Search

STUDY QUESTION Does endothelin-1 (ET-1) regulate matrix metalloproteinase (MMP) 14 and 15 production and invasion of human first trimester trophoblasts? SUMMARY ANSWER ET-1 in pathophysiological concentrations down-regulates MMP14 and MMP15 expression via endothelin receptor (ETR) type B and decreases trophoblast migration and invasion. WHAT IS KNOWN ALREADY MMP14 and MMP15 are involved in trophoblast invasion. Impairment of invasion has been linked to pregnancy complications such as pre-eclampsia (PE). ET-1 is up-regulated in PE. STUDY DESIGN, SIZE, DURATION In vitro study using primary human trophoblasts from 50 first trimester placentas (gestational week 7–12). PARTICIPANTS/MATERIALS, SETTING, METHODS Trophoblasts were cultured in the absence or presence of 10–100 nM ET-1. MMP14 and MMP15 mRNA and protein were quantified by RT-qPCR and Western blotting, respectively. Selective antagonists for ETRA (BQ-123) or ETRB (BQ-788) were used to identify ETR subtypes involved. Functional ET-1 effects were tested in first trimester chorionic villous explants and transwell invasion assays. The roles of tumor necrosis factor (TNF)-α (25 ng/ml) and oxygen (1%) in ET-1 regulation of MMP14 and 15 expression were assessed by Western blotting. MAIN RESULTS AND THE ROLE OF CHANCE ET-1 down-regulated MMP14 and MMP15 mRNA (−21% and −26%, respectively, P < 0.05) and protein levels (–18% and –22%, respectively, P < 0.05). This effect was mediated via ETRB. ET-1 decreased trophoblast outgrowth in placental explants (−24%, P < 0.05) and trophoblast invasion (−26%, P ≤ 0.01). TNF-α enhanced ET-1 mediated MMP15 down-regulation (by 10%, P < 0.05), whereas hypoxia abolished the effect of ET-1 on both MMPs. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Only primary trophoblasts were used in this study. Since trophoblast yield from first trimester placental material is limited, further aspects of MMP14 and 15 regulation could not be characterized. Other anti-invasive factors may be altered by ET-1 in trophoblasts and, thus, contribute to the reduced invasion, but have not been investigated. Oxygen levels similar to those found in the decidua (5–8% O2) were not analyzed in this study. WIDER IMPLICATIONS OF THE FINDINGS ET-1 modifies placental function already during the first trimester of pregnancy, the time-window when the placental changes implicated in PE occur. Thus, our results improve the understanding of the placental mechanisms underlying trophoblast invasion and PE. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the Oesterreichische Nationalbank (Anniversary Fund, project number: 14796) and the Herzfelder'sche Familienstiftung (to J.P.; number: 00685). AMM received funding from the Austrian Science Fund FWF (W1241) and the Medical University Graz through the PhD Program Molecular Fundamentals of Inflammation (DK-MOLIN). The authors have no conflict of interest.

Background: Obesity before pregnancy is associated with impaired metabolic status of the mother and the offspring later in life. These adverse effects have been attributed to epigenetic changes in utero, but little is known about the role of placental metabolism and its contribution to fetal development. Objectives: We examined the impact of maternal pre-pregnancy obesity on the expression of genes involved in placental lipid metabolism in lean and obese women. Subjects/Methods: Seventy-three lean and obese women with healthy pregnancy were recruited at term elective cesarean delivery. Metabolic parameters were measured on maternal venous blood samples. Expression of 88 genes involved in lipid metabolism was measured in whole placenta tissue. Proteins of genes differently expressed in response to maternal obesity were quantified, correlated with maternal parameters and immunolocalized in placenta sections. Isolated primary trophoblasts were used for in vitro assays. Results: Triglyceride (TG) content was increased in placental tissue of obese (1.10, CI 1.04–1.24 mg g−1, P

Hintergrund: Die GWK hat am 16. November 2018 entschieden, nationale Forschungsinfrastrukturen (NFDIs) in Deutschland bis zu 10 Jahre zu fördern [ref:1]; [link:https://www.dfg.de/foerderung/programme/nfdi/*https://www.dfg.de/foerderung/programme/nfdi/].[zum vollständigen Text gelangen Sie über die oben angegebene URL], 64. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V. (GMDS)

