Biophysical Markers Research Articles

\u201cScreening for small-for-gestational age neonates at early third trimester in a high-risk population for preeclampsia\u201d

BackgroundStrategies to improve prenatal detection of small-for-gestational age (SGA) neonates are necessary because its association with poorer perinatal outcome. This study evaluated, in pregnancies with first trimester high risk of early preeclampsia, the performance of a third trimester screening for SGA combining biophysical and biochemical markers.MethodsThis is a prospective longitudinal study on 378 singleton pregnancies identified at high risk of early preeclampsia according to a first trimester multiparametric algorithm with the cutoff corresponding to 15% false positive rate. This cohort included 50 cases that delivered SGA neonates with birthweight < 10th centile (13.2%) and 328 cases with normal birthweight (86.8%). At 27–30 weeks’ gestation, maternal weight, blood pressure, estimated fetal weight, mean uterine artery pulsatility index and maternal biochemical markers (placental growth factor and soluble FMS-Like Tyrosine Kinase-1) were assessed. Different predictive models were created to evaluate their performance to predict SGA neonates.ResultsFor a 15% FPR, a model that combines maternal characteristics, estimated fetal weight, mean uterine artery pulsatility index and placental growth factor achieved a detection rate (DR) of 56% with a negative predictive value of 92.2%. The area under receiver operating characteristic curve (AUC) was 0.79 (95% confidence interval (CI), 0.72–0.86). The DR of a model including maternal characteristics, estimated fetal weight and mean uterine artery pulsatility index was 54% (AUC, 0.77 (95% CI, 0.70–0.84)). The DR of a model that includes maternal characteristics and placental growth factor achieved a similar performance (DR 56%, AUC 0.75, 95% CI (0.67–0.83)).ConclusionsThe performance of screening for SGA neonates at early third trimester combining biophysical and biochemical markers in a high-risk population is poor. However, a high negative predictive value could help in reducing maternal anxiety, avoid iatrogenic interventions and propose a specific plan for higher risk patients.

Predictive values of clinical parameters and biophysical and biochemical markers in the first trimester for the detection of small-for-gestational age fetuses.

To evaluate the predictive values of maternal characteristics, biophysical parameters (mean arterial pressure [MAP] and Doppler uterine artery measurements), and biochemical parameters (pregnancy-associated plasma protein A [PAPP-A] and placental growth factor [PlGF]) alone and in association for small-for-gestational age (SGA) fetuses. We performed a retrospective analysis of a prospective observational study that evaluated 615 pregnant women in the first trimester using ultrasonography. For all the women, information regarding clinical and obstetric histories, MAP, and uterine artery mean pulsatility index (UtA-PI), and blood samples for analysis of biochemical markers (PAPP-A and PlGF) were obtained. The patients were grouped according to birth weight as follows: group I (n=571), >10th percentile (control); group II (n=44), <10th percentile; and group III (n=34), <5th percentile. The predictive values of the variables for the detection of SGA fetuses were calculated using a logistic regression model and an analysis of the area under the receiver-operating characteristic curve (AUC). The sensitivity rates of the maternal characteristics, biophysical markers (MAP and UtA-PI), biochemical markers (PAPP-A and PlGF), and the association between them were: 23.3, 32.5, 25, and 30% respectively, at a false-positive (FP) rate of 10%, in group II and 26.5, 26.5, 23.5, and 23.5%, respectively, at a FP rate of 10% in group III. The predictive performances of the combination of maternal characteristics and biophysical and biochemical parameters were unsatisfactory, with a slight improvement in the predictive capacity for SGA fetuses <10th percentile.

Maternal History and First Trimester Biochemical and Biophysical Markers in the Prediction of Spontaneous Preterm Delivery in Singleton Pregnancies

Maternal History and First Trimester Biochemical and Biophysical Markers in the Prediction of Spontaneous Preterm Delivery in Singleton Pregnancies

The modern approaches for the assessment of fetal well-being

Fetal growth restriction is known as an intrauterine pathological condition that is associated with some diseases in a further lifetime. Fetal distress is a satellite of fetal growth restriction. Timely and true diagnosing of fetal distress is still an issue in perinatology. This case study showed that non-invasive fetal electrocardiography could contribute to better diagnosing of fetal distress. The variables of beat-to-beat variations, fetal heart rate variability and fetal autonomic brain age score should be investigated as the biophysical markers of fetal deterioration.

