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C Hargrove

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https://www.readbyqxmd.com/read/28798862/amiloride-as-a-new-rna-binding-scaffold-with-activity-against-hiv-1-tar
#1
Neeraj N Patwardhan, Laura R Ganser, Gary J Kapral, Christopher S Eubanks, Janghyun Lee, Bharathwaj Sathyamoorthy, Hashim M Al-Hashimi, Amanda E Hargrove
Diversification of RNA-targeted scaffolds offers great promise in the search for selective ligands of therapeutically relevant RNA such as HIV-1 TAR. We herein report the establishment of amiloride as a novel RNA-binding scaffold along with synthetic routes for combinatorial C(5)- and C(6)-diversification. Iterative modifications at the C(5)- and C(6)- positions yielded derivative 24, which demonstrated a 100-fold increase in activity over the parent dimethylamiloride in peptide displacement assays. NMR chemical shift mapping was performed using the 2D SOFAST- [(1)H-(13)C] HMQC NMR method, which allowed for facile and rapid evaluation of binding modes for all library members...
May 1, 2017: MedChemComm
https://www.readbyqxmd.com/read/28740662/treatment-for-sternoclavicular-joint-infections-a-multi-institutional-study
#2
Allen Murga, Hannah Copeland, Rachel Hargrove, Jason M Wallen, Salman Zaheer
BACKGROUND: Sternoclavicular joint (SCJ) infections are rare and difficult to manage. Surgery is necessary for treatment. METHODS: A retrospective chart review of the university hospital and Veterans Administration (VA) hospitals of all patients treated for SCJ infections since 2001 was conducted. Fifteen [15] patients were identified and evaluated for the types of infections, risk factors, treatments and survival. RESULTS: All 15 patients were symptomatic including: pain [13], erythema [9], purulent drainage [3], fever greater than 38...
June 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28731382/external-validation-and-clinical-utility-of-a-prediction-model-for-6-month-mortality-in-patients-undergoing-hemodialysis-for-end-stage-kidney-disease
#3
Brian Forzley, Lee Er, Helen Hl Chiu, Ognjenka Djurdjev, Dan Martinusen, Rachel C Carson, Gaylene Hargrove, Adeera Levin, Mohamud Karim
BACKGROUND: End-stage kidney disease is associated with poor prognosis. Health care professionals must be prepared to address end-of-life issues and identify those at high risk for dying. A 6-month mortality prediction model for patients on dialysis derived in the United States is used but has not been externally validated. AIM: We aimed to assess the external validity and clinical utility in an independent cohort in Canada. DESIGN: We examined the performance of the published 6-month mortality prediction model, using discrimination, calibration, and decision curve analyses...
July 1, 2017: Palliative Medicine
https://www.readbyqxmd.com/read/28461309/crystal-structure-of-the-new-investigational-drug-candidate-vt-1598-in-complex-with-aspergillus-fumigatus-sterol-14%C3%AE-demethylase-provides-insights-into-its-broad-spectrum-antifungal-activity
#4
Tatiana Y Hargrove, Edward P Garvey, William J Hoekstra, Christopher M Yates, Zdzislaw Wawrzak, Girish Rachakonda, Fernando Villalta, Galina I Lepesheva
Within the past few decades, the incidence and complexity of human fungal infections have increased, and therefore, the need for safer and more efficient, broad-spectrum antifungal agents is high. In the study described here, we characterized the new tetrazole-based drug candidate VT-1598 as an inhibitor of sterol 14α-demethylase (CYP51B) from the filamentous fungus Aspergillus fumigatus VT-1598 displayed a high affinity of binding to the enzyme in solution (dissociation constant, 13 ± 1 nM) and in the reconstituted enzymatic reaction was revealed to have an inhibitory potency stronger than the potencies of all other simultaneously tested antifungal drugs, including fluconazole, voriconazole, ketoconazole, and posaconazole...
July 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28443672/heightened-hiv-antibody-responses-in-postpartum-women-as-exemplified-by-recent-infection-assays-implications-for-incidence-estimates
#5
John W Hargrove, Cari van Schalkwyk, Jean H Humphrey, Kuda Mutasa, Robert Ntozini, Sherry Michele Owen, Silvina Masciotra, Bharat S Parekh, Yen T Duong, Trudy Dobbs, Peter H Kilmarx, Elizabeth Gonese
Laboratory assays that identify recent HIV infections are important for assessing impacts of interventions aimed at reducing HIV incidence. Kinetics of HIV humoral responses can vary with inherent assay properties, and between HIV subtypes, populations, and physiological states. They are important in determining mean duration of recent infection (MDRI) for antibody-based assays for detecting recent HIV infections. We determined MDRIs for multi-subtype peptide representing subtypes B, E and D (BED)-capture enzyme immunoassay, limiting antigen (LAg), and Bio-Rad Avidity Incidence (BRAI) assays for 101 seroconverting postpartum women, recruited in Harare from 1997 to 2000 during the Zimbabwe Vitamin A for Mothers and Babies trial, comparing them against published MDRIs estimated from seroconverting cases in the general population...
