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Adverse outcome pathway

A M Cardoso, M G Alves, P P Mathur, P F Oliveira, J E Cavaco, L Rato
In the last decades, several studies evidenced a decrease in male fertility in developed countries. Although the aetiology of this trend in male reproductive health remains a matter of debate, environmental compounds that predispose to weight gain, namely obesogens, are appointed as contributors because of their action as endocrine disruptors. Obesogens favour adipogenesis by an imbalance of metabolic processes and can be found virtually everywhere. These compounds easily accumulate in tissues with high lipid content...
October 24, 2016: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Guillaume Passot, Delphine Vaudoyer, Laurent Villeneuve, Florent Wallet, Annie-Claude Beaujard, Gilles Boschetti, Pascal Rousset, Naoual Bakrin, Eddy Cotte, Olivier Glehen
OBJECTIVE: To determine whether a perioperative, standardized clinical pathway could impact the failure-to-rescue rate after cytoreductive surgery (CRS) for peritoneal carcinomatosis (PC) in a tertiary center. SUMMARY OF BACKGROUND DATA: Morbidity and mortality remain significant after CRS for PC. Clinical pathways have been associated with better outcomes after surgery. The failure-to-rescue rate is a useful metric for evaluating quality in surgery. MATERIALS AND METHODS: This study included 666 patients that received CRS for PC between 2009 and 2014...
April 11, 2016: Annals of Surgery
S Manier, J T Powers, A Sacco, S V Glavey, D Huynh, M R Reagan, K Z Salem, M Moschetta, J Shi, Y Mishima, C Roche-Lestienne, X Leleu, A M Roccaro, G Q Daley, I M Ghobrial
MYC is a major oncogenic driver of Multiple Myeloma (MM) and yet almost no therapeutic agents exist that target MYC in MM. Here we report that the let-7 biogenesis inhibitor LIN28B correlates with MYC expression in MM and is associated with adverse outcome. We also demonstrate that the LIN28B/let-7 axis modulates the expression of MYC, itself a let-7 target. Further, perturbation of the axis regulates the proliferation of MM cells in vivo in a xenograft tumor model. RNA sequencing and gene set enrichment analyses of CRISPR-engineered cells further suggest that the LIN28/let-7 axis regulates MYC and cell cycle pathways in MM...
October 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Julia M Goodman, Sylvia Guendelman, Kristen H Kjerulff
BACKGROUND: Most employed American women work during pregnancy and continue working through the month they deliver. Yet, few studies estimate the relationship between maternity leave taken during pregnancy and maternal health. We evaluate the association of antenatal leave (ANL) uptake with obstetric outcomes, assessing the potential role of protective and adverse selection pathways on this relationship. METHODS: We sample 1,740 employed women who delivered at term from the First Baby Study, a prospective cohort of nulliparous women in Pennsylvania...
October 20, 2016: Women's Health Issues: Official Publication of the Jacobs Institute of Women's Health
Nitin Chakravarti, Doina Ivan, Van A Trinh, Isabella C Glitza, Jonathan L Curry, Carlos Torres-Cabala, Michael T Tetzlaff, Roland L Bassett, Victor G Prieto, Wen-Jen Hwu
Ipilimumab, a fully human monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), is the first immune checkpoint inhibitor approved for the treatment of unresectable melanoma on the basis of its overall survival (OS) benefit. However, ipilimumab is associated with significant immune-related adverse events. We hypothesized that biomarker exploration of pretreatment tumor samples and correlation with clinical outcome would enable patient selection with an increased benefit/risk ratio for ipilimumab therapy...
October 20, 2016: Melanoma Research
Peter G Alexander, Karen L Clark, Rocky S Tuan
Limb congenital defects afflict approximately 0.6:1000 live births. In addition to genetic factors, prenatal exposure to drugs and environmental toxicants, represents a major contributing factor to limb defects. Examples of well-recognized limb teratogenic agents include thalidomide, warfarin, valproic acid, misoprostol, and phenytoin. While the mechanism by which these agents cause dymorphogenesis is increasingly clear, prediction of the limb teratogenicity of many thousands of as yet uncharacterized environmental factors (pollutants) remains inexact...
October 21, 2016: Birth Defects Research. Part C, Embryo Today: Reviews
Alexander W Phillips, Barry Dent, Maziar Navidi, Arul Immanuel, S Michael Griffin
OBJECTIVE: The aim of the present study was to determine whether trainee involvement in esophageal cancer resection is associated with adverse patient outcomes. BACKGROUND: Operative experience for surgical trainees is under threat. A number of factors have been implicated in this leading to fewer hours for training. Esophagogastric cancer training is particularly vulnerable due to the publication of individual surgeon results and a perception that dual consultant operating improves patient outcomes...
