Never too late? Quadruplets at the age of 65 years

Background: We discuss the challenges of multiple pregnancy at very advanced reproductive age. Case presentation: We present the case of a quadruplet pregnancy at the maternal age of 65 following in-vitro fertilization (IVF) with donor eggs and sperm, involving cross-border reproductive care. All children born were at 25 weeks' gestation and survived; however, poor neurodevelopmental outcome remains a major concern in one child. Conclusions: The use of reproductive technology to achieve a multiple pregnancy at such an advanced post-menopausal age generated a debate on ethical, psychosocial and medical questions. We share this debate and highlight the need to reconsider international guidelines for women of advanced reproductive age

Numerical simulation and statistical analysis of a cascaded flexure hinge for use in a cryogenic working environment

Due to their many advantages, flexible structures are increasingly being used as guide and transmission elements in handling systems. Prismatic solid-state joints with a concentrated cross-sectional reduction are predominantly used as flexure pivots for both microscopic and macroscopic designs. A transfer of these geometries to applications in cryogenic working environments is not easily possible at temperatures below -130 °C due to the changed material properties. In this paper, the further development of swivel joints as cascaded solid state joints for such a cryogenic environment is illustrated by the targeted adaptation of certain joint parameters and dimensions. By means of a comprehensive FEM simulation, it can be shown how the influence of specific parameters affects movement accuracy, process forces and shape stability and to what extent these geometric parameters influence each other in their effect

Correlation between Geometric Component Properties and Physical Parameters of an Aerodynamic Feeding System

In previous research, an aerodynamic feeding system was developed, which autonomously adapts to different components by using a genetic algorithm that controls the physical parameters of the system (e.g. angle of inclination, nozzle pressure). The algorithm starts with two individuals with random values, generated within the boundaries of the parameters set by the user. Due to this, the setting time - the time that passes until a satisfactory orientation rate is reached - is hard to predict. The aim of this work is to identify basic interactions of geometric component properties with the physical parameters of the aerodynamic feeding system to determine in which areas of the workspace a satisfactory solution can be expected. By doing so, the initial population of the genetic algorithm can be generated based on certain geometric properties and would therefore no longer be random, presumably reducing setting time. To identify interactions of component properties and system parameters, exemplary components were developed. They represent relevant single properties that have significant impact on the aerodynamic orientation process. These components were then fed into the aerodynamic orientation process and their behavior was documented. To identify correlations between certain geometric properties and physical parameters of the feeding system, the tests were planned and carried out using Design of Experiments methods. The results of the tests were also used to determine the direct interrelations of said properties and the suitability for aerodynamic orientation

Placenta Percreta Presents with Neoangiogenesis of Arteries with Von Willebrand Factor-Negative Endothelium

In placenta percreta cases, large vessels are present on the precrete surface area. As these vessels are not found in normal placentation, we examined their histological structure for features that might explain the pathogenesis of neoangiogenesis induced by placenta accreta spectrum disorders (PAS). In two patients with placenta percreta (FIGO grade 3a) of the anterior uterine wall, one strikingly large vessel of 2 cm length was excised. The samples were formalin fixed and paraffin-embedded. Gomori trichrome staining was used to evaluate the muscular layers and Weigert-Van Gieson staining for elastic fibers. Immunohistochemical staining of the vessel endothelium was performed for Von Willebrand factor (VWF), platelet endothelial cell adhesion molecule (CD31), Ephrin B2, and EPH receptor B4. The structure of the vessel walls appeared artery-like. The vessel of patient one further exhibited an unorderly muscular layer and a lack of elastic laminae, whereas these features appeared normal in the vessel of the other patient. The endothelium of both vessels stained VWF-negative and CD31-positive. In conclusion, this study showed VWF-negative vessel endothelia of epiplacental arteries in placenta accreta spectrum. VWF is known to regulate artery formation, as the absence of VWF has been shown to cause enhanced vascularization. Therefore, we suppose that PAS provokes increased vascularization through suppression of VWF. This process might be associated with the immature vessel architecture as found in one of the vessels and Ephrin B2 and EPH receptor B4 negativity of both artery-like vessels. The underlying pathomechanism needs to be evaluated in a greater set of patients

New genes in the evolution of the neural crest differentiation program

The phylogenetic classification of genes that are ontologically associated with neural crest development reveals that neural crest evolution is associated with the emergence of new signalling peptides

Optimized RNA isolation of FFPE uterine scar tissues for RNA expression analyses delineated by laser microdissection

