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https://www.readbyqxmd.com/read/29352001/keap1-editing-using-crispr-cas9-for-therapeutic-nrf2-activation-in-primary-human-t-lymphocytes
#1
Sanjeev Noel, Sul A Lee, Mohanraj Sadasivam, Abdel R A Hamad, Hamid Rabb
Oxidant stress modifies T lymphocyte activation and function. Previous work demonstrated that murine T cell-specific kelch like-ECH-associated protein 1 (Keap1) deletion enhances antioxidant capacity and protects from experimental acute kidney injury. In this study, we used CRISPR technology to develop clinically translatable human T cell-specific KEAP1 deletion. Delivery of KEAP1 exon 2 specific Cas9:guide RNA in Jurkat T cells led to significant (∼70%) editing and upregulation of NRF2-regulated antioxidant genes NADPH dehydrogenase quinone 1 (NQO1) (up to 11-fold), heme oxygenase 1 (HO1) (up to 11-fold), and GCLM (up to 2-fold)...
January 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29350120/-continued-development-of-drugs-the-path-of-thioguanine
#2
M Simsek, K H N de Boer, C J J Mulder
Continued development of existing drugs ('drug rediscovery') may offer new therapeutic options and be cost-effective. Rediscovered drugs are commonly prescribed off-label, although licensing can be important to allow safe and controlled prescription of the drugs to patients. Licensing of a new indication for a generic drug, however, is a complicated process since there is no blueprint for this and there is little interest from the pharmaceutical industry due to an unattractive cost-recovery model. In this article, we illustrate the successful license-extension for thioguanine - initially developed in 1950 for leukaemia - as a new treatment for patients with inflammatory bowel disease...
2018: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/29349928/problem-behaviours-and-psychotropic-medication-use-in-intellectual-disability-a-multinational-cross-sectional-survey
#3
B I Perry, H F Kwok, J Mendis, K Purandare, A Wijeratne, S Manjubhashini, M Dasari, F Esan, I Gunaratna, R A Naseem, S Hoare, V Chester, A Roy, J Devapriam, R Alexander, S E Cooray
BACKGROUND: Problem behaviours (PBs) are a common cause for clinician contact in people with disorders of intellectual development and may be a common cause for the prescription of psychotropic medication. We aimed to use a large, multinational sample to define the prevalence of PBs, the associations with psychotropic medication use, and to assess for any potential 'diagnostic overshadowing' by the label of PBs in a population of people with disorders of intellectual development. METHOD: A multinational, multi-setting, cross-sectional service evaluation and baseline audit was completed...
February 2018: Journal of Intellectual Disability Research: JIDR
https://www.readbyqxmd.com/read/29349561/sphenopalatine-ganglion-stimulation-for-cluster-headache-results-from-a-large-open-label-european-registry
#4
Mads Barloese, Anja Petersen, Philipp Stude, Tim Jürgens, Rigmor Højland Jensen, Arne May
BACKGROUND: Cluster headache (CH) is a disabling primary headache disorder characterized by severe periorbital pain. A subset of patients does not respond to established pharmacological therapy. This study examines outcomes of a cohort of mainly chronic CH patients treated with sphenopalatine ganglion (SPG) stimulation. METHODS: Patients were followed in an open-label prospective study for 12 months. Ninety-seven CH patients (88 chronic, 9 episodic) underwent trans-oral insertion of a microstimulator targeting the SPG...
January 18, 2018: Journal of Headache and Pain
https://www.readbyqxmd.com/read/29349372/successful-off-label-use-of-the-gore-excluder-iliac-branch-endoprosthesis-to-preserve-gluteal-perfusion-during-staged-endovascular-repair-of-bilateral-isolated-hypogastric-aneurysms
#5
James W Cornwall, Daniel K Han, Daniel I Fremed, Peter L Faries, Ageliki G Vouyouka
Endovascular repair of iliac artery aneurysms has emerged as an alternative to traditional open surgical repair. Although there is little consensus on indications to preserve hypogastric blood flow during aneurysm repair, it is well understood that complications from bilateral hypogastric occlusion may be significant. The GORE EXCLUDER Iliac Branch Endoprosthesis (W. L. Gore and Associates, Flagstaff, Ariz) received United States Food and Drug Administration approval in March 2016 for treatment of common iliac artery and aortoiliac aneurysms...
