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https://www.readbyqxmd.com/read/28328131/recessive-mutations-in-slc35a3-cause-early-onset-epileptic-encephalopathy-with-skeletal-defects
#1
Carla Marini, Katia Hardies, Tiziana Pisano, Patrick May, Sarah Weckhuysen, Elena Cellini, Arvid Suls, Davide Mei, Rudi Balling, Peter D Jonghe, Ingo Helbig, Domenico Garozzo, Renzo Guerrini
We describe the clinical and whole genome sequencing (WGS) study of a non-consanguineous Italian family in which two siblings, a boy and a girl, manifesting a severe epileptic encephalopathy (EE) with skeletal abnormalities, carried novel SLC35A3 compound heterozygous mutations. Both siblings exhibited infantile spasms, associated with focal, and tonic vibratory seizures from early infancy. EEG recordings showed a suppression-burst (SB) pattern and multifocal paroxysmal activity in both. In addition both had quadriplegia, acquired microcephaly, and severe intellectual disability...
April 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28326568/early-response-predicts-a-sustained-response-to-eluxadoline-in-patients-with-irritable-bowel-syndrome-with-diarrhoea-in-two-phase-3-studies
#2
W D Chey, L S Dove, D A Andrae, P S Covington
BACKGROUND: The mixed μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist, eluxadoline, is licensed in the USA for the treatment of irritable bowel syndrome with diarrhoea (IBS-D), based on the results of two large Phase 3 clinical trials. AIM: To understand the time course of treatment benefits with eluxadoline by comparing responder rates over the first month of treatment with responder rates over longer treatment intervals. METHODS: In this post hoc analysis of two Phase 3 studies, composite and adequate relief (AR) responder rates were calculated over month 1 and patients were stratified by their responder status...
March 22, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28323532/comparing-three-regularization-methods-to-avoid-extreme-allocation-probability-in-response-adaptive-randomization
#3
Yining Du, John D Cook, J Jack Lee
We examine three variations of the regularization methods for response-adaptive randomization (RAR) and compare their operating characteristics. A power transformation (PT) is applied to refine the randomization probability. The clip method is used to bound the randomization probability within specified limits. A burn-in period of equal randomization (ER) can be added before adaptive randomization (AR). For each method, more patients are assigned to the superior arm and overall response rate increase as the scheme approximates simple AR, while statistical power increases as it approximates ER...
February 21, 2017: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/28321889/antihyperglycaemic-activity-of-the-methanol-extract-from-leaves-of-eremophila-maculata-scrophulariaceae-in-streptozotocin-induced-diabetic-rats
#4
Fadia S Youssef, Mohamed L Ashour, Sherif S Ebada, Mansour Sobeh, Hesham A El-Beshbishy, Abdel Nasser Singab, Michael Wink
OBJECTIVES: This study was designed to evaluate the antihyperglycaemic activity of the methanol leaf extract of Eremophila maculata (EMM) both in vitro and in vivo. METHODS: The antihyperglycaemic activity was assessed in vitro using differentiated 3T3-L1 adipocytes, whereas in-vivo effect was evaluated in streptozotocin-induced diabetic rats. Chemical profiling of EMM was done using LC-ESI-MS techniques. Molecular modelling experiments of the identified compounds were performed using C-Docker protocol...
March 21, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28317379/optical-emission-from-c2-anions-in-microwave-activated-ch4-h2-plasmas-for-chemical-vapour-deposition-of-diamond
#5
Edward Mahoney, Benjamin S Truscott, Michael N R Ashfold, Yuri A Mankelevich
Visible emission from C2-(B2Σu+) anions has been identified underlying the much stronger Swan band emission from neutral C2(d3Πg) radicals (henceforth C2-* and C2*, respectively) in MW-activated C/H/(Ar) plasmas operating under conditions appropriate for the chemical vapour deposition (CVD) of diamond. Spatially resolved measurements of the C2-* and C2* emissions as functions of the C/H/(Ar) ratio in the input gas mixture, the total pressure, and the applied MW power, together with complementary 2-D(r, z) plasma modelling, identifies dissociative electron attachment (DEA) to C2H radicals in the hot plasma as the dominant source of the observed C2-* emission...
