scholarly journals Ovine fetal testis stage-specific sensitivity to environmental chemical mixtures

Reproduction ◽  
2022 ◽  
Author(s):  
Richard G Lea ◽  
Beatrice Mandon-Pepin ◽  
Benoit Loup ◽  
Elodie Poumerol ◽  
Luc Jouneau ◽  
...  
Keyword(s):  
Real Life ◽  
Late Pregnancy ◽  
Adverse Outcomes ◽  
Environmental Chemicals ◽  
Environmental Chemical ◽  
Fetal Testis ◽  
Short Period ◽  
Androgenic Effect ◽  
Ovine Fetal ◽  
Transcriptomic Changes

Exposure of the fetal testis to numerous individual environmental chemicals is frequently associated with dysregulated development, leading to impaired adult reproductive competence. However, ‘real-life’ exposure involves complex mixtures of environmental chemicals (ECs). Here we test the consequences, for the male fetus, of exposing pregnant ewes to EC mixtures derived from pastures treated with biosolids fertiliser (processed human sewage). Fetal testes from continuously exposed ewes were either unaffected at Day 80 or exhibited a reduced area of testis immunostained for CYP17A1 protein at Day 140. Fetal testes from Day 140 pregnant ewes exposed transiently for 80 day periods during early (0-80 days), mid (30-110 days) or late (60-140 days) pregnancy, had fewer Sertoli cells and reduced testicular area stained for CYP17A1. Male fetuses from ewes exposed during late pregnancy also exhibited reduced fetal body, adrenal and testis mass, anogenital distance and lowered testosterone: collectively indicative of an anti-androgenic effect. Exposure limited to early gestation induced more testis transcriptome changes than observed for continuously exposed Day 140 fetuses. These data suggest that a short period of EC exposure does not allow sufficient time for the testis to adapt. Consequently, testicular transcriptomic changes induced during the first 80 days of gestation may equate with phenotypic effects observed at Day 140. In contrast, relatively fewer changes in the testis transcriptome in fetuses exposed continuously to ECs throughout gestation is associated with less severe consequences. Unless corrected by or during puberty, these differential effects would predictably have adverse outcomes for adult testicular function and fertility.

scholarly journals A non-targeted LC–MS metabolic profiling of pregnancy: longitudinal evidence from healthy and pre-eclamptic pregnancies

Metabolomics ◽  
2021 ◽  
Vol 17 (2) ◽  
Author(s):  
Tiina Jääskeläinen ◽  
◽  
Olli Kärkkäinen ◽  
Jenna Jokkala ◽  
Anton Klåvus ◽  
...  
Keyword(s):  
Large Scale ◽  
Scale Effects ◽  
Late Pregnancy ◽  
Metabolite Profile ◽  
Adverse Outcomes ◽  
Liquid Chromatography Mass Spectrometry ◽  
Targeted Metabolomics ◽  
Serum Samples ◽  
Healthy Women ◽  
Maternal Metabolism

Abstract Introduction Maternal metabolism changes substantially during pregnancy. However, few studies have used metabolomics technologies to characterize changes across gestation. Objectives and methods We applied liquid chromatography–mass spectrometry (LC–MS) based non-targeted metabolomics to determine whether the metabolic profile of serum differs throughout the pregnancy between pre-eclamptic and healthy women in the FINNPEC (Finnish Genetics of Preeclampsia Consortium) Study. Serum samples were available from early and late pregnancy. Results Progression of pregnancy had large-scale effects to the serum metabolite profile. Altogether 50 identified metabolites increased and 49 metabolites decreased when samples of early pregnancy were compared to samples of late pregnancy. The metabolic signatures of pregnancy were largely shared in pre-eclamptic and healthy women, only urea, monoacylglyceride 18:1 and glycerophosphocholine were identified to be increased in the pre-eclamptic women when compared to healthy controls. Conclusions Our study highlights the need of large-scale longitudinal metabolomic studies in non-complicated pregnancies before more detailed understanding of metabolism in adverse outcomes could be provided. Our findings are one of the first steps for a broader metabolic understanding of the physiological changes caused by pregnancy per se.

