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Adverse outcome pathway

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https://www.readbyqxmd.com/read/28819782/the-effects-of-%C3%AE-d-mannuronic-acid-m2000-as-a-novel-nsaid-on-cox1-and-cox2-activities-and-gene-expression-in-ankylosing-spondylitis-patients-and-the-murine-monocyte-macrophage-j774-cell-line
#1
Fahimeh Jafarnezhad-Ansariha, Mir Saeed Yekaninejad, Ahmad-Reza Jamshidi, Reza Mansouri, Mahdi Vojdanian, Mahdi Mahmoudi, Mohammad Javad Fattahi, Seyed Naser Hashemi, Bernd H A Rehm, Hidenori Matsuo, Emanuela Esposito, Salvatore Cuzzocrea, Abbas Mirshafiey
Ankylosing spondylitis (AS) is a debilitating chronic inflammatory disease with genetic predisposition, which is characterized by the involvement of spine and sacroiliac joints. Due to the relatively unsuccessful treatments, we designed β-D-mannuronic (M2000) with the beneficial effects in various experimental models as a novel non-steroidal anti-inflammatory drug (NSAID). The aims of our present study were: first, to compare the therapeutic effects of M2000, as a novel designed NSAID, with naproxen and placebo in Iranian patients with AS during 12 weeks; second, to evaluate the effect of M2000 on gene expression of cyclooxygenase enzyme (COX-1/COX-2), a key enzyme in the initiation of inflammatory pathways in AS patients; and third, to assess the activity of COX-1 and COX-2 enzymes in the presence/absence of M2000 at the different doses in the murine macrophage, J774 cell line...
August 17, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28818046/can-resources-moderate-the-impact-of-levels-of-frailty-on-adverse-outcomes-among-pre-frail-older-people-a-longitudinal-study
#2
Linda P M Op Het Veld, Bart H L Ament, Erik van Rossum, Gertrudis I J M Kempen, Henrica C W de Vet, KlaasJan Hajema, Anna J H M Beurskens
BACKGROUND: Higher levels of frailty result in higher risks of adverse frailty outcomes such as hospitalisation and mortality. There are, however, indications that more factors than solely frailty play a role in the development of these outcomes. The presence of resources, e.g. sufficient income and good self-management abilities, might slow down the pathway from level of frailty to adverse outcomes (e.g. mortality). In the present paper we studied whether resources (i.e. educational level, income, availability of informal care, living situation, sense of mastery and self-management abilities) moderate the impact of the level of frailty on the adverse outcomes mortality, hospitalisation and the development of disability over a two-year period...
August 17, 2017: BMC Geriatrics
https://www.readbyqxmd.com/read/28816105/thiazolidinedione-drugs-in-the-treatment-of-type-2-diabetes-mellitus-past-present-and-future
#3
Melissa A Davidson, Donald R Mattison, Laurent Azoulay, Daniel Krewski
Thiazolidinedione (TZD) drugs used in the treatment of type 2 diabetes mellitus (T2DM) have proven effective in improving insulin sensitivity, hyperglycemia, and lipid metabolism. Though well tolerated by some patients, their mechanism of action as ligands of peroxisome proliferator-activated receptors (PPARs) results in the activation of several pathways in addition to those responsible for glycemic control and lipid homeostasis. These pathways, which include those related to inflammation, bone formation, and cell proliferation, may lead to adverse health outcomes...
August 17, 2017: Critical Reviews in Toxicology
https://www.readbyqxmd.com/read/28808232/analysis-of-the-atr-chk1-and-atm-chk2-pathways-in-male-breast-cancer-revealed-the-prognostic-significance-of-atr-expression
#4
Anna Di Benedetto, Cristiana Ercolani, Marcella Mottolese, Francesca Sperati, Laura Pizzuti, Patrizia Vici, Irene Terrenato, Abeer M Shaaban, Matthew P Humphries, Luigi Di Lauro, Maddalena Barba, Ilio Vitale, Gennaro Ciliberto, Valerie Speirs, Ruggero De Maria, Marcello Maugeri-Saccà
The ATR-Chk1 and ATM-Chk2 pathways are central in DNA damage repair (DDR) and their over-activation may confer aggressive molecular features, being an adaptive response to endogenous DNA damage and oncogene-induced replication stress. Herein we investigated the ATR-Chk1 and ATM-Chk2 signalings in male breast cancer (MBC). The expression of DDR kinases (pATR, pATM, pChk1, pChk2, and pWee1) and DNA damage markers (pRPA32 and γ-H2AX) was evaluated by immunohistochemistry in 289 MBC samples to assess their association...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808156/the-identification-of-staphylococcus-aureus-factors-required-for-pathogenicity-and-growth-in-human-blood
#5
John Connolly, Emma Boldock, Lynne R Prince, Stephen A Renshaw, Moira K Whyte, Simon J Foster
Staphylococcus aureus is a human commensal but also has devastating potential as an opportunist pathogen. S. aureus bacteraemia is often associated with an adverse outcome. To identify potential targets for novel control approaches we have identified S. aureus components that are required for growth on human blood. An ordered transposon mutant library was screened, identifying 9 genes involved specifically in haemolysis or growth on human blood agar compared to the parental strain. Three genes (purA, purB and pabA) were subsequently found to be required for pathogenesis in the zebrafish embryo infection model...
