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This study explored the psychological experience of a small cohort of nursing and midwifery students who had been deployed to work in the NHS during the COVID-19 pandemic. The students were employed on band 4 contracts within an acute NHS Trust in the South of England. Overall, students found the experience of being deployed into clinical practice during a major public health emergency a valuable and unique experience that strengthened their resilience. However, students reported a significant level of personal obligation to opt-in to deployment. Working within clinical areas caused heightened anxiety and uncertainty, which was alleviated by managerial support.

Resilience in nursing and midwifery involves being able to manage ethically adverse situations without suffering moral distress and is key to mental wellbeing, staff retention and patient safety. The aim of this research was to ask what the psychological effects were for nursing and midwifery students who had been deployed to work in the NHS during the COVID-19 pandemic. This study looked at the incidence of burnout in a small cohort of nursing and midwifery students who were employed as band 4 aspirant nurses and midwives in acute NHS trusts in the south of England. The findings suggested that student midwives reported higher levels of emotional exhaustion and depersonalisation than student nurses but overall, both cohorts of students reported moderate levels of burnout. Part 2 will present the lived experience of deployment as described by students.

Afternoon Colleagues, This paper is to be published in June 2020. I have uploaded a post-production final proof without working HTMLs.

KEY POINTS Maternal hypertension is associated with increased rates of pregnancy pathologies, including fetal growth restriction, due at least in part to reductions in nitric oxide (NO) bioavailability and associated vascular dysfunction. Dietary nitrate supplementation, from beetroot juice (BRJ), has been shown to increase NO bioavailability and improve cardiovascular function in both preclinical and clinical studies. This study is the first to investigate effects of dietary nitrate supplementation in a pregnant animal model. Importantly, the effects of nitrate-containing BRJ were compared with both 'placebo' (nitrate-depleted) BRJ as well as water to control for potential nitrate-independent effects. Our data show novel, nitrate-independent effects of BRJ to lower blood pressure and improve vascular function in endothelial nitric oxide synthase knockout (eNOS-/- ) mice. These findings suggest potential beneficial effects of BRJ supplementation in pregnancy, and emphasize the importance of accounting for nitrate-independent effects of BRJ in study design and interpretation. ABSTRACT Maternal hypertension is associated with adverse pregnancy outcomes, including fetal growth restriction (FGR), due in part to reductions in nitric oxide (NO) bioavailability. We hypothesized that maternal dietary nitrate administration would increase NO bioavailability to reduce systolic blood pressure (SBP), improve vascular function and increase fetal growth in pregnant endothelial NO synthase knockout (eNOS-/- ) mice, which exhibit hypertension, endothelial dysfunction and FGR. Pregnant wildtype (WT) and eNOS-/- mice were supplemented with nitrate-containing beetroot juice (BRJ+) from gestational day (GD) 12.5. Control mice received an equivalent dose of nitrate-depleted BRJ (BRJ-) or normal drinking water. At GD17.5, maternal SBP was measured; at GD18.5, maternal nitrate/nitrite concentrations, uterine artery (UtA) blood flow and endothelial function were assessed, and pregnancy outcomes were determined. Plasma nitrate concentrations were increased in both WT and eNOS-/- mice supplemented with BRJ+ (P < 0.001), whereas nitrite concentrations were increased only in eNOS-/- mice (P < 0.001). BRJ- did not alter nitrate/nitrite concentrations. SBP was lowered and UtA endothelial function was enhanced in eNOS-/- mice supplemented with either BRJ+ or BRJ-, indicating nitrate-independent effects of BRJ. Improvements in endothelial function in eNOS-/- mice were abrogated in the presence of 25 mm KCl, implicating enhanced EDH signalling in BRJ- treated animals. At GD18.5, eNOS-/- fetuses were significantly smaller than WT animals (P < 0.001), but BRJ supplementation did not affect fetal weight. BRJ may be a beneficial intervention in pregnancies associated with hypertension, endothelial dysfunction and reduced NO bioavailability. Our data showing biological effects of non-nitrate components of BRJ have implications for both interpretation of previous findings and in the design of future clinical trials.

Fetal growth restriction (FGR), where a fetus fails to reach its genetic growth potential, affects up to 8% of pregnancies and is a major risk factor for stillbirth and adulthood morbidity. There are currently no treatments for FGR, but candidate therapies include the phosphodiesterase-5 inhibitor sildenafil citrate (SC). Randomized clinical trials in women demonstrated no effect of SC on fetal growth in cases of severe early onset FGR; however, long-term health outcomes on the offspring are unknown. This study aimed to assess the effect of antenatal SC treatment on metabolic and cardiovascular health in offspring by assessing postnatal weight gain, glucose tolerance, systolic blood pressure, and resistance artery function in a mouse model of FGR, the placental-specific insulin-like growth factor 2 (PO) knockout mouse. SC was administered subcutaneously (10 mg/kg) daily from embryonic day (E)12.5. Antenatal SC treatment did not alter fetal weight or viability but increased postnatal weight gain in wild-type (WT) female offspring ( P < 0.05) and reduced glucose sensitivity in both WT ( P < 0.01) and P0 ( P < 0.05) female offspring compared with controls. Antenatal SC treatment increased systolic blood pressure in both male (WT vs. WT-SC: 117 ± 2 vs. 140 ± 3 mmHg, P < 0.0001; P0 vs. P0-SC: 113 ± 3 vs. 140 ± 4 mmHg, P < 0.0001; means ± SE) and female (WT vs. WT-SC: 121 ± 2 vs. 140 ± 2 mmHg, P < 0.0001; P0 vs. P0-SC: 117 ± 2 vs. 144 ± 4 mmHg, P < 0.0001) offspring at 8 and 13 wk of age. Increased systolic blood pressure was not attributed to altered mesenteric artery function. In utero exposure to SC may result in metabolic dysfunction and elevated blood pressure in later life. NEW & NOTEWORTHY Sildenafil citrate (SC) is currently used to treat fetal growth restriction (FGR). We demonstrate that SC is ineffective at treating FGR, and leads to a substantial increase systolic blood pressure and alterations in glucose homeostasis in offspring. We therefore urge caution and suggest that further studies are required to assess the safety and efficacy of SC in utero, in addition to the implications on long-term health.

