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To examine the relationship between the English index of multiple deprivation (IMD) and the incidence of pre-eclampsia (PE), evaluate the distribution of IMD in a cohort of ethnically diverse pregnant women in South East England and assess whether IMD improves the prediction of PE compared with that provided by the 'history-only' competing-risks model (based on maternal characteristics and medical history).This was a prospective, observational study of 159 125 women with a singleton pregnancy who attended their first routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation in two maternity hospitals in the UK. The inclusion criteria were delivery at ≥ 24 weeks' gestation of babies without major abnormality. Participants completed a questionnaire on demographic characteristics and obstetric and medical history, which was then reviewed by a doctor together with the woman. Patients were asked to self-identify as white, black, South Asian, East Asian or mixed race. IMD was used as a measure of socioeconomic status, which takes into account income, employment, education, skills and training, health and disability, crime, barriers to housing and services, and living environment. Each neighborhood is ranked according to their level of deprivation relative to that of other areas into one of five equal groups, with Quintile 1 containing the 20% most deprived areas and Quintile 5 containing the 20% least deprived areas. IMD was assigned based on a woman's postcode. Risk factors for PE and its incidence were assessed across IMD using chi-square test or t-test, as appropriate. The relationship between IMD and gestational age at delivery with PE was evaluated by fitting parametric survival models for IMD alone, IMD combined with race and IMD combined with the Fetal Medicine Foundation history-only competing-risks model.The incidence of PE (n = 4088, 2.6%) increased progressively across IMD quintiles, from 2.0% in Quintile 5 (least deprived) to 3.0% in Quintile 1 (most deprived). Compared with white women and those in other racial groups, black women had a higher incidence of PE (4.8%), were less often in IMD Quintiles 4 and 5, and were more often in IMD Quintiles 1 and 2. None of the IMD quintiles improved the prediction of PE compared with that provided by the history-only competing-risks model (which includes race). The history-only competing-risks model with vs without IMD had a similar detection rate for delivery with PE at 37 weeks' gestation (44.1% (95% CI, 41.1-47.2%) vs 43.9% (95% CI, 40.1-47.0%)) and at any gestational age (35.2% (95% CI, 33.8-36.7%) vs 35.1% (95% CI, 33.7-36.6%)), at a 10% screen-positive rate.The incidence of PE is higher in women living in the most deprived areas in South East England and in black women (vs those of other racial groups), who also live in areas of higher deprivation. However, in screening for PE, inclusion of IMD does not improve the prediction of PE provided by race and other maternal characteristics and elements of medical history. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

