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https://www.readbyqxmd.com/read/28541716/investigational-bet-bromodomain-protein-inhibitors-in-early-stage-clinical-trials-for-acute-myelogenous-leukemia-aml
#1
Thorsten Braun, Claude Gardin
Acute myelogenous leukemia (AML) is a heterogeneous group of malignancies driven by genetic mutations and deregulated epigenetic control. Relapse/refractory disease remains frequent in younger patients and even more so in older patients, including treatment with epigenetic drugs in this age group, mainly with hypomethylating agents. New treatment strategies are urgently needed. The recent discovery that epigenetic readers of the bromodomain (BRD) and extraterminal (BET) protein family, are crucial for AML maintenance by transcription of oncogenic c-MYC lead to rapid development of BET inhibitors entering clinical trials...
May 25, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28516829/factors-associated-with-failure-of-emergency-wait-time-targets-for-high-acuity-discharges-and-intensive-care-unit-admissions
#2
Ivy Cheng, Merrick Zwarenstein, Alex Kiss, Maaret Castren, Mats Brommels, Michael Schull
OBJECTIVE: Ontario established emergency department length-of-stay (EDLOS) targets but has difficulty achieving them. We sought to determine predictors of target time failure for discharged high acuity patients and intensive care unit (ICU) admissions. METHODS: This was a retrospective, observational study of 2012 Sunnybrook Hospital emergency department data. The main outcome measure was failing to meet government EDLOS targets for high acuity discharges and ICU emergency admissions...
May 18, 2017: CJEM
https://www.readbyqxmd.com/read/28506208/a-strategy-to-apply-quantitative-epistasis-analysis-on-developmental-traits
#3
Marta K Labocha, Wang Yuan, Boanerges Aleman-Meza, Weiwei Zhong
BACKGROUND: Genetic interactions are keys to understand complex traits and evolution. Epistasis analysis is an effective method to map genetic interactions. Large-scale quantitative epistasis analysis has been well established for single cells. However, there is a substantial lack of such studies in multicellular organisms and their complex phenotypes such as development. Here we present a method to extend quantitative epistasis analysis to developmental traits. METHODS: In the nematode Caenorhabditis elegans, we applied RNA interference on mutants to inactivate two genes, used an imaging system to quantitatively measure phenotypes, and developed a set of statistical methods to extract genetic interactions from phenotypic measurement...
May 15, 2017: BMC Genetics
https://www.readbyqxmd.com/read/28504695/epigenetic-pathway-inhibitors-represent-potential-drugs-for-treating-pancreatic-and-bronchial-neuroendocrine-tumors
#4
K E Lines, M Stevenson, P Filippakopoulos, S Müller, H E Lockstone, B Wright, S Grozinsky-Glasberg, A B Grossman, S Knapp, D Buck, C Bountra, R V Thakker
Cancer is associated with alterations in epigenetic mechanisms such as histone modifications and methylation of DNA, and inhibitors targeting epigenetic mechanisms represent a novel class of anti-cancer drugs. Neuroendocrine tumors (NETs) of the pancreas (PNETs) and bronchus (BNETs), which may have 5-year survivals of <50% and as low as 5%, respectively, represent targets for such drugs, as >40% of PNETs and ~35% of BNETs have mutations of the multiple endocrine neoplasia type 1 (MEN1) gene, which encodes menin that modifies histones by interacting with histone methyltransferases...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28464950/illumina-miseq-16s-amplicon-sequence-analysis-of-bovine-respiratory-disease-associated-bacteria-in-lung-and-mediastinal-lymph-node-tissue
#5
Dayle Johnston, Bernadette Earley, Paul Cormican, Gerard Murray, David Anthony Kenny, Sinead Mary Waters, Mark McGee, Alan Kieran Kelly, Matthew Sean McCabe
BACKGROUND: Bovine respiratory disease (BRD) is caused by growth of single or multiple species of pathogenic bacteria in lung tissue following stress and/or viral infection. Next generation sequencing of 16S ribosomal RNA gene PCR amplicons (NGS 16S amplicon analysis) is a powerful culture-independent open reference method that has recently been used to increase understanding of BRD-associated bacteria in the upper respiratory tract of BRD cattle. However, it has not yet been used to examine the microbiome of the bovine lower respiratory tract...
May 2, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28464093/a-retrospective-analysis-of-risk-factors-associated-with-bovine-respiratory-disease-treatment-failure-in-feedlot-cattle
#6
T D Avra, K M Abell, D D Shane, M E Theurer, R L Larson, B J White
The objective of this project was to identify risk factors associated with the probability of failing to resolve clinical signs of bovine respiratory disease (BRD) after initial antimicrobial treatment. A retrospective data analysis was performed with 194,062 animals treated for BRD with an antimicrobial from 10 U.S. feedlots from 2005 to 2009. A binary variable classified cattle as a treatment failure if they were retreated for BRD or died following an initial BRD treatment. A generalized logistic mixed model was created to evaluate associations of quarter of the year at feedlot arrival, arrival weight, sex, risk classification (high vs...
