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https://www.readbyqxmd.com/read/29156185/maintenance-of-lost-weight-and-long-term-management-of-obesity
#1
REVIEW
Kevin D Hall, Scott Kahan
Weight loss can be achieved through a variety of modalities, but long-term maintenance of lost weight is much more challenging. Obesity interventions typically result in early weight loss followed by a weight plateau and progressive regain. This review describes current understanding of the biological, behavioral, and environmental factors driving this near-ubiquitous body weight trajectory and the implications for long-term weight management. Treatment of obesity requires ongoing clinical attention and weight maintenance-specific counseling to support sustainable healthful behaviors and positive weight regulation...
January 2018: Medical Clinics of North America
https://www.readbyqxmd.com/read/29146306/real-world-vision-in-age-related-macular-degeneration-patients-treated-with-single-anti-vegf-drug-type-for-1-year-in-the-iris-registry
#2
Prethy Rao, Flora Lum, Kevin Wood, Craig Salman, Bhavya Burugapalli, Rebecca Hall, Sukhminder Singh, David W Parke, George A Williams
PURPOSE: The purpose of this study is to compare real-world visual acuity (VA) in patients with neovascular age-related macular degeneration (nAMD) treated with a single anti-vascular endothelial growth factor (VEGF) drug monotherapy for 1 year from the American Academy of Ophthalmology (AAO) Intelligent Research in Sight (IRIS) Registry. DESIGN: Retrospective, nonrandomized, comparative study. PARTICIPANTS: IRIS Registry patients with nAMD who received bevacizumab, ranibizumab, or aflibercept only for 1 year between 2013-2016...
November 13, 2017: Ophthalmology
https://www.readbyqxmd.com/read/29130845/restrictive-or-liberal-red-cell-transfusion-for-cardiac-surgery
#3
C David Mazer, Richard P Whitlock, Dean A Fergusson, Judith Hall, Emilie Belley-Cote, Katherine Connolly, Boris Khanykin, Alexander J Gregory, Étienne de Médicis, Shay McGuinness, Alistair Royse, François M Carrier, Paul J Young, Juan C Villar, Hilary P Grocott, Manfred D Seeberger, Stephen Fremes, François Lellouche, Summer Syed, Kelly Byrne, Sean M Bagshaw, Nian C Hwang, Chirag Mehta, Thomas W Painter, Colin Royse, Subodh Verma, Gregory M T Hare, Ashley Cohen, Kevin E Thorpe, Peter Jüni, Nadine Shehata
Background The effect of a restrictive versus liberal red-cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear. Methods In this multicenter, open-label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery) to a restrictive red-cell transfusion threshold (transfuse if hemoglobin level was <7...
November 12, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29127109/incb040093-is-a-novel-pi3k%C3%AE-inhibitor-for-the-treatment-of-b-cell-lymphoid-malignancies
#4
Niu Shin, Yun-Long Li, Song Mei, Kathy He Wang, Leslie Hall, Kamna Katiyar, Qian Wang, Gengjie Yang, Beth Rumberger, Lynn Leffet, Xin He, Mark Rupar, Kevin Bowman, Margaret Favata, Jun Li, Mike Liu, Yanlong Li, Maryanne Covington, Holly Koblish, Maxim Soloviev, Dana Shuey, Timothy Burn, Sharon Diamond, Jordan Fridman, Andrew Combs, Wenqing Yao, Swamy Yeleswaram, Gregory Hollis, Kris Vaddi, Reid Huber, Robert Newton, Peggy Scherle
PI3Kδ is a critical signaling molecule in B cells and is considered a target for development of therapies against various B cell malignancies. INCB040093 is a novel PI3Kδ small molecule inhibitor and has demonstrated promising efficacy in patients with Hodgkin's lymphoma in clinical studies. Here, we disclose the chemical structure and the preclinical activity of the compound. In biochemical assays, INCB040093 potently inhibits the PI3Kδ kinase, with 74 to >900-fold selectivity against other PI3K family members...
