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https://www.readbyqxmd.com/read/29351429/removal-of-interscapular-brown-adipose-tissue-increases-aortic-stiffness-despite-normal-systemic-glucose-metabolism-in-mice
#1
Zachary Ian Grunewald, Nathan C Winn, Michelle L Gastecki, Makenzie L Woodford, James R Ball, Sarah A Hansen, Harold S Sacks, Victoria J Vieira-Potter, Jaume Padilla
Brown adipose tissue (BAT) is considered protective against obesity and related cardiometabolic dysfunction. Indeed, activation of BAT improves glucose homeostasis and attenuates cardiovascular disease development. However, whether a reduction in BAT mass perturbs metabolic function and increases risk for cardiovascular disease remains largely unknown. To address this question, C57BL/6J male mice underwent sham or surgical bilateral excision of interscapular BAT (iBATx) and were fed a normal chow or Western diet (WD) for 18 weeks, creating four groups (n=10/group)...
December 20, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29348807/discovery-of-spiro-oxazolidinediones-as-selective-orally-bioavailable-inhibitors-of-p300-cbp-histone-acetyltransferases
#2
Michael R Michaelides, Arthur Kluge, Michael Patane, John H Van Drie, Ce Wang, T Matthew Hansen, Roberto M Risi, Robert Mantei, Carmen Hertel, Kannan Karukurichi, Alexandre Nesterov, David McElligott, Peter de Vries, J William Langston, Philip A Cole, Ronen Marmorstein, Hong Liu, Loren Lasko, Kenneth D Bromberg, Albert Lai, Edward A Kesicki
p300 and its paralog CBP can acetylate histones and other proteins and have been implicated in a number of diseases characterized by aberrant gene activation, such as cancer. A novel, highly selective, orally bioavailable histone acetyltransferase (HAT) domain inhibitor has been identified through virtual ligand screening and subsequent optimization of a unique hydantoin screening hit. Conformational restraint in the form of a spirocyclization followed by substitution with a urea led to a significant improvement in potency...
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29348120/apoc3-loss-of-function-mutations-remnant-cholesterol-low-density-lipoprotein-cholesterol-and-cardiovascular-risk-mediation-and-meta-analyses-of-137-895-individuals
#3
Anders B Wulff, Børge G Nordestgaard, Anne Tybjærg-Hansen
OBJECTIVE: Loss-of-function mutations in APOC3 associate with low remnant cholesterol levels and low risk of ischemic vascular disease (IVD). Because some studies show an additional association with low levels of low-density lipoprotein cholesterol (LDL-C), low LDL-C may explain the low risk of IVD in APOC3 loss-of-function heterozygotes. We tested to what extent the low risk of IVD in APOC3 loss-of-function heterozygotes is mediated by low plasma remnant cholesterol and LDL-C. APPROACH AND RESULTS: In APOC3 loss-of-function heterozygotes versus noncarriers, we first determined remnant cholesterol and LDL-C levels in meta-analyses of 137 895 individuals...
January 18, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29346778/diverse-brain-myeloid-expression-profiles-reveal-distinct-microglial-activation-states-and-aspects-of-alzheimer-s-disease-not-evident-in-mouse-models
#4
Brad A Friedman, Karpagam Srinivasan, Gai Ayalon, William J Meilandt, Han Lin, Melanie A Huntley, Yi Cao, Seung-Hye Lee, Patrick C G Haddick, Hai Ngu, Zora Modrusan, Jessica L Larson, Joshua S Kaminker, Marcel P van der Brug, David V Hansen
Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer's disease (AD) model, we identified microglial subsets-distinct from previously reported "disease-associated microglia"-expressing interferon-related or proliferation modules...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29338016/ultrasound-mediated-delivery-and-distribution-of-polymeric-nanoparticles-in-the-normal-brain-parenchyma-of-a-metastatic-brain-tumour-model
#5
Habib Baghirov, Sofie Snipstad, Einar Sulheim, Sigrid Berg, Rune Hansen, Frits Thorsen, Yrr Mørch, Catharina de Lange Davies, Andreas K O Åslund
The treatment of brain diseases is hindered by the blood-brain barrier (BBB) preventing most drugs from entering the brain. Focused ultrasound (FUS) with microbubbles can open the BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate) nanoparticle-stabilized microbubbles to permeabilize the BBB in a melanoma brain metastasis model. With a dual-frequency ultrasound transducer generating FUS at 1...
