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https://www.readbyqxmd.com/read/27911276/the-mtor-inhibitor-everolimus-in-combination-with-azacitidine-in-patients-with-relapsed-refractory-acute-myeloid-leukemia-a-phase-ib-ii-study
#1
Peter Tan, Ing Soo Tiong, Shaun Fleming, Giovanna Pomilio, Nik Cummings, Mark Droogleever, Julie McManus, Anthony Schwarer, John Catalano, Sushrut Patil, Sharon Avery, Andrew Spencer, Andrew Wei
Therapeutic options are limited in relapsed/refractory acute myeloid leukemia (AML). We evaluated the maximum tolerated dose (MTD) and preliminary efficacy of mammalian target of rapamycin (mTOR) inhibitor, everolimus (days 5-21) in combination with azacitidine 75 mg/m2 subcutaneously (days 1-5 and 8-9 every 28 days) in 40 patients with relapsed (n = 27), primary refractory (n = 11) or elderly patients unfit for intensive chemotherapy (n = 2). MTD was not reached following everolimus dose escalation (2.5, 5 or 10 mg; n = 19) to the 10 mg dose level which was expanded (n = 21)...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27909033/ethnic-differences-in-the-prevalence-of-knee-pain-among-adults-of-a-community-in-a-cross-sectional-study
#2
Yook Chin Chia, Hooi Chin Beh, Chirk Jenn Ng, Cheong Lieng Teng, Nik Sherina Hanafi, Wan Yuen Choo, Siew Mooi Ching
OBJECTIVE: To determine the prevalence of knee pain among 3 major ethnic groups in Malaysia. By identifying high-risk groups, preventive measures can be targeted at these populations. DESIGN AND SETTING: A cross-sectional survey was carried out in rural and urban areas in a state in Malaysia. Secondary schools were randomly selected and used as sampling units. PARTICIPANTS: Adults aged ≥18 years old were invited to answer a self-administered questionnaire on pain experienced over the previous 6 months...
December 1, 2016: BMJ Open
https://www.readbyqxmd.com/read/27908766/mechanisms-and-predictors-of-recurrent-tachycardia-following-catheter-ablation-for-d-transposition-of-the-great-arteries-after-the-mustard-or-senning-operation
#3
Roberto G Gallotti, Himani Madnawat, Kevin M Shannon, Jamil A Aboulhosn, Farnoosh Nik-Ahd, Jeremy P Moore
BACKGROUND: The Senning and Mustard operations for DTGA are associated with a heightened risk for supraventricular tachycardia. Catheter ablation has been shown to be acutely successful for achieving rhythm control in this population, but the mechanisms of recurrence are ill-defined. OBJECTIVES: We hypothesized that the type and degree of recurrence would vary by the surgical technique employed. METHODS: All consecutive catheter ablation procedures for DTGA after Mustard/Senning operation between 2004 and 2016 at a single center were reviewed...
November 28, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27905294/glucocorticoids-increase-skeletal-muscle-nf-%C3%AE%C2%BAb-inducing-kinase-nik-links-to-muscle-atrophy
#4
Christopher S Fry, Syed Z Nayeem, Edgar L Dillon, Partha S Sarkar, Batbayar Tumurbaatar, Randall J Urban, Traver J Wright, Melinda Sheffield-Moore, Ronald G Tilton, Sanjeev Choudhary
Glucocorticoids (GC) are a frontline therapy for numerous acute and chronic diseases because of their demonstrated efficacy at reducing systemic inflammation. An unintended side effect of GC therapy is the stimulation of skeletal muscle atrophy. Pathophysiological mechanisms responsible for GC-induced skeletal muscle atrophy have been extensively investigated, and the ability to treat patients with GC without unintended muscle atrophy has yet to be realized. We have reported that a single, standard-of-care dose of Methylprednisolone increases in vivo expression of NF-κB-inducing kinase (NIK), an important upstream regulatory kinase controlling NF-κB activation, along with other key muscle catabolic regulators such as Atrogin-1 and MuRF1 that induce skeletal muscle proteolysis...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27889261/nik-map3k14-regulates-mitochondrial-dynamics-and-trafficking-to-promote-cell-invasion
#5
Ji-Ung Jung, Sowndharya Ravi, Dong W Lee, Kassandra McFadden, Michael L Kamradt, L Gerard Toussaint, Raquel Sitcheran
Although the role of NF-κB-inducing kinase (NIK) in immunity is well established, its relevance in cancer is just emerging. Here we describe novel functions for NIK in regulating mitochondrial dynamics and motility to promote cell invasion. We show that NIK is localized to mitochondria in cancer cell lines, ex vivo tumor tissue, and mouse embryonic fibroblasts (MEFs). NIK promotes mitochondrial fission, velocity, and directional migration, resulting in subcellular distribution of mitochondria to the periphery of migrating cells...
