Using microdialysis with a deuterium oxide tracer to estimate water exchange, water content and active surface area of the probe

Microdialysis is a useful tool for measuring in situ fluxes of soil compounds with minimal disturbance of soil structure and function. Fluxes of sampled compounds are commonly calculated per unit of membrane surface area, assuming that the entire membrane surface is capable of exchange - which is unlikely given varying soil moisture and the occlusion of membrane pores by the soil solid phase. We present a method to quantify the degree of connectivity of the microdialysis probe membrane to the surrounding soil by means of water exchange between a microdialysis perfusate and soil solution using deuterium (2H2O; equilibrated to DHO) as an internal standard. We applied the method to a range of probe membrane surface areas and soil moisture conditions to generate empirical models that estimate membrane surface area active in exchange. Our results suggest that even in a saturated sandy soil, active membrane surface areas reach only 40.3% of the probe surface area, perhaps due to occlusion by soil particles. However, when accounting for volumetric water content of the soil, active surface areas approached 80-90% of the area likely in contact with water, indicating that sampling efficiency of waterfilled pores may still be high, particularly at slow flow rates. Furthermore, our method enables assessment of local soil water content around the probe. Models estimating soil water content were applied to field measurements of DHO exchange in three soil horizons (Organic, B1, B2) at two boreal sites, and in situ estimates were similar to those from conventional soil moisture methods when models were calibrated with the same soil type. We present DHO exchange as a powerful method for improving microdialysis flux interpretations in future studies, and for exploring small-scale water variability in relatively undisturbed soils

Novel Microdialysis Technique Reveals a Dramatic Shift in Metabolite Secretion during the Early Stages of the Interaction between the Ectomycorrhizal Fungus Pisolithus microcarpus and Its Host Eucalyptus grandis

The colonisation of tree roots by ectomycorrhizal (ECM) fungi is the result of numerous signalling exchanges between organisms, many of which occur before physical contact. However, information is lacking about these exchanges and the compounds that are secreted by each organism before contact. This is in part due to a lack of low disturbance sampling methods with sufficient temporal and spatial resolution to capture these exchanges. Using a novel in situ microdialysis approach, we sampled metabolites released from Eucalyptus grandis and Pisolithus microcarpus independently and during indirect contact over a 48-h time-course using UPLC-MS. A total of 560 and 1530 molecular features (MFs; ESI- and ESI+ respectively) were identified with significant differential abundance from control treatments. We observed that indirect contact between organisms altered the secretion of MFs to produce a distinct metabolomic profile compared to either organism independently. Many of these MFs were produced within the first hour of contact and included several phenylpropanoids, fatty acids and organic acids. These findings show that the secreted metabolome, particularly of the ECM fungus, can rapidly shift during the early stages of pre-symbiotic contact and highlight the importance of observing these early interactions in greater detail. We present microdialysis as a useful tool for examining plant-fungal signalling with high temporal resolution and with minimal experimental disturbance

Maternal and newborn plasma oxytocin levels in response to maternal synthetic oxytocin administration during labour, birth and postpartum - a systematic review with implications for the function of the oxytocinergic system

BackgroundThe reproductive hormone oxytocin facilitates labour, birth and postpartum adaptations for women and newborns. Synthetic oxytocin is commonly given to induce or augment labour and to decrease postpartum bleeding.AimTo systematically review studies measuring plasma oxytocin levels in women and newborns following maternal administration of synthetic oxytocin during labour, birth and/or postpartum and to consider possible impacts on endogenous oxytocin and related systems.MethodsSystematic searches of PubMed, CINAHL, PsycInfo and Scopus databases followed PRISMA guidelines, including all peer-reviewed studies in languages understood by the authors. Thirty-five publications met inclusion criteria, including 1373 women and 148 newborns. Studies varied substantially in design and methodology, so classical meta-analysis was not possible. Therefore, results were categorized, analysed and summarised in text and tables.ResultsInfusions of synthetic oxytocin increased maternal plasma oxytocin levels dose-dependently; doubling the infusion rate approximately doubled oxytocin levels. Infusions below 10 milliunits per minute (mU/min) did not raise maternal oxytocin above the range observed in physiological labour. At high intrapartum infusion rates (up to 32 mU/min) maternal plasma oxytocin reached 2-3 times physiological levels.Postpartum synthetic oxytocin regimens used comparatively higher doses with shorter duration compared to labour, giving greater but transient maternal oxytocin elevations. Total postpartum dose was comparable to total intrapartum dose following vaginal birth, but post-caesarean dosages were higher.Newborn oxytocin levels were higher in the umbilical artery vs. umbilical vein, and both were higher than maternal plasma levels, implying substantial fetal oxytocin production in labour. Newborn oxytocin levels were not further elevated following maternal intrapartum synthetic oxytocin, suggesting that synthetic oxytocin at clinical doses does not cross from mother to fetus.ConclusionsSynthetic oxytocin infusion during labour increased maternal plasma oxytocin levels 2-3-fold at the highest doses and was not associated with neonatal plasma oxytocin elevations. Therefore, direct effects from synthetic oxytocin transfer to maternal brain or fetus are unlikely. However, infusions of synthetic oxytocin in labour change uterine contraction patterns. This may influence uterine blood flow and maternal autonomic nervous system activity, potentially harming the fetus and increasing maternal pain and stress

Maternal and newborn plasma oxytocin levels in response to maternal synthetic oxytocin administration during labour, birth and postpartum – a systematic review.

