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The current law on the protection of expectant and nursing mothers largely rules out surgical activities during pregnancy for female doctors who perform surgical roles in hospitals. The proportion of female junior staff in gynaecology amounts to 80 %, and, for many of these women, surgical further training is not possible following official notification of an existing pregnancy. In a Germany-wide survey of female gynaecologists and surgeons using a questionnaire, it was determined to what extent female doctors worked in surgery during pregnancy, whether it led to complications in the pregnancy, when the employer was notified about the pregnancy, and what desire for change there is with regard to the law on the protection of expectant and nursing mothers. The data from 164 female doctors, of which 136 are gynaecologists and 28 surgeons, was evaluated. On average, the pregnancy was announced during the 14th week of pregnancy (WOP), and the doctor was not allowed to perform surgical activities in the 21st WOP. Female doctors in higher professional roles tended to announce the pregnancy later and ended their surgical activities later. There was no link between the time of ceasing surgical activities and an increased occurrence of complaints or complications during the pregnancy. In total, only 53 % of respondents had an appraisal during pregnancy and 75 % wanted a change in the law on the protection of expectant and nursing mothers.Das aktuelle Mutterschutzgesetz schließt eine operative Tätigkeit während der Schwangerschaft für in der Klinik operativ tätige Ärztinnen weitestgehend aus. Der Anteil der Berufseinsteigerinnen liegt in der Gynäkologie bei 80 %, für viele dieser Frauen ist die operative Weiterbildung nach offizieller Mitteilung einer bestehenden Schwangerschaft nicht möglich. In einer deutschlandweiten Umfrage unter Gynäkologinnen und Chirurginnen wurde anhand eines Fragebogens u. a. ermittelt, inwieweit Ärztinnen in der Schwangerschaft operativ tätig waren, ob es zu Komplikationen in der Schwangerschaft kam, wann die Schwangerschaft dem Arbeitgeber mitgeteilt wurde und welche Änderungswünsche bez. des Mutterschutzgesetzes bestehen. Die Daten von 164 Ärztinnen, davon 136 Gynäkologinnen und 28 Chirurginnen, wurden ausgewertet. Die Schwangerschaft wurde im Mittel in der 14. Schwangerschaftswoche (SSW) bekanntgegeben, ein Ausschluss aus der operativen Tätigkeit erfolgte in der 21. SSW. Ärztinnen in höheren beruflichen Positionen gaben tendenziell später die Schwangerschaft bekannt und beendeten später die operative Tätigkeit. Es bestand kein Zusammenhang zwischen dem Zeitpunkt des Ausscheidens aus der operativen Tätigkeit und einem vermehrten Auftreten von Beschwerden oder Komplikationen während der Schwangerschaft. Insgesamt führten nur 53 % der Befragten in der Schwangerschaft ein Personalgespräch und 75 % wünschten sich eine Änderung des Mutterschutzgesetzes.

In healthy bones, mineralization has to be tightly controlled to avoid pathological phenotypes. In this study, we investigated interactions between 1α,25(OH)2D3 (1,25D3) and activin A in the regulation of osteoblast induced mineralization. In human osteoblast cultures, we demonstrated that besides stimulation of mineralization, 1,25D3 also induced activin A, a strong inhibitor of mineralization. Simultaneously, follistatin (FST), the natural antagonist of activin A, was down-regulated by1,25D3. This resulted in an increase in activin A activity during 1,25D3 treatment. We also showed that in 1,25D3-treated osteoblasts, mineralization can be further increased when activin A activity was abrogated by adding exogenous FST. This observation implies that, besides stimulation of mineralization, 1,25D3 also controls activin A-mediated inhibition of mineralization. Besides activin A, 1,25D3 also induces osteocalcin (BGLAP), another inhibitor of mineralization. Warfarin, which has been shown to inactivate osteocalcin, increased 1,25D3-induced mineralization. Interaction between these two systems became evident from the synergistic increase in BGLAP expression upon blocking activin activity in 1,25D3-treated cultures. In conclusion, we demonstrate that 1,25D3 stimulation of mineralization by human osteoblasts is suppressed by concomitant induction of inhibitors of mineralization. Mineralization induction by 1,25D3 may actually be controlled via interplay with activin A and osteocalcin. Finally, this complex regulation of mineralization substantiates the significance of tight control of mineralization to prevent excessive mineralization and consequently reduction in bone quality and strength. J. Cell. Physiol. 228: 2167–2174, 2013. © 2013 Wiley Periodicals, Inc.