November 15, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27886581/a-multi-omic-approach-to-elucidate-low-dose-effects-of-xenobiotics-in-zebrafish-danio-rerio-larvae
#6
Susie S Y Huang, Jonathan P Benskin, Nik Veldhoen, Bharat Chandramouli, Heather Butler, Caren C Helbing, John R Cosgrove
Regulatory-approved toxicity assays such as the OECD Fish Embryo Toxicity Assay (TG236) allow correlation of chemical exposure to adverse morphological phenotypes. However, these assays are ineffective in assessing sub-lethal (i.e. low-dose) effects, or differentiating between similar phenotypes induced by different chemicals. Inclusion of multi-omic analyses in studies investigating xenobiotic action provides improved characterization of biological response, thereby enhancing prediction of toxicological outcomes in whole animals in the absence of morphological effects...
November 18, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/27878469/genetic-diversity-and-population-structure-of-nuphar-submersa-nymphaeaceae-a-critically-endangered-aquatic-plant-endemic-to-japan-and-implications-for-its-conservation
#7
Takashi Shiga, Masashi Yokogawa, Shingo Kaneko, Yuji Isagi
Nuphar submersa (Nymphaeaceae) is a critically endangered freshwater macrophyte indigenous to central Japan, with only four small extant populations represented across its entire range. We investigated the genotypic and genetic diversity as well as the genetic structure of all extant individuals of N. submersa based on analysis of 15 microsatellite loci. Among 278 individual ramets, 52 multilocus genotypes were detected: 30 genotypes in Nikko City (NIK), 18 in Nasukarasuyama City (NAS), 3 in Mooka City (MOK), and 1 in Sakura City (SAK)...
November 22, 2016: Journal of Plant Research
https://www.readbyqxmd.com/read/27876836/nf-kappa%C3%AE-inducing-kinase-regulates-stem-cell-phenotype-in-breast-cancer
#8
Karla Vazquez-Santillan, Jorge Melendez-Zajgla, Luis Enrique Jimenez-Hernandez, Javier Gaytan-Cervantes, Laura Muñoz-Galindo, Patricia Piña-Sanchez, Gustavo Martinez-Ruiz, Javier Torres, Patricia Garcia-Lopez, Carolina Gonzalez-Torres, Victor Ruiz, Federico Avila-Moreno, Marco Velasco-Velazquez, Mayra Perez-Tapia, Vilma Maldonado
Breast cancer stem cells (BCSCs) overexpress components of the Nuclear factor-kappa B (NF-κB) signaling cascade and consequently display high NF-κB activity levels. Breast cancer cell lines with high proportion of CSCs exhibit high NF-κB-inducing kinase (NIK) expression. The role of NIK in the phenotype of cancer stem cell regulation is poorly understood. Expression of NIK was analyzed by quantitative RT-PCR in BCSCs. NIK levels were manipulated through transfection of specific shRNAs or an expression vector...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27873317/b-cell-activating-factor-signalling-pathway-is-associated-with-h-pylori-independence-in-gastric-malt-lymphoma-without-t-11-18-q21-q21
#9
Sung-Hsin Kuo, Hui-Jen Tsai, Chung-Wu Lin, Kun-Huei Yeh, Hsiao-Wei Lee, Ming-Feng Wei, Chia-Tung Shun, Ming-Shiang Wu, Ping-Ning Hsu, Li-Tzong Chen, Ann-Lii Cheng
We previously reported that activation of the B cell-activating factor (BAFF) pathway upregulates NF-κB and induces BCL3 and BCL10 nuclear translocation in H. pylori (HP)-independent gastric diffuse large B-cell lymphoma (DLBCL) tumours with evidence of mucosa-associated lymphoid tissue (DLBCL [MALT]). However, the significance of BAFF expression in HP-independence of gastric low-grade MALT lymphomas (MALT lymphoma) without t(11;18)(q21;q21) remains unexplored. Sixty-four patients who underwent successful HP eradication for localized HP-positive gastric MALT lymphomas without t(11;18)(q21;q21) were studied...
