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https://www.readbyqxmd.com/read/29670076/cathelicidins-prime-platelets-to-mediate-arterial-thrombosis-and-tissue-inflammation
#1
Joachim Pircher, Thomas Czermak, Andreas Ehrlich, Clemens Eberle, Erik Gaitzsch, Andreas Margraf, Jochen Grommes, Prakash Saha, Anna Titova, Hellen Ishikawa-Ankerhold, Konstantin Stark, Tobias Petzold, Thomas Stocker, Ludwig T Weckbach, Julia Novotny, Markus Sperandio, Bernhard Nieswandt, Alberto Smith, Hanna Mannell, Barbara Walzog, David Horst, Oliver Soehnlein, Steffen Massberg, Christian Schulz
Leukocyte-released antimicrobial peptides contribute to pathogen elimination and activation of the immune system. Their role in thrombosis is incompletely understood. Here we show that the cathelicidin LL-37 is abundant in thrombi from patients with acute myocardial infarction. Its mouse homologue, CRAMP, is present in mouse arterial thrombi following vascular injury, and derives mainly from circulating neutrophils. Absence of hematopoietic CRAMP in bone marrow chimeric mice reduces platelet recruitment and thrombus formation...
April 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29666184/atp-sensitive-potassium-channels-in-the-sinoatrial-node-contribute-to-heart-rate-control-and-adaptation-to-hypoxia
#2
Qadeer Aziz, Malcolm Finlay, David Montaigne, Leona Ojake, Yiwen Li, Naomi Anderson, Andreas Ludwig, Andrew Tinker
ATP-sensitive potassium channels (KATP ) contribute to membrane currents in many tissues, are responsive to intracellular metabolism, and open as ATP falls and ADP rises. KATP channels are widely distributed in tissues and are prominently expressed in the heart. They have generally been observed in ventricular tissue, but they are also expressed in the atria and conduction tissues. In this study, we focused on the contribution and role of the inwardly rectifying KATP channel subunit, Kir6.1, in the sinoatrial node (SAN)...
April 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29664627/n-%C3%AE%C2%B5-acryloyllysine-piperazides-as-irreversible-inhibitors-of-transglutaminase-2-synthesis-structure-activity-relationships-and-pharmacokinetic-profiling
#3
Robert Wodtke, Christoph Hauser, Gloria Ruiz-Gomez, Elisabeth Jäckel, David Bauer, Martin Lohse, Alan Wong, Johanna Pufe, Friedrich-Alexander Ludwig, Steffen Fischer, Sandra Hauser, Dieter Greif, Maria Teresa Pisabarro, Jens Pietzsch, Markus Pietsch, Reik Löser
Transglutaminase 2 (TGase 2)-catalysed transamidation represents an important posttranslational mechanism for protein modification with implications in physiological and pathophysiological conditions including fibrotic and neoplastic processes. Consequently, this enzyme is considered a promising target for the diagnosis and therapy of these diseases. In this study, we report on the synthesis and kinetic characterisation of Nε -acryloyllysine piperazides as irreversible inhibitors of TGase 2. Systematic structural modifications on 54 new compounds were performed with a major focus on fluorine-bearing substituents due to the potential of such compounds to serve as radiotracer candidates for positron emission tomography...
April 17, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29576024/source-of-bias-in-sugar-sweetened-beverage-research-a-systematic-review
#4
Ethan A Litman, Steven L Gortmaker, Cara B Ebbeling, David S Ludwig
OBJECTIVE: Financial conflicts of interest involving the food industry have been reported to bias nutrition studies. However, some have hypothesized that independently funded studies may be biased if the authors have strong a priori beliefs about the healthfulness of a food product ('white hat bias'). The extent to which each source of bias may affect the scientific literature has not been examined. We aimed to explore this question with research involving sugar-sweetened beverages (SSB) as a test case, focusing on a period during which scientific consensus about the adverse health effects of SSB emerged from uncertainty...
