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https://www.readbyqxmd.com/read/28806782/the-use-of-18f-fluoro-deoxy-glucose-positron-emission-tomography-18f-fdg-pet-as-a-non-invasive-pharmacodynamic-biomarker-to-determine-the-minimally-pharmacologically-active-dose-of-azd8835-a-novel-pi3k%C3%AE-inhibitor
#1
Juliana Maynard, Sally-Ann Emmas, Francois-Xavier Ble, Herve Barjat, Emily Lawrie, Urs Hancox, Urszula M Polanska, Alison Pritchard, Kevin Hudson
BACKGROUND: The phosphatidyl inositol 3 kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) signal transduction pathway is frequently de-regulated and activated in human cancer and is an important therapeutic target. AZD8835 is a PI3K inhibitor, with selectivity against PI3K α and δ isoforms, which is currently in Phase 1 clinical trials. 18F-Fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) is a non-invasive pharmacodynamic imaging biomarker that has become an integral part of drug development...
2017: PloS One
https://www.readbyqxmd.com/read/28806602/exposure-of-european-sea-bass-dicentrarchus-labrax-to-chemically-dispersed-oil-has-a-chronic-residual-effect-on-hypoxia-tolerance-but-not-aerobic-scope
#2
Yangfan Zhang, Florian Mauduit, Anthony P Farrell, Denis Chabot, Hélène Ollivier, Adrien Rio-Cabello, Stéphane Le Floch, Guy Claireaux
We tested the hypothesis that the chronic residual effects of an acute exposure of European sea bass (Dicentrarchus labrax) to chemically dispersed crude oil is manifest in indices of hypoxic performance rather than aerobic performance. Sea bass were pre-screened with a hypoxia challenge test to establish their incipient lethal oxygen saturation (ILOS), but on discovering a wide breadth for individual ILOS values (2.6-11.0% O2 saturation), fish were subsequently subdivided into either hypoxia sensitive (HS) or hypoxia tolerant (HT) phenotypes, traits that were shown to be experimentally repeatable...
August 1, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28806419/effects-of-short-term-dry-immersion-on-bone-remodeling-markers-insulin-and-adipokines
#3
Marie-Thérèse Linossier, Liubov E Amirova, Mireille Thomas, Myriam Normand, Marie-Pierre Bareille, Guillemette Gauquelin-Koch, Arnaud Beck, Marie-Claude Costes-Salon, Christine Bonneau, Claude Gharib, Marc-Antoine Custaud, Laurence Vico
BACKGROUND: Dry immersion (DI), a ground-based model of microgravity previously used in Russia, has been recently implemented in France. The aim of this study was to analyze early events in a short-term DI model in which all conditions are met to investigate who is first challenged from osteo- or adipo-kines and to what extent they are associated to insulin-regulating hormones. METHODS: Twelve healthy men were submitted to a 3-day DI. Fasting blood was collected during pre-immersion phase for the determination of the baseline data collection (BDC), daily during DI (DI24h, DI48H and DI72h), then after recovery (R+3h and R+24h)...
2017: PloS One
https://www.readbyqxmd.com/read/28806338/isolated-second-implant-adaptation-period-in-sequential-cochlear-implantation-in-adults
#4
Kari Smilsky, Peter R Dixon, Leah Smith, David Shipp, Amy Ng, Tara Millman, Suzanne Stewart, Julian M Nedzelski, Vincent Y Lin, Joseph M Chen
OBJECTIVE: To determine if depriving the use of the first cochlear implant (CI1) impacts adaptation to a sequential implant (CI2). STUDY DESIGN: Prospective cohort. SETTING: Academic center. PATIENTS: Sixteen unilateral cochlear implant recipients undergoing contralateral implantation (sequential bilateral) were matched according to age, etiology, duration of deafness, device age, and delay between implants. INTERVENTION: During a 4-week adaptation period after CI2 activation, patients underwent deprivation of CI1 or were permitted continued use of it...
September 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28806299/the-dynamic-and-transient-immune-microenvironment-in-locally-advanced-esophageal-adenocarcinoma-post-chemoradiation
#5
Ronan J Kelly, Ali H Zaidi, Matthew A Smith, Ashten N Omstead, Juliann E Kosovec, Daisuke Matsui, Samantha A Martin, Christina DiCarlo, E Day Werts, Jan F Silverman, David H Wang, Blair A Jobe
OBJECTIVE: The aim of this study was to assess the impact of chemoradiation on the immune microenvironment to influence and optimally design future neoadjuvant clinical trials. SUMMARY BACKGROUND DATA: Programmed death (PD)-1 inhibitors in metastatic gastroesophageal cancer have demonstrated response rates of approximately 25% in programmed death ligand-1 (PD-L1+) tumors. Unfortunately, the majority of patients do not respond. Therefore, a rationale strategy of combining immunotherapeutic agents with chemoradiation in earlier stage esophageal cancer may prevent metastatic disease in patients...