November 22, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27871061/a-small-molecule-inhibitor-of-nf-%C3%AE%C2%BAb-inducing-kinase-nik-protects-liver-from-toxin-induced-inflammation-oxidative-stress-and-injury
#10
Xiaomeng Ren, Xinzhi Li, Linna Jia, Deheng Chen, Hai Hou, Liangyou Rui, Yujun Zhao, Zheng Chen
Potent and selective chemical probes are valuable tools for discovery of novel treatments for human diseases. NF-κB-inducing kinase (NIK) is a key trigger in the development of liver injury and fibrosis. Whether inhibition of NIK activity by chemical probes ameliorates liver inflammation and injury is largely unknown. In this study, a small-molecule inhibitor (B022) of NIK was found to be a potent and selective chemical probe for liver inflammation and injury. B022 inhibited the NIK signaling pathway, including NIK-induced p100-to-p52 processing and inflammatory gene expression, both in vitro and in vivo Furthermore, in vivo administration of B022 protected against not only NIK but also CCl4-induced liver inflammation and injury...
November 8, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27867007/srf-co-factors-control-the-balance-between-cell-proliferation-and-contractility
#11
Francesco Gualdrini, Cyril Esnault, Stuart Horswell, Aengus Stewart, Nik Matthews, Richard Treisman
The ERK-regulated ternary complex factors (TCFs) act with the transcription factor serum response factor (SRF) to activate mitogen-induced transcription. However, the extent of their involvement in the immediate-early transcriptional response, and their wider functional significance, has remained unclear. We show that, in MEFs, TCF inactivation significantly inhibits over 60% of TPA-inducible gene transcription and impairs cell proliferation. Using integrated SRF ChIP-seq and Hi-C data, we identified over 700 TCF-dependent SRF direct target genes involved in signaling, transcription, and proliferation...
November 5, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27864565/targeting-non-canonical-nuclear-factor-%C3%AE%C2%BAb-signalling-attenuates-neovascularization-in-a-novel-3d-model-of-rheumatoid-arthritis-synovial-angiogenesis
#12
Chrissta X Maracle, Paulina Kucharzewska, Boy Helder, Corine van der Horst, Pedro Correa de Sampaio, Ae-Ri Noort, Katinka van Zoest, Arjan W Griffioen, Henric Olsson, Sander W Tas
OBJECTIVE: Angiogenesis is crucial in RA disease progression. Lymphotoxin β receptor (LTβR)-induced activation of the non-canonical nuclear factor-κB (NF-κB) pathway via NF-κB-inducing kinase (NIK) has been implicated in this process. Consequently, inhibition of this pathway may hold therapeutic potential in RA. We describe a novel three-dimensional (3D) model of synovial angiogenesis incorporating endothelial cells (ECs), RA fibroblast-like synoviocytes (RAFLSs) and RA synovial fluid (RASF) to further investigate the contributions of NF-κB in this process...
November 17, 2016: Rheumatology
https://www.readbyqxmd.com/read/27859827/elevated-phosphodiester-and-t2-levels-can-be-measured-in-the-absence-of-fat-infiltration-in-duchenne-muscular-dystrophy-patients
#13
M T Hooijmans, E H Niks, J Burakiewicz, J J G M Verschuuren, A G Webb, H E Kan
Quantitative MRI and MRS are increasingly important as non-invasive outcome measures in therapy development for Duchenne muscular dystrophy (DMD). Many studies have focussed on individual measures such as fat fraction and metabolite levels in relation to age and functionality, but much less attention has been given to how these indices relate to each other. Here, we assessed spatially resolved metabolic changes in leg muscles of DMD patients, and classified muscles according to the degree of fat replacement compared with healthy controls...
November 17, 2016: NMR in Biomedicine
https://www.readbyqxmd.com/read/27829421/bovine-lactoferrin-free-of-lipopolysaccharide-can-induce-a-proinflammatory-response-of-macrophages
#14
Nada Zemankova, Katarina Chlebova, Jan Matiasovic, Jana Prodelalova, Jan Gebauer, Martin Faldyna
BACKGROUND: Lactoferrin (LF) is an 80 kDa glycoprotein which is known for its effects against bacteria, viruses and other pathogens. It also has a high potential in nutrition therapy and welfare of people and a variety of animals, including piglets. The ability to bind lipopolysaccharide (LPS) is one of the described anti-inflammatory mechanisms of LF. Previous studies suggested that cells can be stimulated even by LPS-free LF. Therefore, the aim of our study was to bring additional information about this possibility...
November 10, 2016: BMC Veterinary Research
https://www.readbyqxmd.com/read/27811275/mutational-signatures-associated-with-tobacco-smoking-in-human-cancer
#15
Ludmil B Alexandrov, Young Seok Ju, Kerstin Haase, Peter Van Loo, Iñigo Martincorena, Serena Nik-Zainal, Yasushi Totoki, Akihiro Fujimoto, Hidewaki Nakagawa, Tatsuhiro Shibata, Peter J Campbell, Paolo Vineis, David H Phillips, Michael R Stratton
Tobacco smoking increases the risk of at least 17 classes of human cancer. We analyzed somatic mutations and DNA methylation in 5243 cancers of types for which tobacco smoking confers an elevated risk. Smoking is associated with increased mutation burdens of multiple distinct mutational signatures, which contribute to different extents in different cancers. One of these signatures, mainly found in cancers derived from tissues directly exposed to tobacco smoke, is attributable to misreplication of DNA damage caused by tobacco carcinogens...
