Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit

Pregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We demonstrate active placental uptake of 25(OH)D3 by endocytosis, placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself. These data demonstrate a complex interplay between vitamin D and the placenta and will inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy.</jats:p

Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit

Funder: Gerald Kerkut Charitable Trust; FundRef: http://dx.doi.org/10.13039/100012166Funder: Rank PrizeFunder: NIHR Clinical LectureshipPregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We demonstrate active placental uptake of 25(OH)D3 by endocytosis, placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself. These data demonstrate a complex interplay between vitamin D and the placenta and will inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy.CS was funded by a Gerald Kerkut Charitable Trust studentship and BA by Rank Prize and University of Southampton Vice Chancellor’s Studentships plus the MRC. KMG was supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (NIHR Senior Investigator [NF-SI-0515-10042], NIHR Southampton 1000DaysPlus Global Nutrition Research Group [17/63/154], and NIHR Southampton Biomedical Research Centre [IS-BRC-1215-20004]), British Heart Foundation (RG/15/17/3174) and the US National Institute on Aging of the National Institutes of Health (Award No. U24AG047867). KSJ was supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (ISBRC-1215-20014). The NIHR Cambridge Biomedical Research Centre is a partnership between Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. Experimental work performed by KSJ and FH at MRC. EWL was supported by Dr Ann Prentice (UK Medical Research Council U105960371). The SWS has been supported by grants from Medical Research Council (MRC) (4050502589 [MRC LEU]), Dunhill Medical Trust, British Heart Foundation, Food Standards Agency, National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, NIHR Oxford Biomedical Research Centre, University of Oxford, and the European Union’s Seventh Framework Programme (FP7/2007-2013), project EarlyNutrition, under grant agreement 289346 and the European Union’s Horizon 2020 research and innovation program (LIFECYCLE, grant agreement no. 733206). EC has been supported by the Wellcome Trust (201268/Z/16/Z) and an NIHR Clinical Lectureship. Work leading to these results was supported by the BBSRC (HDHL-Biomarkers, BB/P028179/1), as part of the ALPHABET project, supported by an award made through the ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL), Horizon 2020 grant agreement number 696295. The proteomic analyses (SDG and AM) were financially supported by the National Institutes of Health (R21AI122389) and the Beckman Institute at the California Institute of Technology. This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement InvADeRS no. 841172 to JMF. The electron microscopy image in Figure 2 was produced with help of the Biomedical imaging unit, Faculty of Medicine, University of Southampton

From staff-mix to skill-mix and beyond: towards a systemic approach to health workforce management

Throughout the world, countries are experiencing shortages of health care workers. Policy-makers and system managers have developed a range of methods and initiatives to optimise the available workforce and achieve the right number and mix of personnel needed to provide high-quality care. Our literature review found that such initiatives often focus more on staff types than on staff members' skills and the effective use of those skills. Our review describes evidence about the benefits and pitfalls of current approaches to human resources optimisation in health care. We conclude that in order to use human resources most effectively, health care organisations must consider a more systemic approach - one that accounts for factors beyond narrowly defined human resources management practices and includes organisational and institutional conditions

The Impacts of Micronutrient Fertility on the Mineral Uptake and Growth of <i>Brassica carinata</i>

Many abiotic factors impact the yield and growth of Brassica carinata (commonly referred to as carinata or Ethiopian mustard). Very little is known about carinata and how mineral nutrients impact its growth, and more specifically, the sufficiency values for fertility over the plant’s growth cycle and life stages. This study explored the impacts that plant nutrients, specifically micronutrients, can have on the growth and development of carinata over its distinct life stages (rosette, bolting, flowering, and pod set). Plants were grown under varying micronutrient concentrations (0, 25, 50, 75, 87.5, and 100%) of a modified Hoagland’s solution. Data were collected on plant height, canopy diameter, leaf tissue mineral nutrient concentrations, and biomass. The results demonstrated that micronutrient fertility has profound impacts on the production of Brassica carinata during different life stages. Boron (B) exclusion had the greatest impact on the growth and reproduction of Brassica carinata, with the death of the apical meristem that resulted in a lack of siliques or seeds at the lowest rate. Optimal relative elemental leaf tissue concentrations varied among micronutrient fertility concentrations and life stages. Certain elements exhibited linear increases in nutrient leaf tissue accumulation as solution concentration increased without reaching a maximum concentration during specific life stages. Other life stages and/or elements produced distinct plateau leaf tissue mineral concentrations despite increasing fertility treatment concentrations such as B in the rosette stage (47.2–50.0 mg·kg−1), copper (Cu) (bolting stage at 6.62–7.57 mg·kg−1), zinc (Zn) (bolting stage at 27.47–39.87 and flowering at 33.98–43.50 mg·kg−1), molybdenum (Mo) (flowering stage at 2.42–3.23 mg·kg−1), and manganese (Mn) (bolting stage at 117.03–161.63 mg·kg−1). This work demonstrates that Brassica carinata has different fertility demands and will accumulate differing leaf tissue concentrations during its life stages. This work serves as a baseline for further uptake and portioning work for Brassica carinata

Poultry manure nitrogen availability influences winter wheat yield and yield components

Published online: February 5, 2016Standard poultry manure use recommendations in North Carolina consider waste analysis but not differences among manure types, cropping seasons, or application timing. This study evaluated poultry manure source, N rate strategy, and application time effects on soft red winter wheat (Triticum aestivum L.) tiller density, yield components, grain yield, and N availability coefficients. Coefficients included fertilizer N equivalence based on grain yield and plant-available N based on aboveground plant N content. Four field experiments used broiler litter (BL) and composted layer manure (CLM), two rates (67 and 134 kg total-N ha−1), and three different application times (incorporated in October preplant, Feekes’ 3 in December/January, or Feekes’ 4 in February). Dual-source treatments received 67 kg N ha−1 of manure plus 67 kg N ha−1 as urea ammonium nitrate (UAN) solution at Feekes’ 5. Fertilizer-N (UAN) rate treatments (0, 39, 78, 117, and 156 kg N ha−1) were also included. Yields responded to N inputs but were lowest when BL and CLM were applied at 67 kg N ha−1 either preplant or at Feekes’ 3. Grain yield and N availability were greater with CLM than with BL (3.0 vs. 2.8 t ha−1 grain and 58 vs. 52 kg ha−1 N uptake, respectively). Availability coefficients ranged from 12 to 32%, lower than the standard assumed values of 50 to 60%. The feasible poultry manure application window includes preplant until Feekes’ 4, but fertilizing winter wheat crops solely with poultry manure may supply less N than intended