April 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28460753/population-level-effects-of-risk-factors-for-bovine-respiratory-disease-in-australian-feedlot-cattle
#7
K E Hay, J M Morton, A C A Clements, T J Mahony, T S Barnes
Results obtained from a nationwide longitudinal study were extended to estimate the population-level effects of selected risk factors on the incidence of bovine respiratory disease (BRD) during the first 50days at risk in medium-sized to large Australian feedlots. Population attributable fractions (PAF) and population attributable risks (PAR) were used to rank selected risk factors in order of importance from the perspective of the Australian feedlot industry within two mutually exclusive categories: 'intervention' risk factors had practical strategies that feedlot managers could implement to avoid exposure of cattle to adverse levels of the risk factor and a precise estimate of the population-level effect while 'others' did not...
May 1, 2017: Preventive Veterinary Medicine
https://www.readbyqxmd.com/read/28446439/pax3-foxo1-establishes-myogenic-super-enhancers-and-confers-bet-bromodomain-vulnerability
#8
Berkley E Gryder, Marielle E Yohe, Hsien-Chao Chou, Xiaohu Zhang, Joana Marques, Marco Wachtel, Beat Schaefer, Nirmalya Sen, Young K Song, Alberto Gualtieri, Silvia Pomella, Rossella Rota, Abigail Cleveland, Xinyu Wen, Sivasish Sindiri, Jun S Wei, Frederic G Barr, Sudipto Das, Thorkell Andresson, Rajarshi Guha, Madhu Lal-Nag, Marc Ferrer, Jack F Shern, Keji Zhao, Craig J Thomas, Javed Khan
Alveolar rhabdomyosarcoma is a life-threatening myogenic cancer of children and adolescent young adults, driven primarily by the chimeric transcription factor PAX3-FOXO1 (P3F). The mechanisms by which P3F dysregulates chromatin are unknown. We find P3F reprograms the cis-regulatory landscape by inducing (de novo) super enhancers (SEs). P3F uses SEs to setup auto-regulatory loops in collaboration with master transcription factors MYOG, MYOD and MYCN. This myogenic SE circuitry is consistent across cell lines and primary tumors...
April 26, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28416404/genomic-and-antigenic-characterization-of-bovine-parainfluenza-3-viruses-in-the-united-states-including-modified-live-virus-vaccine-mlv-strains-and-field-strains-from-cattle
#9
R W Fulton, J D Neill, J T Saliki, C Landis, L J Burge, M E Payton
This study investigated the genetic and antigenic characterization of parainfluenza-3 virus (PI3V) of cattle. Using molecular tests including real time PCR and viral genome sequencing, PI3V strains could be separated into PI3V types, including PI3V A, PI3V B, and PI3V C. Isolates from cattle with bovine respiratory disease clinical signs and commercial vaccines in the U.S. with MLV PI3V were typed using these molecular tests. All the MLV vaccine strains tested were PI3V A. In most cases PI3V field strains from calves receiving MLV vaccines were types heterologous to the vaccine type A...
April 14, 2017: Virus Research
https://www.readbyqxmd.com/read/28390431/mycoplasma-detection-by-triplex-real-time-pcr-in-bronchoalveolar-lavage-fluid-from-bovine-respiratory-disease-complex-cases
#10
Jan B W J Cornelissen, Freddy M de Bree, Fimme J van der Wal, Engbert A Kooi, Miriam G J Koene, Alex Bossers, Bregtje Smid, Adriaan F Antonis, Henk J Wisselink
BACKGROUND: In this study we evaluated the RespoCheck Mycoplasma triplex real-time PCR for the detection in bronchoalveolar lavage fluid (BALF) of Mycoplasma (M.) dispar, M. bovis and M. bovirhinis, all three associated with bovine respiratory disease (BRD). Primers and probes of the RespoCheck Mycoplasma triplex real-time PCR are based on the V3/V4 region of the 16S rRNA gene of the three Mycoplasma species. RESULTS: The analytical sensitivity of the RespoCheck triplex real-time PCR was, as determined by spiking experiments of the Mycoplasma strains in Phosphate Buffered Saline, 300 colony forming units (cfu)/mL for M...