March 26, 2018: Public Health Nutrition
https://www.readbyqxmd.com/read/29575745/evaluation-of-two-dimensional-bruch-s-membrane-opening-minimum-rim-area-for-glaucoma-diagnostics-in-a-large-patient-cohort
#5
Philip Enders, Werner Adler, David Kiessling, Vincent Weber, Friederike Schaub, Manuel M Hermann, Thomas Dietlein, Claus Cursiefen, Ludwig M Heindl
PURPOSE: To characterize the two-dimensional parameter Bruch's membrane opening minimum rim area (BMO-MRA) in spectral domain optical coherence tomography (SD-OCT) of the optic nerve head (ONH) compared to minimum rim width (BMO-MRW) and retinal nerve fibre layer (RNFL) thickness in a large patient cohort. METHODS: Case-control, cross-sectional study of 705 eyes of 445 participants. A total of 449 eyes with glaucoma, 67 eyes with ocular hypertension and 189 healthy controls, underwent SD-OCT and confocal laser scanning tomography (CSLT), visual field testing and clinical examination...
March 24, 2018: Acta Ophthalmologica
https://www.readbyqxmd.com/read/29562167/oncogenic-idh1-mutations-promote-enhanced-proline-synthesis-through-pycr1-to-support-the-maintenance-of-mitochondrial-redox-homeostasis
#6
Kate E R Hollinshead, Haydn Munford, Katherine L Eales, Chiara Bardella, Chunjie Li, Cristina Escribano-Gonzalez, Alpesh Thakker, Yannic Nonnenmacher, Katarina Kluckova, Mark Jeeves, Robert Murren, Federica Cuozzo, Dan Ye, Giulio Laurenti, Wei Zhu, Karsten Hiller, David J Hodson, Wei Hua, Ian P Tomlinson, Christian Ludwig, Ying Mao, Daniel A Tennant
Since the discovery of mutations in isocitrate dehydrogenase 1 (IDH1) in gliomas and other tumors, significant efforts have been made to gain a deeper understanding of the consequences of this oncogenic mutation. One aspect of the neomorphic function of the IDH1 R132H enzyme that has received less attention is the perturbation of cellular redox homeostasis. Here, we describe a biosynthetic pathway exhibited by cells expressing mutant IDH1. By virtue of a change in cellular redox homeostasis, IDH1-mutated cells synthesize excess glutamine-derived proline through enhanced activity of pyrroline 5-carboxylate reductase 1 (PYCR1), coupled to NADH oxidation...
March 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29560379/brain-atrophy-and-disability-worsening-in-primary-progressive-multiple-sclerosis-insights-from-the-informs-study
#7
David H Miller, Fred D Lublin, Maria Pia Sormani, Ludwig Kappos, Özgür Yaldizli, Mark S Freedman, Bruce A C Cree, Howard L Weiner, Catherine Lubetzki, Hans-Peter Hartung, Xavier Montalban, Bernard M J Uitdehaag, David G MacManus, Tarek A Yousry, Claudia A M Gandini Wheeler-Kingshott, Bingbing Li, Norman Putzki, Martin Merschhemke, Dieter A Häring, Jerry S Wolinsky
Objective: To investigate the relationship between brain volume and disability worsening over ≥3 years in the natural history of primary progressive multiple sclerosis using data from the placebo group of the INFORMS trial ( n  = 487; clinicaltrials.gov NCT00731692). Methods: Magnetic resonance imaging scans were collected annually. Brain volume loss was determined using SIENA. Patients were stratified by baseline normalized brain volume after adjusting for demographic and disease-burden covariates...
March 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29554777/multiple-stressor-effects-on-biological-quality-elements-in-the-ebro-river-present-diagnosis-and-predicted-responses
#8
Albert Herrero, Cayetano Gutiérrez-Cánovas, Olga Vigiak, Stefanie Lutz, Rohini Kumar, David Gampe, Verena Huber-García, Ralf Ludwig, Ramon Batalla, Sergi Sabater
Multiple abiotic stressors affect the ecological status of water bodies. The status of waterbodies in the Ebro catchment (NE Spain) is evaluated using the biological quality elements (BQEs) of diatoms, invertebrates and macrophytes. The multi-stressor influence on the three BQEs was evaluated using the monitoring dataset available from the catchment water authority. Nutrient concentrations, especially total phosphorus (TP), affected most of the analyzed BQEs, while changes in mean discharge, water temperature, or river morphology did not show significant influences...
