bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assaying uptake of endocrine disruptor compounds in zebrafish embryos and larvae
Authors: Souder J. Paige , Gorelick Daniel A. 
Published: July 2017

AbstractTo study the effects of environmental endocrine disruptors (EEDs) on aquatic animals, embryos and larvae are typically incubated in water containing defined concentrations of EEDs. However, the amount of EED uptake into the animal is often difficult to determine. Using radiolabeled estradiol ([3H]E2), we previously developed a rapid, straightforward assay to measure estradiol uptake from water into zebrafish embryos and larvae. Here, we extend this approach to measure the uptake of two additional EEDs, bisphenol A (BPA) and ethinyl estradiol (EE2). As with E2, the uptake of each compound by individual larvae was low (< 6%), and increased with increasing concentration, duration, and developmental stage. We found that E2 and EE2 had similar uptake under equivalent exposure conditions, while BPA had comparatively lower uptake. One application of this assay is to test factors that influence EED uptake or efflux. It has been suggested that persistent organic pollutants (POPs) inhibit ABC transporters that may normally efflux EEDs and their metabolites, inducing toxicity in aquatic organisms. We measured [3H]E2 levels in zebrafish in the presence or absence of the POP PDBE-100, and cyclosporine A, a known inhibitor of ABC transporters. Neither chemical significantly affected [3H]E2 levels in zebrafish, suggesting that zebrafish maintain estradiol efflux in the presence of PDBE-100, independently of cyclosporine A-responsive transporters. These uptake results will be a valuable reference for EED exposure studies in developing zebrafish, and provide a rapid assay to screen for chemicals that influence estrogen-like EED levelsin vivo.
Spectrum evaluation‐assisted eicosanoid metabolomics for global eicosanoid profiling in human vascular endothelial cells
Authors: Bao Qiankun , Liu Yajin , Song Hao , Yang Nan , Ai Ding , Zhu Yi , Zhang Xu 
Published: July 2017

SummaryEicosanoids are hundreds of metabolites derived from poly‐unsaturated fatty acids (PUFAs), which regulate biological processes from multiple angles via a complex metabolic network. Targeted eicosanoid metabolomics is used to study the eicosanoid profile in biological samples but only for eicosanoids with available standards. To expand the coverage of eicosanoids detected, we identified the eicosanoids without available standards by estimation of the retention time and comparison of the MS/MS spectra with the reference ones which was collected in a database from literature. Scheduled multiple reaction monitoring‐ information dependent acquisition‐ enhanced product ion (sMRM‐IDA‐EPI) scan mode was applied in this method, which was called Spectrum Evaluation‐assisted Eicosanoid Metabolomics (SEEM). By using this method, 243 eicosanoids (167 without standards) could be relatively quantified with precision over 90 percent. We applied the method to analyze the global profile of eicosanoids secreted by human umbilical vascular endothelial cells at the basal level and with n‐3 PUFA treatment. 26 putative eicosanoids showed altered levels, despite no available standards. In general, n‐3 PUFA treatment increased most of their own metabolites and decreased the epoxy‐, hydroxyl‐ and keto‐ linoleic acid metabolites. The application of the SEEM method proved its potency of identification and quantification of eicosanoids without standards.
The changes in, and relationship between, plasma nitric oxide and corticotropin‐releasing hormone in patients with major depressive disorder
Authors: Lu Yun‐Rong , Zhang Yan , Rao Ying‐Bo , Chen Xi , Lou Han‐Fen , Zhang Yu , Xie Hai‐Yan , Fang Ping , Hu Li‐Wei 
Published: July 2017