October 17, 2016: Annals of Surgery
Rose G Radin, Lindsey A Sjaarda, Neil J Perkins, Robert M Silver, Zhen Chen, Laurie L Lesher, Noya Galai, Jean Wactawski-Wende, Sunni L Mumford, Enrique F Schisterman
CONTEXT: Among women with a single, recent pregnancy loss, daily preconception low-dose aspirin (LDA) increased the live birth rate with no effect on pregnancy loss. The mechanism underlying this effect is unclear, but it may work through ovulation. OBJECTIVE: We estimated the effect of LDA on the per-cycle risk of anovulation among eumenorrheic women. DESIGN: The Effects of Aspirin in Gestation and Reproduction trial, a multi-center, randomized, double-blind, placebo-controlled trial of daily LDA on reproductive outcomes...
October 18, 2016: Journal of Clinical Endocrinology and Metabolism
David John Webb
Treatment-resistant hypertension (TRH) is defined as the failure to achieve an office BP target of <140/90 mmHg (<130/80 mmHg in patients with chronic kidney disease (CKD) or diabetes) in patients with hypertension (HT), despite adherence to at least 3 antihypertensive medications at optimal tolerated doses, ideally including a diuretic (Calhoun et al., Circulation 2008). TRH identifies patients with hard-to-treat HT, who might benefit from specialist investigation and treatment. Although some studies put the prevalence of TRH as >10%, these levels may be inflated by white-coat hypertension and poor adherence...
September 2016: Journal of Hypertension
Kelly K Ferguson, David E Cantonwine, Thomas F McElrath, Bhramar Mukherjee, John D Meeker
Bisphenol-A (BPA) exposure occurs commonly and may adversely impact pregnancy. Endocrine disruption is posited as the primary mechanism of action, but oxidative stress and inflammation pathways may also be important. We investigated associations between BPA exposure and oxidative stress and inflammation in 482 pregnant women. Participants were recruited early in pregnancy and provided urine and plasma at up to four visits. We measured total BPA and two biomarkers of oxidative stress (8-hydroxydeoxyguanosine and 8-isoprostane) in urine from each visit...
October 14, 2016: Reproductive Toxicology
Anthony R Mawson, Nola T Radford, Binu Jacob
Stuttering affects about 1% of the general population and from 8 to 11% of children. The onset of persistent developmental stuttering (PDS) typically occurs between 2 and 4 years of age. The etiology of stuttering is unknown and a unifying hypothesis is lacking. Clues to the pathogenesis of stuttering include the following observations: PDS is associated with adverse perinatal outcomes and birth-associated trauma; stuttering can recur or develop in adulthood following traumatic events such as brain injury and stroke; PDS is associated with structural and functional abnormalities in the brain associated with speech and language; and stuttering resolves spontaneously in a high percentage of affected children...
October 18, 2016: European Neurology
Vipin Tyagi, M D Mustafa, Tusha Sharma, B D Banerjee, Rafat S Ahmed, A K Tripathi, Kiran Guleria
BACKGROUND & OBJECTIVES: Preterm birth (PTB) is an important cause of prenatal death, neonatal morbidity and mortality and adult illness. Increased inflammation occurs in normal parturition, and inflammatory cytokines and oxidative stress are found to be higher in PTB cases. The present study was planned to investigate the association of organochlorine pesticides (OCPs) with mRNA expression of inflammatory pathway genes such as tumour necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) in preterm delivery (PTD) cases...
June 2016: Indian Journal of Medical Research
Philip Mease, Iain B McInnes
INTRODUCTION: Psoriatic arthritis (PsA) is an immune-mediated chronic inflammatory arthropathy associated with impaired physical function and reduced quality of life. Biologic therapies that target tumor necrosis factor (anti-TNF) have significantly improved clinical outcomes. Partial, non- and transient responses remain common comprising significant unmet clinical need. New therapies with novel modes of action are urgently required. OBJECTIVES: The interleukin (IL)-17 pathway has recently been attributed a critical role in the pathogenesis of spondyloarthritides...
