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https://www.readbyqxmd.com/read/28813840/a-novel-protocol-to-evaluate-ankle-movements-during-reaching-tasks-using-pedianklebot
#1
Francesca Martelli, Eduardo Palermo, Stefano Rossi
The aim of the study is to design a novel protocol to characterize the ankle movements during dorsal and plantar flexion reaching tasks using the pediAnklebot. Five healthy children were instructed to control a pointer and hit targets appearing on the monitor, by moving their ankle alternatively up and down. The protocol consisted of 60 targets, 30 up and 30 down, reachable via dorsiflexion and plantarflexion movements, respectively. Ankle angular displacements and torques were gathered by encoders and load cells embedded in the robot...
July 2017: IEEE ... International Conference on Rehabilitation Robotics: [proceedings]
https://www.readbyqxmd.com/read/28789610/management-of-refractory-bleeding-post-cardiopulmonary-bypass-in-an-acute-heparin-induced-thrombocytopenia-type-ii-renal-failure-patient-who-underwent-urgent-cardiac-surgery-with-bivalirudin-angiox-%C3%A2-anticoagulation
#2
Kimberly Hassen, Maria R Maccaroni, Haytham Sabry, Smitangshu Mukherjee, Shankari Serumadar, Inderpaul Birdi
Acute heparin-induced thrombocytopenia (HIT) patients present myriad anticoagulation management challenges in clinical settings where unfractionated heparin (UFH) is the traditional drug of choice. UFH use in cardiac surgery is a known entity that has been subject to rigorous research. Research has, thus, led to its unparalleled use and the development of well-established protocols for cardiac surgery. In comparison to UFH, bivalirudin use for acute HIT patients requiring urgent cardiac surgery with cardiopulmonary bypass (CPB) is still in its infancy...
August 1, 2017: Perfusion
https://www.readbyqxmd.com/read/28766123/screening-the-toxcast-phase-ii-libraries-for-alterations-in-network-function-using-cortical-neurons-grown-on-multi-well-microelectrode-array-mwmea-plates
#3
Jenna D Strickland, Matthew T Martin, Ann M Richard, Keith A Houck, Timothy J Shafer
Methods are needed for rapid screening of environmental compounds for neurotoxicity, particularly ones that assess function. To demonstrate the utility of microelectrode array (MEA)-based approaches as a rapid neurotoxicity screening tool, 1055 chemicals from EPA's phase II ToxCast library were evaluated for effects on neural function and cell health. Primary cortical networks were grown on multi-well microelectrode array (mwMEA) plates. On day in vitro 13, baseline activity (40 min) was recorded prior to exposure to each compound (40 µM)...
August 2, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28728785/operative-strategies-to-reduce-cerebral-embolic-events-during-on-and-off-pump-coronary-artery-bypass-surgery-a-stratified-prospective-randomized-trial
#4
Michael E Halkos, Aaron Anderson, Jose Nilo G Binongo, Anthony Stringer, Yi Lasanajak, Vinod H Thourani, Omar M Lattouf, Robert A Guyton, Kim T Baio, Eric Sarin, William B Keeling, N Renee Cook, Katherine Carssow, Alexis Neill, Kathryn E Glas, John D Puskas
OBJECTIVE: To determine the impact of different aortic clamping strategies on the incidence of cerebral embolic events during coronary artery bypass grafting (CABG). METHODS: Between 2012 and 2015, 142 patients with low-grade aortic disease (epiaortic ultrasound grade I/II) undergoing primary isolated CABG were studied. Those undergoing off-pump CABG were randomized to a partial clamp (n = 36) or clampless facilitating device (CFD; n = 36) strategy. Those undergoing on-pump CABG were randomized to a single-clamp (n = 34) or double-clamp (n = 36) strategy...
June 16, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28704450/a-consensus-layer-v-pyramidal-neuron-can-sustain-interpulse-interval-coding
#5
Chandan Singh, William B Levy
In terms of a single neuron's long-distance communication, interpulse intervals (IPIs) are an attractive alternative to rate and binary codes. As a proxy for an IPI, a neuron's time-to-spike can be found in the biophysical and experimental intracellular literature. Using the current, consensus layer V pyramidal neuron, the present study examines the feasibility of IPI-coding and examines the noise sources that limit the information rate of such an encoding. In descending order of importance, the noise sources are (i) synaptic variability, (ii) sodium channel shot-noise, followed by (iii) thermal noise...
