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Adverse outcome pathway

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https://www.readbyqxmd.com/read/28728110/development-of-a-bioanalytical-test-battery-for-water-quality-monitoring-fingerprinting-identified-micropollutants-and-their-contribution-to-effects-in-surface-water
#1
Peta A Neale, Rolf Altenburger, Selim Aït-Aïssa, François Brion, Wibke Busch, Gisela de Aragão Umbuzeiro, Michael S Denison, David Du Pasquier, Klára Hilscherová, Henner Hollert, Daniel A Morales, Jiří Novák, Rita Schlichting, Thomas-Benjamin Seiler, Helene Serra, Ying Shao, Andrew J Tindall, Knut Erik Tollefsen, Timothy D Williams, Beate I Escher
Surface waters can contain a diverse range of organic pollutants, including pesticides, pharmaceuticals and industrial compounds. While bioassays have been used for water quality monitoring, there is limited knowledge regarding the effects of individual micropollutants and their relationship to the overall mixture effect in water samples. In this study, a battery of in vitro bioassays based on human and fish cell lines and whole organism assays using bacteria, algae, daphnids and fish embryos was assembled for use in water quality monitoring...
July 9, 2017: Water Research
https://www.readbyqxmd.com/read/28723497/pharmacogenomic-markers-of-targeted-therapy-toxicity-in-patients-with-metastatic-renal-cell-carcinoma
#2
Guillermo de Velasco, Kathryn P Gray, Lana Hamieh, Yuksel Urun, Hallie A Carol, Andre P Fay, Sabina Signoretti, David J Kwiatkowski, David F McDermott, Matthew Freedman, Mark M Pomerantz, Toni K Choueiri
BACKGROUND: Targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) may be associated with a high rate of toxicity that undermines treatment efficacy and patient quality of life. Polymorphisms in genes involved in the pharmacokinetic pathways of TTs may predict toxicity. OBJECTIVE: To investigate whether selected single-nucleotide polymorphisms (SNPs) in three core genes involved in the metabolism and transport of sunitinib and the mTOR inhibitors everolimus and temsirolimus are associated with adverse events (AEs)...
December 15, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28716573/htra3-stromal-expression-is-correlated-with-tumor-budding-in-stage-ii-colorectal-cancer
#3
Catherine L Forse, Mahdi Rahimi, Eleftherios P Diamandis, Naziheh Assarzadegan, Heather Dawson, Andrea Grin, Erin Kennedy, Brenda O'Connor, David E Messenger, Robert H Riddell, Richard Kirsch, George S Karagiannis
Tumor budding is a well-established adverse prognostic factor in colorectal carcinoma (CRC). It may represent a form of epithelial-to-mesenchymal transition (EMT), although the underlying mechanisms remain unclear. High-temperature requirement A3 (HtrA3) is an inhibitor of the bone morphogenetic protein pathway, the suppression of which has been linked to EMT. Since HtrA3 is highly expressed in the desmoplastic stroma at the CRC invasive front, we sought to evaluate the relationship between tumor budding and HtrA3 expression in 172 stage II CRC resection specimens...
July 14, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28715416/signatures-of-inflammation-and-impending-multiple-organ-dysfunction-in-the-hyperacute-phase-of-trauma-a-prospective-cohort-study
#4
Claudia P Cabrera, Joanna Manson, Joanna M Shepherd, Hew D Torrance, David Watson, M Paula Longhi, Mimoza Hoti, Minal B Patel, Michael O'Dwyer, Sussan Nourshargh, Daniel J Pennington, Michael R Barnes, Karim Brohi
BACKGROUND: Severe trauma induces a widespread response of the immune system. This "genomic storm" can lead to poor outcomes, including Multiple Organ Dysfunction Syndrome (MODS). MODS carries a high mortality and morbidity rate and adversely affects long-term health outcomes. Contemporary management of MODS is entirely supportive, and no specific therapeutics have been shown to be effective in reducing incidence or severity. The pathogenesis of MODS remains unclear, and several models are proposed, such as excessive inflammation, a second-hit insult, or an imbalance between pro- and anti-inflammatory pathways...
