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Adverse outcome pathway

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https://www.readbyqxmd.com/read/29688820/elucidating-differential-nano-bio-interactions-of-multi-walled-andsingle-walled-carbon-nanotubes-using-subcellular-proteomics
#1
Joseph D T Ndika, Jukka Sund, Harri Alenius, Anne Puustinen
Understanding the relationship between adverse exposure events and specific material properties will facilitate predictive classification of carbon nanotubes (CNTs) according to their mechanisms of action, and a safe-by-design approach for the next generation of CNTs. Mass-spectrometry-based proteomics is a reliable tool to uncover the molecular dynamics of hazardous exposures, yet challenges persist with regards to its limited dynamic range when sampling whole organisms, tissues or cell lysates. Here, the simplicity of the sub-cellular proteome was harnessed to unravel distinctive adverse exposure outcomes at the molecular level, between two CNT subtypes...
April 24, 2018: Nanotoxicology
https://www.readbyqxmd.com/read/29687412/optimal-pharmacological-therapy-in-st-elevation-myocardial-infarction-a-review-a-review-of-antithrombotic-therapies-in-stemi
#2
REVIEW
R S Hermanides, S Kilic, A W J van 't Hof
Antithrombotic therapy is an essential component in the optimisation of clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. There are currently several intravenous anticoagulant drugs available for primary percutaneous coronary intervention. Dual antiplatelet therapy comprising aspirin and P2Y12 inhibitor represents the cornerstone treatment for STEMI. However, these effective treatment strategies may be associated with bleeding complications...
April 23, 2018: Netherlands Heart Journal
https://www.readbyqxmd.com/read/29687077/efficacy-and-outcomes-of-intrathecal-analgesia-as-part-of-an-enhanced-recovery-pathway-in-colon-and-rectal-surgical-patients
#3
Amit Merchea, Jenna K Lovely, Adam K Jacob, Dorin T Colibaseanu, Scott R Kelley, Kellie L Mathis, Grant M Spears, Marianne Huebner, David W Larson
Purpose: Multimodal analgesia is an essential component of an enhanced recovery pathway (ERP). An ERP that includes the use of single-injection intrathecal analgesia (IA) has been shown to decrease morbidity and cost and shorten length of stay (LOS). Limited data exist on safety, feasibility, and the optimal IA regimen. Our objective was to characterize the efficacy, safety, and feasibility of IA within an ERP in a cohort of colorectal surgical patients. Methods: We performed a retrospective review of all consecutive patients aged ≥ 18 years who underwent open or minimally invasive colorectal surgery from October 2012 to December 2013...
2018: Surgery Research and Practice
https://www.readbyqxmd.com/read/29685207/psychiatric-benefits-of-lithium-in-water-supplies-may-be-due-to-protection-from-the-neurotoxicity-of-lead-exposure
#4
Eric E Brown, Philip Gerretsen, Bruce Pollock, Ariel Graff-Guerrero
INTRODUCTION: Lithium is a medication used to treat bipolar disorder and may also prevent cognitive decline and suicide. Lithium is also found naturally, in levels well below clinical doses, in drinking water worldwide, and levels have been inversely associated with rates of psychiatric disorders. Lead (Pb) is another element in the environment but is a toxin of public health concern. Negative effects of chronic lead exposure and possible benefits of environmental lithium exposure appear complementary...
June 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29684431/an-adverse-outcome-pathway-aop-for-forestomach-tumors-induced-by-non-genotoxic-initiating-events
#5
Deborah M Proctor, Mina Suh, Grace Chappell, Susan J Borghoff, Chad M Thompson, Karin Wiench, Lavorgie Finch, Robert Ellis-Hutchings
The utility of rodent forestomach tumor data for hazard and risk assessment has been examined for decades because humans do not have a forestomach, and these tumors occur by varying modes of action (MOAs). We have used the MOA for ethyl acrylate (EA) to develop an Adverse Outcome Pathway (AOP) for forestomach tumors caused by non-genotoxic initiating events. These tumors occur secondary to site of contact induced epithelial cytotoxicity and regenerative repair-driven proliferation. For EA, the critical initiating event (IE) is epithelial cytotoxicity, and supporting key events (KEs) at the cellular and tissue level are increased cell proliferation (KE1) resulting in sustained hyperplasia (KE2), with the adverse outcome of forestomach papillomas and carcinomas...