Circulating Nucleic Acids in Maternal Plasma and Serum in Pregnancy Complications: Are They Really Useful in Clinical Practice? A Systematic Review.

A systematic review was carried out to summarize the available evidence to assess whether circulating nucleic acids in maternal plasma and serum (CNAPS) have the potential to serve as extra and independent markers for the prediction and/or progression monitoring of the most common and severe complications of pregnancy, including preeclampsia, intrauterine growth restriction, preterm delivery, morbidly adherent placenta, gestational diabetes, antiphospholipid syndrome, threatened abortion, intrahepatic cholestasis of pregnancy, and hyperemesis gravidarum. A comprehensive literature search of the MEDLINE (PubMed), EMBASE, and ISI Web of Knowledge databases was conducted to identify relevant studies that included amounts of CNAPS in the abovementioned pregnancy complications. Eighty-three studies met the eligibility criteria. The vast majority of studies were conducted on the quantity of total circulating cell free DNA (cfDNA) and cell free fetal DNA (cffDNA), and some were conducted on messenger RNA (mRNA) species. A few studies have instead evaluated the cell free DNA fetal fraction (cfDNAff), but only in a limited number of pregnancy complications. Despite the growing interest and the abundance of the papers available, little information is available for other new CNAPS, including microRNA (miRNA), long noncoding RNA (lncRNA), mitochondrial DNA (mtDNA), and circular RNA. Due to the heterogeneity of the populations enrolled, the scarcity of the studies that adjusted the CNAPS values for possible confounding factors, and the difficulty in interpreting the published data, no conclusion regarding the statistical robustness and clinical relevance of the data can be made at present. If assayed at the third trimester, the CNAPS have, however, shown better performance, and could be used in populations already at risk of developing complications as suggested by the presence of other clinical features. Other CNAPS, including miRNA, are under investigation, especially for the screening of gestational diabetes mellitus, but no data about their clinical utility are available. Circulating DNA (cfDNA, cffDNA, and cfDNAff) and mRNA have not been properly evaluated yet, especially in patients asymptomatic early in pregnancy but who developed complications later, perhaps because of the high cost of these techniques and the availability of other predictors of pregnancy complications (biochemical, biophysical, and ultrasound markers). Therefore, from the analysis of the data, the positive predictive value is not available. As regards the new CNAPS, including miRNA, there are still no sufficient data to understand if they can be promising markers for pregnancy complications monitoring and screening, since CNAPS are statistically weak and expensive. It is reasonable to currently conclude that the use of the CNAPS in clinical practice is not recommended.

Concordance-analysis and evaluation of different diagnostic algorithms used in first trimester screening for late-onset preeclampsia

ABSTRACT Objective Concordance-analysis and evaluation of existing algorithms detecting late-onset preeclampsia during first trimester screening Methods Retrospective cohort study investigating risk algorithms of late-onset preeclampsia during first trimester screening in a German prenatal center. Three previously developed algorithms including anamnestic factors (Apriori) and biophysical markers (BioM) were investigated by using detection rates (DR) with fixed FPR 10% and fixed cutoff >1:100. Furthermore, we set up a concordance-analysis of test results in late-onset preeclampsia cases to examine the effect of influencing factors and to detect potential weaknesses of the algorithms. Therefore, we modeled the probability of discordances as a function of the influencing factors based on a logistic regression, that was fitted using a Bayesian approach. Results 6,113 pregnancies were considered, whereof 700 have been excluded and 5,413 pregnancies were analyzed. 98 (1.8%) patients developed preeclampsia (79 late-onsets, 19 early-onsets). The Apriori-algorithm reaches a DR of 34.2%, by adding BioM (MAP and UtA-PI) the DR improves to 57.0% (FPR of 10%). In concordance-analysis of Apriori algorithm and Apriori+BioM algorithms, influencing factor BMI<25 increases the chance of discordances sigificantly. Additional, in the subgroup of late-onset preeclampsias with BMI<25 the DR is higher in Apriori+BioM algorithms than in Apriori algorithm alone. If both compared algorithms include BioM, influencing factor MAP decreases the chance of discordances significantly. All other tested influencing factors do not have a statistically significant effect on discordances Conclusion Normal-weight patients benefit more from the integration of MAP and UtA-PI compared to overweight/obese patients.