The competing-risks model for assessment of risk for pre-eclampsia (PE) at 35-37 weeks' gestation identifies the majority of women who are at high risk of subsequent delivery with PE. We aimed to examine the incidence and relative risk of adverse pregnancy outcomes in patient groups stratified according to the estimated risk of delivery with PE.This was a prospective non-interventional, observational study in women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. The risk of delivery with PE for each patient in the study population was estimated using the competing-risks model, combining the prior distribution of gestational age at delivery with PE and the likelihood from multiples of the median values of mean arterial pressure, placental growth factor and soluble fms-like tyrosine kinase-1. The patients were assigned to one of the following five risk categories: Group A, ≥ 1 in 2; Group B, 1 in 5 to 1 in 3; Group C, 1 in 20 to 1 in 6; Group D, 1 in 50 to 1 in 21; and Group E, 1 in 50. The outcome measures were delivery with PE, gestational hypertension (GH), small-for-gestational age (SGA) at birth, delivery by Cesarean section, stillbirth, neonatal death, perinatal death and admission to the neonatal unit (NNU) for at least 48 h. In each risk category, the proportion of women with each adverse outcome was determined and relative risks (RR) were calculated as compared with the lowest-risk Group E.In the study population of 29 035 women, 1.6%, 2.7%, 8.2%, 9.8% and 77.8% were categorized into Groups A, B, C, D and E, respectively. Compared with women in Group E, women in the higher-risk groups were more likely to have an adverse outcome. The RR of delivery with PE in Group A compared with Group E was 65.5 (95% CI, 54.1-79.1) and the respective values were 11.9 (95% CI, 9.1-15.5) for GH, 1.8 (95% CI, 1.5-2.1) for delivery by emergency Cesarean section, 1.5 (95% CI, 1.2-1.8) for delivery by elective Cesarean section, 8.9 (95% CI, 7.4-10.8) for SGA with birth weight 3Pregnant women identified by the competing-risks model to be at high risk of PE are also at increased risk of GH, Cesarean section, stillbirth, SGA and NNU admission for ≥ 48 h. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Objective: there is little evidence related to the effects of the Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant on pregnancy outcomes, particularly in unvaccinated women. This study aimed to compare pregnancy outcomes of unvaccinated women infected with SARS-CoV-2 during the pre-Delta, Delta and Omicron waves. Methods: this was a retrospective cohort study conducted at two tertiary care facilities: Sancaktepe Training and Research Hospital, Istanbul, Turkey, and St George's University Hospitals NHS Foundation Trust, London, UK. Included were women who tested positive for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction (RT-PCR) during pregnancy, between 1 April 2020 and 14 February 2022. The cohort was divided into three periods according to the date of their positive RT-PCR test: (i) pre-Delta (1 April 2020 to 8 June 2021 in Turkey, and 1 April 2020 to 31 July 2021 in the UK), (ii) Delta (9 June 2021 to 27 December 2021 in Turkey, and 1 August 2021 to 27 December 2021 in the UK) and (iii) Omicron (after 27 December 2021 in both Turkey and the UK). Baseline data collected included maternal age, parity, body mass index, gestational age at diagnosis and comorbidities. The primary outcome was the need for oxygen supplementation, classified as oxygen support via nasal cannula or breather mask, non-invasive mechanical ventilation with continuous positive airway pressure (CPAP) or high-flow oxygen, mechanical ventilation with intubation, or extracorporeal membrane oxygenation (ECMO). Inferences were made after balancing of confounders, using an evolutionary search algorithm. Selected confounders were maternal age, body mass index and gestational age at diagnosis of infection. Results: during the study period, 1286 unvaccinated pregnant women with RT-PCR-proven SARS-CoV-2 infection were identified, comprising 870 cases during the pre-Delta period, 339 during the Delta wave and 77 during the Omicron wave. In the confounder-balanced cohort, infection during the Delta wave vs during the pre-Delta period was associated with increased need for nasal oxygen support (risk ratio (RR), 2.53 (95% CI, 1.75-3.65); P < 0.001), CPAP or high-flow oxygen (RR, 2.50 (95% CI, 1.37-4.56); P = 0.002), mechanical ventilation (RR, 4.20 (95% CI, 1.60-11.0); P = 0.003) and ECMO (RR, 11.0 (95% CI, 1.43-84.7); P = 0.021). The maternal mortality rate was 3.6-fold higher during the Delta wave compared to the pre-Delta period (5.3% vs 1.5%, P = 0.010). Infection during the Omicron wave was associated with a similar need for nasal oxygen support (RR, 0.62 (95% CI, 0.25-1.55); P = 0.251), CPAP or high-flow oxygen (RR, 1.07 (95% CI, 0.36-3.12); P = 0.906) and mechanical ventilation (RR, 0.44 (95% CI, 0.06-3.45); P = 0.438) with that in the pre-Delta period. The maternal mortality rate was similar during the Omicron wave and the pre-Delta period (1.3% vs 1.3%, P = 0.999). The need for nasal oxygen support during the Omicron wave was significantly lower compared to the Delta wave (RR, 0.26 (95% CI, 0.11-0.64); P = 0.003). Perinatal outcomes were available for a subset of the confounder-balanced cohort. Preterm birth before 34 weeks' gestation was significantly increased during the Delta wave compared with the pre-Delta period (15.4% vs 4.9%, P < 0.001). Conclusions: among unvaccinated pregnant women, SARS-CoV-2 infection during the Delta wave, in comparison to the pre-Delta period, was associated with increased requirement for oxygen support (including ECMO) and higher maternal mortality. Disease severity and pregnancy complications were similar between the Omicron wave and pre-Delta period. SARS-CoV-2 infection of unvaccinated pregnant women carries considerable risks of morbidity and mortality regardless of variant, and vaccination remains key. Miscommunication of the risks of Omicron infection may impact adversely vaccination uptake among pregnant women, who are at increased risk of complications related to SARS-CoV-2., NA

Author's reply.