The aim of this study was to determine the iron (Fe) concentration profile within the lumen of the S2 renal proximal convoluted tubule (PCT) and to resolve whether this nephron segment transported Fe. To do this, we performed in vivo renal micropuncture on Wistar rats, collected PCT tubular fluid from superficial nephrons, and measured Fe concentration. The Fe concentration profile along the S2 PCT suggested significant Fe reabsorption. Proximal tubules were also microperfused in vivo with physiological solutions containing Fe and Zn, Cu, Mn, or Cd. PCTs perfused with 12μmol.l−1 55FeCl3 reabsorbed 105.2±12.7 fmol.mm−1.min−1 Fe, 435±52pmol.mm-1.min−1 Na, and 2.7±0.2nl.mm−1.min−1 water (mean ± SEM; n=19). Addition of ascorbate (1mmol.l−1) to the perfusate did not significantly alter Fe, Na, or water reabsorption. Supplementing the control perfusate with 60μmol.l−1 FeSO4 significantly decreased 55Fe uptake. Recalculating for the altered molar activity following addition of unlabeled Fe revealed a three-fold increase in Fe flux. Addition to the perfusate 12μmol.l−1 CuSO4, MnSO4, CdSO4, or ZnSO4 did not affect Fe, Na, or water flux. In conclusion, (1) in vivo, S2 PCTs of rat reabsorb Fe and (2) Fe is reabsorbed along the PCT via a pathway that is insensitive to Cu, Mn, Cd, or Zn. Together, these data demonstrate for the first time the hitherto speculated process of renal Fe filtration and subsequent tubular Fe reabsorption in a living mammal.

In preeclampsia, vasospasm, oxidative stress, endothelial dysfunction, and immune dysregulation are key mediators of maternal disease. A new time-of-disease treatment is needed with the potential to treat these areas of pathophysiology. A review of the literature has indicated that metabolites of the kynurenine pathway have the potential to; (i) induce vasorelaxation of resistance arteries and reduce blood pressure; (ii) exert antioxidant effects and reduce the effects of poly-ADP ribose polymerase activation (iii) prevent endothelial dysfunction and promote endothelial nitric oxide production; (iv) cause T cell differentiation into tolerogenic regulatory T cells and induce apoptosis of pro-inflammatory Th1 cells. This has led to the hypothesis that increasing Kynurenine pathway activity may offer a new treatment strategy for preeclampsia.

Nitric oxide (NO) is essential in the control of fetoplacental vascular tone, maintaining a high flow−low resistance circulation that favors oxygen and nutrient delivery to the fetus. Reduced fetoplacental blood flow is associated with pregnancy complications and is one of the major causes of fetal growth restriction (FGR). The reduction of dietary nitrate to nitrite and subsequently NO may provide an alternative source of NO in vivo. We have previously shown that nitrite induces vasorelaxation in placental blood vessels from normal pregnancies, and that this effect is enhanced under conditions of hypoxia. Herein, we aimed to determine whether nitrite could also act as a vasodilator in FGR. Using wire myography, vasorelaxant effects of nitrite were assessed on pre-constricted chorionic plate arteries (CPAs) and veins (CPVs) from normal and FGR pregnancies under normoxic and hypoxic conditions. Responses to the NO donor, sodium nitroprusside (SNP), were assessed in parallel. Nitrate and nitrite concentrations were measured in fetal plasma. Hypoxia significantly enhanced vasorelaxation to nitrite in FGR CPAs (p &lt, 0.001), and in both normal (p &lt, 0.001) and FGR (p &lt, 0.01) CPVs. Vasorelaxation to SNP was also potentiated by hypoxia in both normal (p &lt, 0.0001) and FGR (p &lt, 0.01) CPVs. However, compared to vessels from normal pregnancies, CPVs from FGR pregnancies showed significantly lower reactivity to SNP (p &lt, 0.01). Fetal plasma concentrations of nitrate and nitrite were not different between normal and FGR pregnancies. Together, these data show that nitrite-mediated vasorelaxation is preserved in FGR, suggesting that interventions targeting this pathway have the potential to improve fetoplacental blood flow in FGR pregnancies.

