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https://www.readbyqxmd.com/read/29444985/molecular-pharmacodynamics-guided-scheduling-of-biologically-effective-doses-a-drug-development-paradigm-applied-to-met-tyrosine-kinase-inhibitors
#1
Apurva K Srivastava, Melinda G Hollingshead, Jeevan P Govindharajulu, Joseph M Covey, Dane Liston, Melanie A Simpson, James O Peggins, Donald P Bottaro, John J Wright, Robert J Kinders, James H Doroshow, Ralph E Parchment
The development of molecularly targeted agents has benefited from use of pharmacodynamic (PD) markers to identify "biologically effective doses" (BEDs) below maximum tolerable doses, yet this knowledge remains underutilized in selecting dosage regimens and in comparing the effectiveness of targeted agents within a class. We sought to establish preclinical proof-of-concept for such PD-based BED regimens and effectiveness comparisons using MET kinase small molecule inhibitors. Utilizing PD biomarker measurements of MET signaling (tumor pY 1234/1235 MET/total MET ratio) in a Phase 0-like preclinical setting, we developed optimal dosage regimens for several MET kinase inhibitors and compared their antitumor efficacy in a MET-amplified gastric cancer xenograft model (SNU-5)...
February 14, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29437057/three-groups-of-dissatisfied-patients-exist-after-total-knee-arthroplasty-early-persistent-and-late
#2
N D Clement, M Bardgett, D Weir, J Holland, C Gerrand, D J Deehan
AIMS: The primary aim of this study was to assess whether patient satisfaction one year after total knee arthroplasty (TKA) changed with longer follow-up. The secondary aims were to identify predictors of satisfaction at one year, persistence of patient dissatisfaction, and late onset dissatisfaction in patients that were originally satisfied at one year. PATIENTS AND METHODS: A retrospective cohort consisting of 1369 patients undergoing a primary TKA for osteoarthritis that had not undergone revision were identified from an established arthroplasty database...
February 2018: Bone & Joint Journal
https://www.readbyqxmd.com/read/29427904/lack-of-association-between-aryl-hydrocarbon-receptor-gene-arg554lys-polymorphism-and-male-infertility-risk-a-systematic-review-and-meta-analysis
#3
Yong Wei, Zheng Zhang, Guotao Chen, Leilei Zhu, Hesong Jiang, Baibing Yang, Yun Chen, Yutian Dai, Quanbing Chen
OBJECTIVES: The association between aryl hydrocarbon receptor gene (AhR) polymorphism and male infertility risk remains conflicting. We conducted a meta-analysis to examine the AhR Arg554Lys polymorphism in relation to the susceptibility to male infertility. STUDY DESIGN: Studies concerning the association between AHR polymorphism and male infertility were searched and related information were extracted from the included studies. The STATA 12.0 software was used to perform a meta-analysis...
January 31, 2018: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/29425459/tunable-physical-properties-of-ethylcellulose-gelatin-composite-nanofibers-by-electrospinning
#4
Yuyu Liu, Lingli Deng, Cen Zhang, Fengqin Feng, Hui Zhang
In this work, the ethylcellulose/gelatin blends at various weight ratios in water/ethanol/acetic acid solution were electrospun to fabricate nanofibers with tunable physical properties. The solution compatibility was predicted based on Hansen solubility parameters and evaluated by rheological measurements. The physical properties were characterized by scanning electron microscopy, porosity, differential scanning calorimetry, thermogravimetry, Fourier transform infrared spectroscopy, and water contact angle...
February 9, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29416730/neutrophil-extracellular-traps-contribute-to-the-pathogenesis-of-acid-aspiration-induced-ali-ards
#5
Haitao Li, Xiaoting Zhou, Hongyi Tan, Yongbin Hu, Lemeng Zhang, Shuai Liu, Minhui Dai, Yi Li, Qian Li, Zhi Mao, Pinhua Pan, Xiaoli Su, Chengpin Hu
Background: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a manifestation of systemic inflammation in the lungs, but the factors that trigger inflammation in ALI/ARDS are unclear. We hypothesized that neutrophil extracellular traps (NETs) contribute to the pathogenesis of acid aspiration-induced ALI/ARDS. Results: Analysis of bronchial aspirates from ARDS patients showed that NETs were significantly correlated with the degree of ARDS (r = -0...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29400403/evaluation-of-pet-owner-preferences-for-operative-sterilization-techniques-in-female-dogs-within-the-veterinary-community
#6
Christine Hsueh, Michelle Giuffrida, Philipp D Mayhew, J Brad Case, Ameet Singh, Eric Monnet, David E Holt, Megan Cray, Chiara Curcillo, Jeffrey J Runge
OBJECTIVE: To describe pet owner preferences within the veterinary community when choosing operative techniques for canine spay. STUDY DESIGN: Prospective survey. SAMPLE POPULATION: 1234 respondents from 5 veterinary university teaching hospitals in North America. METHODS: An electronic survey was distributed to faculty, students, and staff that currently are or previously were dog owners. Responses were analyzed to determine what spay technique respondents would choose for their own dogs...
