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https://www.readbyqxmd.com/read/28102950/quantitative-impact-of-changes-in-marrow-cellularity-skeletal-size-and-bone-mineral-density-on-active-marrow-dosimetry-based-upon-a-reference-model
#1
Amy M Geyer, Bryan C Schwarz, Robert F Hobbs, George Sgouros, Wesley E Bolch
PURPOSE: The hematopoietically active tissues of skeletal bone marrow are a prime target for computational dosimetry given potential risks of leukemia and, at higher dose levels, acute marrow toxicity. The complex three-dimensional geometry of trabecular spongiosa, however, complicates schema for dose assessment in such a way that only a few reference skeletal models have been developed to date, and which are based upon microimaging of a limited number of cadaveric bone spongiosa cores...
January 2017: Medical Physics
https://www.readbyqxmd.com/read/28101531/osteopontin-is-a-blood-biomarker-for-microglial-activation-and-brain-injury-in-experimental-hypoxic-ischemic-encephalopathy
#2
Yikun Li, Eric B Dammer, Xiaohui Zhang-Brotzge, Scott Chen, Duc M Duong, Nicholas T Seyfried, Chia-Yi Kuan, Yu-Yo Sun
Clinical management of neonatal hypoxic-ischemic encephalopathy (HIE) suffers from the lack of reliable surrogate marker tests. Proteomic analysis may identify such biomarkers in blood, but there has been no proof-of-principle evidence to support this approach. Here we performed in-gel trypsin digestion of plasma proteins from four groups of 10-d-old mice [untouched and 24 h after low-dose lipopolysaccharide (LPS) exposure, hypoxia-ischemia (HI), or LPS/HI injury; n = 3 in each group) followed by liquid chromatography-tandem mass spectrometry and bioinformatics analysis to search for HI- and LPS/HI-associated brain injury biomarkers...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28100968/direct-measurement-of-left-atrial-pressure-during-routine-transradial-catheterization
#3
Faisal Fa'ak, Bahaeddin Shabaneh, George Younis
Left atrial pressure indicates the left ventricular filling pressure in patients who have systolic or diastolic left ventricular dysfunction or valvular heart disease. The use of indirect surrogate methods to determine left atrial pressure has been essential in the modern evaluation and treatment of cardiovascular disease because of the difficulty and inherent risks associated with direct methods (typically the transseptal approach). One method that has been widely used to determine left atrial pressure indirectly is Swan-Ganz catheterization, in which a balloon-flotation technique is applied to measure pulmonary capillary wedge pressure; however, this approach has been associated with several limitations and potential risks...
December 2016: Texas Heart Institute Journal
https://www.readbyqxmd.com/read/28100776/crystallographic-snapshots-of-class-a-%C3%AE-lactamase-catalysis-reveal-structural-changes-that-facilitate-%C3%AE-lactam-hydrolysis
#4
Xuehua Pan, Yunjiao He, Jinping Lei, Xuhui Huang, Yanxiang Zhao
β-lactamases confer resistance to β-lactam-based antibiotics. There is great interest in understanding their mechanisms to enable the development of β-lactamase-specific inhibitors. The mechanism of Class A β-lactamases has been studied extensively, revealing Lys73 and Glu166 as general bases that assist the catalytic residue Ser70. However, the specific roles of these two residues within the catalytic cycle remains not fully understood. To help resolve this question, we first identified a Glu166His mutant that is functional but kinetically slowed...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28099439/single-versus-serial-measurements-of-neuron-specific-enolase-and-prediction-of-poor-neurological-outcome-in-persistently-unconscious-patients-after-out-of-hospital-cardiac-arrest-a-ttm-trial-substudy
#5
Sebastian Wiberg, Christian Hassager, Pascal Stammet, Matilde Winther-Jensen, Jakob Hartvig Thomsen, David Erlinge, Michael Wanscher, Niklas Nielsen, Tommaso Pellis, Anders Åneman, Hans Friberg, Jan Hovdenes, Janneke Horn, Jørn Wetterslev, John Bro-Jeppesen, Matthew P Wise, Michael Kuiper, Tobias Cronberg, Yvan Gasche, Yvan Devaux, Jesper Kjaergaard
BACKGROUND: Prediction of neurological outcome is a crucial part of post cardiac arrest care and prediction in patients remaining unconscious and/or sedated after rewarming from targeted temperature management (TTM) remains difficult. Current guidelines suggest the use of serial measurements of the biomarker neuron-specific enolase (NSE) in combination with other predictors of outcome in patients admitted after out-of-hospital cardiac arrest (OHCA). This study sought to investigate the ability of NSE to predict poor outcome in patients remaining unconscious at day three after OHCA...