2017: PloS One
https://www.readbyqxmd.com/read/28696944/mitoriboscins-mitochondrial-based-therapeutics-targeting-cancer-stem-cells-cscs-bacteria-and-pathogenic-yeast
#6
Bela Ozsvari, Marco Fiorillo, Gloria Bonuccelli, Anna Rita Cappello, Luca Frattaruolo, Federica Sotgia, Rachel Trowbridge, Richard Foster, Michael P Lisanti
The "endo-symbiotic theory of mitochondrial evolution" states that mitochondrial organelles evolved from engulfed aerobic bacteria, after millions of years of symbiosis and adaptation. Here, we have exploited this premise to design new antibiotics and novel anti-cancer therapies, using a convergent approach. First, virtual high-throughput screening (vHTS) and computational chemistry were used to identify novel compounds binding to the 3D structure of the mammalian mitochondrial ribosome. The resulting library of ~880 compounds was then subjected to phenotypic drug screening on human cancer cells, to identify which compounds functionally induce ATP-depletion, which is characteristic of mitochondrial inhibition...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28688202/influence-of-human-leukocyte-antigen-hla-alleles-and-killer-cell-immunoglobulin-like-receptors-kir-types-on-heparin-induced-thrombocytopenia-hit
#7
Jason H Karnes, Christian M Shaffer, Robert Cronin, Lisa Bastarache, Silvana Gaudieri, Ian James, Rebecca Pavlos, Heidi Steiner, Jonathan D Mosley, Simon Mallal, Joshua C Denny, Elizabeth J Phillips, Dan M Roden
OBJECTIVES: Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT...
July 8, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28686598/processing-closely-spaced-lesions-during-nucleotide-excision-repair-triggers-mutagenesis-in-e-coli
#8
Régine Janel-Bintz, Rita L Napolitano, Asako Isogawa, Shingo Fujii, Robert P Fuchs
It is generally assumed that most point mutations are fixed when damage containing template DNA undergoes replication, either right at the fork or behind the fork during gap filling. Here we provide genetic evidence for a pathway, dependent on Nucleotide Excision Repair, that induces mutations when processing closely spaced lesions. This pathway, referred to as Nucleotide Excision Repair-induced Mutagenesis (NERiM), exhibits several characteristics distinct from mutations that occur within the course of replication: i) following UV irradiation, NER-induced mutations are fixed much more rapidly (t ½ ≈ 30 min) than replication dependent mutations (t ½ ≈ 80-100 min) ii) NERiM specifically requires DNA Pol IV in addition to Pol V iii) NERiM exhibits a two-hit dose-response curve that suggests processing of closely spaced lesions...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28667245/a-screen-for-inducers-of-bhlh-activity-identifies-pitavastatin-as-a-regulator-of-p21-rb-phosphorylation-and-e2f-target-gene-expression-in-pancreatic-cancer
#9
Nicholas Villarino, Lia Signaevskaia, Jaco van Niekerk, Rachel Medal, Heejung Kim, Reyhaneh Lahmy, Kathleen Scully, Anthony Pinkerton, SangWun Kim, Andrew Lowy, Pamela Itkin-Ansari
The average survival for patients with Pancreatic Ductal Adenocarcinoma (PDA) is merely 6 months, underscoring the need for new therapeutic approaches. During PDA progression, pancreatic acinar cells lose activity of the ClassI/II bHLH factors that regulate quiescence. We previously found that promoting transcriptional activity of the Class I bHLH factor E47 in highly aggressive PDA cells induced stable growth arrest in vitro and in vivo. To translate these findings for clinical utility, we developed a high throughput screening platform to identify small molecule inducers of Class I/II bHLH activity...
June 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28665353/identification-of-direct-activator-of-adenosine-monophosphate-activated-protein-kinase-ampk-by-structure-based-virtual-screening-and-molecular-docking-approach
#10
Tonghui Huang, Jie Sun, Shanshan Zhou, Jian Gao, Yi Liu
Adenosine monophosphate-activated protein kinase (AMPK) plays a critical role in the regulation of energy metabolism and has been targeted for drug development of therapeutic intervention in Type II diabetes and related diseases. Recently, there has been renewed interest in the development of direct β1-selective AMPK activators to treat patients with diabetic nephropathy. To investigate the details of AMPK domain structure, sequence alignment and structural comparison were used to identify the key amino acids involved in the interaction with activators and the structure difference between β1 and β2 subunits...