May 24, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28258218/structural-analyses-of-candida-albicans-sterol-14%C3%AE-demethylase-complexed-with-azole-drugs-address-the-molecular-basis-of-azole-mediated-inhibition-of-fungal-sterol-biosynthesis
#6
Tatiana Y Hargrove, Laura Friggeri, Zdzislaw Wawrzak, Aidong Qi, William J Hoekstra, Robert J Schotzinger, John D York, F Peter Guengerich, Galina I Lepesheva
With some advances in modern medicine (such as cancer chemotherapy, broad exposure to antibiotics, and immunosuppression), the incidence of opportunistic fungal pathogens such as Candida albicans has increased. Cases of drug resistance among these pathogens have become more frequent, requiring the development of new drugs and a better understanding of the targeted enzymes. Sterol 14α-demethylase (CYP51) is a cytochrome P450 enzyme required for biosynthesis of sterols in eukaryotic cells and is the major target of clinical drugs for managing fungal pathogens, but some of the CYP51 key features important for rational drug design have remained obscure...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28120369/bile-duct-ligation-induced-biliary-hyperplasia-hepatic-injury-and-fibrosis-are-reduced-in-mast-cell-deficient-kit-w-sh-mice
#7
Laura Hargrove, Lindsey Kennedy, Jennifer Demieville, Hannah Jones, Fanyin Meng, Sharon DeMorrow, Walker Karstens, Taronish Madeka, John Greene, Heather Francis
Activated mast cells (MCs) release histamine (HA) and MCs infiltrate the liver following bile duct ligation (BDL), increasing intrahepatic bile duct mass (IBDM) and fibrosis. We evaluated the effects of BDL in MC-deficient (Kit(W-sh) ) mice. Wild-type (WT) and Kit(W-sh) mice were subjected to sham or BDL for up to 7 days and Kit(W-sh) mice were injected with cultured mast cells or 1× phosphate-buffered saline (PBS) before collecting serum, liver, and cholangiocytes. Liver damage was assessed by hematoxylin and eosin and alanine aminotransferase levels...
June 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28092717/the-culture-war-modern-economics-and-environmental-education-in-the-united-states
#8
Eugene C Hargrove
Teaching ethics in public schools in the United States has been made almost impossible because of the Culture War and Modern Economics. When Catholics began to migrate to the United States in the early nineteenth century, they found that Protestant religion and ethics were taught in public schools and they created their own parochial schools. This controversy has continued for two hundred years. To encourage the Catholics to send their children to the public schools, by 1860 religion and ethics had been removed from the public schools...
September 2016: Cuadernos de Bioética: Revista Oficial de la Asociación Española de Bioética y Ética Médica
https://www.readbyqxmd.com/read/27910442/a-comparison-of-flat-fielding-techniques-for-x-ray-framing-cameras
#9
L R Benedetti, C Trosseille, J P Holder, K Piston, D Hargrove, D K Bradley, P Bell, J Raimbourg, M Prat, L A Pickworth, S F Khan
Gain can vary across the active area of an x-ray framing camera by a factor of 4 (or more!) due to the voltage loss and dispersion associated with pulse transmission in a microstripline-coated microchannel plate. In order to make quantitative measurements, it is consequently important to measure the gain variation ("flat field"). Moreover, because of electromagnetic cross talk, gain variation depends on specific operational parameters, and ideally a flat field would be obtained at all operating conditions. As part of a collaboration between Lawrence Livermore National Laboratory's National Ignition Facility and the Commissariat à l'Énergie Atomique, we have been able to evaluate the consistency of three different methods of measuring x-ray flat fields...
November 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27910309/spatial-resolution-measurements-of-the-advanced-radiographic-capability-x-ray-imaging-system-at-energies-relevant-to-compton-radiography
#10
G N Hall, N Izumi, O L Landen, R Tommasini, J P Holder, D Hargrove, D K Bradley, A Lumbard, J G Cruz, K Piston, J J Lee, E Romano, P M Bell, A C Carpenter, N E Palmer, B Felker, V Rekow, F V Allen
Compton radiography provides a means to measure the integrity, ρR and symmetry of the DT fuel in an inertial confinement fusion implosion near peak compression. Upcoming experiments at the National Ignition Facility will use the ARC (Advanced Radiography Capability) laser to drive backlighter sources for Compton radiography experiments and will use the newly commissioned AXIS (ARC X-ray Imaging System) instrument as the detector. AXIS uses a dual-MCP (micro-channel plate) to provide gating and high DQE at the 40-200 keV x-ray range required for Compton radiography, but introduces many effects that contribute to the spatial resolution...
November 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27474361/loperamide-related-deaths-in-north-carolina
#11
Sandra C Bishop-Freeman, Marc S Feaster, Jennifer Beal, Alison Miller, Robert L Hargrove, Justin O Brower, Ruth E Winecker
Loperamide (Imodium(®)) has been accepted as a safe, effective, over-the-counter anti-diarrheal drug with low potential for abuse. It is a synthetic opioid that lacks central nervous system activity at prescribed doses, rendering it ineffective for abuse. Since 2012, however, the North Carolina Office of the Chief Medical Examiner has seen cases involving loperamide at supratherapeutic levels that indicate abuse. The recommended dose associated with loperamide should not exceed 16 mg per day, although users seeking an opioid-like high reportedly take it in excess of 100 mg per dose...
October 2016: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/27343253/establishment-of-reference-intervals-for-osteoarthritis-related-soluble-biomarkers-the-fnih-oarsi-oa-biomarkers-consortium
#12
Virginia B Kraus, David E Hargrove, David J Hunter, Jordan B Renner, Joanne M Jordan
OBJECTIVE: To establish reference intervals for osteoarthritis (OA)-related biomarkers used in the Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium Project. METHODS: A total of 129 'multijoint controls' were selected from 2722 African-American and Caucasian men and women in the Johnston County Osteoarthritis Project. The majority (79%) of those eligible (with biospecimens and baseline data) also had one or more follow-up evaluations 5-15 years later...
January 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27318775/the-impact-of-deep-versus-moderate-hypothermia-on-postoperative-kidney-function-after-elective-aortic-hemiarch-repair
#13
COMPARATIVE STUDY
George J Arnaoutakis, Prashanth Vallabhajosyula, Joseph E Bavaria, Ibrahim Sultan, Mary Siki, Suveeksha Naidu, Rita K Milewski, Matthew L Williams, W Clark Hargrove, Nimesh D Desai, Wilson Y Szeto
BACKGROUND: There remains concern that moderate hypothermic circulatory arrest (MHCA) with antegrade cerebral perfusion (ACP) may provide suboptimal distal organ protection compared with deep hypothermic circulatory arrest (DHCA) with retrograde cerebral perfusion (RCP). We compared postoperative acute kidney injury (AKI) in in patients who underwent elective hemiarch repair with either DHCA/RCP or MHCA/ACP. METHODS: This was a retrospective review of all patients undergoing elective aortic hemiarch reconstruction for aneurysmal disease between 2009 and 2014...
October 2016: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/27296323/predictive-validity-of-biochemical-biomarkers-in-knee-osteoarthritis-data-from-the-fnih-oa-biomarkers-consortium
#14
Virginia Byers Kraus, Jamie E Collins, David Hargrove, Elena Losina, Michael Nevitt, Jeffrey N Katz, Susanne X Wang, Linda J Sandell, Steven C Hoffmann, David J Hunter
OBJECTIVE: To investigate a targeted set of biochemical biomarkers as predictors of clinically relevant osteoarthritis (OA) progression. METHODS: Eighteen biomarkers were measured at baseline, 12 months (M) and 24 M in serum (s) and/or urine (u) of cases (n=194) from the OA initiative cohort with knee OA and radiographic and persistent pain worsening from 24 to 48 M and controls (n=406) not meeting both end point criteria. Primary analyses used multivariable regression models to evaluate the association between biomarkers (baseline and time-integrated concentrations (TICs) over 12 and 24 M, transposed to z values) and case status, adjusted for age, sex, body mass index, race, baseline radiographic joint space width, Kellgren-Lawrence grade, pain and pain medication use...
January 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27101341/an-examination-of-two-positive-organizational-interventions-for-whom-do-these-interventions-work
#15
Carolyn J Winslow, Seth A Kaplan, Jill C Bradley-Geist, Alex P Lindsey, Afra S Ahmad, Amber K Hargrove
Owing to the importance of employee psychological well-being for a variety of work- and non-work-related outcomes, practitioners and scholars have begun to broaden the scope of workplace well-being interventions by incorporating principles from positive psychology. Among such positive interventions, gratitude exercises have arguably emerged as the "gold standard" practice, with much research pointing to their effectiveness. However, existing workplace interventions lack a true (i.e., no intervention) control group, and effects have been observed for some-but not all-outcomes tested...
