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Introduction: Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in uterine tissues. This includes increased leukocyte infiltration, and subsequent increase in chemokine and cytokine levels, activation of pro-inflammatory transcription factors as NF-κB and increased prostaglandin synthesis. Prostaglandin F2α (PGF2α) is one of the myometrial activators and stimulators. Methods: Here we investigated the role of PGF2α in pro-inflammatory signalling pathways in human myometrial cells isolated from term non-labouring uterine tissue. Primary myometrial cells were treated with G protein inhibitors, calcium chelators and/or PGF2α. Nuclear extracts were analysed by TranSignal cAMP/Calcium Protein/DNA Array. Whole cell protein lysates were analysed by Western blotting. mRNA levels of target genes were analysed by RT-PCR. Results: The results show that PGF2α increases inflammation in myometrial cells through increased activation of NF-κB and MAP kinases and increased expression of COX-2. PGF2α was found to activate several calcium/cAMP-dependent transcription factors, such as CREB and C/EBP-β. mRNA levels of NF-κB-regulated cytokines and chemokines were also elevated with PGF2α stimulation. We have shown that the increase in PGF2α-mediated COX-2 expression in myometrial cells requires coupling of the FP receptor to both Gαq and Gαi proteins. Additionally, PGF2α-induced calcium response was also mediated through Gαq and Gαi coupling. Discussion: In summary, our findings suggest that PGF2α-induced inflammation in myometrial cells involves activation of several transcription factors – NF-κB, MAP kinases, CREB and C/EBP-β. Our results indicate that the FP receptor signals via Gαq and Gαi coupling in myometrium. This work provides insight into PGF2α pro-inflammatory signalling in term myometrium prior to the onset of labour and suggests that PGF2α signalling pathways could be a potential target for management of preterm labour.

Welcome to the Book of Abstracts for the 2021 SPARC conference. Our conference is called “Against All Odds” as we celebrate the achievements of our PGRs and their supervisors, who have continued to excel despite the most challenging circumstances. For this reason, we showcase the work of our PGRs alongside the outstanding supervision that they receive, with our Doctoral School Best Supervisor awards. We also focus on developing resilience and maintaining good mental health in the research environment, supported by exceptional keynote speakers, including our very own Dr Michelle Howarth and Ruby Wax OBE, which makes this year’s conference extra special.

Congenital uterine anomalies are associated with late miscarriage and spontaneous preterm birth.Our aim was 1) to determine the rate of spontaneous preterm birth in each type of congenital uterine anomaly, and 2) to assess the performance of quantitative fetal fibronectin and cervical length measurement by transvaginal ultrasound in asymptomatic women with congenital uterine anomalies for the prediction of spontaneous preterm birth at34 and37 weeks of gestation.This was a retrospective cohort of women with congenital uterine anomalies asymptomatic for spontaneous preterm birth, from 4 tertiary referral centers in the United Kingdom (2001-2016). Congenital uterine anomalies were categorized into fusion (unicornuate, didelphic, and bicornuate uteri) or resorption defects (septate, with or without resection, and arcuate uteri), based on prepregnancy diagnosis. All women underwent serial transvaginal ultrasound cervical length assessment in the second trimester (16 to 24 weeks' gestation); a subgroup underwent quantitative fetal fibronectin testing from 18 weeks' gestation. We investigated the relationship between congenital uterine anomalies and predictive test performance for spontaneous preterm birth at34 and37 weeks' gestation.A total of 319 women were identified as having congenital uterine anomalies in our high-risk population. Of the women, 7% (23/319) delivered spontaneously at34 weeks' gestation and 18% (56/319) at37 weeks' gestation. Rates of spontaneous preterm birth by type were as follows: 26% (7/27) for unicornuate, 21% (7/34) for didelphic, 16% (31/189) for bicornuate, 13% (7/56) for septate, and 31% (4/13) for arcuate. In all, 80% (45/56) of women who had spontaneous preterm birth at37 weeks did not develop a short cervical length (25 mm) during the surveillance period (16-24 weeks). The diagnostic accuracy of short cervical length had a low sensitivity (20.3) for predicting spontaneous preterm birth at34 weeks. Cervical length had an area under the receiver operating curve of 0.56 (95% confidence interval, 0.48-0.64) and 0.59 (95% confidence interval, 0.55-0.64) for prediction of spontaneous preterm birth at34 and37 weeks, respectively. The area under the curve for cervical length to predict spontaneous preterm birth at34 weeks was 0.48 for fusion defects (95% confidence interval, 0.39-0.57) but 0.78 (95% confidence interval, 0.66-0.91) for women with resorption defects. Overall quantitative fetal fibronectin had an area under the curve of 0.63 (95% confidence interval, 0.49-0.77) and 0.58 (95% confidence interval, 0.49- 0.68) for prediction of spontaneous preterm birth at34 and37 weeks, respectively. The area under the curve for prediction of spontaneous preterm birth at37 weeks with quantitative fetal fibronectin for fusion defects was 0.52 (95% confidence interval, 0.41-0.63) but 0.79 (95% confidence interval, 0.63-0.95) for women with resorption defects. Results were similar when women with intervention were excluded.The commonly used markers cervical length and quantitative fetal fibronectin have utility in prediction of spontaneous preterm birth in resorption congenital uterine defects but not in fusion defects. This is contrary to findings in other high-risk populations. These findings need to be accounted for when planning antenatal care, and have potential implications for predictive tests used in spontaneous preterm birth surveillance and intervention.

