ORCID Profile
0000-0002-6253-4919
Current Organisations
Imperial College Healthcare NHS Trust
,
Imperial College London
,
Macquarie University
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Publisher: Portland Press Ltd.
Date: 30-11-2017
DOI: 10.1042/ETLS20170042
Abstract: Microbial communities of the urogenital tract have long been recognised to play an important role in disease states. A revolution in methodological approaches is permitting the assessment of complex urogenital tract microbiota–host interactions and the metabolic and protein milieu of the mucosal interface. There is now great potential for significant advances in biomarker discovery and disease risk stratification, and for the elucidation of mechanisms underpinning the microbial community dynamics involved in urogenital tract pathology. Microbiota–host interactions in the female genital tract have a particular significance, because unlike in the male, there is direct communication between the external genitalia, the uterus and the peritoneal cavity. This review examines the microbial community composition at differing sites of the female urogenital tract and its relationship with health and disease. Key factors involved in the modulation of vaginal microbiome stability and structure, such as endocrine, immune and inflammatory pathways, are considered in the context of a woman's life cycle and disease pathogenesis.
Publisher: The Endocrine Society
Date: 02-2014
DOI: 10.1210/EN.2013-1761
Abstract: Prostaglandin (PG) E2 (PGE2) plays a central role in the regulation of smooth muscle contractions. Classically, PGE2 stimulates contractions via EP1 and EP3 receptors, whereas EP2 and EP4 maintain quiescence. Labor involves a change from myometrial quiescence to contractions with a shift from anti- to proinflammatory pathways. EP2, a Gαs-coupled receptor, is known to mediate its actions via cAMP signaling. However, we have recently shown that EP2 also activates the proinflammatory PG G/H synthase-2 (PGHS-2). Here, we identify the mechanism underlying the ability of EP2 to maintain uterine quiescence and activate a proinflammatory rolabor response in term-pregnant human myometrium. Human myometrial biopsies for in vivo and in vitro studies were taken at cesarean section at term, before or after the onset of labor. Activation of EP2 increased intracellular levels of cAMP and reduced contractility. Contrastingly, EP2 stimulation increased levels of PGHS-2, membrane-associated PGE synthase-1, and PGE2. This was entirely dependent on EP2-mediated activation of calcium signaling. Both calcium signaling and up-regulation of PGHS-2 were insensitive to the Gαi inhibitor pertussis toxin but inhibited by small interfering RNA knockdown of Gαq/11. There were no differences in EP2 mRNA or protein levels between upper or lower segment myometrium or between pre- and postlabor myometrium. However, in myocytes taken after the onset of labor, cAMP signaling was markedly attenuated, whereas activation of calcium and PGHS-2 was preserved. Overall, the dual coupling of EP2 to Gαs-cAMP and Gαq/11-calcium pathways underlies its ability to mediate contrasting functions in term pregnancy and the “switching” to a prolabor receptor.
Publisher: Springer Science and Business Media LLC
Date: 10-10-2022
DOI: 10.1038/S41598-022-20608-7
Abstract: Human cervicovaginal fluid (CVF) is a complex, functionally important and glycan rich biological fluid, fundamental in mediating physiological events associated with reproductive health. Using a comprehensive glycomic strategy we reveal an extremely rich and complex N-glycome in CVF of pregnant and non-pregnant women, abundant in paucimannose and high mannose glycans, complex glycans with 2–4 N-Acetyllactosamine (LacNAc) antennae, and Poly-LacNAc glycans decorated with fucosylation and sialylation. N-glycosylation profiles were observed to differ in relation to pregnancy status, microbial composition, immune activation, and pregnancy outcome. Compared to CVF from women experiencing term birth, CVF from women who subsequently experienced preterm birth showed lower sialylation, which correlated to the presence of a erse microbiome, and higher fucosylation, which correlated positively to pro-inflammatory cytokine concentration. This study is the first step towards better understanding the role of cervicovaginal glycans in reproductive health, their contribution to the mechanism of microbial driven preterm birth, and their potential for preventative therapy.
Publisher: Elsevier BV
Date: 04-2003
DOI: 10.1067/MOB.2003.236
Abstract: The purpose of this study was to investigate whether purified CD34(+) cells from first-trimester fetal blood are a source of primitive and committed hemopoietic progenitors. CD34(+) cells from first-trimester fetal blood and term cord blood were assayed for committed hemopoietic progenitor cells, high proliferative potential colony-forming cells, and long-term culture-initiating cells. First-trimester CD34(+) cells that were compared with cells at term generated fewer hemopoietic progenitor cells and fewer high proliferative potential colony-forming cells with lower recloning efficiency(P <.001). First-trimester CD34(+) cells tended to contain more long-term culture-initiating cells, both in bulk cultures and by limiting dilution analysis. The ratio between committed and primitive progenitors was 3 in the first-trimester and 20 in the term cord blood, respectively. First-trimester fetal blood is enriched in primitive (compared with committed) hemopoietic progenitors and may be an advantageous source of stem cells for prenatal therapy.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Informa UK Limited
Date: 2003
Publisher: Springer Science and Business Media LLC
Date: 04-11-2021
DOI: 10.1186/S13073-021-00977-W
Abstract: Vaginal microbiota (VMB) composition is altered in women with cervical intra-epithelial neoplasia (CIN) compared to healthy controls and is associated with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This observational study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines. We s led 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also s led. We used metataxonomics to group vaginal swab s les into community state types (CSTs) and ELISA to quantify cytokine and AMP levels in matched vaginal secretions. Analyses were performed to compare the bacterial composition and immune analyte levels before and after CIN excision and in healthy controls. Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV 21/103, 20% vs 1/39, 3%, p = 0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV 19/103, 20% vs 1/39, 3%, p = 0.0142). Prevotella bivia and Sneathia amnii were significantly higher in s les before treatment compared to untreated controls, and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1β and IL-8 remained significantly elevated pre- ( p 0.0001 and p = 0.0014, respectively) and post-treatment ( p 0.0001 and p = 0.0035, respectively) compared to untreated controls. Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision ( p 0.0001) however, their levels remained lower than controls post-treatment. Women with CIN have an increased prevalence of Lactobacillus sp. depletion, high- ersity VMB composition, and higher levels of proinflammatory cytokines and AMPs compared to normal controls. Surgical excision of the disease reduces levels of vaginal AMPs but does not alter VMB composition or cytokine levels. These findings suggest that women with CIN have an inherent predisposition to a high- ersity proinflammatory environment that is not corrected by disease excision. The failure to re-establish a Lactobacillus -enriched CST may explain why women remain at high risk of pre-invasive and invasive disease recurrence.
Publisher: Wiley
Date: 09-2015
Abstract: To assess the effect of gestational age (GA) and cervical length (CL) measurements at transvaginal ultrasound (TVUS) in the prediction of preterm birth in twin pregnancy. In idual patient data (IPD) meta-analysis. International multicentre study. Asymptomatic twin pregnancy. MEDLINE and EMBASE searches were performed and IPD obtained from authors of relevant studies. Multinomial logistic regression analysis determined probabilities for birth at ≤28(+0) , 28(+1) to 32(+0) , 32(+1) to 36(+0) , and ≥36(+1) weeks as a function of GA at screening and CL measurements. Predicted probabilities for preterm birth at ≤28(+0) , 28(+1) to 32(+0) , and 32(+1) to 36(+0) . A total of 6188 CL measurements were performed on 4409 twin pregnancies in 12 studies. Both GA at screening and CL had a significant and non-linear effect on GA at birth. The best prediction of birth at ≤28(+0) weeks was provided by screening at ≤18(+0) weeks (P < 0.001), whereas the best prediction of birth between 28(+1) and 36(+0) weeks was provided by screening at ≥24(+0) weeks (P < 0.001). Negative prediction value of 100% for birth at ≤28(+0) weeks is achieved at CL 65 mm and 43 mm at ultrasound GA at ≤18(+0) weeks and at 22(+1) to 24(+0) weeks, respectively. In twin pregnancies, prediction of preterm birth depends on both CL and the GA at screening. When CL is 22(+0) weeks is most predictive of delivery at 28(+1) to 36(+0) weeks. In twins, we recommend CL screening in twins to commence from ≤18(+0) weeks. An in idual patient meta-analysis assessing gestation and CL in the prediction of preterm birth in twins.
Publisher: Equinox Publishing
Date: 16-06-2017
DOI: 10.1558/CAM.28953
Abstract: Effective communication skills are important in the health care setting in order to develop rapport and trust with patients, provide reassurance, assess patients effectively and provide education in a way that patients easily understand (Candlin and Candlin, 2003). However with many nurses from culturally and linguistically erse (CALD) backgrounds being recruited to fill the workforce shortfall in Australia, communication across cultures with the potential for miscommunication and ensuing risks to patient safety has gained increasing focus in recent years (Shakya and Horsefall, 2000 Chiang and Crickmore, 2009). This paper reports on the first phase of a study that examines intercultural nurse patient communication from the perspective of four Registered Nurses from CALD backgrounds working in Australia. Five interrelating themes that were derived from thematic analysis of semi-structured interviews are discussed. The central theme of ‘adjustment’ was identified as fundamental to the experiences of the RNs and this theme interrelated with each of the other themes that emerged: professional experiences with communication, ways of showing respect, displaying empathy, and vulnerability.
Publisher: Springer Science and Business Media LLC
Date: 17-11-2015
DOI: 10.1038/SREP16865
Abstract: Persistent infection with oncogenic Human Papillomavirus (HPV) is necessary for cervical carcinogenesis. Although evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of HPV infections, this has yet to be described in women with cervical intra-epithelial neoplasia (CIN). We hypothesised that increasing microbiome ersity is associated with increasing CIN severity. llumina MiSeq sequencing of 16S rRNA gene licons was used to characterise the vaginal microbiota of women with low-grade squamous intra-epithelial lesions (LSIL n = 52), high-grade (HSIL n = 92), invasive cervical cancer (ICC n = 5) and healthy controls (n = 20). Hierarchical clustering analysis revealed an increased prevalence of microbiomes characterised by high- ersity and low levels of Lactobacillus spp. (community state type-CST IV) with increasing disease severity, irrespective of HPV status (Normal = 2/20,10% LSIL = 11/52,21% HSIL = 25/92,27% ICC = 2/5,40%). Increasing disease severity was associated with decreasing relative abundance of Lactobacillus spp. The vaginal microbiome in HSIL was characterised by higher levels of Sneathia sanguinegens (P 0.01), Anaerococcus tetradius (P 0.05) and Peptostreptococcus anaerobius (P 0.05) and lower levels of Lactobacillus jensenii (P 0.01) compared to LSIL. Our results suggest advancing CIN disease severity is associated with increasing vaginal microbiota ersity and may be involved in regulating viral persistence and disease progression.
Publisher: Springer Science and Business Media LLC
Date: 15-06-2021
DOI: 10.1038/S41522-021-00220-9
Abstract: Bacteria use carbohydrate-binding proteins (CBPs), such as lectins and carbohydrate-binding modules (CBMs), to anchor to specific sugars on host surfaces. CBPs in the gut microbiome are well studied, but their roles in the vagina microbiome and involvement in sexually transmitted infections, cervical cancer and preterm birth are largely unknown. We established a classification system for lectins and designed Hidden Markov Model (HMM) profiles for data mining of bacterial genomes, resulting in identification of ,000 predicted bacterial lectins available at unilectin.eu/bacteria. Genome screening of 90 isolates from 21 vaginal bacterial species shows that those associated with infection and inflammation produce a larger CBPs repertoire, thus enabling them to potentially bind a wider array of glycans in the vagina. Both the number of predicted bacterial CBPs and their specificities correlated with pathogenicity. This study provides new insights into potential mechanisms of colonisation by commensals and potential pathogens of the reproductive tract that underpin health and disease states.
Publisher: Bioscientifica
Date: 08-2014
DOI: 10.1530/REP-13-0587
Abstract: Preterm birth occurs in 10–12% of pregnancies and is the primary cause of neonatal mortality and morbidity. Tocolytic therapies have long been the focus for the prevention of preterm labour, yet they do not significantly improve neonatal outcome. A direct causal link exists between infection-induced inflammation and preterm labour. As inflammation and infection are independent risk factors for poor neonatal outcome, recent research focus has been shifted towards exploring the potential for anti-inflammatory strategies. Nuclear factor kappa B (NFκB) is a transcription factor that controls the expression of many labour-associated genes including PTGS2 ( COX2 ), prostaglandins ( PG s) and the oxytocin receptor ( OXTR ) as well as key inflammatory genes. Targeting the inhibition of NFκB is therefore an attractive therapeutic approach for both the prevention of preterm labour and for reducing neonatal exposure to inflammation. While PGs are considered to be pro-labour and pro-inflammatory, the cyclopentenone PG 15-deoxy-Δ 12,14 PGJ 2 (15d-PGJ 2 ) exhibits anti-inflammatory properties via the inhibition of NFκB in human amniocytes, myocytes and peripheral blood mononuclear cells in vitro . 15d-PGJ 2 also delays inflammation-induced preterm labour in the mouse and significantly increases pup survival. This review examines the current understanding of inflammation in the context of labour and discusses how anti-inflammatory PGs may hold promise for the prevention of preterm labour and improved neonatal outcome.
Publisher: Cold Spring Harbor Laboratory
Date: 24-11-2021
DOI: 10.1101/2021.11.24.21266804
Abstract: Mutations in the FUT2 gene that result in a lack of expression of histo-blood group antigens on secreted glycoproteins may shape the vaginal microbiota with consequences for birth outcome. To test this, we analysed the relationship between secretor status, vaginal microbiota and gestational length in an ethnically erse cohort of 313 pregnant women, including 91 who delivered prematurely. Lactobacillus species were found to co-occur less often with other microbial taxa in non-secretors. Moreover, non-secretors with Lactobacillus spp. depleted vaginal microbiota in early pregnancy had significantly shorter gestational length than Lactobacillus spp. dominated non-secretors (mean of 245.5 (SD=44.5) versus 265.9 (23.6)) p=0.045), but not compared to Lactobacillus spp. dominated (261.8 (27.5)) and depleted (264.3 days (21.2)) secretors. In identifying a relationship between blood-group antigen expression and vaginal microbiota-host interactions, our results point towards stratification by secretor status as an important factor for considering preterm birth risk and prevention.
Publisher: Springer Science and Business Media LLC
Date: 19-01-2017
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.PEC.2016.09.017
Abstract: Patient education is an important part of nurses' roles however the inconsistent quality of communication skills, including those of registered nurses (RNs) from culturally and linguistically erse (CALD) backgrounds, risk patient safety. Empowerment in patient education has been found to influence patients' self-efficacy and participation in decision-making. Discourse analysis of a whole interaction is used in this paper to trace the consequences of patient education where empowering discourse is displayed by an RN from a CALD background. Ethnographic techniques of participant observation and audio recordings of naturally occurring interactions between nurses from CALD backgrounds and their patients were conducted and analysed using interactional sociolinguistic (IS) and theme oriented discourse analytic approaches. The interactional consequences of the nurse's empowering approach are readily observable in the data. The RN addresses the patient's education needs through a respectful encounter that illustrates the patient's active involvement. Examining the interactional consequences of empowering discourse demonstrates its effectiveness, and illustrates how empowering behaviour can be integrated into patient education, thus offering an alternative to traditional approaches. Greater awareness of how to use empowering discourse will offer an alternative and consistent approach that enables nurses to facilitate patient-centred education.
Publisher: Wiley
Date: 10-2015
DOI: 10.1002/UOG.14758
Abstract: The true growth potential of a fetus is difficult to predict but recently a new definition, independent of fetal weight, using cerebroplacental (cerebro-umbilical) ratio (CPR) < 0.6765 multiples of the median (MoM), was reported. We applied this definition to a cohort of low-risk pregnancies recruited prospectively to determine if fetuses with CPR < 0.6765 are at increased risk of developing signs of intrapartum fetal compromise. Recruitment to this prospective observational study took place between March 2011 and March 2014. All women with low-risk singleton pregnancies at term were eligible. Women with known or suspected placental dysfunction were excluded, as were women with fetuses with an estimated fetal weight < 10(th) centile. All participants underwent ultrasound examination prior to active labor (≤ 4 cm cervical dilatation), during which fetal biometry as well as umbilical artery and fetal middle cerebral artery blood flow were assessed. Following delivery, intrapartum and neonatal outcomes were compared between fetuses that had a CPR < 0.6765 MoM and those that had a CPR ≥ 0.6765 MoM. In total, 775 women were recruited. Fetuses with CPR < 0.6765 MoM were significantly more likely to require Cesarean delivery because of presumed fetal compromise (P < 0.001). These fetuses were also at increased risk of compromise at any time during labor and were less likely to be delivered vaginally, spontaneously or otherwise, than were those with CPR ≥ 0.6765 MoM. CPR < 0.6765 MoM gave a positive predictive value (PPV) for Cesarean delivery because of presumed fetal compromise of 36.7% and a negative predictive value of 88.7%, with a sensitivity of 18% and a specificity of 95.4%. Fetuses that failed to achieve their growth potential (defined as CPR < 0.6765 MoM) were at increased risk of intrapartum compromise and were less likely to be delivered vaginally. However, a low negative predictive value was observed for fetal compromise and further studies are required to support the translation of this technique into clinical practice.
Publisher: Wiley
Date: 10-03-2019
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.AJOG.2013.08.042
Abstract: The objective of the study was to investigate the distribution of umbilical venous flow rates, measured in early labor, in a cohort of normal term pregnancies and to establish the relationship between umbilical venous flow and subsequent intrapartum outcome. Five hundred eighty-nine women with uncomplicated, term, singleton pregnancies were recruited to this prospective observational study prior to active labor (dilation of 4 cm or less) at Queen Charlotte's and Chelsea Hospital (London, UK). All participants underwent an ultrasound examination, during which fetal biometry, umbilical venous flow velocity, and umbilical vein diameter were recorded. Umbilical venous flow rate was then calculated. Following delivery, intrapartum and neonatal outcomes were correlated with the ultrasound findings. Cases were sub ided according to mode of delivery, and mean umbilical venous flow rates were compared between the groups. Cases were also sub ided according to umbilical venous flow rate (less than the 20th centile, 20th-80th centile, and greater than the 80th centile), and the incidence of diagnoses of fetal compromise was compared. Fetuses delivered by emergency cesarean for presumed fetal compromise had the lowest umbilical venous flow rates (both corrected for and uncorrected for birthweight) (P = .02 and P = .001, respectively). Fetuses with the lowest umbilical venous flow rates were significantly more likely to require emergency cesarean for presumed fetal compromise than those with the highest flow rates (15.7% vs 5.6%, relative risk, 2.83 95% confidence interval, 1.16-6.91). Fetuses with the lowest umbilical venous flow rates are at increased risk of a subsequent diagnosis of intrapartum fetal compromise. Measurement of umbilical venous flow could contribute to the risk stratification of pregnancies prior to labor.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.YMETH.2018.04.022
Abstract: There is increasing appreciation of the role that vaginal microbiota play in health and disease throughout a woman's lifespan. This has been driven partly by molecular techniques that enable detailed identification and characterisation of microbial community structures. However, these methods do not enable assessment of the biochemical and immunological interactions between host and vaginal microbiota involved in pathophysiology. This review examines our current knowledge of the relationships that exist between vaginal microbiota and the host at the level of the vaginal mucosal interface. We also consider methodological approaches to microbiomic, immunologic and metabolic profiling that permit assessment of these interactions. Integration of information derived from these platforms brings the potential for biomarker discovery, disease risk stratification and improved understanding of the mechanisms regulating vaginal microbial community dynamics in health and disease.
