Read by QxMD icon Read

Adverse outcome pathway

Laura H Rossi, Janine Ezendam
Over the recent years development toward assessing skin sensitization hazard has moved toward non-animal testing methods. These methods are based on the key events as described in the OECD Adverse Outcome Pathway (AOP) for skin sensitization initiated by covalent binding to proteins. As these individual methods address mainly one mechanistic event (key event) in the initiation of skin sensitization, combination of different methods are needed to conclude on the skin sensitization hazard. Validated and regulatory adopted (EU and OECD) in chemico/in vitro methods are available for KEs 1-3 and are presented here...
2018: Methods in Molecular Biology
Dario Maglione, Marcella Caputi, Benedetta Moretti, Simona Scaini
BACKGROUND: In the last years, several studies focused on the role of Gene-Environment interactions (GxE) in influencing psychopathological outcomes among maltreated children and adolescents. These studies analysed the effect of different genetic variations. AIMS: The aim of the present review is to provide an overview of studies investigating GxE effects among maltreated children and adolescents. METHODS AND PROCEDURES: A systematic literature review was performed by using the following keywords: "Child maltreatment" and "GxE", "Child maltreatment" and "Psychopathology", "Gene-Environment interaction", "Gene-environment correlation", "GxE and psychopathology", "Childhood trauma" and "Psychiatric symptoms", "Early adverse life events", "Early life stress", "Antisocial behaviour", "Depression", "Internalizing symptoms", through the following electronic databases: PubMed, Scopus and PsycINFO, from 2006 to 2017, finding a total of 31 papers...
June 20, 2018: Research in Developmental Disabilities
S E Baldeweg, S Ball, A Brooke, H K Gleeson, M J Levy, M Prentice, J Wass
Cranial diabetes insipidus (CDI) is a treatable chronic condition that can potentially develop into a life-threatening medical emergency. CDI is due to the relative or absolute lack of the posterior pituitary hormone vasopressin (AVP), also known as anti-diuretic hormone. AVP deficiency results in uncontrolled diuresis. Complete deficiency can lead to polyuria exceeding 10 L/24 h. Given a functioning thirst mechanism and free access to water, patients with CDI can normally maintain adequate fluid balance through increased drinking...
July 2018: Endocrine Connections
Jennifer E Dominguez, Ashraf S Habib, Andrew D Krystal
Obesity is prevalent among pregnant women in the United States; 15-20% of obese pregnant women have obstructive sleep apnea. The prevalence of obstructive sleep apnea increases along with body mass index, age and in the presence of other co-morbidities. Untreated obstructive sleep apnea in women is associated with a range of cardiovascular, pulmonary and metabolic co-morbidities; recent studies suggest that women with obstructive sleep apnea in pregnancy may be at significantly greater risk of entering pregnancy with chronic hypertension and/or of developing hypertensive disorders of pregnancy: gestational hypertension; preeclampsia; or eclampsia...
May 28, 2018: Sleep Medicine Reviews
Eleonora Iob, Clemens Kirschbaum, Andrew Steptoe
INTRODUCTION: While positive social support is associated with lower prevalence of disease and better treatment outcomes, negative social relationships can instead have unfavourable consequences for several physical and mental health conditions. However, the specific mechanisms by which this nexus might operate remain poorly understood. Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity owing to psychosocial stress has been proposed as a potential pathway underlying the link between social support and health...
June 12, 2018: Psychoneuroendocrinology
Jason P Stopyra, Robert F Riley, Brian C Hiestand, Gregory B Russell, James W Hoekstra, Cedric W Lefebvre, Bret A Nicks, David M Cline, Kim L Askew, Stephanie B Elliott, David M Herrington, Gregory L Burke, Chadwick D Miller, Simon A Mahler
OBJECTIVE: To determine the impact of the HEART Pathway on healthcare utilization and safety outomes at 1 year in patients with acute chest pain. METHODS: Adult Emergency Department (ED) patients with chest pain (N=282) were randomized to the HEART Pathway or usual care. In the HEART Pathway arm, ED providers used the HEART score and troponin measures (0 and 3-hours) to risk stratify patients. Usual care was based on ACC/AHA guidelines. Major adverse cardiac events (MACE: cardiac death, myocardial infarction [MI], or coronary revascularization), objective testing (stress testing or coronary angiography), and cardiac hospitalizations and ED visits were assessed at 1 year...
June 19, 2018: Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine
Mario Di Gioacchino, Luca Di Giampaolo, Alessia Gatta, Annalisa Flacco, Rocco Mangifesta, Qiao Niu, Claudia Petrarca
OBJECTIVES: The first essential aspect for the prevention of occupational allergy is related to the accurate allergen identification and characterization. At present many efforts are made to characterize the potential for a chemical to be a sensitizing agent. METHODS: 'Omics' show great promise to identify key cellular and molecular events relevant to development of an adverse outcome pathway for respiratory sensitizers. One approach that shows promise is based on the measurement of the peptide reactivity of chemicals; the potential to form stable associations with protein/peptide being a key requirement for the induction of sensitization...