Supplemental Digital Content is available in the text., Rationale: Activation of the kynurenine pathway of tryptophan catabolism by infection and inflammation contributes to the development of systemic hypotension. Commercially-available kynurenine has direct vasorelaxant effects on arteries from several species and reduces systemic blood pressure when administered to normotensive or hypertensive rats. Objectives: To determine whether kynurenine promotes relaxation of human resistance arteries from normotensive and hypertensive pregnant women and to identify the vascular mechanism of its effects. Methods and Results: In isolated omental and myometrial resistance arteries from normotensive pregnant women, kynurenine (1 mmol/L) significantly reduced U46619-induced constriction (omentum N=14, P=2.4×10−3; myometrium N=21–25, P=2.6×10−4) and relaxed preconstricted arteries (N=53, P=1.0×10−11; N=20, P=8.8×10−3). Vasorelaxation persisted following endothelium removal (N=7, P=1.6×10−4) but was completely prevented by inhibition of large-conductance Ca2+-activated K+ channels (BKCa) channels with iberiotoxin (N=9, P=5.7×10−4) or paxilline (N=10, P=2.1×10−17). Accordingly, in isolated vascular smooth muscle cells from omental arteries, kynurenine increased the BKCa current (n=5–8, P=0.022) and the amplitude of spontaneous transient outward currents (n=6, P=0.031) but did not affect spontaneous transient outward current frequency. Kynurenine also increased Ca2+ spark frequency of pressurized omental arteries (n=8, P=0.031). Vasorelaxant effects of kynurenine persisted following inhibition of ryanodine receptors (N=7, P=0.48) but were moderately reduced by inhibition of adenylate cyclase (N=9, P=0.024). In arteries from women with preeclampsia, kynurenine similarly attenuated vasoconstriction (N=15, P=1.3×10−5) and induced BKCa-mediated vasodilation (N=16, P=2.0×10−4). Vasorelaxation in response to kynurenine and a specific BKCa activator, NS11021, was absent in fetal-derived placental resistance arteries in normal pregnancy and preeclampsia. Conclusions: Kynurenine dilates systemic arteries from multiple territories via BKCa activation. Notably, the vasorelaxatory capacity of kynurenine is preserved in preeclampsia, suggesting this approach may have translational potential for the treatment of hypertension in pregnancy. The data warrant further investigation of the potential to exploit this endogenous vasorelaxant as a new treatment for hypertensive pathologies.

Maternal hypertension is associated with increased rates of pregnancy pathologies, including fetal growth restriction, due at least in part to reductions in nitric oxide (NO) bioavailability and associated vascular dysfunction. Dietary nitrate supplementation, from beetroot juice (BRJ), has been shown to increase NO bioavailability and improve cardiovascular function in both preclinical and clinical studies. This study is the first to investigate effects of dietary nitrate supplementation in a pregnant animal model. Importantly, the effects of nitrate-containing BRJ were compared with both 'placebo' (nitrate-depleted) BRJ as well as water to control for potential nitrate-independent effects. Our data show novel, nitrate-independent effects of BRJ to lower blood pressure and improve vascular function in endothelial nitric oxide synthase knockout (eNOSMaternal hypertension is associated with adverse pregnancy outcomes, including fetal growth restriction (FGR), due in part to reductions in nitric oxide (NO) bioavailability. We hypothesized that maternal dietary nitrate administration would increase NO bioavailability to reduce systolic blood pressure (SBP), improve vascular function and increase fetal growth in pregnant endothelial NO synthase knockout (eNOS

Quality clinical placements for pre-registration nursing students are particularly important at a time when there is a recruitment crisis within nursing. A study was conducted to identify what impact clinical placements have on pre-registration adult nursing students' choice of clinical specialty as a newly qualified nurse (NQN). Data were collected from students on their final day of a BSc (Hons) programme at two campus sites at a university in the east of England. Participants judged the desirability of a clinical placement on the basis of the quality of the learning, working and clinical environment and the nature of the specialty. The influence of clinical placements on the choice of first destination of NQNs more than doubles within the final year of study. Clinical placements generate vivid experiences, which exert a strong influence on the first employment destination decisions of NQNs.

Aim Underlying mechanisms of poor pregnancy outcome in obese (OB) mothers (body mass index [BMI] ≥ 30 kg/m2) are unknown. Our studies demonstrate that OB pregnant women have altered myometrial artery (MA) function related to the thromboxane and nitric oxide pathways. In obesity, increased central fat mass is associated with an altered endocrine milieu. We tested the hypothesis that in OB pregnant women the omentum, a central fat store, releases factors that promote dysfunction in normal MAs. Methods Myometrial and omental adipose tissue biopsies were obtained from women with uncomplicated term pregnancies. Omental adipose tissue explants from six normal weight (NW; BMI 18.5–24.9 kg/m2) and six OB (BMI ≥ 30 kg/m2) women were cultured and the conditioned medium collected and pooled to produce NW medium and OB medium. Adipokine concentrations were measured using enzyme-linked immunosorbent assays. Wire myography was used to assess the effect of conditioned medium (NW or OB; N = 7) or leptin (100 nM; N = 5) exposure on MA responses to U46619 (thromboxane-mimetic) and bradykinin (endothelial-dependent vasodilator). Results OB medium had higher leptin and lower adiponectin levels than NW medium. U46619 and bradykinin concentration response curves shifted upwards in MAs exposed to OB medium but were unaffected by leptin. Conclusions Omental adipose tissue from OB pregnant women produced altered concentrations of adipokines. Acute OB medium exposure induced MA dysfunction, an effect not mirrored by exposure to leptin. These data suggest that an aberrant endocrine environment created by increased central adiposity in OB pregnant women induces vascular endothelial dysregulation, which may predispose them to a poor pregnancy outcome.