July 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28712160/perspectives-on-childhood-resilience-among-the-aboriginal-community-an-interview-study
#5
Christian Young, Allison Tong, Janice Nixon, Peter Fernando, Deanna Kalucy, Simone Sherriff, Kathleen Clapham, Jonathan C Craig, Anna Williamson
OBJECTIVE: To describe Aboriginal community members' perspectives on the outcomes and origins of resilience among Aboriginal children. METHODS: Face-to-face interviews were conducted with 36 Aboriginal adults (15 health service professionals, 8 youth workers and 13 community members) at two urban and one regional Aboriginal Community Controlled Health Service in New South Wales. Interviews were transcribed and analysed thematically. RESULTS: We identified six themes: withstanding risk (displaying normative development, possessing inner fortitude); adapting to adversity (necessary endurance, masking inner vulnerabilities); positive social influences (secure family environments, role modelling healthy behaviours and relationships); instilling cultural identity (investing in Aboriginal knowledge, building a strong cultural self-concept); community safeguards (offering strategic sustainable services, holistic support, shared responsibility, providing enriching opportunities); and personal empowerment (awareness of positive pathways, developing self-respect, fostering positive decision making)...
July 16, 2017: Australian and New Zealand Journal of Public Health
https://www.readbyqxmd.com/read/28705220/the-role-of-sports-clubs-in-helping-older-people-to-stay-active-and-prevent-frailty-a-longitudinal-mediation-analysis
#6
Paul Watts, Elizabeth Webb, Gopalakrishnan Netuveli
BACKGROUND: Frailty is a common syndrome in older adults characterised by increased vulnerability to adverse health outcomes as a result of decline in functional and physiological measures. Frailty predicts a range of poor health and social outcomes and is associated with increased risk of hospital admission. The health benefits of sport and physical activity and the health risks of inactivity are well known. However, less is known about the role of sports clubs and physical activity in preventing and managing frailty in older adults...
July 14, 2017: International Journal of Behavioral Nutrition and Physical Activity
https://www.readbyqxmd.com/read/28705116/alex3-suppresses-non-small-cell-lung-cancer-invasion-via-akt-slug-e-cadherin-pathway
#7
Jiang Du, Xiupeng Zhang, Haijing Zhou, Yuan Miao, Yong Han, Qiang Han, Enhua Wang
Alex3, is a newly identified mitochondrial protein, regulates mitochondrial dynamics and is involved in neural development. However, its expression pattern and clinicopathological relevance in human tumors are still unclear. In this study, Immunohistochemistry assay was performed in 109 cases of lung cancer samples and found that Alex 3 expression in lung cancer tissues was significantly lower than adjacent normal lung tissues (28.4% vs 52.6%, p < 0.001). Sequent statistical analysis indicated that negative Alex3 expression was significantly associated with advanced tumor-node-metastasis stages (p = 0...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28704660/pathway-analysis-of-systemic-transcriptome-responses-to-injected-polystyrene-particles-in-zebrafish-larvae
#8
Wouter J Veneman, Herman P Spaink, Nadja R Brun, Thijs Bosker, Martina G Vijver
Microplastics are a contaminant of emergent concern in the environment, however, to date there is a limited understanding on their movement within organisms and the response of organisms. In the current study zebrafish embryos at different development stages were exposed to 700nm fluorescent polystyrene (PS) particles and the response pathway after exposure was investigated using imaging and transcriptomics. Our results show limited spreading of particles within the larvae after injection during the blastula stage...
July 4, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28704568/correction-tissue-factor-pathway-inhibitor-for-prediction-of-placenta-mediated-adverse-pregnancy-outcomes-in-high-risk-women-angiopred-study
#9
Aurélie Di Bartolomeo, Céline Chauleur, Brigitte Tardy, Michèle Piot, Jean-Christophe Gris, Céline Chapelle, Edouard Noblot, Silvy Laporte, Tiphaine Raia-Barjat
[This corrects the article DOI: 10.1371/journal.pone.0173596.].
2017: PloS One
https://www.readbyqxmd.com/read/28704465/lipoprotein-a-in-patients-with-aortic-stenosis-insights-from-cardiovascular-magnetic-resonance
#10
Vassilios S Vassiliou, Paul D Flynn, Claire E Raphael, Simon Newsome, Tina Khan, Aamir Ali, Brian Halliday, Annina Studer Bruengger, Tamir Malley, Pranev Sharma, Subothini Selvendran, Nikhil Aggarwal, Anita Sri, Helen Berry, Jackie Donovan, Willis Lam, Dominique Auger, Stuart A Cook, Dudley J Pennell, Sanjay K Prasad
BACKGROUND: Aortic stenosis is the most common age-related valvular pathology. Patients with aortic stenosis and myocardial fibrosis have worse outcome but the underlying mechanism is unclear. Lipoprotein(a) is associated with adverse cardiovascular risk and is elevated in patients with aortic stenosis. Although mechanistic pathways could link Lipoprotein(a) with myocardial fibrosis, whether the two are related has not been previously explored. In this study, we investigated whether elevated Lipoprotein(a) was associated with the presence of myocardial replacement fibrosis...
