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https://www.readbyqxmd.com/read/28324649/sulfonamides-as-selective-nav1-7-inhibitors-optimizing-potency-pharmacokinetics-and-metabolic-properties-to-obtain-atropisomeric-quinolinone-am-0466-that-affords-robust-in-vivo-activity
#1
Russell F Graceffa, Alessandro A Boezio, Jessica Able, Steven Altmann, Loren M Berry, Christiane M Boezio, John R Butler, Margaret Y Chu-Moyer, Melanie Cooke, Erin F DiMauro, Thomas A Dineen, Elma Feric Bojic, Robert S Foti, Robert T Fremeau, Angel Guzman-Perez, Hua Gao, Hakan Gunaydin, Hongbing Huang, Liyue Huang, Christopher Ilch, Michael Jarosh, Thomas Kornecook, Charles R Kreiman, Daniel S La, Joseph Ligutti, Benjamin Charles Milgram, Min-Hwa Jasmine Lin, Isaac E Marx, Hanh Nho Nguyen, Emily A Peterson, Gwen Rescourio, John Roberts, Laurie B Schenkel, Roman Shimanovich, Brian Andrew Sparling, John Stellwagen, Kristin Taborn, Karina R Vaida, Jean Wang, John T S Yeoman, Violeta L Yu, Dawn Zhu, Bryan D Moyer, Matthew M Weiss
Due to its strong genetic validation, NaV1.7 has attracted significant interest as a target for the treatment of pain. We have previously reported on a number of structurally distinct bicyclic heteroarylsulfonamides as NaV1.7 inhibitors that demonstrate high levels of selectivity over other NaV isoforms. Herein, we report the discovery and optimization of a novel series of atropisomeric quinolinone sulfonamide inhibitors of NaV1.7, which demonstrate nanomolar inhibition of NaV1.7 and exhibit high levels of selectivity over other sodium channel isoforms...
March 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28323502/head-injury-and-substance-use-in-young-adults
#2
Lisa A Kort-Butler
BACKGROUND: Prior studies suggest a link between head injuries and substance use but do not routinely capture mechanisms connecting the two. OBJECTIVES: The goal of the study was to explore whether past head injuries predicted current substance use among young adults, taking factors such as stress, self-esteem, temper, and risk-taking into consideration. METHODS: Data were drawn from a web-based survey conducted in 2014 and 2015 at a public university in the United States (n = 897)...
March 21, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28319469/understanding-traditional-research-impact-metrics
#3
Joseph S Butler, Arjun S Sebastian, I David Kaye, Scott C Wagner, Patrick B Morrissey, Gregory D Schroeder, Christopher K Kepler, Alexander R Vaccaro
Traditionally, the success of a researcher has been judged by the number of publications he or she has published in peer-review, indexed, high impact journals. However, to quantify the impact of research in the wider scientific community, a number of traditional metrics have been used, including Impact Factor, SCImago Journal Rank, Eigenfactor Score, and Article Influence Score. This article attempts to provide a broad overview of the main traditional impact metrics that have been used to assess scholarly output and research impact...
March 17, 2017: Clinical Spine Surgery
https://www.readbyqxmd.com/read/28319006/high-rates-of-severe-hypoglycemia-among-african-american-patients-with-diabetes-the-surveillance-prevention-and-management-of-diabetes-mellitus-supreme-dm-network
#4
Andrew J Karter, Kasia J Lipska, Patrick J O'Connor, Jennifer Y Liu, Howard H Moffet, Emily B Schroeder, Jean M Lawrence, Gregory A Nichols, Katherine M Newton, Ram D Pathak, Jay Desai, Beth Waitzfelder, Melissa G Butler, Abraham Thomas, John F Steiner
AIMS: Seven-year surveillance study (2005-2011) to evaluate race/ethnic differences in the trends in rates of severe hypoglycemia (SH) in a population of insured, at-risk adults with diabetes. METHODS: SH events were identified via any primary or principal diagnosis from emergency department or inpatient encounters among African American, Asian, Latino and White adult diabetes patients treated with insulin or secretagogues (Sulfonylureas or Meglitinides), receiving care from integrated healthcare delivery systems across the United States...