Fetal growth restriction (FGR) affects around 5% of pregnancies and is associated with significant short- and long-term adverse outcomes. A number of factors can increase the risk of FGR, one of which is poor maternal diet. In terms of pathology, both clinically and in many experimental models of FGR, impaired uteroplacental vascular function is implicated, leading to a reduction in the delivery of oxygen and nutrients to the developing fetus. Whilst mechanisms underpinning impaired uteroplacental vascular function are not fully understood, interventions aimed at enhancing nitric oxide (NO) bioavailability remain a key area of interest in obstetric research. In addition to endogenous NO production from the amino acid l-arginine, via nitric oxide synthase (NOS) enzymes, research in recent years has established that significant NO can be derived from dietary nitrate, via the 'alternative NO pathway'. Dietary nitrate, abundant in green leafy vegetables and beetroot, can increase NO bioactivity, conferring beneficial effects on cardiovascular function and blood flow. Given the beneficial effects of dietary nitrate supplementation to date in non-pregnant humans and animals, current investigations aim to assess the therapeutic potential of this approach in pregnancy to enhance NO bioactivity, improve uteroplacental vascular function and increase fetal growth.

The endothelium is an established modulator of vascular tone; however, the recent discovery of the anti-contractile nature of perivascular adipose tissue (PVAT) suggests that the fat, which surrounds many blood vessels, can also modulate vascular tone. Both the endothelium and PVAT secrete vasoactive substances, which regulate vascular function. Many of these factors are common to both the endothelium and PVAT; therefore, this review will highlight the potential shared mechanisms in the modulation of vascular tone. Endothelial dysfunction is a hallmark of many vascular diseases, including hypertension and obesity. Moreover, PVAT dysfunction is now being reported in several cardio-metabolic disorders. Thus, this review will also discuss the mechanistic insights into endothelial and PVAT dysfunction in order to evaluate whether PVAT modulation of vascular contractility is similar to that of the endothelium in health and disease. Linked Articles This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue – Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc

Rationale: Maternal obesity pre-programmes offspring to develop obesity and associated cardiovascular disease. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the vasculature, which is reduced in hypertension and obesity. Objective: The objective of this study was to determine whether maternal obesity pre-programmes offspring to develop PVAT dysfunction in later life. Methods: Female Sprague–Dawley rats were fed a diet containing 10% (control) or 45% fat (high fat diet, HFD) for 12 weeks prior to mating and during pregnancy and lactation. Male offspring were killed at 12 or 24 weeks of age and tension in PVAT-intact or -denuded mesenteric artery segments was measured isometrically. Concentration–response curves were constructed to U46619 and norepinephrine. Results: Only 24-week-old HFD offspring were hypertensive (PM l-NMMA attenuated the anti-contractile effect of PVAT and increased contractility of PVAT-denuded arteries (PPPM A769662) was anti-contractile in PVAT-denuded (PPPP Conclusions: The diminished anti-contractile effects of PVAT in offspring of HFD dams are primarily due to release of a PVAT-derived contractile factor and reduced NO bioavailability.

Chronic hypertension in pregnancy is associated with significant adverse pregnancy outcomes, increasing the risk of pre-eclampsia, fetal growth restriction and preterm birth. Dietary nitrate, abundant in green leafy vegetables and beetroot, is reduced in vivo to nitrite and subsequently nitric oxide, and has been demonstrated to lower blood pressure, improve vascular compliance and enhance blood flow in non-pregnant humans and animals.\ud \ud The primary aims of this study were to determine the acceptability and efficacy of dietary nitrate supplementation, in the form of beetroot juice, to lower blood pressure in hypertensive pregnant women. In this double-blind, placebo-controlled feasibility trial, 40 pregnant women received either daily nitrate supplementation (70 mL beetroot juice, n = 20) or placebo (70 mL nitrate-depleted beetroot juice, n = 20) for 8 days. Blood pressure, cardiovascular function and uteroplacental blood flow was assessed at baseline and following acute (3 h) and prolonged (8 days) supplementation. Plasma and salivary samples were collected for analysis of nitrate and nitrite concentrations and acceptability of this dietary intervention was assessed based on questionnaire feedback. Dietary nitrate significantly increased plasma and salivary nitrate/nitrite concentrations compared with placebo juice (p

WHAT IS KNOWN ON THE SUBJECT?: There is increasing demand for clinical placements for pre-registration nursing students. New models of mentorship have been developed to meet the demand for clinical placements by increasing the number of students within each placement. At present there are no published research studies into the effectiveness of team mentorship utilized by pre-registration nursing students within in-patient mental health settings. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: This paper reports findings from a study that explored the experiences of mental health students within the social world of their clinical placement, adopting a new approach to practice learning where students support each other's learning. Students found their engagement in the pilot project as valuable as being exposed to the new team mentorship model which introduced them to peer-assisted learning. The learning that arose from peer-assisted learning within team mentorship appeared to provide learning opportunities that enabled students' to develop greater self-awareness and confidence. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Peer-assisted learning where students support the learning of each other, can lead to a wider range of learning opportunities for, as well as between, nursing students. In order for students to participate in care and become a "learning team," suitable in-patient mental health wards need to be identified that can support this new approach to the supervision, assessment and support of students. The establishment of team mentorship within mental health in-patient settings is dependent on the support provided by practice educators and university link lecturers to nurse mentors and coaches which in turn, determines the quality of the student experience. Abstract Introduction This paper presents findings from a study that evaluated mental health nursing students' experience of a team mentoring model called Coaching and peer-assisted learning (C-PAL). At present there are no published research studies into the effectiveness of team mentorship utilized by nursing students within in-patient mental health settings. Aim The study utilized an interpretivist methodology where the focus was on individuals in their social world. Method Two focus groups were held with fifteen students who had experienced C-PAL in four in-patient wards. Findings Students' overall experience of piloting C-PAL was positive. Learning opportunities (Theme 3) appeared to be dependent on the quality of peer support (Theme 5) which in turn, enhanced the learner experience and increased the level of student confidence (Theme 6). Less positive experiences included inadequate preparation (Theme 1), poor understanding of the model and competition for learning experiences. Implications for practice We tentatively suggest that team mentorship models such as C-PAL may be suitable for acute in-patient mental health settings. The success of C-PAL depends upon the preparation of nursing staff, mentors (Theme 4), coaches and students in relation to role expectations, shift rostering (Theme 2) and the implementation of "huddling" to promote opportunistic learning.

