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Adverse outcome pathway

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https://www.readbyqxmd.com/read/29240775/ornithine-decarboxylase-as-a-therapeutic-target-for-endometrial-cancer
#1
Hong Im Kim, Chad R Schultz, Andrea L Buras, Elizabeth Friedman, Alyssa Fedorko, Leigh Seamon, Gadisetti V R Chandramouli, G Larry Maxwell, André S Bachmann, John I Risinger
Ornithine Decarboxylase (ODC) a key enzyme in polyamine biosynthesis is often overexpressed in cancers and contributes to polyamine-induced cell proliferation. We noted ubiquitous expression of ODC1 in our published endometrial cancer gene array data and confirmed this in the cancer genome atlas (TCGA) with highest expression in non-endometrioid, high grade, and copy number high cancers, which have the worst clinical outcomes. ODC1 expression was associated with worse overall survival and increased recurrence in three endometrial cancer gene expression datasets...
2017: PloS One
https://www.readbyqxmd.com/read/29240761/microorganisms-in-the-human-placenta-are-associated-with-altered-cpg-methylation-of-immune-and-inflammation-related-genes
#2
Martha Scott Tomlinson, Paige A Bommarito, Elizabeth M Martin, Lisa Smeester, Raina N Fichorova, Andrew B Onderdonk, Karl C K Kuban, T Michael O'Shea, Rebecca C Fry
Microorganisms in the placenta have been linked to adverse pregnancy outcomes as well as neonatal illness. Inflammation in the placenta has been identified as a contributing factor in this association, but the underlying biological mechanisms are not yet fully understood. The placental epigenome may serve as an intermediate between placental microbes and inflammation, contributing to adverse outcomes in the offspring. In the present study, genome-wide DNA methylation (n = 486,428 CpG sites) of 84 placentas was analyzed in relation to 16 species of placental microorganisms using samples collected from the Extremely Low Gestation Age Newborns (ELGAN) cohort...
2017: PloS One
https://www.readbyqxmd.com/read/29236470/a-case-study-application-of-the-aggregate-exposure-pathway-aep-and-adverse-outcome-pathway-aop-frameworks-to-facilitate-the-integration-of-human-health-and-ecological-endpoints-for-cumulative-risk-assessment-cra
#3
David E Hines, Stephen Edwards, Rory B Conolly, Annie M Jarabek
Cumulative risk assessment (CRA) methods promote the use of a conceptual site model (CSM) to apportion exposures and integrate risk from multiple stressors. While CSMs may encompass multiple species, evaluating endpoints across taxa can be challenging due to data availability and physiological differences among organisms. Adverse Outcome Pathways (AOPs) describe biological mechanisms leading to adverse outcomes (AOs) by assembling causal pathways with measurable intermediate steps termed key events (KEs), thereby providing a framework for integrating data across species...
December 13, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29230915/periapical-infection-may-affect-birth-outcomes-via-systemic-inflammation
#4
U Harjunmaa, R Doyle, J Järnstedt, S Kamiza, J M Jorgensen, C P Stewart, L Shaw, L Hallamaa, U Ashorn, N Klein, K G Dewey, K Maleta, P Ashorn
OBJECTIVES: Maternal dental periapical infections are associated with preterm birth and intrauterine growth restriction. This study investigates if the association is mediated through bacterial spread from periapical lesions to placenta (direct pathway) or systemic inflammatory reaction (indirect pathway). MATERIALS AND METHODS: We compared birth outcomes in Malawian mothers with and without periapical infection. As markers of a direct pathway, we identified placental bacteria using a 16S rDNA approach, and assessed histological evidence of inflammation in the placenta and amniotic membranes...