February 21, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28318990/junctional-hemorrhage-control-for-tactical-combat-casualty-care
#5
REVIEW
Russ S Kotwal, Frank K Butler
During historic, as well as more recent, conflicts, most combat casualties who die from their injuries do so in the prehospital setting. Although many of the injuries incurred by these casualties are nonsurvivable, a number of injuries are still potentially survivable. Of those injuries that are potentially survivable, the majority are truncal, junctional, and extremity hemorrhage. Novel and effective approaches directed toward prehospital hemorrhage control have emerged in recent years, some of which can prove useful in the management of junctional hemorrhage whether in a military or civilian setting...
March 16, 2017: Wilderness & Environmental Medicine
https://www.readbyqxmd.com/read/28316971/exercise-associated-hyponatremia-2017-update
#6
REVIEW
Tamara Hew-Butler, Valentina Loi, Antonello Pani, Mitchell H Rosner
Exercise-associated hyponatremia (EAH) was initially described in the 1980s in endurance athletes, and work done since then has conclusively identified that overdrinking beyond thirst and non-osmotic arginine vasopressin release are the most common etiologic factors. In recent years, EAH has been described in a broader variety of athletic events and also has been linked to the development of rhabdomyolysis. The potential role of volume and sodium depletion in a subset of athletes has also been described. This review focuses on the most recent literature in the field of EAH and summarizes key new findings in the epidemiology, pathophysiology, treatment, and prevention of this condition...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28302766/csf-clearance-in-alzheimer-disease-measured-with-dynamic-pet
#7
Mony J de Leon, Yi Li, Nobuyuki Okamura, Wai H Tsui, Les A Saint Louis, Lidia Glodzik, Ricardo S Osorio, Juan Fortea, Tracy Butler, Elizabeth Pirraglia, Silvia Fossati, Hee-Jin Kim, Roxana O Carare, Maiken Nedergaard, Helene Benveniste, Henry Rusinek
Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer's disease (AD) comes from primarily from rodent models. However, unlike rodents where predominant extra-cranial CSF egress is via olfactory nerves traversing the cribriform plate, human CSF clearance pathways are not well characterized. Using dynamic Positron Emission Tomography (PET) with (18)F-THK5117 a tracer for tau pathology, the ventricular CSF time activity was used as a biomarker for CSF clearance...
March 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28300113/global-warming-and-recurrent-mass-bleaching-of-corals
#8
Terry P Hughes, James T Kerry, Mariana Álvarez-Noriega, Jorge G Álvarez-Romero, Kristen D Anderson, Andrew H Baird, Russell C Babcock, Maria Beger, David R Bellwood, Ray Berkelmans, Tom C Bridge, Ian R Butler, Maria Byrne, Neal E Cantin, Steeve Comeau, Sean R Connolly, Graeme S Cumming, Steven J Dalton, Guillermo Diaz-Pulido, C Mark Eakin, Will F Figueira, James P Gilmour, Hugo B Harrison, Scott F Heron, Andrew S Hoey, Jean-Paul A Hobbs, Mia O Hoogenboom, Emma V Kennedy, Chao-Yang Kuo, Janice M Lough, Ryan J Lowe, Gang Liu, Malcolm T McCulloch, Hamish A Malcolm, Michael J McWilliam, John M Pandolfi, Rachel J Pears, Morgan S Pratchett, Verena Schoepf, Tristan Simpson, William J Skirving, Brigitte Sommer, Gergely Torda, David R Wachenfeld, Bette L Willis, Shaun K Wilson
During 2015-2016, record temperatures triggered a pan-tropical episode of coral bleaching, the third global-scale event since mass bleaching was first documented in the 1980s. Here we examine how and why the severity of recurrent major bleaching events has varied at multiple scales, using aerial and underwater surveys of Australian reefs combined with satellite-derived sea surface temperatures. The distinctive geographic footprints of recurrent bleaching on the Great Barrier Reef in 1998, 2002 and 2016 were determined by the spatial pattern of sea temperatures in each year...
March 15, 2017: Nature
https://www.readbyqxmd.com/read/28297906/pumping-of-electrolytes-by-electrical-forces-induced-on-the-diffusion-layer-a-weakly-nonlinear-analysis
#9
Pablo García-Sánchez, Neophytos G Loucaides, Antonio Ramos
Pumping of electrolytes in microchannels can be achieved with the use of microelectrodes subjected to AC potentials. Experiments have shown an influence of Faradaic currents in the pumping performance, and theoretical studies for asymmetric electrolytes suggest that induced charges in the diffusion layer play an important role. In this work we consider the case of a diffusion layer induced by an array of electrodes subjected to a traveling wave potential and we include Faradaic currents. Previous theoretical studies considered the case of very small applied voltages, which allowed for two major simplifications: (i) Butler-Volmer (B-V) equation was linearized, and (ii) the presence of gradients in ion concentration was neglected...