To err is system; a comparison of methodologies for the investigation of adverse outcomes in healthcare

2021 ◽  
pp. 251604352199026
Author(s):  
Peter Isherwood ◽  
Patrick Waterson
Keyword(s):  
Patient Safety ◽  
System Performance ◽  
Healthcare Delivery ◽  
Healthcare Providers ◽  
Real Life ◽  
Adverse Outcomes ◽  
System Level ◽  
Future Performance ◽  
System A ◽  
Regulatory Bodies

Patient safety, staff moral and system performance are at the heart of healthcare delivery. Investigation of adverse outcomes is one strategy that enables organisations to learn and improve. Healthcare is now understood as a complex, possibly the most complex, socio-technological system. Despite this the use of a 20th century linear investigation model is still recommended for the investigation of adverse outcomes. In this review the authors use data gathered from the investigation of a real life healthcare near incident and apply three different methodologies to the analysis of this data. They compare both the methodologies themselves and the outputs generated. This illustrates how different methodologies generate different system level recommendations. The authors conclude that system based models generate the strongest barriers to improve future performance. Healthcare providers and their regulatory bodies need to embrace system based methodologies if they are to effectively learn from, and reduce future, adverse outcomes.

scholarly journals ALVIC versus the Internet: Redesigning a Networked Virtual Environment Architecture

2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
Peter Quax ◽  
Jeroen Dierckx ◽  
Bart Cornelissen ◽  
Wim Lamotte
Keyword(s):  
Virtual Environment ◽  
Large Scale ◽  
Virtual Communities ◽  
Real Life ◽  
Point Of View ◽  
The Internet ◽  
Generic Framework ◽  
Short Period ◽  
Networked Virtual Environment ◽  
Near Future

The explosive growth of the number of applications based on networked virtual environment technology, both games and virtual communities, shows that these types of applications have become commonplace in a short period of time. However, from a research point of view, the inherent weaknesses in their architectures are quickly exposed. The Architecture for Large-Scale Virtual Interactive Communities (ALVICs) was originally developed to serve as a generic framework to deploy networked virtual environment applications on the Internet. While it has been shown to effectively scale to the numbers originally put forward, our findings have shown that, on a real-life network, such as the Internet, several drawbacks will not be overcome in the near future. It is, therefore, that we have recently started with the development of ALVIC-NG, which, while incorporating the findings from our previous research, makes several improvements on the original version, making it suitable for deployment on the Internet as it exists today.

On the origin of dehydroepiandrosterone sulphate in the blood of fetal sheep

1985 ◽  
Vol 104 (2) ◽  
pp. 279-283 ◽  
Author(s):  
G. C. Liggins ◽  
J.-C. Schellenberg ◽  
F. Amato ◽  
B. Godfrey ◽  
R. F. Seamark
Keyword(s):  
Significant Contribution ◽  
Late Pregnancy ◽  
Dehydroepiandrosterone Sulphate ◽  
Fetal Sheep ◽  
Intact Group ◽  
The Mean ◽  
Ovine Fetal

ABSTRACT Total sulphoconjugated and unconjugated dehydroepiandrosterone (DHA) and total oestrone were measured in plasma of intact sheep fetuses, fetuses hypophysectomized at 104–112 days and fetuses bilaterally adrenalectomized at 98–101 days. At 120–127 days, the mean concentrations of total DHA and oestrone in intact fetuses (n = 13) were 29·7 ± 4·2 (s.e.m.) nmol/l and 14·3 ± 2·8 nmol/l respectively. At term, the values for total DHA and oestrone in hypophysectomized fetuses (n = 13) of 18·0 ± 1·9 nmol/l and 9·1 ±2·0 nmol/l were significantly (P <0·05) lower than the intact group whereas in the adrenalectomized fetuses (n = 8) total DHA (80·8±13·0 nmol/l) was higher (P < 0·05) and total oestrone values were similar to the intact animals. Intrafetal infusion of cortisol at term (1 mg/h for 84 h) raised levels of total oestrone in intact (n = 6; 12·3 ± 2·9 vs 31·6± 8·5 nmol/l) and adrenalectomized (n = 4; 14·2 ± 2·6 vs 190·6 ± 53·0 nmol/l) fetuses and of total DHA in hypophysectomized fetuses (n = 7; 16·0±1·9 vs 31·6 ± 8·5 nmol/l) while infusion of ACTH(1–24) (5 μg/h) was without significant effect in any group. It is concluded that the ovine fetal adrenal in late pregnancy makes no significant contribution either to the high circulating concentrations of DHA sulphate or to the substrates for placental oestrogen synthesis. J. Endocr. (1985) 104, 279–283

Analysis of Autoignition Chemistry in Aeroderivative Premixers At Engine Conditions

2021 ◽  
Author(s):  
Sandeep Jella ◽  
Gilles Bourque ◽  
Pierre Gauthier ◽  
Philippe Versailles ◽  
Jeffrey M. Bergthorson ◽  
...  
Keyword(s):  
Residence Time ◽  
Real Life ◽  
Precursor Chemistry ◽  
Mode Analysis ◽  
Safety Factors ◽  
Eddy Simulation ◽  
Reduced Mechanism ◽  
Short Period ◽  
Large Eddy ◽  
Pure Methane