Background Postanalytic issues of Ki67 assessment in breast cancers like counting method standardisation and interrater bias have been subject of various studies, but little is known about analytic variability of Ki67 staining between pathology labs. Our aim was to study interlaboratory variability of Ki67 staining in breast cancer using tissue microarrays (TMAs) and central assessment to minimise preanalytic and postanalytic influences. Methods Thirty European pathology labs stained serial slides of a TMA set of breast cancer tissues with Ki67 according to their routine in-house protocol. The Ki67-labelling index (Ki67-LI) of 70 matched samples was centrally assessed by one observer who counted all cancer cells per sample. We then tested for differences between the labs in Ki67-LI medians by analysing variance on ranks and in proportions of tumours classified as luminal A after dichotomising oestrogen receptor–positive cancers into cancers showing low (

Consider the wreath product of a finite group H with a finitely generated group G. We show that the Assouad–Nagata dimension of this product depends on the growth of G as follows. If the growth of G is not bounded by a linear function then the dimension is infinite; otherwise it is equal to the Assouad–Nagata dimension of G which is 1 or 0.

The new expert recommendation from the Austrian Society of Obstetrics and Gynaecology (OEGGG) comprises an interpretation and summary of guidelines from the leading specialist organisations worldwide (RCOG, ACOG, SOGC, CNGOF, WHO, NIH, NICE, UpToDate). In essence it outlines alternatives to the direct pathway to elective repeat caesarean section (ERCS). In so doing it aligns with international trends, according to which a differentiated, individualised clinical approach is recommended that considers benefits and risks to both mother and child, provides detailed counselling and takes the patient's wishes into account. In view of good success rates (60-85 %) for vaginal birth after caesarean section (VBAC) the consideration of predictive factors during antenatal birth planning has become increasingly important. This publication provides a compact management recommendation for the majority of standard clinical situations. However it cannot and does not claim to cover all possible scenarios. The consideration of all relevant factors in each individual case, and thus the ultimate decision on mode of delivery, remains the discretion and responsibility of the treating obstetrician.Die neue Expertenempfehlung der Österreichischen Gesellschaft für Gynäkologie und Geburtshilfe (OEGGG) stellt eine Zusammenfassung und Interpretation der Guidelines der weltweit führenden Fachgesellschaften und Organisationen (RCOG, ACOG, SOGC, CNGOF, WHO, NIH, NICE, UpToDate) dar. In ihrer Kernaussage zeigt die Empfehlung Alternativen zum direkten Weg zur geplanten Re-Sectio auf. Sie folgt damit dem internationalen Trend, der stattdessen ein differenziertes, individualisiertes klinisches Management unter Abwägen mütterlicher und kindlicher Vorteile und Risiken sowie eine detaillierte Aufklärung und Miteinbeziehung der Wünsche der Schwangeren empfiehlt. Angesichts guter Erfolgsraten für eine vaginale Geburt nach Kaiserschnitt von 60–85 % gewinnt das Einbeziehen von prädiktiven Faktoren in die antenatale Geburtsplanung zunehmend an Wichtigkeit. Die Empfehlung versteht sich als kompakte Handlungsempfehlung für die meisten klinischen Standardsituationen, kann jedoch niemals alle potenziellen Einzelsituationen abdecken. Das individuelle Bewerten aller Faktoren und damit die Entscheidung über den tatsächlichen Entbindungsmodus bleibt letztendlich im Ermessen des behandelnden Facharzts/der behandelnden Fachärztin.

Background: First rank symptoms (FRS) of schizophrenia have been used for decades for diagnostic purposes. In the new version of the DSM-5, the American Psychiatric Association (APA) has abolished any further reference to FRS of schizophrenia and treats them like any other "criterion A' symptom (e.g. any kind of hallucination or delusion) with regard to their diagnostic implication. The ICD-10 is currently under revision and may follow suit. In this review, we discuss central points of criticism that are directed against the continuous use of first rank symptoms (FRS) to diagnose schizophrenia.

