A possible new approach in the prediction of late gestational hypertension: The role of the fetal aortic intima-media thickness

The aim was to determine the predictive role of combined screening for late-onset gestational hypertension by fetal ultrasound measurements, third trimester uterine arteries (UtAs) Doppler imaging, and maternal history. This prospective study on singleton pregnancies was conducted at the tertiary center of Maternal and Fetal Medicine of the University of Padua during the period between January 2012 and December 2014. Ultrasound examination (fetal biometry, fetal wellbeing, maternal Doppler study, fetal abdominal aorta intima-media thickness [aIMT], and fetal kidney volumes), clinical data (mother age, prepregnancy body mass index [BMI], and parity), and pregnancy outcomes were collected. The P value <0.05 was defined significant considering a 2-sided alternative hypothesis. The distribution normality of variables were assessed using Kolmogorov–Smirnoff test. Data were presented by mean (±standard deviation), median and interquartile range, or percentage and absolute values. We considered data from 1381 ultrasound examinations at 29 to 32 weeks’ gestation, and in 73 cases late gestational hypertension developed after 34 weeks’ gestation. The final multivariate model found that fetal aIMT as well as fetal umbilical artery pulsatility index (PI), maternal age, maternal prepregnacy BMI, parity, and mean PI of maternal UtAs, assessed at ultrasound examination of 29 to 32 weeks’ gestation, were significant and independent predictors for the development of gestational hypertension after 34 weeks’ gestation. The area under the curve of the model was 81.07% (95% confidence interval, 75.83%–86.32%). A nomogram was developed starting from multivariate logistic regression coefficients. Late-gestational hypertension could be independently predicted by fetal aIMT assessment at 29 to 32 weeks’ gestation, ultrasound Doppler waveforms, and maternal clinical parameters

Integrated structural biology approaches for the study of nucleic acid binding proteins

Proteins are the ultimate effectors of biological mechanisms and are involved in every aspect of cellular life. The functional properties of proteins depend on their three-dimensional structure. Indeed, proteins are not rigid entities and internal motions, on a wide range of timescales and distances, are necessary to accomplish a specific function. While certain proteins adopt a compact conformation and undergo small-scale rearrangements, others are more flexible and withstand more dramatic movements. Proteins that exhibit a regulatory role function by binding multiple partners, such as small molecules, DNA, RNA, other proteins. Increased levels of flexibility favour this binding promiscuity. A long-standing goal in molecular biology has been the development of new methods to enable the determination of three-dimensional structures of proteins that exhibit a high level of dynamic complexity. In fact, it is becoming clearer every day that individual structural techniques have several limitations. An integrative structural biology approach provides the tools to decipher the dynamic configuration of proteins by combining information from multiple sources, including biochemical, bioinformatics and biophysical methods. In this thesis, an integrated approach is used to structurally characterize two extremely different nucleic acids binding proteins, the human Staufen1 protein and the archaeal Pyrococcus abyssi MCM complex. In this study, I show that an integrated structural biology approach is not only essential to determine the architecture of small, flexible proteins, which are traditionally difficult targets for conventional approaches, but it is also beneficial to understand the dynamic behavior of large, more compact macromolecular complexes

Programmazione fetale, ritardo di crescita intrauterino e funzionalit\ue0 renale nelle gravidanze gemellari