INTRODUCTION: Potassium (K(+)) channels are key regulators of vascular smooth muscle cell (VSMC) excitability. In systemic small arteries, Kv7 channel expression/activity has been noted and a role in vascular tone regulation demonstrated. We aimed to demonstrate functional Kv7 channels in human fetoplacental small arteries. METHODS: Human placental chorionic plate arteries (CPAs) were obtained at term. CPA responses to Kv7 channel modulators was determined by wire myography. Presence of Kv7 channel mRNA (encoded by KCNQ1-5) and protein expression were assessed by RT-PCR and immunohistochemistry/immunofluorescence, respectively. RESULTS: Kv7 channel blockade with linopirdine increased CPA basal tone and AVP-induced contraction. Pre-contracted CPAs (AVP; 80 mM K(+) depolarization solution) exhibited significant relaxation to flupirtine, retigabine, the acrylamide (S)-1, and (S) BMS-204352, differential activators of Kv7.1 - Kv7.5 channels. All CPAs assessed expressed KCNQ1 and KCNQ3-5 mRNA; KCNQ2 was expressed only in a subset of CPAs. Kv7 protein expression was confirmed in intact CPAs and isolated VSMCs. DISCUSSION: Kv7 channels are present and active in fetoplacental vessels, contributing to vascular tone regulation in normal pregnancy. Targeting these channels may represent a therapeutic intervention in pregnancies complicated by increased vascular resistance.

Background: This article presents findings from a study that sought to explore the extent to which clinical placements have an impact on nursing students' decisions regarding their first staff nurse post. Within the UK, nursing is facing a recruitment crisis with particular difficulty recruiting to areas such as primary care and care of older people. Transitioning into a new role is challenging in any occupation, but it is a particular problem in nursing where the realities of professional practice often differ from students' perception of the staff nurse role as shaped by their clinical placements. Aim: This pilot study aimed to explore the influence of practice placements on final-year adult nursing students' career decisions. Method: Qualitative and quantitative data were collected in a single phase using a questionnaire distributed to nursing students on the final day of their course. A total of 35 completed questionnaires were returned (response rate 57%). Results: Half of the participants entered the course with preconceived preferences for clinical specialisms. However, only five participants (14%) applied for first-destination posts in that specialism. The overall importance of placements in career choice increased across the three years of the programme. Although placements in all three years are important, the experiences in year 3 are pivotal, with 74% ranking these as ‘significantly influential’ in their decision-making process. Analysis of the data obtained from the free-text responses from the questionnaire suggested that working environment; the level of support provided by mentors and clinical staff; the opportunity to make a difference to patients' lives and the variety of placements, were key influences on nursing students' decision regarding their first staff nurse post. Conclusions: This study highlights the key role of practice placements in the career choices of student nurses, particularly during the final year of their programme. It shows that students are likely to apply for posts in the placement area they found to be most supportive and developmental.

Fetal growth restriction (FGR) affects 3–8% of human pregnancies. Mouse models have provided important etiological data on FGR; they permit the assessment of treatment strategies on the physiological function of both mother and her developing offspring. Our study aimed to 1) develop a method to assess vascular function in fetal mice and 2) as a proof of principle ascertain whether a high dose of sildenafil citrate (SC; Viagra) administered to the pregnant dam affected fetal vascular reactivity. We developed a wire myography methodology for evaluation of fetal vascular function in vitro using the placenta-specific insulin-like growth factor II ( Igf2) knockout mouse (P0; a model of FGR). Vascular function was determined in abdominal aortas isolated from P0 and wild-type (WT) fetuses at embryonic day (E) 18.5 of gestation. A subset of dams received SC 0.8 mg/ml via drinking water from E12.5; data were compared with water-only controls. Using wire myography, we found that fetal aortic rings exhibited significant agonist-induced contraction, and endothelium-dependent and endothelium-independent relaxation. Sex-specific alterations in reactivity were noted in both strains. Maternal treatment with SC significantly attenuated endothelium-dependent and endothelium-independent relaxation of fetal aortic rings. Mouse fetal abdominal aortas reproducibly respond to vasoactive agents. Study of these vessels in mouse genetic models of pregnancy complications may 1) help to delineate early signs of abnormal vascular reactivity and 2) inform whether treatments given to the mother during pregnancy may impact upon fetal vascular function.

This paper presents findings from an evaluation of student satisfaction with work-based learning as experienced by 57 Foundation degree (Fd) Health & Social Care students. The study participants were all employed by the National Health Service (NHS) in a range of clinical settings in the English Midlands. Three cohorts of students completed a questionnaire which sought to uncover the individual circumstances, behaviour, attitudes and beliefs of work-based learners. Students undertaking the acute care, long-term conditions, children and mental health study pathways were supported by a workplace mentor and assessor, while students studying the diagnostic radiography, radiotherapy and mammography pathways had their work-based learning supported by a clinical learning facilitator (CLF). Most of the participants were undertaking the Fd to make the transition from radiography helper or healthcare assistant (HCA) to assistant practitioner (AP). The findings distinguish the individual circumstances of students in the context of their study pathways and on the basis of their contracted hours and the role that they hoped to fill on completion of the programme. Student behaviour was characterised by the regularity with which students worked with their mentors, assessors or CLFs and their engagement in a range of work-based learning activities including practice-based assessments, knowledge and skills acquisition and, with particular regard to radiography students, the learning of new procedures. Although the level of student satisfaction with work-based learning was high, several participants perceived that their colleagues seemed reluctant to recognise them as students in their own right and lacked an awareness of the role of the AP. Participants believed that their confidence had increased and that they were playing a greater role in their clinical teams as a result of gaining knowledge and skills that had helped them to engage in new ways of working.

The human fetoplacental vasculature is a low-resistance circulation with deoxygenated arterial relative to venous blood. The placenta lacks neuronal innervation suggesting that local physical (e.g., oxygenation; flow rate), paracrine (e.g., endothelial cell nitric oxide), and circulating (e.g., angiotensin II) factors will contribute to blood flow regulation in small fetoplacental vessels. Oxygenation (specifically hypoxia) has received particular attention. At the macro-level, hypoxic challenge increases vascular resistance, but the data's physiological relevance remains questionable. K(+) channels are a diverse family of proteins known to play important roles in the normal physiological functions of endothelial and smooth muscle cells of a variety of vascular beds. K(+) channels are categorized by their predicted transmembrane structure or gating properties. A small number of perfused placental cotyledon and isolated blood vessels studies have assessed K(+) channel activity. Specific activator/inhibitor application suggests functional voltage-gated channels, whereas toxin inhibitor studies have documented KCa channel activity. Pharmacological KATP channel activation significantly dilates preconstricted placental arteries and veins. There is a paucity of cell subtype-specific expression studies of placental K(+) channels. This review focuses on the roles of K(+) channels and oxygenation in controlling reactivity of small fetoplacental blood vessels.

Introduction There are no effective therapies for pre-eclampsia (PE), which remains a leading cause of considerable materno-fetal morbidity and mortality. Statins, widely utilized in cardiovascular disease, represent a candidate therapy for PE. Determination of statins’ ability to ameliorate the observed endothelial dysfunction in PE is lacking. Objective To determine the effect of short-term pitavastatin and pravastatin exposure on chorionic plate arteries (CPAs) and omental arteries (OAs) from normal and PE pregnancies. Methods CPAs and OAs from normal pregnancy (NP; N = 43 placentas, N = 20 biopsies) and PE (N = 18 placentas, N = 5 biopsies) pregnancies were mounted on a wire myograph. Contraction was assessed with KPSS (120 mM) and thromboxane-mimetic U46619 (0.1 nM–2 μM). Arteries were incubated for 2 h with 1 μM pitavastatin or pravastatin; time-controls in parallel. U46619 dose–response curves were repeated or NO-donor SNP (1 nM–100 μM) or endothelium-dependent bradykinin (0.1–1000 nM/L) following U46619 pre-constriction. All data are mean ± SEM. Results Neither statin significantly altered vascular reactivity in NP CPAs. CPAs show blunted SNP-induced relaxation in PE vs. NP (38 ± 10% vs. 28 ± 12% respectively; p = 0.038; Two-way ANOVA). Additionally, 1μM pitavastatin attenuated PE CPAs vasoconstriction compared to control (Emax, 152 ± 30% and 165 ± 33% respectively; p = 0.013; Two-way ANOVA) but vasodilation was unaffected. In NP OAs, 1μM pravastatin reduced vasoconstriction compared to time-control (111 ± 20% and 123 ± 23% respectively; p = 0.044; Two-way ANOVA) but did not affect vasodilation. Preliminary PE OA data suggests neither statin had a significant effect on vasoconstriction or vasodilatation (P > 0.05; Two-way ANOVA; N = 5). Discussion Data suggests statins are unlikely to be deleterious to placental vascular function in NP. Pitavastatin (PE CPAs) and pravastatin (NP OAs) have the ability to blunt agonist-induced vasoconstriction. Future work will focus on whether pitavastatin and pravastatin improve endothelial function in OAs from women with PE.