February 5, 2018: Veterinary Surgery: VS
https://www.readbyqxmd.com/read/29391619/bacteriophage-application-for-biocontrolling-shigella-flexneri-in-contaminated-foods
#7
Khashayar Shahin, Majid Bouzari
Shigellosis (bacillary dysentery) is an acute enteric infection caused by members of Shigella genus. It causes annual deaths of approximately five million children in developing countries. Among Shigella spp., S. flexneri causes more serious forms of dysentery than other Shigella species. Due to the appearance of multidrug-resistant strains of Shigella spp., it is necessary to find alternative antimicrobial agents. The aims of this study were the isolation of a novel species-specific phage against S. flexneri and to evaluate its potential and efficacy for biocontrolling of S...
February 2018: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/29379144/carbohydrate-and-fiber-intake-and-the-risk-of-premenstrual-syndrome
#8
Serena C Houghton, JoAnn E Manson, Brian W Whitcomb, Susan E Hankinson, Lisa M Troy, Carol Bigelow, Elizabeth R Bertone-Johnson
BACKGROUND/OBJECTIVES: Women with premenstrual syndrome (PMS) are encouraged to reduce sugar and increase fiber intake to reduce symptoms. However, research supporting these recommendations is limited, and their role in PMS development is unclear. This study examines the relation between carbohydrate and fiber intake and the risk of PMS nested within the prospective Nurses' Health Study II cohort. SUBJECTS/METHODS: Carbohydrate and fiber intake were assessed at baseline and three additional times during follow up by food frequency questionnaire...
January 29, 2018: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/29356953/the-use-of-pipac-pressurized-intraperitoneal-aerosol-chemotherapy-in-gynecological-oncology-a-statement-by-the-german-arbeitsgemeinschaft-gynaekologische-onkologie-studiengruppe-ovarialkarzinom-ago-ovar-the-swiss-and-austrian-ago-and-the-north-eastern-german
#9
REVIEW
A M Dueckelmann, D Fink, P Harter, V Heinzelmann, C Marth, M Mueller, A Reinthaller, K Tamussino, P Wimberger, J Sehouli
BACKGROUND: Ovarian, tubal, and peritoneal carcinomas primarily affect the peritoneal cavity, and they are typically diagnosed at an advanced tumor stage (Foley, Rauh-Hain, del Carmen in Oncology (Williston Park) 27:288-294, 2013). In the course of primary surgery, postoperative tumor residuals are, apart from the tumor stage, the strongest independent factors of prognosis (du Bois, Reuss, Pujade-Lauraine, Harter, Ray-Coquard, Pfisterer in Cancer 115:1234-1244, 2009). Due to improved surgical techniques, including the use of multi-visceral procedures, macroscopic tumor clearance can be achieved in oncological centers, in most cases (Harter, Muallem, Buhrmann et al in Gynecol Oncol 121:615-619, 2011)...
January 22, 2018: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/29335831/quality-of-inter-hospital-transportation-in-431-transport-survivor-patients-suffering-from-acute-respiratory-distress-syndrome-referred-to-specialist-centers
#10
Sebastian Blecha, Frank Dodoo-Schittko, Susanne Brandstetter, Magdalena Brandl, Michael Dittmar, Bernhard M Graf, Christian Karagiannidis, Christian Apfelbacher, Thomas Bein
BACKGROUND: The acute respiratory distress syndrome (ARDS) is a life-threatening condition. In special situations, these critically ill patients must be transferred to specialized centers for escalating treatment. The aim of this study was to evaluate the quality of inter-hospital transport (IHT) of ARDS patients. METHODS: We evaluated medical and organizational aspects of structural and procedural quality relating to IHT of patients with ARDS in a prospective nationwide ARDS study...