Pregnant women are at an increased risk of mortality and morbidity owing to COVID-19. Many studies have reported on the association of COVID-19 with pregnancy-specific adverse outcomes, but prediction models utilizing large cohorts of pregnant women are still lacking for estimating the risk of maternal morbidity and other adverse events.The main aim of this study was to develop a prediction model to quantify the risk of progression to critical COVID-19 and intensive care unit admission in pregnant women with symptomatic infection.This was a multicenter retrospective cohort study including 8 hospitals from 4 countries (the United Kingdom, Austria, Greece, and Turkey). The data extraction was from February 2020 until May 2021. Included were consecutive pregnant and early postpartum women (within 10 days of birth); reverse transcriptase polymerase chain reaction confirmed SARS-CoV-2 infection. The primary outcome was progression to critical illness requiring intensive care. The secondary outcomes included maternal death, preeclampsia, and stillbirth. The association between the primary outcome and 12 candidate predictors having a known association with severe COVID-19 in pregnancy was analyzed with log-binomial mixed-effects regression and reported as adjusted risk ratios. All the potential predictors were evaluated in 1 model and only the baseline factors in another. The predictive accuracy was assessed by the area under the receiver operating characteristic curves.Of the 793 pregnant women who were positive for SARS-CoV-2 and were symptomatic, 44 (5.5%) were admitted to intensive care, of whom 10 died (1.3%). The 'mini-COvid Maternal Intensive Therapy' model included the following demographic and clinical variables available at disease onset: maternal age (adjusted risk ratio, 1.45; 95% confidence interval, 1.07-1.95; P=.015); body mass index (adjusted risk ratio, 1.34; 95% confidence interval, 1.06-1.66; P=.010); and diagnosis in the third trimester of pregnancy (adjusted risk ratio, 3.64; 95% confidence interval, 1.78-8.46; P=.001). The optimism-adjusted area under the receiver operating characteristic curve was 0.73. The 'full-COvid Maternal Intensive Therapy' model included body mass index (adjusted risk ratio, 1.39; 95% confidence interval, 1.07-1.95; P=.015), lower respiratory symptoms (adjusted risk ratio, 5.11; 95% confidence interval, 1.81-21.4; P=.007), neutrophil to lymphocyte ratio (adjusted risk ratio, 1.62; 95% confidence interval, 1.36-1.89; P.001); and serum C-reactive protein (adjusted risk ratio, 1.30; 95% confidence interval, 1.15-1.44; P.001), with an optimism-adjusted area under the receiver operating characteristic curve of 0.85. Neither model showed signs of a poor fit. Categorization as high-risk by either model was associated with a shorter diagnosis to intensive care unit admission interval (log-rank test P.001, both), higher maternal death (5.2% vs 0.2%; P.001), and preeclampsia (5.7% vs 1.0%; P.001). A spreadsheet calculator is available for risk estimation.At presentation with symptomatic COVID-19, pregnant and recently postpartum women can be stratified into high- and low-risk for progression to critical disease, even where resources are limited. This can support the nature and place of care. These models also highlight the independent risk for severe disease associated with obesity and should further emphasize that even in the absence of other comorbidities, vaccination is particularly important for these women. Finally, the model also provides useful information for policy makers when prioritizing national vaccination programs to quickly protect those at the highest risk of critical and fatal COVID-19.