March 20, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/28314364/effect-of-ge-content-on-the-formation-of-ge-nanoclusters-in-magnetron-sputtered-gezrox-based-structures
#6
L Khomenkova, D Lehninger, O Kondratenko, S Ponomaryov, O Gudymenko, Z Tsybrii, V Yukhymchuk, V Kladko, J von Borany, J Heitmann
Ge-rich ZrO2 films, fabricated by confocal RF magnetron sputtering of pure Ge and ZrO2 targets in Ar plasma, were studied by multi-angle laser ellipsometry, Raman scattering, Auger electron spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction for varied deposition conditions and annealing treatments. It was found that as-deposited films are homogeneous for all Ge contents, thermal treatment stimulated a phase separation and a formation of crystalline Ge and ZrO2. The "start point" of this process is in the range of 640-700 °C depending on the Ge content...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28306720/inhibition-of-androgen-receptor-by-decoy-molecules-delays-progression-to-castration-recurrent-prostate-cancer
#7
Jae-Kyung Myung, Gang Wang, Helen H L Chiu, Jun Wang, Nasrin R Mawji, Marianne D Sadar
Androgen receptor (AR) is a member of the steroid receptor family and a therapeutic target for all stages of prostate cancer. AR is activated by ligand binding within its C-terminus ligand-binding domain (LBD). Here we show that overexpression of the AR NTD to generate decoy molecules inhibited both the growth and progression of prostate cancer in castrated hosts. Specifically, it was shown that lentivirus delivery of decoys delayed hormonal progression in castrated hosts as indicated by increased doubling time of tumor volume, prolonged time to achieve pre-castrate levels of serum prostate-specific antigen (PSA) and PSA nadir...
2017: PloS One
https://www.readbyqxmd.com/read/28302679/disrupting-androgen-receptor-signaling-induces-snail-mediated-epithelial-mesenchymal-plasticity-in-prostate-cancer
#8
Lu Miao, Lin Yang, Rui Li, Daniel Nava Rodrigues, Mateus Crespo, Jer-Tsong Hsieh, Wayne D Tilley, Johann S de Bono, Luke A Selth, Ganesh V Raj
Epithelial to mesenchymal plasticity (EMP) has been linked to metastasis, stemness, and drug resistance. In prostate cancer (PCa), EMP has been associated with both suppression and activation of androgen receptor (AR) signaling. Here we investigated the effect of the potent AR antagonist enzalutamide on EMP in multiple preclinical models of PCa and patient tissues. Enzalutamide treatment significantly enhanced the expression of EMP drivers (ZEB1, ZEB2, Snail, Twist, and FOXC2) and mesenchymal markers (N-cadherin, fibronectin, and vimentin) in PCa cells, enhanced PCa cell migration, and induced PCa transformation to a spindle, fibroblast-like morphology...
March 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28300864/whole-exome-sequencing-in-the-framingham-heart-study-identifies-rare-variation-in-hyal2-that-influences-platelet-aggregation
#9
John D Eicher, Ming-Huei Chen, Achilleas N Pitsillides, Honghuang Lin, Narayanan Veeraraghavan, Jennifer A Brody, Ginger A Metcalf, Donna M Muzny, Richard A Gibbs, Diane M Becker, Lewis C Becker, Nauder Faraday, Rasika A Mathias, Lisa R Yanek, Eric Boerwinkle, L Adrienne Cupples, Andrew D Johnson
Inhibition of platelet reactivity is a common therapeutic strategy in secondary prevention of cardiovascular disease. Genetic and environmental factors influence inter-individual variation in platelet reactivity. Identifying genes that contribute to platelet reactivity can reveal new biological mechanisms and possible therapeutic targets. Here, we examined rare coding variation to identify genes associated with platelet reactivity in a population-based cohort. To do so, we performed whole exome sequencing in the Framingham Heart Study and conducted single variant and gene-based association tests against platelet reactivity to collagen, adenosine diphosphate (ADP), and epinephrine agonists in up to 1,211 individuals...
March 16, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28300329/insulin-resistance-and-the-igf-i-cortical-bone-relationship-in-children-ages-9-13-years
#10
Joseph M Kindler, Norman K Pollock, Emma M Laing, Assaf Oshri, Nathan T Jenkins, Carlos M Isales, Mark W Hamrick, Ke-Hong Ding, Dorothy B Hausman, George P McCabe, Berdine R Martin, Kathleen M Hill Gallant, Stuart J Warden, Connie M Weaver, Munro Peacock, Richard D Lewis
IGF-I is a pivotal hormone in pediatric musculoskeletal development. Though recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone...
March 16, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28296039/outcome-of-implantation-of-a-second-self-expanding-valve-for-the-treatment-of-residual-significant-aortic-regurgitation
#11
Edward Koifman, Nirav Patel, Gaby Weissman, Sarkis Kiramijyan, Romain Didier, Rebecca Torguson, Sandeep Kumar, Arpi Tavil-Shatelyan, Itsik Ben-Dor, Lowell F Satler, Augusto D Pichard, Ron Waksman
BACKGROUND: Residual aortic regurgitation (AR) following transcatheter aortic valve replacement (TAVR) is associated with adverse outcome. We sought to evaluate the efficacy and safety of second CoreValve (CV) implantation to treat residual AR following the initial CV deployment. METHODS AND RESULTS: TAVR patients treated with a second CV due to moderate and above residual AR were compared to single device implantation. Valvular function parameters were compared at baseline, post procedure, and 30 days...
March 15, 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/28295526/pharmacological-treatments-in-asthma-affected-horses-a-pair-wise-and-network-meta-analysis
#12
L Calzetta, P Roncada, D di Cave, L Bonizzi, A Urbani, E Pistocchini, P Rogliani, M G Matera
BACKGROUND: Equine asthma is a disease characterised by reversible airflow obstruction, bronchial hyperresponsiveness and airway inflammation following exposure of susceptible horses to specific airborne agents. Although clinical remission can be achieved in a low-airborne dust environment, repeated exacerbations may lead to irreversible airway remodelling. The available data on the pharmacotherapy of equine asthma results from several small studies, and no head-to-head clinical trials have been conducted among the available medications...
March 10, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/28294517/osteogenic-differentiation-of-mesenchymal-stem-cells-using-hybrid-nanofibers-with-different-configurations-and-dimensionality
#13
D Gugutkov, F Awaja, K Belemezova, M Keremidarska, N Krasteva, S Kuyrkchiev, G GallegoFerrer, S Seker, A E Elcin, Y M Elcin, G Altankov
Novel hybrid, fibrinogen/polylactic acid (FBG/PLA) nanofibers with different configuration (random vs. aligned) and dimensionality (2D vs.3D environment) were used to control the overall behaviour and the osteogenic differentiation of human Adipose Derived Mesenchymal Stem Cells (ADMSCs). Aligned nanofibers in both the 2D and 3D configurations are proved to be favoured for osteo-differentiation. Morphologically we found that on randomly configured nanofibers, the cells developed a stellate-like morphology with multiple projections, however, time-lapse analysis showed significantly diminished cell movements...
March 11, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28292441/spop-mutation-drives-prostate-tumorigenesis-in%C3%A2-vivo-through-coordinate-regulation-of-pi3k-mtor-and-ar-signaling
#14
Mirjam Blattner, Deli Liu, Brian D Robinson, Dennis Huang, Anton Poliakov, Dong Gao, Srilakshmi Nataraj, Lesa D Deonarine, Michael A Augello, Verena Sailer, Lalit Ponnala, Michael Ittmann, Arul M Chinnaiyan, Andrea Sboner, Yu Chen, Mark A Rubin, Christopher E Barbieri
Recurrent point mutations in SPOP define a distinct molecular subclass of prostate cancer. Here, we describe a mouse model showing that mutant SPOP drives prostate tumorigenesis in vivo. Conditional expression of mutant SPOP in the prostate dramatically altered phenotypes in the setting of Pten loss, with early neoplastic lesions (high-grade prostatic intraepithelial neoplasia) with striking nuclear atypia and invasive, poorly differentiated carcinoma. In mouse prostate organoids, mutant SPOP drove increased proliferation and a transcriptional signature consistent with human prostate cancer...
March 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28279171/single-amino-acid-substitutions-in-the-selectivity-filter-render-nbxip1-1%C3%AE-aquaporin-water-permeable
#15
Henry Ampah-Korsah, Yonathan Sonntag, Angelica Engfors, Andreas Kirscht, Per Kjellbom, Urban Johanson
BACKGROUND: Aquaporins (AQPs) are integral membrane proteins that facilitate transport of water and/or other small neutral solutes across membranes in all forms of life. The X Intrinsic Proteins (XIPs) are the most recently recognized and the least characterized aquaporin subfamily in higher plants. XIP1s have been shown to be impermeable to water but permeable to boric acid, glycerol, hydrogen peroxide and urea. However, uncertainty regarding the determinants for selectivity and lack of an activity that is easy to quantify have hindered functional investigations...
March 9, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28272589/standardized-attending-rounds-to-improve-the-patient-experience-a-pragmatic-cluster-randomized-controlled-trial
#16
Bradley Monash, Nader Najafi, Michelle Mourad, Alvin Rajkomar, Sumant R Ranji, Margaret C Fang, Marcia Glass, Dimiter Milev, Yile Ding, Andy Shen, Bradley A Sharpe, James D Harrison
BACKGROUND: At academic medical centers, attending rounds (AR) serve to coordinate patient care and educate trainees, yet variably involve patients. OBJECTIVE: To determine the impact of standardized bedside AR on patient satisfaction with rounds. DESIGN: Cluster randomized controlled trial. SETTING: 500-bed urban, quaternary care hospital. PATIENTS: 1200 patients admitted to the medicine service...
March 2017: Journal of Hospital Medicine: An Official Publication of the Society of Hospital Medicine
https://www.readbyqxmd.com/read/28270498/a-randomized-phase-ii-neoadjuvant-study-of-cisplatin-paclitaxel-with-or-without-everolimus-in-patients-with-stage-ii-iii-triple-negative-breast-cancer-tnbc
#17
Bojana Jovanovic, Ingrid A Mayer, Erica L Mayer, Vandana G Abramson, Aditya Bardia, Melinda Sanders, Maria G Kuba, Monica Valeria Estrada, J Scott Beeler, Timothy M Shaver, Kimberly N Johnson, Violeta Sanchez, Jennifer M Rosenbluth, Patrick M Dillon, Andres Forrero-Torres, Jenny C Chang, Ingrid Meszoely, Ana Grau, Brian D Lehmann, Yu Shyr, Quanhu Sheng, Sheau-Chiann Chen, Carlos L Arteaga, Jennifer A Pietenpol
PURPOSE: Due to inherent disease heterogeneity, targeted therapies have eluded TNBC, and biomarkers predictive of treatment response have not yet been identified. This study was designed to determine if the mTOR inhibitor everolimus with cisplatin and paclitaxel would provide synergistic anti-tumor effects in TNBC. EXPERIMENTAL DESIGN: Stage II/III patients with TNBC were enrolled in a randomized phase II trial of preoperative weekly cisplatin, paclitaxel and daily everolimus or placebo for 12 weeks, until definitive surgery...
March 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28263822/low-testosterone-levels-result-in-decreased-periurethral-vascularity-via-an-androgen-receptor-mediated-process-pilot-study-in-urethral-stricture-tissue
#18
Matthias D Hofer, Payal Kapur, Billy H Cordon, Farrah Hamoun, David Russell, Jeremy M Scott, Claus G Roehrborn, Allen F Morey
OBJECTIVE: To compare expression of androgen receptor (AR) and angiopoietin 1 receptor TIE-2 and vessel density of urethral stricture tissue among eugonadal and hypogonadal men to identify a pathophysiological basis for our observations that low testosterone is associated with urethral atrophy. METHODS: Among 1200 men having urethroplasty at our institution, we retrospectively identified 11 patients with testosterone levels drawn within 2 years of surgery. Low testosterone was defined as <280 ng/dL and detected in 5 of 11 (45...
March 2, 2017: Urology
https://www.readbyqxmd.com/read/28245126/approaching-the-hartree-fock-limit-through-the-cabs-singles-correction-and-auxiliary-basis-sets
#19
Robert A Shaw, J Grant Hill
Auxiliary basis sets for use in the resolution of the identity (RI) approximation in explicitly correlated methods are presented for the elements H-Ar. These extend the cc-pVnZ-F12/OptRI (n = D-Q) auxiliary basis sets of Peterson and coworkers by the addition of a small number of s- and p-functions, optimized so as to yield the great- est complementary auxiliary basis set (CABS) singles correction to the Hartree-Fock energy. The new sets, denoted OptRI+, also lead to a reduction in errors due to the RI approximation and hence an improvement in correlation energies...
February 28, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28239205/a-study-of-the-dissociative-recombination-of-cao-with-electrons-implications-for-ca-chemistry-in-the-upper-atmosphere
#20
D L Bones, M Gerding, J Höffner, Juan Carlos Gómez Martín, J M C Plane
The dissociative recombination of CaO(+) ions with electrons has been studied in a flowing afterglow reactor. CaO(+) was generated by the pulsed laser ablation of a Ca target, followed by entrainment in an Ar(+) ion/electron plasma. A kinetic model describing the gas-phase chemistry and diffusion to the reactor walls was fitted to the experimental data, yielding a rate coefficient of (3.0 ± 1.0) × 10(-7) cm(3) molecule(-1) s(-1) at 295 K. This result has two atmospheric implications. First, the surprising observation that the Ca(+)/Fe(+) ratio is ~8 times larger than Ca/Fe between 90 and 100 km in the atmosphere can now be explained quantitatively by the known ion-molecule chemistry of these two metals...
December 28, 2016: Geophysical Research Letters
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