Predicting risk of stillbirth and preterm pregnancies with machine learning

Modelling the risk of abnormal pregnancy-related outcomes such as stillbirth and preterm birth have been proposed in the past. Commonly they utilize maternal demographic and medical history information as predictors, and they are based on conventional statistical modelling techniques. In this study, we utilize state-of-the-art machine learning methods in the task of predicting early stillbirth, late stillbirth and preterm birth pregnancies. The aim of this experimentation is to discover novel risk models that could be utilized in a clinical setting. A CDC data set of almost sixteen million observations was used conduct feature selection, parameter optimization and verification of proposed models. An additional NYC data set was used for external validation. Algorithms such as logistic regression, artificial neural network and gradient boosting decision tree were used to construct individual classifiers. Ensemble learning strategies of these classifiers were also experimented with. The best performing machine learning models achieved 0.76 AUC for early stillbirth, 0.63 for late stillbirth and 0.64 for preterm birth while using a external NYC test data. The repeatable performance of our models demonstrates robustness that is required in this context. Our proposed novel models provide a solid foundation for risk prediction and could be further improved with the addition of biochemical and/or biophysical markers.

Актуальні питання прогнозування і профілактики передчасних пологів

Premature birth is a significant problem in modern medicine. The main aspects of its solution are the prediction and prevention of premature birth. Nowadays, among a large number of biophysical and biochemical markers of preterm birth, ultrasonic cevicometry is the most popular one. It is known that «short cervix syndrome» is not the equivalent of cervical insufficiency. The known strategies of preventive combinations are used in case of an increased risk of preterm birth. Therefore, the issue of developing a differentiated approach to the combined or separate use of progesterone, pessary, or cerclage has not been answered yet. It should be added that in most practical recommendations based on the principles of evidence-based medicine, there are no differences according to the possible pathogenesis of preterm birth. A therapeutic strategy should be set based on the possible use or misuse of any preventive combination, taking into account maternal and fetal contraindications. The combined testing on ultrasound cervicometry and biochemical markers could ameliorate the identification of patients at risk of preterm birth. The fetal fibronectin is known to be the best among all biochemical markers of preterm birth. However, the prognostic value of this test, as well as the phosphorylated transport protein insulin-like growth factor, when used separately, is limited. In pregnant women with a length of the cervix between 1.5 cm and 3 cm, it is recommended to use the analysis for placental alpha-microglobulin-1. The administration of corticosteroids should only be performed when the risk of preterm delivery is confirmed by decreased cervical length and a positive test for placental alpha-microglobulin-1 (there is a high risk of preterm delivery within 7 days). The cerclage is indicated in patients with cervical insufficiency before 16 weeks of gestation. In the presence of a «short cervix» and the lack of anamnestic data, the strategy should be individualized. The efficacy of cerclage or pessary application has not been proven. It is necessary to start with vaginal progesterone administration. In the process of the patient observation (cervicometry in dynamics) will allow you to find out an effective method: cerclage or pessary and vaginal progesterone. In the case of progredient cervical effacement in the second trimester, it is advisable to perform an urgent cerclage. In the case of incompetent cervical stitch, the additional application of a pessary is possible. In women with multiple pregnancies, there is no evidence of elective cerclage or pessary efficacy. However, it is possible to use heroic cerclage, pessary in combination with vaginal progesterone or vaginal progesterone monotherapy. Key words: preterm delivery, prediction, prevention.

Acoustic Cell Separation Based on Density and Mechanical Properties.

Density and mechanical properties (e.g., compressibility or bulk modulus) are important cellular biophysical markers. As such, developing a method to separate cells directly based on these properties can benefit various applications including biological research, diagnosis, prognosis, and therapeutics. As a potential solution, surface acoustic wave (SAW)-based cell separation has demonstrated advantages in terms of biocompatibility and compact device size. However, most SAW-reliant cell separations are achieved using an entangled effect of density, various mechanical properties, and size. In this work, we demonstrate SAW-based separation of cells/particles based on their density and compressibility, irrespective of their sizes, by manipulating the acoustic properties of the fluidic medium. Using our platform, SAW-based separation is achieved by varying the dimensions of the microfluidic channels, the wavelengths of acoustic signals, and the properties of the fluid media. Our method was applied to separate paraformaldehyde-treated and fresh Hela cells based on differences in mechanical properties; a recovery rate of 85% for fixed cells was achieved. It was also applied to separate red blood cells (RBCs) and white blood cells (WBCs) which have different densities. A recovery rate of 80.5% for WBCs was achieved.