Background and objective: Intrauterine growth restriction (IUGR) may be associated with significantly higher aortic intima\u2013media thickening (aIMT) values. Twin pregnancy is a natural model of growth retardation that allows to study a different phenotypic expression in the same fetal uterine environment . A reduced renal vasculature after a redistribution of the circle can lead to progressive glomerular injury that is evidenced by the detection of proteinuria and microalbuminuria. NGAL ( Neutrophil Gelatinous - Associated Lipocalin ) is a glycoprotein expressed by neutrophils and various epithelial cells , with multiple functions (prostaglandins , retinoids, arachidonic acid , fatty acids , steroids , iron and metalloproteinases ). Its concentration increases in cases of inflammation , infection, heart disease and kidney disease. It is not known whether an increased thickness of the fetal aortic intima media can be associated in twin pregnancies with glomerulosclerosis and increased concentrations of amniotic microalbuminuria (ACR ratio creatinuria / albuminuria ) and NGAL in the prenatal period. Design, setting, participants, and measurements: Fetal aIMT, the ACR ratio and the concentration of NGAL are valued in the amniotic fluid of 197 twin patients recruited by the Obstetrics Gynecology Department of Woman\u2019s and Child\u2019s Health, University of Padua. The IUGR twin fetuses were classified into two groups: Group A were those fetuses whose estimated fetal weight (EFW) was 2 standard deviations (SD), while Group B those fetuses whose EFW <10th centile but without ultrasound Doppler abnormalities. wins of weight for age (AGA) (Group C) had an EFW between the 10th and the 90th percentile. AGA (appropriate for gestational age, Group C) fetuses were those twins whose EFW was between 10 th and 90th percentile. Results: The median fetal aIMT was significantly different in the three groups (Group A 0.88 mm , Group B 0.7 mm and Group C 0.5 mm) ( p < 0.0001) . In particular, it was higher in Group A than in the AGA Group ( p < 0.0001 ), and in Group B than in Group C (p = 0.003 ). Moreover, aIMT was greater in Group A than in Group B (p <0.05 ) . The ACR ratio appeared different in the three groups : Group A 183.500 mg / g , Group B 6.4720 mg / g and Group C 8.2750 mg / g (p = 0.0002 ). It was significantly greater in Group A than in AGA Group (p 0.03) and than in Group B (p 0.02), respectively . The concentration of NGAL was statistically different in IUGR Group (169.3 ng / mL) than in AGA Group C (158 ng / mL , p < 0.05) , while there were not differences between Group B (128.4 ng / mL) and AGA one (p 0.28 ) . There were no significant differences in respect to the concentration of sodium, potassium and chlorine. It was also found in the IUGR Group A a negative correlation between the concentration of NGAL and renal volumes (p 0.05). Conclusions: Twin fetuses with intrauterine growth restriction and Doppler alterations have an increased aIMT, higher concentration of amniotic microalbuminuria, ACR ratio and an increased levels of NGAL, all possible markers of preclinical intrauterine atherosclerosis and early glomerulosclerosis.Background Il ritardo di crescita intrauterino (IUGR) si pu\uf2 associare ad un aumento dello spessore intima medio aortico (aIMT). La gravidanza gemellare rappresenta un modello naturale di ritardo di crescita che consente di studiare una diversa espressione fenotipica fetale nel medesimo ambiente uterino. Una ridotta vascolarizzazione renale successiva a una ridistribuzione del circolo pu\uf2 portare a un progressivo danno glomerulare che si evidenzia mediante il riscontro di proteinuria e microalbuminuria. NGAL (Neutrophil Gelatinose-Associated Lipocalin) \ue8 una glicoproteina espressa da neutrofili e diverse cellule epiteliali, con molteplici funzioni, immunitarie e di trasporto (prostaglandine, retinoidi, acido arachidonico, acidi grassi, steroidi, ferro e metalloproteinasi). La sua concentrazione aumenta in casi di infiammazione, infezione, patologie cardiache e renali. Non \ue8 noto se un aumentato spessore aortico si possa associare a glomerulosclerosi ed aumento delle concentrazioni amniotiche di microalbuminuria, ACR (rapporto creatinuria/albuminuria) ed NGAL in epoca prenatale nell\u2019ambito delle gravidanze gemellari. Materiali e metodi Si sono valutati aIMT, il rapporto ACR e la concentrazione di NGAL nel liquido amniotico di 197 pazienti gemellari afferite alla Clinica Ostetrica Ginecologica del Dipartimento della Salute della Donna e del Bambino dell\u2019Universit\ue0 di Padova. I gemelli IUGR sono stati classificati in due gruppi: Gruppo A quelli con peso fetale stimato (EFW) 2 deviazioni standard (SD), mentre il Gruppo B quelli con un EFW <10\ub0 centile ma senza anomalie ecografiche flussimetriche. I gemelli di peso appropriato per epoca (AGA) (Gruppo C) presentavano un EFW tra il 10\ub0 e il 90\ub0 centile. Risultati Lo spessore aIMT risultava significativamente differente all\u2019interno dei tre gruppi (Gruppo A 0.88 mm, gruppo B 0.7 mm e Gruppo C 0.5 mm) (p< 0.0001). In particolare, l\u2019aIMT del Gruppo A era maggiore del Gruppo C (p<0.0001); l\u2019aIMT del Gruppo B era maggiore rispetto al Gruppo C (p=0.003), ed era maggiore nel Gruppo A rispetto al Gruppo B (p<0.05). Il rapporto ACR si presentava in tal modo nei tre gruppi: Gruppo A 183,500 mg/g, Gruppo B 6,4720 mg/g e Gruppo C 8,2750 mg/g (p=0.0002). Risultava significativamente maggiore nel gruppo A rispetto al gruppo C (p 0.03) e rispetto al Gruppo B (p 0.02), rispettivamente. La concentrazione del marcatore urinario NGAL risultava statisticamente differente nel Gruppo A (IUGR) (169,3 ng/mL) verso il Gruppo C (AGA) (158 ng/mL, p<0,05), mentre tra il Gruppo B (SGA) (128,4 ng/mL) ed AGA non si riscontravano differenze significative (p 0.28). Non esistevano differenze significative in merito alla concentrazione di sodio, potassio e cloro. Si era rilevata inoltre una correlazione negativa tra concentrazione di NGAL e volumi renali nel gruppo IUGR rispetto al gruppo AGA. Conclusioni Feti gemelli con ritardo di crescita intrauterino ed alterazioni velocimetriche presentano un aumento dello spessore aIMT, della concentrazione amniotica di microalbuminuria, un aumentato rapporto ACR e di NGAL, possibili markers preclinici intrauterini di aterosclerosi e precoce glomerulosclerosi

