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https://www.readbyqxmd.com/read/28340513/mendelian-randomisation-implicates-hyperlipidaemia-as-a-risk-factor-for-colorectal-cancer
#1
Henry Rodriguez-Broadbent, Philip J Law, Amit Sud, Kimmo Palin, Sari Tuupanen, Alexandra Gylfe, Ulrika A Hänninen, Tatiana Cajuso, Tomas Tanskanen, Johanna Kondelin, Eevi Kaasinen, Antti-Pekka Sarin, Samuli Ripatti, Johan G Eriksson, Harri Rissanen, Paul Knekt, Eero Pukkala, Pekka Jousilahti, Veikko Salomaa, Aarno Palotie, Laura Renkonen-Sinisalo, Anna Lepistö, Jan Böhm, Jukka-Pekka Mecklin, Nada A Al-Tassan, Claire Palles, Lynn Martin, Ella Barclay, Susan M Farrington, Maria N Timofeeva, Brian F Meyer, Salma M Wakil, Harry Campbell, Christopher G Smith, Shelley Idziaszczyk, Timothy S Maughan, Richard Kaplan, Rachel Kerr, David Kerr, Michael N Passarelli, Jane C Figueiredo, Daniel D Buchanan, Aung K Win, John L Hopper, Mark A Jenkins, Noralane M Lindor, Polly A Newcomb, Steven Gallinger, David Conti, Fred Schumacher, Graham Casey, Lauri A Aaltonen, Jeremy P Cheadle, Ian P Tomlinson, Malcolm G Dunlop, Richard S Houlston
While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP-CRC associations from 9,254 cases and 18,386 controls...
March 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28339581/rationale-and-design-of-the-budapest-crt-upgrade-study-a-prospective-randomized-multicentre-clinical-trial
#2
Bela Merkely, Annamaria Kosztin, Attila Roka, Laszlo Geller, Endre Zima, Attila Kovacs, Andras Mihaly Boros, Helmut Klein, Jerzy K Wranicz, Gerhard Hindricks, Marcell Clemens, Gabor Z Duray, Arthur J Moss, Ilan Goldenberg, Valentina Kutyifa
Aims: There is lack of conclusive evidence from randomized clinical trials on the efficacy and safety of upgrade to cardiac resynchronization therapy (CRT) in patients with implanted pacemakers (PM) or defibrillators (ICD) with reduced left ventricular ejection fraction (LVEF) and chronic heart failure (HF). The BUDAPEST-CRT Upgrade Study was designed to compare the efficacy and safety of CRT upgrade from conventional PM or ICD therapy in patients with intermittent or permanent right ventricular (RV) septal/apical pacing, reduced LVEF, and symptomatic HF...
October 6, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28339579/left-univentricular-pacing-for-cardiac-resynchronization-therapy
#3
Haran Burri, Frits W Prinzen, Maurizio Gasparini, Christophe Leclercq
This review describes the rationale and published evidence for left univentricular pacing for cardiac resynchronization therapy, gives an overview of the existing optimization algorithms featuring this mode, and discusses future perspectives.
October 6, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28339410/unimanual-versus-bimanual-therapy-in-children-with-unilateral-cerebral-palsy-same-same-but-different
#4
Brian Hoare, Susan Greaves
BACKGROUND: There is high-level evidence supporting constraint-induced movement therapy (CIMT) and bimanual therapy for children with unilateral cerebral palsy. Evidence-based intervention includes time-limited, goal-directed, skills-based, intensive blocks of practice based on motor learning theory. AIM AND METHODS: Using supporting literature and clinical insight, we provide a theoretical rationale to highlight previously unreported differences between CIMT and bimanual therapy...
2017: Journal of Pediatric Rehabilitation Medicine
https://www.readbyqxmd.com/read/28339136/eosinophilic-oesophagitis-phenotypes-ready-for-primetime
#5
REVIEW
Dan Atkins, Glenn T Furuta, Chris A Liacouras, Jonathan M Spergel
Eosinophilic Oesophagitis (EoE) is one of the most common causes of reflux like symptoms and feeding problems in children and food impaction and dysphagia in adults with a prevalence of 1:2500. Therapeutic options include diet, use of swallowed corticosteroids or dilation. In the last several years, recent clinical and translational research have identified some common and distinctive features, for example, the varying response to diet and medications. As EoE shares some characteristics with both asthma and inflammatory bowel disease, the advances in these fields suggests that various phenotypes may also exist in patients with EoE...
