Evidence for uteroplacental malperfusion in fetuses with major congenital heart defects.

AIMS: Fetuses affected by congenital heart defects (CHD) are considered to be at increased risk of fetal growth restriction and intrauterine demise. Whether these risks are a direct consequence of fetal CHD or a result of associated uteroplacental dysfunction is not evident from the data of recent studies. The aim of this study was to investigate the prevalence of uteroplacental dysfunction reflected by abnormal uterine artery Doppler indices and reduced fetal growth in CHD pregnancies. METHODS: This is a retrospective case-control study including singleton pregnancies referred for detailed fetal cardiac assessment subsequently diagnosed with or without CHD. Mid-trimester uterine artery Doppler assessment at 20-24 weeks as well as third trimester fetal biometry and arterial Doppler pulsatility indices (PI) were performed. All fetal biometry were converted into centiles and Doppler values to multiples of median (MoM) to adjust for physiological changes with gestation. RESULTS: The study included 811 pregnancies including 153 cases where the fetus was diagnosed with CHD. Mid-pregnancy uterine artery PI was significantly higher in women with fetal CHD compared to controls (0.90MoM vs 0.83MoM; p = 0.006). In the third trimester, median centiles for fetal head circumference (45.4 vs 57.07; p<0.001), abdominal circumference (51.17 vs 55.71; p = 0.014), estimated fetal weight (33.6 vs 56.7; p<0.001) and cerebroplacental ratio (CPR: 0.84MoM vs 0.95MoM; p<0.001) were significantly lower in fetuses with CHD compared to controls. The percentage of small for gestational age births <10th centile (24.0% vs 10.7%; <0.001) and low CPR <0.6MoM (11.7% vs 2.5%; p<0.001) were significantly higher in the fetal CHD cohort. CONCLUSIONS: Mid-pregnancy uterine artery resistance is increased and subsequent fetal biometry reduced in pregnancies with CHD fetuses. These findings suggest that fetal CHD are associated with uteroplacental dysfunction, secondary to impaired maternal uteroplacental perfusion resulting in relative fetal hypoxaemia and reduced fetal growth

Monitoring of Plant Species and Communities on Coastal Cliffs: Is the Use of Unmanned Aerial Vehicles Suitable?

Cliffs are reservoirs of biodiversity; therefore, many plant species and communities of inland and coastal cliffs are protected by Council Directive 92/43/EEC (European Economic Community), and their monitoring is mandatory in European Union countries. Surveying plants on coastal cliff by traditional methods is challenging and alternatives are needed. We tested the use of a small Unmanned Aerial Vehicle (UAV) as an alternative survey tool, gathering aerial images of cliffs at Palinuro Cape (Southern Italy). Four photo-interpreters analysed independently the derived orthomosaic and plotted data needed for the monitoring activity. Data showed to be not affected by photo-interpreters and reliable for the prescribed monitoring in the European Union (EU). Using the GIS analysis tools, we were able to: (a) recognise and map the plant species, (b) derive and measure the area of distribution on the cliff of habitat and species, and (c) count Eokochia saxicola individuals and gather quantitative data on their projected area. Quality of the images represented the main constraint, but incoming technological improvements of sensors and UAVs may overcome this problem. Overall results support the use of UAVs as an affordable and fast survey technique that can rapidly increase the number of studies on cliff habitats and improve ecological knowledge on their plant species and communitie

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

Role of fetal MRI in the evaluation of isolated and non-isolated corpus callosum dysgenesis: results of a cross-sectional study

PURPOSE: The aims of this study were to characterize isolated and non-isolated forms of corpus callosum dysgenesis (CCD) at fetal magnetic resonance imaging (MRI) and to identify early predictors of associated anomalies. METHODS: We retrospectively analyzed 104 fetuses with CCD undergoing MRI between 2006 and 2016. Corpus callosum, cavum septi pellucidi, biometry, presence of ventriculomegaly, gyration anomalies, cranio-encephalic abnormalities and body malformations were evaluated. Results of genetic tests were also recorded. RESULTS: At MRI, isolated CCD was 26.9%, the rest being associated to other abnormalities. In the isolated group, median gestational age at MRI was lower in complete agenesis than in hypoplasia (22 vs 28 weeks). In the group with additional findings, cortical dysplasia was the most frequently associated feature (P = 0.008), with a more frequent occurrence in complete agenesis (70%) versus other forms; mesial frontal lobes were more often involved than other cortical regions (P = 0.006), with polymicrogyria as the most frequent cortical malformation (40%). Multivariate analysis confirmed the association between complete agenesis and cortical dysplasia (odds ratio = 7.29, 95% confidence interval 1.51-35.21). CONCLUSIONS: CCD is often complicated by other intra-cranial and extra-cranial findings (cortical dysplasias as the most prevalent) that significantly affect the postnatal prognosis. The present study showed CCD with associated anomalies as more frequent than isolated (73.1%). In isolated forms, severe ventriculomegaly was a reliable herald of future appearance of associated features

Reversal of aging-induced increases in aortic stiffness by targeting cytoskeletal protein-protein interfaces