April 20, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29682628/the-adverse-outcome-pathway-a-multifaceted-framework-supporting-21-st-century-toxicology
#6
Gerald T Ankley, Stephen W Edwards
The adverse outcome pathway (AOP) framework serves as a knowledge assembly, interpretation, and communication tool designed to support the translation of pathway-specific mechanistic data into responses relevant to assessing and managing risks of chemicals to human health and the environment. As such, AOPs facilitate the use of data streams often not employed by risk assessors, including information from in silico models, in vitro assays and short-term in vivo tests with molecular/biochemical endpoints. This translational capability can increase the capacity and efficiency of safety assessments both for single chemicals and chemical mixtures...
June 1, 2018: Current Opinion in Toxicology
https://www.readbyqxmd.com/read/29676641/toxic-and-genomic-influences-of-inhaled-nanomaterials-as-a-basis-for-predicting-adverse-outcome
#7
Penny Nymark, Pekka Kohonen, Vesa Hongisto, Roland C Grafström
An immense variety of different types of engineered nanomaterials are currently being developed and increasingly applied to consumer products. Importantly, engineered nanomaterials may pose unexplored adverse health effects because of their small size. Particularly in occupational settings, the dustiness of certain engineered nanomaterials involves risk of inhalation and influences on lung function. These facts call for quick and cost-effective safety testing practices, such as that obtained through multiparametric high-throughput screening using cultured human lung cells...
April 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29675582/multifunctional-opioid-ligands
#8
Jessica P Anand, Deanna Montgomery
The opioid receptor system plays a major role in the regulation of mood, reward, and pain. The opioid receptors therefore make attractive targets for the treatment of many different conditions, including pain, depression, and addiction. However, stimulation or blockade of any one opioid receptor type often leads to on-target adverse effects that limit the clinical utility of a selective opioid agonist or antagonist. Literature precedent suggests that the opioid receptors do not act in isolation and that interactions among the opioid receptors and between the opioid receptors and other proteins may produce clinically useful targets...
April 20, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29672100/childhood-trauma-pubertal-timing-and-cardiovascular-risk-in-adulthood
#9
Man-Kit Lei, Steven R H Beach, Ronald L Simons
OBJECTIVE: An association between childhood trauma and adult health outcomes has been widely reported, but little is known about the developmental pathways through which childhood trauma influences adult cardiovascular disease (CVD). METHOD: Hypotheses were tested with a sample of 405 African Americans from the Family and Community Health Study (FACHS). Path modeling was used to test our theoretical model. RESULTS: Replicating prior research, exposure to childhood trauma was associated positively with increases in symptoms of CVD risk across young adulthood even after controlling for a variety of health-related and health behavior covariates...
April 19, 2018: Health Psychology: Official Journal of the Division of Health Psychology, American Psychological Association
https://www.readbyqxmd.com/read/29671256/effects-of-growth-hormone-on-pregnancy-rates-of-patients-with-thin-endometrium
#10
N Cui, A-M Li, Z-Y Luo, Z-M Zhao, Y-M Xu, J Zhang, A-M Yang, L-L Wang, G-M Hao, B-L Gao
PURPOSE: To investigate whether growth hormone (GH) could improve pregnancy rates of patients with thin endometrium by clinical study and laboratory experiments. MATERIALS AND METHODS: Ninety-three patients were randomized to either the GH-received group (40) or the routine exogenous administration of estrogens control group (53) for clinical study. The human endometrial carcinoma cell line RL95-2 was used for testing the role of GH with Western blot and real-time PCR by exposure to various concentrations of GH (0...
