Assessment of the Sensitizing Potential of Processed Peanut Proteins in Brown Norway Rats: Roasting Does Not Enhance Allergenicity

Background: IgE-binding of process-modified foods or proteins is the most common method for examination of how food processing affects allergenicity of food allergens. How processing affects sensitization capacity is generally studied by administration of purified food proteins or food extracts and not allergens present in their natural food matrix. [br/] Objectives: The aim was to investigate if thermal processing increases sensitization potential of whole peanuts via the oral route. In parallel, the effect of heating on sensitization potential of the major peanut allergen Ara h 1 was assessed via the intraperitoneal route. Methods: Sensitization potential of processed peanut products and Ara h 1 was examined in Brown Norway (BN) rats by oral administration of blanched or oil-roasted peanuts or peanut butter or by intraperitoneal immunization of purified native (N-), heated (H-) or heat glycated (G-) Ara h 1. Levels of specific IgG and IgE were determined by ELISA and IgE functionality was examined by rat basophilic leukemia (RBL) cell assay. [br/] Results: In rats dosed orally, roasted peanuts induced significant higher levels of specific IgE to NAra h 1 and 2 than blanched peanuts or peanut butter but with the lowest level of RBL degranulation. However, extract from roasted peanuts was found to be a superior elicitor of RBL degranulation. Process-modified Ara h 1 had similar sensitizing capacity as NAra h 1 but specific IgE reacted more readily with process-modified Ara h 1 than with native. [br/] Conclusions: Peanut products induce functional specific IgE when dosed orally to BN rats. Roasted peanuts do not have a higher sensitizing capacity than blanched peanuts. In spite of this, extract from roasted peanuts is a superior elicitor of RBL cell degranulation irrespectively of the peanut product used for sensitization. The results also suggest that new epitopes are formed or disclosed by heating Ara h 1 without glucose

Decision-to-delivery interval of emergency cesarean section in Uganda: a retrospective cohort study

Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; doi: http://dx.doi.org/10.13039/501100002927Funder: Isaac Newton Trust[12.21(a)]/Wellcome Trust ISSF [105602/Z/14/Z]/ University of Cambridge Joint Research GrantAbstract: Background: In many low and medium human development index countries, the rate of maternal and neonatal morbidity and mortality is high. One factor which may influence this is the decision-to-delivery interval of emergency cesarean section. We aimed to investigate the maternal risk factors, indications and decision-to-delivery interval of emergency cesarean section in a large, under-resourced obstetric setting in Uganda. Methods: Records of 344 singleton pregnancies delivered at ≥24 weeks throughout June 2017 at Mulago National Referral Hospital were analysed using Cox proportional hazards models and multivariate logistic regression models. Results: An emergency cesarean section was performed every 104 min and the median decision-to-delivery interval was 5.5 h. Longer interval was associated with preeclampsia and premature rupture of membranes/oligohydramnios. Fetal distress was associated with a shorter interval (p 0.05). Mothers waited on average 6 h longer for deliveries between 00:00–08:00 compared to those between 12:00–20:00 (p < 0.01). The risk of perinatal death was higher in neonates where the decision to deliver was made between 20:00–02:00 compared to 08:00–12:00 (p < 0.01). Conclusion: In this setting, the average decision-to-delivery interval is longer than targets adopted in high development index countries. Decision-to-delivery interval varies diurnally, with decisions and deliveries made at night carrying a higher risk of adverse perinatal outcomes. This suggests a need for targeting the improvement of service provision overnight

A Novel TGFβ Modulator that Uncouples R-Smad/I-Smad-Mediated Negative Feedback from R-Smad/Ligand-Driven Positive Feedback

As some of the most widely utilised intercellular signalling molecules, transforming growth factor β (TGFβ) superfamily members play critical roles in normal development and become disrupted in human disease. Establishing appropriate levels of TGFβ signalling involves positive and negative feedback, which are coupled and driven by the same signal transduction components (R-Smad transcription factor complexes), but whether and how the regulation of the two can be distinguished are unknown. Genome-wide comparison of published ChIP-seq datasets suggests that LIM dom

Maternal left ventricular function and adverse neonatal outcomes in women with cardiac disease.

PURPOSE: To evaluate the relationship between maternal left ventricular systolic function, utero-placental circulation, and risk of adverse neonatal outcomes in women with cardiac disease. METHODS: 119 women managed in the pregnancy heart clinic (2019-2021) were identified. Women were classified by their primary cardiac condition. Adverse neonatal outcomes were: low birth weight ( 20 weeks' gestation). Parameters of left ventricular systolic function (global longitudinal strain, radial strain, ejection fraction, average S', and cardiac output) were calculated and pulsatility index was recorded from last growth scan. RESULTS: Adverse neonatal outcomes occurred in 28 neonates (24%); most frequently in valvular heart disease (n = 8) and cardiomyopathy (n = 7). Small-for-gestational-age neonates were most common in women with cardiomyopathy (p = 0.016). Early pregnancy average S' (p = 0.03), late pregnancy average S' (p = 0.02), and late pregnancy cardiac output (p = 0.008) were significantly lower in women with adverse neonatal outcomes than in those with healthy neonates. There was a significant association between neonatal birth-weight centile and global longitudinal strain (p = 0.04) and cardiac output (p = 0.0002) in late pregnancy. Pulsatility index was highest in women with cardiomyopathy (p = 0.007), and correlated with average S' (p < 0.0001) and global longitudinal strain (p = 0.03) in late pregnancy. CONCLUSION: Women with cardiac disease may not tolerate cardiovascular adaptations required during pregnancy to support fetal growth. Adverse neonatal outcomes were associated with reduced left ventricular systolic function and higher pulsatility index. The association between impaired systolic function and reduced fetal growth is supported by insufficient utero-placental circulation.CEA is supported by a Medical Research Council New Investigator Grant (MR/T016701/1) and the NIHR Cambridge Biomedical Research Centr