SummaryThere is strong evidence of roles of the hypothalamus‐pituitary‐adrenal axis and nitric oxide (NO) synthase‐NO system in depression, but the relationship between them is unknown. The aim of this study, therefore, was to elucidate whether there is any correlation between NO and corticotropin‐releasing hormone (CRH) in major depressive disorder (MDD) patients. In 16 outpatients with MDD and 18 healthy controls, the plasma amino acids citrulline (Cit) and arginine (Arg) were determined by high‐performance liquid chromatography, and CRH levels was measured by radioimmunoassay. The Cit/Arg ratio was calculated as an index of NO synthesis. Correlations between NO and CRH were examined with the Spearman test. Before treatment, no significant correlation was observed between the plasma NO level and CRH levels in MDD patients. The plasma NO levels were significantly higher in MDD patients. A significant correlation was found between NO levels and Hamilton Depression Rating Scale (HAMD) scores in MDD patients. The plasma CRH levels were significantly higher in MDD patients than in controls. After monotherapy for 2 months, the NO levels had dramatically declined but were also higher than those in the controls. This study is the first report of the absence of a significant correlation between plasma NO and CRH levels, although both levels are elevated in MDD patients. Furthermore, the strong links between the plasma NO levels and the HAMD scores, as well as the increased NO reduction after remission, suggest that NO plays a key role in depression and may be an indicator of therapeutic success.
Defining definitions: a Delphi study to develop a core outcome set for conditions of severe maternal morbidity
Authors: Schaap T , Bloemenkamp K , Deneux‐Tharaux C , Knight M , Langhoff‐Roos J , Sullivan E , van den Akker T ,   INOSS
Published: July 2017

ObjectiveDevelop a core outcome set of international consensus definitions for severe maternal morbidities.DesignElectronic Delphi study.SettingInternational.PopulationEight expert panels.MethodsAll 13 high‐income countries represented in the International Network of Obstetric Surveillance Systems (INOSS) nominated five experts per condition of morbidity, who submitted possible definitions. From these suggestions, a steering committee distilled critical components: eclampsia: 23, amniotic fluid embolism: 15, pregnancy‐related hysterectomy: 11, severe primary postpartum haemorrhage: 19, uterine rupture: 20, abnormally invasive placentation: 12, spontaneous haemoperitoneum in pregnancy: 16, and cardiac arrest in pregnancy: 10. These components were assessed by the expert panel using a 5‐point Likert scale, following which a framework for an encompassing definition was constructed. Possible definitions were evaluated in rounds until a rate of agreement of more than 70% was reached. Expert commentaries were used in each round to improve definitions.Main outcome measuresDefinitions with a rate of agreement of more than 70%.ResultsThe invitation to participate in one or more of eight Delphi processes was accepted by 103 experts from 13 high‐income countries. Consensus definitions were developed for all of the conditions.ConclusionConsensus definitions for eight morbidity conditions were successfully developed using the Delphi process. These should be used in national registrations and international studies, and should be taken up by the Core Outcomes in Women's and Newborn Health initiative.Tweetable abstractConsensus definitions for eight morbidity conditions were successfully developed using the Delphi process.
Diagnostic accuracy of haptoglobin within ovarian cyst fluid as a potential point‐of‐care test for epithelial ovarian cancer: an observational study
Authors: Mahyuddin AP , Liu L , Zhao C , Kothandaraman N , Salto‐Tellez M , Pang BNK , Lim DGS , Annalamai L , Chan JKY , Lim TYK , Biswas A , Rice G , Razvi K , Choolani M 
Published: July 2017

ObjectiveTo investigate haptoglobin within ovarian cyst fluid (OCF) as a diagnostic biomarker for epithelial ovarian cancer (EOC) and develop an in vitro diagnostic point‐of‐care device test (IVDPCT) for use in the operating theatre.DesignRetrospective and prospective cohort study.SettingSouth‐East Asia.PopulationWomen with suspicious ovarian cysts.MethodsProteomic, immunohistochemical and ELISA methods measured haptoglobin in OCF to differentiate benign and EOCs. Diagnostic performance of haptoglobin was compared with CA125, risk malignancy indices (RMI) and frozen section. Blinded validation of the IVDPCT was performed.Main outcome measuresPrediction of malignancy.ResultsHaptoglobin concentration measured by ELISA was 0.70 ± 0.09 mg/ml in patients with benign cysts (n = 87), 6.22 ± 0.53 mg/ml in early stage‐EOC (n = 17), and 6.57 ± 0.65 mg/ml in late stage‐EOC (n = 20). Haptoglobin in EOCs was significantly higher than in benign cysts (P < 0.0001). Haptoglobin using rapid colorimetric assay (RCA) on a training set had a sensitivity of 97.3% and a specificity 92.0%, comparable to ELISA and frozen sections. The haptoglobin AUROC curve was 0.999 (95% CI 0.997–1.000) compared with 0.895 (95% CI 0.814–0.977, P < 0.05) for CA125. Haptoglobin performed significantly better than all the RMIs (P < 0.01). Blinded validation studies showed a minor drop in average diagnostic performance (sensitivity 85.2% and specificity 90.5%) compared with the training set. However, when compared with frozen section, haptoglobin was no worse in diagnostic accuracy for malignancy.ConclusionHaptoglobin was identified as a biomarker for the detection of EOC with potential as a point‐of‐care diagnostic tool.Tweetable abstractHaptoglobin within ovarian cyst fluid: a biomarker for epithelial ovarian cancer and point‐of‐care diagnostics.
Diagnosis and management of endometriosis: a systematic review of international and national guidelines
Authors: Hirsch M , Begum MR , Paniz É , Barker C , Davis CJ , Duffy JMN 
Published: July 2017