April 18, 2018: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29670654/toxicities-associated-with-cisplatin-based-chemotherapy-and-radiotherapy-in-long-term-testicular-cancer-survivors
#11
REVIEW
Chunkit Fung, Paul Dinh, Shirin Ardeshir-Rouhani-Fard, Kerry Schaffer, Sophie D Fossa, Lois B Travis
Testicular cancer has become the paradigm of adult-onset cancer survivorship, due to the young age at diagnosis and 10-year relative survival of 95%. This clinical review presents the current status of various treatment-related complications experienced by long-term testicular cancer survivors (TCS) free of disease for 5 or more years after primary treatment. Cardiovascular disease and second malignant neoplasms represent the most common potentially life-threatening late effects. Other long-term adverse outcomes include neuro- and ototoxicity, pulmonary complications, nephrotoxicity, hypogonadism, infertility, and avascular necrosis...
2018: Advances in Urology
https://www.readbyqxmd.com/read/29669405/projecting-age-stratified-risk-of-exposure-to-inland-flooding-and-wildfire-smoke-in-the-united-states-under-two-climate-scenarios
#12
David Mills, Russell Jones, Cameron Wobus, Julia Ekstrom, Lesley Jantarasami, Alexis St Juliana, Allison Crimmins
BACKGROUND: The public health community readily recognizes flooding and wildfires as climate-related health hazards, but few studies quantify changes in risk of exposure, particularly for vulnerable children and older adults. OBJECTIVES: This study quantifies future populations potentially exposed to inland flooding and wildfire smoke under two climate scenarios, highlighting the populations in particularly vulnerable age groups (≤4 y old and ≥65 y old)...
April 17, 2018: Environmental Health Perspectives
https://www.readbyqxmd.com/read/29669403/epigenetic-applications-in-adverse-outcome-pathways-and-environmental-risk-evaluation
#13
Michelle M Angrish, Patrick Allard, Shaun D McCullough, Ingrid L Druwe, Lisa Helbling Chadwick, Erin Hines, Brian N Chorley
BACKGROUND: The epigenome may be an important interface between environmental chemical exposures and human health. However, the links between epigenetic modifications and health outcomes are often correlative and do not distinguish between cause and effect or common-cause relationships. The Adverse Outcome Pathway (AOP) framework has the potential to demonstrate, by way of an inference- and science-based analysis, the causal relationship between chemical exposures, epigenome, and adverse health outcomes...
April 12, 2018: Environmental Health Perspectives
https://www.readbyqxmd.com/read/29664656/maternal-anthropometric-characteristics-and-adverse-pregnancy-outcomes-in-iranian-women-a-confirmation-analysis
#14
Hayedeh Hoorsan, Hamid Alavi Majd, Shahla Chaichian, Abolfazl Mehdizadehkashi, Roza Hoorsan, Meisam Akhlaqghdoust, Yousef Moradi
BACKGROUND: Adverse pregnancy outcome are frequent in developing countries. Pregnancy outcomes are influenced by numerous factors. It seems that maternal anthropometric indices are among the most important factors in this era. The aim of this study was to determine any association between maternal anthropometric characteristics and adverse pregnancy outcomes in Iranian women and provide a predictive model by using factors affecting birth weight (BW) via the pathway analysis. METHODS: This study was performed in Alborz province between September 2014 and December 2016...
February 1, 2018: Archives of Iranian Medicine
https://www.readbyqxmd.com/read/29663434/improvement-in-clinical-outcomes-of-patients-with-heart-failure-and-active-cocaine-use-after-%C3%AE-blocker-therapy
#15
Persio D Lopez, Adedoyin Akinlonu, Tuoyo O Mene-Afejuku, Carissa Dumancas, Mohammed Saeed, Eder H Cativo, Ferdinand Visco, Savi Mushiyev, Gerald Pekler
BACKGROUND: Cocaine use has a high prevalence in the United States and can be associated with significant cardiovascular disease, even in asymptomatic users. β-Adrenergic receptor hyperactivation is the underlying pathophysiologic pathway of cocaine cardiotoxicity. β-Blocker therapy is controversial in patients with active cocaine use. HYPOTHESIS: β-Blocker therapy is associated with clinical improvement in patients with heart failure despite active cocaine use...