March 2017: Journal of Vascular Surgery Cases and Innovative Techniques
https://www.readbyqxmd.com/read/29345736/palbociclib-in-combination-with-letrozole-as-first-line-treatment-for-advanced-breast-cancer-a-japanese-phase-ii-study
#6
Norikazu Masuda, Reiki Nishimura, Masato Takahashi, Kenichi Inoue, Shinji Ohno, Hiroji Iwata, Yuko Mori, Satoshi Hashigaki, Yasuaki Muramatsu, Takashi Nagasawa, Yoshiko Umeyama, Masakazu Toi
This single-arm, open-label, phase II study in 42 Japanese postmenopausal patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer evaluated the efficacy, safety, and pharmacokinetics of first-line palbociclib (125 mg once daily, 3 weeks on/1 week off) coadministered with letrozole (2.5 mg once daily). The primary endpoint of investigator-assessed 1-year progression-free survival probability was 75.0% (90% CI, 61.3%-84.4%), far surpassing the 40% lower limit of the 90% CI supporting efficacy...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29343137/hybrid-aortic-arch-and-frozen-elephant-trunk-reconstruction-bridging-the-gap-between-conventional-and-total-endovascular-arch-repair
#7
Sabin J Bozso, Abigail White, Jeevan Nagendran, Michael C Moon, Michael W A Chu
Novel endovascular techniques hope to offer patients aortic arch repair with reduced morbidity compared to conventional arch surgery; however, current endovascular strategies remain challenged by the proximal seal zone, higher stroke rates, long-term durability and select anatomy. Hybrid arch repair offers patients a less invasive alternative that can treat more distal aorta than conventional arch repair yet still be performed via standard sternotomy. Areas Covered: This review will discuss the current evidence and future development of hybrid aortic arch and frozen elephant trunk reconstruction...
January 18, 2018: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/29341591/the-development-of-benzimidazole-based-clickable-probes-for-the-efficient-labeling-of-cellular-protein-arginine-deiminases-pads
#8
Venkatesh J Nemmara, Venkataraman Subramanian, Aaron Muth, Santanu Mondal, Ari J Salinger, Aaron J Maurais, Ronak Tilvawala, Eranthie Weerapana, Paul R Thompson
Citrullination is the post-translational hydrolysis of peptidyl-arginines to form peptidyl-citrulline, a reaction that is catalyzed by the protein arginine deiminases (PADs), a family of calcium-regulated enzymes. Aberrantly increased protein citrullination is associated with a slew of autoimmune diseases (e.g., rheumatoid arthritis (RA), multiple sclerosis, lupus, and ulcerative colitis) and certain cancers. Given the clear link between increased PAD activity and human disease, the PADs are therapeutically relevant targets...
January 17, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29339626/estimation-of-the-dilution-field-near-a-marine-outfall-by-using-effluent-turbidity-as-an-environmental-tracer-and-comparison-with-dye-tracer-data
#9
José Otavio Goulart Pecly
The alternative use of effluent turbidity to determine the dilution field of a domestic marine outfall located off the city of Rio de Janeiro was evaluated through field work comprising fluorescent dye tracer injection and tracking with simultaneous monitoring of sea water turbidity. A preliminary laboratory assessment was carried out with a sample of the outfall effluent whose turbidity was measured by the nephelometric method before and during a serial dilution process. During the field campaign, the dye tracer was monitored with field fluorometers and the turbidity was observed with an optical backscattering sensor interfaced to an OEM data acquisition system...
January 2018: Water Science and Technology: a Journal of the International Association on Water Pollution Research
https://www.readbyqxmd.com/read/29337341/m%C3%A3-sslingsvaccin-kan-ges-vid-6-m%C3%A3-naders-%C3%A3-lder-i-s%C3%A3-rskilda-fall-vid-risk-f%C3%A3-r-smitta-kan-off-label-anv%C3%A3-ndning-%C3%A3-verv%C3%A3-gas-enligt-en-litteraturgenomg%C3%A3-ng
#10
Sara Sjöberg, Susannah Leach
MMR vaccination in 6-9 month olds Vaccination against measles using the MMR vaccine is licensed from 9 months of age, but is used off-label from 6 months of age during or when travelling to areas with an ongoing measles outbreak. In this review of the published literature, studies on MMR vaccination in this age group are limited and small in size. Immunogenicity studies indicate that infants under 9 months respond with lower antibody titres but comparable T cell responses against measles. The safety profile of the vaccine does not appear to differ between infants vaccinated earlier or later...