BackgroundThe development of clinical guidelines requires standardised methods informed by robust evidence synthesis.ObjectivesWe evaluated the methodological quality of endometriosis guidelines, mapped their recommendations, and explored the relationships between recommendations and research evidence.Search strategyWe searched EMBASE, MEDLINE, and PubMed from inception to February 2016.Selection criteriaWe included guidelines related to the diagnosis and management of endometriosis.Data collection and analysisThe search strategy identified 879 titles and abstracts. We include two international and five national guidelines. Four independent authors assessed the methodological quality of the included guidelines, using the Appraisal of Guidelines for Research & Evaluation (AGREE‐II) instrument, and systematically extracted the guideline recommendations and supporting research evidence.Main resultsOne hundred and fifty‐two different recommendations were made. Ten recommendations (7%) were comparable across guidelines. The European Society of Human Reproduction and Embryology was objectively evaluated as the highest quality guideline (methodological quality score: 88/100). There was substantial variation between the supporting evidence presented by individual guidelines for comparable recommendations. Forty‐two recommendations (28%) were not supported by research evidence. No guideline followed the standardised guideline development methods (AGREE‐II).ConclusionsThere is substantial variation in the recommendations and methodological quality of endometriosis guidelines. Future guidelines should be developed with reference to high‐quality methods in consultation with key stakeholders, including women with endometriosis, ensuring that their scope can truly inform clinical practice and eliminate unwarranted and unjustified variations in clinical practice.Tweetable abstract#Endometriosis guidelines vary in recommendations and quality. @EndometriosisUK
The effectiveness of surgical interventions for women with FGM/C: a systematic review
Authors: Berg RC , Taraldsen S , Said MA , Sørbye IK , Vangen S 
Published: July 2017

BackgroundFemale genital mutilation/cutting (FGM/C) changes normal genital functionality and can cause complications. There is an increasing demand for treatment of FGM/C‐related complications.ObjectivesWe conducted a systematic review of empirical quantitative research on the outcomes of interventions for women with FGM/C‐related complications.Search strategyA search specialist searched 16 electronic databases.Selection criteriaSelection was performed independently by two researchers. We accepted quantitative studies that examined the outcome of an intervention for an FGM/C‐related concern.Data collection and analysisWe extracted data into a pre‐designed form, calculated effect estimates, and performed meta‐analyses.Main resultsWe included 62 studies (5829 women), which investigated the effect of defibulation, excision of cysts, and clitoral reconstruction. Meta‐analyses of defibulation versus no defibulation showed a significantly lower risk of caesarean section (relative risk, RR: 0.33; 95% confidence interval, 95% CI: 0.25–0.45) and perineal tears with defibulation: second‐degree tear (RR: 0.44, 95% CI: 0.24–0.79), third‐degree tear (RR: 0.21, 95% CI: 0.05–0.94), fourth‐degree tear (RR: 0.06, 95% CI: 0.01–0.41). The meta‐analyses detected no significant differences in obstetric outcomes of antenatal versus intrapartum defibulation. Except for one study, none of the studies on the excision of cysts indicated any complications, and the results were deemed favourable. Reconstructive surgery resulted in a visible clitoris in about 77% of women. Most women self‐reported improvements in their sexual life, but up to 22% experienced a worsening in sexuality‐related outcomes after reconstruction.ConclusionsWomen with FGM/C who seek therapeutic surgery should be informed about the scarcity of evidence for benefits and the potential harms of the available procedures.Tweetable abstractSystematic review shows defibulation after FGM/C has obstetric benefits; effect of reconstruction is uncertain.
Do Managers of U.S. Defined Benefit Pension Plan Sponsors Use Regulatory Freedom Strategically?
Authors: KISSER MICHAEL , KIFF JOHN , SOTO MAURICIO 
Published: July 2017