March 24, 2017: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/28338487/the-evolution-of-disease-chronic-lung-disease-of-infancy-and-pulmonary-hypertension
#6
Michael C Tracy, David N Cornfield
PURPOSE OF REVIEW: Bronchopulmonary dysplasia (BPD) or chronic lung disease of infancy BPD was originally described 50 years ago, in 1967 by Northway et al. This article possesses two fundamental objectives to provide: a brief historical perspective on BPD; and an update relative to current notions of epidemiology, pathophysiology, evaluation, and clinical management of BPD complicated by vascular disease. The review highlights areas of consensus and ongoing uncertainty. RECENT FINDINGS: The clinical cause and presentation of infants with BPD has evolved over the past several decades...
March 23, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28338402/testosterone-plus-finasteride-prevents-bone-loss-without-prostate-growth-in-a-rodent-spinal-cord-injury-model
#7
Joshua F Yarrow, Ean G Phillips, Christine F Conover, Taylor E Bassett, Cong Chen, Tyler Teurlings, Andrea Vasconez, Jonathan Alerte, Hannah M Prock, Jessica M Jiron, Micah Flores, J Ignacio Aguirre, Stephen E Borst, Fan Ye
We have reported that testosterone-enanthate (TE) prevents the musculoskeletal decline occurring acutely after spinal cord injury (SCI), but results in a near doubling of prostate mass. Our purpose was to test the hypothesis that administration of TE plus finasteride (FIN, type II 5α-reductase inhibitor) would prevent the chronic musculoskeletal deficits in our rodent severe contusion SCI model, without inducing prostate enlargement. Forty-three 16-week old male Sprague-Dawley rats received: (1) SHAM surgery (T9 laminectomy), (2) severe (250 kdyne) contusion SCI, (3) SCI+TE (7...
March 24, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28337968/crispr-cas9-mutagenesis-invalidates-a-putative-cancer-dependency-targeted-in-on-going-clinical-trials
#8
Ann Lin, Christopher J Giuliano, Nicole M Sayles, Jason M Sheltzer
The Maternal Embryonic Leucine Zipper Kinase (MELK) has been reported to be a genetic dependency in several cancer types. MELK RNAi and small-molecule inhibitors of MELK block the proliferation of various cancer cell lines, and MELK knockdown has been described as particularly effective against the highly-aggressive basal/triple-negative subtype of breast cancer. Based on these preclinical results, the MELK inhibitor OTS167 is currently being tested as a novel chemotherapy agent in several clinical trials. Here, we report that mutagenizing MELK with CRISPR/Cas9 has no effect on the fitness of basal breast cancer cell lines or cell lines from six other cancer types...
March 24, 2017: ELife
https://www.readbyqxmd.com/read/28337964/targeting-cd47-enhances-the-efficacy-of-anti-pd-1-and-ctla-4-in-esophageal-squamous-cell-cancer-preclinical-model
#9
Hua Tao, Pudong Qian, Feijiang Wang, Hongliang Yu, Yesong Guo
Esophageal squamous cell cancer is a highly aggressive cancer with dismal five-year survival rate. CD47 is a cell transmembrane protein that is involved in cell apoptosis, proliferation, adhesion, migration, and antigen presenting of the immune system. Via interacting with signal regulatory protein-alpha expressed in antigen presenting cells (APCs), CD47 acts as an antiphagocytic mechanism to inhibit APCs dependent antigen presenting. Overxpression of CD47 was found in various cancer types. However, its role in esophageal squamous cell cancer is not clear yet...
March 23, 2017: Oncology Research
https://www.readbyqxmd.com/read/28337781/rationale-and-design-of-a-multicenter-international-and-collaborative-coronary-artery-aneurysm-registry-caar
#10
Iván J Núñez-Gil, Luis Nombela-Franco, Rodrigo Bagur, Mario Bollati, Enrico Cerrato, Emilio Alfonso, Christoph Liebetrau, José María De la Torre Hernandez, Benjamín Camacho, Rafael Mila, Ignacio J Amat-Santos, Fernando Alfonso, Ramón Rodríguez-Olivares, Santiago J Camacho Freire, Íñigo Lozano, Víctor Alfonso Jiménez Díaz, Davide Piraino, Roberto Adriano Latini, Gisela Feltes, Jose Antonio Linares, Massimo Mancone, Alfonso Ielasi, Alejandro Sánchez-Grande Flecha, Agustín Fernández Cisnal, Fabrizio Ugo, Jesús M Jiménez Mazuecos, Pierluigi Omedè, Marco Pavani, Pedro A Villablanca, Boshra F Louka, Antonio Fernández-Ortiz
Coronary artery aneurysm is defined as a coronary dilation that exceeds the diameter of adjacent segments or the diameter of the patient's largest normal coronary vessel by 1.5×. It is an uncommon disease that has been diagnosed with increasing frequency since the widespread appearance of coronary angiography. The published incidence varies from 1.5% to 5%, suggesting male dominance and a predilection for the right coronary artery. Although several causes have been described, atherosclerosis accounts for ≥50% of coronary aneurysms in adults...