Maternal left ventricular function and adverse neonatal outcomes in women with cardiac disease

Purpose: To evaluate the relationship between maternal left ventricular systolic function, utero-placental circulation, and risk of adverse neonatal outcomes in women with cardiac disease. Methods: 119 women managed in the pregnancy heart clinic (2019–2021) were identified. Women were classified by their primary cardiac condition. Adverse neonatal outcomes were: low birth weight ( 20 weeks’ gestation). Parameters of left ventricular systolic function (global longitudinal strain, radial strain, ejection fraction, average S’, and cardiac output) were calculated and pulsatility index was recorded from last growth scan. Results: Adverse neonatal outcomes occurred in 28 neonates (24%); most frequently in valvular heart disease (n = 8) and cardiomyopathy (n = 7). Small-for-gestational-age neonates were most common in women with cardiomyopathy (p = 0.016). Early pregnancy average S’ (p = 0.03), late pregnancy average S’ (p = 0.02), and late pregnancy cardiac output (p = 0.008) were significantly lower in women with adverse neonatal outcomes than in those with healthy neonates. There was a significant association between neonatal birth-weight centile and global longitudinal strain (p = 0.04) and cardiac output (p = 0.0002) in late pregnancy. Pulsatility index was highest in women with cardiomyopathy (p = 0.007), and correlated with average S’ (p < 0.0001) and global longitudinal strain (p = 0.03) in late pregnancy. Conclusion: Women with cardiac disease may not tolerate cardiovascular adaptations required during pregnancy to support fetal growth. Adverse neonatal outcomes were associated with reduced left ventricular systolic function and higher pulsatility index. The association between impaired systolic function and reduced fetal growth is supported by insufficient utero-placental circulation

Temporal variations in maternal treatment requirements and early neonatal outcomes in patients with gestational diabetes

Funder: NIHR Cambridge Biomedical Research CentreAbstract: Aims: There is seasonal variation in the incidence of gestational diabetes (GDM) and delivery outcomes of affected patients. We assessed whether there was also evidence of temporal variation in maternal treatment requirements and early neonatal outcomes. Methods: We performed a retrospective analysis of women diagnosed with GDM (75 g oral glucose tolerance test, 0 h ≥ 5.1; 1 h ≥ 10.0; 2 h ≥ 8.5 mmol/L) in a UK tertiary obstetric centre (2015–2019) with a singleton infant. Data regarding demographic characteristics, total insulin requirements and neonatal outcomes were extracted from contemporaneous electronic medical records. Linear/logistic regression models using month of the year as a predictor of outcomes were used to assess annual variation. Results: In all, 791 women (50.6% receiving pharmacological treatment) and 790 neonates were included. The likelihood of requiring insulin treatment was highest in November (p < 0.05). The average total daily insulin dose was higher at peak (January) compared to average by 19 units/day (p < 0.05). There was no temporal variation in neonatal intensive care admission, or neonatal capillary blood glucose. However, rates of neonatal hypoglycaemia (defined as <2.6 mmol/L) were highest in December (40% above average; p < 0.05). Conclusions: Women with GDM diagnosed in winter are more likely to require insulin treatment and to require higher insulin doses. Neonates born to winter‐diagnosed mothers had a corresponding increased risk of neonatal hypoglycaemia. Maternal treatment requirements and neonatal outcomes of GDM vary significantly throughout the year, even in a relatively temperate climate

Composition of peanut extracts determined by densitometric analysis of lanes from SDS PAGE gel.

<p>*PE: peanut extract, PB: peanut butter.</p

Allergen-specific degranulation of RBL cells sensitized with sera from rats dosed orally with peanut products.

<p>RBL cells were passively sensitized with serum pools (undiluted) from groups of BN rats dosed orally by gavage for 42 days with with blanched peanuts (<b>A</b>), roasted peanuts (<b>B</b>) and peanut butter (<b>C</b>) corresponding to approximately 2 mg Ara h 1 per rat per day. Peanut-water mixtures were prepared using blanched or roasted peanuts or peanut butter. For degranulation, cells were stimulated with dilutions of extracts of peanut-water mixtures (blanched PE, roasted PE or PB extract). Data are presented as percentage <i>β</i>–hexosaminidase release of total biological release induced by stimulation with 125 ng/well of anti-rat IgE. Symbols represent mean values ± SD for each serum pool. It was not possible to detect any degranulation of RBL cells when sensitized cells were stimulated with native or processed Ara h 1. The experiment was performed twice. Data were analyzed by two-way ANOVA. Statistical difference between extracts to induce allergen-specific degranulation is only indicated for least significant lines; ***: <i>p</i> ≤ 0.001. RBL: rat basophilic leukemia, PE: peanut extract, PB: peanut butter.</p