ABSTRACTWe use historical particularities of pension funding law to investigate whether managers of U.S. corporate defined benefit pension plan sponsors strategically use regulatory freedom to lower the reported value of pension liabilities, and hence required cash contributions. For some years, pension plans were required to estimate two liabilities—one with mandated discount rates and mortality assumptions, and another where these could be chosen freely. Using a sample of 11,963 plans, we find that the regulated liability exceeds the unregulated measure by 10% and the difference further increases for underfunded pension plans. Underfunded plans tend to assume substantially higher discount rates and lower life expectancy. The effect persists both in the cross‐section of plans and over time and it serves to reduce cash contributions. We further show that plan sponsor managers use the freed‐up cash for corporate investment and that credit risk is unlikely to explain the finding.
Short term in vivo precision of whole body composition measurements on the Horizon A densitometer
Authors: Nowitz Michael , Monahan Paula 
Published: July 2017

AbstractIntroductionDual‐energy X‐ray absorptiometry (DXA) is increasingly being used to assess abnormalities in body composition associated with a wide variety of conditions including obesity, sarcopenia, diabetes, anorexia, human immunodeficiency virus lipodystrophy, malabsorption and neuromuscular disorders. The objective of this study was to determine the short‐term in vivo precision and least significant change in serial body composition measurements provided by the Hologic Horizon A densitometer as there is no published, peer reviewed body composition precision data on Horizon scanners in the medical literature.MethodsAfter acquiring two new Hologic Horizon A densitometers, short term precision scanning was performed on the two scanners using different groups of 30 volunteers, who had duplicate scans with all scans performed by the same operator. Using the International Society of Clinical Densitometry's advanced precision tool, the scan data were recorded and the coefficient of variation (CV) and least significant change (LSC) determined for total fat, lean and bone mineral content (BMC) and bone mineral density (BMD).ResultsCoefficients of variation of 0.78% and 0.77% were achieved for total fat (LSC at 95% confidence 2.15%) and 0.52% and 0.40% for total lean (LSC at 95% confidence 1.45% and 1.11%).ConclusionsThese results indicate that the two Horizon A scanners in this study exceeded the minimum acceptable precision values by roughly a factor of four and are therefore capable of detecting small differences in lean and fat mass of 1–2% between two measurements at 95% confidence.
Epac1, PDE4, and PKC protein expression and their association with AKAP95, Cx43, and cyclinD2/E1 in breast cancer tissues
Authors: Huang Ping , Sun Qian , Zhuang Wenxin , Peng Kuan , Wang Dai , Yao Youliang , Guo Dongbei , Zhang Lu , Shen Chuhan , Sun Mengyun , Tang Chaoying , Teng Bogang , Zhang Yongxing 
Published: July 2017

BackgroundThis study was conducted to investigate the exchange protein directly activated by cAMP (Epac1), PDE4, and PKC expression in breast cancer tissues, and the correlation between these proteins and AKAP95, Cx43, cyclin D2, and cyclin E1.MethodsPV‐9000 two‐step immunohistochemistry was used to analyze protein expression.ResultsThe positive rate of Epac1 protein expression in breast cancer tissues (58%) was higher than in para‐carcinoma tissues (10%) (P < 0.05). There were no significant differences in the positive rates of PDE4 and PKC expression between breast cancer and para‐carcinoma tissues (P > 0.05). The positive expression rate of PDE4 was higher in the P53 protein positive group compared to the P53 negative group (P < 0.05). Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins were observed (P < 0.05).ConclusionEpac1 expression in breast cancer tissues was increased, suggesting that the protein may be involved in the development of breast cancer. Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins suggested synergistic effects among these proteins in the development of breast cancer.
Blood and nasal epigenetics correlate with allergic rhinitis symptom development in the environmental exposure unit
Authors: North M. L. , Jones M. J. , MacIsaac J. L. , Morin A. M. , Steacy L. M. , Gregor A. , Kobor M. S. , Ellis A. K. 
Published: July 2017