December 12, 2017: Oral Diseases
https://www.readbyqxmd.com/read/29230179/transplacental-nutrient-transport-mechanisms-of-intrauterine-growth-restriction-in-rodent-models-and-humans
#5
REVIEW
Elke Winterhager, Alexandra Gellhaus
Although the causes of intrauterine growth restriction (IUGR) have been intensively investigated, important information is still lacking about the role of the placenta as a link from adverse maternal environment to adverse pregnancy outcomes of IUGR and preterm birth. IUGR is associated with an increased risk of cardiovascular, metabolic, and neurological diseases later in life. Determination of the most important pathways that regulate transplacental transport systems is necessary for identifying marker genes as diagnostic tools and for developing drugs that target the molecular pathways...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29228656/increased-pdgfr-beta-and-vegfr-2-protein-levels-are-associated-with-resistance-to-platinum-based-chemotherapy-and-adverse-outcome-of-ovarian-cancer-patients
#6
Stefanie Avril, Yasemin Dincer, Katharina Malinowsky, Claudia Wolff, Sibylle Gündisch, Alexander Hapfelmeier, Melanie Boxberg, Holger Bronger, Karl-Friedrich Becker, Barbara Schmalfeldt
Despite frequent initial response rates of epithelial ovarian cancer to platinum-based chemotherapy the majority of patients develop drug resistance. Our aim was to evaluate differential expression of signaling-pathway proteins in platinum-sensitive versus platinum-resistant primary epithelial ovarian cancer specimens to identify predictive biomarkers for treatment response. 192 patients were studied comprising of independent training (n = 89) and validation (n = 103) cohorts. Full-length proteins were extracted from paraffin-embedded samples including multiple regions per tumor to account for intratumoral heterogeneity...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228154/comparative-transcriptomic-analysis-of-human-placentae-at-term-and-preterm-delivery
#7
Alison G Paquette, Heather M Brockway, Nathan D Price, Louis J Muglia
Purpose: Preterm birth affects 1 out of every 10 infants in the United States, resulting in substantial neonatal morbidity and mortality. Currently, there are few predictive markers and few treatment options to prevent preterm birth. A healthy, functioning placenta is essential to positive pregnancy outcomes. Previous studies have suggested that placental pathology may play a role in preterm birth etiology. Therefore, we tested the hypothesis that preterm placentae may exhibit unique transcriptomic signatures compared to term samples reflective of their abnormal biology leading to this adverse outcome...
December 4, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29226339/development-of-an-artificial-neural-network-model-for-risk-assessment-of-skin-sensitization-using-human-cell-line-activation-test-direct-peptide-reactivity-assay-keratinosens%C3%A2-and-in-silico-structure-alert-parameter
#8
Morihiko Hirota, Takao Ashikaga, Hirokazu Kouzuki
It is important to predict the potential of cosmetic ingredients to cause skin sensitization, and in accordance with the European Union cosmetic directive for the replacement of animal tests, several in vitro tests based on the adverse outcome pathway have been developed for hazard identification, such as the direct peptide reactivity assay, KeratinoSens™ and the human cell line activation test. Here, we describe the development of an artificial neural network (ANN) prediction model for skin sensitization risk assessment based on the integrated testing strategy concept, using direct peptide reactivity assay, KeratinoSens™, human cell line activation test and an in silico or structure alert parameter...
December 10, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29225932/potential-applications-of-telenephrology-to-enhance-global-kidney-care
#9
REVIEW
Mohamed A Osman, Julius Okel, Ikechi G Okpechi, Kailash Jindal, Aminu K Bello
Chronic kidney disease (CKD) is an important public health issue that increasingly affects more patients globally and is associated with adverse clinical consequences with huge economic impact. Effective management of patients with CKD requires delivery of kidney care in a primary care setting where possible and at a higher level with a nephrologist when necessary to improve outcomes. In many instances and for various reasons, it is not possible to follow this pathway of care delivery. With improving telecommunication technologies worldwide, it is hoped that increasing utilisation of electronic communication devices can be used to facilitate kidney care to improve the quality of care delivered to patients, especially those who live in remote regions...
2017: BMJ Global Health
https://www.readbyqxmd.com/read/29225804/angiotensinogen-as-a-biomarker-of-acute-kidney-injury
#10
REVIEW
Sheeba Habeeb Ba Aqeel, Alejandro Sanchez, Daniel Batlle
Early recognition of acute kidney injury (AKI) is critical to prevent its associated complications as well as its progression to long term adverse outcomes like chronic kidney disease. A growing body of evidence from both laboratory and clinical studies suggests that inflammation is a key factor contributing to the progression of AKI regardless of the initiating event. Biomarkers of inflammation are therefore of interest in the evaluation of AKI pathogenesis and prognosis. There is evidence that the renin angiotensin aldosterone system is activated in AKI, which leads to an increase in angiotensin II (Ang II) formation within the kidney...