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the dataBackground: The reproductive hormone oxytocin facilitates labour, birth and postpartum adaptations for women and newborns. Synthetic oxytocin is commonly given to induce or augment labour and to decrease postpartum bleeding. Aim: To systematically review studies measuring plasma oxytocin levels in women and newborns following maternal administration of synthetic oxytocin during labour, birth and/or postpartum and to consider possible impacts on endogenous oxytocin and related systems. Methods: Systematic searches of PubMed, CINAHL, PsycInfo and Scopus databases followed PRISMA guidelines, including all peer-reviewed studies in languages understood by the authors. Thirty-fve publications met inclusion cri teria, including 1373 women and 148 newborns. Studies varied substantially in design and methodology, so classical meta-analysis was not possible. Therefore, results were categorized, analysed and summarised in text and tables. Results: Infusions of synthetic oxytocin increased maternal plasma oxytocin levels dose-dependently; doubling the infusion rate approximately doubled oxytocin levels. Infusions below 10 milliunits per minute (mU/min) did not raise maternal oxytocin above the range observed in physiological labour. At high intrapartum infusion rates (up to 32mU/ min) maternal plasma oxytocin reached 2–3 times physiological levels. Postpartum synthetic oxytocin regimens used comparatively higher doses with shorter duration compared to labour, giving greater but transient maternal oxytocin elevations. Total postpartum dose was comparable to total intrapartum dose following vaginal birth, but post-caesarean dosages were higher Newborn oxytocin levels were higher in the umbilical artery vs. umbilical vein, and both were higher than maternal plasma levels, implying substantial fetal oxytocin production in labour. Newborn oxytocin levels were not further elevated following maternal intrapartum synthetic oxytocin, suggesting that synthetic oxytocin at clinical doses does not cross from mother to fetus. Conclusions: Synthetic oxytocin infusion during labour increased maternal plasma oxytocin levels 2–3-fold at the highest doses and was not associated with neonatal plasma oxytocin elevations. Therefore, direct efects from synthetic oxytocin transfer to maternal brain or fetus are unlikely. However, infusions of synthetic oxytocin in labour change uterine contraction patterns. This may infuence uterine blood fow and maternal autonomic nervous system activity, potentially harming the fetus and increasing maternal pain and stress.publishedVersio

Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency

One of the severe combined immunodeficiencies (SCIDs), which is caused by a genetic defect in the signal transduction pathways involved in T-cell activation, is the ZAP70 deficiency. Mutations in ZAP70 lead to both abnormal thymic development and defective T-cell receptor (TCR) signaling of peripheral T-cells. In contrast to the lymphopenia in most SCID patients, ZAP70-deficient patients have lymphocytosis, despite the selective absence of CD8+ T-cells. The clinical presentation is usually before 2 years of age with typical findings of SCID. Here, we present three new ZAP70-deficient patients who vary in their clinical presentation. One of the ZAP70-deficient patients presented as a classical SCID, the second patient presented as a healthy looking wheezy infant, whereas the third patient came to clinical attention for the eczematous skin lesions simulating atopic dermatitis with eosinophilia and elevated immunoglobulin E (IgE), similar to the Omenn syndrome. This study illustrates that awareness of the clinical heterogeneity of ZAP70 deficiency is of utmost importance for making a fast and accurate diagnosis, which will contribute to the improvement of the adequate treatment of this severe immunodeficiency

She said she was in the family way': Pregnancy and infancy in modern Ireland

'She said she was in the family way' examines the subject of pregnancy and infancy in Ireland from the seventeenth to the twentieth century. It draws on exciting and innovative research by early-career and established academics, and consider topics that have been largely ignored by historians in Ireland. The book will make an important contribution to Irish women’s history, family history, childhood history, social history, crime history and medical history, and will provide a reference point for academics interested in themes of sexuality, childbirth, infanthood and parenthood

SVOP Is a Nucleotide Binding Protein

Background: Synaptic Vesicle Protein 2 (SV2) and SV2-related protein (SVOP) are transporter-like proteins that localize to neurotransmitter-containing vesicles. Both proteins share structural similarity with the major facilitator (MF) family of small molecule transporters. We recently reported that SV2 binds nucleotides, a feature that has also been reported for another MF family member, the human glucose transporter 1 (Glut1). In the case of Glut1, nucleotide binding affects transport activity. In this study, we determined if SVOP also binds nucleotides and assessed its nucleotide binding properties. Methodology/Principal Findings: We performed in vitro photoaffinity labeling experiments with the photoreactive ATP analogue, 8-azido-ATP[c] biotin and purified recombinant SVOP-FLAG fusion protein. We found that SVOP is a nucleotide-binding protein, although both its substrate specificity and binding site differ from that of SV2. Within the nucleotides tested, ATP, GTP and NAD show same level of inhibition on SVOP-FLAG labeling. Dose dependent studies indicated that SVOP demonstrates the highest affinity for NAD, in contrast to SV2, which binds both NAD and ATP with equal affinity. Mapping of the binding site revealed a single region spanning transmembrane domains 9–12, which contrasts to the two binding sites in the large cytoplasmic domains in SV2A. Conclusions/Significance: SVOP is the third MF family member to be found to bind nucleotides. Given that the binding sites are unique in SVOP, SV2 and Glut1, this feature appears to have arisen separately

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy