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https://www.readbyqxmd.com/read/28811331/targeting-a-single-alternative-polyadenylation-site-coordinately-blocks-expression-of-androgen-receptor-mrna-splice-variants-in-prostate%C3%A2-cancer
#1
Jamie L Van Etten, Michael Nyquist, Yingming Li, Rendong Yang, Yeung Ho, Rachel M Johnson, Olivia Ondigi, Daniel F Voytas, Christine Henzler, Scott M Dehm
Prostate cancer is the second leading cause of male cancer deaths due to disease progression to castration resistant prostate cancer (CRPC). Androgen receptor (AR) splice variants including AR-V7 function as constitutively active transcription factors in CRPC cells, thereby promoting resistance to AR-targeted therapies. To date, there are no AR variant specific treatments for CRPC. Here we report that the splicing of AR variants AR-V7 as well as AR-V1 and AR-V9 is regulated coordinately by a single polyadenylation signal in AR intron 3...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28809467/multidimensional-control-of-cas9-by-evolved-rna-polymerase-based-biosensors
#2
Jinyue Pu, Kaitlin Kentala, Bryan C Dickinson
Systems to control Cas9 with spatial and temporal precision offer opportunities to decrease side effects, protect sensitive tissues, and create gene therapies that are only activated at defined times and places. Here, we present the design of new Cas9 controllers based on RNA polymerase (RNAP)-based biosensors that produce gRNAs, thereby regulating target knockout. After development and validation of a new abscisic acid-inducible biosensor to control Cas9, we lowered the background of the system using continuous evolution...
August 15, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28808507/cyp2c19-genetic-variation-and-individualized-clopidogrel-prescription-in-a-cardiology-clinic
#3
Seyed Abbas Mirabbasi, Koroush Khalighi, Yin Wu, Stanley Walker, Bahar Khalighi, Wuqiang Fan, Archana Kodali, Gang Cheng
Background: Clopidogrel (Plavix) is an antiplatelet medication that is routinely used in patients with cardiovascular disease. Cytochrome P2C19 enzymes play a major role in its metabolism, which determines its varied therapeutic level and its effectiveness. Objectives: To customize clopidogrel therapy and evaluate its efficacy by using CYP2C19 genotypic and phenotypic information to improve clinical outcomes in patients. Methods: A total of 465 patients with underlying cardiovascular disease were selected from our out-patient cardiology clinic...
July 2017: Journal of Community Hospital Internal Medicine Perspectives
https://www.readbyqxmd.com/read/28807988/high-flow-nasal-cannula-therapy-versus-intermittent-noninvasive-ventilation-in-obese-subjects-after-cardiothoracic-surgery
#4
François Stéphan, Laurence Bérard, Saida Rézaiguia-Delclaux, Priscilla Amaru
BACKGROUND: Obese patients are considered at risk of respiratory failure after cardiothoracic surgery. High-flow nasal cannula has demonstrated its non-inferiority after cardiothoracic surgery compared to noninvasive ventilation (NIV), which is the recommended treatment in obese patients. We hypothesized that NIV was superior to high-flow nasal cannula for preventing or resolving acute respiratory failure after cardiothoracic surgery in this population. METHODS: We performed a post hoc analysis of a randomized, controlled trial...
August 14, 2017: Respiratory Care
https://www.readbyqxmd.com/read/28806390/combination-antipsychotic-therapies-an-analysis-from-a-longitudinal-pragmatic-trial
#5
Adriana Foster, Peter Buckley, John Lauriello, Stephen Looney, Nina Schooler
BACKGROUND: Combination antipsychotics (CAs) are prescribed in schizophrenia despite limited evidence of efficacy. To explore the effect of switching from CA to monotherapy, we performed an exploratory analysis of the PROACTIVE (Preventing Relapse in Schizophrenia: Oral Antipsychotics Compared with Injectables: Evaluating Efficacy) study data, in which 305 patients with schizophrenia and schizoaffective disorder were followed for 30 months after randomization to long-acting injectable (LAI) risperidone or second-generation oral antipsychotic (OA)...