August 14, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28808078/relationship-of-kidney-injury-biomarkers-with-long-term-cardiovascular-outcomes-after-cardiac-surgery
#6
Chirag R Parikh, Jeremy Puthumana, Michael G Shlipak, Jay L Koyner, Heather Thiessen-Philbrook, Eric McArthur, Kathleen Kerr, Peter Kavsak, Richard P Whitlock, Amit X Garg, Steven G Coca
Clinical AKI, measured by serum creatinine elevation, is associated with long-term risks of adverse cardiovascular (CV) events and mortality in patients after cardiac surgery. To evaluate the relative contributions of urine kidney injury biomarkers and plasma cardiac injury biomarkers in adverse events, we conducted a multicenter prospective cohort study of 968 adults undergoing cardiac surgery. On postoperative days 1-3, we measured five urine biomarkers of kidney injury (IL-18, NGAL, KIM-1, L-FABP, and albumin) and five plasma biomarkers of cardiac injury (NT-proBNP, H-FABP, hs-cTnT, cTnI, and CK-MB)...
August 14, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28808027/de-novo-mutations-in-inhibitors-of-wnt-bmp-and-ras-erk-signaling-pathways-in-non-syndromic-midline-craniosynostosis
#7
Andrew T Timberlake, Charuta G Furey, Jungmin Choi, Carol Nelson-Williams, Erin Loring, Amy Galm, Kristopher T Kahle, Derek M Steinbacher, Dawid Larysz, John A Persing, Richard P Lifton
Non-syndromic craniosynostosis (NSC) is a frequent congenital malformation in which one or more cranial sutures fuse prematurely. Mutations causing rare syndromic craniosynostoses in humans and engineered mouse models commonly increase signaling of the Wnt, bone morphogenetic protein (BMP), or Ras/ERK pathways, converging on shared nuclear targets that promote bone formation. In contrast, the genetics of NSC is largely unexplored. More than 95% of NSC is sporadic, suggesting a role for de novo mutations. Exome sequencing of 291 parent-offspring trios with midline NSC revealed 15 probands with heterozygous damaging de novo mutations in 12 negative regulators of Wnt, BMP, and Ras/ERK signaling (10...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28807133/the-tense-the-hostile-and-the-distressed-multidimensional-psychosocial-risk-profiles-based-on-the-esc-interview-in-coronary-artery-disease-patients-the-thoresci-study
#8
Eveline van Montfort, Johan Denollet, Jeroen K Vermunt, Jos Widdershoven, Nina Kupper
BACKGROUND: While single psychosocial factors have been associated with cardiovascular outcomes, it is still unclear how they cluster. Therefore, we examined whether latent multidimensional psychosocial risk profiles could be identified in the European Society of Cardiology (ESC) psychosocial screening interview. Additionally we examined whether these profiles were associated with specific sociodemographic, clinical, and psychosocial characteristics. METHOD: 681 coronary artery disease patients (age=64...
July 2017: General Hospital Psychiatry
https://www.readbyqxmd.com/read/28805174/socioeconomic-position-and-depression-in-south-african-adults-with-long-term-health-conditions-a-longitudinal-study-of-causal-pathways
#9
T Elwell-Sutton, N Folb, A Clark, L R Fairall, C Lund, M O Bachmann
AIMS: There is convincing evidence that lower socioeconomic position is associated with increased risk of mental disorders. However, the mechanisms involved are not well understood. This study aims to elucidate the causal pathways between socioeconomic position and depression symptoms in South African adults. Two possible causal theories are examined: social causation, which suggests that poor socioeconomic conditions cause mental ill health; and social drift, which suggests that those with poor mental health are more likely to drift into poor socioeconomic circumstances...
August 14, 2017: Epidemiology and Psychiatric Sciences
https://www.readbyqxmd.com/read/28802908/apoptosis-signaling-and-bcl-2-pathways-provide-opportunities-for-novel-targeted-therapeutic-strategies-in-hematologic-malignances
#10
REVIEW
Huanling Wu, L Jeffrey Medeiros, Ken H Young
Apoptosis is an essential biological process involved in tissue homeostasis and immunity. Aberrations of the two main apoptotic pathways, extrinsic and intrinsic, have been identified in hematological malignancies; many of these aberrations are associated with pathogenesis, prognosis and resistance to standard chemotherapeutic agents. Targeting components of the apoptotic pathways, especially the chief regulatory BCL-2 family in the intrinsic pathway, has proved to be a promising therapeutic approach for patients with hematological malignances, with the expectation of enhanced efficacy and reduced adverse events...