Both vitamin D receptor (VDR) and peroxisome proliferator-activated receptor gamma (PPAR-gamma) are ligand-activated nuclear transcription factors that are instrumental for bone health. While 1 alpha,25-dihydroxyvitamin D3 (1,25D3), the ligand for VDR, is essential for the development and maintenance of healthy bone, PPAR-gamma agonists cause detrimental skeletal effects. Recent studies have revealed evidence for a cross-talk between 1,25D3- and PPAR-alpha/-delta ligand-mediated signaling but there is a current lack of knowledge regarding cross-talk between signaling of 1,25D3 and the PPAR-gamma ligand mediated signaling. In this study, we investigated the cross-talk between 1,25D3- and PPAR-gamma agonist rosiglitazone-mediated signaling in human osteoblasts. 1,25D3 slightly but significantly induced expression of the primary PPAR-gamma target gene ANGPTL4 but did not influence FABP4 1,25D3 did not change rosiglitazone regulation of ANGPTL4 and FABP4. The other way around, rosiglitazone reduced CYP24A1 gene expression but this did not change CYP24A1 induction by 1,25D3. The findings regarding CYP24A1 gene expression are in line with the observation that 1,25D3 levels in medium were not affected by rosiglitazone. Furthermore, rosiglitazone significantly inhibited 1,25D3-induction of BGLAP while rosiglitazone alone did not change BGLAP. Additionally, 1,25D3 and rosiglitazone increase osteoblast alkaline phosphatase activity and synergistically stimulated extracellular matrix mineralization. In conclusion, these data provide evidence for a cross-talk between rosiglitazone- and 1,25D3-mediated signaling leading to an acceleration of extracellular matrix mineralization. The data suggest that the reduction of the mineralization inhibitor BGLAP and the increased differentiation status underlie the increased mineralization. (c) 2012 Elsevier B.V. All rights reserved.

It is well established that 1a-25-dihydroxyvitamin D3 (1,25D3) regulates osteoblast function and stimulates mineralization by human osteoblasts. The aim of this study was to identify processes underlying the 1,25D3 effects on mineralization. We started with gene expression profiling analyses of differentiating human pre-osteoblast treated with 1,25D3. Bioinformatic analyses showed interferon-related and -regulated genes (ISG) to be overrepresented in the set of 1,25D3-regulated genes. 1,25D3 down-regulated ISGs predominantly during the pre-mineralization period. This pointed to an interaction between the vitamin D and IFN signaling cascades in the regulation of osteoblast function. Separately, 1,25D3 enhances while IFN beta inhibits mineralization. Treatment of human osteoblasts with 1,25D3 and IFN beta showed that 1,25D3 completely overrules the IFN beta inhibition of mineralization. This was supported by analyses of extracellular matrix gene expression, showing a dominant effect of 1,25D3 over the inhibitory effect of IFN beta. We identified processes shared by IFN beta- and 1,25D3-mediated signaling by performing gene expression profiling during early osteoblast differentiation. Bioinformatic analyses revealed that genes being correlated or anti-correlated with interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) were associated with osteoblast proliferation. In conclusion, the current study demonstrates a cross talk between 1,25D3 and IFN beta in osteoblast differentiation and bone formation/mineralization. The interaction is complex and depends on the process but importantly, 1,25D3 stimulation of mineralization is dominant over the inhibitory effect of IFN beta. These observations are of potential clinical relevance considering the impact of the immune system on bone metabolism in conditions such as rheumatoid arthritis. J. Cell. Physiol. 227: 32583266, 2012. (C) 2011 Wiley Periodicals, Inc.

Osteoimmunology is an emerging field of research focused on the interaction of the immune system and bone. In this study we demonstrate that human osteoblasts are sensitive to the immune cytokine interferon (IFN)beta. Osteoblasts respond to IFN beta as shown by the induction of several known IFN target genes such as interferon-induced (IFI) proteins (IFIT1, IFI44L), interferon-stimulated gene factor 3 (ISGF3) complex and the induction of IFN beta itself. We demonstrated that IFN beta has severe inhibitory effects on mineralization of osteoblast-derived extracellular matrix (ECM). Analysis of the timing of the IFN beta effects revealed that committed osteoblasts in early stage of differentiation are most sensitive to IFN beta inhibition of mineralization. A single IFN beta treatment was as effective as multiple treatments. During the progress of differentiation osteoblasts become desensitized for IFN beta. This pinpoints to a complex pattern of IFN beta sensitivity in osteoblasts. Focusing on early osteoblasts, we showed that IFN beta decreased gene expression of ECM-related genes, such as type I Collagen (COL1A1), fibronectin (FN1), fibullin (FBLN1), fibrillin (FBN2), and laminin (LAMA1). Additionally, ECM produced by IFN beta-treated osteoblasts contained less collagen protein. IFN beta stimulated gene expression of osteopontin (OPN), annexin2 (ANXA2), and hyaluronan synthase 1 (HAS1), which are important factors in the adhesion of hematopoietic stem cells (HSC) in the HSC niche. In conclusion, IFN beta directly modifies human osteoblast function by inhibiting ECM synthesis eventually resulting in delayed bone formation and mineralization and induces a HSC niche supporting phenotype. These effects are highly dependent on timing of treatment in the early phase of osteoblast differentiation. J. Cell. Physiol. 227: 26682676, 2012. (c) 2011 Wiley Periodicals, Inc.