August 10, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28805798/repeated-aav-mediated-gene-transfer-by-serotype-switching-enables-long-lasting-therapeutic-levels-of-hugt1a1-enzyme-in-a-mouse-model-of-crigler-najjar-syndrome-type-i
#6
L Bočkor, G Bortolussi, A Iaconcig, G Chiaruttini, C Tiribelli, M Giacca, F Benvenuti, L Zentilin, A F Muro
Adeno-associated virus (AAV)-mediated gene therapy is a promising strategy to treat liver-based monogenic diseases. However, two major obstacles limit its success: first, vector dilution in actively dividing cells, such as hepatocytes in neonates/children, due to the non-integrating nature of the vector; second, development of an immune response against the transgene and/or viral vector. Crigler-Najjar Syndrome Type I (CNSI) is a rare monogenic disease with neonatal onset, caused by mutations in the liver-specific UGT1 gene, with toxic accumulation of unconjugated bilirubin in plasma, tissues and brain...
August 14, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28805783/-effect-of-the-cytoflavin-on-the-distal-polyneuropathy-severity-in-patients-with-diabetic-foot-syndrome-with-arteries-mediacalcinosis
#7
V D Skripko, A L Kovalenko, V A Zaplutanov
The aim of the study was to evaluate the effectiveness of cytoflavin in the complex treatment of patients with diabetic foot syndrome. MATERIAL AND METHODS: The research is based on the results of a comprehensive survey of 140 people with diabetic foot syndrome. Depending on the treatment, all patients were divided into 2 groups. The first group (n=35) received basic therapy. The second group (n=35) in addition to basic therapy received cytoflavin 10 ml (+200 ml 0.9% NaCl) for 10 days, followed by switching to the tablet form of the drug 2 tablets twice a day for 1 month...
2017: Khirurgiia
https://www.readbyqxmd.com/read/28805525/pace-gate-an-alternative-view-on-a-study-with-a-poor-trial-protocol
#8
Bart Stouten
The controversies surrounding the effectiveness of cognitive behavioural therapy and graded exercise therapy for chronic fatigue syndrome are explained using Cohen's d effect sizes rather than arbitrary thresholds for 'success'. This article shows that the treatment effects vanish when switching to objective outcomes. The preference for subjective outcomes by the PACE trial team leads to false hope. This article provides a more realistic view, which will help patients and their doctors to evaluate the pros and cons...
August 2017: Journal of Health Psychology
https://www.readbyqxmd.com/read/28805471/prolonged-release-oxycodone-and-naloxone-treatment-counteracts-opioid-induced-constipation-in-patients-with-severe-pain-compared-to-previous-analgesic-treatment
#9
Gineke Koopmans-Klein, Joeri Van Op den Bosch, Yvonne van Megen, Hans Prenen, Frank Huygen, Isabelle Mancini
OBJECTIVE: Treatment with prolonged-release oxycodone/naloxone (PR OXN) has been shown to improve opioid induced constipation (OIC) in constipated patients. This publication reports on a real-life observational study investigating the efficacy of PR OXN with regard to bowel function in patients switching to PR OXN from WHO-step 1, step 2 and step 3 opioids. METHODS: Patients with chronic pain experiencing insufficient pain relief and/or unacceptable side effects were switched to PR OXN and monitored in this observational study with respect to efficacy regarding bowel function and efficacy regarding pain relief in comparison with previous analgesic therapy...
August 14, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28803431/sb2-an-infliximab-biosimilar
#10
Yvette N Lamb, Lesley J Scott, Emma D Deeks
SB2 is a biosimilar of the reference anti-TNF-α antibody infliximab. In May 2015, it was approved in the EU for use in all indications for which reference infliximab is approved, including rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriatic arthritis and psoriasis. It is also approved in these indications in several other countries, including Korea, the USA and Australia. Characterization of SB2 in preclinical studies showed that it is similar to reference infliximab...
August 12, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28801181/the-use-of-oral-corticosteroids-in-inflammatory-bowel-diseases-in-italy-an-ig-ibd-survey
#11
Federica Fascì-Spurio, Gianmichele Meucci, Claudio Papi, Simone Saibeni
AIM: To evaluate how Italian gastroenterologists use corticosteroids in clinical practice for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). MATERIAL AND METHODS: All members of the Italian Group for Inflammatory Bowel Disease (IG-IBD) were invited to fill in a web-based questionnaire. RESULTS: 131/448 (29.2%) members completed the survey. In mild-to-moderate UC and CD relapses, low-bioavailability steroids (LBS) are first-line therapy for 37% and 42% of clinicians, respectively...