February 2017: Physical Review. E
https://www.readbyqxmd.com/read/28297579/endothelial-cells-promote-expansion-of-long-term-engrafting-marrow-hematopoietic-stem-and-progenitor-cells-in-primates
#10
Jennifer L Gori, Jason M Butler, Balvir Kunar, Michael G Poulos, Michael Ginsberg, Daniel J Nolan, Zachary K Norgaard, Jennifer E Adair, Shahin Rafii, Hans-Peter Kiem
Successful expansion of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) would benefit many HSPC transplantation and gene therapy/editing applications. However, current expansion technologies have been limited by a loss of multipotency and self-renewal properties ex vivo. We hypothesized that an ex vivo vascular niche would provide prohematopoietic signals to expand HSPCs while maintaining multipotency and self-renewal. To test this hypothesis, BM autologous CD34(+) cells were expanded in endothelial cell (EC) coculture and transplanted in nonhuman primates...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28294152/melanocortin-3-receptors-expressed-in-nkx2-1-ve-neurons-are-sufficient-for-controlling-appetitive-responses-to-hypocaloric-conditioning
#11
Clémence Girardet, Maria M Mavrikaki, Joseph R Stevens, Courtney A Miller, Daniel L Marks, Andrew A Butler
Melanocortin-3 receptors (MC3R) have a contextual role in appetite control that is amplified with hypocaloric conditioning. C57BL/6J (B6) mice subjected to hypocaloric feeding schedules (HFS) exhibit compulsive behavioral responses involving food anticipatory activity (FAA) and caloric loading following food access. These homeostatic responses to calorie-poor environs are attenuated in B6 mice in which Mc3r transcription is suppressed by a lox-stop-lox sequence in the 5'UTR (Mc3r(TB/TB)). Here, we report that optimization of caloric loading in B6 mice subject to HFS, characterized by increased meal size and duration, is not observed in Mc3r(TB/TB) mice...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28293032/planar-cell-polarity-in-development-and-disease
#12
REVIEW
Mitchell T Butler, John B Wallingford
Planar cell polarity (PCP) is an essential feature of animal tissues, whereby distinct polarity is established within the plane of a cell sheet. Tissue-wide establishment of PCP is driven by multiple global cues, including gradients of gene expression, gradients of secreted WNT ligands and anisotropic tissue strain. These cues guide the dynamic, subcellular enrichment of PCP proteins, which can self-assemble into mutually exclusive complexes at opposite sides of a cell. Endocytosis, endosomal trafficking and degradation dynamics of PCP components further regulate planar tissue patterning...
March 15, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28291467/a-retrospective-cohort-analysis-of-battle-injury-versus-disease-non-battle-injury-two-validating-flight-surgeons-experience
#13
William P Butler, Lawrence W Steinkraus, Brittany L Fouts, Jennifer L Serres
Today, military combat medical care is the best it has ever been. Regulated U.S. Air Force aeromedical evacuation (AE) is one important reason. The Theater Validating Flight Surgeon (TVFS) validates that a patient is ready for flight. Two TVFSs' experiences, successively deployed in 2007, are the focus of this study. A unique operational worksheet used to manage the AE queue was used for approximately 5 months. A descriptive analysis of the worksheet's 1,389 patients found the majority male (94%), median age 30 years, and mostly Army enlisted soldiers (63%)...
March 2017: Military Medicine
https://www.readbyqxmd.com/read/28290925/two-decades-of-saving-lives-on-the-battlefield-tactical-combat-casualty-care-turns-20
#14
Frank K Butler
BACKGROUND: Twenty years ago, the original Tactical Combat Casualty Care (TCCC) article was published in this journal. Since TCCC is essentially a set of best-practice prehospital trauma care guidelines customized for use on the battlefield, the presence of a journal with a specific focus on military medicine was a profound benefit to the initial presentation of TCCC to the U.S. Military. METHODS: In the two ensuing decades, which included the longest continuous period of armed conflict in our nation's history, TCCC steadily evolved as the prehospital trauma care evidence base was augmented and as feedback from user medics, corpsmen, and pararescuemen was obtained...