2017: PloS One
https://www.readbyqxmd.com/read/28099164/investigation-of-time-resolved-proton-radiography-using-x-ray-flat-panel-imaging-system
#6
Kyung-Wook Jee, Rongxiao Zhang, El Bentefour, Paul Doolan, Ethan Cascio, Gregory Sharp, Jacob Flanz, Hsiao-Ming Lu
Proton beam therapy benefits from the Bragg peak and delivers highly conformal dose distributions. However, the location of the end-of-range is subject to uncertainties related to the accuracy of the relative proton stopping power estimates and thereby the water-equivalent path length (WEPL) along the beam. To remedy the range uncertainty, an in vivo measurement of the WEPL through the patient, i.e. a proton-range radiograph, is highly desirable. Towards that goal, we have explored a novel method of proton radiography based on the time-resolved dose measured by a flat panel imager (FPI)...
January 18, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28098926/relevance-of-osteoclast-specific-enzyme-activities-in-cell-based-in-vitro-resorption-assays
#7
A Bernhardt, K Koperski, M Schumacher, M Gelinsky
Cell-based in vitro resorption assays are an important tool to simulate the in vivo biodegradation of resorbable bone graft materials and to predict their clinical performance. The present study analyses the activity of osteoclast-specific enzymes as potential surrogate measures for classical pit assay, which is not applicable on irregular structured materials. Osteoclasts derived from human peripheral blood mononuclear cells were cultivated on different surfaces: calcium phosphate bone cements (CPC), dentin discs, osteoblast-derived extracellular matrix (ECM) and tissue culture polystyrene as control...
January 18, 2017: European Cells & Materials
https://www.readbyqxmd.com/read/28097936/experimental-study-on-tissue-phantoms-to-understand-the-effect-of-injury-and-suturing-on-human-skin-mechanical-properties
#8
Arnab Chanda, Vinu Unnikrishnan, Zachary Flynn, Kim Lackey
Skin injuries are the most common type of injuries occurring in day-to-day life. A skin injury usually manifests itself in the form of a wound or a cut. While a shallow wound may heal by itself within a short time, deep wounds require surgical interventions such as suturing for timely healing. To date, suturing practices are based on a surgeon's experience and may vary widely from one situation to another. Understanding the mechanics of wound closure and suturing of the skin is crucial to improve clinical suturing practices and also to plan automated robotic surgeries...
January 2017: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine
https://www.readbyqxmd.com/read/28097506/bioequivalence-methodologies-for-topical-drug-products-in-vitro-and-ex-vivo-studies-with-a-corticosteroid-and-an-anti-fungal-drug
#9
Leila Bastos Leal, Sarah F Cordery, M Begoña Delgado-Charro, Annette L Bunge, Richard H Guy
OBJECTIVE: To examine whether in vitro and ex vivo measurements of topical drug product performance correlate with in vivo outcomes, such that more efficient experimental approaches can be reliably and reproducibly used to establish (in)equivalence between formulations for skin application. MATERIALS AND METHODS: In vitro drug release through artificial membranes, and drug penetration into porcine skin ex vivo, were compared with published human in vivo studies...
January 17, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28097317/surrogate-end-points-for-all-cause-mortality-in-men-with-localized-unfavorable-risk-prostate-cancer-treated-with-radiation-therapy-vs-radiation-therapy-plus-androgen-deprivation-therapy-a-secondary-analysis-of-a-randomized-clinical-trial
#10
Trevor J Royce, Ming-Hui Chen, Jing Wu, Marian Loffredo, Andrew A Renshaw, Philip W Kantoff, Anthony V D'Amico
Importance: Several surrogates for prostate cancer-specific mortality satisfying the Prentice criteria exist, but whether these are surrogates for all-cause mortality, and how their performance compares, is unknown. Objective: To ascertain and compare the performance of 4 candidate surrogates (prostate-specific antigen [PSA] failure, PSA nadir >0.5 ng/mL, PSA doubling time <9 months, and interval to PSA failure <30 months) for all-cause mortality using the proportion of treatment-effect metric...