November 10, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29126651/effects-of-noise-exposure-on-young-adults-with-normal-audiograms-ii-behavioral-measures
#5
Garreth Prendergast, Rebecca E Millman, Hannah Guest, Kevin J Munro, Karolina Kluk, Rebecca S Dewey, Deborah A Hall, Michael G Heinz, Christopher J Plack
An estimate of lifetime noise exposure was used as the primary predictor of performance on a range of behavioral tasks: frequency and intensity difference limens, amplitude modulation detection, interaural phase discrimination, the digit triplet speech test, the co-ordinate response speech measure, an auditory localization task, a musical consonance task and a subjective report of hearing ability. One hundred and thirty-eight participants (81 females) aged 18-36 years were tested, with a wide range of self-reported noise exposure...
October 25, 2017: Hearing Research
https://www.readbyqxmd.com/read/29071809/proportional-feedback-control-of-energy-intake-during-obesity-pharmacotherapy
#6
Kevin D Hall, Arjun Sanghvi, Britta Göbel
OBJECTIVE: Obesity pharmacotherapies result in an exponential time course for energy intake whereby large early decreases dissipate over time. This pattern of declining drug efficacy to decrease energy intake results in a weight loss plateau within approximately 1 year. This study aimed to elucidate the physiology underlying the exponential decay of drug effects on energy intake. METHODS: Placebo-subtracted energy intake time courses were examined during long-term obesity pharmacotherapy trials for 14 different drugs or drug combinations within the theoretical framework of a proportional feedback control system regulating human body weight...
October 25, 2017: Obesity
https://www.readbyqxmd.com/read/29030483/rbpj-cbf1-interacts-with-l3mbtl3-mbt1-to-promote-repression-of-notch-signaling-via-histone-demethylase-kdm1a-lsd1
#7
Tao Xu, Sung-Soo Park, Benedetto Daniele Giaimo, Daniel Hall, Francesca Ferrante, Diana M Ho, Kazuya Hori, Lucas Anhezini, Iris Ertl, Marek Bartkuhn, Honglai Zhang, Eléna Milon, Kimberly Ha, Kevin P Conlon, Rork Kuick, Brandon Govindarajoo, Yang Zhang, Yuqing Sun, Yali Dou, Venkatesha Basrur, Kojo Sj Elenitoba-Johnson, Alexey I Nesvizhskii, Julian Ceron, Cheng-Yu Lee, Tilman Borggrefe, Rhett A Kovall, Jean-François Rual
Notch signaling is an evolutionarily conserved signal transduction pathway that is essential for metazoan development. Upon ligand binding, the Notch intracellular domain (NOTCH ICD) translocates into the nucleus and forms a complex with the transcription factor RBPJ (also known as CBF1 or CSL) to activate expression of Notch target genes. In the absence of a Notch signal, RBPJ acts as a transcriptional repressor. Using a proteomic approach, we identified L3MBTL3 (also known as MBT1) as a novel RBPJ interactor...
November 2, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29023806/the-percutaneous-toxicokinetics-of-vx-in-a-damaged-skin-porcine-model-and-the-evaluation-of-woundstat%C3%A2-as-a-topical-decontaminant
#8
Helen Lydon, Charlotte Hall, Hazem Matar, Christopher Dalton, J Kevin Chipman, John S Graham, Robert P Chilcott
This study used a damaged skin, porcine model to evaluate the in vivo efficacy of WoundStat™ for the decontamination of superficial, nerve agent-contaminated wounds. Anaesthetized animals were randomly assigned to either control (n = 7), no decontamination (n = 12) or WoundStat™ (n = 12) treatment groups. Pigs were exposed to a 5× LD50 dose of neat, radiolabelled S-[2-(diisopropylamino)ethyl]-O-ethyl methyl-phosphonothioate (VX; or equivalent volume of sterile saline for the control group) via an area of superficially damaged skin on the ear...
October 10, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28853336/the-percutaneous-absorption-of-soman-in-a-damaged-skin-porcine-model-and-the-evaluation-of-woundstat%C3%A2-as-a-topical-decontaminant
#9
Christopher Dalton, Charlotte Hall, Helen Lydon, John Jenner, J Kevin Chipman, John S Graham, Robert P Chilcott
PURPOSE: The aim of this study was to evaluate a candidate haemostat (WoundStat™), down-selected from previous in vitro studies, for efficacy as a potential skin decontaminant against the chemical warfare agent pinacoyl methylfluorophosphonate (Soman, GD) using an in vivo pig model. MATERIALS AND METHODS: An area of approximately 3 cm(2) was dermatomed from the dorsal ear skin to a nominal depth of 100 µm. A discrete droplet of (14)C-GD (300 µg kg(-1)) was applied directly onto the surface of the damaged skin at the centre of the dosing site...