ABSTRACT Samples for histological analyses are often formalin-fixed paraffin-embedded (FFPE) and slide-mounted, which complicates RNA extraction for many downstream molecular applications. Furthermore, when the region of interest is extremely small due to isolation with lasermicrodissection (LMD), extracting RNA of adequate quality and quantity is difficult. We describe an optimized protocol for maximizing RNA output from FFPE tissue devised to identify and analyze gene expression of humanmaternal uterine scar tissue obtained fromuterotomy scars resulting from prior cesarean deliveries. Gomori trichrome staining allowed for region identification for LMD. Successful RNA isolation, reverse transcription and, importantly, quantitative real-time PCR (qRT-PCR) were performed. This report provides an optimized step-by-step protocol yielding sufficient RNA for qRT-PCR analyses from challenging tissue/LMD-FFPE samples. METHOD SUMMARY FFPE sample sections weremounted on glass slides and stained with hematoxylin and eosin (HE). A corresponding slide was stained according to Gomori trichrome for orientation. Regions of interest in HE-stained samples weremarked using lasermicrodissection (LMD) and subsequently scratched off the slide with a sterile scalpel. RNA extraction and cDNA synthesis were carried out, and quantitative real-time PCR with TaqMan probes was performed. TWEETABLE ABSTRACT We describe a protocol for maximized RNA output from FFPE tissue delineated by laser microdissection devised to analyze gene expression of human maternal uterine scar tissue obtained from uterotomy scars of prior cesarean deliveries

Reply to: “Hysterectomy versus continuing conservative management: which is better for disseminated intravascular coagulation?”; Shinya Matsuzaki, MD, PhD, Yoshikazu Nagase, MD, Masayuki Endo, MD, PhD, Tadashi Kimura, MD, PhD

Purpose!#!Enzymes with epigenetic functions play an essential part in development of cancer. However, the significance of epigenetic changes in cervical carcinoma as a prognostic factor has not been fully investigated. Nuclear receptor corepressor (NCoR) presents itself as a potentially important element for epigenetic modification and as a potential prognostic aspect in cervical cancer.!##!Methods!#!By immunohistochemical staining of 250 tumor samples, the expression strength of NCoR was measured and evaluated by immunoreactive score (IRS) in the nucleus and cytoplasm.!##!Results!#!A low expression of NCoR in our patients was a disadvantage in overall survival. Expression of NCoR was negatively correlated with viral oncoprotein E6, acetylated histone H3 acetyl K9 and FIGO status, and positively correlated to p53.!##!Conclusions!#!Our study has identified epigenetic modification of tumor cells thus seems to be of relevance in cervical cancer as well for diagnosis, as a marker or as a potential therapeutic target in patients with advanced cervical carcinoma

Maternal Serum VEGF Predicts Abnormally Invasive Placenta Better than NT-proBNP: a Multicenter Case-Control Study

The aim of this study was to test if maternal serum vascular endothelial growth factor (VEGF) or N-terminal pro B-type natriuretic peptide (NT-proBNP) predicts abnormally invasive placenta (AIP) better. Secondary objective was to test whether the serum levels of VEGF and NT-proBNP can predict the degree of invasion. In a multicenter case–control study design, gestational age-matched serum samples from pregnant women with AIP (n = 44) and uncomplicated pregnancies (n = 55) who had been enrolled at Charité – Universitätsmedizin Berlin, Germany and Centre Hospitalier Régional de la Citadelle in Liège, Belgium were analyzed. Maternal blood serum VEGF and NT-proBNP levels were immunoassayed from samples taken immediately before delivery (GA median: 35 weeks). Biomarker levels were compared between AIP and control group. The correlation of biomarker levels with the clinical AIP degree was assessed. The predictive biomarker ability was characterized through a multivariate regression model and receiver operating characteristic curves. Women with AIP had significantly lower maternal serum VEGF levels (AIP mean 285 pg/ml, 95% CI 248–322, vs. control: 391 pg/ml, 95% CI 356–426, p < 0.01) and higher NT-proBNP levels (AIP median 329 pg/ml, IQR 287–385, vs. control 295 pg/ml, IQR 273–356, p = 0.03). Maternal serum VEGF levels were able to predict AIP better (AUC = 0.729, 0.622–0.836, p < 0.001; VEGF + number of previous cesarean deliveries: AUC = 0.915, 0.853–0.977, p < 0.001). Maternal serum VEGF levels correlated inversely with the clinical AIP degree (r = − 0.32, p < 0.01). In short, maternal serum VEGF, more than NT-proBNP, can help in predicting AIP and hints at the degree of invasion