A simulation model of Escherichia coli osmoregulatory switch using E-CELL system

BACKGROUND: Bacterial signal transduction mechanism referred to as a "two component regulatory systems" contributes to the overall adaptability of the bacteria by regulating the gene expression. Osmoregulation is one of the well-studied two component regulatory systems comprising of the sensor, EnvZ and the cognate response regulator, OmpR, which together control the expression of OmpC and OmpF porins in response to the osmolyte concentration. RESULTS: A quantitative model of the osmoregulatory switch operative in Escherichia coli was constructed by integrating the enzyme rate equations using E-CELL system. Using the substance reactor logic of the E-CELL system, a total of 28 reactions were defined from the injection of osmolyte till the regulated expression of porins by employing the experimental kinetic constants as reported in literature. In the case of low osmolarity, steady state production of OmpF and repression of OmpC was significant. In this model we show that the steady state – production of OmpF is dramatically reduced in the high osmolarity medium. The rate of OmpC production increased after sucrose addition, which is comparable with literature results. The relative porin production seems to be unaltered with changes in cell volume changes, ATP, EnvZ and OmpR at low and high osmolarity conditions. But the reach of saturation was rapid at high and low osmolarity with altered levels of the above components. CONCLUSIONS: The E-CELL system allows us to perform virtual experiments on the bacterial osmoregulation model. This model does not take into account interaction with other networks in the cell. It suggests that the regulation of OmpF and OmpC is a direct consequence of the level of OmpRP in the cell and is dependent on the way in which OmpRP interacts with ompF and ompC regulatory regions. The preliminary simulation experiment indicates that both reaching steady state expression and saturation is delayed in the case of OmpC compared to OmpF. Experimental analysis will help improve the model. The model captures the basic features of the generally accepted view of EnvZ-OmpR signaling and is a reasonable starting point for building sophisticated models and explaining quantitative features of the system

“Something that helped the whole picture”: Experiences of parents offered rapid prenatal exome sequencing in routine clinical care in the English National Health Service

Objectives In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England. This study aimed to explore parent experiences and their information and support needs from the perspective of parents offered pES and of health professionals involved in its delivery. Methods in this qualitative study, semi-structured interviews were conducted with 42 women and 6 male partners and 63 fetal medicine and genetic health professionals. Interviews were transcribed verbatim and analysed using thematic analysis. Results Overall views about pES were positive and parents were grateful to be offered the test. Highlighted benefits of pES included the value of the additional information for pregnancy management and planning for future pregnancies. An anxious wait for results was common, often associated with the need to make decisions near to 24 weeks in pregnancy when there are legal restrictions for late termination. Descriptions of dealing with uncertainty were also common, even once results had been returned. Many parents described pES results informing decision-making around whether or not to terminate pregnancy. Some professionals were concerned that a non-informative result could be overly reassuring and highlighted that careful counselling was needed to ensure parents have a good understanding of what the result means for their pregnancy. Emotional support from professionals was valued, however some parents felt that post-test support was lacking. Conclusion Parents and professionals welcomed the introduction of pES. Results inform parents’ decision making around termination of pregnancy. When there are no diagnostic findings or uncertain findings from pES, personalised counselling that considers scans and other tests is crucial. Directing parents to reliable online sources of information and providing emotional support throughout could improve their experiences of care

Survival of pregnancies with small for gestational age detected before 24 weeks gestation

Abstract Objective Counselling women where severe growth abnormalities are detected early in the pregnancy is often difficult due to a paucity of outcome data of this specific subset of early onset disease. This study therefore aimed to assess the outcome of pregnancies where an estimated fetal weight less than the third centile were detected prior to 24 weeks gestation. Study design A retrospective study in two London teaching hospitals, over an eight year period was performed, analysing all pregnancies with an ultrasound estimated fetal weight less than the third centile prior to 24 weeks gestation. Outcome data: intrauterine death, neonatal death, survival to discharge, gestation at delivery and birthweight were collected. Results Out of 20 pregnancies included in the analysis, six died in utero, two died in the neonatal period and 12 (60%) survived until discharge. Of the livebirths, 67% delivered preterm and 100% percent of livebirths were delivered by Caesarean Section. Conclusion When severe growth abnormalities were detected before 24 weeks, more than half of pregnancies resulted in survival to neonatal discharge. There was an increased incidence of preterm delivery, caesarean section and neonatal unit admission. This information is useful in counselling parents

Foetal congenital heart disease:obstetric management and time to first cardiac intervention in babies delivered at a tertiary centre

AbstractObjectives: The aim of this study was to determine the timing of neonatal cardiac intervention in babies with antenatally diagnosed congenital heart disease and the impact on obstetric management. Methods: A retrospective review of all deliveries between January, 2008 and December, 2009 was conducted in a tertiary centre with foetal and paediatric cardiology, maternal–foetal medicine, and obstetric units. All live births with antenatally detected congenital heart disease were included. Data were collected from foetal, paediatric cardiology, and maternity databases and records. Induction, delivery mode, and timing of the first cardiac intervention in the neonate were studied. Results: 205 deliveries were included. Induction and elective Caesarean section rates were 51.2% (105/205) and 14.1% (29/205), respectively. The vaginal delivery rate was 56% (115/205). There was a non-significant trend towards a higher rate of vaginal delivery after spontaneous labour than after induction (75% versus 66%; p = 0.234). The rate of neonatal cardiac intervention during the initial stay was 59.5% (122/205); it was 18.5% (38/205) within 48 hours and 25.8% (53/205) within 72 hours. The median time to first intervention was 4 days (interquartile range 2–8). Babies with hypoplastic left heart syndrome (median 3, interquartile range 2–6), transposition of the great arteries (median 1, interquartile range 0–4.5), and arrhythmia (median 0.5, interquartile range 0–1) had a significantly earlier time to first intervention compared with those with other conditions (p = 0.001). Conclusion: Vaginal delivery can be achieved in women delivering babies with major congenital heart disease at a tertiary centre. Delivery in or near a tertiary centre is recommended for patients requiring early intervention, of which many can be identified in advance.</jats:p