Publisher: Informa UK Limited
Date: 24-03-2018
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/416739
Abstract: Pregnancy is a complex immunological state in which a bias towards T helper 2 (Th2) protects the fetus. Evidence suggests that proinflammatory cytokines increase the risk of poor neonatal outcome, independently of the direct effect of preterm labour. The anti-inflammatory prostaglandin 15-deoxy-Δ 12,14 -Prostaglandin J 2 (15dPGJ 2 ) inhibits nuclear factor Kappa B (NF- κ B) in amniocytes and myocytes in vitro and is a ligand for the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptor. Here we examine the Th1:Th2 cytokine bias in pregnancy and whether 15dPGJ 2 could be used to inhibit the production of the proinflammatory cytokines through inhibition of NF- κ B while simultaneously promoting Th2 interleukin 4 (IL-4) synthesis via CRTH2 in T helper cells. Peripheral blood mononuclear cells (PBMCs) from women at 28 weeks, term pre-labour, term labour as well as non-pregnant female controls were cultured with 15dPGJ 2 or vehicle control and stimulated with phorbol myristyl acetate (PMA)/ionomycin. The percentage of CD4 + cells producing interferon gamma (IFN- γ ) and tumor necrosis factor alpha (TNF- α ) in response to PMA/ionomycin was significantly reduced in pregnancy. 15dPGJ 2 reduced IFN- γ and TNF- α production in stimulated T helper cells, but did not alter IL-4 production in CRTH2 +ve cells. 15dPGJ 2 also reduced phospho-p65 in stimulated PBMCs. In summary, 15dPGJ 2 suppresses the Th1 response of PBMCs during pregnancy and active labour whilst maintaining the Th2 response suggesting a therapeutic benefit in reducing neonatal morbidity in inflammation-induced PTL.
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.MCE.2014.11.008
Abstract: Human labour, both at term and preterm, is preceded by NF-κB-mediated inflammatory activation within the uterus, leading to myometrial activation, fetal membrane remodelling and cervical ripening. The stimuli triggering inflammatory activation in normal human parturition are not fully understood. We show that the neurohypophyseal peptide, oxytocin (OT), activates NF-κB and stimulates downstream inflammatory pathways in human gestational tissues. OT stimulation (1 pM-100 nM) specifically via its receptor (OTR) in human myometrial and amnion primary cells led to MAPK and NF-κB activation within 15 min and maximal p65-subunit nuclear translocation within 30 min. Both in human myometrium and amnion, OT-induced activation of the canonical NF-κB pathway upregulated key inflammatory labour-associated genes including IL-8, CCL5, IL-6 and COX-2. IKKβ inhibition (TPCA1 10 µM) suppressed OT-induced NF-κB-p65 phosphorylation, whereas p65-siRNA knockdown reduced basal and OT-induced COX-2 levels in myometrium and amnion. In both gestational tissues, MEK1/2 (U0126 10 µM) or p38 inhibition (SB203580 10 µM) suppressed OT-induced COX-2 expression, but OT-induced p65-phosphorylation was only inhibited in amnion, suggesting OT activation of NF-κB in amnion is MAPK-dependent. Our data provide new insight into the OT/OTR system in human parturition and suggest that its therapeutic modulation could be a strategy for regulating both contractile and inflammatory pathways in the clinical context of term reterm labour.
Publisher: Elsevier BV
Date: 04-2016
Publisher: Informa UK Limited
Date: 13-03-2012
DOI: 10.3109/14767058.2012.666114
Abstract: Pregnancy is characterized by a complex interplay of inflammatory events regulated by both the innate and acquired immune systems. Similarly, parturition can be viewed as the activation of "pro-labour" inflammatory pathways, which drive cervical ripening and myometrial activation. Premature activation of these pathways, for ex le, by infection, can lead to preterm labour and birth. Nuclear factor κβ is a key modulator of these pathways and functions by regulating the expression of prostaglandins, chemokines and pro-inflammatory cytokines involved in both term and preterm labour. Future design of therapeutics that target key mediators of inflammation and immune activation would therefore be a rational approach for preventing preterm labour and immune-mediated neonatal brain damage.
Publisher: Elsevier BV
Date: 04-2003
DOI: 10.1067/MOB.2003.255
Abstract: The purpose of this study was to establish whether nimesulide causes fewer fetal side effects than indomethacin or sulindac after short-term maternal exposure for tocolysis. This was a double-blind, double-dummy prospective randomized study with three drug treatment groups (n = 10 per group) that were comprised of subjects who were at 28 to 32 weeks of gestation with preterm contractions. The subjects were treated in the delivery suites of two busy inner-city teaching hospitals the intervention consisted of 48 hours of treatment and with 72 hours of follow-up observation with indomethacin 100 mg (twice daily), sulindac 200 mg (twice daily), or nimesulide 200 mg (twice daily). The amniotic fluid index, hourly fetal urine production, and ductal Doppler pulsatility index observations were monitored before the treatment and at 4, 24, 48, 72, and 120 hours after the treatment was started. The statistical analysis used repeated measures analysis of variance, Bonferroni test, and Bland-Altman agreement. Significance assumed when the probability value was <.05. Each drug caused a significant reduction in all three observations over the 48-hour treatment period, which recovered to pretreatment levels by 72 hours after treatment. There were no significant differences among drugs for any of these effects. Nimesulide causes similar short-term fetal side effects to indomethacin and sulindac.
Publisher: Elsevier BV
Date: 09-2023
Publisher: Research Square Platform LLC
Date: 24-10-2022
DOI: 10.21203/RS.3.RS-2102199/V1
Abstract: Endometrial cancer is a multifactorial disease with inflammatory, metabolic and potentially microbial cues involved in disease pathogenesis. Here we s led different regions of the reproductive tract (vagina, cervix, endometrium, fallopian tubes and ovaries) of 61 patients and showed that the upper genital tract of a subset of women with and without endometrial cancer harbour microbiota quantitatively and compositionally distinguishable from background contaminants. A microbial continuum, defined by detection of common bacterial species along the genital tract, was noted in most women without cancer while the continuum was less cohesive in endometrial cancer patients. Vaginal microbiota were poorly correlated with rectal microbiota in the studied cohorts. Endometrial cancer was associated with reduced cervicovaginal and rectal bacterial load together with depletion of Lactobacillus species relative abundance, including L. crispatus , increased bacterial ersity and enrichment of Porphyromonas , Prevotella, Peptoniphilus and Anaerococcus in the lower genital tract and endometrium. Treatment of benign and malignant endometrial organoids with L. crispatus conditioned media had minimal impact on cytokine and chemokine profiles. Our findings provide evidence that the upper female reproductive tract of some women contains detectable levels of bacteria, the composition of which is associated with endometrial cancer. Whether this is a cause or consequence of cancer pathophysiology remains to be elucidated.
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/967629
Abstract: Pregnancy is a unique immunological state in which a balance of immune tolerance and suppression is needed to protect the fetus without compromising the mother. It has long been established that a bias from the T helper 1 cytokine profile towards the T helper 2 profile contributes towards successful pregnancy maintenance. The majority of publications that report on aberrant Th1:Th2 balance focus on early pregnancy loss and preecl sia. Over the last few decades, there has been an increased awareness of the role of infection and inflammation in preterm labour, and the search for new biomarkers to predict preterm labour continues. In this paper, we explore the evidence for an aberrant Th1:Th2 profile associated with preterm labour. We also consider the potential for its use in screening women at high risk of preterm labour and for prophylactic therapeutic measures for the prevention of preterm labour and associated neonatal adverse outcomes.
Publisher: Oxford University Press (OUP)
Date: 14-11-2017
Abstract: The role of progesterone (P4) in the regulation of the local (uterine) and systemic innate immune system, myometrial expression of connexin 43 (Cx-43) and cyclooxygenase 2 (COX-2), and the onset of parturition was examined in (i) naïve mice delivering at term (ii) E16 mice treated with RU486 (P4-antagonist) to induce preterm parturition and (iii) in mice treated with P4 to prevent term parturition. In naïve mice, myometrial neutrophil and monocyte numbers peaked at E18 and declined with the onset of parturition. In contrast, circulating monocytes did not change and although neutrophils were increased with pregnancy, they did not change across gestation. The myometrial mRNA and protein levels of most chemokines/cytokines, Cx-43, and COX-2 increased with, but not before, parturition. With RU486-induced parturition, myometrial and systemic neutrophil numbers increased before and myometrial monocyte numbers increased with parturition only. Myometrial chemokine/cytokine mRNA abundance increased with parturition, but protein levels peaked earlier at between 4.5 and 9 h post-RU486. Cx-43, but not COX-2, mRNA expression and protein levels increased prior to the onset of parturition. In mice treated with P4, the gestation-linked increase in myometrial monocyte, but not neutrophil, numbers was prevented, and expression of Cx-43 and COX-2 was reduced. On E20 of P4 supplementation, myometrial chemokine/cytokine and leukocyte numbers, but not Cx-43 and COX-2 expression, increased. These data show that during pregnancy P4 controls myometrial monocyte infiltration, cytokine and prolabor factor synthesis via mRNA-dependent and independent mechanisms and, with prolonged P4 supplementation, P4 action is repressed resulting in increased myometrial inflammation.
Publisher: Public Library of Science (PLoS)
Date: 20-02-2013
Publisher: Elsevier BV
Date: 09-2023
Publisher: Public Library of Science (PLoS)
Date: 03-11-2016
Publisher: Wiley
Date: 31-10-2019
Publisher: Wiley
Date: 03-11-2015
DOI: 10.1111/IMM.12534
Publisher: Wiley
Date: 04-02-2014
DOI: 10.1096/FJ.13-247783
Abstract: Activation of uterine inflammatory pathways leads to preterm labor (PTL), associated with high rates of neonatal mortality and morbidity. The transcription factors nuclear factor κB (NFκB) and activator protein 1 (AP-1) regulate key proinflammatory and procontractile genes involved in normal labor and PTL. Here we show that NFκB activation normally occurs in the mouse myometrium at gestation day E18, prior to labor, whereas AP-1 and JNK activation occurs at labor onset. Where labor was induced using the progesterone receptor antagonist RU486, NFkB and AP-1/JNK activation both occurred at the time of labor (20 h compared to 60 h in DMSO-treated controls). Using an LPS (Escherichia coli: serotype O111)-induced PTL model that selectively activates AP-1 but not NFkB, we show that myometrial AP-1 activation drives production of cytokines (Il-6, Il-8, and Il-1β), metalloproteinases (Mmp3 and Mmp10), and procontractile proteins (Cox-2 and Cx43) resulting in PTL after 7 h. Protein levels of CX43 and IL-1β, and IL-1β cleavage, were increased following LPS-induced activation of AP-1. Inhibition of JNK by SP600125 (30 mg/kg) delayed PTL by 6 h (7.5 vs. 13.5 h P<0.05). Our data reveal that NFκB activation is not a functional requirement for infection/inflammation-induced preterm labor and that AP-1 activation is sufficient to drive inflammatory pathways that cause PTL.