July 22, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28800384/exploring-conditions-for-redistribution-of-anti-tnfs-to-reduce-spillage-a-study-on-the-quality-of-anti-tnf-home-storage
#12
Marin J de Jong, Marieke J Pierik, Andy Peters, Mark Roemers, Veronique Hilhorst, Astrid van Tubergen
BACKGROUND AND AIM: Biologicals are potent drugs for immune mediated inflammatory diseases (IMIDs). After discontinuation or switch of therapy, many patients have unused biological injectors left. We aimed to evaluate potential redistribution of unused injectors to prevent spillage of these costly drugs by assessing 1) the quality of transport and home storage through the proportion of injectors stored within the recommended temperature range (2°C-8°C) and 2) acceptance of redistribution by patients...
August 11, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28797579/an-acid-seeking-carrier-free-drug-achieves-high-antitumor-activity-via-a-solution-particle-transition
#13
Xiaoying Zhang, Cuifeng Wang, Jiamin Wu, Yajun Liu, Zeping Yang, Ye Zhang, Xiaofeng Sui, Min Li, Min Feng
Drug nanocarriers that have long been expected to revolutionize cancer therapy have yet to achieve the significant clinical success. Therefore, it remains controversial to pursue a complex drug nanocarrier that lacks clinical relevance. Herein, we developed an easily-synthesized anti-tumor drug that actively seeks the acidic tumor microenvironment while ignoring the normal tissue without the aid of additional carriers. This called "carrier-free" drug (CFD) is capable of switching its morphology from the unstructured solution to the spherical structure in response to tumor acidity...
August 8, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28794632/risperidone-induced-reversible-neutropenia
#14
Vasanth Kattalai Kailasam, Victoria Chima, Uchechukwu Nnamdi, Kavita Sharma, Kairav Shah
This case report presents a 44-year-old man with a history of schizophrenia who developed neutropenia on risperidone therapy. The patient's laboratory reports showed a gradual decline of leukocytes and neutrophils after resolution and rechallenging. This was reversed with the discontinuation of risperidone and by switching to olanzapine. In this case report, we also discuss the updated evidence base for management of risperidone-induced neutropenia.
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28794382/edoxaban-was-effective-for-treating-renal-vein-thrombosis-in-a-patient-with-nephrotic-syndrome
#15
Yoshitaka Shimada, Yasushi Nagaba, Hide Nagaba, Mariko Kamata, Junya Murano, Fumi Kamata, Chikako Okina, Hiroshi Nonoguchi, Hajime Shimada, Yasuo Takeuchi
A 39-year-old man with nephrotic syndrome was admitted due to right dorsal pain. Contrast-enhanced CT led to a diagnosis of renal vein thrombosis and segmental pulmonary thromboembolism. Treatment with heparin and warfarin was started. After 1 month, pulmonary thromboembolism recurred. Warfarin was switched to edoxaban, and steroid therapy was initiated, which led to the remission of nephrotic syndrome and the disappearance of renal vein thrombosis. The efficacy of edoxaban was demonstrated; however, this drug has not been routinely selected for patients with renal disease...
August 10, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28794072/ruxolitinib-versus-best-available-therapy-for-et-intolerant-or-resistant-to-hydroxycarbamide-in-a-randomized-trial
#16
Claire N Harrison, Adam J Mead, Anesh Panchal, Sonia Fox, Christina Yap, Emmanouela Gbandi, Aimee Houlton, Samah Alimam, Joanne Ewing, Marion Wood, Frederick Chen, Jason Coppell, Nicki Panoskaltsis, Steven Knapper, Sahra Ali, Angela Hamblin, Ruben Scherber, Amylou C Dueck, Nicholas C P Cross, Ruben Mesa, Mary Frances McMullin
Treatments for high-risk essential thrombocythemia (ET) address thrombocytosis, disease-related symptoms, as well as risks of thrombosis, hemorrhage, transformation to myelofibrosis and leukemia. Patients resistant/intolerant to hydroxycarbamide (HC) have a poor outlook. MAJIC (ISRCTN61925716) is a randomized phase II trial of ruxolitinib (JAK1/2 inhibitor) vs Best Available Therapy (BAT) in ET and polycythemia vera (PV) patients resistant or intolerant to HC. Here findings of MAJIC-ET are reported, where the modified intention-to-treat population included 58 & 52 patients randomized to receive ruxolitinib or BAT respectively...