March 10, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29528499/population-pharmacokinetics-and-exposure-response-analyses-of-eslicarbazepine-acetate-efficacy-and-safety-in-monotherapy-of-partial-onset-seizures
#9
Soujanya Sunkaraneni, Elizabeth A Ludwig, Julie A Passarell, David Blum, Todd Grinnell, Jill Fiedler-Kelly
Eslicarbazepine acetate (ESL) is a once-daily oral antiepileptic drug (AED) indicated for partial-onset seizures (POS). ESL pharmacokinetics (PK) and exposure-response analyses were supported by 2 phase 3 conversion to ESL (1200, 1600 mg) monotherapy studies. The PK model development included 10 phase 1-2 studies (ESL 600-1200 mg daily). Seizure diaries were completed daily; subjects exited if seizures worsened. Exposure-response models were developed for time to study exit, probability of seizure freedom, time to first occurrence of dizziness, headache, and nausea; serum sodium levels were explored...
March 12, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29526521/stressful-life-events-and-maltreatment-in-conversion-functional-neurological-disorder-systematic-review-and-meta-analysis-of-case-control-studies
#10
Lea Ludwig, Joëlle A Pasman, Timothy Nicholson, Selma Aybek, Anthony S David, Sharon Tuck, Richard A Kanaan, Karin Roelofs, Alan Carson, Jon Stone
BACKGROUND: Stressful life events and maltreatment have traditionally been considered crucial in the development of conversion (functional neurological) disorder, but the evidence underpinning this association is not clear. We aimed to assess the association between stressors and functional neurological disorder. METHODS: We systematically reviewed controlled studies reporting stressors occurring in childhood or adulthood, such as stressful life events and maltreatment (including sexual, physical abuse, and emotional neglect) and functional neurological disorder...
March 8, 2018: Lancet Psychiatry
https://www.readbyqxmd.com/read/29483198/epidemic-childhood-obesity-not-yet-the-end-of-the-beginning
#11
David S Ludwig
No abstract text is available yet for this article.
February 26, 2018: Pediatrics
https://www.readbyqxmd.com/read/29472442/ancient-genomes-revisit-the-ancestry-of-domestic-and-przewalski-s-horses
#12
Charleen Gaunitz, Antoine Fages, Kristian Hanghøj, Anders Albrechtsen, Naveed Khan, Mikkel Schubert, Andaine Seguin-Orlando, Ivy J Owens, Sabine Felkel, Olivier Bignon-Lau, Peter de Barros Damgaard, Alissa Mittnik, Azadeh F Mohaseb, Hossein Davoudi, Saleh Alquraishi, Ahmed H Alfarhan, Khaled A S Al-Rasheid, Eric Crubézy, Norbert Benecke, Sandra Olsen, Dorcas Brown, David Anthony, Ken Massy, Vladimir Pitulko, Aleksei Kasparov, Gottfried Brem, Michael Hofreiter, Gulmira Mukhtarova, Nurbol Baimukhanov, Lembi Lõugas, Vedat Onar, Philipp W Stockhammer, Johannes Krause, Bazartseren Boldgiv, Sainbileg Undrakhbold, Diimaajav Erdenebaatar, Sébastien Lepetz, Marjan Mashkour, Arne Ludwig, Barbara Wallner, Victor Merz, Ilja Merz, Viktor Zaibert, Eske Willerslev, Pablo Librado, Alan K Outram, Ludovic Orlando
The Eneolithic Botai culture of the Central Asian steppes provides the earliest archaeological evidence for horse husbandry, ~5,500 ya, but the exact nature of early horse domestication remains controversial. We generated 42 ancient horse genomes, including 20 from Botai. Compared to 46 published ancient and modern horse genomes, our data indicate that Przewalski's horses are the feral descendants of horses herded at Botai and not truly wild horses. All domestic horses dated from ~4,000 ya to present only show ~2...