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

Objective Pre-eclampsia involves a maternal inflammatory response that differs from both normal pregnancy and normotensive intrauterine growth restriction (IUGR). Our objective was to examine neutrophil Toll-like receptor (TLR), cryopyrin, nuclear factor-κB (NF-κB) subunit and interleukin-1β (IL-1β), and inflammatory cytokine profiles in women with pre-eclampsia or normotensive IUGR, as well as in normal pregnancy and non-pregnancy controls. Design and method A case–control study was performed. We examined the messenger RNA (mRNA) and protein expressions of TLR4 and TLR2, mRNA levels of cryopyrin, IL-1β, NF-κB subunits p50 and p65, as well as maternal serum inflammatory cytokine profiles (IL-2, IL-6, tumour necrosis factor-α [TNF-α], interferon-γ [IFN-γ] and IL-10) in women with and without pre-eclampsia using real-time reverse transcription polymerase chain reactions, flow cytometry and multiplex immunoassays. Setting A single tertiary maternity hospital in Vancouver, Canada. Population Women with early-onset pre-eclampsia (

SummarySignal transducer and activator of transcription-3 (STAT3) activation has been associated with suppressed inflammatory processes in experimental animals, murine myeloid cells and macrophage cell lines. Manipulation of STAT3 activity may therefore be a focus for pharmacological intervention of inflammatory diseases in humans. However, the ability of STAT3 to reduce the production of inflammatory mediators by activated human monocytes and macrophages has been characterized inadequately. To establish this, we used a recently optimized adenoviral approach to study the effect of overexpressed STAT3 or a transcriptionally inactive mutant STAT3 in lipopolysaccharide (LPS)-stimulated human monocytes. STAT3 activated by LPS did not directly regulate inhibitor of kappa B α (IκBα) activation or tumour necrosis factor (TNF)-α production, a process dependent on the transcriptional activity of nuclear factor kappa B (NFκB), although the transcriptional activity of STAT3 contributed to the mechanism by which interleukin (IL)-10 suppressed LPS-induced TNF-α levels. This contrasted with the efficient block in IL-10 induction of suppressor of cytokine signalling-3 (SOCS3) in monocytes infected with an adenovirus expressing mutant STAT3. These results indicate that STAT3 activation cannot directly regulate LPS-signalling in human monocytes and represents only part of the mechanism by which IL-10 suppresses TNF-α production by activated human monocytes. This study concludes that pharmacological manipulation of STAT3 transcriptional activity alone would be insufficient to control NFκB-associated inflammation in humans.

Satisfaction with maternity care is strongly related to the patient-caregiver relationship and involvement in the decision-making process. We sought to compare women's views about their care in a randomized trial of 'less tight' vs. 'tight' control of non-proteinuric pre-existing or gestational hypertension in pregnancy.In the CHIPS Pilot Trial, women completed a postpartum questionnaire to assess their likes and dislikes about their blood pressure (BP) management and trial participation. Comparisons were descriptive.Baseline information was similar for the 'less tight' and 'tight' control groups. Of 132 women, 126 (95.5%) from 17 centers completed a postpartum questionnaire, usually within days of delivery. At least 90% of women in both groups were satisfied with their care, and would be willing to participate again or recommend participation to a friend. Women in both the 'less tight' and 'tight' groups were satisfied with BP management (98.4% vs. 95.1%), and the frequency of tests of maternal and fetal well being. Half of women in both groups perceived that their BP was too high and that caregivers thought that their BP was too high. More women in the 'less tight' (vs. the 'tight') control group took less medication than expected (71.7% vs. 38.2%). More women in the 'tight' (vs. the 'less tight') group took more medication than they expected (60.0% vs. 22.2%). At least 60% of all women used home BP monitoring.In the CHIPS Pilot Trial, while women stated that they were satisfied with their BP management and care, a surprising 50% in both groups thought that their BP was too high. The majority of women used home BP monitoring, the role of which must be further defined in hypertensive pregnancies.