Publisher: Informa UK Limited
Date: 07-08-2015
DOI: 10.1080/10410236.2014.894603
Abstract: The study of computer use during consultations and in clinical communication teaching has generated considerable research interest in recent decades, but few studies have investigated how the use of other technological devices such as the dictaphone may be linked to the acquisition of interpersonal communication skills. Research on the dictaphone has focused on "backstage" activity such as dictating consultation letters after consultations, and largely neglected its potential in "frontstage" interactions with patients or as an educational tool in teaching clinical communication. This article draws on 28 consultations recorded in a gastrointestinal clinic and a follow-up interview with the participating surgeon to explore the use of the dictaphone during consultations. All data were transcribed and reiterative thematic analyses were conducted. The analyses presented here show how the dictaphone can serve a range of important relational and medical functions when used to co-construct consultation letters with patients. These functions include establishing and maintaining rapport, building trust, checking and clarifying information, aiding information accuracy, and closing the consultation. This study shows how a technological device usually reserved for "backstage" medical communication can be successfully used as a communicative tool in "frontstage" interactions and illustrates the multifaceted and beneficial functions of the dictaphone.
Publisher: Oxford University Press (OUP)
Date: 30-11-2016
DOI: 10.1093/BIOINFORMATICS/BTW705
Abstract: KODAMA, a novel learning algorithm for unsupervised feature extraction, is specifically designed for analysing noisy and high-dimensional datasets. Here we present an R package of the algorithm with additional functions that allow improved interpretation of high-dimensional data. The package requires no additional software and runs on all major platforms. KODAMA is freely available from the R archive CRAN (cran.r-project.org). The software is distributed under the GNU General Public License (version 3 or later). Supplementary data are available at Bioinformatics online.
Publisher: Elsevier BV
Date: 09-2015
Publisher: Oxford University Press (OUP)
Date: 04-2003
Abstract: Isolating fetal erythroblasts from first trimester maternal blood offers a promising non-invasive alternative for prenatal diagnosis. The aim of this study was to characterize the biological properties of first trimester primitive erythroblasts to facilitate their enrichment from first trimester maternal blood. Primitive erythroblasts were the predominant cell type until 12 weeks gestation, after which time their numbers declined steeply 100% were epsilon-globin-positive versus <0.06% definitive erythroblasts. Buoyant densities of first trimester fetal erythroblasts ranged from 1.077 to 1.130 g/ml, and optimal recoveries were obtained with Percoll 1118. Although primitive erythroblasts carried a negative surface charge and were resistant to NH(4)Cl lysis, these properties had only a limited role in fetal cell enrichment. Immunophenotyping showed that primitive, like definitive, erythroblasts were GPA+, CD47+, CD45- and CD35-, whereas CD71 expression was weak/undetectable on primitive erythroblasts but strongly positive on 100% of definitive erythroblasts primitive erythroblasts were also CD36- whereas definitive erythroblasts were CD36+. We therefore used CD45/GPA selection of Percoll 1118-separated cells to demonstrate successful enrichment of male epsilon-globin-positive fetal erythroblasts from model mixtures, and as proof of principle from some first trimester maternal blood s les. Fetal cell enrichment protocols based on first trimester epsilon-globin-positive primitive erythroblasts may allow reliable enrichment of fetal cells from maternal blood for early non-invasive prenatal diagnosis of genetic disorders.
Publisher: Bioscientifica
Date: 10-2015
DOI: 10.1530/REP-15-0258
Abstract: Preterm labour (PTL) is commonly associated with infection and/or inflammation. Lipopolysaccharide (LPS) from different bacteria can be used to independently or mutually activate Jun N-terminal kinase (JNK)/AP1- or NF-κB-driven inflammatory pathways that lead to PTL. Previous studies using Salmonella abortus LPS, which activates both JNK/AP-1 and NF-κB, showed that selective inhibition of NF-κB delays labour and improves pup outcome. Where labour is induced using Escherichia coli LPS (O111), which upregulates JNK/AP-1 but not NF-κB, inhibition of JNK/AP-1 activation also delays labour. In this study, to determine the potential role of JNK as a therapeutic target in PTL, we investigated the specific contribution of JNK signalling to S. Abortus LPS-induced PTL in mice. Intrauterine administration of S. Abortus LPS to pregnant mice resulted in the activation of JNK in the maternal uterus and fetal brain, upregulation of pro-inflammatory proteins COX-2, CXCL1, and CCL2, phosphorylation of cPLA2 in myometrium, and induction of PTL. Specific inhibition of JNK by co-administration of specific D-JNK inhibitory peptide (D-JNKI) delayed LPS-induced preterm delivery and reduced fetal mortality. This is associated with inhibition of myometrial cPLA2 phosphorylation and proinflammatory proteins synthesis. In addition, we report that D-JNKI inhibits the activation of JNK/JNK3 and caspase-3, which are important mediators of neural cell death in the neonatal brain. Our data demonstrate that specific inhibition of TLR4-activated JNK signalling pathways has potential as a therapeutic approach in the management of infection/inflammation-associated PTL and prevention of the associated detrimental effects to the neonatal brain.
Publisher: American Society of Hematology
Date: 08-2001
Abstract: Isolating fetal erythroblasts from maternal blood offers a promising noninvasive alternative for prenatal diagnosis. The current immunoenzymatic methods of identifying fetal cells from background maternal cells postenrichment by labeling γ-globin are problematic. They are nonspecific because maternal cells may produce γ-globin, give poor hybridization efficiencies with chromosomal fluorescence in situ hybridization (FISH), and do not permit simultaneous visualization of the fetal cell identifier and the FISH signal. We describe a novel technique that allows simultaneous visualization of fetal erythroblast morphology, chromosomal FISH, and ε-globin labeled with AMCA (7-amino-4-methylcoumarin-3-acetic acid). AMCA was chosen as the fluorescent label to circumvent the problem of heme autofluorescence because the mean difference in relative fluorescence intensity between fetal erythroblasts stained positive for antiglobin antibody and autofluorescence of unstained cells was greater with AMCA (mean 43.2 95% confidence interval [CI], 34.6-51.9 SD = 14.0) as the reporting label compared with fluorescein isothiocyanate (mean 24.2 95% CI, 16.4-31.9 SD = 12.4) or phycoerythrin (mean 9.8 95% CI, 4.8-14.8 SD = 8.0). Median FISH hybridization efficiency was 97%, comparable to the 98% (n = 5 paired s les) using Carnoy fixative. One ε-positive fetal erythroblast was identified among 105 maternal nucleated cells in 6 paired mixture experiments of fetal erythroblasts in maternal blood (P & .001). Male ε-positive fetal erythroblasts were clearly distinguishable from adult female ε-negative erythroblasts, with no false positives (n = 1000). The frequency of fetal erythroblasts expressing ε-globin declines linearly from 7 to 14 weeks' gestation (y = −15.8 × + 230.8 R2 = 0.8 P & .001). We describe a rapid and accurate method to detect simultaneously fetal erythroblast morphology, intracytoplasmic ε-globin, and nuclear FISH.
Publisher: Frontiers Media SA
Date: 25-08-2020
Publisher: Portland Press Ltd.
Date: 09-2021
DOI: 10.1042/BSR20203908
Abstract: The reproductive tract microbiota plays a crucial role in maintenance of normal pregnancy and influences reproductive outcomes. Microbe–host interactions in pregnancy remain poorly understood and their role in shaping immune modulation is still being uncovered. In this review, we describe the composition of vaginal microbial communities in the reproductive tract and their association with reproductive outcomes. We also consider strategies for manipulating microbiota composition by using live biotherapeutics, selective eradication of pathogenic bacteria with antibiotics and vaginal microbiota transplantation. Finally, future developments in this field and the need for mechanistic studies to explore the functional significance of reproductive tract microbial communities are highlighted.
Publisher: Springer Science and Business Media LLC
Date: 29-08-2017
DOI: 10.1038/S41598-017-09844-4
Abstract: Evidence suggests the vaginal microbiota (VM) may influence risk of persistent Human Papillomavirus (HPV) infection and cervical carcinogenesis. Established cytology biobanks, typically collected with a cytobrush, constitute a unique resource to study such associations longitudinally. It is plausible that compared to rayon swabs the most commonly used s ling devices, cytobrushes may disrupt biofilms leading to variation in VM composition. Cervico-vaginal s les were collected with cytobrush and rayon swabs from 30 women with high-grade cervical precancer. Quantitative PCR was used to compare bacterial load and Illumina MiSeq sequencing of the V1-V3 regions of the 16S rRNA gene used to compare VM composition. Cytobrushes collected a higher total bacterial load. Relative abundance of bacterial species was highly comparable between s ling devices (R 2 = 0.993). However, in women with a Lactobacillus -depleted, high- ersity VM, significantly less correlation in relative species abundance was observed between devices when compared to those with a Lactobacillus species-dominant VM (p = 0.0049). Cytobrush and swab s ling provide a comparable VM composition. In a small proportion of cases the cytobrush was able to detect underlying high- ersity community structure, not realized with swab s ling. This study highlights the need to consider s ling devices as potential confounders when comparing multiple studies and datasets.