January 15, 2018: Läkartidningen
https://www.readbyqxmd.com/read/29336603/comparison-of-unlicensed-and-off-label-use-of-antipsychotics-prescribed-to-child-and-adolescent-psychiatric-outpatients-for-treatment-of-mental-and-behavioral-disorders-with-different-guidelines-the-china-food-and-drug-administration-versus-the-fda
#11
Xiuqing Zhu, Jinqing Hu, Bin Sun, Shuhua Deng, Yuguan Wen, Weijia Chen, Chang Qiu, Dewei Shang, Ming Zhang
OBJECTIVES: This study aims to compare the prevalence of unlicensed and off-label use of antipsychotics among child and adolescent psychiatric outpatients with guidelines proposed by the China Food and Drug Administration (CFDA) and the U.S. Food and Drug Administration (FDA), and to identify factors associated with inconsistencies between the two regulations. METHODS: A retrospective analysis of 29,326 drug prescriptions for child and adolescent outpatients from the Affiliated Brain Hospital of Guangzhou Medical University was conducted...
January 16, 2018: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/29336323/nivolumab-for-recurrent-cutaneous-squamous-cell-carcinoma-three-cases
#12
Veronika Blum, Beat Müller, Silvia Hofer, Esther Pardo, Kristin Zeidler, Joachim Diebold, Klaus Strobel, Christoph Brand, Stefan Aebi, Oliver Gautschi
Programmed cell death ligand 1 (PD-L1) is frequently expressed in cutaneous squamous cell cancer (CSCC) and preliminary data from an ongoing clinical trial suggest that programmed death receptor 1 (PD-1) checkpoint inhibitors may be useful to treat patients with metastatic non-melanoma skin cancer. To report a series of three patients with advanced CSCC treated with nivolumab, showing that commercially available PD-1 checkpoint inhibitors may be useful in non-melanoma skin cancer patients without access to a clinical trial...
January 16, 2018: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/29335823/-drugs-for-intravenous-induction-of-anesthesia-propofol
#13
D Bolkenius, C Dumps, E Halbeck
In a series of articles dealing with hypnotics for induction of anesthesia, this article describes the development and current value of propofol. Its significance far exceeds that of a pure induction hypnotic (sedation in diagnostic and therapeutic procedures and on the intensive care unit). Propofol is also used for sedation in diagnostic and therapeutic procedures and on the intensive care unit. In the field of induction of anesthesia, the alternatives are barely used. Some contraindications are still controversial whereas others are no longer sufficiently anchored in the users' awareness (widespread off-label use)...
January 15, 2018: Der Anaesthesist
https://www.readbyqxmd.com/read/29334841/tocilizumab-in-the-treatment-of-myocardial-infarction
#14
Matthew B Carroll
Tocilizumab (TCZ) is an important biologic response modifier that Rheumatologists routinely employ in the treatment of several systemic autoimmune diseases. TCZ binds to interleukin (IL)-6 receptors, inhibits cellular activation, and mitigates inflammation by IL-6. In mid-2017 TCZ was approved by the U.S. Food and Drug Administration for its first non-rheumatologic condition, the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome in patients 2 years of age or older...
January 16, 2018: Modern Rheumatology
https://www.readbyqxmd.com/read/29334610/phase-ii-study-of-dovitinib-in-patients-with-castration-resistant-prostate-cancer-kcsg-gu11-05
#15
Yoon Ji Choi, Hye Sook Kim, Se Hoon Park, Bong-Seog Kim, Kyoung Ha Kim, Hyo Jin Lee, Hong Suk Song, Dong-Yeop Shin, Ha Young Lee, Hoon-Gu Kim, Kyung Hee Lee, Jae Lyun Lee, Kyong Hwa Park
Purpose: Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC). Materials and Methods: This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500mg/day (5-days-on/2-days-off schedule)...