Association of Body Mass Index with Activin-A and Inhibin-A in Gestational Diabetic Women

Objective: The objective of the study was to assess the association of body mass index (BMI) with Activin-A and Inhibin-A (biomarkers) irrespective to age in women with gestational diabetes mellitus (GDM).Methods: This study was a case-controlled study, in which sixty (60) diagnosed cases of gestational diabetic women with and without obesity and thirty (30) pregnant women without diabetes or any other complications were included in the study after taking informed written consent. The duration of the study was from January 2018 to June 2018. The enrolled participants were ninety (90) who were fulfilling the criteria in the duration of the study. Participants were placed into three groups A, B and C. In group A, thirty (30) pregnant females without complications, in group B thirty (30) non-obese pregnant women with gestationaldiabetes and in group C thirty (30) obese pregnant females with gestational diabetes mellitus (GDM). The biophysical parameters including weight, height and blood pressure were measured through standard protocols. Blood tests for biomarkers Activin-A and Inhibin-A levels were measured through Human Activin-A enzyme-linked immunosorbent assay(ELISA) kit and Human Inhibin-A ELISA kit respectively.Results: The results of the study revealed that the biophysical markers Actin-A and Inhibin-A had associations with gestational diabetes, the significant (p-value&lt;0.05) association was observed between Activin-A and body mass index but Inhibin-A had an insignificant association with it. However, the levels of bothbiomarkers (Activin-A and Inhibin-A) were found to be raised in both obese and non-obese gestational diabetic women when compared with normal pregnant women. The secondary outcome of the study is, there is significant (p-value&gt;0.05) relation between age and body mass index of obese GDM.Conclusion: The study concluded that the level of Activin-A was raised significantly (p-value&gt;0.05) in obese and non-obese gestational diabetic women as compared to normal pregnant women and non-significant increases in inhibin-A were observed in obese and non-obese gestational diabetic women as compared to normal pregnant women. A secondary outcome was, that there is significant (p-value&gt;0.05) association found between body mass index and age of the pregnant women.

Aspirin for prevention of preeclampsia and fetal growth restriction.

For the past decades, growing attention has been given to aspirin use during pregnancy. It favors placentation by its proangiogenic, antithrombotic, and anti-inflammatory effects. Therefore, low doses of aspirin are prescribed in the prevention of placenta-mediated complications, mainly preeclampsia and fetal growth restriction. However, questions regarding its clinical application are still debated. Aspirin is effective in preventing preeclampsia in a high-risk population. Most guidelines recommend that risk stratification should rely on medical history. Nevertheless, screening performances dramatically improve if biochemical and biophysical markers are included. Concerning the appropriate timing and dose, latest studies suggest aspirin should be started before 16 weeks of pregnancy and at a daily dose of 100 mg or more. Further studies are needed to improve the identification of patients likely to benefit from prophylactic aspirin. Besides, the role of aspirin in the prevention of fetal growth restriction is still questioned.

