Optimal villi density for maximal oxygen uptake in the human placenta

We present a stream-tube model of oxygen exchange inside a human placenta functional unit (a placentone). The effect of villi density on oxygen transfer efficiency is assessed by numerically solving the diffusion-convection equation in a 2D+1D geometry for a wide range of villi densities. For each set of physiological parameters, we observe the existence of an optimal villi density providing a maximal oxygen uptake as a trade-off between the incoming oxygen flow and the absorbing villus surface. The predicted optimal villi density $0.47\pm0.06$ is compatible to previous experimental measurements. Several other ways to experimentally validate the model are also proposed. The proposed stream-tube model can serve as a basis for analyzing the efficiency of human placentas, detecting possible pathologies and diagnosing placental health risks for newborns by using routine histology sections collected after birth

Sugar-sweetened beverage consumption, correlates and interventions among Australian Aboriginal and Torres Strait Islander communities: a scoping review protocol

Introduction: Aboriginal and Torres Strait Islander communities of Australia experience poorer health outcomes in the areas of overweight and obesity, diabetes and cardiovascular disease. Contributing to this burden of disease in the Australian community generally and in Aboriginal and Torres Strait Islander communities, is the consumption of sugar-sweetened beverages (SSBs). We have described a protocol for a review to systematically scope articles that document use of SSBs and interventions to reduce their consumption with Aboriginal and Torres Strait Islander people. These results will inform future work that investigates interventions aimed at reducing harm associated with SSB consumption. Methods and analysis: This scoping review draws on a methodology that uses a six-step approach to search databases including PubMed, SCOPUS, CINAHL, Informit (including Informit: Indigenous Peoples), Joanna Briggs Institute EBP Database and Mura, between January 1980 and February 2017. Two reviewers will be engaged to search for and screen studies independently, using formulated selection criteria, for inclusion in our review. We will include primary research studies, systematic reviews including meta-analysis or meta-synthesis, reports and unpublished grey literature. Results will be entered into a table identifying study details and characteristics, summarised using a Preferred Reporting Items for Systematic Reviews and Meta-Analysis chart and then critically analysed. Ethics and dissemination: This review will not require ethics committee review. Results will be disseminated at appropriate scientific meetings, as well as through the Aboriginal and Torres Strait Islander community.Jodie C Avery, Jacqueline A Bowden, Joanne Dono, Odette R Gibson, Aimee Brownbill, Wendy Keech, David Roder, Caroline L Mille

Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction

Placental dysfunction is the underlying cause of pregnancy complications such as fetal growth restriction (FGR) and pre-eclampsia. No therapies are available to treat a poorly functioning placenta, primarily due to the risks of adverse side effects in both the mother and the fetus resulting from systemic drug delivery. The use of targeted liposomes to selectively deliver payloads to the placenta has the potential to overcome these issues. In this study, we assessed the safety and efficacy of epidermal growth factor (EGF)-loaded, peptide-decorated liposomes to improve different aspects of placental function, using tissue from healthy control pregnancies at term, and pregnancies complicated by FGR. Phage screening identified a peptide sequence, CGPSARAPC (GPS), which selectively homed to mouse placentas in vivo, and bound to the outer syncytiotrophoblast layer of human placental explants ex vivo. GPS-decorated liposomes were prepared containing PBS or EGF (50–100 ng/mL), and placental explants were cultured with liposomes for up to 48 h. Undecorated and GPS-decorated liposomes containing PBS did not affect the basal rate of amino acid transport, human chorionic gonadotropin (hCG) release or cell turnover in placental explants from healthy controls. GPS-decorated liposomes containing EGF significantly increased amino acid transporter activity in healthy control explants, but not in placental explants from women with FGR. hCG secretion and cell turnover were unaffected by EGF delivery; however, differential activation of downstream protein kinases was observed when EGF was delivered via GPS-decorated vs. undecorated liposomes. These data indicate that targeted liposomes represent a safe and useful tool for the development of new therapies for placental dysfunction, recapitulating the effects of free EGF

Sugar-sweetened beverage (SSB) consumption, correlates and interventions among Australian Aboriginal and Torres Strait Islander communities: a scoping review