Micro-organisms isolated from composts were assayed in vitro for inhibition of mycelial growth and conidium germination of Fusarium culmorum. Eleven bacterial isolates inhibited mycelial growth, and of these seven also inhibited germination of conidia. However, inhibition of mycelial growth was only reproducible for three bacteria. Five fungal isolates were found to have antagonistic effects on F. culmorum mycelial growth. Of these five, three isolates gave reproducible results and also suppressed germination of F. culmorum conidia. An oat seedling bioassay was developed to determine the potential of microbial antagonists for use as seed treatments against F. culmorum in soil inoculated with the pathogen. Three bacterial isolates were selected for methodology development for in vivo evaluations. The effect of F. culmorum inoculation technique, growth substrate and assessment method were investigated.

OBJECTIVE To examine erythropoiesis in renal transplant pregnancies. METHODS Retrospective cohort study of 30 renal transplant cases and 30 age, smoking and parity-matched healthy controls with normal index pregnancy. Retrospective chart review and assay of frozen antenatal serum (for serum erythropoietin concentration [serum EPO]), transferrin receptor protein [TfR], ferritin, folate and B12) were performed. The linear regression equation for normal pregnancy controls was used to calculate predicted [serum EPO] and the observed/predicted (O/P) log [serum EPO] was plotted. The relationship between [serum EPO] and haemoglobin (Hb) among transplant cases was considered to be different from that among controls if the slope of the O/P log [serum EPO] versus Hb regression was significantly different from zero. RESULTS The transplant (14 cadaveric) to conception interval was (median [range]) 33.5 [4, 189] months. Immunosuppressants were azathioprine (n = 25), cyclosporine (n = 22) and/or prednisone (n = 25). Cases were more often primiparous (20 vs. 7 [controls]; p = 0.01), had pre-existent hypertension (20 vs. 0 [controls]; p < 0.001), developed new/increased hypertension or pre-eclampsia (28 vs. 0 [controls]; p < 0.001) and an antenatal rise in creatinine (14 vs. 2 [controls]; p < 0.001). In early pregnancy, cases had similar EPO (15.2 [2.6, 84.6] vs. 15.7 [6.4, 41.0] [controls] U/L) but lower Hb (101 [65, 129] vs. 116 [106, 150] g/L; p < 0.001). Twenty-two (73%) cases had Hb < 100 g/L (vs. 4 [controls]; p < 0.0001); Hb was comparable at 6 wk postpartum. With advancing gestational age (GA), Hb remained stable and serum EPO increased in both groups. The slope of the O/P log [serum EPO] versus Hb for transplant cases was significantly different from zero within both the 17-28 wk (slope +/- SEM: 0.010 +/- 0.002; p < 0.0001) and the 29-42 wk GA categories (0.006 +/- 0.003; p = 0.02). Cases showed smaller rises in serum TfR (change 481 [- 1471, 2780]) vs. 1119 [- 698, 4195] [controls] ng/mL; p = 0.005). CONCLUSIONS Anaemia frequently complicates renal transplant pregnancies, in which serum EPO is inappropriately low and the rate of erythropoiesis blunted.

The fullPIERS (Pre-eclampsia Integrated Estimate of RiSk) model is a promising tool for the prediction of adverse outcomes in pre-eclampsia, developed using the worst values for predictor variables measured within 48 hours of admission. We reassessed the performance of fullPIERS using predictor variables obtained within 6 and 24 hours of admission, and found that the stratification capacity, calibration ability, and classification accuracy of the model remained high. The fullPIERS model is accurate as a rule-in test for adverse maternal outcome, with a likelihood ratio of 14.8 (95% CI 9.1-24.1) or 17.5 (95% CI 11.7-26.3) based on 6- and 24-hour data, respectively, for the women identified to be at highest risk (predicted probability ≥ 30%).