ObjectivesTo characterise Chorionic Plate Artery (CPA) function in maternal obesity, and investigate whether leptin exposure reproduces the obese CPA phenotype in normal-BMI women.Study designCPA responses to the thromboxane-A2 mimetic U46619 (pre/post leptin incubation), to the nitric oxide donor sodium nitroprusside (SNP) and the occurrence of tone oscillations (pre/post leptin incubation) were assessed in 46 term placentas from women of normal (18.5–24.9) or obese (>30) Body Mass Index (BMI).Outcome measuresArea Under the dose response Curve (AUC), maximum response (Vmax), sensitivity (EC50) to U46619 (pre/post leptin) and SNP; average vessel tone, oscillation amplitude and frequency (pre/post leptin).ResultsU46619 vasoconstriction was similar between BMI categories (p > 0.05), however vasodilatation to SNP was reduced in obesity (AUC p = 0.02, Vmaxp = 0.04) compared to normal-BMI women. Leptin incubation altered responses to U46619 in both normal-BMI (EC50 at 100 ng/ml leptin; p < 0.05) and obese women (AUC at 50 ng/ml; p < 0.05) but vasomotion was unaffected (p > 0.05).ConclusionsMaternal obesity is associated with altered placental vascular function which may adversely affect placental oxygen and nutrient transport, placing the fetus at risk. Leptin incubation altered CPA vascular function but did not reproduce the obese phenotype.

Adequate blood flow through placental chorionic plate resistance arteries (CPAs) is necessary for oxygen and nutrient transfer to the fetus and a successful pregnancy. In non-placental vascular smooth muscle cells (SMCs), K(+) channels regulate contraction, vascular tone and blood flow. Previous studies showed that K(+) channel modulators alter CPA tone, but did not distinguish between effects on K(+) channels in endothelial cells and SMCs. In this study, we developed a preparation of freshly isolated CPASMCs of normal pregnancy and investigated K(+) channel expression and function. CPASMCs were isolated from normal human term placentas using enzymatic digestion. Purity and phenotype was confirmed with immunocytochemistry. Whole-cell patch clamp was used to assess K(+) channel currents, and mRNA and protein expression was determined in intact CPAs and isolated SMCs with RT-PCR and immunostaining. Isolated SMCs expressed α-actin but not CD31, a marker of endothelial cells. CPASMCs and intact CPAs expressed h-caldesmon and non-muscle myosin heavy chain-2; phenotypic markers of contractile and synthetic SMCs respectively. Whole-cell currents were inhibited by 4-AP, TEA, charybdotoxin and iberiotoxin implicating functional K(v) and BK(Ca) channels. 1-EBIO enhanced whole cell currents which were abolished by TRAM-34 and reduced by apamin indicating activation of IK(Ca) and SK(Ca) respectively. BK(Ca), IK(Ca) and SK(Ca)3 mRNA and/or protein were expressed in CPASMCs and intact CPAs. This study provides the first direct evidence for functional K(v), BK(Ca,) IK(Ca) and SK(Ca) channels in CPASMCs. These cells display a mixed phenotype implicating a dual role for CPASMCs in controlling both fetoplacental vascular resistance and vasculogenesis.

Fetal growth restriction (FGR) is the inability of a fetus to reach its genetically predetermined growth potential. In the absence of a genetic anomaly or maternal undernutrition, FGR is attributable to “placental insufficiency”: inappropriate maternal/fetal blood flow, reduced nutrient transport or morphological abnormalities of the placenta (e.g., altered barrier thickness). It is not known whether these diverse factors act singly, or in combination, having additive effects that may lead to greater FGR severity. We suggest that multiplicity of such dysfunction might underlie the diverse FGR phenotypes seen in humans. Pregnant endothelial nitric oxide synthase knockout (eNOS−/−) dams exhibit dysregulated vascular adaptations to pregnancy, and eNOS−/− fetuses of such dams display FGR. We investigated the hypothesis that both altered vascular function and placental nutrient transport contribute to the FGR phenotype. eNOS−/− dams were hypertensive prior to and during pregnancy and at embryonic day (E) 18.5 were proteinuric. Isolated uterine artery constriction was significantly increased, and endothelium-dependent relaxation significantly reduced, compared with wild-type (WT) mice. eNOS−/− fetal weight and abdominal circumference were significantly reduced compared with WT. Unidirectional maternofetal 14C-methylaminoisobutyric acid (MeAIB) clearance and sodium-dependent 14C-MeAIB uptake into mouse placental vesicles were both significantly lower in eNOS−/− fetuses, indicating diminished placental nutrient transport. eNOS−/− mouse placentas demonstrated increased hypoxia at E17.5, with elevated superoxide compared with WT. We propose that aberrant uterine artery reactivity in eNOS−/− mice promotes placental hypoxia with free radical formation, reducing placental nutrient transport capacity and fetal growth. We further postulate that this mouse model demonstrates “uteroplacental hypoxia,” providing a new framework for understanding the etiology of FGR in human pregnancy.

Introduction The important immunoregulatory role of Kynurenine (Kyn) pathway tryptophan metabolism in the placenta is well established. Activity of this pathway is reduced in pre-eclampsia. Recently Kyn was shown to relax blood vessels and reduce blood pressure in animal models [1] . In a small study of non-pregnant humans (n = 5), Kyn relaxed omental arteries; this was attenuated by Linopirdine (Lin; 10 μM), an inhibitor of type 7 voltage-gated potassium (Kv7) channels [2] . Objectives To determine if Kyn contributes to regulation of vascular tone in systemic resistance arteries in pregnancy. Materials and methods Omental resistance arteries ( Results Treatment with 1, 3 or 6 mM Kyn dose-dependently attenuated arterial constriction to U46619 (N = 4–8, p = 0.003); greatest effect was observed at an intermediate U46619 dose of 10–7 M (change in constriction: control −0.19 ± 0.08 vs Kyn 6 mM −0.61 ± 0.13). Kyn induced relaxation of pre-constricted omental arteries (N = 7, p = 0.032; 0.70 ± 0.11 vs. 0.35 ± 0.08). Treatment with Lin 10 μM had no effect on Kyn-induced relaxation (N = 5, p = ns; 0.22 ± 0.12 vs. 0.17 ± 0.03). Conclusion This is the first study to demonstrate that Kyn has vasorelaxant effects on systemic resistance arteries in pregnancy. This supports our hypothesis that restoring Kyn pathway activity in pre-eclampsia could be a novel therapeutic target to attenuate maternal features of the disease. Kyn-induced relaxation was not inhibited by Lin 10 μM as previously reported outwith pregnancy, suggesting incomplete inhibition of Kv7 channels or an alternate compensatory mechanism.