April 8, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28381328/long-term-effect-of-a-chronic-low-protein-multideficient-diet-on-the-heart-hypertension-and-heart-failure-in-chronically-malnourished-young-adult-rats
#11
Luiza V P Mendes, Sabrina R Gonsalez, Leonardo M Oliveira-Pinto, Amaury Pereira-Acácio, Christina M Takiya, José H M Nascimento, Marcelo Einicker-Lamas, Adalberto Vieyra, Valéria M N Cunha, Lucienne S Lara
BACKGROUND: We investigated whether a chronic low-protein multideficient diet (BRD) from weaning turns on cardiovascular adaptive responses that could culminate in hypertension and heart failure. METHODS AND RESULTS: Systolic pressure (SP) and heart rate (HR) were determined in CTRL (normal diet) and BRD rats. Plasma albumin, plasma urea and urinary urea excretion decreased in BRD rats. In this group, echocardiography and the Langendorff technique showed: (i) increased HR and hypertension; (ii) decreased LVDP, dP/dtmax, dP/dtmin, cardiac output, ejection fraction, stroke volume and left ventricular diameter...
March 27, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28380607/a-mixed-treatment-comparison-meta-analysis-of-metaphylaxis-treatments-for-bovine-respiratory-disease-in-beef-cattle
#12
K M Abell, M E Theurer, R L Larson, B J White, M Apley
The objective of this project was to evaluate the effects of antimicrobials approved for parenteral metaphylactic use in feeder and stocker calves on morbidity and mortality for bovine respiratory disease with the use of a mixed treatment comparison meta-analysis. An initial literature review was conducted in April 2016 through Pubmed, Agricola, and CAB (Commonwealth Agricultural Bureau) for randomized controlled trials for metaphylaxis antimicrobial administered parentally to incoming feedlot or stocker calves within 48 h of arrival...
February 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28380515/prevalence-of-multi-drug-antimicrobial-resistance-in-isolated-from-high-risk-stocker-cattle-at-arrival-and-two-weeks-after-processing
#13
E Snyder, B Credille, R Berghaus, S Giguère
Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in North American beef cattle. () is the bacterial pathogen most frequently isolated from cattle with BRD and the prevalence of antimicrobial resistance in this pathogen has been increasing. Administration of antimicrobials to prevent BRD is commonplace in stocker cattle, but the impact of this practice on emergence of resistance in is unknown. High risk, sale barn origin bull and steer calves ( = 169) were transported to a stocker facility in central Georgia and sampled via deep nasopharyngeal swab (NPS) at arrival processing...
March 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28330466/the-nasopharyngeal-microbiota-of-beef-cattle-before-and-after-transport-to-a-feedlot
#14
Devin B Holman, Edouard Timsit, Samat Amat, D Wade Abbott, Andre G Buret, Trevor W Alexander
BACKGROUND: The nasopharyngeal (NP) microbiota plays an important role in bovine health, comprising a rich and diverse microbial community. The nasopharynx is also the niche for potentially pathogenic agents which are associated with bovine respiratory disease (BRD), a serious and costly illness in feedlot cattle. We used 14 beef heifers from a closed and disease-free herd to assess the dynamics of the NP microbiota of cattle that are transported to a feedlot. Cattle were sampled prior to transport to the feedlot (day 0) and at days 2, 7, and 14...
March 22, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28300771/inhibitors-of-brd4-protein-from-a-marine-derived-fungus-alternaria-sp-nh-f6
#15
Hui Ding, Dashan Zhang, Biao Zhou, Zhongjun Ma
Bromodomains (BRD) are readers of the epigenetic code that regulate gene transcription through their recognition of acetyl-lysine modified histone tails. Recently, bromodomain-containing proteins such as BRD4 have been demonstrated to be druggable through the discovery of potent inhibitors. These protein-protein interaction inhibitors have the potential to modulate multiple diseases by their profound anti-inflammatory and antiproliferative effects. In order to explore new BRD4 inhibitors as well as lead compounds for the development of new drugs, the secondary metabolites of Alternaria sp...
March 16, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28295570/agreement-among-4-sampling-methods-to-identify-respiratory-pathogens-in-dairy-calves-with-acute-bovine-respiratory-disease
#16
D Doyle, B Credille, T W Lehenbauer, R Berghaus, S S Aly, J Champagne, P Blanchard, B Crossley, L Berghaus, S Cochran, A Woolums
BACKGROUND: Four sampling techniques commonly are used for antemortem identification of pathogens from cattle with bovine respiratory disease (BRD): the nasal swab (NS), guarded nasopharyngeal swab (NPS), bronchoalveolar lavage (BAL), and transtracheal wash (TTW). Agreement among these methods has not been well characterized. OBJECTIVE: To evaluate agreement among TTW and NS, NPS, or BAL for identification of viral and bacterial pathogens in dairy calves with BRD...