The Canadian Perinatal Network (CPN) is a national database focused on threatened very pre-term birth. Women with one or more conditions most commonly associated with very pre-term birth are included if admitted to a participating tertiary perinatal unit at 22 weeks and 0 days to 28 weeks and 6 days.At BC Women's Hospital and Health Centre, we compared traditional paper-based ward logs and a search of the Canadian Institute for Health Information (CIHI) electronic database of inpatient discharges to identify patients.The study identified 244 women potentially eligible for inclusion in the CPN admitted between April and December 2007. Of the 155 eligible women entered into the CPN database, each method identified a similar number of unique records (142 and 147) not ascertained by the other: 10 (6.4%) by CIHI search and 5 (3.2%) by ward log review. However, CIHI search achieved these results after reviewing fewer records (206 vs. 223) in less time (0.67 vs. 13.6 hours for ward logs).Either method is appropriate for identification of potential research subjects using gestational age criteria. Although electronic methods are less time-consuming, they cannot be performed until after the patient is discharged and records and charts are reviewed. Each method's advantages and disadvantages will dictate use for a specific project.

Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)5th percentile] and either the gestational age was25(+0) weeks or an estimate of the fetal weight was600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies.

To determine the optimal timing of delivery in pregnancies with pre-existing (chronic) hypertension by quantifying the gestational age-specific risks of stillbirth associated with ongoing pregnancy and the gestational age-specific risks of neonatal mortality or serious neonatal morbidity following the induction of labour.Population-based cohort study.USA.A total of 171 669 singleton births to women with pre-existing hypertension between 1995 and 2005. Pregnancies additionally complicated by diabetes mellitus, cardiac, pulmonary or renal disease were excluded.The week-specific risks of stillbirth between 36 and 41 completed weeks of gestation were contrasted with the week-specific risks of neonatal mortality or serious neonatal morbidity among births following induction of labour in women with pre-existing hypertension.Stillbirth, neonatal mortality or serious neonatal morbidity (defined as a composite outcome which included any of the following: neonatal seizures, severe respiratory morbidity or 5-minute Apgar score ≤3).The risk of stillbirth in women with pre-existing hypertension remained stable at 1.0-1.1 per 1000 ongoing pregnancies until 38 weeks, before rising steadily to 3.5 per 1000 [95% confidence interval (CI): 2.4, 5.0] at 41 weeks. The risk of serious neonatal morbidity/neonatal mortality decreased sharply between 36 and 38 weeks from 137 [95% CI: 127, 146] to 26 [95% CI: 24, 29] per 1000 induced births, before stabilising beyond 39 weeks.Among women with otherwise uncomplicated pre-existing hypertension, delivery at 38 or 39 weeks appears to provide the optimal trade-off between the risk of adverse fetal and adverse neonatal outcomes.

Pre-eclampsia involves a maternal inflammatory response that differs from both normal pregnancy and normotensive intrauterine growth restriction (IUGR). Our objective was to examine neutrophil Toll-like receptor (TLR), cryopyrin, nuclear factor-kappaB (NF-kappaB) subunit and interleukin-1beta (IL-1beta), and inflammatory cytokine profiles in women with pre-eclampsia or normotensive IUGR, as well as in normal pregnancy and non-pregnancy controls.A case-control study was performed. We examined the messenger RNA (mRNA) and protein expressions of TLR4 and TLR2, mRNA levels of cryopyrin, IL-1beta, NF-kappaB subunits p50 and p65, as well as maternal serum inflammatory cytokine profiles (IL-2, IL-6, tumour necrosis factor-alpha [TNF-alpha], interferon-gamma [IFN-gamma] and IL-10) in women with and without pre-eclampsia using real-time reverse transcription polymerase chain reactions, flow cytometry and multiplex immunoassays.A single tertiary maternity hospital in Vancouver, Canada.Women with early-onset pre-eclampsia (34 weeks of gestation, n = 25), women with late-onset pre-eclampsia (or=34(+0) weeks of gestation, n = 25), women with normotensive IUGR (n = 25), women with normal pregnancy (n = 75) and non-pregnancy (n = 25) controls.Women with pre-eclampsia (as a single combined group of early- and late-onset, and particularly in women with early-onset pre-eclampsia) had increased TLR2 and TLR4 mRNA and protein expressions elevated cryopyrin, NF-kappaB subunit, and IL-1beta mRNA expression, and TNF-alpha:IL-10 and IL-6:IL-10 ratios compared with other groups.These data suggest that TLRs and cryopyrin may modulate the innate immune response of the maternal syndrome of pre-eclampsia, and might also trigger the differential inflammatory response existing between early onset pre-eclampsia and normotensive IUGR.