Abstract The minimization of autoignition risk is critical to premixer design. Safety factors based on ignition delays of homogeneous mixtures, are generally used to guide the choice of a residence time for a given premixer. However, autoignition chemistry at aeroderivative conditions is fast (0.5-2 milliseconds) and can be initiated within typical premixer residence times. The analysis of what takes place in this short period involves the study of low-temperature precursor chemistry. By coupling the evolution of the Chemical Explosive Modes to turbulence, it is possible to obtain a measure of spatial autoignition risk where both chemical (e.g. ignition delay) and aerodynamic (e.g. local residence time) influences are unified. In this article, we describe a method that couples Large Eddy Simulation to newly developed, reduced autoignition chemical kinetics to study autoignition precursors in an example premixer representative of real life geometric complexity. A blend of pure methane and dimethyl ether (DME), a common fuel used for experimental autoignition studies, was transported using the reduced mechanism (38 species / 238 reactions) at engine conditions at increasing levels of DME concentration until exothermic autoignition kernels were formed. The Chemical Explosive Mode analysis closely follows the large thermochemical changes in the premixer as a function of DME concentration and identifies where the premixer is sensitive and flame anchoring is likely to occur.

A scalable workflow for the human exposome

2020 ◽  
Author(s):  
Xin Hu ◽  
Douglas Walker ◽  
YongLiang Liang ◽  
Matthew Smith ◽  
Michael Orr ◽  
...  
Keyword(s):  
High Resolution ◽  
High Resolution Mass Spectrometry ◽  
A Priori ◽  
Population Level ◽  
Sample Volume ◽  
Single Step ◽  
Environmental Chemicals ◽  
Environmental Chemical ◽  
Mass Spectral ◽  
Sensitivity And Selectivity

Abstract Complementing the genome with an understanding of the human exposome is an important challenge for contemporary science and technology. Tens of thousands of chemicals are used in commerce, yet cost for targeted environmental chemical analysis limits surveillance to a few hundred known hazards. To overcome limitations which prevent scaling to thousands of chemicals, we developed a single-step express liquid extraction (XLE), gas chromatography high-resolution mass spectrometry (GC-HRMS) analysis and computational pipeline to operationalize the human exposome. We show that the workflow supports quantification of environmental chemicals in small human plasma (200 µL) and tissue (≤ 100 mg) samples. The method also provides high resolution, sensitivity and selectivity for exposome epidemiology of mass spectral features without a priori knowledge of chemical identity. The simplicity of the method can facilitate harmonization of environmental biomonitoring between laboratories and enable population level human exposome research with limited sample volume.

scholarly journals Metabolic Signatures of the Exposome—Quantifying the Impact of Exposure to Environmental Chemicals on Human Health

Metabolites ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 454
Author(s):  
Matej Orešič ◽  
Aidan McGlinchey ◽  
Craig E. Wheelock ◽  
Tuulia Hyötyläinen
Keyword(s):  
Human Health ◽  
Well Being ◽  
Adverse Outcomes ◽  
Environmental Chemicals ◽  
Chemical Exposures ◽  
Intermediate Phenotypes ◽  
Disease Risks ◽  
External Exposures ◽  
The Impact ◽  
Made In

Human health and well-being are intricately linked to environmental quality. Environmental exposures can have lifelong consequences. In particular, exposures during the vulnerable fetal or early development period can affect structure, physiology and metabolism, causing potential adverse, often permanent, health effects at any point in life. External exposures, such as the “chemical exposome” (exposures to environmental chemicals), affect the host’s metabolism and immune system, which, in turn, mediate the risk of various diseases. Linking such exposures to adverse outcomes, via intermediate phenotypes such as the metabolome, is one of the central themes of exposome research. Much progress has been made in this line of research, including addressing some key challenges such as analytical coverage of the exposome and metabolome, as well as the integration of heterogeneous, multi-omics data. There is strong evidence that chemical exposures have a marked impact on the metabolome, associating with specific disease risks. Herein, we review recent progress in the field of exposome research as related to human health as well as selected metabolic and autoimmune diseases, with specific emphasis on the impacts of chemical exposures on the host metabolome.