November 2017: Giornale Italiano di Medicina del Lavoro Ed Ergonomia
Benjamin M Nowotny, Erwin Loh, Katherine Lorenz, Euan M Wallace
Learning from medical errors to prevent their recurrence is an important component of any healthcare system's quality and safety improvement functions. Traditionally, this been achieved principally from review of adverse clinical outcomes. The opportunity to learn systematically and in a system manner from patient complaints and litigation has been less well harnessed. Herein we describe the pathways and processes for both patient complaints and medicolegal claims in Victoria, and Australia more broadly, and assess the potential for these to be used for system improvement...
June 19, 2018: Australian Health Review: a Publication of the Australian Hospital Association
Helen Richmond, Clare Lait, Cynthia Srikesavan, Esther Williamson, Jane Moser, Meredith Newman, Lauren Betteley, Beth Fordham, Sophie Rees, Sarah E Lamb, Julie Bruce
BACKGROUND: Musculoskeletal shoulder problems are common after breast cancer treatment. There is some evidence to suggest that early postoperative exercise is safe and may improve shoulder function. We describe the development and delivery of a complex intervention for evaluation within a randomised controlled trial (RCT), designed to target prevention of musculoskeletal shoulder problems after breast cancer surgery (The Prevention of Shoulder Problems Trial; PROSPER). METHODS: A pragmatic, multicentre RCT to compare the clinical and cost-effectiveness of best practice usual care versus a physiotherapy-led exercise and behavioural support intervention in women at high risk of shoulder problems after breast cancer treatment...
June 18, 2018: BMC Health Services Research
István Gera
Data from epidemiological and clinical studies published in the past two decades indicate certain association between periodontal disease and increased risk for preterm birth or low birth weight. Although the strength of those observed associations is weak, periodontitis today is considered as one of the potentially modifiable risk factors for adverse pregnancy outcomes. The aims of the publication are to summarize the epidemiological and clinical evidence for the impact of periodontal disease on adverse pregnancy outcomes and to make an attempt to overview the potential biological mechanism behind this association...
June 2018: Orvosi Hetilap
Amy J Clippinger, David Allen, Holger Behrsing, Kelly A BéruBé, Michael B Bolger, Warren Casey, Michael DeLorme, Marianna Gaça, Sean C Gehen, Kyle Glover, Patrick Hayden, Paul Hinderliter, Jon A Hotchkiss, Anita Iskandar, Brian Keyser, Karsta Luettich, Lan Ma-Hock, Anna G Maione, Patrudu Makena, Jodie Melbourne, Lawrence Milchak, Sheung P Ng, Alicia Paini, Kathryn Page, Grace Patlewicz, Pilar Prieto, Hans Raabe, Emily N Reinke, Clive Roper, Jane Rose, Monita Sharma, Wayne Spoo, Peter S Thorne, Daniel M Wilson, Annie M Jarabek
New approaches are needed to assess the effects of inhaled substances on human health. These approaches will be based on mechanisms of toxicity, an understanding of dosimetry, and the use of in silico modeling and in vitro test methods. In order to accelerate wider implementation of such approaches, development of adverse outcome pathways (AOPs) can help identify and address gaps in our understanding of relevant parameters for model input and mechanisms, and optimize non-animal approaches that can be used to investigate key events of toxicity...
June 13, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Alexander Edwards, Lottie Roscoe, Christopher Longmore, Fiona Bailey, Bushra Sim, Carol Treasure
Skin sensitisers are substances that can elicit allergic responses following skin contact and the process by which this occurs is described as skin sensitisation. Skin sensitisation is defined as a series of key events, that form an adverse outcome pathway (AOP). Key event three in the AOP is dendritic cell activation that can be modelled by the human Cell Line Activation Test (h-CLAT) and is typified by changes in cell surface markers CD54 and CD86 in dendritic cells. The h-CLAT is accepted at a regulatory level (OECD Test-Guideline (TG)442E) and can be used to assess skin sensitisation potential as part of an integrated approach to testing and assessment (IATA)...
June 13, 2018: ALTEX
P Naidoo, R N Naidoo, P Ramkaran, S Muttoo, K Asharam, A A Chuturgoon
OBJECTIVE: Nitrogen oxide (NOx) pollution and human immunodeficiency virus (HIV)/AIDS intensify inflammation during pregnancy and linked with adverse birth outcomes (ABOs). MicroRNA (miRNA)-146a plays a crucial role in regulating inflammation in the NF-κB pathway. The G/C rs2910164 dampens miRNA-146a activity and linked with inflammatory diseases. The present study investigated whether HIV/AIDS and NOx exposure throughout pregnancy further intensifies ABO in Black South African women genotyped for the rs2910164...