Objectives Sugar-sweetened beverage (SSB) consumption in Australian Aboriginal and Torres Strait Islander people is reported to be disproportionally high compared with the general Australian population. This review aimed to scope the literature documenting SSB consumption and interventions to reduce SSB consumption among Australian Aboriginal and Torres Strait Islander people. Findings will inform strategies to address SSB consumption in Aboriginal and Torres Strait Islander communities. Methods PubMed, SCOPUS, CINAHL, Informit, Joanna Briggs Institute EBP, Mura databases and grey literature were searched for articles published between January 1980 and June 2018. Studies were included if providing data specific to an Australian Aboriginal and/or Torres Strait Islander population’s SSB consumption or an intervention that focused on reducing SSB consumption in this population. Design Systematic scoping review. Results 59 articles were included (1846 screened). While reported SSB consumption was high, there were age-related and community-related differences observed in some studies. Most studies were conducted in remote or rural settings. Implementation of nutrition interventions that included an SSB component has built progressively in remote communities since the 1980s with a growing focus on community-driven, culturally sensitive approaches. More recent studies have focused exclusively on SSB consumption. Key SSB-related intervention elements included incentivising healthier options; reducing availability of less-healthy options; nutrition education; multifaceted or policy implementation (store nutrition or government policy). Conclusions There was a relatively large number of studies reporting data on SSB consumption and/or sales, predominantly from remote and rural settings. During analysis it was subjectively clear that the more impactful studies were those which were community driven or involved extensive community consultation and collaboration. Extracting additional SSB-specific consumption data from an existing nationally representative survey of Aboriginal and Torres Strait Islander people could provide detailed information for demographic subgroups and benchmarks for future interventions. It is recommended that a consistent, culturally appropriate, set of consumption measures be developed.Kathleen M Wright, Joanne Dono, Aimee L Brownbill, Odette Pearson, nee Gibson, Jacqueline Bowden, Thomas P Wycherley, Wendy Keech, Kerin O'Dea, David Roder, Jodie C Avery, Caroline L Mille

Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-17, pub-electronic 2021-10-25Publication status: PublishedFunder: Medical Research Council; Grant(s): MR/P023401/1Funder: European Regional Development Fund; Grant(s): 2014-2020.4.01.15-0012Funder: Estonian Research Council; Grant(s): PRG230Placental dysfunction is the underlying cause of pregnancy complications such as fetal growth restriction (FGR) and pre-eclampsia. No therapies are available to treat a poorly functioning placenta, primarily due to the risks of adverse side effects in both the mother and the fetus resulting from systemic drug delivery. The use of targeted liposomes to selectively deliver payloads to the placenta has the potential to overcome these issues. In this study, we assessed the safety and efficacy of epidermal growth factor (EGF)-loaded, peptide-decorated liposomes to improve different aspects of placental function, using tissue from healthy control pregnancies at term, and pregnancies complicated by FGR. Phage screening identified a peptide sequence, CGPSARAPC (GPS), which selectively homed to mouse placentas in vivo, and bound to the outer syncytiotrophoblast layer of human placental explants ex vivo. GPS-decorated liposomes were prepared containing PBS or EGF (50–100 ng/mL), and placental explants were cultured with liposomes for up to 48 h. Undecorated and GPS-decorated liposomes containing PBS did not affect the basal rate of amino acid transport, human chorionic gonadotropin (hCG) release or cell turnover in placental explants from healthy controls. GPS-decorated liposomes containing EGF significantly increased amino acid transporter activity in healthy control explants, but not in placental explants from women with FGR. hCG secretion and cell turnover were unaffected by EGF delivery; however, differential activation of downstream protein kinases was observed when EGF was delivered via GPS-decorated vs. undecorated liposomes. These data indicate that targeted liposomes represent a safe and useful tool for the development of new therapies for placental dysfunction, recapitulating the effects of free EGF

Liquid phase blending of metal-organic frameworks.

The liquid and glass states of metal-organic frameworks (MOFs) have recently become of interest due to the potential for liquid-phase separations and ion transport, alongside the fundamental nature of the latter as a new, fourth category of melt-quenched glass. Here we show that the MOF liquid state can be blended with another MOF component, resulting in a domain structured MOF glass with a single, tailorable glass transition. Intra-domain connectivity and short range order is confirmed by nuclear magnetic resonance spectroscopy and pair distribution function measurements. The interfacial binding between MOF domains in the glass state is evidenced by electron tomography, and the relationship between domain size and Tg investigated. Nanoindentation experiments are also performed to place this new class of MOF materials into context with organic blends and inorganic alloys

Dysregulated flow-mediated vasodilatation in the human placenta in fetal growth restriction