August 8, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28801349/c-myc-expression-in-adrenocortical-tumours
#11
Mirkka Pennanen, Jaana Hagström, Ilkka Heiskanen, Timo Sane, Harri Mustonen, Johanna Arola, Caj Haglund
AIMS: Widespread use of high-resolution imaging techniques and thus increased prevalence of adrenal lesions has made diagnostics of adrenocortical tumours an increasingly important clinical issue. In non-metastatic tumours, diagnosis is based on histology. New or enhanced information for clinicopathological diagnosis, revealing the malignant potential of the tumour, could emerge by means of biomarkers. The connection of proto-oncogene c-myc to adrenocortical neoplasias is poorly known, although the Wnt/beta-catenin pathway, one of the signalling pathways leading to induction of c-myc expression, has been connected to development of adrenocortical neoplasias...
August 11, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28797945/pathways-after-inpatient-admission-in-very-advanced-age-a-portuguese-nationwide-study
#12
Daniela Brandão, Alberto Freitas, Oscar Ribeiro, Constança Paúl
INTRODUCTION: Oldest old patients often have complex and multiple medical conditions, which are associated with higher rates of use of healthcare services, and a higher risk of experiencing adverse outcomes, such as mortality. This study investigated (a) the in-hospital mortality rate and predictors in patients aged 80+; (b) the destination patients have after hospital discharge. METHODS: Nationwide study. All inpatient admissions by individuals aged 80 years and older between 2011 and 2014 in Portugal were considered...
July 29, 2017: Archives of Gerontology and Geriatrics
https://www.readbyqxmd.com/read/28795057/side-effects-of-indomethacin-in-refractory-post-traumatic-intracranial-hypertension-a-comprehensive-case-study-and-review
#13
REVIEW
Daniel Agustín Godoy, Pablo David Guerrero Suarez, Luis Rafael Moscote-Salazar, Mario Di Napoli
Intracranial hypertension (IH) is one of the final pathways of acute brain injury. In severe traumatic brain injury (sTBI), it independently predicts poor outcomes. Its control represents a key aspect of the management. Lack of response to conventional therapies signals a state of ''refractory IH'', with an associated mortality rate of 80-100%. In such cases, hypothermia, barbiturates at high doses (BBT), decompressive craniectomy (DC), and extreme hyperventilation are utilized. However, none of them has proven efficacy...
July 2017: Bulletin of Emergency and Trauma
https://www.readbyqxmd.com/read/28782412/gestational-weight-gain-in-obese-pregnancy-impact-on-maternal-and-foetal-metabolic-parameters-and-birthweight
#14
Karen L Lindsay, Lorraine Brennan, Ann Rath, Orla C Maguire, Thomas Smith, Fionnuala M McAuliffe
The aim of this prospective, observational study was to investigate the impact of gestational weight gain (GWG) among euglycaemic obese pregnant women on maternal and foetal metabolic parameters and neonatal outcome. Total GWG was recorded for 101 obese, non-diabetic women with a singleton pregnancy. At 28 weeks of gestation, fasting maternal blood samples were analysed for glucose, insulin, c-peptide and lipids. Cord bloods were collected at delivery for analysis of glucose, c-peptide and lipids. GWG (mean ± SD =10...
August 6, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28780500/perinatal-risk-factors-for-neonatal-encephalopathy-an-unmatched-case-control-study
#15
Cally J Tann, Margaret Nakakeeto, Barbara A Willey, Margaret Sewegaba, Emily L Webb, Ibby Oke, Emmanuel Derek Mutuuza, Donald Peebles, Margaret Musoke, Kathryn A Harris, Neil J Sebire, Nigel Klein, Jennifer J Kurinczuk, Alison M Elliott, Nicola J Robertson
OBJECTIVE: Neonatal encephalopathy (NE) is the third leading cause of child mortality. Preclinical studies suggest infection and inflammation can sensitise or precondition the newborn brain to injury. This study examined perinatal risks factor for NE in Uganda. DESIGN: Unmatched case-control study. SETTING: Mulago National Referral Hospital, Kampala, Uganda. METHODS: 210 term infants with NE and 409 unaffected term infants as controls were recruited over 13 months...