2018: PloS One
https://www.readbyqxmd.com/read/29336711/circulating-serum-interleukin-6-serum-chitinase-3-like-protein-1-and-plasma-vascular-endothelial-growth-factor-are-not-predictive-for-remission-and-radiographic-progression-in-patients-with-early-rheumatoid-arthritis-post-hoc-explorative-and-validation-studies
#6
C H Brahe, C Dehlendorff, M Østergaard, J S Johansen, L M Ørnbjerg, K Hørslev-Petersen, K Stengaard-Pedersen, P Junker, T Ellingsen, H Lindegaard, I Hansen, T Lottenburger, S Jacobsen, A G Jurik, M L Hetland
OBJECTIVE: To investigate serum interleukin-6 (IL-6), serum chitinase-3-like protein-1 (YKL-40), and plasma vascular endothelial growth factor (VEGF) as measures of disease activity and predictors of clinical remission and radiographic progression in two early rheumatoid arthritis (RA) randomized controlled trials (RCTs). METHOD: Treatment-naïve patients with early RA (< 6 months' duration) and active disease, participating in two investigator-initiated RCTs, were treated according to a predefined treat-to-target algorithm aiming at inflammatory control, using methotrexate (MTX) + cyclosporine versus MTX + placebo (CIMESTRA study, n = 150, 5 year follow-up) or MTX + adalimumab versus MTX + placebo (OPERA study, n = 180, 2 year follow-up)...
January 16, 2018: Scandinavian Journal of Rheumatology
https://www.readbyqxmd.com/read/29335347/smoking-is-the-most-significant-modifiable-lung-cancer-risk-factor-in-systemic-lupus-erythematosus
#7
Sasha Bernatsky, Rosalind Ramsey-Goldman, Michelle Petri, Murray B Urowitz, Dafna D Gladman, Paul R Fortin, Edward H Yelin, Ellen Ginzler, John G Hanly, Christine Peschken, Caroline Gordon, Ola Nived, Cynthia Aranow, Sang-Cheol Bae, David Isenberg, Anisur Rahman, James E Hansen, Yvan St Pierre, Ann E Clarke
OBJECTIVE: To assess lung cancer risk in systemic lupus erythematosus (SLE), relative to demographics, drug exposures, smoking, and disease activity. METHODS: We analyzed data from 14 SLE cohorts. We calculated adjusted HR estimates for lung cancer in SLE, relative to demographics, smoking, time-dependent medication exposures, and cumulative disease activity [mean adjusted SLE Disease Activity Index (SLEDAI) scores]. This project was approved by the ethics boards of all participating institutions, including the Institutional Review Board of the McGill University Health Centre...
January 15, 2018: Journal of Rheumatology
https://www.readbyqxmd.com/read/29335008/multi-omics-differentially-classify-disease-state-and-treatment-outcome-in-pediatric-crohn-s-disease
#8
Gavin M Douglas, Richard Hansen, Casey M A Jones, Katherine A Dunn, André M Comeau, Joseph P Bielawski, Rachel Tayler, Emad M El-Omar, Richard K Russell, Georgina L Hold, Morgan G I Langille, Johan Van Limbergen
BACKGROUND: Crohn's disease (CD) has an unclear etiology, but there is growing evidence of a direct link with a dysbiotic microbiome. Many gut microbes have previously been associated with CD, but these have mainly been confounded with patients' ongoing treatments. Additionally, most analyses of CD patients' microbiomes have focused on microbes in stool samples, which yield different insights than profiling biopsy samples. RESULTS: We sequenced the 16S rRNA gene (16S) and carried out shotgun metagenomics (MGS) from the intestinal biopsies of 20 treatment-naïve CD and 20 control pediatric patients...