August 30, 2017: Cutaneous and Ocular Toxicology
https://www.readbyqxmd.com/read/28838362/improving-the-appropriate-use-of-transthoracic-echocardiography-the-echo-wisely-trial
#10
RANDOMIZED CONTROLLED TRIAL
R Sacha Bhatia, Noah M Ivers, X Cindy Yin, Dorothy Myers, Gillian C Nesbitt, Jeremy Edwards, Kibar Yared, Rishi K Wadhera, Justina C Wu, Aaron P Kithcart, Brian M Wong, Mark S Hansen, Adina S Weinerman, Steven Shadowitz, Debra Elman, Michael E Farkouh, Paaladinesh Thavendiranathan, Jacob A Udell, Amer M Johri, Chi-Ming Chow, Judith Hall, Zachary Bouck, Ashley Cohen, Kevin E Thorpe, Harry Rakowski, Michael H Picard, Rory B Weiner
BACKGROUND: Appropriate use criteria (AUC) have defined transthoracic echocardiogram (TTE) indications for which there is a clear lack of benefit as rarely appropriate (rA). OBJECTIVES: This study sought to investigate the impact of an AUC-based educational intervention on outpatient TTE ordering by cardiologists and primary care providers. METHODS: The authors conducted a prospective, investigator-blinded, multicenter, randomized controlled trial of an AUC-based educational intervention aimed at reducing rA outpatient TTEs...
August 29, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28821240/avbd1-nucleotide-polymorphisms-peptide-antimicrobial-activities-and-microbial-colonisation-of-the-broiler-chicken-gut
#11
Kevin Cadwell, Sherko S Niranji, Vanessa L Armstrong, Catherine A Mowbray, Richard Bailey, Kellie A Watson, Judith Hall
BACKGROUND: The importance of poultry as a global source of protein underpins the chicken genome and associated SNP data as key tools in selecting and breeding healthy robust birds with improved disease resistance. SNPs affecting host peptides involved in the innate defences tend to be rare, but three non-synonymous SNPs in the avian β-defensin (AvBD1) gene encoding the variant peptides NYH, SSY and NYY were identified that segregated specifically to three lines of commercial broiler chickens Line X (LX), Line Y(LY) and Line Z...
August 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28814343/stable-inheritance-of-dna-methylation-allows-creation-of-epigenotype-maps-and-the-study-of-epiallele-inheritance-patterns-in-the-absence-of-genetic-variation
#12
Brigitte T Hofmeister, Kevin Lee, Nicholas A Rohr, David W Hall, Robert J Schmitz
BACKGROUND: Differences in DNA methylation can arise as epialleles, which are loci that differ in chromatin state and are inherited over generations. Epialleles offer an additional source of variation that can affect phenotypic diversity beyond changes to nucleotide sequence. Previous research has looked at the rate at which spontaneous epialleles arise but it is currently unknown how they are maintained across generations. RESULTS: We used two Arabidopsis thaliana mutation accumulation (MA) lines and determined that over 99...
August 16, 2017: Genome Biology
https://www.readbyqxmd.com/read/28802046/replication-transcription-conflicts-generate-r-loops-that-orchestrate-bacterial-stress-survival-and-pathogenesis
#13
Kevin S Lang, Ashley N Hall, Christopher N Merrikh, Mark Ragheb, Hannah Tabakh, Alex J Pollock, Joshua J Woodward, Julia E Dreifus, Houra Merrikh
Replication-transcription collisions shape genomes, influence evolution, and promote genetic diseases. Although unclear why, head-on transcription (lagging strand genes) is especially disruptive to replication and promotes genomic instability. Here, we find that head-on collisions promote R-loop formation in Bacillus subtilis. We show that pervasive R-loop formation at head-on collision regions completely blocks replication, elevates mutagenesis, and inhibits gene expression. Accordingly, the activity of the R-loop processing enzyme RNase HIII at collision regions is crucial for stress survival in B...
