Searching the web: a survey on the quality of advice on postnatal sequelae of intrauterine growth restriction and the implication of developmental origins of health and disease.

Intrauterine growth restriction (IUGR) and fetal growth restriction (FGR) are pregnancy complications associated with morbidity in later life. Despite a growing body of evidence from current research on developmental origins of health and disease (DOHaD), little information is currently provided to parents on long-term metabolic, cardiovascular and neurologic consequences. As parents strongly rely on internet-based health-related information, we examined the quality of information on IUGR/FGR sequelae and DOHaD in webpages used by laypersons. Simulating non-clinicians experience, we entered the terms 'IUGR consequences' and 'FGR consequences' into Google and Yahoo search engines. The quality of the top search-hits was analyzed with regard to the certification through the Health On the Net Foundation (HON), currentness of cited references, while reliability of information and DOHaD-related consequences were assessed via the DISCERN Plus score (DPS). Overall the citation status was not up-to-date and only a few websites were HON-certified. The results of our analysis showed a dichotomy between the growing body of evidence regarding IUGR/FGR-related sequelae and lack of current guidelines, leaving parents without clear directions. Furthermore, detailed information on the concept of DOHaD is not provided. These findings emphasize the responsibility of the individual physician for providing advice on IUGR/FGR-related sequelae, monitoring and follow-up.

Spectrum, Applicability and Diagnostic Capacity of Contrast-Enhanced Ultrasound in Pediatric Patients and Young Adults after Intravenous Application - A Retrospective Trial.

Purpose: To investigate the spectrum, applicability and diagnostic capacity of intravenous contrast-enhanced ultrasound imaging (CEUS) in a pediatric population. Materials and Methods: From 08/2005 to 11/2015, n = 40 pediatric patients and young adults from 0 - 26 years (Ø 11.4 ±â€Š7.5) and 3.0 - 85.3 kg (Ø 40.8 ± 25.6) with n = 55 investigations received n = 79 IV applications of ultrasound contrast agent (UCA). UCA dose and side effects were documented. Scanned organs were the liver (n = 42), spleen (n = 9), kidney (n = 3), and testis (n = 1). Histology, surgery or reference imaging was compared to CEUS and clinical follow-up. Results: The UCA dose < 20 kg was 0.4 ±â€Š0.3 ml, (0.05 ±â€Š0.02 ml/kg) and > 20 kg was 1.0 ±â€Š0.4 ml (p< 0.0001) (0.02 ±â€Š0.01 ml/kg, p< 0.0001). Adverse effects occurred in 2/79 applications (2.5 %). Agreement CEUS/gold standard resulted in 32/34 investigations. For liver diagnostics (gold standard: MRI, CT, histology, serology), n = 11 malignant and n = 15 benign focal liver lesions were included. The specificity was 100 % (95 % CI: 0.77 - 1.00), the sensitivity was 82 % (95 % CI: 0.48 - 0.98), the positive predictive value was 100 % (95 % CI: 0.69 - 1.00) and the negative predictive value was 88 % (95 % CI: 0.62 - 0.98, p< 0.0001). In n = 2 reference imaging misdiagnosed and CEUS was in accordance with clinical follow-up. All splenic/renal lesions were diagnosed correctly. In n = 1 an insufficient testicular perfusion was ruled out. The observation time was 30.4 ±â€Š30.5 months. Conclusion: CEUS is a well-tolerated and diagnostically equivalent modality in pediatric care, providing fundamental advantages compared to currently approved imaging modalities for these age groups.

The placental mTOR-pathway: correlation with early growth trajectories following intrauterine growth restriction?

Idiopathic intrauterine growth restriction (IUGR) is a result of impaired placental nutrient supply. Newborns with IUGR exhibiting postnatal catch-up growth are of higher risk for cardiovascular and metabolic co-morbidities in adult life. Mammalian target of rapamycin (mTOR) was recently shown to function as a placental nutrient sensor. Thus, we determined possible correlations of members of the placental mTOR signaling cascade with auxologic parameters of postnatal growth. The protein expression and activity of mTOR-pathway signaling components, Akt, AMP-activated protein kinase α, mTOR, p70S6kinase1 and insulin receptor substrate-1 were analysed via western blotting in IUGR v. matched appropriate-for-gestational age (AGA) placentas. Moreover, mTOR was immunohistochemically stained in placental sections. Data from western blot analyses were correlated with retrospective auxological follow-up data at 1 year of age. We found significant catch-up growth in the 1st year of life in the IUGR group. MTOR and its activated form are immunohistochemically detected in multiple placental compartments. We identified correlations of placental mTOR-pathway signaling components to auxological data at birth and at 1 year of life in IUGR. Analysis of the protein expression and phosphorylation level of mTOR-pathway components in IUGR and AGA placentas postpartum, however, did not reveal pathognomonic changes. Our findings suggest that the level of activated mTOR correlates with early catch-up growth following IUGR. However, the complexity of signals converging at the mTOR nexus and its cellular distribution pattern seem to limit its potential as biomarker in this setting.

The tumor suppressor gastrokine-1 is expressed in placenta and contributes to the regulation of trophoblast migration.

INTRODUCTION: Gastrokine-1 (GKN1) is a secreted auto-/paracrine protein, described to be expressed in the gastric mucosa. In gastric cancers GKN1 expression is commonly down-regulated. While current research focusses on the exploration of tumor-suppressive properties of GKN1 with regard to its potential clinical use in the treatment of gastroenterologic tumor disease, nothing is known about GKN1 expression and function in other organ systems. We investigated GKN1 expression in placental tissue and cells. MATERIALS AND METHODS: GKN1 was localized using immunohistochemistry in first and third trimester placental tissue, hydatidiform moles and various gestational trophoblastic neoplasias. We determined the expression of GKN1 in immunomagnetic bead-separated term placental cells and in choriocarcinoma cell lines. The role of GKN1 for JEG-3 migration was studied using live cell imaging. E-cadherin, MMP-2 and -9, TIMP-1 and -2, as well as urokinase (uPA) expression levels were determined. RESULTS: GKN1 is expressed in healthy third trimester placentas. Its expression is specifically limited to the extravillous trophoblast (EVT). GKN1 expression is significantly reduced in choriocarcinoma cell lines and gestational trophoblastic neoplasias. GKN1 attenuates the migration of JEG-3 choriocarcinoma cells in vitro, possibly via AKT-mediated induction of E-cadherin. GKN1 treatment reduced MMP-9 expression in JEG-3. DISCUSSION: Besides its role in gastric physiology our results clearly indicate regulatory functions of GKN1 in the EVT at the feto-maternal interface during pregnancy. Based on our findings in the JEG-3 choriocarcinoma cell line, an auto-/paracrine role of GKN1 for EVT motility and villous anchorage at the basal plate is conceivable. Thus, the tumor suppressor GKN1 is expressed in placental EVT and might contribute to the regulation of EVT migration/invasion.

Early course of Berardinelli-Seip congenital lipodystrophy (BSCL).

Berardinelli-Seip congenital lipodystrophy (BSCL) is a very rare autosomal recessive disease. In the described patient diagnostic relevant symptoms developed at 3 week age.