August 5, 2017: Archives of Disease in Childhood. Fetal and Neonatal Edition
https://www.readbyqxmd.com/read/28774557/fibroblast-growth-factor-21-plays-an-inhibitory-role-in-vascular-calcification-in-vitro-through-opg-rankl-system
#16
Fangying Cao, Xiaoxiao Liu, Xiangrong Cao, Shaoping Wang, Kun Fu, Yejing Zhao, Fang Shen, Jinghua Liu
Vascular calcification is prevalent and associated with adverse outcome without available therapy. The benefits of fibroblast growth factor (FGF)-21 on metabolism and atherosclerosis make it a promising therapeutic agent for vascular calcification. We investigated the effects of FGF21 on vascular smooth muscle cell (VSMC) calcification by culturing rat VSMCs in a calcifying medium for 9days. FGF21 markedly attenuated mineral deposition and apoptosis at the indicated time points. In the presence of FGF21, the expression levels of osteoblastic protein including bone morphogenic protein-2, alkaline phosphatase(ALP), runt-related transcription factor(RUNX)-2 and nuclear factor-kappa B ligand (RANKL) were down-regulated, whereas the expression of osteoprotegerin (OPG) increased...
July 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28768411/larval-red-drum-sciaenops-ocellatus-sublethal-exposure-to-weathered-deepwater-horizon-crude-oil-developmental-and-transcriptomic-consequences
#17
Elvis Genbo Xu, Alex J Khursigara, Jason Magnuson, E Starr Hazard, Gary Hardiman, Andrew J Esbaugh, Aaron P Roberts, Daniel Schlenk
The Deepwater Horizon (DWH) incident resulted in extensive oiling of the pelagic zone and shoreline habitats of many commercially important fish species. Exposure to the water-accommodated fraction (WAF) of oil from the spill causes developmental toxicity through cardiac defects in pelagic fish species. However, few studies have evaluated the effects of the oil on near-shore estuarine fish species such as red drum (Sciaenops ocellatus). Following exposure to a certified weathered slick oil (4.74 μg/L ∑PAH50) from the DWH event, significant sublethal impacts were observed ranging from impaired nervous system development [average 17 and 22% reductions in brain and eye area at 48 h postfertilization (hpf), respectively] to abnormal cardiac morphology (100% incidence at 24, 48, and 72 hpf) in red drum larvae...
August 18, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28764640/geographical-differences-in-perinatal-health-and-child-welfare-in-the-netherlands-rationale-for-the-healthy-pregnancy-4-all-2-program
#18
Adja J M Waelput, Meertien K Sijpkens, Jacqueline Lagendijk, Minke R C van Minde, Hein Raat, Hiske E Ernst-Smelt, Marlou L A de Kroon, Ageeth N Rosman, Jasper V Been, Loes C M Bertens, Eric A P Steegers
BACKGROUND: Geographical inequalities in perinatal health and child welfare require attention. To improve the identification, and care, of mothers and young children at risk of adverse health outcomes, the HP4All-2 program was developed. The program consists of three studies, focusing on creating a continuum for risk selection and tailored care pathways from preconception and antenatal care towards 1) postpartum care, 2) early childhood care, as well as 3) interconception care. The program has been implemented in ten municipalities in the Netherlands, aiming to target communities with a relatively disadvantageous position with regard to perinatal and child health outcomes...
August 1, 2017: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/28763097/obesity-and-adverse-breast-cancer-risk-and-outcome-mechanistic-insights-and-strategies-for-intervention
#19
REVIEW
Manuel Picon-Ruiz, Cynthia Morata-Tarifa, Janeiro J Valle-Goffin, Eitan R Friedman, Joyce M Slingerland
Answer questions and earn CME/CNE Recent decades have seen an unprecedented rise in obesity, and the health impact thereof is increasingly evident. In 2014, worldwide, more than 1.9 billion adults were overweight (body mass index [BMI], 25-29.9 kg/m(2) ), and of these, over 600 million were obese (BMI ≥30 kg/m(2) ). Although the association between obesity and the risk of diabetes and coronary artery disease is widely known, the impact of obesity on cancer incidence, morbidity, and mortality is not fully appreciated...
August 1, 2017: CA: a Cancer Journal for Clinicians
https://www.readbyqxmd.com/read/28753381/molecular-and-clinical-approach-to-intra-abdominal-adverse-effects-of-targeted-cancer-therapies
#20
Stephanie T Chang, Christine O Menias, Meghan G Lubner, Vincent M Mellnick, Amy K Hara, Terry S Desser
Targeted cancer therapies encompass an exponentially growing number of agents that involve a myriad of molecular pathways. To excel within this rapidly changing field of clinical oncology, radiologists must eschew traditional organ system-based approaches of cataloging adverse effects in favor of a conceptual framework that incorporates molecular mechanisms and associated clinical outcomes. Understanding molecular mechanisms that underlie imaging manifestations of adverse effects and known associations with treatment response allows radiologists to more effectively recognize adverse effects and differentiate them from tumor progression...
July 28, 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
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