August 10, 2017: Cell
https://www.readbyqxmd.com/read/28783044/phenotypic-and-pharmacogenetic-evaluation-of-patients-with-thiazide-induced-hyponatremia
#14
James S Ware, Louise V Wain, Sarath K Channavajjhala, Victoria E Jackson, Elizabeth Edwards, Run Lu, Keith Siew, Wenjing Jia, Nick Shrine, Sue Kinnear, Mahli Jalland, Amanda P Henry, Jenny Clayton, Kevin M O'Shaughnessy, Martin D Tobin, Victor L Schuster, Stuart Cook, Ian P Hall, Mark Glover
Thiazide diuretics are among the most widely used treatments for hypertension, but thiazide-induced hyponatremia (TIH), a clinically significant adverse effect, is poorly understood. Here, we have studied the phenotypic and genetic characteristics of patients hospitalized with TIH. In a cohort of 109 TIH patients, those with severe TIH displayed an extended phenotype of intravascular volume expansion, increased free water reabsorption, urinary prostaglandin E2 excretion, and reduced excretion of serum chloride, magnesium, zinc, and antidiuretic hormone...
September 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28717194/rapid-production-of-human-liver-scaffolds-for-functional-tissue-engineering-by-high-shear-stress-oscillation-decellularization
#15
Giuseppe Mazza, Walid Al-Akkad, Andrea Telese, Lisa Longato, Luca Urbani, Benjamin Robinson, Andrew Hall, Kenny Kong, Luca Frenguelli, Giusi Marrone, Oliver Willacy, Mohsen Shaeri, Alan Burns, Massimo Malago, Janet Gilbertson, Nigel Rendell, Kevin Moore, David Hughes, Ioan Notingher, Gavin Jell, Armando Del Rio Hernandez, Paolo De Coppi, Krista Rombouts, Massimo Pinzani
The development of human liver scaffolds retaining their 3-dimensional structure and extra-cellular matrix (ECM) composition is essential for the advancement of liver tissue engineering. We report the design and validation of a new methodology for the rapid and accurate production of human acellular liver tissue cubes (ALTCs) using normal liver tissue unsuitable for transplantation. The application of high shear stress is a key methodological determinant accelerating the process of tissue decellularization while maintaining ECM protein composition, 3D-architecture and physico-chemical properties of the native tissue...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714849/proposal-for-a-unified-classification-system-and-nomenclature-of-lagoviruses
#16
Jacques Le Pendu, Joana Abrantes, Stéphane Bertagnoli, Jean-Sébastien Guitton, Ghislaine Le Gall-Reculé, Ana Margarida Lopes, Stéphane Marchandeau, Fernando Alda, Tereza Almeida, Alves Paulo Célio, Juan Bárcena, Galina Burmakina, Esther Blanco, Carlos Calvete, Patrizia Cavadini, Brian Cooke, Kevin Dalton, Miguel Delibes Mateos, Wieslaw Deptula, John Sebastian Eden, Fang Wang, Catarina C Ferreira, Paula Ferreira, Pilar Foronda, David Gonçalves, Dolores Gavier-Widén, Robin Hall, Beata Hukowska-Szematowicz, Peter Kerr, John Kovaliski, Antonio Lavazza, Jackie Mahar, Alexander Malogolovkin, Raquel M Marques, Sara Marques, Aaron Martin-Alonso, Pedro Monterroso, Sacramento Moreno, Greg Mutze, Aleksija Neimanis, Paulina Niedzwiedzka-Rystwej, David Peacock, Francisco Parra, Mara Rocchi, Carlos Rouco, Nathalie Ruvoën-Clouet, Eliane Silva, Diogo Silvério, Tanja Strive, Gertrudes Thompson, Beata Tokarz-Deptula, Pedro Esteves
Lagoviruses belong to the Caliciviridae family. They were first recognized as highly pathogenic viruses of the European rabbit (Oryctolagus cuniculus) and European brown hare (Lepus europaeus) that emerged in the 1970-1980s, namely, rabbit haemorrhagic disease virus (RHDV) and European brown hare syndrome virus (EBHSV), according to the host species from which they had been first detected. However, the diversity of lagoviruses has recently expanded to include new related viruses with varying pathogenicity, geographic distribution and host ranges...