A new model for screening for early-onset preeclampsia

Early identification of women with an increased risk for preeclampsia is of utmost importance to minimize adverse perinatal events. Models developed until now (mainly multiparametric algorithms) are thought to be overfitted to the derivation population, which may affect their reliability when applied to other populations. Options allowing adaptation to a variety of populations are needed. The objective of the study was to assess the performance of a first-trimester multivariate Gaussian distribution model including maternal characteristics and biophysical/biochemical parameters for screening of early-onset preeclampsia (delivery <34 weeks of gestation) in a routine care low-risk setting. Early-onset preeclampsia screening was undertaken in a prospective cohort of singleton pregnancies undergoing routine first-trimester screening (8 weeks 0/7 days to 13 weeks 6/7 days of gestation), mainly using a 2-step scheme, at 2 hospitals from March 2014 to September 2017. A multivariate Gaussian distribution model including maternal characteristics (a priori risk), serum pregnancy-associated plasma protein-A and placental growth factor assessed at 8 weeks 0/7 days to 13 weeks 6/7 days and mean arterial pressure and uterine artery pulsatility index measured at 11.0-13.6 weeks was used. A total of 7908 pregnancies underwent examination, of which 6893 were included in the analysis. Incidence of global preeclampsia was 2.3% (n= 161), while of early-onset preeclampsia was 0.2% (n= 17). The combination of maternal characteristics, biophysical parameters, and placental growth factor showed the best detection rate, which was 59% for a 5% false-positive rate and 94% for a 10% false-positive rate (area under the curve, 0.96, 95% confidence interval, 0.94-0.98). The addition of placental growth factor to biophysical markers significantly improved the detection rate from 59% to 94%. The multivariate Gaussian distribution model including maternal factors, early placental growth factor determination (at 8 weeks 0/7 days to 13 weeks 6/7 days), and biophysical variables (mean arterial pressure and uterine artery pulsatility index) at 11 weeks 0/7 days to 13 weeks 6/7 days is a feasible tool for early-onset preeclampsia screening in the routine care setting. Performance of this model should be compared with predicting models based on regression analysis.

Particular Aspects of Inflammatory Biochemical Markers in Preeclamsia

Preeclampsia is a rapidly progressive disorder characterized by high blood pressure and usually the presence of proteinuria. It occurs after 20 weeks of gestation and up to six weeks postpartum. It requires proper prenatal care which is essential to diagnose and manage this disease. Our study show the correlations between the statistical data and the epidemiology issues, in order to outline a pregnancy profile with preeclampsia. We considered clinical and biophysical markers of preeclampsia in a 138 patient group. Our results encourage us to deepen this topic by enlarging the patient group number and to perform cohort multicentric evaluations. Keywords: preeclampsia biophysical markers, clinical markers, statistic evaluation

Development of label-free biophysical markers in osteogenic maturation

The spatial and temporal changes of morphological and mechanical properties of living cells reflect complex functionally-associated processes. Monitoring these modifications could provide a direct information on the cellular functional state. Here we present an integrated biophysical approach to the quantification of the morphological and mechanical phenotype of single cells along a maturation pathway. Specifically, quantitative phase microscopy and single cell biomechanical testing were applied to the characterization of the maturation of human foetal osteoblasts, demonstrating the ability to identify effective label-free biomarkers along this fundamental biological process.

Soft Wearable Systems for Colorimetric and Electrochemical Analysis of Biofluids

AbstractWearable monitoring systems provide valuable insights about the state of wellness, performance, and progression of diseases. Although conventional wearable systems have been effective in measuring a few key biophysical markers, they offer limited insights into biochemical activity and are otherwise cumbersome in ambulatory modes of use, relying on wired connections, mechanical straps, and bulky electronics. Recent advances in skin‐interfaced microfluidics, stretchable/flexible electronics, and mechanics have created new wearable systems with capabilities in real‐time, noninvasive analysis of sweat biochemistry in combination with biophysical metrics. Here, the latest technologies in multifunctional sweat sensing systems are presented with a focus on novel microfluidic designs, fully‐integrated wireless electrochemical sensors, and hybrid biochemical/biophysical sensing capabilities, creating real‐time physiological insights.

Establishing a Differential Marker Profile for Pregnancy Complications Near Delivery