SOCS1 can regulate TLR-mediated signal transduction, yet mechanistic studies in murine macrophages have been confusing and contradictory. This study has used an adenoviral transfection system to determine the role of SOCS1 in the regulation of TNF-α production by activated human monocytes. Monocytes were infected with AdV-SOCS1 or with an empty vector control, AdV-GFP, for 24 h before activation with the TLR4 ligand, LPS. SOCS1 did not regulate TNF-α mRNA or protein production within the first two hours of TLR4 activation. However, SOCS1 suppressed the sustained production of TNF-α by primary human monocytes and synovial fluid macrophages ex vivo. In addition, SOCS1 regulated the production of IL-6, but not IL-10, by monocytes. Analysis of the early signaling pathway downstream of TLR4 demonstrated that SOCS1 had no regulatory effect on the activation or on the DNA binding capacity of NFκB. The late effects of LPS are mediated in part through the MyD88-independent pathway activating IRF3 and initiating the production of IFN-β. In response to adenoviral infection and before LPS exposure, monocytes expressed enhanced levels of IFN-β and Myxovirus A mRNA, an anti-viral molecule characterizing IFN-β activity. These two genes were reduced in AdV-SOCS1-infected cells. Further, SOCS1 regulated IFN-dependent pathways in LPS-activated cells as evidenced by reduced IFN-β production and STAT1 phosphorylation. Using AdV-infection to dissect SOCS1 control of IFN-dependent pathways, this study suggests that SOCS1-regulation of the IFN-dependent component of the LPS-induced TLR4 signaling pathway may contribute to the down-regulation of inflammatory cytokine production by AdV-SOCS1-infected human monocytes.

In the present work we examine the behavior of two types of microelectrode arrays in a channel flow cell under both steady-state and dynamic conditions. The main points examined are the extent to which the favorable characteristics of microelectrodes suggested above are attained with conventional conditions and the extent to which conclusions derived from steady-state measurements can be generalized to the more common dynamic conditions of chromatography

Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that suppresses the production of tumour necrosis factor-alpha (TNF-alpha) by monocytes and macrophages. Suppressor of cytokine signalling-3 (SOCS3), a negative regulator of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, is induced following IL-10 exposure but recent studies in mice suggest that SOCS3 only targets gp-130-dependent signal transduction pathways. Understanding the signalling pathways responsible for IL-10-mediated effects in primary human monocytes is relevant to human inflammatory disease and necessary for the identification of potential therapeutic targets. An adenoviral transfection system was used to express different levels of SOCS3 (quantified experimentally with its tag green fluorescent protein (GFP)) with the aim of investigating the role of SOCS3 in LPS-induced and IL-10-mediated suppression of TNF-alpha production by non-transformed human monocytes. SOCS3 over-expression had no effect on TNF-alpha mRNA levels induced by LPS or LPS plus IL-10, or on IL-10 phosphorylation of STAT3, STAT1 and ERK1/2. When data from all donors were combined, adenoviral overexpression of SOCS3 significantly reversed the suppressive effects of IL-10 on LPS-induced TNF-alpha production after 2 hr. However, there was a direct correlation between mean GFP intensity (extent of viral infection) and extent of reversal of IL-10's inhibitory effects. Physiological levels of SOCS3 detected in IL-10-exposed human monocytes had no effect on LPS-induced TNF-alpha production. Although overexpression of SOCS3 to supraphysiological levels transiently antagonized the regulatory properties of IL-10 by a post-transcriptional mechanism, these findings suggest that under pathological conditions SOCS3 does not control LPS-activation or the anti-inflammatory properties of IL-10 in primary human monocytes.