February 22, 2018: Science
https://www.readbyqxmd.com/read/29428885/occurrence-of-staphylococcus-aureus-in-swine-and-swine-workplace-environments-on-industrial-and-antibiotic-free-hog-operations-in-north-carolina-usa-a-one-health-pilot-study
#13
Meghan F Davis, Nora Pisanic, Sarah M Rhodes, Alexis Brown, Haley Keller, Maya Nadimpalli, Andrea Christ, Shanna Ludwig, Carly Ordak, Kristoffer Spicer, David C Love, Jesper Larsen, Asher Wright, Sarah Blacklin, Billy Flowers, Jill Stewart, Kenneth G Sexton, Ana M Rule, Christopher D Heaney
Occupational exposure to swine has been associated with increased Staphylococcus aureus carriage, including antimicrobial-resistant strains, and increased risk of infections. To characterize animal and environmental routes of worker exposure, we optimized methods to identify S. aureus on operations that raise swine in confinement with antibiotics (industrial hog operation: IHO) versus on pasture without antibiotics (antibiotic-free hog operation: AFHO). We associated findings from tested swine and environmental samples with those from personal inhalable air samplers on worker surrogates at one IHO and three AFHOs in North Carolina using a new One Health approach...
February 8, 2018: Environmental Research
https://www.readbyqxmd.com/read/29389342/should-dental-care-make-a-transition
#14
EDITORIAL
David C Ludwig, Shane D Morrison
No abstract text is available yet for this article.
February 2018: Journal of the American Dental Association
https://www.readbyqxmd.com/read/29382827/probability-of-phenotypically-detectable-protein-damage-by-enu-induced-mutations-in-the-mutagenetix-database
#15
Tao Wang, Chun Hui Bu, Sara Hildebrand, Gaoxiang Jia, Owen M Siggs, Stephen Lyon, David Pratt, Lindsay Scott, Jamie Russell, Sara Ludwig, Anne R Murray, Eva Marie Y Moresco, Bruce Beutler
Computational inference of mutation effects is necessary for genetic studies in which many mutations must be considered as etiologic candidates. Programs such as PolyPhen-2 predict the relative severity of damage caused by missense mutations, but not the actual probability that a mutation will reduce/eliminate protein function. Based on genotype and phenotype data for 116,330 ENU-induced mutations in the Mutagenetix database, we calculate that putative null mutations, and PolyPhen-2-classified "probably damaging", "possibly damaging", or "probably benign" mutations have, respectively, 61%, 17%, 9...
January 30, 2018: Nature Communications
https://www.readbyqxmd.com/read/29377580/bringing-european-physiologists-together
#16
EDITORIAL
Peter Bie, Ralf Brandes, Susan Deuchars, David Eisner, Joachim Fandrey, Markus Hecker, William Louch, Tomi Taira, Bayram Yilmaz
The modern science of physiology began in Europe. Deciding on exactly who the first physiologist was is not easy but excellent candidates include Claude Bernard and Carl Ludwig. The Nobel Prize in Physiology or Medicine was inaugurated in 1901 with the first award mentioning the word "physiology" being made to Ivan Pavlov (Russia) in 1904. This article is protected by copyright. All rights reserved.