Utilizzo di test di vitalità cellulare nella determinazione di citotossicità di dispositivi medici

Le analisi oggetto di questo elaborato sono saggi di irritazione cutanea e oculare.ope

Real-time diameter of the fetal aorta from ultrasound

The automatic analysis of ultrasound sequences can substantially improve the efficiency of clinical diagnosis. This article presents an attempt to automate the challenging task of measuring the vascular diameter of the fetal abdominal aorta from ultrasound images. We propose a neural network architecture consisting of three blocks: a convolutional neural network (CNN) for the extraction of imaging features, a convolution gated recurrent unit (C-GRU) for exploiting the temporal redundancy of the signal, and a regularized loss function, called CyclicLoss, to impose our prior knowledge about the periodicity of the observed signal. The solution is investigated with a cohort of 25 ultrasound sequences acquired during the third-trimester pregnancy check, and with 1000 synthetic sequences. In the extraction of features, it is shown that a shallow CNN outperforms two other deep CNNs with both the real and synthetic cohorts, suggesting that echocardiographic features are optimally captured by a reduced number of CNN layers. The proposed architecture, working with the shallow CNN, reaches an accuracy substantially superior to previously reported methods, providing an average reduction of the mean squared error from 0.31 (state-of-the-art) to 0.09 mm2, and a relative error reduction from 8.1 to 5.3%. The mean execution speed of the proposed approach of 289 frames per second makes it suitable for real-time clinical use

Temporal Convolution Networks for Real-Time Abdominal Fetal Aorta Analysis with Ultrasound

The automatic analysis of ultrasound sequences can substantially improve the efficiency of clinical diagnosis. In this work we present our attempt to automate the challenging task of measuring the vascular diameter of the fetal abdominal aorta from ultrasound images. We propose a neural network architecture consisting of three blocks: a convolutional layer for the extraction of imaging features, a Convolution Gated Recurrent Unit (C-GRU) for enforcing the temporal coherence across video frames and exploiting the temporal redundancy of a signal, and a regularized loss function, called \textit{CyclicLoss}, to impose our prior knowledge about the periodicity of the observed signal. We present experimental evidence suggesting that the proposed architecture can reach an accuracy substantially superior to previously proposed methods, providing an average reduction of the mean squared error from $0.31 mm^2$ (state-of-art) to $0.09 mm^2$, and a relative error reduction from $8.1\%$ to $5.3\%$. The mean execution speed of the proposed approach of 289 frames per second makes it suitable for real time clinical use.Comment: 10 pages, 2 figure

Inositol for the prevention of gestational diabetes: a systematic review and meta-analysis of randomized controlled trials

PURPOSE: Inositol (ISL) embraces a family of simple carbohydrates with insulin-sensitizing properties, whose most common isoforms are Myo-inositol (MYO) and D-chiro inositol (DCI). The aim of the present study was to assess the efficacy and safety of ISL supplementation during pregnancy for the prevention of gestational diabetes (GDM). METHODS: We conducted a systematic literature search in electronic databases until October 2017. We included all randomized controlled trials (RCTs) comparing pregnant women with GDM who were randomized to either ISL (i.e., intervention group) or either placebo or no treatment (i.e., control group). The primary outcome was the preventive effect on GDM, defined as the rate of GDM in women without a prior diagnosis of GDM. Pooled results were expressed as odds ratio (OR) with a 95% confidence interval (95% CI). RESULTS: Five RCTs were included (including 965 participants). ISL supplementation was associated with lower rate of GDM (OR 0.49, 95% CI 0.24-1.03, p = 0.01) and lower preterm delivery rate (OR 0.35, 95% CI 0.17-0.74, p = 0.006). No adverse effects were reported. Adjusting for the type of intervention (MYO 2 g twice daily vs MYO 1100 mg plus DCI 27.6 mg daily), a significant effect was found only in patients receiving 2 g MYO twice daily. CONCLUSIONS: ISLs administration during pregnancy appears to be safe and may represent a novel strategy for GDM prevention. In particular, the double administration of MYO 2 g per day may improve the glycemic homeostasis and may reduce GDM rate and preterm delivery rate