Publisher: Springer Science and Business Media LLC
Date: 11-2016
Publisher: Elsevier BV
Date: 08-2020
Publisher: Frontiers Media SA
Date: 11-02-2021
DOI: 10.3389/FCIMB.2020.596917
Abstract: Pregnant women living with HIV-1 infection (PWLWH) have an elevated risk of preterm birth (PTB) of unknown aetiology, which remains after successful suppression of HIV. Women at high risk for HIV have a common bacterial profile which has been associated with poor birth outcomes. We set out to explore factors associated with gestational age at delivery of PWLWH in a UK population. Prospective study of PWLWH (n = 53) in whom the vaginal microbiota and cervicovaginal cytokine milieu were assessed using metataxonomics and multiplexed immunoassays, respectively. Cross-sectional characterisation of vaginal microbiota in PWLWH were compared with 22 HIV uninfected pregnant women (HUPW) at a similar second trimester timepoint. Within PWLWH the relationships between bacterial composition, inflammatory response, and gestational age at delivery were explored. There was a high rate of PTB among PWLWH (12%). In the second trimester the vaginal microbiota was more erse in PWLWH than in HUPW (Inverse Simpson Index, p = 0.0004 and Species Observed, p = 0.009). PWLWH had a lower prevalence of L. crispatus dominant vaginal microbiota group (VMB I, 15 vs 54%) than HUPW and higher prevalence of L. iners dominant (VMB III, 36 vs 9% and VMB IIIB, 15 vs 5%) and mixed anaerobes (VMB IV, 21 vs 0%). Across the second and third trimesters in PWLWH, VMB III/IIIB and IV were associated with PTB and with increased local inflammation [cervicovaginal fluid (CVF) cytokine concentrations in upper quartile]. High bacterial ersity and anaerobic bacterial abundance were also associated with CVF pro-inflammatory cytokines, most notably IL-1β. There is an association between local inflammation, vaginal dysbiosis and PTB in PWLWH. Understanding the potential of antiretroviral therapies to influence this cascade will be important to improve birth outcomes in this population.
Publisher: Springer Science and Business Media LLC
Date: 13-10-2021
DOI: 10.1038/S41467-021-26215-W
Abstract: The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for s le preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160 455 swabs VMET II, n = 205 573 swabs). By integrating metataxonomics and immune profiling data from matched s les, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.
Publisher: Wiley
Date: 28-06-2020
Publisher: American Society of Hematology
Date: 12-2008
DOI: 10.1182/BLOOD-2008-04-152967
Abstract: Down syndrome (DS) children have a high frequency of acute megakaryoblastic leukemia (AMKL) in early childhood. At least 2 in utero genetic events are required, although not sufficient, for DS-AMKL: trisomy 21 (T21) and N-terminal–truncating GATA1 mutations. To investigate the role of T21 in DS-AMKL, we compared second trimester hemopoiesis in DS without GATA1 mutations to gestation-matched normal controls. In all DS fetal livers (FLs), but not marrows, megakaryocyte-erythroid progenitor frequency was increased (55.9% ± 4% vs 17.1% ± 3%, CD34+CD38+ cells P .001) with common myeloid progenitors (19.6% ± 2% vs 44.0% ± 7%) and granulocyte-monocyte (GM) progenitors (15.8% ± 4% vs 34.5% ± 9%) commensurately reduced. Clonogenicity of DS-FL versus normal FL CD34+ cells was markedly increased (78% ± 7% vs 15% ± 3%) affecting megakaryocyte-erythroid (∼ 7-fold higher) and GM and colony-forming unit–granulocyte, erythrocyte macrophage, megakaryocyte (CFU-GEMM) progenitors. Replating efficiency of CFU-GEMM was also markedly increased. These data indicate that T21 itself profoundly disturbs FL hemopoiesis and they provide a testable hypothesis to explain the increased susceptibility to GATA1 mutations in DS-AMKL and DS-associated transient myeloproliferative disorder.
Publisher: Elsevier BV
Date: 10-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2014
Publisher: MDPI AG
Date: 30-05-2022
Abstract: Several non-genetic factors have been associated with ovarian cancer incidence or mortality. To evaluate the strength and validity of the evidence we conducted an umbrella review of the literature that included systematic reviews/meta-analyses that evaluated the link between non-genetic risk factors and ovarian cancer incidence and mortality. We searched PubMed, EMBASE, Cochrane Database of Systematic Reviews and performed a manual screening of references. Evidence was graded into strong, highly suggestive, suggestive or weak based on statistical significance of the random effects summary estimate and the largest study in a meta-analysis, the number of cases, between-study heterogeneity, 95% prediction intervals, small study effects, and presence of excess significance bias. We identified 212 meta-analyses, investigating 55 non-genetic risk factors for ovarian cancer. Risk factors were grouped in eight broad categories: anthropometric indices, dietary intake, physical activity, pre-existing medical conditions, past drug history, biochemical markers, past gynaecological history and smoking. Of the 174 meta-analyses of cohort studies assessing 44 factors, six associations were graded with strong evidence. Greater height (RR per 10 cm 1.16, 95% confidence interval (CI) 1.11–1.20), body mass index (BMI) (RR ≥ 30 kg/m2 versus normal 1.27, 95% CI 1.17–1.38) and three exposures of varying preparations and usage related to hormone replacement therapy (HRT) use increased the risk of developing ovarian cancer. Use of oral contraceptive pill reduced the risk (RR 0.74, 95% CI 0.69–0.80). Refining the significance of genuine risk factors for the development of ovarian cancer may potentially increase awareness in women at risk, aid prevention and early detection.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.MCE.2015.11.012
Abstract: Oxytocin (OT) plays an important role in the onset of human labour by stimulating uterine contractions and promoting prostaglandin/inflammatory cytokine synthesis in amnion via oxytocin receptor (OTR) coupling. The OTR-antagonist, Atosiban, is widely used as a tocolytic for the management of acute preterm labour. We found that in primary human amniocytes, Atosiban (10 μM) signals via PTX-sensitive Gαi to activate transcription factor NF-κB p65, ERK1/2, and p38 which subsequently drives upregulation of the prostaglandin synthesis enzymes, COX-2 and phospho-cPLA2 and excretion of prostaglandins (PGE2) (n = 6 p < 0.05, ANOVA). Moreover, Atosiban treatment increased expression and excretion of the inflammatory cytokines, IL-6 and CCL5. We also showed that OT-simulated activation of NF-κB, ERK1/2, and p38 and subsequent prostaglandin and inflammatory cytokine synthesis is via Gαi-2 and Gαi-3 but not Gαq, and is not inhibited by Atosiban. Activation or exacerbation of inflammation is not a desirable effect of tocolytics. Therefore therapeutic modulation of the OT/OTR system for clinical management of term reterm labour should consider the effects of differential G-protein coupling of the OTR and the role of OT or selective OTR agonists/antagonists in activating proinflammatory pathways.
Publisher: Elsevier BV
Date: 12-2020
Publisher: American Association for the Advancement of Science (AAAS)
Date: 03-08-2016
DOI: 10.1126/SCITRANSLMED.AAG1026
Abstract: Cervical cerclage using braided suture material disrupts vaginal microbial stability and increases inflammation.
Publisher: Elsevier BV
Date: 05-2021
Publisher: American Chemical Society (ACS)
Date: 04-10-2017
DOI: 10.1021/ACS.JPROTEOME.7B00568
Abstract: Lower urinary tract symptoms (LUTS), including urinary incontinence, urgency and nocturia, affect approximately half of women worldwide. Current diagnostic methods for LUTS are invasive and costly, while available treatments are limited by side effects leading to poor patient compliance. In this study, we aimed to identify urine metabolic signatures associated with LUTS using proton nuclear magnetic resonance (
Publisher: Wiley
Date: 12-2014
DOI: 10.1002/UOG.13332
Abstract: Pregnancy complications, particularly those associated with placental dysfunction, occur more frequently in nulliparous than in parous women. This difference may be a consequence of improved trophoblastic invasion and, as a result, improved placental function following previous pregnancy. Placental dysfunction in cases of fetal growth restriction may be identified by ultrasound assessment of fetoplacental hemodynamics and amniotic fluid volume. In this prospective observational study, we investigated whether differences in these measures of placental function exist between nulliparous and parous women, prior to active labor. Over a 2-year period, 456 nulliparous and 152 parous women with uncomplicated singleton pregnancies were recruited to this prospective observational study. Each participant underwent an ultrasound assessment prior to active labor, during which fetal biometry, umbilical artery, middle cerebral artery and umbilical venous Dopplers, as well as amniotic fluid volume, were assessed. All cases were followed up within 48 h of delivery. Ultrasound parameters and intrapartum outcomes were then compared between the nulliparous and parous groups. Compared with nulliparous women, parous women had significantly higher fetal middle cerebral artery pulsatility index, cerebroplacental ratio and amniotic fluid volume. In nulliparous women, middle cerebral artery flow rate was also significantly higher and represented a greater percentage of umbilical venous flow than was observed in parous women. Prior to the active phase of labor, ultrasound parameters indicative of placental function differ significantly between nulliparous and parous pregnancy, even amongst an uncomplicated, low-risk cohort.
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.COLEGN.2015.09.001
Abstract: Effective communication is essential in developing rapport with patients, and many nursing roles such as patient assessment, education, and counselling consist only of dialogue. With increasing cultural ersity among nurses and patients in Australia, there are growing concerns relating to the potential for miscommunication, as differences in language and culture can cause misunderstandings which can have serious impacts on health outcomes and patient safety (Hamilton & Woodward-Kron, 2010). According to Grant and Luxford (2011)) there is little research into the way health professionals approach working with cultural difference or how this impacts on their everyday practice. Furthermore, there has been minimal examination of intercultural nurse–patient communication from a linguistic perspective. Applying linguistic frameworks to nursing practice can help nurses understand what is happening in their communication with patients, particularly where people from different cultures are interacting. This paper discusses intercultural nurse–patient communication and refers to theoretical frameworks from applied linguistics to explain how miscommunication may occur. It illustrates how such approaches will help to raise awareness of underlying causes and potentially lead to more effective communication skills, therapeutic relationships and therefore patient satisfaction and safety.