OBJECTIVES: Deletion of the placental-specific P0 transcript of the insulin-like growth factor gene (Igf2) reduces placental growth from early pregnancy onwards. In Igf2 P0 knockout fetuses (P0), maternofetal flux of (14)C-methylaminoisobutyric acid ((14)C-MeAIB) mediated by system A amino acid transporter activity is increased at embryonic day 16 (E16), but this stimulation is not sustained, and by E19, fetal growth restriction (FGR) ensues. Here, we investigated whether upregulated (14)C-MeAIB transfer does occur concomitantly with a change in System A amino acid transporter activity and whether altered uteroplacental vascular function contributes to the FGR. We tested the hypothesis that FGR in P0 mice is attributable to altered nutrient transport rather than aberrant uteroplacental vascular function. METHODS: Plasma membrane vesicles were isolated from placentas of P0 and wild-type (WT) fetuses at E16 and E19. System A amino acid transporter activity was measured as sodium-dependent (14)C-MeAIB uptake over 60s. Wire myography was performed on uterine artery branches supplying P0 or WT implantation sites and agonist-induced constriction and dilation measured. RESULTS: Sodium-dependent uptake of (14)C-MeAIB (at 60s) was significantly (P�

Aim: The human fetoplacental vasculature has been suggested to be a low resistance/high flow system, but the mechanisms by which this state is achieved are unclear. Methods: This study assessed the effects of intraluminal flow and local oxygenation on isolated human placental chorionic plate arteries and veins at term using pressure myography. Results: Chorionic plate arteries and veins exhibit myogenic tone. A small but significant arterial vasodilatation was observed following exposure to hypoxia; chorionic plate veins contracted to a similar hypoxic stimulus. Under physiological conditions of pressure and oxygenation, increased luminal flow induced contraction in both chorionic plate arteries and veins. [Correction added after online publication 15th November 2011: ‘induced vasodilatation’ has been changed to ‘induced contraction’] Conclusions: Human fetoplacental vascular tone can be manipulated by local physical factors.

Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was

Despite their fundamental importance for normal cellular function, potassium (K) channels have been poorly studied in placental vascular tissues. This lack of experimental focus may relate to the fact that, as yet, no pregnancy complications have been directly attributable to a specific "channelopathy". K channel activity is central to normal cellular function. Vascular smooth muscle and endothelial cells within the fetoplacental circulation would be expected to be heavily influenced by the behaviour of K channels, as has been well-documented in other vascular beds. In this review, we summarise current understanding of K channel expression and activity in fetoplacental vasculature in normal and complicated pregnancies.

Aims and objectives. This paper presents findings from a small piece of interpretive research into the lived experience of trained nurses who fulfilled the role of workplace mentors for Foundation degree students. The interprofessional landscape of workplace learning is also examined. Background. The participants were all employed in acute care settings in a large UK National Health Service hospital and provided mentorship to Healthcare Assistants studying the adult pathway of a Foundation degree in Health and Social Care; in preparation for the role of the Assistant Practitioner. Design. A purposive sample of eight workplace mentors (who had supported at least one Foundation degree student) were interviewed using a semi-structured questionnaire. Method. All interviews were audio recorded and subsequently transcribed. A hermeneutic phenomenological approach was used to uncover the lived experience of workplace mentors and 10 major themes were generated from the data. Results. The findings suggest that the mentorship of work-based learners presents mentors with a range of challenges that are quite different from pre-registration students given the situatedness of the learner in their clinical team. Conclusion. While the mentorship of work-based learners in busy clinical environments is challenging, the relationship between mentor and mentee appears to have greater equality due to the situatedness of the student in the clinical team. As a result workplace mentors seem to benefit from a relationship lacking in the hierarchical features that characterise traditional mentoring. Awareness of the unique experience of work-based learners and mentors needs to be raised, particularly where students are seeking to complete their Foundation degree to emerge as Assistant Practitioners. Relevance to clinical practice. Trained nurses undertaking the role of workplace mentor in support of Foundation degree students, do so to provide coaching that (in a developmental relationship), places them in the vanguard of an emerging professional group; the Assistant Practitioner.

The obesity epidemic, including childhood obesity, is rapidly gaining strength as one of the most significant challenges to the health of the global community in the 21st Century. The proportion of women who are obese at the beginning of pregnancy is also increasing. These women and their babies are at high risk of pregnancy complications, and of programming for metabolic disease in adult life. In particular, maternal obesity is associated with aberrant fetal growth, encompassing both growth restricted and large for gestational age, or macrosomic fetuses. This article considers the potential effect of obesity and adipose tissue on placental nutrient exchange mechanisms in relation to aberrant fetal growth. The review emphasizes the dearth of work on this topic to date despite its importance to current and future healthcare of the population.