April 17, 2018: Clinical Cardiology
https://www.readbyqxmd.com/read/29661777/interferon-stimulated-genes-are-involved-in-cross-resistance-to-radiotherapy-in-tamoxifen-resistant-breast-cancer
#16
Annemarie E M Post, Marcel Smid, Anika Nagelkerke, John W M Martens, Johan Bussink, Fred Cjg Sweep, Paul N Span
PURPOSE: Treatment resistance is a main cause of adverse disease outcome in breast cancer patients. Here we aimed to investigate common features in tamoxifen-resistant and radioresistant breast cancer, since tamoxifen-resistant breast cancer cells are cross-resistant to irradiation in vitro. EXPERIMENTAL DESIGN: RNA sequencing of tamoxifen-resistant and radioresistant breast cancer cells was performed and validated by quantitative PCR. Pathways were further investigated in vitro and in breast cancer patient cohorts to establish their relation with treatment resistance...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29655877/endocrine-and-haemodynamic-changes-in-resistant-hypertension-and-blood-pressure-responses-to-spironolactone-or-amiloride-the-pathway-2-mechanisms-substudies
#17
Bryan Williams, Thomas M MacDonald, Steve V Morant, David J Webb, Peter Sever, Gordon T McInnes, Ian Ford, J Kennedy Cruickshank, Mark J Caulfield, Sandosh Padmanabhan, Isla S Mackenzie, Jackie Salsbury, Morris J Brown
BACKGROUND: In the PATHWAY-2 study of resistant hypertension, spironolactone reduced blood pressure substantially more than conventional antihypertensive drugs. We did three substudies to assess the mechanisms underlying this superiority and the pathogenesis of resistant hypertension. METHODS: PATHWAY-2 was a randomised, double-blind crossover trial done at 14 UK primary and secondary care sites in 314 patients with resistant hypertension. Patients were given 12 weeks of once daily treatment with each of placebo, spironolactone 25-50 mg, bisoprolol 5-10 mg, and doxazosin 4-8 mg and the change in home systolic blood pressure was assessed as the primary outcome...
April 11, 2018: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/29650353/reprint-of-environmental-toxicology-and-omics-a-question-of-sex
#18
Xuefang Liang, April Feswick, Denina Simmons, Christopher J Martyniuk
Molecular initiating events and downstream transcriptional/proteomic responses provide valuable information for adverse outcome pathways, which can be used predict the effects of chemicals on physiological systems. There has been a paucity of research that addresses sex-specific expression profiling in toxicology and due to cost, time, and logistic considerations, sex as a variable has not been widely considered. In response to this deficiency, federal agencies in the United States, Canada, and Europe have highlighted the importance of including sex as a variable in scientific investigations...
April 10, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29643338/causal-pathways-from-blood-pressure-to-larger-qrs-amplitudes-a-mendelian-randomization-study
#19
M Yldau Van Der Ende, Tom Hendriks, Dirk J Van Veldhuisen, Harold Snieder, Niek Verweij, Pim Van Der Harst
Abnormal QRS duration and amplitudes on the electrocardiogram are indicative of cardiac pathology and are associated with adverse outcomes. The causal nature of these associations remains uncertain and could be due to QRS abnormalities being a symptom of cardiac damage rather than a factor on the causal pathway. By performing Mendelian randomization (MR) analyses using summary statistics of genome wide association study consortia with sample sizes between 20,687 and 339,224 individuals, we aimed to determine which cardiovascular risk factors causally lead to changes in QRS duration and amplitude (Sokolow-Lyon, Cornell and 12-leadsum products)...
April 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29628283/weathering-the-storm-a-review-of-pre-pregnancy-stress-and-risk-of-spontaneous-abortion
#20
REVIEW
Tyralynn Frazier, Carol J Rowland Hogue, Elizabeth A Bonney, Kathryn M Yount, Brad D Pearce
The Weathering Effect is a theory that links stress exposure, over the life-course, with racial disparities in reproductive outcomes, through the effects of social adversity on a woman's body. The concept of maternal "weathering" captures cumulative somatic and psychological adversities that can exacerbate the effects of aging. Much of the evidence for weathering comes from observational studies linking self-report measures with reproductive outcomes. The purpose of this review is to explore biological mechanisms that underlie these observations...
March 1, 2018: Psychoneuroendocrinology
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