Publisher: Informa UK Limited
Date: 03-10-2022
Publisher: Frontiers Media SA
Date: 14-01-2021
DOI: 10.3389/FGENE.2021.818334
Abstract: MicroRNAs (miRNAs) can exhibit aberrant expression under different physiological and pathological conditions. Therefore, differentially expressed circulating miRNAs have been a focus of biomarker discovery research. However, the use of circulating miRNAs comes with challenges which may hinder the reliability for their clinical application. These include varied s le collection protocols, storage times/conditions, s le processing and analysis methods. This study focused on examining the effect of whole blood holding time on the stability of plasma miRNA expression profiles. Whole blood s les were collected from healthy pregnant women and were held at 4°C for 30 min, 2 h, 6 h or 24 h prior to processing for plasma isolation. Plasma RNA was extracted and the expression of 179 miRNAs were analyzed. Unsupervised principal component analysis demonstrated that whole blood holding time was a major source of variation in miRNA expression profiles with 53 of 179 miRNAs showing significant changes in expression. Levels of specific miRNAs previously reported to be associated with pregnancy-associated complications such as hsa-miR-150-5p, hsa-miR-191-5p, and hsa-miR-29a-3p, as well as commonly used endogenous miRNA controls, hsa-miR-16-5p, hsa-miR-25-3p, and hsa-miR-223-3p were significantly altered with increase in blood holding time. Current protocols for plasma-based miRNA profiling for diagnostics describe major differences in whole blood holding periods ranging from immediately after collection to 26 h after. Our results demonstrate holding time can have dramatic effects on analytical reliability and reproducibility. This highlights the importance of standardization of blood holding time prior to processing for plasma in order to minimize introduction of non-biological variance in miRNA profiles.
Publisher: Springer Science and Business Media LLC
Date: 24-04-2020
DOI: 10.1038/S41467-020-15856-Y
Abstract: Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN) however, causal inference remains uncertain. Here, we use bacterial DNA sequencing from serially collected vaginal s les from a cohort of 87 adolescent and young women aged 16–26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus- dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies.
Publisher: Springer Science and Business Media LLC
Date: 13-06-2016
Publisher: Oxford University Press (OUP)
Date: 10-10-2019
Abstract: In our earlier work, we found that intrauterine (i.u.) and intraperitoneal (i.p.) injection of LPS (10-μg serotype 0111:B4) induced preterm labor (PTL) with high pup mortality, marked systemic inflammatory response and hypotension. Here, we used both i.u. and i.p. LPS models in pregnant wild-type (wt) and CCR2 knockout (CCR2−/−) mice on E16 to investigate the role played by the CCL2/CCR2 system in the response to LPS. Basally, lower numbers of monocytes and macrophages and higher numbers of neutrophils were found in the myometrium, placenta, and blood of CCR2−/− vs. wt mice. After i.u. LPS, parturition occurred at 14 h in both groups of mice. At 7 h post-injection, 70% of wt pups were dead vs. 10% of CCR2−/− pups, but at delivery 100% of wt and 90% of CCR2−/− pups were dead. Myometrial and placental monocytes and macrophages were generally lower in CCR2−/− mice, but this was less consistent in the circulation, lung, and liver. At 7 h post-LPS, myometrial ERK activation was greater and JNK and p65 lower and the mRNA levels of chemokines were higher and of inflammatory cytokines lower in CCR2−/− vs. wt mice. Pup brain and placental inflammation were similar. Using the IP LPS model, we found that all measures of arterial pressure increased in CCR2−/− but declined in wt mice. These data suggest that the CCL2/CCR2 system plays a critical role in the cardiovascular response to LPS and contributes to pup death but does not influence the onset of inflammation-induced PTL.
Publisher: Elsevier BV
Date: 03-2001
Publisher: Springer Science and Business Media LLC
Date: 24-01-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2018
DOI: 10.1161/HYPERTENSIONAHA.118.11092
Abstract: Preecl sia and fetal growth restriction during pregnancy are associated with increased risk of maternal cardiovascular disease later in life. It is unclear whether this association is causal or driven by similar antecedent risk factors. Clarification requires recruitment before conception which is methodologically difficult with high attrition rates and loss of outcome numbers to nonconception/miscarriage. Few prospective studies have, therefore, been adequately powered to address these questions. We recruited 530 healthy women (mean age: 35.0 years) intending to conceive and assessed cardiac output, cardiac index, stroke volume, total peripheral resistance, mean arterial pressure, and heart rate before pregnancy. Participants were followed to completion of subsequent pregnancy with repeat longitudinal assessments. Of 356 spontaneously conceived pregnancies, 15 (4.2%) were affected by preecl sia and fetal growth restriction. Women who subsequently developed preecl sia/fetal growth restriction had lower preconception cardiac output (4.9 versus 5.8 L/min P =0.002) and cardiac index (2.9 versus 3.3 L/min per meter 2 P =0.031) while mean arterial pressure (87.1 versus 82.3 mm Hg P =0.05) and total peripheral resistance (1396.4 versus 1156.1 dynes sec cm − 5 P .001) were higher. Longitudinal trajectories for cardiac output and total peripheral resistance were similar between affected and healthy pregnancies, but the former group showed a more exaggerated fall in mean arterial pressure in the first trimester, followed by a steeper rise and a steeper fall to postpartum values. Significant relationships were observed between cardiac output, total peripheral resistance, and mean arterial pressure and gestational epoch. We conclude that in healthy women, an altered prepregnancy hemodynamic phenotype is associated with the subsequent development of preecl sia/fetal growth restriction.
Publisher: Springer Science and Business Media LLC
Date: 28-05-2021
DOI: 10.1186/S40168-021-01011-2
Abstract: Obesity and vaginal microbiome (VMB) dysbiosis are each risk factors for adverse reproductive and oncological health outcomes in women. Here, we investigated the relationship between obesity, vaginal bacterial composition, local inflammation and bariatric surgery. Vaginal bacterial composition assessed by high-throughput sequencing of bacterial 16S rRNA genes and local cytokine levels measured using a multiplexed Magnetic Luminex Screening Assay were compared between 67 obese and 42 non-obese women. We further assessed temporal changes in the microbiota and cytokines in a subset of 27 women who underwent bariatric surgery. The bacterial component of the vaginal microbiota in obese women was characterised by a lower prevalence of a Lactobacillus -dominant VMB and higher prevalence of a high ersity ( Lactobacillus spp., and Gardnerella - spp. depleted) VMB, compared with non-obese subjects ( p .001). Obese women had higher relative abundance of Dialister species ( p .001), Anaerococcus vaginalis ( p =0.021), and Prevotella timonensis ( p =0.020) and decreased relative abundance of Lactobacillus crispatus ( p =0.014). Local vaginal IL-1β, IL-4, IL-6, IL-8, IFNγ, MIP-1α and TNFα levels were all higher among obese women, however, only IL-1β and IL-8 correlated with VMB species ersity. In a subset of obese women undergoing bariatric surgery, there were no significant overall differences in VMB following surgery however, 75% of these women remained obese at 6 months. Prior to surgery, there was no relationship between body mass index (BMI) and VMB structure however, post-surgery women with a Lactobacillus -dominant VMB had a significantly lower BMI than those with a high ersity VMB. Obese women have a significantly different vaginal microbiota composition with increased levels of local inflammation compared to non-obese women. Bariatric surgery does not change the VMB however, those with the greatest weight loss 6-month post-surgery are most likely to have a Lactobacillus -dominant VMB.
Publisher: Oxford University Press (OUP)
Date: 19-10-2016
Publisher: Wiley
Date: 08-08-2019
Abstract: Women with congenital absolute uterine factor infertility (AUFI) often need vaginal restoration to optimise sexual function. Given their lack of procreative ability, little consideration has previously been given to the resultant vaginal microbiome (VM). Uterine transplantation (UTx) now offers the opportunity to restore these women's reproductive potential. The structure of the VM is associated with clinical and reproductive implications that are intricately intertwined with the process of UTx. Consideration of how vaginal restoration methods impact VM is now warranted and assessment of the VM in future UTx procedures is essential to understand the interrelation of the VM and clinical and reproductive outcomes. TWEETABLE ABSTRACT: The vaginal microbiome has numerous implications for clinical and reproductive outcomes in the context of uterine transplantation.
Publisher: Research Square Platform LLC
Date: 10-09-2020
DOI: 10.21203/RS.3.RS-73123/V1
Abstract: Background: Vaginal microbiota (VMB) are altered in women with cervical intra-epithelial neoplasia (CIN) and associate with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This interventional study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines. We s led 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also s led. We used metataxonomics to group vaginal swab s les into community state types (CSTs) and ELISA to quantify cytokine and AMPs levels in matched vaginal secretions. Analyses were performed to compare bacterial composition and immune analyte levels before and after CIN excision and in healthy controls. Results: Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV: 21/103, 20% vs 1/39, 3%, p=0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV: 19/103, 20% vs 1/39, 3%, p=0.0142). Prevotella bivia and Sneathia amnii were significantly higher in s les before treatment compared to untreated controls and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1 and IL-8 remained significantly elevated pre- (p .0001 and p=0.0014 respectively) and post-treatment compared to untreated controls (p .0001 and p=0.0035 respectively). Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p .0001), however their levels remained lower than controls post-treatment. Conclusions: Women with CIN have increased prevalence of Lactobacillus spp. depleted, high- ersity VMB, proinflammatory cytokines and AMPs than normal controls. Surgical excision of the disease reduces levels of vaginal AMPs but does not alter VMB composition or cytokine levels. These findings suggest that women with CIN have an inherent predisposition to a high- ersity proinflammatory environment that is not corrected by disease excision. The failure to re-establish a Lactobacillus enriched CST may explain why women remain at high risk of pre-invasive and invasive disease recurrence.
Publisher: SAGE Publications Ltd
Date: 2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2021
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9CC05607F
Abstract: Low-cost detection of miRNA biomarkers from maternal blood is achieved via a highly sequence-specific templated reaction on nitrocellulose paper strips to enable early prediction of preterm birth in a minimally invasive manner.
Publisher: Public Library of Science (PLoS)
Date: 30-11-2012
Publisher: Elsevier BV
Date: 05-2018
Publisher: Wiley
Date: 06-2002
DOI: 10.1002/PD.350
Abstract: Selective lification of rare fetal cells in maternal blood is a potential strategy for non-invasive prenatal diagnosis. We assessed the proliferative potential of first trimester fetal progenitors compared to maternal ones. Fetal and maternal haemopoietic progenitors were cultured separately and in two model mixtures: (i) co-cultures of male fetal nucleated cells mixed with maternal nucleated cells and (ii) co-cultures of malefetal CD34+ cells with maternal CD34+ cells. Cell origin was detected by X-Y fluorescence in situ hybridisation (FISH) RESULTS: The frequency of haemopoietic progenitors in first trimester fetal blood (predominantly CFU-GEMM) differed from those in peripheral blood from pregnant women (predominantly BFU-e). First trimester haemopoietic progenitors formed larger colonies (p=0.0001) and their haemoglobinisation was accelerated compared to those of maternal origin (p<0.001). CD34+ fetal haemopoietic progenitor cells could be expanded four times more than their maternal counterparts (median 235.8-fold, range 174.0-968.0 vs 71.9-fold, range 41.1-192.0 p=0.003). While selective expansion of fetal cells was not observed in the mononuclear cell model, the CD34+ cell rare event mixtures produced a 463.2-fold (range 128.0-2915.0) expansion of fetal cells. Selective expansion of first trimester fetal haemopoietic progenitors may be useful for lifying fetal cells from maternal blood.