The objective of this research was to develop a yield monitoring system primarily for sugar beets by applying ultra-wideband (UWB) radar technology. Like radar systems used in geological engineering, these devices acquire data via electromagnetic waves. The basic idea was to use such data to identify sugar beets in agricultural soils, which would provide non-invasive in-soil detection of sugar beets in order to enable counting of individual sugar beets and determination of single sugar beet root mass. Further goals were to enhance the methods and procedures of the UWB radar technology for other applications in agriculture, as a general goal, and to define applicability restrictions of the system for sugar beet and other root crops. In the first phase of the research, laboratory experiments were used to develop, test, and consequently improve the data acquisition and processing procedures. In this first phase, the feasibility of detecting sugar beets in soil in laboratory conditions using the reflected energy with a simple threshold approach was confirmed. In the second phase, the potential detectability and size estimation of sugar beets based on the distribution and consistency of backscattered energy amounts obtained in field conditions was researched. Based on the data recorded in field conditions, visual detectability was above 90%, with good correlations between sugar beet positions and energy peak positions. The best correlations between mass of sugar beets and the amounts of backscattered energy exceeded 80%.

In healthy bones, mineralization has to be tightly controlled to avoid pathological phenotypes. In this study, we investigated interactions between 1,25(OH)(2)D-3 (1,25D3) and activin A in the regulation of osteoblast induced mineralization. In human osteoblast cultures, we demonstrated that besides stimulation of mineralization, 1,25D3 also induced activin A, a strong inhibitor of mineralization. Simultaneously, follistatin (FS BGLAP expression upon blocking activin activity in 1,25D3-treated cultures. In conclusion, we demonstrate that 1,25D3 stimulation of mineralization by human osteoblasts is suppressed by concomitant induction of inhibitors of mineralization. Mineralization induction by 1,25D3 may actually be controlled via interplay with activin A and osteocalcin. Finally, this complex regulation of mineralization substantiates the significance of tight control of mineralization to prevent excessive mineralization and consequently reduction in bone quality and strength. J. Cell. Physiol. 228: 2167-2174, 2013. (c) 2013 Wiley Periodicals, Inc.

In healthy bones, mineralization has to be tightly controlled to avoid pathological phenotypes. In this study, we investigated interactions between 1α,25(OH)2 D3 (1,25D3) and activin A in the regulation of osteoblast induced mineralization. In human osteoblast cultures, we demonstrated that besides stimulation of mineralization, 1,25D3 also induced activin A, a strong inhibitor of mineralization. Simultaneously, follistatin (FST), the natural antagonist of activin A, was down-regulated by1,25D3. This resulted in an increase in activin A activity during 1,25D3 treatment. We also showed that in 1,25D3-treated osteoblasts, mineralization can be further increased when activin A activity was abrogated by adding exogenous FST. This observation implies that, besides stimulation of mineralization, 1,25D3 also controls activin A-mediated inhibition of mineralization. Besides activin A, 1,25D3 also induces osteocalcin (BGLAP), another inhibitor of mineralization. Warfarin, which has been shown to inactivate osteocalcin, increased 1,25D3-induced mineralization. Interaction between these two systems became evident from the synergistic increase in BGLAP expression upon blocking activin activity in 1,25D3-treated cultures. In conclusion, we demonstrate that 1,25D3 stimulation of mineralization by human osteoblasts is suppressed by concomitant induction of inhibitors of mineralization. Mineralization induction by 1,25D3 may actually be controlled via interplay with activin A and osteocalcin. Finally, this complex regulation of mineralization substantiates the significance of tight control of mineralization to prevent excessive mineralization and consequently reduction in bone quality and strength.