November 4, 2016: Science
https://www.readbyqxmd.com/read/27802293/implementation-of-novel-design-features-for-qpcr-based-edna-assessment
#16
Nik Veldhoen, Jared Hobbs, Georgios Ikonomou, Michael Hii, Mary Lesperance, Caren C Helbing
Environmental stewardship requires timely, accurate information related to the status of a given ecosystem and the species that occupy it. Recent advances in the application of the highly sensitive real-time quantitative polymerase chain reaction (qPCR) towards identification of constituents within environmental DNA (eDNA) now allow targeted detection of the presence of species-specific biological material within a localized geographic region. However, as with all molecular techniques predicated on the specificity and sensitivity of the PCR assay, careful validation of each eDNA qPCR assay in development must be performed both under controlled laboratory conditions and when challenged with field-derived eDNA samples...
2016: PloS One
https://www.readbyqxmd.com/read/27799450/mobile-health-mhealth-for-headache-disorders-a-review-of-the-evidence-base
#17
Mahsa Mosadeghi-Nik, Marzyeh S Askari, Farhad Fatehi
The aim of this review was to explore and summarise the evidence base for using mobile apps for the management of headache disorders. PubMed, Web of Science, Embase and Scopus were searched for studies reporting the use of mobile health applications (apps) for managing headache disorders. Different combinations of keywords for mobile health, smartphone and headache were used for electronic search. Six studies (two journal papers and four conference papers) met the inclusion criteria and were reviewed. All of the reviewed studies were categorised as the lowest level (level IV) of evidence according to the National Health and Medical Research Council (NHMRC) hierarchy of evidence...
December 2016: Journal of Telemedicine and Telecare
https://www.readbyqxmd.com/read/27781105/impact-of-orphan-status-on-hiv-treatment-outcomes-and-retention-in-care-of-children-and-adolescents-in-asia
#18
EDITORIAL
Bui Vu Huy, Sirinya Teeraananchai, Le Ngoc Oanh, John Tucker, Nia Kurniati, Rawiwan Hansudewechakul, Khanh Huu Truong, Vohith Khol, Lam Van Nguyen, Viet Chau Do, Pagakrong Lumbiganon, Nantaka Kongstan, Torsak Bunupuradah, Tavitiya Sudjaritruk, Nagalingeswaran Kumarasamy, Nik Khairulddin Nik Yusoff, Kamarul Azahar Mohd Razali, Dewi Kumara Wati, Moy Siew Fong, Revathy Nallusamy, Azar Kariminia, Annette H Sohn
An analysis of the impact of orphanhood at antiretroviral therapy (ART) initiation on HIV outcomes in Asia included 4300 children; 51% were male. At ART initiation, 1805 (42%) were non-orphans (median age: 3 years), 1437 (33%) were single orphans (6 years) and 1058 (25%) were double orphans (7 years). Ten-year post-ART survival was 93.4-95.2% across orphan categories. Clinic transfers were higher among single and double orphans than non-orphans (41% vs 11%, P<0.001). On multivariate analysis, children ≥3 years at ART initiation (hazard ratio 1...
October 5, 2016: Journal of Virus Eradication
https://www.readbyqxmd.com/read/27772923/self-sampling-versus-physician-sampling-for-cervical-cancer-screening-the-agreement-of-cytological-diagnoses
#19
Fatma Hariati Mohamad Zaki, Nik Hazlina Nik Hussain, Pazuddin Ismail, Wan Zahanim Wan Yusoff, Nor Hayati Othman
No abstract text is available yet for this article.
February 2016: Pathology
https://www.readbyqxmd.com/read/27770125/a-case-report-of-aluminium-phosphide-poisoning
#20
N A Nik Muhamad, R Hawari, H Shafie
Aluminium phosphide (ALP) is highly toxic and poisoning can result in high mortality rates. A 26-year-old female who allegedly ingested a toxic dose of ALP presented with vomiting and diarrhoea. She developed cardiac arrest with refractory pulseless ventricular tachycardia. Despite aggressive resuscitation, she succumbed to death seven hours following ingestion. In cases like this, a better outcome can be achieved with early arrival, prompt diagnosis, aggressive resuscitation and intensive monitoring.
August 2016: Medical Journal of Malaysia
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