The hypertensive disorders of pregnancy remain a leading cause of maternal and perinatal morbidity and mortality in Europe and North America. Pre-eclampsia, which is proteinuric gestational hypertension, accounts for the majority of the excess risks and is defined by the maternal syndrome. The maternal syndrome of pre-eclampsia is characterised by a systemic inflammatory response and its sequelae. Systematic multisystem evaluation of pre-eclampsia, evidence-based antihypertensive therapy, and the use of MgSO4 to prevent and treat the seizures of eclampsia can reduce maternal risks. For mild-to-moderate pregnancy hypertension, maternal risks are small, and there may be adverse perinatal consequences of blood pressure normalisation. Early-onset and severe pre-eclampsia predict an excess risk of later cardiovascular morbidity and mortality. Both Chlamydophila pneumoniae and cytomegalovirus have bee associated with pre-eclampsia and atherosclerosis, and may provide a mechanistic link between pre-eclampsia and the recognised cardiovascular risk. Women with a history of either early-onset and/or severe pre-eclampsia should be considered to be at increased risk for later cardiovascular disease, and it may be prudent for them to have regular lipid profiles and tests for urinary microalbumin excretion.

Fifty per cent of pregnancies are unplanned, and 1-6% of young women have pre-existing hypertension. However, no commonly used antihypertensive agent is known to be teratogenic. ACE inhibitors (and angiotensin-receptor antagonists) should be discontinued due to fetotoxicity. Five to 10% of pregnant women have hypertension, of which pre-existing hypertension is but one type. There is consensus that severe maternal hypertension (blood pressureor=170/110 mmHg) should be treated to minimize the risk of acute cerebrovascular complications. Parenteral hydralazine may be associated with a higher risk of maternal hypotension, and intravenous labetalol with neonatal bradycardia. There is no consensus that mild-to-moderate hypertension in pregnancy should be treated. Clinical trials indicate that transient severe hypertension, antenatal hospitalization, proteinuria at delivery and neonatal respiratory distress syndrome may be decreased by normalizing blood pressure, but intrauterine fetal growth restriction may be increased. Methodological problems with published trials warrant cautious interpretation of these findings. Methyldopa and beta-blockers have been used most extensively, although atenolol may impair fetal growth in particular and should be avoided.

Nausea and vomiting of pregnancy is the most common condition in pregnancy and affects up to 80% of all pregnant women. There are a large number of pharmacological agents that are effective for the treatment of nausea and vomiting associated with conditions such as motion sickness and gastrointestinal conditions; however, their use in pregnancy is limited by the lack of sufficient data on their potential teratogenic effects. The efficacy of the delayed-release combination of doxylamine and pyridoxine (Bendectin, Diclectin) has been shown in several randomized, controlled trials. The present review aims to refute the unsubstantiated beliefs that Diclectin is unsafe when used in the treatment of nausea and vomiting of pregnancy.

Cardiovascular disease is the leading cause of death in women.1 Although its incidence is declining in men, this is not the case in women.2

Intra- and extrahepatic bile-duct strictures, papillary stenosis and acalculous cholecystitis have all been described in ill patients with acquired immunodeficiency syndrome (AIDS). Acalculous cholecystitis associated with cytomegalovirus (CMV), Cryptosporidium or Campylobacter organisms has typically been described in critically ill or moribund patients. The authors report a case of acute acalculous CMV cholecystitis in a 28-year-old man who presented with abdominal pain. The patient was infected with the human immunodeficiency virus (HIV) but was ambulatory and had had no AIDS-defining illness. The patient did not have any well-recognized risk factors for acalculous cholecystitis, showing that this entity can occur in relatively healthy HIV-infected patients as well as in the terminal stages of AIDS. The diagnosis should be considered when such a patient presents with abdominal pain. Furthermore, this patient had sclerosing cholangitis of the intra- and extrahepatic bile ducts as well as papillary stenosis. The cause of the acalculous cholecystitis was presumed to be CMV, but the disease progressed despite therapy with foscarnet.