Postpartum hemorrhage (PPH) is one of the main causes of maternal deaths even in industrialized countries. It represents an emergency situation which necessitates a rapid decision and in particular an exact diagnosis and root cause analysis in order to initiate the correct therapeutic measures in an interdisciplinary cooperation. In addition to established guidelines, the benefits of standardized therapy algorithms have been demonstrated. A therapy algorithm for the obstetric emergency of postpartum hemorrhage in the German language is not yet available. The establishment of an international (Germany, Austria and Switzerland D-A-CH) "treatment algorithm for postpartum hemorrhage" was an interdisciplinary project based on the guidelines of the corresponding specialist societies (anesthesia and intensive care medicine and obstetrics) in the three countries as well as comparable international algorithms for therapy of PPH.The obstetrics and anesthesiology personnel must possess sufficient expertise for emergency situations despite lower case numbers. The rarity of occurrence for individual patients and the life-threatening situation necessitate a structured approach according to predetermined treatment algorithms. This can then be carried out according to the established algorithm. Furthermore, this algorithm presents the opportunity to train for emergency situations in an interdisciplinary team., Die postpartale Blutung (PPH) zählt zu den Hauptursachen der Müttersterblichkeit auch in der westlichen Welt. Die PPH stellt eine Notfallsituation dar, die eine rasche Entscheidung und v. a. eine exakte Diagnose und Ursachenanalyse notwendig macht, um die korrekten therapeutischen Maßnahmen in interdisziplinärer Zusammenarbeit rechtzeitig einzuleiten. Neben etablierten Leitlinien ist der Nutzen standardisierter Therapiealgorithmen belegt. Ein Therapiealgorithmus für den geburtshilflichen Notfall „postpartale Hämorrhagie“ fehlte bisher im deutschsprachigen Raum. Die Erstellung des länderübergreifenden (Deutschland, Österreich und Schweiz: D-A-CH) „Handlungsalgorithmus Postpartale Blutung“ erfolgte interdisziplinär, basierend auf den bisherigen Leitlinien der jeweiligen Fachgesellschaften (Anästhesie und Intensivmedizin, Geburtshilfe) der 3 Länder sowie internationalen vergleichbaren Algorithmen zur Therapie der PPH. Das geburtshilfliche und anästhesiologische Personal muss für den Notfall eine ausreichende Expertise trotz geringer Fallzahl besitzen. Die Seltenheit, mit der das Ereignis für die einzelne Patientin auftritt, sowie die vitale Bedrohung in der Situation, erfordern ein strukturiertes Vorgehen nach vorgegebenen Handlungsalgorithmen. Dies kann mit dem nun ausgearbeiteten Algorithmus erfolgen. Darüber hinaus bietet dieser Algorithmus die Möglichkeit, den Notfall im interdisziplinären Team zu trainieren.

Hintergrund: Seit der Einführung der Kardiotokographie vor 50 Jahren hat die Zahl der intrapartalen Asphyxien als Hauptursache von nachhaltigen neurologischen Schädigungen dramatisch abgenommen. Unverändert jedoch ist eine Prävalenz von 2 in 1000 Geburten, bei denen es zu einer schweren[for full text, please go to the a.m. URL], Jahrestagung der Gesellschaft für Medizinische Ausbildung (GMA)

Consider the wreath product $H\wr G$, where $H\ne 1$ is finite and $G$ is finitely generated. We show that the Assouad-Nagata dimension $\dim_{AN}(H\wr G)$ of $H\wr G$ depends on the growth of $G$ as follows: If the growth of $G$ is not bounded by a linear function, then $\dim_{AN}(H\wr G)=\infty$, otherwise $\dim_{AN}(H\wr G)=\dim_{AN}(G)\leq 1$., 11 pages, new references added