March 2017: Military Medicine
https://www.readbyqxmd.com/read/28289483/dielectrophoresis-study-of-temporal-change-in-internal-conductivity-of-single-cho-cells-after-electroporation-by-pulsed-electric-fields
#15
E Salimi, K Braasch, M Butler, D J Thomson, G E Bridges
Applying sufficiently strong pulsed electric fields to a cell can permeabilize the membrane and subsequently affect its dielectric properties. In this study, we employ a microfluidic dielectrophoresis cytometry technique to simultaneously electroporate and measure the time-dependent dielectric response of single Chinese hamster ovary cells. Using experimental measurements along with numerical simulations, we present quantitative results for the changes in the cytoplasm conductivity of single cells within seconds after exposure to 100 μs duration pulsed electric fields with various intensities...
January 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/28289111/oral-and-topical-antibiotics-for-clinically-infected-eczema-in-children-a-pragmatic-randomized-controlled-trial-in-ambulatory-care
#16
Nick A Francis, Matthew J Ridd, Emma Thomas-Jones, Christopher C Butler, Kerenza Hood, Victoria Shepherd, Charis A Marwick, Chao Huang, Mirella Longo, Mandy Wootton, Frank Sullivan
PURPOSE: Eczema may flare because of bacterial infection, but evidence supporting antibiotic treatment is of low quality. We aimed to determine the effect of oral and topical antibiotics in addition to topical emollient and corticosteroids in children with clinically infected eczema. METHODS: We employed a 3-arm, blinded, randomized controlled trial in UK ambulatory care. Children with clinical, non-severely infected eczema were randomized to receive oral and topical placebos (control), oral antibiotic (flucloxacillin) and topical placebo, or topical antibiotic (fusidic acid) and oral placebo, for 1 week...
March 2017: Annals of Family Medicine
https://www.readbyqxmd.com/read/28285493/the-use-of-pelvic-binders-in-tactical-combat-casualty-care-tccc-guidelines-change-1602-7-november-2016
#17
Stacy Shackelford, Rick Hammesfahr, Daniel Morissette, Harold R Montgomery, Win Kerr, Michael Broussard, Brad L Bennett, Warren C Dorlac, Stephen Bree, Frank K Butler
No abstract text is available yet for this article.
2017: Journal of Special Operations Medicine: a Peer Reviewed Journal for SOF Medical Professionals
https://www.readbyqxmd.com/read/28285402/a-semi-empirical-glycosylation-model-of-a-camelid-monoclonal-antibody-under-hypothermia-cell-culture-conditions
#18
Hengameh Aghamohseni, Maureen Spearman, Kaveh Ohadi, Katrin Braasch, Murray Moo-Young, Michael Butler, Hector M Budman
The impact of cell culture environment on the glycan distribution of a monoclonal antibody (mAb) has been investigated through a combination of experiments and modeling. A newly developed CHO DUXB cell line was cultivated at two levels of initial Glutamine (Gln) concentrations (0, 4 mM) and incubation temperatures of (33 and 37 °C) in batch operation mode. Hypothermia was applied either through the entire culture duration or only during the post-exponential phase. Beyond reducing cell growth and increasing productivity, hypothermia significantly altered the galactosylation index profiles as compared to control conditions...
March 11, 2017: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28284484/tactical-combat-casualty-care-transitioning-battlefield-lessons-learned-to-other-austere-environments
#19
EDITORIAL
Brad Bennett, Ian Wedmore, Frank Butler
No abstract text is available yet for this article.
March 8, 2017: Wilderness & Environmental Medicine
https://www.readbyqxmd.com/read/28284483/tactical-combat-casualty-care-beginnings
#20
REVIEW
Frank K Butler
Tactical Combat Casualty Care (TCCC) is a set of evidence-based, best-practice prehospital trauma care guidelines customized for use on the battlefield. The origins of TCCC were nontraditional. The TCCC program began as a Naval Special Warfare biomedical research effort launched after the realization that extremity hemorrhage, a leading cause of preventable death on the battlefield, was not being treated with a readily available and highly effective intervention: the tourniquet. This insight prompted a systematic reevaluation of all aspects of battlefield trauma care that was conducted from 1993 to 1996 as a joint effort by special operations medical personnel and the Uniformed Services University of the Health Sciences...
March 8, 2017: Wilderness & Environmental Medicine
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