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.AJOG.2012.11.016
Abstract: To investigate the use of the fetal cerebroumbilical ratio to predict intrapartum compromise in appropriately grown fetuses. A prospective observational study set at Queen Charlotte's and Chelsea hospital, London, UK. Fetal biometry and Doppler resistance indices were measured in 400 women immediately before established labor. Labor was then managed according to local protocols and guidelines, and intrapartum and neonatal outcome details recorded. Infants delivered by cesarean section for fetal compromise had significantly lower cerebroumbilical ratios than those born by spontaneous vaginal delivery (1.52 vs 1.82, P ≤ .001). Infants with a cerebroumbilical ratio 90th percentile appears protective of cesarean section for fetal compromise (negative predictive value 100%). The fetal cerebroumbilical ratio can identify fetuses at high and low risk of a subsequent diagnosis of intrapartum compromise, and may be used to risk stratify pregnancies before labor.
Publisher: Springer Science and Business Media LLC
Date: 11-03-2015
DOI: 10.1038/SREP08988
Abstract: The composition and structure of the pregnancy vaginal microbiome may influence susceptibility to adverse pregnancy outcomes. Studies on the pregnant vaginal microbiome have largely been limited to Northern American populations. Using MiSeq sequencing of 16S rRNA gene licons, we characterised the vaginal microbiota of a mixed British cohort of women (n = 42) who experienced uncomplicated term delivery and who were s led longitudinally throughout pregnancy (8–12, 20–22, 28–30 and 34–36 weeks gestation) and 6 weeks postpartum. We show that vaginal microbiome composition dramatically changes postpartum to become less Lactobacillus spp. dominant with increased alpha- ersity irrespective of the community structure during pregnancy and independent of ethnicity. While the pregnancy vaginal microbiome was characteristically dominated by Lactobacillus spp. and low alpha- ersity, unlike Northern American populations, a significant number of pregnant women this British population had a L. jensenii -dominated microbiome characterised by low alpha- ersity. L. jensenii was predominantly observed in women of Asian and Caucasian ethnicity whereas L. gasseri was absent in s les from Black women. This study reveals new insights into biogeographical and ethnic effects upon the pregnancy and postpartum vaginal microbiome and has important implications for future studies exploring relationships between the vaginal microbiome, host health and pregnancy outcomes.
Publisher: Public Library of Science (PLoS)
Date: 02-04-2012
Publisher: Springer Science and Business Media LLC
Date: 20-12-2021
DOI: 10.1038/S41522-021-00261-0
Abstract: Vaginal microbiota-host interactions are linked to preterm birth (PTB), which continues to be the primary cause of global childhood mortality. Due to population size, the majority of PTB occurs in Asia, yet there have been few studies of the pregnancy vaginal microbiota in Asian populations. Here, we characterized the vaginal microbiome of 2689 pregnant Chinese women using metataxonomics and in a subset ( n = 819), the relationship between vaginal microbiota composition, sialidase activity and leukocyte presence and pregnancy outcomes. Vaginal microbiota were most frequently dominated by Lactobacillus crispatus or L. iners , with the latter associated with vaginal leukocyte presence. Women with high sialidase activity were enriched for bacterial vaginosis-associated genera including Gardnerella, Atopobium and Prevotella . Vaginal microbiota composition, high sialidase activity and/or leukocyte presence was not associated with PTB risk suggesting underlying differences in the vaginal microbiota and/or host immune responses of Chinese women, possibly accounting for low PTB rates in this population.
Publisher: Cambridge University Press (CUP)
Date: 02-2014
DOI: 10.1017/S0965539514000059
Abstract: Preterm birth (PTB) has a global prevalence of 11.1% accounting for almost 15 million babies born each year before 37 weeks of gestation. It is a risk factor in over 50% of all neonatal deaths, which amounts to 1.1 million deaths annually. Preterm birth, especially at early gestational ages is associated with a high risk of long-term morbidity in survivors. Despite much research effort, PTB rates continue to rise, placing immense financial and emotional burden on society. In the US, the annual societal economic cost associated with PTB is $26.2 billion with an average of $51,600 being spent per infant born preterm. Preterm labour (PTL) accounts for 70% of these births, of which 25% are preceded by preterm pre-labour rupture of membranes (PPROM).
Publisher: Springer Science and Business Media LLC
Date: 08-2020
DOI: 10.1007/S00281-020-00817-W
Abstract: Preterm birth is a global health concern and continues to contribute to substantial neonatal morbidity and mortality despite advances in obstetric and neonatal care. The underlying aetiology is multi-factorial and remains incompletely understood. In this review, the complex interplay between the vaginal microbiome in pregnancy and its association with preterm birth is discussed in depth. Advances in the study of bacteriology and an improved understanding of the human microbiome have seen an improved awareness of the vaginal microbiota in both health and in disease.
Publisher: Wiley
Date: 07-02-2017
DOI: 10.1111/IJAL.12166
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.AJOG.2015.03.015
Abstract: MicroRNAs (miRNAs) play a modulatory role in pathways that lead to labor onset, although oxytocin is known to modulate gene expression within the myometrium. We aimed to identify miRNAs whose expression is regulated by oxytocin in pregnant human myometrium. Myometrial miRNA expression profiles were compared between s les collected from women at term before the onset of labor (no labor n = 8) and after labor onset after early exogenous oxytocin treatment (n = 8). Multivariate modelling was used to assess differences in miRNA profiles. Biologic validation was undertaken on 3 independent patient cohorts (no labor, n = 10 labor induced with oxytocin, n = 8 and spontaneous labor with no oxytocin treatment, n = 10). In vitro studies that used primary myocytes were undertaken to assess target miRNA expression after oxytocin treatment. Target genes of candidate miRNAs were identified in silico and cross-referenced with genes that are known to be associated with labor or expressed in myometrium. In total, 1309 miRNAs were analyzed by microarray, of which 494 were detected in human myometrium. Multivariate modeling identified 12 target miRNAs the differential expression of which was most responsible for the observed separation of the 2 patient populations in the primary discovery cohorts. Biologic validation in the independent secondary s le cohorts showed that oxytocin independently regulated 5 miRNAs (hsa-miR-146b-3p, hsa-miR-196b-3p, hsa-miR-223-3p, hsa-miR-873-5p, and hsa-miR-876-5p). Additionally, hsa-miR-146b-3p was increased both in labor that was induced with oxytocin and in myometrium from spontaneous labor with no oxytocin treatment compared with no labor s les. Four of the validated miRNAs (hsa-miR-146a-5p, hsa-miR-146b-3p, hsa-miR-196b-3p, and hsa-miR-876-5p) were expressed in primary human myocytes oxytocin treatment of these cells replicated the directional changes that were observed in vivo. Oxytocin alters the expression of a unique set of myometrial miRNAs. These results suggest a further role for oxytocin as a signaling molecule that is involved in the regulation of gene expression during parturition.
Publisher: Frontiers Media SA
Date: 29-11-2021
DOI: 10.3389/FCIMB.2021.750103
Abstract: Pregnant women living with HIV infection (PWLWH) have elevated rates of preterm birth (PTB) in which HIV and cART are implicated. PWLWH also have a high prevalence of adverse vaginal microbiota, which associate with genital tract inflammation. The mechanism underlying PTB in PWLWH is unknown. We present the first data in PWLWH on genital-tract matrix-metalloproteinase-9(MMP-9), an important collagenase implicated in labour onset, and tissue inhibitor of metalloproteinases-1(TIMP-1) and explore correlations with local inflammation and vaginal bacteria. Cervical vaginal fluid (CVF) collected by a soft cup and high vaginal swabs (HVS) were obtained from PWLWH and HIV uninfected pregnant women (HUPW) at three antenatal time points. Maternal characteristics, combination antiretroviral therapy (cART) exposure, and pregnancy outcome were recorded. Concentrations of MMP-9, TIMP-1 and ten cytokines were measured by immunoassays. Vaginal microbiota composition was determined through 16S rRNA licon sequencing. MMP-9, TIMP-1 and cytokine concentrations were compared by HIV status, cART, and prematurity and in PWLWH correlations with polymorphonuclear leucocytes, cytokines and bacterial genera were explored. CVF was available for 50 PWLWH (108 s les) and 12 HUPW (20 s les) between gestation weeks 14-38. Thirty-six PWLWH conceived on cART and 14 initiated post-conception. There were five and one PTB outcomes in PWLWH and HUPW respectively. PWLWH had higher mean CVF concentrations of MMP-9 (p& .001) and TIMP-1 (p=0.035) in the second trimester compared with HUPW with a similar trend in the third trimester. PWLWH also had higher CVF values of cytokines: IL-1β, IL-8, IL-12 and TNF-α in both trimesters compared to HUPW (p ≤ 0.003). In PWLWH, MMP-9 positively correlated with TIMP-1 (r=0.31, p=0.002) and CVF polymorphonuclear leucocytes (r=0.57, p=0.02). Correlations were observed between MMP-9 and three cytokines: IL-1β (r=0.61), IL-8 (r=0.57) and TNF-α (r=0.64), p& .001, similarly for TIMP-1. Abundance of anaerobic pathobionts correlated with MMP-9: Gardnerella (r=0.44, p& .001), Atopobium (r=0.33, p=0.005), and Prevotella genera (r=0.39, p& .001). Conversely proportion of Lactobacillus genera negatively correlated with MMP-9 (rho=-0.46, p& .001). MMP-9/TIMP-1 ratio increased with gestational age at s ling in PWLWH, but this was no longer significant after adjusting for confounders and no difference by prematurity was observed in this sub-study. Here we show strong correlations of MMP-9 to genital tract inflammation and sub-optimal bacterial genera in PWLWH indicating the ascending genital tract infection pathway may be a contributory mechanism to the high risk of PTB.