Background: The proximal aorta normally functions as a critical shock absorber that protects small downstream vessels from damage by pressure and flow pulsatility generated by the heart during systole. This shock absorber function is impaired with age because of aortic stiffening. Methods and Results: We examined the contribution of common genetic variation to aortic stiffness in humans by interrogating results from the AortaGen Consortium genome-wide association study of carotid-femoral pulse wave velocity. Common genetic variation in the N-WASP (WASL) locus is associated with carotid-femoral pulse wave velocity (rs600420, P=0.0051). Thus, we tested the hypothesis that decoy proteins designed to disrupt the interaction of cytoskeletal proteins such as N-WASP with its binding partners in the vascular smooth muscle cytoskeleton could decrease ex vivo stiffness of aortas from a mouse model of aging. A synthetic decoy peptide construct of N-WASP significantly reduced activated stiffness in ex vivo aortas of aged mice. Two other cytoskeletal constructs targeted to VASP and talin-vinculin interfaces similarly decreased aging-induced ex vivo active stiffness by on-target specific actions. Furthermore, packaging these decoy peptides into microbubbles enables the peptides to be ultrasound-targeted to the wall of the proximal aorta to attenuate ex vivo active stiffness. Conclusions: We conclude that decoy peptides targeted to vascular smooth muscle cytoskeletal protein-protein interfaces and microbubble packaged can decrease aortic stiffness ex vivo. Our results provide proof of concept at the ex vivo level that decoy peptides targeted to cytoskeletal protein-protein interfaces may lead to substantive dynamic modulation of aortic stiffness

Vegetation associated with Wollemia nobilis (Araucariaceae)

Wollemia nobilis Jones et al. (Wollemi Pine) is restricted to four sites growing in warm temperate rainforest typical of the canyons in the Blue Mountains and Wollemi National Parks. 88 vascular plant species were recorded from four sites. The tree canopy at all sites is dominated by Wollemia nobilis, Ceratopetalum apetalum, Doryphora sassafras and Acmena smithii. A large number of fern and vine species dominate the forest floor. Site 1 contains more species than the other sites, possibly due to its diversity of topographic features. Similarity analysis indicates that sites 2 and 3 are the most similar and sites 1 and 4 are least similar in floristic composition. 54% of plant species were recorded at one site only. Ceratopetalum apetalum, Blechnum cartilagineum and Wollemia nobilis were found to contribute most to the similarity between sites

Effect of Uveal Melanocytes on Choroidal Morphology in Rhesus Macaques and Humans on Enhanced-Depth Imaging Optical Coherence Tomography.

PurposeTo compare cross-sectional choroidal morphology in rhesus macaque and human eyes using enhanced-depth imaging optical coherence tomography (EDI-OCT) and histologic analysis.MethodsEnhanced-depth imaging-OCT images from 25 rhesus macaque and 30 human eyes were evaluated for choriocapillaris and choroidal-scleral junction (CSJ) visibility in the central macula based on OCT reflectivity profiles, and compared with age-matched histologic sections. Semiautomated segmentation of the choriocapillaris and CSJ was used to measure choriocapillary and choroidal thickness, respectively. Multivariate regression was performed to determine the association of age, refractive error, and race with choriocapillaris and CSJ visibility.ResultsRhesus macaques exhibit a distinct hyporeflective choriocapillaris layer on EDI-OCT, while the CSJ cannot be visualized. In contrast, humans show variable reflectivities of the choriocapillaris, with a distinct CSJ seen in many subjects. Histologic sections demonstrate large, darkly pigmented melanocytes that are densely distributed in the macaque choroid, while melanocytes in humans are smaller, less pigmented, and variably distributed. Optical coherence tomography reflectivity patterns of the choroid appear to correspond to the density, size, and pigmentation of choroidal melanocytes. Mean choriocapillary thickness was similar between the two species (19.3 ± 3.4 vs. 19.8 ± 3.4 μm, P = 0.615), but choroidal thickness may be lower in macaques than in humans (191.2 ± 43.0 vs. 266.8 ± 78.0 μm, P &lt; 0.001). Racial differences in uveal pigmentation also appear to affect the visibility of the choriocapillaris and CSJ on EDI-OCT.ConclusionsPigmented uveal melanocytes affect choroidal morphology on EDI-OCT in rhesus macaque and human eyes. Racial differences in pigmentation may affect choriocapillaris and CSJ visibility, and may influence the accuracy of choroidal thickness measurements

Reversal of aging-induced increases in aortic stiffness by targeting cytoskeletal protein-protein interfaces

BACKGROUND: The proximal aorta normally functions as a critical shock absorber that protects small downstream vessels from damage by pressure and flow pulsatility generated by the heart during systole. This shock absorber function is impaired with age because of aortic stiffening. METHODS AND RESULTS: We examined the contribution of common genetic variation to aortic stiffness in humans by interrogating results from the AortaGen Consortium genome‐wide association study of carotid‐femoral pulse wave velocity. Common genetic variation in the N‐WASP (WASL) locus is associated with carotid‐femoral pulse wave velocity (rs600420, P=0.0051). Thus, we tested the hypothesis that decoy proteins designed to disrupt the interaction of cytoskeletal proteins such as N‐WASP with its binding partners in the vascular smooth muscle cytoskeleton could decrease ex vivo stiffness of aortas from a mouse model of aging. A synthetic decoy peptide construct of N‐WASP significantly reduced activated stiffness in ex vivo aortas of aged mice. Two other cytoskeletal constructs targeted to VASP and talin‐vinculin interfaces similarly decreased aging‐induced ex vivo active stiffness by on‐target specific actions. Furthermore, packaging these decoy peptides into microbubbles enables the peptides to be ultrasound‐targeted to the wall of the proximal aorta to attenuate ex vivo active stiffness. CONCLUSIONS: We conclude that decoy peptides targeted to vascular smooth muscle cytoskeletal protein‐protein interfaces and microbubble packaged can decrease aortic stiffness ex vivo. Our results provide proof of concept at the ex vivo level that decoy peptides targeted to cytoskeletal protein‐protein interfaces may lead to substantive dynamic modulation of aortic stiffness.Published versio

Associations of maternal retinal vasculature with subsequent fetal growth and birth size

10.1371/journal.pone.0118250PLoS ONE104e0118250GUSTO (Growing up towards Healthy Outcomes