March 24, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28337317/structural-requirements-of-hdac-inhibitors-saha-analogues-modified-at-the-c2-position-display-hdac6-8-selectivity
#11
Ahmed T Negmeldin, Geetha Padige, Anton V Bieliauskas, Mary Kay H Pflum
Histone deacetylase (HDAC) proteins are epigenetic regulators that deacetylate protein substrates, leading to subsequent changes in cell function. HDAC proteins are implicated in cancers, and several HDAC inhibitors have been approved by the FDA as anticancer drugs, including SAHA (suberoylanilide hydroxamic acid; Vorinostat and Zolinza). Unfortunately, SAHA inhibits most HDAC isoforms, which limits its use as a pharmacological tool and may lead to side effects in the clinic. In this work SAHA analogues substituted at the C2 position were synthesized and screened for HDAC isoform selectivity in vitro and in cells...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28337282/chronic-intermittent-hypoxia-affects-endogenous-serotonergic-inputs-and-expression-of-synaptic-proteins-in-rat-hypoglossal-nucleus
#12
Xu Wu, Huan Lu, Lijuan Hu, Wankun Gong, Juan Wang, Cuiping Fu, Zilong Liu, Shanqun Li
Evidence has shown that hypoxic episodes elicit hypoglossal neuroplasticity which depends on elevated serotonin (5-HT), in contrast to the rationale of obstructive sleep apnea (OSA) that deficient serotonergic input to HMs fails to keep airway patency. Therefore, understanding of the 5-HT dynamic changes at hypoglossal nucleus (HN) during chronic intermittent hypoxia (CIH) will be essential to central pathogenic mechanism and pharmacological therapy of OSA. Moreover, the effect of CIH on BDNF-TrkB signaling proteins was quantified in an attempt to elucidate cellular cascades/synaptic mechanisms following 5-HT alteration...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28336782/functional-imaging-signature-of-patients-presenting-with-polycythemia-paraganglioma-syndromes
#13
Ingo Janssen, Clara Chi Chen, Zhenping Zhuang, Corina M Millo, Katherine Wolf, Alexander Ling, Frank I Lin, Karen T Adams, Peter Herscovitch, Richard A Feelders, Antonio T Fojo, David Taieb, Electron Kebebew, Karel Pacak
Rationale: Pheochromocytoma/paraganglioma (PPGL) syndromes associated with polycythemia have previously been described in association with mutations in the von Hippel-Lindau (VHL) gene. Recently, mutations in the prolyl hydroxylase gene (PHD) 1 and 2 and in the hypoxia-inducible factor 2 alpha (HIF2A) were also found to be associated with multiple and recurrent PPGL. Such patients also presented with PPGL and polycythemia, and later on, some presented with duodenal somatostatinoma. In additional patients presenting with PPGL and polycythemia, no further mutations have been discovered...
March 23, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28336670/pi3k-pathway-regulates-er-dependent-transcription-in-breast-cancer-through-the-epigenetic-regulator-kmt2d
#14
Eneda Toska, Hatice U Osmanbeyoglu, Pau Castel, Carmen Chan, Ronald C Hendrickson, Moshe Elkabets, Maura N Dickler, Maurizio Scaltriti, Christina S Leslie, Scott A Armstrong, José Baselga
Activating mutations in PIK3CA, the gene encoding phosphoinositide-(3)-kinase α (PI3Kα), are frequently found in estrogen receptor (ER)-positive breast cancer. PI3Kα inhibitors, now in late-stage clinical development, elicit a robust compensatory increase in ER-dependent transcription that limits therapeutic efficacy. We investigated the chromatin-based mechanisms leading to the activation of ER upon PI3Kα inhibition. We found that PI3Kα inhibition mediates an open chromatin state at the ER target loci in breast cancer models and clinical samples...