Publisher: Wiley
Date: 29-04-2014
DOI: 10.1111/AJO.12216
Abstract: The incidence of cerebral palsy in term infants has not changed over the last 30 years. Current intrapartum monitoring techniques are limited by their inherent poor specificity. Changes in fetal haemodynamics in the term fetus, similar to those seen in fetal growth restriction, have been associated with an increased risk of subsequent intrapartum fetal compromise. Alterations in first-trimester β-hCG and PAPP-A levels are predictive of fetal growth restriction. In this study, we aimed to establish whether first-trimester β-hCG and PAPP-A levels were predictive of fetal compromise in labour and whether these first-trimester markers could be correlated with fetal haemodynamics at term in a low-risk population. Over a two-year period, 427 women with low risk, uncomplicated pregnancies were recruited to this study. All participants underwent a prelabour ultrasound examination during which fetal biometry and haemodynamics were assessed. First-trimester β-hCG and PAPP-A levels were recorded from the case notes. All cases were followed up within 48 hours of delivery, and first-trimester β-hCG and PAPP-A levels correlated with intrapartum outcomes and fetal haemodynamics. No significant relationship between first-trimester β-hCG and PAPP-A levels and subsequent intrapartum fetal compromise was observed. Weak but significant correlations were observed between β-hCG levels and umbilical venous flow rate, as well as PAPP-A levels and uterine artery pulsatility index. β-hCG and PAPP-A levels measured during the first trimester are not predictive of subsequent intrapartum fetal compromise within a low-risk population.
Publisher: American Society of Hematology
Date: 15-10-2001
Abstract: Human mesenchymal stem rogenitor cells (MSCs) have been identified in adult bone marrow, but little is known about their presence during fetal life. MSCs were isolated and characterized in first-trimester fetal blood, liver, and bone marrow. When 106 fetal blood nucleated cells (median gestational age, 10+2 weeks [10 weeks, 2 days]) were cultured in 10% fetal bovine serum, the mean number (± SEM) of adherent fibroblastlike colonies was 8.2 ± 0.6/106 nucleated cells (69.6 ± 10/μL fetal blood). Frequency declined with advancing gestation. Fetal blood MSCs could be expanded for at least 20 passages with a mean cumulative population doubling of 50.3 ± 4.5. In their undifferentiated state, fetal blood MSCs were CD29+, CD44+, SH2+, SH3+, and SH4+ produced prolyl-4-hydroxylase, α-smooth muscle actin, fibronectin, laminin, and vimentin and were CD45−, CD34−, CD14−, CD68−, vWF−, and HLA-DR−. Fetal blood MSCs cultured in adipogenic, osteogenic, or chondrogenic media differentiated, respectively, into adipocytes, osteocytes, and chondrocytes. Fetal blood MSCs supported the proliferation and differentiation of cord blood CD34+cells in long-term culture. MSCs were also detected in first-trimester fetal liver (11.3 ± 2.0/106 nucleated cells) and bone marrow (12.6 ± 3.6/106 nucleated cells). Their morphology, growth kinetics, and immunophenotype were comparable to those of fetal blood-derived MSCs and similarly differentiated along adipogenic, osteogenic, and chondrogenic lineages, even after sorting and expansion of a single mesenchymal cell. MSCs similar to those derived from adult bone marrow, fetal liver, and fetal bone marrow circulate in first-trimester human blood and may provide novel targets for in utero cellular and gene therapy.
Publisher: Wiley
Date: 03-2001
DOI: 10.1046/J.1469-0705.2001.00376.X
Abstract: To apply digital imaging techniques to the quantification of placental vascularity using power Doppler. Regional placental blood flow was measured in a case of large placental abruption, shortly after presentation and 1 week later. Images were stored digitally and analysed using purpose-designed software (CQ Analysis) to extract and measure vascular energy information. The integrated color energy (ICE) was determined in the main body of placental tissue and in a cotyledon isolated by the retroplacental clot. Initial assessment at 25 weeks showed only a small difference in integrated energy between normal placenta and the isolated cotyledon (ICE ratio 1.44, P < 0.04). One week later, perfusion in the isolated cotyledon had fallen both on qualitative and quantitative assessment (ICE ratio 3.98, P < 0.0001). This area subsequently became devascularized. Placental perfusion may be quantified using digital power Doppler analysis. Further studies are indicated to evaluate its role in assessing regional and/or global placental perfusion as well as fetal organ perfusion.
Publisher: Springer Science and Business Media LLC
Date: 21-02-2022
DOI: 10.1038/S41467-022-28620-1
Abstract: There has been a surge in studies implicating a role of vaginal microbiota in spontaneous preterm birth (sPTB), but most are associative without mechanistic insight. Here we show a comprehensive approach to understand the causative factors of preterm birth, based on the integration of longitudinal vaginal microbiota and cervicovaginal fluid (CVF) immunophenotype data collected from 133 women at high-risk of sPTB. We show that vaginal depletion of Lactobacillus species and high bacterial ersity leads to increased mannose binding lectin (MBL), IgM, IgG, C3b, C5, IL-8, IL-6 and IL-1β and to increased risk of sPTB. Cervical shortening, which often precedes preterm birth, is associated with Lactobacillus iners and elevated levels of IgM, C3b, C5, C5a and IL-6. These data demonstrate a role for the complement system in microbial-driven sPTB and provide a scientific rationale for the development of live biotherapeutics and complement therapeutics to prevent sPTB.
Publisher: Proceedings of the National Academy of Sciences
Date: 16-03-2020
Abstract: Clearance of surgical margins in cervical cancer prevents the need for adjuvant chemoradiation and allows fertility preservation. In this study, we determined the capacity of the rapid evaporative ionization mass spectrometry (REIMS), also known as intelligent knife (iKnife), to discriminate between healthy, preinvasive, and invasive cervical tissue. Cervical tissue s les were collected from women with healthy, human papilloma virus (HPV) ± cervical intraepithelial neoplasia (CIN), or cervical cancer. A handheld diathermy device generated surgical aerosol, which was transferred into a mass spectrometer for subsequent chemical analysis. Combination of principal component and linear discriminant analysis and least absolute shrinkage and selection operator was employed to study the spectral differences between groups. Significance of discriminatory m/z features was tested using univariate statistics and tandem MS performed to elucidate the structure of the significant peaks allowing separation of the two classes. We analyzed 87 s les (normal = 16, HPV ± CIN = 50, cancer = 21 patients). The iKnife discriminated with 100% accuracy normal (100%) vs. HPV ± CIN (100%) vs. cancer (100%) when compared to histology as the gold standard. When comparing normal vs. cancer s les, the accuracy was 100% with a sensitivity of 100% (95% CI 83.9 to 100) and specificity 100% (79.4 to 100). Univariate analysis revealed significant MS peaks in the cancer-to-normal separation belonging to various classes of complex lipids. The iKnife discriminates healthy from premalignant and invasive cervical lesions with high accuracy and can improve oncological outcomes and fertility preservation of women treated surgically for cervical cancer. Larger in vivo research cohorts are required to validate these findings.
Publisher: American Chemical Society (ACS)
Date: 11-01-2017
DOI: 10.1021/ACS.ANALCHEM.6B03405
Abstract: Medical swabs are routinely used worldwide to s le human mucosa for microbiological screening with culture methods. These are usually time-consuming and have a narrow focus on screening for particular microorganism species. As an alternative, direct mass spectrometric profiling of the mucosal metabolome provides a broader window into the mucosal ecosystem. We present for the first time a minimal effort/minimal-disruption technique for augmenting the information obtained from clinical swab analysis with mucosal metabolome profiling using desorption electrospray ionization mass spectrometry (DESI-MS) analysis. Ionization of mucosal biomass occurs directly from a standard rayon swab mounted on a rotating device and analyzed by DESI MS using an optimized protocol considering swab-inlet geometry, tip-s le angles and distances, rotation speeds, and reproducibility. Multivariate modeling of mass spectral fingerprints obtained in this way readily discriminate between different mucosal surfaces and display the ability to characterize biochemical alterations induced by pregnancy and bacterial vaginosis (BV). The method was also applied directly to bacterial biomass to confirm the ability to detect intact bacterial species from a swab. These results highlight the potential of direct swab analysis by DESI-MS for a wide range of clinical applications including rapid mucosal diagnostics for microbiology, immune responses, and biochemistry.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9CC90472G
Abstract: Correction for ‘Oligonucleotide-templated lateral flow assays for lification-free sensing of circulating microRNAs’ by Suraj Pavagada et al. , Chem. Commun. , 2019, 55 , 12451–12454.
Publisher: The Endocrine Society
Date: 02-2012
DOI: 10.1210/JC.2011-1991
Abstract: Prostaglandins are central to the processes of human labor. Prostaglandin E(2) (PGE(2)) synthesized within the uterus mediates cervical ripening and uterine contractions. PGE receptors, EP1 and EP3, may each mediate contractions, and represent potential therapeutic targets in the management of preterm labor. Studies of the expression and function of EP1 and EP3 in pregnant myometrium are inconsistent. The objective of the study was to determine the relative importance of EP1 and EP3 in human myometrial contractility. We studied the expression of EP1 and EP3 in upper- and lower-segment myometrium at term in vivo and the effects of specific inhibitors on contractions in vitro. Myometrial biopsies for both in vivo and in vitro studies were taken at cesarean section at term before or in labor in uncomplicated pregnancies. We found no differences in the expression of EP1 or EP3 at mRNA or protein level between the upper and lower segment myometrium and no overall changes associated with the onset of labor. Upon labor, EP1, but not EP3, was found to relocalize to the nucleus. In studies of contractility, we found no differences in spontaneous or PGE(2)-induced contractility between the upper- and lower-segment s les. Spontaneous contractions were inhibited by acetylsalicylic acid and were rescued by PGE(2). Although an EP1 antagonist, ZD6416, had no effect, an EP3 antagonist, L798106, inhibited both spontaneous and PGE(2)-induced contractions. EP3 is the primary receptor subtype that mediates PGE(2) induced contractility in human pregnant myometrium at term and represents a possible therapeutic target.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Phillip Bennett.