2017: PloS One
https://www.readbyqxmd.com/read/28696913/linking-physiological-parameters-to-perturbations-in-the-human-exposome-environmental-exposures-modify-blood-pressure-and-lung-function-via-inflammatory-cytokine-pathway
#11
Matthew A Stiegel, Joachim D Pleil, Jon R Sobus, Tina Stevens, Michael C Madden
Human biomonitoring is an indispensable tool for evaluating the systemic effects derived from external stressors including environmental pollutants, chemicals from consumer products, and pharmaceuticals. The aim of this study was to explore consequences of environmental exposures to diesel exhaust (DE) and ozone (O3) and ultimately to interpret these parameters from the perspective of in vitro to in vivo extrapolation. In particular, the objective was to use cytokine expression at the cellular level as a biomarker for physiological systemic responses such as blood pressure and lung function at the systemic level...
July 11, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28695261/molecular-mechanisms-of-crude-oil-developmental-toxicity-in-fish
#12
John P Incardona
With major oil spills in Korea, the United States, and China in the past decade, there has been a dramatic increase in the number of studies characterizing the developmental toxicity of crude oil and its associated polycyclic aromatic compounds (PACs). The use of model fish species with associated tools for genetic manipulation, combined with high throughput genomics techniques in nonmodel fish species, has led to significant advances in understanding the cellular and molecular bases of functional and morphological defects arising from embryonic exposure to crude oil...
July 2017: Archives of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/28694387/inhibition-of-autophagy-limits-vertical-transmission-of-zika-virus-in-pregnant-mice
#13
Bin Cao, Lindsay A Parnell, Michael S Diamond, Indira U Mysorekar
Zika virus (ZIKV) infection during pregnancy leads to devastating fetal outcomes, including intrauterine growth restriction and microcephaly. Greater understanding of mechanisms underlying ZIKV maternal-fetal transmission is needed to develop new therapeutic interventions. Here, we define an important role for the autophagy pathway in ZIKV vertical transmission. ZIKV infection induced autophagic activity in human trophoblasts and pharmacological inhibition limited ZIKV infectivity. Furthermore, deficiency in an essential autophagy gene, Atg16l1, in mice limited ZIKV vertical transmission and placental and fetal damage and overall improved placental and fetal outcomes...
July 10, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28693416/whole-transcriptome-analysis-delineates-the-human-placenta-gene-network-and-its-associations-with-fetal-growth
#14
Maya A Deyssenroth, Shouneng Peng, Ke Hao, Luca Lambertini, Carmen J Marsit, Jia Chen
BACKGROUND: The placenta is the principal organ regulating intrauterine growth and development, performing critical functions on behalf of the developing fetus. The delineation of functional networks and pathways driving placental processes has the potential to provide key insight into intrauterine perturbations that result in adverse birth as well as later life health outcomes. RESULTS: We generated the transcriptome-wide profile of 200 term human placenta using the Illumina HiSeq 2500 platform and characterized the functional placental gene network using weighted gene coexpression network analysis (WGCNA)...
July 10, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28692011/far-forward-diagnostics-in-toxic-industrial-chemical-and-material-exposure-scenarios-and-biomarker-identification
#15
Charles C Young, Danielle L Ippolito
: This study describes key technical solutions for detecting environmental toxicants and diagnosing adverse health effects in military operational settings as outlined at a symposium cosponsored by the Department of Defense and the Johns Hopkins University-Applied Physics Laboratory (October 27 to 28, 2015). Such technologies are urgently needed in order to provide critical decision-aid tools and prognostic assessment of potential clinical sequelae. This review summarizes the state-of-the-science on (1) prioritization of adverse health effects, (2) existing technologies and diagnostic tools available for use in theater, (3) challenges to advancing diagnostic tools far-forward, and (4) the potential utility of anchoring diagnostic tools to adverse outcome pathways...