International audience

OBJECTIVE To determine the dose dependency of the anti-anginal and antiischemic effects of the selective beta-blocker talinolol administered once-daily in a randomized, double-blind, placebo-controlled multicenter study in patients with stable angina pectoris. METHODS Standardized bicycle ergometry at baseline and after 3 and 6 weeks of treatment was used to assess exercise capacity. The primary endpoint was the change in the maximum exercise time (MET) 24 +/- 1 h after the last intake of study medication compared to baseline. Secondary efficacy parameters were time to onset of angina, time to 1 mm ST segment depression, angina attacks, consumption of short-acting nitrates, blood pressure and pulse rate. Patients were randomly allocated to treatment with talinolol (100, 200 or 300 mg once daily) or placebo for a period of 6 weeks. RESULTS A total of 241 outpatients (204 male and 37 female) aged between 34 and 83 years, were randomized in 31 centers in Germany, Poland and the Czech Republic. At the end of treatment, the primary endpoint (change in MET compared to baseline) showed no significant difference between the talinolol groups and placebo. The means of MET prolongation ranged from 27.4 sec under placebo to a maximum of 47.6 sec in the 200 mg group. However, the time to 1 mm ST segment depression during exercise increased markedly with talinolol, the difference to placebo reaching statistical significance with the 200 mg/d dose (80.1 +/- 32.7 sec, p = 0.0182) and 300 mg/d dose (82.0 +/- 31.6 sec, p = 0.0127). In the case of the other secondary variables, the most pronounced effects were recorded for talinolol doses of 200 and 300 mg/d. Talinolol significantly inhibited the exercise-induced increase in heart rate and blood pressure. The decrease in rate pressure product at 100 W workload was statistically significant with all administered talinolol doses (delta from baseline to final visit 3090, 4351 and 4291 for 100, 200 and 300 mg/d, respectively, p < 0.0001). Despite once-daily dosing, talinolol at doses up to 300 mg/d was very well tolerated. No unexpected adverse drug reactions were observed. CONCLUSION The results show that talinolol administered once daily in a dosage of 200 - 300 mg/d is effective and safe in the management of chronic stable angina.

OBJECTIVE We report on a 3-year experience using single-shot, ultrasonography-guided, percutaneous ethanol ablation (PEA) of hyperplastic parathyroid glands in chronic dialysis patients suffering from secondary or tertiary hyperparathyroidism. MATERIALS AND METHODS Seventeen uraemic patients (mean age 52 +/- 14 years) with hypercalcaemia and elevated serum levels of parathyroid hormone were assessed for ethanol ablation. Ten patients did not fulfil the inclusion criteria and underwent surgical parathyroidectomy. Seven patients were treated using PEA. RESULTS All patients treated with PEA tolerated the procedure well, and no major complications were observed. Three out of seven patients underwent further ethanol ablation due to recurrent symptomatic hyperparathyroidism. Following the procedures, serum values of total calcium and parathyroid hormone remained within target range with concomitant medical therapy in all patients. CONCLUSION PEA performed as a single-shot therapy can be used as a minimally invasive and safe supplement to medical therapy in the treatment of secondary or tertiary hyperparathyroidism in selected patients. In case of recurrence, treatment can be repeated without any problems.

Background: Type 1 diabetes mellitus is common in Europeans. Optimal glucometabolic control at conception and during early pregnancy is necessary to reduce the risk of early miscarriage and congenital malformations. Safe and effective contraceptive methods are essential for these women in order to have a “planned pregnancy” under optimal conditions. Aim: To find out which recommendations Greek gynaecologists give to young patients with type 1 diabetes mellitus with respect to contraception. To regard the experience of Greek gynaecologists in counselling with women. To compare the Greek gynaecologists with German gynaecologists in a previously published similar survey. Subjects and methods: A structured questionnaire containing questions about attitude, health care and contraception in young women with type 1 diabetes was given to 400 Greek gynaecologists working in Athens. Results: Only 70 (17.5%) of the Greek gynaecologists returned the questionnaire. Condoms were the preferred recommendation as contraceptive method for young women with diabetes, mellitus type 1 in 64%. About 57% of the gynaecologists recommended this type of contraception as first line contraceptives for young women with diabetes type 1 who smoke. The two most important criteria for selection of a contraceptive method for Greek gynaecologists were the safety and the diabetes specific problems. The Greek gynaecologists had only limited experience in regard to counselling and treating young and adolescent women with type 1 diabetes. Conclusion: There was no consensus with respect to contraception among Greek gynaecologists. This is similar to our previous findings in a survey involving German gynaecologists. Practical experience in counselling and treating adolescent and young women with type 1 diabetes was limited among the gynaecologists who participated in this study. Working out proper recommendations for contraception crucial for optimal medical care for type 1 diabetic women in Europe. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Glycopeptides with TN antigen (GalNAc)Ser/Thr and T-antigen structures (beta Gall-3GalNAc)Ser/Thr, described as tumor-associated antigens, were synthesized and coupled to bovine serum albumin. Alternatively, synthetic methods for the construction of beta-anomeric analogues of the TN and T-antigen glycopeptides were developed, aiming at antigenic structures having a varied stereochemistry of the linkage between the carbohydrate and the peptide moiety. As a further type of potential tumor-associated antigen, fucosyl-chitobiose asparagine glycopeptides were synthesized, deprotected, and coupled to bovine serum albumin. The chemical methods developed now make the complex sensitive glycoprotein partial structures accessible in analytically pure form and in preparative amounts.