Increased vascular resistance and reduced fetoplacental blood flow are putative aetiologies in the pathogenesis of fetal growth restriction (FGR); however, the regulating sites and mechanisms remain unclear. We hypothesised that placental vessels dictate fetoplacental resistance and in FGR exhibit endothelial dysfunction and reduced flow-mediated vasodilatation (FMVD). Resistance was measured in normal pregnancies (n = 10) and FGR (n = 10) both in vivo by umbilical artery Doppler velocimetry and ex vivo by dual placental perfusion. Ex vivo FMVD is the reduction in fetal-side inflow hydrostatic pressure (FIHP) following increased flow rate. Results demonstrated a significant correlation between vascular resistance measured in vivo and ex vivo in normal pregnancy, but not in FGR. In perfused FGR placentas, vascular resistance was significantly elevated compared to normal placentas (58 ± 7.7 mmHg and 36.8 ± 4.5 mmHg, respectively; 8 ml min−1; means ± SEM; P < 0.0001) and FMVD was severely reduced (3.9 ± 1.3% and 9.1 ± 1.2%, respectively). In normal pregnancies only, the highest level of ex vivo FMVD was associated with the lowest in vivo resistance. Inhibition of NO synthesis during perfusion (100 μM L-NNA) moderately elevated FIHP in the normal group, but substantially in the FGR group. Human placenta artery endothelial cells from FGR groups exhibited increased shear stress-induced NO generation, iNOS expression and eNOS expression compared with normal groups. In conclusion, fetoplacental resistance is determined by placental vessels, and is increased in FGR. The latter also exhibit reduced FMVD, but with a partial compensatory increased NO generation capacity. The data support our hypothesis, which highlights the importance of FMVD regulation in normal and dysfunctional placentation

A massively multi-scale approach to characterizing tissue architecture by synchrotron micro-CT applied to the human placenta

From The Royal Society via Jisc Publications RouterHistory: received 2021-02-16, accepted 2021-05-06, collection 2021-06, pub-electronic 2021-06-02Article version: VoRPublication status: PublishedFunder: Engineering and Physical Sciences Research Council; Id: http://dx.doi.org/10.13039/501100000266; Grant(s): EP/M023877/1, EP/T008725/1Funder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100000265; Grant(s): MR/N011538/1Funder: Wellcome Trust; Id: http://dx.doi.org/10.13039/100004440; Grant(s): 212980/Z/18/ZFunder: Great Britain Sasakawa Foundation; Id: http://dx.doi.org/10.13039/501100000625Multi-scale structural assessment of biological soft tissue is challenging but essential to gain insight into structure–function relationships of tissue/organ. Using the human placenta as an example, this study brings together sophisticated sample preparation protocols, advanced imaging and robust, validated machine-learning segmentation techniques to provide the first massively multi-scale and multi-domain information that enables detailed morphological and functional analyses of both maternal and fetal placental domains. Finally, we quantify the scale-dependent error in morphological metrics of heterogeneous placental tissue, estimating the minimal tissue scale needed in extracting meaningful biological data. The developed protocol is beneficial for high-throughput investigation of structure–function relationships in both normal and diseased placentas, allowing us to optimize therapeutic approaches for pathological pregnancies. In addition, the methodology presented is applicable in the characterization of tissue architecture and physiological behaviours of other complex organs with similarity to the placenta, where an exchange barrier possesses circulating vascular and avascular fluid spaces

Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells

Maternal exposure during pregnancy to toxins can occasionally lead to miscarriage and malformation. It is currently thought that toxins pass through the placental barrier, albeit bilayered in the first trimester, and damage the fetus directly, albeit at low concentration. Here we examined the responses of human embryonic stem (hES) cells in tissue culture to two metals at low concentration. We compared direct exposures with indirect exposures across a bi-layered model of the placenta cell barrier. Direct exposure caused increased DNA damage without apoptosis or a loss of cell number but with some evidence of altered differentiation. Indirect exposure caused increased DNA damage and apoptosis but without loss of pluripotency. This was not caused by metal ions passing through the barrier. Instead the hES cells responded to signalling molecules (including TNF-α) secreted by the barrier cells. This mechanism was dependent on connexin 43 mediated intercellular ‘bystander signalling’ both within and between the trophoblast barrier and the hES colonies. These results highlight key differences between direct and indirect exposure of hES cells across a trophoblast barrier to metal toxins. It offers a theoretical possibility that an indirectly mediated toxicity of hES cells might have biological relevance to fetal development