January 12, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28097003/application-of-a-systems-pharmacology-model-for-translational-prediction-of-herg-mediated-qtc-prolongation
#11
Verena Gotta, Zhiyi Yu, Frank Cools, Karel van Ammel, David J Gallacher, Sandra A G Visser, Frederick Sannajust, Pierre Morissette, Meindert Danhof, Piet H van der Graaf
Drug-induced QTc interval prolongation (Δ QTc) is a main surrogate for proarrhythmic risk assessment. A higher in vivo than in vitro potency for hERG-mediated QTc prolongation has been suggested. Also, in vivo between-species and patient populations' sensitivity to drug-induced QTc prolongation seems to differ. Here, a systems pharmacology model integrating preclinical in vitro (hERG binding) and in vivo (conscious dog Δ QTc) data of three hERG blockers (dofetilide, sotalol, moxifloxacin) was applied (1) to compare the operational efficacy of the three drugs in vivo and (2) to quantify dog-human differences in sensitivity to drug-induced QTc prolongation (for dofetilide only)...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28096937/sunitinib-side-effects-as-surrogate-biomarkers-of-efficacy
#12
REVIEW
Christian Kollmannsberger
With the proliferation of treatment options for the management of metastatic renal cell carcinoma (mRCC) over the past decade, predictive markers of response to therapy are becoming increasingly important. Sunitinib is commonly used in the first-line treatment of mRCC. Common mechanism-based adverse events, including hypertension, hypothyroidism, hand-foot syndrome, and neutropenia, have been explored as potential biomarkers of the clinical efficacy of sunitinib in mRCC and are reviewed in this article.
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28096530/associations-between-body-mass-index-related-genetic-variants-and-adult-body-composition-the-fenland-cohort-study
#13
E A D Clifton, F R Day, E De Lucia Rolfe, N G Forouhi, S Brage, S J Griffin, N J Wareham, K K Ong
BACKGROUND/OBJECTIVE: Body mass index (BMI) is a surrogate measure of adiposity but does not distinguish fat from lean or bone mass. The genetic determinants of BMI are thought to predominantly influence adiposity but this has not been confirmed. Here we characterise the association between BMI-related genetic variants and body composition in adults. SUBJECTS/METHODS: Among 9667 adults aged 29-64 years from the Fenland study, a genetic risk score for BMI (BMI-GRS) was calculated for each individual as the weighted sum of BMI-increasing alleles across 96 reported BMI-related variants...
January 18, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28096437/phase-angle-predicts-arterial-stiffness-and-vascular-calcification-in-peritoneal-dialysis-patients
#14
Margarida Sarmento-Dias, Carla Santos-Araújo, Rui Poínhos, Bruno Oliveira, Maria Sousa, Liliana S Silva, Isabel S Silva, Flora Correia, Manuel Pestana
♦ Objectives: Fluid overload (FO) is frequently present in peritoneal dialysis (PD) patients and is associated with markers of malnutrition, inflammation, and atherosclerosis/calcification (MIAC) syndrome. We examined the relationships in stable PD patients between phase angle (PhA) and the spectrum of uremic vasculopathy including vascular calcification and arterial stiffness and between PhA and changes in serum fetuin-A levels. ♦ Methods: Sixty-one stable adult PD patients were evaluated in a cross-sectional study (ST1)...
January 17, 2017: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
https://www.readbyqxmd.com/read/28096239/skin-to-skin-care-in-preterm-infants-receiving-respiratory-support-does-not-lead-to-physiological-instability
#15
Laila Lorenz, Jennifer A Dawson, Hannah Jones, Susan E Jacobs, Jeanie L Cheong, Susan M Donath, Peter G Davis, C Omar F Kamlin
OBJECTIVE: Providing skin-to-skin care (SSC) to preterm infants is standard practice in many neonatal intensive care units. There are conflicting reports on the stability of oxygen saturation (SpO2) during SSC, which may create a barrier to a wider implementation of SSC to infants receiving respiratory support. Regional cerebral oxygenation (rcO2) measured using near-infrared spectroscopy can serve as a surrogate parameter for cerebral oxygen delivery and consumption. We hypothesised that rcO2 during SSC would be similar to standard care in preterm infants receiving respiratory support...
January 17, 2017: Archives of Disease in Childhood. Fetal and Neonatal Edition
https://www.readbyqxmd.com/read/28095794/development-of-an-algorithm-for-phenotypic-screening-of-carbapenemase-producing-enterobacteriaceae-in-the-routine-laboratory
#16
Jérôme Robert, Alix Pantel, Audrey Merens, Elodie Meiller, Jean-Philippe Lavigne, Marie-Hélène Nicolas-Chanoine
BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) are difficult to identify among carbapenem non-susceptible Enterobacteriaceae (NSE). We designed phenotypic strategies giving priority to high sensitivity for screening putative CPE before further testing. METHODS: Presence of carbapenemase-encoding genes in ertapenem NSE (MIC > 0.5 mg/l) consecutively isolated in 80 French laboratories between November 2011 and April 2012 was determined by the Check-MDR-CT103 array method...
January 17, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28095171/drug-interaction-database-sensitivity-with-oral-antineoplastics-an-exploratory-analysis
#17
John B Bossaer, Christan M Thomas
PURPOSE: Drug interactions are a concern in oncology with the shift toward oral antineoplastics (OAs). Using electronic databases to screen for drug interactions with OAs is a common practice. There is little literature to guide clinicians on the reliability of these systems with OAs. The primary objective of this study was to explore the sensitivity of commonly available drug interaction databases in detecting drug interactions with OAs. METHODS: A list of 20 drug interactions with OAs was developed by two Board-certified oncology pharmacists...
January 17, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28095160/minimal-loss-of-lifetime-for-patients-with-diffuse-large-b-cell-lymphoma-in-remission-and-event-free-24-months-after-treatment-a-danish-population-based-study
#18
Lasse Hjort Jakobsen, Martin Bøgsted, Peter de Nully Brown, Bente Arboe, Judit Jørgensen, Thomas Stauffer Larsen, Maja Bech Juul, Lene Schurmann, Linda Højberg, Olav Jonas Bergmann, Therese Lassen, Pär Lars Josefsson, Paw Jensen, Hans Erik Johnsen, Tarec Christoffer El-Galaly
Purpose The general outlook for patients with diffuse large B-cell lymphoma (DLBCL) in first remission is important information for patients and for planning post-treatment follow-up. The purpose of this study was to evaluate the survival of patients with DLBCL in remission compared with a matched general population. Methods A total of 1,621 patients from the Danish Lymphoma Registry who were newly diagnosed with DLBCL between 2003 and 2011 were included in this study. All patients were ≥ 16 years of age at diagnosis and had achieved complete remission or complete remission unconfirmed after first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like therapy...
January 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28094937/click-qms-identifies-piwil3-as-a-mechanistic-target-of-rna-interference-activator-enoxacin-in-cancer-cells
#19
Nathan Abell, Marvin Mercado, Tatiana Cañeque, Raphaël Rodriguez, Blerta Xhemalce
Enoxacin is a small molecule that stimulates RNA interference (RNAi) and acts as a growth inhibitor selectively in cancer but not in untransformed cells. Here, we used alkenox, a clickable enoxacin surrogate, coupled with quantitative Mass Spectrometry, to identify PIWIL3 as a mechanistic target of enoxacin. PIWIL3 is an Argonaut protein of the PIWI subfamily that is mainly expressed in the germline and that mediates RNAi through piRNAs. Our results suggest that cancer cells re-express PIWIL3 to repress RNAi through miRNAs and thus open a new opportunity for cancer specific targeting...
January 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28094846/chronic-drug-induced-effects-on-contractile-motion-properties-and-cardiac-biomarkers-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#20
Ivan Kopljar, An De Bondt, Petra Vinken, Ard Teisman, Bruce Damiano, Nick Goeminne, Ilse Van den Wyngaert, David J Gallacher, Hua Rong Lu
BACKGROUND AND PURPOSE: Risk assessment of chronic cardiac safety liabilities within the pharmaceutical industry is mostly performed during late stages of pre-clinical drug development using in vivo animal models. Here, we explored the potential of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to detect chronic cardiac risks such as drug-induced cardiomyocyte toxicity. EXPERIMENTAL APPROACH: Video microscopy-based motion field imaging was applied to evaluate chronic effect (over 72 h) of cardiotoxic drugs on the contractile motion of hiPS-CMs...
January 17, 2017: British Journal of Pharmacology
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