January 29, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29360462/association-between-portosystemic-shunts-and-increased-complications-and-mortality-in-patients-with-cirrhosis
#17
Macarena Simón-Talero, Davide Roccarina, Javier Martínez, Katharina Lampichler, Anna Baiges, Gavin Low, Elba Llop, Michael Praktiknjo, Martin H Maurer, Alexander Zipprich, Michela Triolo, Guillaume Vangrinsven, Rita Garcia-Martinez, Annette Dam, Avik Majumdar, Carmen Picón, Daniel Toth, Anna Darnell, Juan G Abraldes, Marta Lopez, Guido Kukuk, Aleksander Krag, Rafael Bañares, Wim Laleman, Vincenzo La Mura, Cristina Ripoll, Annalisa Berzigotti, Jonel Trebicka, Jose Luis Calleja, Puneeta Tandon, Virginia Hernandez-Gea, Thomas Reiberger, Agustín Albillos, Emmanuel A Tsochatzis, Salvador Augustin, Joan Genescà
BACKGROUND & AIMS: Spontaneous portosystemic shunts (SPSS) have been associated with hepatic encephalopathy (HE). Little is known about their prevalence among patients with cirrhosis or clinical effects. We investigated the prevalence and characteristics of SPSS in patients with cirrhosis and their outcomes. METHODS: We performed a retrospective study of 1729 patients with cirrhosis who underwent abdominal computed tomography or magnetic resonance imaging analysis from 2010 through 2015 at 14 centers in Canada and Europe...
January 31, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29353550/ectrims-ean-guideline-on-the-pharmacological-treatment-of-people-with-multiple-sclerosis
#18
Xavier Montalban, Ralf Gold, Alan J Thompson, Susana Otero-Romero, Maria Pia Amato, Dhia Chandraratna, Michel Clanet, Giancarlo Comi, Tobias Derfuss, Franz Fazekas, Hans Peter Hartung, Eva Havrdova, Bernhard Hemmer, Ludwig Kappos, Roland Liblau, Catherine Lubetzki, Elena Marcus, David H Miller, Tomas Olsson, Steve Pilling, Krysztof Selmaj, Axel Siva, Per Soelberg Sorensen, Maria Pia Sormani, Christoph Thalheim, Heinz Wiendl, Frauke Zipp
BACKGROUND: Multiple sclerosis (MS) is a complex disease with new drugs becoming available in the past years. There is a need for a reference tool compiling current data to aid professionals in treatment decisions. OBJECTIVES: To develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS. METHODS: This guideline has been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and following the updated EAN recommendations...
February 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29341834/improvement-in-overall-survival-with-carfilzomib-lenalidomide-and-dexamethasone-in-patients-with-relapsed-or-refractory-multiple-myeloma
#19
David S Siegel, Meletios A Dimopoulos, Heinz Ludwig, Thierry Facon, Hartmut Goldschmidt, Andrzej Jakubowiak, Jesus San-Miguel, Mihaela Obreja, Julie Blaedel, A Keith Stewart
Purpose In the ASPIRE study of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide plus dexamethasone (Rd) in patients with relapsed or refractory multiple myeloma, progression-free survival was significantly improved in the carfilzomib group (hazard ratio, 0.69; two-sided P < .001). This prespecified analysis reports final overall survival (OS) data and updated safety results. Patients and Methods Adults with relapsed multiple myeloma (one to three prior lines of therapy) were eligible and randomly assigned at a one-to-one ratio to receive KRd or Rd in 28-day cycles until withdrawal of consent, disease progression, or occurrence of unacceptable toxicity...
January 17, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29295838/genetic-evidence-that-carbohydrate-stimulated-insulin-secretion-leads-to-obesity
#20
Christina M Astley, Jennifer N Todd, Rany M Salem, Sailaja Vedantam, Cara B Ebbeling, Paul L Huang, David S Ludwig, Joel N Hirschhorn, Jose C Florez
BACKGROUND: A fundamental precept of the carbohydrate-insulin model of obesity is that insulin secretion drives weight gain. However, fasting hyperinsulinemia can also be driven by obesity-induced insulin resistance. We used genetic variation to isolate and estimate the potentially causal effect of insulin secretion on body weight. METHODS: Genetic instruments of variation of insulin secretion [assessed as insulin concentration 30 min after oral glucose (insulin-30)] were used to estimate the causal relationship between increased insulin secretion and body mass index (BMI), using bidirectional Mendelian randomization analysis of genome-wide association studies...
January 2018: Clinical Chemistry
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