January 15, 2018: Annals of Intensive Care
https://www.readbyqxmd.com/read/29262369/sarcomere-stiffness-during-stretching-and-shortening-of-rigor-skeletal-myofibrils
#11
Nabil Shalabi, Malin Persson, Alf Månsson, Srikar Vengallatore, Dilson E Rassier
In this study, we measured the stiffness of skeletal muscle myofibrils in rigor. Using a custom-built atomic force microscope, myofibrils were first placed in a rigor state then stretched and shortened at different displacements (0.1-0.3 μm per sarcomere) and nominal speeds (0.4 and 0.8 μm/s). During stretching, the myofibril stiffness was independent of both displacement and speed (average of 987 nN/μm). During shortening, the myofibril stiffness was independent of displacement, but dependent on speed (1234 nN/μm at 0...
December 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29238243/analysis-of-time-motion-and-heart-rate-in-elite-male-and-female-beach-handball
#12
Basilio Pueo, Jose M Jimenez-Olmedo, Alfonso Penichet-Tomas, Manuel Ortega Becerra, Jose J Espina Agullo
Beach handball is a spectacular new team sport; however, scientific knowledge about the demands in beach handball is very low. Consequently, the aim of this study was to analyze the physical demands of elite beach handball players by means of time-motion analysis with GPS technology and physiological response with Heart Rate (HR). Both male (n = 12) and female (n = 12) players from the Spanish Beach Handball National Team were recruited for this study. The sample consisted in four matches of two 10-min periods each...
December 2017: Journal of Sports Science & Medicine
https://www.readbyqxmd.com/read/29235458/the-ideal-harvest-time-for-seeds-of-hybrid-maize-zea-mays-l-xy335-and-zd958-produced-in-multiple-environments
#13
Riliang Gu, Li Li, Xiaolin Liang, Yanbo Wang, Tinglu Fan, Ying Wang, Jianhua Wang
To identify the ideal harvest time (IHT) for the seed production of XY335 and ZD958, six seed-related traits were evaluated in seeds harvested at 11 harvest stages in 8 environments. Standard germination (SG), accelerated aging germination (AAG) and cold test germination (CTG) were vigor traits; hundred-seed weight (HSW) and seed moisture content (SMC) were physiological traits; and ≥10 °C accumulated temperature from pollination to harvest (AT10ph) was an ecological trait. All the traits were significantly affected by harvest stage...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29209947/copy-number-variation-arising-from-gene-conversion-on-the-human-y-chromosome
#14
Wentao Shi, Andrea Massaia, Sandra Louzada, Ruby Banerjee, Pille Hallast, Yuan Chen, Anders Bergström, Yong Gu, Steven Leonard, Michael A Quail, Qasim Ayub, Fengtang Yang, Chris Tyler-Smith, Yali Xue
We describe the variation in copy number of a ~ 10 kb region overlapping the long intergenic noncoding RNA (lincRNA) gene, TTTY22, within the IR3 inverted repeat on the short arm of the human Y chromosome, leading to individuals with 0-3 copies of this region in the general population. Variation of this CNV is common, with 266 individuals having 0 copies, 943 (including the reference sequence) having 1, 23 having 2 copies, and two having 3 copies, and was validated by breakpoint PCR, fibre-FISH, and 10× Genomics Chromium linked-read sequencing in subsets of 1234 individuals from the 1000 Genomes Project...
December 5, 2017: Human Genetics
https://www.readbyqxmd.com/read/29205592/increase-of-prostaglandin-e2-in-the-reversal-of-ductal-constriction-after-polyphenol-restriction
#15
Izabele Vian, Paulo Zielinsky, Ana Maria Zílio, Maximiliano I Schaun, Camila Brum, Kenya Venusa Lampert, Nataly De Ávila, Giovana Baldissera, Tamires Mezzomo Klanovicz, Karina Zenki, Jesus Zurita-Peralta, Alessandro Olszewski, Antonio Piccoli, Luiz Henrique Nicoloso, Natássia Sulis, Luiza Van Der Sand, Melissa Markoski
OBJECTIVE: Anti-inflammatory substances that inhibit the synthesis of prostaglandins, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and polyphenol-rich foods, can cause constriction of the fetal ductus arteriosus. This study aimed to test the hypothesis that reversal of fetal ductal constriction after maternal restriction of polyphenol-rich foods, in the third trimester of pregnancy, is accompanied by increased prostaglandin E2(PGE2) plasma levels. METHOD: A controlled clinical trial was designed...