Der Einfluß von Hydroxyäthylstärke auf die intra- sowie postoperative Blutgerinnung, Fibrinolyse und Plättchenfunktionen wurde in einer klinischen Studie bei Patienten mit einer orthopädischen Operation kontrolliert. Hydroxyäthylstärke scheint neben einer Präzipitation und beschleunigten Polymerisation einzelner Gerinnungsfaktoren die Struktur des Fibringerinnsels sowie die Plättchenfunktionen zu beeinflussen. Wenngleich kein antithromboplastischer Effekt erkennbar war, so könnte der Effekt einer möglichen Thromboseprophylaxe neben der zirkulationsfördernden Wirkung in einer erleichterten Lysierbarkeit strukturell geänderter Gerinnsel begründet sein.

Virtual Reality (VR) in conjunction with Immersive Projection Technology (IPT) are well introduced and highly accepted in the international society of institutional research. But does the (manufacturing) industry share this excitement about recent stereo projection technology? What are the key factors of successfully creating a VR solution with production quality? How to identify fields of application and how to get return on invest? These questions will be addressed especially for the automotive industry. While some of the considerations hold for other manufacturing industries as well, some do not. Problems and solutions will be discussed on sample installations and applications for the automotive industry. These VR systems help engineers to deal with different problems: • evaluation of exterior car design, • analysis of thermal comfort in a car cabin, • visualization of a production line • acceptance of tools for deep drawing We will outline the different projection and software technologies used for these engineering tasks as well as the user interface aspects, because there is a special correlation between used projection technology and useful user interaction. The careful design of a special purpose 3D user interface is one of the keys for user productivity and user acceptance.

Acute foetal asphyxia, caused by arrest of uterine blood flow, increases both sympathetic activity and peripheral vascular resistance and decreases blood flow to peripheral organs (Jensen et al., J. Dev. Physiol., 9, 543-559). The rapidity and uniformity of this peripheral vasoconstriction suggest that the sympatho-neuronal system may reflexly cause these initial blood flow changes during acute asphyxia. To test this hypothesis, we studied 5 intact and 6 chemically sympathectomized (6-hydroxy-dopamine, 46.1 +/- 6 mg/kg foetal weight) chronically prepared normoxaemic foetal sheep in utero at 0.9 of gestation. Organ blood flows (microsphere method), plasma concentrations of catecholamines, vasopressin, and angiotensin II, acid-base balance and blood gases were measured before, during and after arrest of uterine blood flow for 2 min, i.e., at 0, 1, 2, 3, 430 min. In intact foetuses there was a progressive increase in arterial blood pressure and a rapid circulatory centralization in favour of the brain stem and heart and at the expense of most of the peripheral organs. The changes in peripheral blood flow during and after asphyxia were well reflected by those in the skin and scalp. In chemically sympathectomized foetuses, arterial blood pressure fell transiently at 1 min of asphyxia and cardiac output was redistributed towards the carcass and intestinal organs at the expense of the heart, spinal medulla, and placenta. We conclude that in foetal sheep at 0.9 of gestation, the short-term adaptation to arrest of uterine blood flow is a rapid and profound peripheral vasoconstriction to effect an increase in arterial blood pressure. This initial response during circulatory centralization, which is necessary to increase or maintain blood flow to the heart, brain stem, and placenta, is blunted by sympathectomy. Thus, the foetal sympatho-neuronal system is important for short-term adaptation to and intact survival of asphyxia.

