381 research outputs found

    High maternal serum ferritin in early pregnancy and risk of spontaneous preterm birth

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    Previous studies have reported inconsistent associations between maternal serum ferritin concentrations and risk of preterm birth. The aim of this study was to examine the association between iron biomarkers, including serum ferritin and risk of total, early and moderate-to-late spontaneous preterm birth (sPTB). This cohort study included women with singleton pregnancies who were attending first-trimester screening in New South Wales, Australia. sPTB births included births 75th percentile (ā‰„43 Ī¼g/L) (OR: 1.49, 95% CI: 1.06, 2.10) and >90th percentile (ā‰„68 Ī¼g/L) (OR: 1.92, 95% CI: 1.25, 2.96). Increased odds of early and moderate-to late sPTB were associated with ferritin levels >90th (OR: 2.50, 95% CI: 1.32, 4.73) and >75th (OR: 1.56, 95% CI: 1.03, 2.37) percentiles, respectively. No association was found between sPTB, and elevated sTfR levels or iron deficiency. In conclusion, elevated early pregnancy maternal serum ferritin levels are associated with increased risk of sPTB from 34 weeks gestation. The usefulness of early pregnancy ferritin levels in identifying women at risk of sPTB warrants further investigation.NHMR

    Iron deficiency in early pregnancy using serum ferritin and soluble transferrin receptor concentrations are associated with pregnancy and birth outcomes.

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    Background: There are several biomarkers for measuring iron deficiency (ID) in pregnancy, but evidence of their prevalence in association with inflammation and adverse pregnancy outcomes is inconclusive. Objectives: To describe the prevalence and determinants of ID in women in the first trimester of pregnancy and associations with pregnancy and birth outcomes. Design: A record-linkage cohort study of archived serum samples of women attending first trimester screening and birth and hospital data to ascertain maternal characteristics and pregnancy outcomes. Sera were analysed for iron stores (ferritin; Ī¼g/L), tissue iron (soluble transferrin receptor, sTfR; nmol/L) and inflammatory (C-reactive protein, CRP; mg/L) biomarkers. Total body iron (TBI) was calculated from serum ferritin and sTfR concentrations. Multivariate logistic regression analyzed risk factors and pregnancy outcomes associated with ID using the definitions: serum ferritin <12 Ī¼g/L, TfR ā‰„21.0 nmol/L and TBI<0 mg/kg. Results: Of 4,420 women, the prevalence of ID based on ferritin, sTfR and TBI was 19.6%, 15.3% and 15.7%, respectively. Risk factors of ID varied depending on which iron parameter was used and included maternal age <25 years, multiparity, socioeconomic disadvantage, high maternal body weight and inflammation. ID was associated with reduced risk of gestational diabetes (GDM) defined using serum ferritin and TBI, but not sTfR and increased risk of large for gestation age (LGA) infants defined using TBI only. Conclusions: Nearly 1 in 5 Australian women begin pregnancy with ID. Evidence suggests excess maternal weight and inflammation play a role in the relationships between ID and GDM and LGA infants.NHMR

    High maternal iron status, dietary iron intake and iron supplement use in pregnancy and risk of gestational diabetes mellitus: In-house study and systematic review

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    Background: High iron measured using dietary and serum biomarkers have been associated with type 2 diabetes; however it is uncertain whether a similar association exists for gestational diabetes mellitus (GDM). Objectives: To conduct a cohort study examining first trimester body iron stores and subsequent risk of GDM and to include these findings in a systematic review of all studies examining the association between maternal iron status, iron intake (dietary and supplemental) and the risk of GDM. Methods: Serum samples for women with first trimester screening were linked to birth and hospital records for data on maternal characteristics and GDM diagnosis. Blood was analysed for ferritin, soluble transferrin receptor (sTfR) and C-reactive protein (CRP). Associations between iron biomarkers and GDM were assessed using multivariate logistic regression. A systematic review and meta-analysis, registered with PROSPERO (CRD42014013663) included all studies published in English from Jan 1995 to March 2014 that examined the association between iron and GDM and included an appropriate comparison group. Results: Of 3, 776 women, 3.4% subsequently developed GDM. Adjusted analyses found increased odds of GDM for ferritin (OR 1.41; 95% CI: 1.11, 1.78) but not for sTfR (OR 1.00, 95% CI: 0.97, 1.03) levels. Two trials of iron supplementation in early pregnancy found no association with GDM. Increased risk of GDM was associated with higher levels of maternal ferritin and serum iron and dietary heme iron intakes. Conclusions: Increased risk of GDM among women with high serum ferritin and iron levels and dietary heme iron intakes warrants further investigation.NHMR

    Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges

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    We investigated the diagnostic and clinical performance of exome sequencing (ES) in fetuses with sonographic abnormalities with normal karyotype, microarray and, in some cases, normal gene specific sequencing