July 6, 2017: Journal of Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/28687347/hestat-study-protocol-for-a-phase-ii-iii-randomized-placebo-controlled-single-blind-study-to-evaluate-the-new-hemostatic-agent-tt-173-in-total-knee-arthroplasty
#16
Aránzazu Gonzalez-Osuna, Sebastián Videla, Esther Cánovas, Gerard Urrútia, Santiago Rojas, Ramón López, Jesús Murat, Xavier Aguilera
BACKGROUND: Total knee arthroplasty is associated with postsurgical bleeding that often requires blood transfusion. Several hemostatic treatments have been evaluated with different degree of success. TT-173 is a topical hemostatic agent consisting in yeast derived vesicles containing recombinant tissue factor (rhFT) that activates the extrinsic pathway of coagulation. This trial sought to evaluate the efficacy and safety of TT-173 in total knee arthroplasty. METHODS/DESIGN: This is a phase II/III, sequential, simple blind, randomized, multicenter, placebo controlled and parallel clinical trial that will recruit 189 evaluable patients...
July 4, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28684143/what-s-new-in-clinical-obstetric-anesthesia-in-2015
#17
REVIEW
P E Hess
Each calendar year the Society for Obstetric Anesthesia and Perinatology invites an individual to conduct a review of the medical literature, identifying clinically relevant publications of interest to the obstetric anesthesia provider. This report of that effort covers the publications from 2015 and includes the categories of anesthesia and analgesia, complications of neuraxial procedures, and the effects of anesthesia on the fetus. Neuraxial procedures represent the foundation of obstetric anesthesia; advances in anesthesia and analgesia include novel modes of administration, and refinements in care of the medically complex patient...
March 18, 2017: International Journal of Obstetric Anesthesia
https://www.readbyqxmd.com/read/28681717/clinical-effectiveness-cost-effectiveness-and-acceptability-of-low-intensity-interventions-in-the-management-of-obsessive-compulsive-disorder-the-obsessive-compulsive-treatment-efficacy-randomised-controlled-trial-octet
#18
Karina Lovell, Peter Bower, Judith Gellatly, Sarah Byford, Penny Bee, Dean McMillan, Catherine Arundel, Simon Gilbody, Lina Gega, Gillian Hardy, Shirley Reynolds, Michael Barkham, Patricia Mottram, Nicola Lidbetter, Rebecca Pedley, Jo Molle, Emily Peckham, Jasmin Knopp-Hoffer, Owen Price, Janice Connell, Margaret Heslin, Christopher Foley, Faye Plummer, Christopher Roberts
BACKGROUND: The Obsessive-Compulsive Treatment Efficacy randomised controlled Trial emerged from a research recommendation in National Institute for Health and Care Excellence obsessive-compulsive disorder (OCD) guidelines, which specified the need to evaluate cognitive-behavioural therapy (CBT) treatment intensity formats. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of two low-intensity CBT interventions [supported computerised cognitive-behavioural therapy (cCBT) and guided self-help]: (1) compared with waiting list for high-intensity CBT in adults with OCD at 3 months; and (2) plus high-intensity CBT compared with waiting list plus high-intensity CBT in adults with OCD at 12 months...
June 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28679301/tp53-in-adult-acute-lymphoblastic-leukemia
#19
Silvia Salmoiraghi, Alessandro Rambaldi, Orietta Spinelli
Acute lymphoblastic leukemia (ALL) is characterized by a great biological and clinical heterogeneity. Despite most adult patients enter complete hematologic remission after induction therapy only 40% survive five or more years. Over the last 20 years, the definition of an accurate biologic leukemia profile and the minimal residual disease evaluation in addition to conventional risk criteria led to a significant improvement for the risk stratification. The alterations of the oncosuppressor gene TP53, including deletions, sequence mutations and defect in its expression due to regulatory defects, define a new important predictor of adverse outcome...
July 6, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28675057/multiple-receptors-shape-the-estrogen-response-pathway-and-are-critical-considerations-for-the-future-of-in-vitro-based-risk-assessment-efforts
#20
Michelle M Miller, Patrick D McMullen, Melvin E Andersen, Rebecca A Clewell
Current in life toxicity testing paradigms are being challenged as the future of risk assessment moves towards more comprehensive mode of action/adverse outcome pathway based approaches. In particular, endocrine disruption screening is now a global activity and key initiatives in the United States focus on the use of high throughput in vitro assays to prioritize compounds for further testing of estrogen, androgen or thyroid disruption. Of these pathways, much of the emphasis to date has been on high-throughput methods for estrogenic activity primarily using ligand binding and trans-activation assays...
July 4, 2017: Critical Reviews in Toxicology
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