Exposure to environmental chemicals and type 1 diabetes: an update

2019 ◽  
Vol 73 (6) ◽  
pp. 483-488 ◽  
Author(s):  
Sarah G Howard
Keyword(s):  
Type 1 Diabetes ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Environmental Chemicals ◽  
Exposure Level ◽  
Environmental Chemical ◽  
Timing Of Exposure

This narrative review summarises recently published epidemiological and in vivo experimental studies on exposure to environmental chemicals and their potential role in the development of type 1 diabetes mellitus (T1DM). These studies focus on a variety of environmental chemical exposures, including to air pollution, arsenic, some persistent organic pollutants, pesticides, bisphenol A and phthalates. Of the 15 epidemiological studies identified, 14 include measurements of exposures during childhood, 2 include prenatal exposures and 1 includes adults over age 21. Together, they illustrate that the role of chemicals in T1DM may be complex and may depend on a variety of factors, such as exposure level, timing of exposure, nutritional status and chemical metabolism. While the evidence that these exposures may increase the risk of T1DM is still preliminary, it is critical to investigate this possibility further as a means of preventing T1DM.

Consent and anaesthetic risk

2016 ◽  
Author(s):  
Kath Jenkins
Keyword(s):  
Informed Consent ◽  
Real Life ◽  
Adverse Outcomes ◽  
Risk Patient ◽  
Good Knowledge ◽  
Perioperative Mortality ◽  
Mortality And Morbidity ◽  
Anaesthetic Practice

This chapter describes the importance of obtaining informed consent for anaesthesia. It covers some ethical points to guide this process. Informed consent requires good knowledge of the risks of anaesthetic practice and their likelihood. The chapter contains a detailed table of perioperative adverse outcomes, linked to real-life examples to aid clarity of communication to the patient. There are detailed suggestions of how to identify the higher-risk patient and estimate their risk of perioperative mortality and morbidity.

scholarly journals P724 Delaying an infliximab infusion by more than 3 days is associated with a significant reduction in trough levels

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S583-S583
Author(s):  
B Ungar ◽  
Z Ben-Shatach ◽  
T Ziv-Baran ◽  
E Fudim ◽  
M Yavzori ◽  
...  
Keyword(s):  
Clinical Remission ◽  
Real Life ◽  
Mean Difference ◽  
Infliximab Therapy ◽  
Therapy Outcome ◽  
Maintenance Period ◽  
Therapy Regimen ◽  
Short Period ◽  
Infusion Schedule ◽  
Trough Levels

Abstract Background An association between higher infliximab-trough-levels (TL) and better outcomes has been demonstrated among IBD patients. Although standard scheduled infliximab therapy regimen consists of infusions at pre-defined time-points (weeks 0, 2, 6 and every 8 weeks), short-period deviations from therapeutic schedule are common in ‘real life’, especially during maintenance period (due to weekends, holidays, concurrent illnesses, etc.). We aimed to determine whether short-period deviations from infusion-schedule affect infliximab-TL and therapy outcome. Methods This was a retrospective study, analysing sera from all IBD patients receiving infliximab maintenance-therapy every 8 weeks in a tertiary medical centre. Associations between time since last infusion and TL were analysed. Clinical scores were recorded prospectively on infusion days and baseline demographic parameters were derived from patients’ charts. Statistical analysis was performed using generalised estimating equations. Results In total, 2088 sera of 302 maintenance-period infliximab-therapy-patients were included (median TL 4.1 μg/ml, IQR 2.3–6.5 μg/ml). A delay beyond 3 days in infusion (n &gt; 59 days since last infusion) was demonstrated as significantly affecting TL (mean difference in TL 1 μg/ml, 95% CI 0.03–1.9 μg/ml, p &lt; 0.04). A sub-analysis was performed for 60 maintenance-period infliximab-therapy-patients with &gt;10 consecutive TL measurements (1226 measurements in total), with adjustment for background parameters (gender, infliximab dose, disease type, concomitant immunomodulator, age and weight). A delay of &gt;4 days from scheduled infusion resulted in a statistically significant decline in infliximab trough levels (mean difference in TL 1.45 μg/ml, 95% CI 0.61–2.2 μg/ml, p &lt; 0.001). Finally, deviation from infusion schedule was analysed in association with clinical remission status. Patients that were in clinical remission were more likely to arrive late, rather than early, for scheduled therapy, compared with patients with active disease (OR 2.92 CI 1.75–4.85, p &lt; 0.0001). Conclusion Real life delays of &lt;4 days from infusion protocol can probably be allowed. Delays beyond that would significantly decrease TL and might negatively affect therapy outcome. As patients arriving late for an infusion had higher rates of clinical remission than those arriving early, we assume clinical factors mainly drive patients to receive an earlier-then-scheduled infusion.

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