    Taselisib (GDC-0032), a Potent Ā -Sparing Small Molecule Inhibitor of PI3K, Radiosensitizes Head and Neck Squamous Carcinomas Containing Activating PIK3CA Alterations

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    Activating PIK3CA genomic alterations are frequent in head and neck squamous cell carcinoma (HNSCC), and there is an association between phosphoinositide 3-kinase (PI3K) signaling and radioresistance. Hence, we investigated the therapeutic efficacy of inhibiting PI3K with GDC-0032, a PI3K inhibitor with potent activity against p110Ī±, in combination with radiation in HNSCC

    Community access to primary care is an important geographic disparity among ovarian cancer patients undergoing cytoreductive surgery

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    OBJECTIVE: Given the importance of understanding neighborhood context and geographic access to care on individual health outcomes, we sought to investigate the association of community primary care (PC) access on postoperative outcomes and survival in ovarian cancer patients. METHODS: This was a retrospective cohort study of Stage III-IV ovarian cancer patients who underwent surgery at a single academic, tertiary care hospital between 2012 and 2015. PC access was determined using a Health Resources and Services Administration designation. Outcomes included 30-day surgical and medical complications, extended hospital stay, ICU admission, hospital readmission, progression-free and overall survival. Descriptive statistics and chi-squared analyses were used to analyze differences between patients from PC-shortage vs not PC-shortage areas. RESULTS: Among 217 ovarian cancer patients, 54.4 % lived in PC-shortage areas. They were more likely to have Medicaid or no insurance and live in rural areas with higher poverty rates, significantly further from the treating cancer center and its affiliated hospital. Nevertheless, 49.2 % of patients from PC-shortage areas lived in urban communities. Residing in a PC-shortage area was not associated with increased surgical or medical complications, ICU admission, or hospital readmission, but was linked to more frequent prolonged hospitalization (26.3 % vs 14.1 %, p = 0.04). PC-shortage did not impact progression-free or overall survival. CONCLUSIONS: Patients from PC-shortage areas may require longer inpatient perioperative care in order to achieve the same 30-day postoperative outcomes as patients who live in non-PC shortage areas. Community access to PC is a critical factor to better understanding and reducing disparities among ovarian cancer patients

    Compliance or pragmatism: How do academics deal with managerialism in higher education? A comparative study in three countries

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    Universities throughout Europe have adopted organisational strategies, structures, technologies, management instruments and values that are commonly found in the private sector. While these alleged managerial measures may be considered useful, and have a positive effect on the quality of teaching and research, there is also evidence of detrimental effects on primary tasks. The consequences of such managerial measures were investigated through 48 interviews with staff members at 10 universities in the Netherlands, Sweden and the UK. The results were analysed and interpreted within the framework of institutional and professional theory, by linking them to three central themes: 'symbolic compliance', 'professional pragmatism' and 'formal instrumentality'. These themes explain why and how the respondents dissociated themselves from the managerial measures imposed upon them. This occurred often for pragmatic and occasionally for principled reasons. Ā© 2012 Society for Research into Higher Education

    Phenotypic Anchoring of Acetaminophen-Induced Oxidative Stress with Gene Expression Profiles in Rat Liver

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    Toxicogenomics provides the ability to examine in greater detail the underlying molecular events that precede and accompany toxicity, thus allowing prediction of adverse events at much earlier times compared to classical toxicological endpoints. Acetaminophen (APAP) is a pharmaceutical that has similar metabolic and toxic responses in rodents and humans. Recent gene expression profiling studies with APAP found an oxidative stress signature at a sub-toxic dose that we hypothesized can be phenotypically anchored to conventional biomarkers of oxidative stress. Liver tissue was obtained from experimental animals used to generate microarray data where male rats were given APAP at sub-toxic (150 mg/kg), or overtly toxic (1500 and 2000 mg/kg) doses and sacrificed at 6, 24, or 48 hrs. Oxidative stress in liver was evaluated by a diverse panel of markers that included assessing expression of base excision repair (BER) genes, quantifying oxidative lesions in genomic DNA, and evaluating protein and lipid oxidation. A sub-toxic dose of APAP produced significant accumulation of nitrotyrosine protein adducts, while both sub-toxic and toxic doses caused a significant increase in 8-hydroxy-deoxyguanosine. Only toxic doses of APAP significantly induced expression levels of BER genes. None of the doses examined resulted in a significant increase in the number of abasic sites, or in the amount of lipid peroxidation. The accumulation of nitrotyrosine and 8-hydroxy-deoxyguanosine adducts phenotypically anchors the oxidative stress gene expression signature observed with a sub-toxic dose of APAP, lending support to the validity of gene expression studies as a sensitive and biologically-meaningful endpoint in toxicology
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