August 10, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28806290/-clinical-and-quantitative-isokinetic-comparison-of-abdominal-morbidity-and-dynamics-following-diep-versus-muscle-sparing-free-tram-flap-breast-reconstruction
#6
Hirokazu Uda, Hideaki Kamochi, Syunji Sarukawa, Ataru Sunaga, Yasusih Sugawara, Kotaro Yoshimura
BACKGROUND: The deep inferior epigastric perforator (DIEP) flap, which is a modification of the muscle-sparing free transverse rectus abdominis musculocutaneous (msTRAM) flap, is being more frequently used in an effort to reduce postoperative abdominal morbidity. However, there is no consensus as to which of these flaps is superior. We aimed to compare quantitative measurements of abdominal function obtained with an isokinetic dynamometer after DIEP and msTRAM flap elevation. METHODS: Patients who underwent unilateral single-pedicled DIEP (n = 42) or msTRAM flap (n = 36) breast reconstruction performed by a single surgeon were included in this study...
August 3, 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28806201/brain-gut-microbiota-axis-and-mental-health
#7
Timothy G Dinan, John F Cryan
OBJECTIVE: The brain-gut-microbiota axis has been put forward as a new paradigm in neuroscience, which may be of relevance to mental illness. The mechanisms of signal transmission in the brain-gut-microbiota axis are complex and involve bidirectional communications which enables gut microbes to communicate with the brain, and the brain to communicate with the microbes. This review assesses the potential usefulness and limitations of the paradigm. METHODS: A selective literature review was conducted to evaluate the current knowledge in clinical and pre-clinical brain-gut-microbiota interactions as related to psychiatric disorders...
August 11, 2017: Psychosomatic Medicine
https://www.readbyqxmd.com/read/28806197/frailty-is-strongly-associated-with-increased-risk-of-recurrent-falls-among-older-hiv-infected-adults-a-prospective-cohort-study
#8
Katherine Tassiopoulos, Mona Abdo, Kunling Wu, Susan L Koletar, Frank J Palella, Robert Kalayjian, Babafemi Taiwo, Kristine M Erlandson
OBJECTIVE: Both frailty and falls occur at earlier than expected ages among HIV-infected individuals, but the contribution of frailty to fall risk in this population is not well understood. We examined this association among participants enrolled in AIDS Clinical Trials Group (ACTG) A5322. DESIGN: A prospective, multi-center cohort study of HIV-infected men and women ≥40 years. METHODS: Frailty assessment included a 4-meter walk, grip strength, and self-reported weight loss, exhaustion, and low physical activity...
August 12, 2017: AIDS
https://www.readbyqxmd.com/read/28805950/management-of-osteonecrosis-of-the-femoral-head-with-pedicled-iliac-bone-flap-transfer-a-multicenter-study-of-2190-patients
#9
Dewei Zhao, Hui Xie, Yongqing Xu, Yisheng Wang, Aixi Yu, Youwen Liu, Aimin Wang, Wei He, Xiuli Wang, Zirong Li, Wei Sun, Simiao Tian, Benjie Wang, Baoyi Liu
BACKGROUND: Osteonecrosis of the femoral head (ONFH) often affects young active adults and leads to destruction of the hip joint and disabling arthritis. Several procedures have been developed to arrest the progress of osteonecrosis and postpone the procedure of total hip replacement especially in young patients. The aim of this multicenter study was to analyze the results of the use of the vascularized iliac bone flap transfer for management of ONFH. METHODS: From January 1985 to December 2012, a total of 2190 patients (2690 hips) with the mean age of 43...
August 14, 2017: Microsurgery
https://www.readbyqxmd.com/read/28805936/characterizing-hypoxia-in-human-glioma-a-simultaneous-multimodal-mri-and-pet-study
#10
Christine Preibisch, Kuangyu Shi, Anne Kluge, Mathias Lukas, Benedikt Wiestler, Jens Göttler, Jens Gempt, Florian Ringel, Mohamed Al Jaberi, Jürgen Schlegel, Bernhard Meyer, Claus Zimmer, Thomas Pyka, Stefan Förster
Hypoxia plays an important role for the prognosis and therapy response of cancer. Thus, hypoxia imaging would be a valuable tool for pre-therapeutic assessment of tumor malignancy. However, there is no standard validated technique for clinical application available yet. Therefore, we performed a study in 12 patients with high-grade glioma, where we directly compared the two currently most promising techniques, namely the MR-based relative oxygen extraction fraction (MR-rOEF) and the PET hypoxia marker H-1-(3-[(18) F]-fluoro-2-hydroxypropyl)-2-nitroimidazole ([(18) F]-FMISO)...
August 14, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28805829/lineage-specific-dynamic-and-pre-established-enhancer-promoter-contacts-cooperate-in-terminal-differentiation
#11
Adam J Rubin, Brook C Barajas, Mayra Furlan-Magaril, Vanessa Lopez-Pajares, Maxwell R Mumbach, Imani Howard, Daniel S Kim, Lisa D Boxer, Jonathan Cairns, Mikhail Spivakov, Steven W Wingett, Minyi Shi, Zhixin Zhao, William J Greenleaf, Anshul Kundaje, Michael Snyder, Howard Y Chang, Peter Fraser, Paul A Khavari
Chromosome conformation is an important feature of metazoan gene regulation; however, enhancer-promoter contact remodeling during cellular differentiation remains poorly understood. To address this, genome-wide promoter capture Hi-C (CHi-C) was performed during epidermal differentiation. Two classes of enhancer-promoter contacts associated with differentiation-induced genes were identified. The first class ('gained') increased in contact strength during differentiation in concert with enhancer acquisition of the H3K27ac activation mark...
August 14, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28805543/exploring-the-relationship-of-phase-and-peak-frequency-eeg-alpha-band-and-beta-band-activity-to-temporal-judgments-of-stimulus-duration
#12
Alex Milton, Christopher Pleydell-Pearce
Pre-stimulus phase has been shown to influence temporal judgments concerning order, causality and simultaneity. One hypothesis is that phase cycles frame discrete perceptual snapshots over time. Yet, existing studies have explored the effect of pre-stimulus phase on fine-grained temporal judgments whereas no study has shown whether pre-stimulus phase influences sub-second temporal judgments lasting several phase cycles. If effects of phase on fine-grained temporal judgments reflect perceptual framing, then the perception of longer intervals might show some dependency on the frequency of phase cycles...
August 14, 2017: Cognitive Neuroscience
https://www.readbyqxmd.com/read/28804614/protective-effect-of-bioactive-compounds-from-echinophora-cinerea-against-cisplatin-induced-oxidative-stress-and-apoptosis-in-the-pc12-cell-line
#13
Yald Shokoohinia, Shekoufeh Khajouei, Farahnaz Ahmadi, Nastaran Ghiasvand, Leila Hosseinzadeh
OBJECTIVES: The present study aims to evaluate the protective effect of the compounds isolated from Echinophora cinerea (E. cinerea) against oxidative stress and apoptosis induced by cisplatin (CIS) in PC12 cells. MATERIALS AND METHODS: Six compounds were isolated as quercetrin-3-O-β-D-glucopyranoside (QUE), osthol (OST), verbenone-5-O-β-D-glycopyranoside (VER), Isoimperatorin (ISO), kaempferol-3-O-β-D-glucopyranoside (KAM), and echinophorin B (ECH). For this study, we used MTT reduction assay for detection of protective effects of isolated compounds on CIS-induced cytotoxicity in PC12 cells...
April 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28804580/growth-pattern-in-children-with-systemic-lupus-erythematosus
#14
Eiman Abdalla, Lakshamanan Jeyaseelan, Irfan Ullah, Reem Abdwani
OBJECTIVES: Children with childhood-onset systemic lupus erythematosus (cSLE) enter adulthood with considerable morbidity. Of the recognized morbidities, growth failure is unique to cSLE. The aim of this study was to evaluate the growth pattern in children with cSLE longitudinally and identify possible risk factors. METHODS: Serial anthropometric measurements of cSLE patients were obtained over two years and expressed as z-scores. Parental heights were obtained to calculate target height...