August 9, 2017: Blood
https://www.readbyqxmd.com/read/28793876/patient-satisfaction-with-extavipro%C3%A2-30g-a-new-auto-injector-for-administering-interferon-%C3%AE-1b-in-multiple-sclerosis-results-from-a-real-world-observational-exchange-study
#17
Frank A Hoffmann, Anastasiya Trenova, Miguel A Llaneza, Johannes Fischer, Giacomo Lus, Dorothea von Bredow, Núria Lara, Elaine Lam, Marlies Van Hoef, Rajesh Bakshi
BACKGROUND: Patients with multiple sclerosis (MS) receiving long-term, subcutaneous interferon β-1b (IFN β-1b; Extavia®) often experience injection-site reactions and injection-site pain, which together with other side-effects (such as flu-like symptoms) result in suboptimal treatment compliance/adherence. The EXCHANGE study evaluated patient satisfaction with IFN β-1b treatment, administered using ExtaviPro™ 30G, a new auto-injector, in a real-world setting. METHODS: This 26-week, open-label, prospective, non-interventional, observational, multi-country multi-centre study enrolled patients with MS who had been treated with IFN β-1b or other disease-modifying therapies with a self-administered auto-injector for ≥3 months and who were planned to switch to IFN β-1b treatment administered using ExtaviPro™ 30G as part of routine clinical care...
August 9, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28793863/cardiovascular-risk-and-dyslipidemia-among-persons-living-with-hiv-a-review
#18
REVIEW
Paolo Maggi, Antonio Di Biagio, Stefano Rusconi, Stefania Cicalini, Maurizio D'Abbraccio, Gabriella d'Ettorre, Canio Martinelli, Giuseppe Nunnari, Laura Sighinolfi, Vincenzo Spagnuolo, Nicola Squillace
BACKGROUND: Aim of this review is to focus the attention on people living with HIV infection at risk of developing a cardiovascular event. What is or what would be the most suitable antiretroviral therapy? Which statin or fibrate to reduce the risk? How to influence behavior and lifestyles? DISCUSSION: Prevention of cardiovascular disease (CVD) risk remains the first and essential step in a medical intervention on these patients. The lifestyle modification, including smoking cessation, increased physical activity, weight reduction, and the education on healthy dietary practices are the main instruments...
August 9, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28793781/second-line-antiretroviral-therapy-in-sub-saharan-africa-it-s-time-to-mind-the-gaps
#19
Richard Andrew Murphy, Richard Court, Gary Maartens, Henry Sunpath
The delay between first-line antiretroviral therapy (ART) failure and initiation of second-line ART - in resource-limited settings - can be prolonged. Increasing evidence links delayed antiretroviral switch with increased risk for opportunistic infection (OI) and death, particularly in patients with advanced HIV at the time of first-line failure. As access to viral load monitoring widens beyond a few countries, mechanisms are needed to optimize the use of routine virologic monitoring and assure that first-line regimen failure results in prompt second-line switch...
August 10, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28793186/an-engineered-optogenetic-switch-for-spatiotemporal-control-of-gene-expression-cell-differentiation-and-tissue-morphogenesis
#20
Lauren Polstein, Mark Juhas, Gabi Hanna, Nenad Bursac, Charles A Gersbach
The precise spatial and temporal control of gene expression, cell differentiation, and tissue morphogenesis has widespread application in regenerative medicine and the study of tissue development. In this work, we applied optogenetics to control cell differentiation and new tissue formation. Specifically, we engineered an optogenetic "on" switch that provides permanent transgene expression following a transient dose of blue light illumination. To demonstrate its utility in controlling cell differentiation and reprogramming, we incorporated an engineered form of the master myogenic factor MyoD into this system in multipotent cells...
August 9, 2017: ACS Synthetic Biology
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