Reconstruction of the vermilion of the upper lip can be very challenging, especially in tumorous relapse conditions, due to the limited local mucosa available. This accounts even more for resections solely involving mucosa or even skin of the upper lip leaving the orbicularis oris muscle intact. In these cases, an aesthetic reconstruction of the red/white border or the white roll is very hard to achieve. Even the color of the reconstructed vermilion is very important. Sometimes an appealing shape of the cupid bow and color of the “vermilion” can only be achieved by a tattoo. We present a case of multiple vermilion and skin resections of the upper lip due to a lentigo maligna melanoma. In the last step, we had to resect even the whole vermilion mucosa of the upper lip, including parts of the oral mucosa of the vestibule leaving a bare orbicularis oris muscle. Due to the fact that we reconstructed the vermilion of the upper lip several times with local tanspositional flaps or even crosswise pedicled mucosa flaps from the vermilion of the lower lip, we now had to harvest mucosa transplants for the reconstruction of the upper vermilion without impairing lip or cheek function. For this purpose, we performed a mucosa-free flap from genital mucosa (labia minora).

Precise inline process analysis, as an instrument for securing product qualities and enhanced process efficiency, nowadays often requires not only a temporal but also a spatial investigation of relevant physical process parameters. From the variety of available methods that allow for a tempo-spatial medium analysis, a tomographic approach based on capacitive and ultrasonic sensor arrays to monitor multiphase liquid mixtures in-line is discussed in the present contribution. The approach aims for the localization of variable phase boundaries and the physical characterization of spatially distributed phases. Favoring a real time processing a reduced number of transducers in combination with a fast linear modeling is used. Theoretical and experimental results of a layered 3-phase-system illustrate the potential and limit in physical resolution.

There are hints for changes in phospholipid membrane metabolism and structure in the brain of adolescents with anorexia nervosa (AN) using either proton ((1)H) or phosphorus ((31)P) magnetic resonance spectroscopic imaging (MRSI). We aimed to specify these pathological metabolite changes by combining both methods with additional focus on the neuronal metabolites glutamate (Glu) and N-acetyl-l-aspartate (NAA).Twenty-one female patients (mean 14.4 ± 1.9 years) and 29 female controls (mean 16 ± 1.6 years) underwent (1)H and (31)P MRSI at 3 T applied to the centrum semiovale including the anterior cingulate cortex. We assessed gray matter (GM) and white matter (WM) metabolite concentration changes of the frontal and parietal brain measuring choline(Cho)- and ethanolamine(Eth)-containing compounds, Glutamate (Glu) and glutamine (Gln) and their sum (Glx), myoinositol, NAA, and high-energy phosphates.For (1)H MRSI, a clear discrimination between GM and WM concentrations was possible, showing an increase of Glx (p 0.001), NAA (frontal p 0.05), pooled creatine (tCr) (p 0.001), and choline (tCho) (p 0.05) in the GM of AN patients. The lipid catabolites glycerophosphocholine (p 0.07) and glycerophosphoethanolamine (p 0.03) were increased in the parietal region.Significant changes in GM metabolite concentrations were observed in AN possibly triggered by elevated excitotoxin Glu. Increased tCho may indicate modifications of membrane phospholipids due to increased catabolism in the parietal region. Since no significant changes in phosphorylated choline compounds were found for the frontal region, the tCho increase in this region may hint to fluidity changes.