Objective: The aim of this work was to define a differential marker profile for pregnancy complications near delivery. Methods: We enrolled pregnant women who were referred to the outpatient pregnancy clinic of the University Medical Center, Ljubljana, Slovenia, due to symptoms of pregnancy complications and women with a history of pregnancy complications attending the high-risk hospital clinic for close surveillance. They were evaluated for prior risk and were tested for biophysical and biochemical markers at the time of enrolment. Biochemical markers included the pro- and anti-angiogenic markers, along with additional previously reported markers of potential value, all tested by various formats of immuno-diagnostics. Biophysical markers included blood pressure, sonographic markers, and EndoPAT. Statistical differences were determined with Kruskal-Wallis and Mann-Whitney tests for continuous parameters, and Pearson χ² for categorical values. p < 0.05 was considered significant. Results: The cohort included 125 pregnant patients, 31 developed preeclampsia (PE) alone (13 were <34 weeks’ gestation), 16 had intrauterine growth restriction (IUGR) alone (12 were <34 weeks), 42 had both IUGR and PE (22 were <34 weeks), and 15 had an iatrogenic preterm delivery (PTD; 6 were <34 weeks). Twenty-one were unaffected and delivered a healthy baby at term. Mean arterial blood pressure and proteinuria were significantly higher in PE and PE+IUGR but not in pure IUGR or PTD. In PE, IUGR, and PE+IUGR, the levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) were significantly higher, while placental growth factor (PlGF) was very low compared to unaffected controls and PTD. PE, IUGR, and PE+IUGR also had a high anti-angiogenic ratio (sFlt-1/PlGF) and a low proangiogenic ratio of PlGF/(sFlt-1+Eng). Levels of inhibin A were significantly higher in pure PE across subgroups but had many extreme values, which made it a poor differentiator. Higher uterine artery Doppler pulsatility indexes were detected in PE, IUGR, and PE+IUGR, with similar resistance indexes and peaks of systolic velocity. A significantly different marker level between PE and IUGR was found using arterial stiffness that was 10 times higher in PE; concurrently with an increase of the reactive hyperemia index, both were accompanied by a slight increase in placental protein 13. Higher tumor necrosis factor alpha (TNFα) differentially identified iatrogenic very early PTD (<34 weeks). Conclusion: Arterial stiffness can serve as a major marker to differentiate PE (with/without IUGR) from pure IUGR near delivery. TNFα can differentiate iatrogenic early PTD from other complications of pregnancy and term IUGR.

Performance of Fetal Medicine Foundation Software for Pre-Eclampsia Prediction Upon Marker Customization: Cross-Sectional Study.

BackgroundFMF2012 is an algorithm developed by the Fetal Medicine Foundation (FMF) to predict pre-eclampsia on the basis of maternal characteristics combined with biophysical and biochemical markers. Afro-Caribbean ethnicity is the second risk factor, in magnitude, found in populations tested by FMF, which was not confirmed in a Brazilian setting.ObjectiveThis study aimed to analyze the performance of pre-eclampsia prediction software by customization of maternal ethnicity.MethodsThis was a cross-sectional observational study, with secondary evaluation of data from FMF first trimester screening tests of singleton pregnancies. Risk scores were calculated from maternal characteristics and biophysical markers, and they were presented as the risk for early pre-eclampsia (PE34) and preterm pre-eclampsia (PE37). The following steps were followed: (1) identification of women characterized as black ethnicity; (2) calculation of early and preterm pre-eclampsia risk, reclassifying them as white, which generated a new score; (3) comparison of the proportions of women categorized as high risk between the original and new scores; (4) construction of the receiver operator characteristic curve; (5) calculation of the area under the curve, sensitivity, and false positive rate; and (6) comparison of the area under the curve, sensitivity, and false positive rate of the original with the new risk by chi-square test.ResultsA total of 1531 cases were included in the final sample, with 219 out of 1531 cases (14.30; 95% CI 12.5-16.0) and 182 out of 1531 cases (11.88%; 95% CI 10.3-13.5) classified as high risk for pre-eclampsia development, originally and after recalculating the new risk, respectively. The comparison of FMF2012 predictive model performance between the originally estimated risks and the estimated new risks showed that the difference was not significant for sensitivity and area under the curve, but it was significant for false positive rate.ConclusionsWe conclude that black ethnicity classification of Brazilian pregnant women by the FMF2012 algorithm increases the false positive rate. Suppressing ethnicity effect did not improve the test sensitivity. By modifying demographic characteristics, it is possible to improve some performance aspects of clinical prediction tests.

Lipid Thermal Fingerprints of Long-term Stored Seeds of Brassicaceae

Thermal fingerprints for seeds of 20 crop wild relatives of Brassicaceae stored for 8 to 44 years at the Plant Germplasm Bank—Universidad Politécnica de Madrid and the Royal Botanic Gardens, Kew’s Millennium Seed Bank—were generated using differential scanning calorimetry (DSC) and analyzed in relation to storage stability. Relatively poor storing oily seeds at −20 °C tended to have lipids with crystallization and melting transitions spread over a wide temperature range (c. 40 °C) that spanned the storage temperature, plus a melting end temperature of around 15 °C. We postulated that in dry storage, the variable longevity in Brassicaceae seeds could be associated with the presence of a metastable lipid phase at the temperature at which they are being stored. Consistent with that, when high-quality seed samples of various species were assessed after banking at −5 to −10 °C for c. 40 years, melting end temperatures were observed to be much lower (c. 0 to −30 °C) and multiple lipid phases did not occur at the storage temperature. We conclude that multiple features of the seed lipid thermal fingerprint could be used as biophysical markers to predict potential poor performance of oily seeds during long-term, decadal storage.