December 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/29224359/a-reduced-transcriptome-approach-to-assess-environmental-toxicants-using-zebrafish-embryo-test
#11
Pingping Wang, Pu Xia, Jianghua Yang, Zhihao Wang, Ying Peng, Wei Shi, Daniel L Villeneuve, Hongxia Yu, Xiaowei Zhang
Omics approaches can monitor responses and alterations of biological pathways at genome-scale, which are useful to predict potential adverse effects by environmental toxicants. However, high throughput application of transcriptomics in chemical assessment is limited due to the high cost and lack of "standardized" toxicogenomic methods. Here, a reduced zebrafish transcriptome (RZT) approach was developed to represent the whole transcriptome and to profile bioactivity of chemical and environmental mixtures in zebrafish embryo...
December 11, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29217695/harmonizing-methods-for-estimating-the-impact-of-contraceptive-use-on-unintended-pregnancy-abortion-and-maternal-health
#12
Ian Askew, Michelle Weinberger, Aisha Dasgupta, Jacqueline Darroch, Ellen Smith, John Stover, Melanie Yahner
Estimates of the potential impacts of contraceptive use on averting unintended pregnancies, total and unsafe abortions, maternal deaths, and newborn, infant, and child deaths provide evidence of the value of investments in family planning programs and thus are critically important for policy makers, donors, and advocates alike. Several research teams have independently developed mathematical models that estimate the number of adverse health outcomes averted due to contraceptive use. However, each modeling approach was designed for different purposes, and as such the methodological assumptions, data inputs, and mathematical algorithms initially used in each model differed; consequently, the models did not produce comparable estimates for the same outcome indicators...
December 7, 2017: Global Health, Science and Practice
https://www.readbyqxmd.com/read/29211833/a-prospective-phase-ii-study-of-combined-androgen-blockade-in-patients-with-androgen-receptor-positive-metastatic-or-locally-advanced-unresectable-salivary-gland-carcinoma
#13
C Fushimi, Y Tada, H Takahashi, T Nagao, H Ojiri, T Masubuchi, T Matsuki, K Miura, D Kawakita, H Hirai, E Hoshino, S Kamata, T Saotome
Background: There is no standard first-line chemotherapy for recurrent/metastatic or unresectable locally advanced salivary gland carcinoma (SGC). Patients and methods: We conducted a single institution, open-label, single arm, phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)-positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of 3.75 mg every 4 weeks. Bicalutamide was administered orally at a daily dose of 80 mg...
December 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29209747/an-adverse-outcome-pathway-for-parkinsonian-motor-deficits-associated-with-mitochondrial-complex-i-inhibition
#14
REVIEW
Andrea Terron, Anna Bal-Price, Alicia Paini, Florianne Monnet-Tschudi, Susanne Hougaard Bennekou, Marcel Leist, Stefan Schildknecht
Epidemiological studies have observed an association between pesticide exposure and the development of Parkinson's disease, but have not established causality. The concept of an adverse outcome pathway (AOP) has been developed as a framework for the organization of available information linking the modulation of a molecular target [molecular initiating event (MIE)], via a sequence of essential biological key events (KEs), with an adverse outcome (AO). Here, we present an AOP covering the toxicological pathways that link the binding of an inhibitor to mitochondrial complex I (i...
December 5, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29205204/mthfr-ts-and-xrcc1-genetic-variants-may-affect-survival-in-patients-with-myelodysplastic-syndromes-treated-with-supportive-care-or-azacitidine
#15
G Visani, F Loscocco, A Ruzzo, S Galimberti, F Graziano, M T Voso, E Giacomini, C Finelli, E Ciabatti, E Fabiani, S Barulli, A Volpe, D Magro, P Piccaluga, F Fuligni, M Vignetti, P Fazi, A Piciocchi, E Gabucci, M Rocchi, M Magnani, A Isidori
We evaluated the impact of genomic polymorphisms in folate-metabolizing, DNA synthesis and DNA repair enzymes on the clinical outcome of 108 patients with myelodysplastic syndromes (MDS) receiving best supportive care (BSC) or azacitidine. A statistically significant association between methylenetetrahydrofolate reductase (MTHFR) 677T/T, thymidylate synthase (TS) 5'-untranslated region (UTR) 3RG, TS 3'-UTR -6 bp/-6 bp, XRCC1 399G/G genotypes and short survival was found in patients receiving BSC by multivariate analysis (P<0...