January 2, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29332554/evaluating-the-dose-dependent-mechanism-of-action-of-trazodone-by-estimation-of-occupancies-for-different-brain-neurotransmitter-targets
#16
Luca Settimo, David Taylor
Trazodone is a drug that was introduced in the clinic almost 40 years ago. It is licensed to treat depression, but it is also commonly used off-label to treat insomnia. A recent study shows that it could be promising in preventing neurodegeneration in mice, and clinical trials to assess its possible beneficial effects on dementia and Alzheimer's disease are expected to start soon in humans. In this study, we describe the dose-dependent pharmacology of trazodone by carrying out pharmacokinetic simulations aiming to predict the brain concentrations of trazodone for different drug-dosing regimens and calculating occupancy for 28 different targets for which published trazodone-binding data are available...
January 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29332420/activated-factor-7-versus-4-factor-prothrombin-complex-concentrate-for-critical-bleeding-post-cardiac-surgery
#17
Sarah L Mehringer, Zachary Klick, Jonathan Bain, Elizabeth B McNeely, Sreekumar Subramanian, Lawrence J Pass, Davis Drinkwater, V Seenu Reddy
BACKGROUND: Recombinant and plasma-derived factor products, such as activated factor seven (rFVIIa) and four-factor prothrombin complex concentrate (4-factor PCC), have been used off-label for bleeding after cardiac surgery, but little evidence has been published regarding their efficacy and safety. OBJECTIVE: To determine whether there is a difference in chest tube output in patients who have received 4-factor PCC or rFVIIa for critical postoperative bleeding associated with cardiovascular surgery...
January 1, 2018: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29332090/impaired-value-of-99m-tc-gsa-scintigraphy-as-an-independent-risk-factor-for-posthepatectomy-liver-failure-in-patients-with-hepatocellular-carcinoma
#18
Ikuo Nakamura, Yuji Iimuro, Seikan Hai, Yuichi Kondo, Etsuro Hatano, Jiro Fujimoto
BACKGROUND: Posthepatectomy liver failure (PHLF) was recently defined with the corresponding recommendations as follows: grade A, no change in clinical management; grade B, clinical management with noninvasive treatment; and grade C, clinical management with invasive treatment. In this study, we identified the risk factors for grade B and C PHLF in patients with hepatocellular carcinoma (HCC). METHODS: Of 339 HCC patients who underwent curative hepatic resection, 218 were included for analysis...
January 12, 2018: European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes
https://www.readbyqxmd.com/read/29331424/ultra-narrow-surface-lattice-resonances-in-plasmonic-metamaterial-arrays-for-biosensing-applications
#19
Artem Danilov, Gleb Tselikov, Fan Wu, Vasyl G Kravets, Igor Ozerov, Frederic Bedu, Alexander N Grigorenko, Andrei V Kabashin
When excited over a periodic metamaterial lattice of gold nanoparticles (~ 100nm), localized plasmon resonances (LPR) can be coupled by a diffraction wave propagating along the array plane, which leads to a drastic narrowing of plasmon resonance lineshapes (down to a few nm full-width-at-half-maximum) and the generation of singularities of phase of reflected light. These phenomena look very promising for the improvement of performance of plasmonic biosensors, but conditions of implementation of such diffractively coupled plasmonic resonances, also referred to as plasmonic surface lattice resonances (PSLR), are not always compatible with biosensing arrangement implying the placement of the nanoparticles between a glass substrate and a sample medium (air, water)...
December 9, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29330235/primary-care-physician-perspectives-about-antipsychotics-and-other-medications-for-symptoms-of-dementia
#20
J William Kerns, Jonathan D Winter, Katherine M Winter, Terry Boyd, Rebecca S Etz
BACKGROUND: Guidelines, policies, and warnings have been applied to reduce the use of medications for behavioral and psychological symptoms of dementia (BPSD). Because of rare dangerous side effects, antipsychotics have been singled out in these efforts. However, antipsychotics are still prescribed "off label" to hundreds of thousands of seniors residing in nursing homes and communities. Our objective was to evaluate how and why primary-care physicians (PCPs) employ nonpharmacologic strategies and drugs for BPSD...
January 2018: Journal of the American Board of Family Medicine: JABFM
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