March 24, 2017: Science
https://www.readbyqxmd.com/read/28336227/aqueous-calyxes-extract-of-roselle-or-hibiscus-sabdariffa-linn-supplementation-improves-liver-morphology-in-streptozotocin-induced-diabetic-rats
#15
Akhtar Husin Nazratun Nafizah, Siti Balkis Budin, Abd Hamid Zaryantey, Abd Rahman Mariati, Raj Louis Santhana, Mohamad Osman, Md Idris Muhd Hanis, Mohamed Jamaludin
BACKGROUND AND STUDY AIMS: The complex series of deleterious events among diabetes patients leads to multiple organ failure. Therefore, a holistic approach of treatment is urgently required to prevent worsening of complications. The present investigation was carried out to study the possible protective effects of Roselle or Hibiscus sabdariffa Linn (HSL) calyxes aqueous extract, as an antidiabetic and antioxidant agent against oxidative liver injury in streptozotocin-induced diabetic rats...
March 20, 2017: Arab Journal of Gastroenterology: the Official Publication of the Pan-Arab Association of Gastroenterology
https://www.readbyqxmd.com/read/28336109/multivitamin-mineral-supplements-rationale-and-safety
#16
REVIEW
Hans K Biesalski, Jana Tinz
Multivitamin/mineral supplements (MVMs) are widely used in many populations. MVMs, together with iron and folic acid, are recommended for pregnant women to improve birth outcome and to reduce low-birthweight and rates of miscarriage. However, MVM use is common in the general population as well. The aim of the present review was to evaluate the safety of long-term use of these supplements. To examine the safety of MVM use, we performed a literature search for randomized controlled studies involving supplementation with a combination of at least nine vitamins and three minerals at a maximum concentration of 100% of the Recommended Dietary Allowance...
April 2017: Nutrition
https://www.readbyqxmd.com/read/28335790/physical-mechanism-and-modeling-of-heat-generation-and-transfer-in-magnetic-fluid-hyperthermia-through-n%C3%A3-elian-and-brownian-relaxation-a-review
#17
REVIEW
Suriyanto, E Y K Ng, S D Kumar
Current clinically accepted technologies for cancer treatment still have limitations which lead to the exploration of new therapeutic methods. Since the past few decades, the hyperthermia treatment has attracted the attention of investigators owing to its strong biological rationales in applying hyperthermia as a cancer treatment modality. Advancement of nanotechnology offers a potential new heating method for hyperthermia by using nanoparticles which is termed as magnetic fluid hyperthermia (MFH). In MFH, superparamagnetic nanoparticles dissipate heat through Néelian and Brownian relaxation in the presence of an alternating magnetic field...
March 23, 2017: Biomedical Engineering Online
https://www.readbyqxmd.com/read/28335781/tailored-design-of-nkt-stimulatory-glycolipids-for-polarization-of-immune-responses
#18
REVIEW
Jung-Tung Hung, Jing-Rong Huang, Alice L Yu
Natural killer T (NKT) cell is a distinct population of T lymphocytes that can rapidly release massive amount of Th1 and Th2 cytokines upon the engagement of their T cell receptor with glycolipids presented by CD1d. The secreted cytokines can promote cell-mediated immunity to kill tumor cells and intracellular pathogens, or suppress autoreactive immune cells in autoimmune diseases. Thus, NKT cell is an attractive target for developing new therapeutics to manipulate immune system. The best-known glycolipid to activate NKT cells is α-galactosylceramide (α-GalCer), which has been used as a prototype for designing new NKT stimulatory glycolipids...
March 23, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28335646/synthesis-of-an-acridine-orange-sulfonamide-derivative-with-potent-carbonic-anhydrase-ix-inhibitory-action
#19
Marco Bragagni, Fabrizio Carta, Sameh M Osman, Zeid AlOthman, Claudiu T Supuran
Acridine orange (AO) a fluorescent cationic dye used for the management of human musculoskeletal sarcomas, due to its strong tumoricidal action and accumulation in the acidic environment typical of hypoxic tumors, was used for the preparation of a primary sulfonamide derivative. The rationale behind the drug design is the fact that hypoxic, acidic tumors overexpress carbonic anhydrase (CA, EC 4.2.1.1) isoforms, such as CA IX, which is involved in pH regulation, proliferation, cell migration and invasion, and this enzyme is strongly inhibited by primary sulfonamides...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28335106/fast-track-endovascular-aneurysm-repair-rationale-and-design-of-the-multicenter-least-invasive-fast-track-evar-life-registry
#20
Hiranya A Rajasinghe
No abstract text is available yet for this article.
January 2017: Annals of Vascular Surgery
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