AbstractBackgroundEpigenetic alterations may represent new therapeutic targets and/or biomarkers of allergic rhinitis (AR). Our aim was to examine genome‐wide epigenetic changes induced by controlled pollen exposure in the environmental exposure unit (EEU).Methods38 AR sufferers and eight nonallergic controls were exposed to grass pollen for 3 hours on two consecutive days. We interrogated DNA methylation at baseline and 3 hours in peripheral blood mononuclear cells (PBMCs) using the Infinium Methylation 450K array. We corrected for demographics, cell composition, and multiple testing (Benjamini‐Hochberg) and verified hits using bisulfite PCR pyrosequencing and qPCR. To extend these findings to a clinically relevant tissue, we investigated DNA methylation and gene expression of mucin 4 (MUC4), in nasal brushings from a separate validation cohort exposed to birch pollen.ResultsIn PBMCs of allergic rhinitis participants, 42 sites showed significant DNA methylation changes of 2% or greater. DNA methylation changes in tryptase gamma 1 (TPSG1), schlafen 12 (SLFN12), and MUC4 in response to exposure were validated by pyrosequencing. SLFN12 DNA methylation significantly correlated with symptoms (P < 0.05), and baseline DNA methylation pattern was found to be predictive of symptom severity upon grass allergen exposure (P = 0.029). Changes in MUC4 DNA methylation in nasal brushings in the validation cohort correlated with drop in peak nasal inspiratory flow (Spearman's r = 0.314, P = 0.034), and MUC4 gene expression was significantly increased (P < 0.0001).ConclusionThis study revealed novel and rapid epigenetic changes upon exposure in a controlled allergen challenge facility, and identified baseline epigenetic status as a predictor of symptom severity.
Antibiotic‐induced dysbiosis of the microbiota impairs gut neuromuscular function in juvenile mice
Authors: Caputi Valentina , Marsilio Ilaria , Filpa Viviana , Cerantola Silvia , Orso Genny , Bistoletti Michela , Paccagnella Nicola , De Martin Sara , Montopoli Monica , Dall'Acqua Stefano , Crema Francesca , Di Gangi Iole‐Maria , Galuppini Francesca , Lante Isabella , Bogialli Sara , Rugge Massimo , Debetto Patrizia , Giaroni Cristina , Giron Maria Cecilia 
Published: July 2017

Background and PurposeGut microbiota is essential for the development of the gastrointestinal system, including the enteric nervous system (ENS). Perturbations of gut microbiota in early life have the potential to alter neurodevelopment leading to functional bowel disorders later in life. We examined the hypothesis that gut dysbiosis impairs the structural and functional integrity of the ENS, leading to gut dysmotility in juvenile mice.Experimental ApproachTo induce gut dysbiosis, broad‐spectrum antibiotics were administered by gavage to juvenile (3weeks old) male C57Bl/6 mice for 14 days. Bile acid composition in the intestinal lumen was analysed by liquid chromatography‐mass spectrometry. Changes in intestinal motility were evaluated by stool frequency, transit of a fluorescent‐labelled marker and isometric muscle responses of ileal full‐thickness preparations to receptor and non‐receptor‐mediated stimuli. Alterations in ENS integrity were assessed by immunohistochemistry and Western blot analysis.Key ResultsAntibiotic treatment altered gastrointestinal transit, luminal bile acid metabolism and bowel architecture. Gut dysbiosis resulted in distorted glial network, loss of myenteric plexus neurons, altered cholinergic, tachykininergic and nitrergic neurotransmission associated with reduced number of nNOS neurons and different ileal distribution of the toll‐like receptor TLR2. Functional defects were partly reversed by activation of TLR2 signalling.Conclusions and ImplicationsGut dysbiosis caused complex morpho‐functional neuromuscular rearrangements, characterized by structural defects of the ENS and increased tachykininergic neurotransmission. Altogether, our findings support the beneficial role of enteric microbiota for ENS homeostasis instrumental in ensuring proper gut neuromuscular function during critical stages of development.