December 5, 2017: Ultrasound in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29203490/mutations-in-genes-encoding-penicillin-binding-proteins-and-efflux-pumps-play-a-role-in-%C3%AE-lactam-resistance-in-helicobacter-cinaedi
#16
Emiko Rimbara, Shigetarou Mori, Hyun Kim, Masato Suzuki, Keigo Shibayama
β-Lactams are often used to treat Helicobacter cinaedi infections; however, the mechanism underlying β-lactam resistance is unknown. In this study, we investigated β-lactam resistance in a H. cinaedi strain, MRY12-0051 (MIC of AMX and CRO: 32 and 128 μg/ml; obtained from human feces). Based on a comparative whole genome analysis of MRY12-0051 and the CRO-susceptible H. cinaedi strain MRY08-1234 (MIC of AMX and CRO: 1 and 4 μg/ml; obtained from human blood), we identified five mutations in genes encoding penicillin-binding proteins (PBPs), including two in pbpA, one in pbp2, and two in ftsI Transformation and penicillin-binding assays indicated that CRO resistance was mainly associated with mutations in pbpA; mutations in ftsI also led to increased resistance to AMX...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29170310/13%C3%A2-prophylactic-antibiotics-for-penetrating-injury-a-review-of-practice-at-a-major-trauma-centre-literature-review-and-recommendations
#17
Marharyta Kamarova, Richard Kendall
BACKGROUND: There is a lack of clarity regarding the use of prophylactic antibiotics for patients presenting with penetrating injuries. A structured literature review and review of penetrating injury records in an MTC was undertaken with a view to help guide clinical practice. METHOD: Searches were conducted on Medline (1946-2017), Embase (1974-2017), and Cochrane (up to 2017) using key words pertaining to penetrating trauma, prophylactic antibiotics and infection...
December 2017: Emergency Medicine Journal: EMJ
https://www.readbyqxmd.com/read/29167390/early-elevated-troponin-levels-after-ischemic-stroke-suggests-a-cardioembolic-source
#18
Shadi Yaghi, Andrew D Chang, Brittany A Ricci, Mahesh V Jayaraman, Ryan A McTaggart, Morgan Hemendinger, Priya Narwal, Katarina Dakay, Brian Mac Grory, Shawna M Cutting, Tina M Burton, Christopher Song, Emile Mehanna, Matthew Siket, Tracy E Madsen, Michael Reznik, Alexander E Merkler, Michael P Lerario, Hooman Kamel, Mitchell S V Elkind, Karen L Furie
BACKGROUND AND PURPOSE: Elevated cardiac troponin is a marker of cardiac disease and has been recently shown to be associated with embolic stroke risk. We hypothesize that early elevated troponin levels in the acute stroke setting are more prevalent in patients with embolic stroke subtypes (cardioembolic and embolic stroke of unknown source) as opposed to noncardioembolic subtypes (large-vessel disease, small-vessel disease, and other). METHODS: We abstracted data from our prospective ischemic stroke database and included all patients with ischemic stroke during an 18-month period...
January 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29160917/visualization-of-calcium-phosphate-cement-in-teeth-by-zero-echo-time-1-h-mri-at-high-field
#19
Weiqiang Dou, Simone Mastrogiacomo, Andor Veltien, Hamdan S Alghamdi, X Frank Walboomers, Arend Heerschap
(1) H magnetic resonance imaging (MRI) by a zero echo time (ZTE) sequence is an excellent method to image teeth. Calcium phosphate cement (CPC) materials are applied in the restoration of tooth lesions, but it has not yet been investigated whether they can be detected by computed tomography (CT) or MRI. The aim of this study was to optimize high-field ZTE imaging to enable the visualization of a new CPC formulation implanted in teeth and to apply this in the assessment of its decomposition in vivo. CPC was implanted in three human and three goat teeth ex vivo and in three goat teeth in vivo...
November 21, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/29137197/effect-of-age-on-glasgow-coma-scale-in-patients-with-moderate-and-severe-traumatic-brain-injury-an-approach-with-propensity-score-matched-population
#20
Cheng-Shyuan Rau, Shao-Chun Wu, Yi-Chun Chen, Peng-Chen Chien, Hsiao-Yun Hsieh, Pao-Jen Kuo, Ching-Hua Hsieh
Background: The most widely used methods of describing traumatic brain injury (TBI) are the Glasgow Coma Scale (GCS) and the Abbreviated Injury Scale (AIS). Recent evidence suggests that presenting GCS in older patients may be higher than that in younger patients for an equivalent anatomical severity of TBI. This study aimed to assess these observations with a propensity-score matching approach using the data from Trauma Registry System in a Level I trauma center. Methods: We included all adult patients (aged ≥20 years old) with moderate to severe TBI from 1 January 2009 to 31 December 2016...
November 13, 2017: International Journal of Environmental Research and Public Health
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