July 2017: Oman Medical Journal
https://www.readbyqxmd.com/read/28804474/a-longitudinal-electromyography-study-of-complex-movements-in-poststroke-therapy-1-heterogeneous-changes-despite-consistent-improvements-in-clinical-assessments
#15
Negin Hesam-Shariati, Terry Trinh, Angelica G Thompson-Butel, Christine T Shiner, Penelope A McNulty
Poststroke weakness on the more-affected side may arise from reduced corticospinal drive, disuse muscle atrophy, spasticity, and abnormal coordination. This study investigated changes in muscle activation patterns to understand therapy-induced improvements in motor-function in chronic stroke compared to clinical assessments and to identify the effect of motor-function level on muscle activation changes. Electromyography (EMG) was recorded from five upper limb muscles on the more-affected side of 24 patients during early and late therapy sessions of an intensive 14-day program of Wii-based Movement Therapy (WMT) and for a subset of 13 patients at 6-month follow-up...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28803811/office-operative-hysteroscopy-an-update
#16
REVIEW
Christina Alicia Salazar, Keith Isaacson
Hysteroscopy is considered the gold standard for evaluation of intracavitary pathology associated with both pre- and postmenopausal patients with abnormal uterine bleeding as well as part of the evaluation of infertility patients with suspected cavity abnormalities. Office-based operative hysteroscopy allows patients to resume activities immediately and successfully integrates clinical practice into a "see and treat" modality, avoiding the added risks of undergoing anesthesia and the inconvenience of going to the operating room...
August 10, 2017: Journal of Minimally Invasive Gynecology
https://www.readbyqxmd.com/read/28803749/the-effects-of-17%C3%AE-estradiol-on-blood-brain-barrier-integrity-in-the-absence-of-the-estrogen-receptor-alpha-an-in-vitro-model
#17
Serap Erdem Kuruca, Sabriye Karadenizli, Kadriye Akgun-Dar, Aysegul Kapucu, Zulal Kaptan, Gulay Uzum
The blood-brain barrier (BBB), which saves the brain from toxic substances, is formed by endothelial cells. It is mainly composed of tight junction (TJ) proteins existing between endothelial cells. Estrogen is an important regulatory hormone of BBB permeability. It protects the BBB before menopause, but may increase BBB permeability with aging. In addition, nitric oxide modulates BBB permeability. Alcohol impairs the integrity of the BBB with oxidants and inflammatory mediators such as iNOS. We investigated the effects of estrogen on BBB integrity in an in vitro BBB model created with ERα-free HUVEC (human umbilical vein endothelial-like cells) to mimics the menopausal period...
August 10, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28803692/a-janus-faced-im30-ring-involved-in-thylakoid-membrane-fusion-is-assembled-from-im30-tetramers
#18
Michael Saur, Raoul Hennig, Phoebe Young, Kristiane Rusitzka, Nadja Hellmann, Jennifer Heidrich, Nina Morgner, Jürgen Markl, Dirk Schneider
Biogenesis and dynamics of thylakoid membranes likely involves membrane fusion events. Membrane attachment of the inner membrane-associated protein of 30 kDa (IM30) affects the structure of the lipid bilayer, finally resulting in membrane fusion. Yet, how IM30 triggers membrane fusion is largely unclear. IM30 monomers pre-assemble into stable tetrameric building blocks, which further align to form oligomeric ring structures, and differently sized IM30 rings bind to membranes. Based on a 3D reconstruction of IM30 rings, we locate the IM30 loop 2 region at the bottom of the ring and show intact membrane binding but missing fusogenic activity of loop 2 mutants...
August 2, 2017: Structure
https://www.readbyqxmd.com/read/28803652/long-term-follow-up-evaluation-of-autologous-chondrocyte-implantation-for-symptomatic-cartilage-lesions-of-the-knee-a-single-centre-prospective-study
#19
M Berruto, P Ferrua, S Pasqualotto, F Uboldi, A Maione, D Tradati, E Usellini
INTRODUCTION: Autologous Chondrocyte Implantation (ACI) has been the first technique in reconstruction of a valid articular surface. The aim of this study was to evaluate clinical results of this technique at an average follow up of 162±27months (range 88-208) in a group of patients who underwent ACI. MATERIALS AND METHODS: 32 patients were operated between 1997 and 2007 for chondral lesions or osteochondritis dissecans of the knee. Mean size of the defect was 5...
August 4, 2017: Injury
https://www.readbyqxmd.com/read/28803507/what-box-a-task-for-assessing-language-lateralization-in-young-children
#20
Nicholas A Badcock, Rachael Spooner, Jessica Hofmann, Atlanta Flitton, Scott Elliott, Lisa Kurylowicz, Louise M Lavrencic, Heather M Payne, Georgina K Holt, Anneka Holden, Owen F Churches, Mark J Kohler, Hannah A D Keage
The assessment of active language lateralization in infants and toddlers is challenging. It requires an imaging tool that is unintimidating, quick to setup, and robust to movement, in addition to an engaging and cognitively simple language processing task. Functional Transcranial Doppler Ultrasound (fTCD) offers a suitable technique and here we report on a suitable method to elicit active language production in young children. The 34-second "What Box" trial presents an animated face "searching" for an object...
August 13, 2017: Laterality
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