June 2016: Rheumatol Ther
Xi-Wen Bi, Hua Wang, Wen-Wen Zhang, Jing-Hua Wang, Wen-Jian Liu, Zhong-Jun Xia, Hui-Qiang Huang, Wen-Qi Jiang, Yu-Jing Zhang, Liang Wang
BACKGROUND: Natural killer/T-cell lymphoma (NKTCL) is an Epstein-Barr virus (EBV)-associated, highly aggressive lymphoma. Treatment outcome remains sub-optimal, especially for advanced-stage or relapsed diseases. Programmed cell death receptor 1 (PD-1) and PD ligand 1 (PD-L1) have become promising therapeutic targets for various malignancies, but their role in the pathogenesis and their interactions with EBV in NKTCL remains to be investigated. METHODS: Expression of PD-L1 was measured in NK-92 (EBV-negative) and SNK-6 (EBV-positive) cells by western blot, quantitative real-time PCR and enzyme-linked immunosorbent assay, and flow cytometry, respectively...
October 13, 2016: Journal of Hematology & Oncology
David J Collins, Aine Macnamara, Neil McCarthy
There seems to be general agreement on the importance of challenge for effective development on the athlete pathway. What seems less coherent, however, are ideas on how much, when and how this challenge should be used. Reflecting our own experience as applied practitioners and our ongoing research, we offer a perspective on this work from a practitioner stance. The literature suggests that differences between levels of adult achievement relate more to what performers bring to the challenges than what they experience...
2016: Frontiers in Psychology
Alexander J Shackman, Do P M Tromp, Melissa D Stockbridge, Claire M Kaplan, Rachael M Tillman, Andrew S Fox
Dispositional negativity-the propensity to experience and express more frequent, intense, or enduring negative affect-is a fundamental dimension of childhood temperament and adult personality. Elevated levels of dispositional negativity can have profound consequences for health, wealth, and happiness, drawing the attention of clinicians, researchers, and policymakers. Here, we highlight recent advances in our understanding of the psychological and neurobiological processes linking stable individual differences in dispositional negativity to momentary emotional states...
October 10, 2016: Psychological Bulletin
C Raspé, L Flöther, R Schneider, M Bucher, P Piso
Due to the significantly improved outcome and quality of life of patients with different tumor entities after cytoreductive surgery (CRS) and HIPEC, there is an increasing number of centers performing CRS and HIPEC procedures. As this procedure is technically challenging with potential high morbidity and mortality, respectively, institutional experience also in the anesthetic and intensive care departments is essential for optimal treatment and prevention of adverse events. Clinical pathways have to be developed to achieve also good results in more comorbid patients with border line indications and extensive surgical procedures...
September 28, 2016: European Journal of Surgical Oncology
Thomas Hartung
No abstract text is available yet for this article.
October 8, 2016: Expert Opinion on Drug Metabolism & Toxicology
Rebecca Milsk, Jenna E Cavallin, Elizabeth J Durhan, Kathleen M Jensen, Michael D Kahl, Elizabeth A Makynen, Dalma Martinović-Weigelt, Nathan Mueller, Anthony Schroeder, Daniel L Villeneuve, Gerald T Ankley
The aim of this study was to investigate temporal changes in the hypothalamic-pituitary-gonadal (HPG) axis of fathead minnows (Pimephales promelas) treated with the model androgen receptor (AR) antagonist flutamide. Reproductively-mature fish were exposed in a flow-through test to analytically-confirmed concentrations of either 50 or 500μg flutamide/L for 8 d, followed by an 8-d recovery period in clean water. Fish were sampled at 1, 2, 4 and 8days during each phase of the experiment. Flutamide (500μg/L) caused significant reductions in relative gonad size of the females on day 8 of the exposure and day 1 of the recovery, and reduced expression of secondary sex characteristics in males during the exposure phase of the experiment...
October 1, 2016: Aquatic Toxicology
Juan Ma, Ruibin Li, Guangbo Qu, Huiyu Liu, Bing Yan, Tian Xia, Yajun Liu, Sijin Liu
Carbon nanotubes (CNTs) have promising applications in a wide range of biomedical fields, including imaging, drug/gene delivery and other therapeutics; however, the biosafety concerns of CNTs should be addressed. To date, many reports have documented the toxicological effects on the cells, tissue or organs that are in direct contact with the tubes; however, there is limited evidence to unravel the secondary toxicity upon CNT treatment. Moreover, more effort is needed to gain a definitive understanding of the adverse outcome pathway (AOP) for CNTs, and a pragmatic framework for risk assessment has not been established yet...
September 29, 2016: Nanoscale
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