April 2017: Journal of Occupational Health Psychology
https://www.readbyqxmd.com/read/26963517/d-methionine-d-met-significantly-reduces-kanamycin-induced-ototoxicity-in-pigmented-guinea-pigs
#16
Kathleen C M Campbell, Seth M Martin, Robert P Meech, Tim L Hargrove, Steven J Verhulst, Daniel J Fox
OBJECTIVE: Test D-methionine (D-met) as an otoprotectant from kanamycin-induced ototoxicity and determine the lowest maximally protective D-met dose. DESIGN: Auditory brainstem responses (ABR) were measured at 4, 8, 14, and 20 kHz at baseline and two, four, and six weeks after kanamycin and D-met administration initiation. ABR threshold shifts assessed auditory function. Following six-week ABR testing, animals were decapitated and cochleae collected for outer hair cell (OHC) quantification...
2016: International Journal of Audiology
https://www.readbyqxmd.com/read/26931853/advances-in-x-ray-framing-cameras-at-the-national-ignition-facility-to-improve-quantitative-precision-in-x-ray-imaging
#17
L R Benedetti, J P Holder, M Perkins, C G Brown, C S Anderson, F V Allen, R B Petre, D Hargrove, S M Glenn, N Simanovskaia, D K Bradley, P Bell
We describe an experimental method to measure the gate profile of an x-ray framing camera and to determine several important functional parameters: relative gain (between strips), relative gain droop (within each strip), gate propagation velocity, gate width, and actual inter-strip timing. Several of these parameters cannot be measured accurately by any other technique. This method is then used to document cross talk-induced gain variations and artifacts created by radiation that arrives before the framing camera is actively amplifying x-rays...
February 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/26725716/direct-innominate-artery-cannulation-an-alternate-technique-for-antegrade-cerebral-perfusion-during-aortic-hemiarch-reconstruction
#18
Arminder S Jassar, Prashanth Vallabhajosyula, Joseph E Bavaria, Jacob Gutsche, Nimesh D Desai, Matthew L Williams, Rita K Milewski, W Clark Hargrove, Wilson Y Szeto
OBJECTIVE: We describe an alternate technique for establishing antegrade cerebral perfusion (ACP) during hypothermic circulatory arrest via direct, central cannulation of the innominate artery. METHODS: From 2009 to 2015, 100 elective hemiarch reconstructions for proximal aortic aneurysms were performed under moderate hypothermic circulatory arrest (MHCA). Cerebral perfusion was instituted with ACP via direct cannulation of the innominate artery. RESULTS: Mean patient age was 63 ± 13 years (72 men; 72%)...
April 2016: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/26643331/clinical-candidate-vt-1161-s-antiparasitic-effect-in-vitro-activity-in-a-murine-model-of-chagas-disease-and-structural-characterization-in-complex-with-the-target-enzyme-cyp51-from-trypanosoma-cruzi
#19
William J Hoekstra, Tatiana Y Hargrove, Zdzislaw Wawrzak, Denise da Gama Jaen Batista, Cristiane F da Silva, Aline S G Nefertiti, Girish Rachakonda, Robert J Schotzinger, Fernando Villalta, Maria de Nazaré C Soeiro, Galina I Lepesheva
A novel antifungal drug candidate, the 1-tetrazole-based agent VT-1161 [(R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-{5-[4-(2,2,2-trifluoroethoxy)phenyl]pyridin-2-yl}propan-2-ol], which is currently in two phase 2b antifungal clinical trials, was found to be a tight-binding ligand (apparent dissociation constant [Kd], 24 nM) and a potent inhibitor of cytochrome P450 sterol 14α-demethylase (CYP51) from the protozoan pathogen Trypanosoma cruzi. Moreover, VT-1161 revealed a high level of antiparasitic activity against amastigotes of the Tulahuen strain of T...
February 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/26597881/inhibition-of-mast-cell-derived-histamine-decreases-human-cholangiocarcinoma-growth-and-differentiation-via-c-kit-stem-cell-factor-dependent-signaling
#20
Christopher Johnson, Victoria Huynh, Laura Hargrove, Lindsey Kennedy, Allyson Graf-Eaton, Jennifer Owens, Jerome P Trzeciakowski, Kyle Hodges, Sharon DeMorrow, Yuyan Han, Lucas Wong, Gianfranco Alpini, Heather Francis
The tumor microenvironment of cholangiocarcinoma (CCA) is composed of numerous cells, including mast cells (MCs). MCs release histamine, which increases CCA progression and angiogenesis. Cholangiocytes secrete stem cell factor, which functions via the MC growth factor receptor c-Kit. Here, we show that cholangiocytes express histidine decarboxylase and its inhibition reduces CCA growth. MC recruitment in the tumor microenvironment increased CCA growth. MC infiltration and MC markers were detected by toluidine blue staining and real-time PCR in human biopsies and in tumors from athymic mice treated with saline, histamine, histidine decarboxylase inhibitor, or cromolyn sodium...
January 2016: American Journal of Pathology
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