May 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28282443/the-bovine-paranasal-sinuses-bacterial-flora-epithelial-expression-of-nitric-oxide-and-potential-role-in-the-in-herd-persistence-of-respiratory-disease-pathogens
#17
Gerard M Murray, Rónan G O'Neill, Alison M Lee, Máire C McElroy, Simon J More, Aisling Monagle, Bernadette Earley, Joseph P Cassidy
The bovine paranasal sinuses are a group of complex cavernous air-filled spaces, lined by respiratory epithelium, the exact function of which is unclear. While lesions affecting these sinuses are occasionally reported in cattle, their microbial flora has not been defined. Furthermore, given that the various bacterial and viral pathogens causing bovine respiratory disease (BRD) persist within herds, we speculated that the paranasal sinuses may serve as a refuge for such infectious agents. The paranasal sinuses of clinically normal cattle (n = 99) and of cattle submitted for post-mortem examination (PME: n = 34) were examined by microbial culture, PCR and serology to include bacterial and viral pathogens typically associated with BRD: Mycoplasma bovis, Histophilus somni, Mannheimia haemolytica and Pasteurella multocida, bovine respiratory syncytial virus (BRSV) and bovine parainfluenza-3 virus (BPIV-3)...
2017: PloS One
https://www.readbyqxmd.com/read/28265460/thoracoscopy-as-a-safe-and-effective-technique-for-exploring-calves-affected-with-bovine-respiratory-disease
#18
Natividad Perez-Villalobos, Iñaki Espinosa-Crespo, José Sampayo-Cabrera, Juan-Vicente González-Martín, Antonio Gonzalez-Bulnes, Susana Astiz
BACKGROUND: Bovine respiratory disease (BRD) is one of the leading causes of economic losses in the beef and dairy industry. Reliable antemortem tools for diagnosing BRD would improve the efficacy of treatment and reduce costs. Here we examined whether the relatively simple technique of thoracoscopy can support BRD diagnosis under field conditions. We also compared various equipment set-ups in order to optimize the safety and efficacy of the procedure. A total of 24 thoracoscopic procedures were performed in 17 calves diagnosed with BRD and in 2 healthy control calves...
2017: Journal of Animal Science and Technology
https://www.readbyqxmd.com/read/28265070/bet-n-terminal-bromodomain-inhibition-selectively-blocks-th17-cell-differentiation-and-ameliorates-colitis-in-mice
#19
Kalung Cheung, Geming Lu, Rajal Sharma, Adam Vincek, Ruihua Zhang, Alexander N Plotnikov, Fan Zhang, Qiang Zhang, Ying Ju, Yuan Hu, Li Zhao, Xinye Han, Jamel Meslamani, Feihong Xu, Anbalagan Jaganathan, Tong Shen, Hongfa Zhu, Elena Rusinova, Lei Zeng, Jiachi Zhou, Jianjun Yang, Liang Peng, Michael Ohlmeyer, Martin J Walsh, David Y Zhang, Huabao Xiong, Ming-Ming Zhou
T-helper 17 (Th17) cells have important functions in adaptor immunity and have also been implicated in inflammatory disorders. The bromodomain and extraterminal domain (BET) family proteins regulate gene transcription during lineage-specific differentiation of naïve CD4(+) T cells to produce mature T-helper cells. Inhibition of acetyl-lysine binding of the BET proteins by pan-BET bromodomain (BrD) inhibitors, such as JQ1, broadly affects differentiation of Th17, Th1, and Th2 cells that have distinct immune functions, thus limiting their therapeutic potential...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28240958/comparison-of-the-diagnostic-performance-of-bacterial-culture-of-nasopharyngeal-swab-and-bronchoalveolar-lavage-fluid-samples-obtained-from-calves-with-bovine-respiratory-disease
#20
Sarah F Capik, Brad J White, Brian V Lubbers, Michael D Apley, Keith D DeDonder, Robert L Larson, Greg P Harhay, Carol G Chitko-McKown, Dayna M Harhay, Ted S Kalbfleisch, Gennie Schuller, Michael L Clawson
OBJECTIVE To compare predictive values, extent of agreement, and gamithromycin susceptibility between bacterial culture results of nasopharyngeal swab (NPS) and bronchoalveolar lavage fluid (BALF) samples obtained from calves with bovine respiratory disease (BRD). ANIMALS 28 beef calves with clinical BRD. PROCEDURES Pooled bilateral NPS samples and BALF samples were obtained for bacterial culture from calves immediately before and at various times during the 5 days after gamithromycin (6 mg/kg, SC, once) administration...
March 2017: American Journal of Veterinary Research
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