart Failure
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