January 1, 2018: Human & Experimental Toxicology
Katja L Vogt, Charlotte Summers, Edwin R Chilvers, Alison M Condliffe
The activation status of neutrophils can cycle from basal through primed to fully activated ('green-amber-red'), and at least in vitro, primed cells can spontaneously revert to a near basal phenotype. This broad range of neutrophil responsiveness confers extensive functional flexibility, allowing neutrophils to respond rapidly and appropriately to varied and evolving threats throughout the body. Primed and activated cells display dramatically enhanced bactericidal capacity (including augmented respiratory burst activity, degranulation and longevity), but this enhancement also confers the capacity for significant unintended tissue injury...
June 13, 2018: European Journal of Clinical Investigation
Anupriya Tripathi, Alexey V Melnik, Jin Xue, Orit Poulsen, Michael J Meehan, Gregory Humphrey, Lingjing Jiang, Gail Ackermann, Daniel McDonald, Dan Zhou, Rob Knight, Pieter C Dorrestein, Gabriel G Haddad
Obstructive sleep apnea (OSA) is a common disorder characterized by episodic obstruction to breathing due to upper airway collapse during sleep. Because of the episodic airway obstruction, intermittently low O2 (hypoxia) and high CO2 (hypercapnia) ensue. OSA has been associated with adverse cardiovascular and metabolic outcomes, although data regarding potential causal pathways are still evolving. As changes in inspired O2 and CO2 can affect the ecology of the gut microbiota and the microbiota has been shown to contribute to various cardiometabolic disorders, we hypothesized that OSA alters the gut ecosystem, which, in turn, exacerbates the downstream physiological consequences...
May 2018: MSystems
Ya Zhang, Xiangxiang Zhou, Ying Li, Yangyang Xu, Kang Lu, Peipei Li, Xin Wang
TP53 pathway defects contributed to therapy resistance and adverse clinical outcome in chronic lymphocytic leukemia (CLL), which represents an unmet clinical need with few therapeutic options. Maternal embryonic leucine zipper kinase (MELK) is a novel oncogene, which plays crucial roles in mitotic progression and stem cell maintenance. OTSSP167, an orally administrated inhibitor targeting MELK, is currently in a phase I/II clinical trial in patients with advanced breast cancer and acute myeloid leukemia. Yet, no investigation has been elucidated to date regarding the oncogenic role of MELK and effects of OTSSP167 in chronic lymphocytic leukemia (CLL)...
June 12, 2018: Oncogene
Dharmesh Gopalakrishnan, Vadim S Koshkin, Moshe C Ornstein, Athanasios Papatsoris, Petros Grivas
Bladder cancer is the sixth most common cancer in the US and most tumors have urothelial (transitional cell) histology. Platinum-based chemotherapy has long been the standard of care in advanced disease, but long-term outcomes have largely remained poor. Since the peak incidence of bladder cancer is in the eighth decade of life and beyond, medical comorbidities may often limit the use of chemotherapy. Immune checkpoint inhibitors with their favorable toxicity profiles and notable antitumor activity have ushered in a new era in the treatment of advanced urothelial cancer (UC) with five agents targeting the PD-1/PD-L1 pathway being recently approved by the US Food and Drug administration...
2018: Therapeutics and Clinical Risk Management
Erin T Carey, Janelle K Moulder
Enhanced recovery after surgery (ERAS) programs are a multimodal approach to optimize the surgical experience. Intraoperative and postoperative pain management is essential because the stress of surgery results in significant neurohormonal and metabolic shifts that can influence patient analgesia. Enhanced recovery after surgery programs address the physiologic and psychological factors that contribute to pain outcomes and overall satisfaction scores. A multimodal approach to recovery throughout the perioperative surgical experience is representative of successful pathways...
June 6, 2018: Obstetrics and Gynecology
Juergen Pauluhn
This paper compares the pulmonary kinetics of inhaled nano-CeO2 from two published repeated inhalation studies of 13-week duration in rats. This database was used to predict the outcome of a 2-year chronic inhalation study with a focus on the no observed adverse effect level (NOAEL) and range of conditions causing kinetic lung overload up to and beyond the maximum tolerated dose (MTD). Modeling identified nano-CeO2 to be typical poorly soluble, low-toxicity particles (PSLTs), although even partial dissolution may lead to interactions with pulmonary surfactants, eventually resulting in pulmonary phospholipidosis and fibrosis...
June 6, 2018: Regulatory Toxicology and Pharmacology: RTP
Leonie Segal, Sophie Guy, Matthew Leach, Aaron Groves, Catherine Turnbull, Gareth Furber
BACKGROUND: High-quality mental health services for infants, children, adolescents, and their families can improve outcomes for children exposed to early trauma. We sought to estimate the workforce needed to deliver tertiary-level community mental health care to all infants, children, adolescents, and their families in need using a generalisable model, applied to South Australia (SA). METHODS: Workforce estimates were determined using a workforce planning model...
June 2018: Lancet. Public Health
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"