BackgroundFirst rank symptoms (FRS) of schizophrenia have been used for decades for diagnostic purposes. In the new version of the DSM-5, the American Psychiatric Association (APA) has abolished any further reference to FRS of schizophrenia and treats them like any other “criterion A” symptom (e.g. any kind of hallucination or delusion) with regard to their diagnostic implication. The ICD-10 is currently under revision and may follow suit. In this review, we discuss central points of criticism that are directed against the continuous use of first rank symptoms (FRS) to diagnose schizophrenia.MethodsWe describe the specific circumstances in which Schneider articulated his approach to schizophrenia diagnosis and discuss the relevance of his approach today. Further, we discuss anthropological and phenomenological aspects of FRS and highlight the importance of self-disorder (as part of FRS) for the diagnosis of schizophrenia. Finally, we will conclude by suggesting that the theory and rationale behind the definition of FRS is still important for psychopathological as well as neurobiological approaches today.ResultsResults of a pivotal meta-analysis and other studies show relatively poor sensitivity, yet relatively high specificity for FRS as diagnostic marker for schizophrenia. Several methodological issues impede a systematic assessment of the usefulness of FRS in the diagnosis of schizophrenia. However, there is good evidence that FRS may still be useful to differentiate schizophrenia from somatic causes of psychotic states. This may be particularly important in countries or situations with little access to other diagnostic tests. FRS may thus still represent a useful aid for clinicians in the diagnostic process.ConclusionIn conclusion, we suggest to continue a tradition of careful clinical observation and fine-grained psychopathological assessment, including a focus on symptoms regarding self-disorders, which reflects a key aspect of psychosis. We suggest that the importance of FRS may indeed be scaled down to a degree that the occurrence of a single FRS alone should not suffice to diagnose schizophrenia, but, on the other hand, absence of FRS should be regarded as a warning sign that the diagnosis of schizophrenia or schizoaffective disorder is not warranted and requires specific care to rule out other causes, particularly neurological and other somatic disorders. With respect to the current stage of the development of ICD-11, we appreciate the fact that self-disorders are explicitly mentioned (and distinguished from delusions) in the list of mandatory symptoms but still feel that delusional perceptions and complex hallucinations as defined by Schneider should be distinguished from delusions or hallucinations of “any kind”. Finally, we encourage future research to explore the psychopathological context and the neurobiological correlates of self-disorders as a potential phenotypic trait marker of schizophrenia.

We prove that every \( \lambda \)-Lipschitz map \( f : S \to Y \) defined on a subset of an arbitrary metric space X possesses a \( c \lambda \)-Lipschitz extension \( \bar{f} : X \to Y \) for some \( c = c(Y) \ge 1 \) provided Y is a Hadamard manifold which satisfies one of the following conditions: (i) Y has pinched negative sectional curvature, (ii) Y is homogeneous, (iii) Y is two-dimensional. In case (i) the constant c depends only on the dimension of Y and the pinching constant, in case (iii) one may take \( c = 4\sqrt{2} \). We obtain similar results for large classes of Hadamard spaces Y in the sense of Alexandrov.

We generalize Kirszbraun's extension theorem for Lipschitz maps between (subsets of) euclidean spaces to metric spaces with upper or lower curvature bounds in the sense of A.D. Alexandrov. As a by-product we develop new tools in the theory of tangent cones of these spaces and obtain new characterization results which may be of independent interest.

Let X be a simply connected, complete geodesic metric space which is nonpositively curved in the sense of Alexandrov. We assume that X contains a k-flat F of maximal dimension and consider quasiisometric embeddings f: ℝk∼ → X whose distance function from F satisfies a certain asymptotic growth condition. We prove that if X is locally compact and cocompact, then the Hausdorff distance between f(ℝk) and F is uniformly bounded. This generalizes a well-known lemma of Mostow on quasiflats in symmetric spaces of noncompact type.

Apart from long-term cardiovascular and metabolic effects of intrauterine deficiency or oversupply situations of the fetus, cerebral, renal and reproductive functions also seem to be influenced by a disturbed intrauterine environment.