January 15, 2018: Microbiome
https://www.readbyqxmd.com/read/29334373/prevention-of-tuberculosis-in-rhesus-macaques-by-a-cytomegalovirus-based-vaccine
#9
Scott G Hansen, Daniel E Zak, Guangwu Xu, Julia C Ford, Emily E Marshall, Daniel Malouli, Roxanne M Gilbride, Colette M Hughes, Abigail B Ventura, Emily Ainslie, Kurt T Randall, Andrea N Selseth, Parker Rundstrom, Lauren Herlache, Matthew S Lewis, Haesun Park, Shannon L Planer, John M Turner, Miranda Fischer, Christina Armstrong, Robert C Zweig, Joseph Valvo, Jackie M Braun, Smitha Shankar, Lenette Lu, Andrew W Sylwester, Alfred W Legasse, Martin Messerle, Michael A Jarvis, Lynn M Amon, Alan Aderem, Galit Alter, Dominick J Laddy, Michele Stone, Aurelio Bonavia, Thomas G Evans, Michael K Axthelm, Klaus Früh, Paul T Edlefsen, Louis J Picker
Despite widespread use of the bacille Calmette-Guérin (BCG) vaccine, tuberculosis (TB) remains a leading cause of global mortality from a single infectious agent (Mycobacterium tuberculosis or Mtb). Here, over two independent Mtb challenge studies, we demonstrate that subcutaneous vaccination of rhesus macaques (RMs) with rhesus cytomegalovirus vectors encoding Mtb antigen inserts (hereafter referred to as RhCMV/TB)-which elicit and maintain highly effector-differentiated, circulating and tissue-resident Mtb-specific CD4+ and CD8+ memory T cell responses-can reduce the overall (pulmonary and extrapulmonary) extent of Mtb infection and disease by 68%, as compared to that in unvaccinated controls, after intrabronchial challenge with the Erdman strain of Mtb at ∼1 year after the first vaccination...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29331311/prediction-of-mortality-in-patients-with-chronic-obstructive-pulmonary-disease-with-the-new-global-initiative-for-chronic-obstructive-lung-disease-2017-classification-a-cohort-study
#10
Anne Gedebjerg, Szimonetta Komjáthiné Szépligeti, Laura-Maria Holm Wackerhausen, Erzsébet Horváth-Puhó, Ronald Dahl, Jens Georg Hansen, Henrik Toft Sørensen, Mette Nørgaard, Peter Lange, Reimar Wernich Thomsen
BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 classification separates the spirometric 1-4 staging from the ABCD groups defined by symptoms and exacerbations. Little is known about how this new classification predicts mortality in patients with chronic obstructive pulmonary disease (COPD). We aimed to establish the predictive ability of the GOLD 2017 classification, compared with earlier classifications, for all-cause and respiratory mortality, both when using its main ABCD groups and when further subdividing according to spirometric 1-4 staging...
January 10, 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29331164/adherence-to-the-danish-food-based-dietary-guidelines-and-risk-of-myocardial-infarction-a-cohort-study
#11
Camilla Plambeck Hansen, Kim Overvad, Inge Tetens, Anne Tjønneland, Erik Thorlund Parner, Marianne Uhre Jakobsen, Christina Catherine Dahm
OBJECTIVE: A direct way to evaluate food-based dietary guidelines is to assess if adherence is associated with development of non-communicable diseases. Thus, the objective was to develop an index to assess adherence to the 2013 Danish food-based dietary guidelines and to investigate the association between adherence to the index and risk of myocardial infarction (MI). DESIGN: Population-based cohort study with recruitment of participants in 1993-1997. Information on dietary intake was collected at baseline using an FFQ and an index ranging from 0 to 6 points was created to assess adherence to the 2013 Danish food-based dietary guidelines...
January 14, 2018: Public Health Nutrition
https://www.readbyqxmd.com/read/29330278/multiple-cranial-nerve-palsies-secondary-to-a-recurrence-of-hansen-s-disease
#12
Preet Mukesh Shah, Vijay Waman Dhakre, Abhijeet Prasad, Pratit Samdani
No abstract text is available yet for this article.
January 12, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29320294/arresting-leprosy-therapeutic-outcomes-besides-cure
#13
Raúl Necochea López
This essay focuses on the use of the concept of "arrest" in Hansen's disease (leprosy) in the United States in the early to middle part of the 20th century, as well as the transformations the concept underwent with the arrival of sulfone drugs and the implications of these changes for patients and public health officers. An "arrest" was a therapeutic outcome characterized by a long course of treatment, noncontagiousness, a very small chance of reactivation, and a need for postdischarge maintenance that depended on sociomedical infrastructures beyond the clinic as well as self-imposed lifestyle limitations...
February 2018: American Journal of Public Health
https://www.readbyqxmd.com/read/29318966/chronic-inflammatory-diseases-and-atherosclerotic-cardiovascular-disease-innocent-bystanders-or-partners-in-crime
#14
Peter Riis Hansen
Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research...
January 9, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29317276/accuracy-of-the-enhanced-liver-fibrosis-test-vs-fibrotest-elastography-and-indirect-markers-in-detection-of-advanced-fibrosis-in-patients-with-alcoholic-liver-disease
#15
Maja Thiele, Bjørn Stæhr Madsen, Janne Fuglsang Hansen, Sönke Detlefsen, Steen Antonsen, Aleksander Krag
BACKGROUND & AIMS: Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). METHODS: We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day...