July 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28627929/design-of-the-hptn-065-tlc-plus-study-a-study-to-evaluate-the-feasibility-of-an-enhanced-test-link-to-care-plus-treat-approach-for-hiv-prevention-in-the-united-states
#17
Theresa Gamble, Bernard Branson, Deborah Donnell, H Irene Hall, Georgette King, Blayne Cutler, Shannon Hader, David Burns, Jason Leider, Angela Fulwood Wood, Kevin G Volpp, Kate Buchacz, Wafaa M El-Sadr
Background/Aims HIV continues to be a major public health threat in the United States, and mathematical modeling has demonstrated that the universal effective use of antiretroviral therapy among all HIV-positive individuals (i.e. the "test and treat" approach) has the potential to control HIV. However, to accomplish this, all the steps that define the HIV care continuum must be achieved at high levels, including HIV testing and diagnosis, linkage to and retention in clinical care, antiretroviral medication initiation, and adherence to achieve and maintain viral suppression...
August 2017: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/28601820/axillary-versus-innominate-artery-cannulation-for-antegrade-cerebral-perfusion-in-aortic-surgery-design-of-the-aortic-surgery-cerebral-protection-evaluation-ace-cardiolink-3-randomised-trial
#18
Vinay Garg, Mark D Peterson, Michael Wa Chu, Maral Ouzounian, Roderick Gg MacArthur, John Bozinovski, Ismail El-Hamamsy, F Victor Chu, Ankit Garg, Judith Hall, Kevin E Thorpe, Natasha Dhingra, Hwee Teoh, Thomas R Marotta, David A Latter, Adrian Quan, Muhammad Mamdani, Peter Juni, C David Mazer, Subodh Verma
INTRODUCTION: Neurological injury remains the major cause of morbidity and mortality following open aortic arch repair. Systemic hypothermia along with antegrade cerebral perfusion (ACP) is the accepted cerebral protection approach, with axillary artery cannulation being the most common technique used to establish ACP. More recently, innominate artery cannulation has been shown to be a safe and efficacious method for establishing ACP. Inasmuch as there is a lack of high-quality data comparing axillary and innominate artery ACP, we have designed a randomised, multi-centre clinical trial to compare both cerebral perfusion strategies with regards to brain morphological injury using diffusion-weighted MRI (DW-MRI)...
June 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28589124/a-multidisciplinary-phenotyping-and-genotyping-analysis-of-a-mapping-population-enables-quality-to-be-combined-with-yield-in-rice
#19
Mariafe Calingacion, Roland Mumm, Kevin Tan, Lenie Quiatchon-Baeza, Jeanaflor C T Concepcion, Jos A Hageman, Sangeeta Prakash, Melissa Fitzgerald, Robert D Hall
In this study a mapping population (F8) of ca 200 progeny from a cross between the commercial rice varieties Apo and IR64 has been both genotyped and phenotyped. A genotyping-by-sequencing approach was first used to identify 2,681 polymorphic SNP markers which gave dense coverage of the genome with a good distribution across all 12 chromosomes. The coefficient of parentage was also low, at 0.13, confirming that the parents are genetically distant from each other. The progeny, together with both parents, were grown under irrigated and water restricted conditions in a randomised block design...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28581512/structural-basis-for-the-cooperative-allosteric-activation-of-the-free-fatty-acid-receptor-gpr40
#20
Jun Lu, Noel Byrne, John Wang, Gerard Bricogne, Frank K Brown, Harry R Chobanian, Steven L Colletti, Jerry Di Salvo, Brande Thomas-Fowlkes, Yan Guo, Dawn L Hall, Jennifer Hadix, Nicholas B Hastings, Jeffrey D Hermes, Thu Ho, Andrew D Howard, Hubert Josien, Maria Kornienko, Kevin J Lumb, Michael W Miller, Sangita B Patel, Barbara Pio, Christopher W Plummer, Bradley S Sherborne, Payal Sheth, Sarah Souza, Srivanya Tummala, Clemens Vonrhein, Maria Webb, Samantha J Allen, Jennifer M Johnston, Adam B Weinglass, Sujata Sharma, Stephen M Soisson
Clinical studies indicate that partial agonists of the G-protein-coupled, free fatty acid receptor 1 GPR40 enhance glucose-dependent insulin secretion and represent a potential mechanism for the treatment of type 2 diabetes mellitus. Full allosteric agonists (AgoPAMs) of GPR40 bind to a site distinct from partial agonists and can provide additional efficacy. We report the 3.2-Å crystal structure of human GPR40 (hGPR40) in complex with both the partial agonist MK-8666 and an AgoPAM, which exposes a novel lipid-facing AgoPAM-binding pocket outside the transmembrane helical bundle...
July 2017: Nature Structural & Molecular Biology
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