June 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28653555/usher-s-syndrome-type-ii-a-comparative-study-of-genetic-mutations-and-vestibular-system-evaluation
#11
Giuseppe Magliulo, Giannicola Iannella, Silvia Gagliardi, Nicola Iozzo, Rocco Plateroti, Alessandro Mariottini, Francesca Torricelli
Objective Usher's syndrome type II (USH2) is characterized by moderate to profound congenital hearing loss, later onset of retinitis pigmentosa, and normal vestibular function. Recently, a study investigating the vestibular function of USH2 patients demonstrated a pathologic response to vestibular tests. In this cross-sectional study we performed vestibular tests of a group patients with genetic diagnosis of USH2 syndrome to demonstrate if vestibular damage is present in USH2 patients. Study Design Cross-sectional study...
June 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28646182/high-intensity-interval-training-improves-mitochondrial-function-and-suppresses-thrombin-generation-in-platelets-undergoing-hypoxic-stress
#12
Li-Hua Wu, Shao-Chiang Chang, Tieh-Cheng Fu, Ching-Hui Huang, Jong-Shyan Wang
This study elucidates how high-intensity interval training (HIT) and moderate-intensity continuous training (MCT) affect mitochondrial functionality and thrombin generation (TG) in platelets following hypoxic exercise (HE, 100 W under 12% O2 for 30 min). Forty-five healthy sedentary males were randomized to engage either HIT (3-minute intervals at 40% and 80%VO2max, n = 15) or MCT (sustained 60%VO2max, n = 15) for 30 minutes/day, 5 days/week for 6 weeks, or to a control group (CTL, n = 15) that did not received exercise intervention...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28638354/investigating-team-coordination-in-baseball-using-a-novel-joint-decision-making-paradigm
#13
Rob Gray, Nancy J Cooke, Nathan J McNeese, Jaimie McNabb
A novel joint decision making paradigm for assessing team coordination was developed and tested using baseball infielders. Balls launched onto an infield at different trajectories were filmed using four video cameras that were each placed at one of the typical positions of the four infielders. Each participant viewed temporally occluded videos for one of the four positions and were asked to say either "ball" if they would attempt to field it or the name of the bag that they would cover. The evaluation of two experienced coaches was used to assign a group coordination score for each trajectory and group decision times were calculated...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28624695/first-in-human-phase-i-study-of-oral-s49076-a-unique-met-axl-fgfr-inhibitor-in-advanced-solid-tumours
#14
Jordi Rodon, Sophie Postel-Vinay, Antoine Hollebecque, Paolo Nuciforo, Analia Azaro, Valérie Cattan, Lucie Marfai, Isabelle Sudey, Karl Brendel, Audrey Delmas, Stéphanie Malasse, Jean-Charles Soria
BACKGROUND AND OBJECTIVES: S49076 is a novel ATP-competitive tyrosine kinase inhibitor of MET, AXL and FGFR with a unique selectivity profile. A phase I open-label study was undertaken to establish the tolerability profile and determine the recommended dose (RD) and administration schedule. MATERIALS AND METHODS: Patients with advanced solid tumours received S49076 orally once-daily (qd) or twice-daily (bid) in continuous 21-day cycles at escalating doses guided by a 3 + 3 design and followed by an expansion phase at the RD...
August 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28622697/vitamin-c-and-doxycycline-a-synthetic-lethal-combination-therapy-targeting-metabolic-flexibility-in-cancer-stem-cells-cscs
#15
Ernestina Marianna De Francesco, Gloria Bonuccelli, Marcello Maggiolini, Federica Sotgia, Michael P Lisanti
Here, we developed a new synthetic lethal strategy for further optimizing the eradication of cancer stem cells (CSCs). Briefly, we show that chronic treatment with the FDA-approved antibiotic Doxycycline effectively reduces cellular respiration, by targeting mitochondrial protein translation. The expression of four mitochondrial DNA encoded proteins (MT-ND3, MT-CO2, MT-ATP6 and MT-ATP8) is suppressed, by up to 35-fold. This high selection pressure metabolically synchronizes the surviving cancer cell sub-population towards a predominantly glycolytic phenotype, resulting in metabolic inflexibility...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28589758/identification-of-type-i-and-type-ii-inhibitors-of-c-yes-kinase-using-in-silico-and-experimental-techniques
#16
Chandrasekaran Ramakrishnan, Anthony Mary Thangakani, Devadasan Velmurugan, Dhanabalan Anantha Krishnan, Masakazu Sekijima, Yutaka Akiyama, M Michael Gromiha
c-Yes kinase is considered as one of the attractive targets for anti-cancer drug design. The DFG (Asp-Phe-Gly) motif present in most of the kinases will adopt active and inactive conformations, known as DFG-in and DFG-out and their inhibitors are classified into type I and type II, respectively. In the present study, two screening protocols were followed for identification of c-Yes kinase inhibitors. (i) Structure-based virtual screening (SBVS) and (ii) Structure-based (SB) and Pharmacophore-based (PB) tandem screening...