January 6, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29311744/mutations-in-vps15-perturb-neuronal-migration-in-mice-and-are-associated-with-neurodevelopmental-disease-in-humans
#16
Thomas Gstrein, Andrew Edwards, Anna Přistoupilová, Ines Leca, Martin Breuss, Sandra Pilat-Carotta, Andi H Hansen, Ratna Tripathy, Anna K Traunbauer, Tobias Hochstoeger, Gavril Rosoklija, Marco Repic, Lukas Landler, Viktor Stránecký, Gerhard Dürnberger, Thomas M Keane, Johannes Zuber, David J Adams, Jonathan Flint, Tomas Honzik, Marta Gut, Sergi Beltran, Karl Mechtler, Elliott Sherr, Stanislav Kmoch, Ivo Gut, David A Keays
The formation of the vertebrate brain requires the generation, migration, differentiation and survival of neurons. Genetic mutations that perturb these critical cellular events can result in malformations of the telencephalon, providing a molecular window into brain development. Here we report the identification of an N-ethyl-N-nitrosourea-induced mouse mutant characterized by a fractured hippocampal pyramidal cell layer, attributable to defects in neuronal migration. We show that this is caused by a hypomorphic mutation in Vps15 that perturbs endosomal-lysosomal trafficking and autophagy, resulting in an upregulation of Nischarin, which inhibits Pak1 signaling...
January 8, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29311636/loss-of-function-variants-in-adcy3-increase-risk-of-obesity-and-type-2-diabetes
#17
Niels Grarup, Ida Moltke, Mette K Andersen, Maria Dalby, Kristoffer Vitting-Seerup, Timo Kern, Yuvaraj Mahendran, Emil Jørsboe, Christina V L Larsen, Inger K Dahl-Petersen, Arthur Gilly, Daniel Suveges, George Dedoussis, Eleftheria Zeggini, Oluf Pedersen, Robin Andersson, Peter Bjerregaard, Marit E Jørgensen, Anders Albrechtsen, Torben Hansen
We have identified a variant in ADCY3 (encoding adenylate cyclase 3) associated with markedly increased risk of obesity and type 2 diabetes in the Greenlandic population. The variant disrupts a splice acceptor site, and carriers have decreased ADCY3 RNA expression. Additionally, we observe an enrichment of rare ADCY3 loss-of-function variants among individuals with type 2 diabetes in trans-ancestry cohorts. These findings provide new information on disease etiology relevant for future treatment strategies.
January 8, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29311533/a-modern-history-of-imperial-medicine-surrounding-hansen-s-disease-strategies-to-manage-public-opinion-in-modern-japanese-media
#18
Gijae Seo
The purpose of this study is to understand the reality of imperial medicine by exploring the strategic attitude of the Japanese authority targeting the public who were not patients of Hansen's disease. For this purpose, this study examines the mass media data related to Hansen's disease published in Korea and Japan during the Japanese colonial rule. Research on Hansen's disease can be divided into medical, sociohistorical, social welfare, and human rights approach. There are medical studies and statistics on the dissemination of medical information about Hansen's disease and management measures, the history of the management of the disease, guarantee of the rights of the patients and the welfare environment, and studies on the autobiographical, literary writings and oral statements on the life and psychological conflicts of the patients...
December 2017: Ŭi Sahak
https://www.readbyqxmd.com/read/29311135/clinical-pharmacokinetics-and-the-impact-of-genetic-polymorphism-on-a-cyp2c19-substrate-bms-823778-in-healthy-subjects
#19
Jiachang Gong, Lars Hansen, Lisa Iacono
BMS-823778 is a potent and selective inhibitor of 11beta-HSD1, an enzyme that regulates tissue specific intracellular glucocorticoid metabolism and a compelling target for the treatment of metabolic diseases. Metabolism of BMS-823778 was mainly mediated by polymorphic CYP2C19 with minor contribution from CYP3A3/5 and UGT1A4. Clinical PK of BMS-823778 was first investigated in healthy volunteers after single and multiple ascending doses. BMS-823778 was rapidly absorbed after oral dose, and systemic exposure at steady state increased proportionally to the dose...
January 8, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29306320/infection-dynamics-and-tissue-tropism-of-parvicapsula-pseudobranchicola-myxozoa-myxosporea-in-farmed-atlantic-salmon-salmo-salar
#20
Are Nylund, Haakon Hansen, Øyvind J Brevik, Håvard Hustoft, Turhan Markussen, Heidrun Plarre, Egil Karlsbakk
BACKGROUND: The myxosporean parasite Parvicapsula pseudobranchicola commonly infects farmed Atlantic salmon in northern Norway. Heavy infections are associated with pseudobranch lesions, runting and mortality in the salmon populations. The life-cycle of the parasite is unknown, preventing controlled challenge experiments. The infection dynamics, duration of sporogony, tissue tropism and ability to develop immunity to the parasite in farmed Atlantic salmon is poorly known. We conducted a field experiment, aiming at examining these aspects...
January 6, 2018: Parasites & Vectors
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