237 Skin barrier integrity is enhanced after topical application of emulsions with an acidic pH

The pH of the stratum corneum is slightly acidic (mean 4.9) and tightly regulated. This is important for antimicrobial defense and the formation of the physical barrier. The acidic pH inhibits the growth of pathogenic Staphylococcus aureus and enables optimal activity of enzymes for lipid synthesis, epidermal differentiation and desquamation. Here we asked whether topical application of an oil-in-water emulsions adjusted to pH 4 or pH 5.8 and the untreated control influence biophysical markers and mechanical stability of the skin barrier, Stratum corneum morphology and inflammation. Twenty-four healthy volunteers aged 18 to 75 years were treated in a randomized way on the lower arms for 28 days; pH, TEWL, SC hydration, mechanical stability, corneocyte size and inflammation were recorded. After 28 days, skin surface pH was significantly more reduced by the pH 4 compared to the pH 5.8 emulsion. TEWL as a marker of skin barrier function was slightly reduced by both emulsions. SC hydration was significantly increased to the same level by both emulsions. The number of D-Squame® tape-strips to disrupt the skin barrier to a threefold increase in TEWL as a marker for skin integrity was significantly increased by both emulsions compared to untreated control, but slightly more by the pH 4 emulsion. Inflammation after tape-stripping as determined by clinical grading of erythema was considerable reduced by the pH 4 emulsion, and IL-1α protein expression was significantly reduced by both emulsions, but the reduction was higher with the pH 4 preparation. The size of corneocytes attached to the tape-strips as a marker for epidermal differentiation and desquamation was significantly increased after treatment with the pH 4 compared to the pH 5.8 emulsion and the control. In summary, treatment with a pH 4 emulsion positively influenced SC pH, TEWL, SC hydration, epidermal differentiation/desquamation resulting in increased mechanically stability and reduced inflammation against tape-stripping induced irritation.

Assessment of the Fetal Myocardial Performance Index in Well-Controlled Gestational Diabetics and to Determine Whether It Is Predictive of Adverse Perinatal Outcome.

This study was aimed at determining if the myocardial performance index (MPI) is altered in well-controlled gestational diabetics and if so whether it is predictive of adverse perinatal outcome. In a prospective cross-sectional study, 54 consecutive women with well-controlled gestational diabetes controlled on insulin or metformin in the third trimester were recruited and matched with 54 women with normal pregnancies (control group). Using Doppler echocardiography, the MPI was calculated. Sonographic biophysical and placental resistance Doppler markers in both groups were also determined. An abnormal outcome was defined as any of the following: stillbirth; neonatal death; neonatal intensive care admissions; tachypnea with pulmonary edema; neonatal cord pH < 7.15; 5-min Apgar score < 7, polycythemia; and nucleated red blood cells > 10/100 white blood cell counts, hypoglycemia. The MPI was significantly higher in the diabetic group compared to controls (p < 0.0001). Rate of adverse outcome was 22% in the diabetic group. The diabetic group with adverse outcomes had significantly elevated MPI values compared to the diabetic group with normal outcomes. There were 26 diabetics controlled on metformin and 28 controlled on insulin. The adverse outcome rate was slightly higher in the IDDM group compared to the non-insulin-dependent group but was not statistically significant. The main adverse outcomes were low Apgars (18%), hypoglycemia (22%), polycythemia (13%) and low pH in 7%. All control births had normal outcomes. MPI served as an independent predictor of adverse outcome. The MPI z-score had a good diagnostic accuracy as evidenced by the area under the ROC curve of 0.83. An MPI z-score exceeding 4.55 conferred a 90% sensitivity and 74% specificity, with 77% of outcomes correctly classified with a likelihood ratio of 3.5. The MPI is impaired in fetuses in well-controlled gestational diabetes, with fetuses with an adverse outcome having significantly higher MPI values compared to the fetuses with normal outcome in the diabetic group. MPI has the potential to improve fetal surveillance in gestational diabetes.