CACNA1Cencodes the Cav1.2 L-type voltage-gated calcium channel. Generic variation in CACNA1C has been consistently identified as associated with risk for psychiatric disorders including schizophrenia, bipolar disorder, major depressive disorder and autism. Psychiatric risk loci are also enriched for genes involved in the regulation of synaptic plasticity. Here, we show that the expression of Cacna1c is regulated in the rat hippocampus after context exposure, contextual fear conditioning and fear memory retrieval in a manner that correlates to specific memory processes. Using quantitative in situ hybridisation, the expression was down-regulated in CA1 by brief exposure to a novel context and to a conditioned context, and up-regulated in the dentate gyrus after contextual fear conditioning. No changes were measured after prolonged context exposure followed by conditioning, a procedure that retards fear conditioning (latent inhibition), nor with fear memory recall leading to extinction. These results are consistent with a selective role for Cav1.2 in the consolidation of context memory and contextual fear memory, and with processes associated with the maintenance of the fear memory after recall. The dysregulation of CACNA1C may thus be related to associative memory dysfunction in schizophrenia and other psychiatric disorders.

INTRODUCTION: Brittleness and low strength render conventional ceramic systems unsuitable for routine restorative use in molars. Modern, high-strength ceramic core materials such as high purity aluminum oxide (Al2O3) and yttrium - partially stabilized zirconia (Y-PSZ) have been designed for aesthetic, metal-free, all-ceramics in posterior teeth. AIMS AND OBJECTIVES: 1. To compare the biaxial flexural strengths of these two core materials. 2. To compare the strengths of Y-PSZ samples produced by two manufacturers. MATERIALS AND METHODS: Three groups of discs measuring 16mm diameter and 2mm thickness were prepared for each of the sample materials, high purity Al2O3, commercially available as Turkom-Cera, and Y-PSZ, commercially available as Cercon and LAVA. The Biaxial flexural strengths were measured using a Zwick Z010 Material Testing Machine. Reliability was compared using Weibull Moduli. RESULTS: Mean strengths for LAVA, Cercon and Turkom-Cera were 866.44, 586.92, 155.71 MPa respectively. Statistically significant differences were shown between the mean values. DISCUSSION AND CONCLUSIONS: This project showed that the samples of Y-PSZ had higher biaxial flexural strengths than those of high purity Al2O3. The biaxial flexural strengths of Y-PSZ, sourced from two manufacturers, are significantly different. It is suggested that Y-PSZ is suitable and indicated for restorative use in molar regions.

OBJECTIVES: The aim of this in-vitro study was to assess the long-term effects of hydrochloric acid on the surface roughness of three all-ceramic restorative materials CEREC VITABLOC® Mark II CAD, IPS Empress CAD® and IPS e.max CAD®. MATERIALS AND METHODS: Six cylindrical specimens (10mm diameter, 3mm height) of each material type were prepared, using the CEREC CAD/CAM machine. The unpolished samples were immersed in 15ml hydrochloric acid (pH 2) at 370C. Before immersion (baseline) and at periods of 7.5 hours, 45 hours and 91 hours, the specimens were removed from the acid and two randomised areas (10µm X 10µm) were selected and tested on each. The atomic force microscope (Bruker Dimension icon) was used to assess surface roughness and surface area at baseline and after each exposure time. The materials were compared over time with respect to surface roughness and surface area (baseline, 1 month, 6 months, 1 year) in a repeated measures analysis of variance (ANOVA). RESULTS: Sample groups differed significantly for roughness (p

The effect of thyrotrophin suppression on bone mineral density (BMD) and serum cholesterol concentration was assessed in 31 treated hypothyroid women. Measurements of the BMD of the lumbar spine and femoral neck were repeated in seven of those with the lowest value after an average period of 22.7 months. Final cholesterol concentrations were compared with values before thyroxine was started. The dose of thyroxine was based on clinical assessment, serum triiodothyronine concentrations kept within the normal range, and thyrotrophin values within the normal range or suppressed. The patients had taken thyroxine replacement for a mean of 12.7 years. Two-thirds (21 subjects) had suppressed thyrotrophin concentrations, and it was normal in one-third (10). Fifteen subjects had a past history of thyrotoxicosis. BMD and cholesterol concentrations were compared between those with suppressed and normal thyrotrophin concentrations and between those with and without a past history of thyrotoxicosis. No patient had a pathological fracture. One had a Z value for the femoral neck of -1.6, denoting early but definite osteoporosis, and five had borderline osteoporosis with Z values for one or other site between -1.1 and -1.5. None of the seven with the lowest BMDs had any significant change when measurements were repeated. The difference in Z values between subjects with suppressed and normal thyrotrophin concentrations was not significant for either the lumbar spine (p = 0.68) or the femoral neck (p = 0.28). A past history of thyrotoxicosis had a greater effect on BMD for both sites than thyrotrophin suppression, but again the difference between those with and without a past history of thyrotoxicosis was significant neither for the lumbar spine (p = 0.18) nor for the femoral neck (p = 0.34). The combination of thyrotrophin suppression and a past history of thyrotoxicosis also failed significantly to reduce the BMD of the lumbar spine (p = 0.38) or femoral neck (p = 0.30) in comparison with those who had neither thyrotrophin suppression nor a past history of thyrotoxicosis. The mean fall in serum cholesterol concentration was 2.1 mmol/l (SD 1.78) (p = 0.001) in those with a suppressed thyrotrophin concentration taking a mean daily dose of thyroxine of 171 micrograms (SD: 34.7), compared with a fall of 0.89 mmol/l (SD: 1.04) (p = 0.065) in those whose thyrotrophin concentration was not suppressed on a mean daily thyroxine dose of 140 micrograms (SD: 50). No patient had atrial fibrillation or cardiographic evidence of coronary artery disease (CAD). The serum cholesterol concentration should play at least as important a part in influencing the dose of thyroxine as a fear of osteoporosis. Fractures are not a feature in the natural history of treated hypothyroidism, whereas CAD is a common cause of death in these patients.

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