June 7, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28571491/insights-into-unbound-bound-states-of-gpr142-receptor-in-a-membrane-aqueous-system-using-molecular-dynamics-simulations
#17
Aman Chandra Kaushik, Shakti Sahi
G protein coupled receptors (GPCRs) are source machinery in signal transduction pathways and being one of the major therapeutic targets play a significant in drug discovery. GPR142, an orphan GPCR, has been implicated in the regulation of insulin, thereby having a crucial role in Type II diabetes management. Deciphering of the structures of orphan GPCRs (O-GPCRs) offer better prospects for advancements in research in ion translocation and transduction of extracellular signals. As the crystallographic structure of GPR142 is not available in PDB, therefore, threading and abinitio based approaches were used for 3D modeling of GPR142...
June 1, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28566208/development-of-wnk-signaling-inhibitors-as-a-new-class-of-antihypertensive-drugs
#18
Mari Ishigami-Yuasa, Yuko Watanabe, Takayasu Mori, Hiroyuki Masuno, Shinya Fujii, Eriko Kikuchi, Shinichi Uchida, Hiroyuki Kagechika
Pseudohypoaldosteronism type II (PHAII) is characterized by hyperkalemia and hypertension despite a normal glomerular filtration rate. Abnormal activation of the signal cascade of with-no-lysine kinase (WNK) with OSR1 (oxidative stress-responsive kinase 1)/SPAK (STE20/SPS1-related proline/alanine-rich kinase) and NCC (NaCl cotransporter) results in characteristic salt-sensitive hypertension. Thus, inhibitors of the WNK-OSR1/SPAK-NCC cascade are candidates for a new class of antihypertensive drugs. In this study, we developed novel inhibitors of this signal cascade from the 9-aminoacridine lead compound 1, one of the hit compounds obtained by screening our chemical library for WNK-SPAK binding inhibitors...
July 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28553255/development-of-the-korean-facial-emotion-stimuli-korea-university-facial-expression-collection-2nd-edition
#19
Sun-Min Kim, Ye-Jin Kwon, Soo-Yun Jung, Min-Ji Kim, Yang Seok Cho, Hyun Taek Kim, Ki-Chun Nam, Hackjin Kim, Kee-Hong Choi, June-Seek Choi
Background: Developing valid emotional facial stimuli for specific ethnicities creates ample opportunities to investigate both the nature of emotional facial information processing in general and clinical populations as well as the underlying mechanisms of facial emotion processing within and across cultures. Given that most entries in emotional facial stimuli databases were developed with western samples, and given that very few of the eastern emotional facial stimuli sets were based strictly on the Ekman's Facial Action Coding System, developing valid emotional facial stimuli of eastern samples remains a high priority...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28544026/immobilization-and-high-platelet-count-are-associated-with-thromboembolic-complications-in-heparin-induced-thrombocytopenia
#20
Juliane Bolbrinker, Edeltraut Garbe, Antonios Douros, Matthias Huber, Elisabeth Bronder, Andreas Klimpel, Frank Andersohn, Oliver Meyer, Abdulgabar Salama, Reinhold Kreutz
PURPOSE: Immune-mediated heparin-induced thrombocytopenia (HIT type II, HIT) is a potentially serious adverse drug reaction characterized by an increased risk of venous and arterial thrombosis. This study aimed to identify risk factors associated with the development of these complications. METHODS: Our study cohort included patients with HIT assembled in our pharmacovigilance center by reports from 51 collaborating hospitals in Berlin, Germany. To identify risk factors for thromboembolic complications, patients with thromboembolic events (cases) were compared to those without thromboembolic events (controls) in a case-control design...
May 24, 2017: Pharmacoepidemiology and Drug Safety
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