December 5, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29194005/patient-characteristics-length-of-stay-and-functional-improvement-for-schizophrenia-spectrum-disorders-a-population-study-of-inpatient-care-in-ontario-2005-to-2015
#16
Sheng Chen, April Collins, Kelly Anderson, Kwame McKenzie, Sean Kidd
OBJECTIVES: Schizophrenia and associated illnesses account for a large proportion of mental illness burden and health care expenditures, with the majority of expense involving inpatient care. To date, the literature exploring factors associated with length of stay (LOS) and functional improvement during inpatient care is underdeveloped. In response, this study examined the association between patient characteristics, LOS, and functional improvement using Ontario Mental Health Reporting System (OMHRS) data from 2005 to 2015...
December 2017: Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
https://www.readbyqxmd.com/read/29183839/the-role-of-ethyl-acrylate-induced-gsh-depletion-in-the-rodent-forestomach-and-its-impact-on-mtd-and-in-vivo-genotoxicity-in-developing-an-adverse-outcome-pathway-aop
#17
R Ellis-Hutchings, J Giuliani, M Hayashi, S Masumori, E L McClymont, S Murphy, K Wiench
Adverse outcome pathways (AOP) and mode of action (MOA) frameworks help evaluate the toxicity findings of animal studies and their relevance to humans. To effectively use these tools to improve hazard identification and risk assessments for ethyl acrylate (EA), knowledge gaps in metabolism and genotoxicity were identified and addressed. For EA, hypothesized early key events relate to its irritation potential: concentration dependent irritation and cytotoxicity, progressing to regenerative proliferation and forestomach carcinogenicity after repeated oral bolus application in rodents...
November 25, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29182751/adverse-childhood-experiences-and-access-and-utilization-of-health-care
#18
Héctor E Alcalá, Annalyn Valdez-Dadia, Ondine S von Ehrenstein
Background: Adverse childhood experiences (ACEs) have been associated with a variety of negative health outcomes. However, the association between ACEs and access and utilization of health care have been largely ignored. Methods: This study examined data from the 2011 Behavioral Risk Factor Surveillance System (N = 101 527). We conducted logistic regression analyses, with nine ACEs as independent variables, in relation to the odds of being insured, having a personal health care provider and receiving a physician checkup in the past year...
November 22, 2017: Journal of Public Health
https://www.readbyqxmd.com/read/29179034/effects-of-exposure-to-water-disinfection-by-products-in-a-swimming-pool-a-metabolome-wide-association-study
#19
Karin van Veldhoven, Pekka Keski-Rahkonen, Dinesh K Barupal, Cristina M Villanueva, Laia Font-Ribera, Augustin Scalbert, Barbara Bodinier, Joan O Grimalt, Christian Zwiener, Jelle Vlaanderen, Lützen Portengen, Roel Vermeulen, Paolo Vineis, Marc Chadeau-Hyam, Manolis Kogevinas
BACKGROUND: Exposure to disinfection by-products (DBPs) in drinking water and chlorinated swimming pools are associated with adverse health outcomes, but biological mechanisms remain poorly understood. OBJECTIVES: Evaluate short-term changes in metabolic profiles in response to DBP exposure while swimming in a chlorinated pool. MATERIALS AND METHODS: The PISCINA-II study (EXPOsOMICS project) includes 60 volunteers swimming 40min in an indoor pool...
November 24, 2017: Environment International
https://www.readbyqxmd.com/read/29178980/ambient-ultrafine-particles-activate-human-monocytes-effect-of-dose-differentiation-state-and-age-of-donors
#20
Bishop Bliss, Kevin Ivan Tran, Constantinos Sioutas, Arezoo Campbell
Exposure to ambient particulate matter (PM) has been linked to adverse pulmonary and cardiovascular health effects. Activation of both inflammatory and oxidative stress pathways has been observed and may be a probable cause of these outcomes. We tested the hypothesis that in human monocytes, PM-induced oxidative and inflammatory responses are interrelated. A human monocytic cell line (THP-1) was used to determine if dose and differentiation state plays a role in the cellular response after a 24hr exposure to particles...
November 24, 2017: Environmental Research
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