Zusammenfassung Im Rahmen industrieller Anwendungen bietet die nicht-invasive Clamp-On-Konfiguration von UltraschallMesssystemen die Moglichkeit der Prozessanbindung an bereits im Betrieb befindliche Reaktoren oder Rohrsysteme, ohne den Prozess stoppen zu mussen. Trotz unkomplizierter und kostengunstiger Inbetriebnahme birgt das Prinzip auch Nachteile, da aufgrund von Mehrfachreflexionen an den Grenzflachen oder sekundaren Ausbreitungswegen uber die Rohrwand (Festkorper-Storschall) unerwunschte (Stor)-Signale entstehen, die die gesuchten Signalinformationen uberlagern konnen. Die genaue Erfassung der eigentlichen Messgrose ist dadurch erheblich erschwert, im Extremfall sogar unmoglich. Um die Zuverlassigkeit der Clamp-On-Systeme zu verbessern und Storgrosen sicher vom gesuchten Nutzsignal trennen zu konnen, ist eine anspruchsvolle Signalanalyse sowie genaue Kenntnis aller Ausbreitungswege in Abhangigkeit von der Ultraschallwandlerposition und der jeweiligen Ausbreitungseigenschaften notwendig ([1], [2]). Der Beitrag adressiert folglich Phanomene der multimodalen Clamp-On-Schallausbreitung in flussigkeitsgefullten Rohren und stellt dabei als konkrete Anwendung die Ultraschall-Tomografie zur ortsaufgelosten Prozesscharakterisierung in den Mittelpunkt, welche die Applikation mehrerer uber den Umfang verteilter Wandler erfordert. Auf Basis einer reduzierten Modellierung werden mogliche Ausbreitungspfade, SchallLaufzeiten und Mehrfachreflexion im Rohr abgeschatzt. Mit Hilfe erganzender FEM-Analysen soll der Einfluss von Modenkonversionseffekten auf das Messsignal beurteilt und so storende, oftmals dominierende Anteile im Gesamtsignal bewertet werden. Dabei ist von Interesse, inwieweit die Veranderung bestimmter Parameter der Impulsantwort entlang einer definierten Ubertragungsstrecke vorhergesagt oder Zeitfenster im aufgezeichneten Messsignal, in denen keine signifikanten Storeffekte (Mehrfachreflexion, dispersive Schallausbreitung) auftreten, identifiziert werden konnen. Die Arbeiten sollen so dazu beitragen, die Leistungsfahigkeit und Zuverlassigkeit der Clamp-On-Messsysteme zu verbessern und eine grosere Toleranz gegenuber unerwunschten (Stor-)Signalen zu erreichen.

1 alpha,25-dihydroxyitamin D-3 (1,25D3) deficiency leads to impaired bone mineralization. We used the human pre-osteoblastic cell line SV-HFO, which forms within 19 days of culture an extracellular matrix that starts to mineralize around day 12, to examine the mechanism by which 1,25D3 regulates osteoblasts and directly stimulates mineralization. Time phase studies showed that 1,25D3 treatment prior to the onset of mineralization, rather than during mineralization led to accelerated and enhanced mineralization. This is supported by the observation of unaltered stimulation by 1,25D3 even when osteoblasts were devitalized just prior to onset of mineralization and after 1,25D3 treatment. Gene Chip expression profiling identified the pre-mineralization and mineralization phase as two strongly distinctive transcriptional periods with only 0.6% overlap of genes regulated by 1,25D3. In neither phase 1,25D3 significantly altered expression of extracellular matrix genes. 1,25D3 significantly accelerated the production of mature matrix vesicles (MVs) in the pre-mineralization. Duration rather than timing determined the extent of the 1,25D3 effect. We propose the concept that besides indirect effects via intestinal calcium uptake 1,25D3 directly accelerates osteoblast-mediated mineralization via increased production of mature MVs in the period prior to mineralization. The accelerated deposition of mature MVs leads to an earlier onset and higher rate of mineralization. These effects are independent of changes in extracellular matrix protein composition. These data on 1,25D3, mineralization, and MV biology add new insights into the role of 1,25D3 in bone metabolism and emphasize the importance of MVs in bone and maintaining bone health and strength by optimal mineralization status. J. Cell. Physiol. 225: 593-600, 2010. (C) 2010 Wiley-Liss, Inc.

There is an increasing demand for accurate preoperative and intraoperative staging of bronchial carcinoma with respect to neoadjuvant therapy protocols and parenchyma-sparing operations. This study prospectively evaluated accuracy of computed tomographic scan and surgical assessment for staging of bronchial carcinoma in 108 consecutive patients. The stage of the primary tumor (T stage) was correctly determined in 85% of the patients, and surgical evaluation correctly determined the T stage in 92%. Invasion of major mediastinal structures posed a major problem for computed tomographic scan. On a node-by-node basis, computed tomographic scan predicted involvement of lymph nodes in 81% (sensitivity 29%, specificity 93%, positive predictive value 49%, negative predictive value 85%). The surgeon correctly determined the lymph node status in 69% of lymph nodes (sensitivity 90%, specificity 63%, positive predictive value 39%, negative predictive value 96%). On a patient-by-patient basis, computed tomographic scan correctly predicted the nodal status in 58% of patients. Accuracy of computed tomographic scan and surgical assessment in determination of the lymph node status strongly depended on tumor type and lymph node region (hilar or mediastinal region) studied. This was partly due to the fact that adenocarcinomas exhibited a high proportion of tumor-positive normal-sized lymph nodes, whereas squamous cell carcinomas showed a high proportion of enlarged tumor-free lymph nodes. In conclusion, computed tomographic scan and surgical assessment are sufficiently accurate for determination of the tumor stage but are insufficient in determining the nodal status. (J T horac C ardiovasc S urg 1992;104:413-20)

Background and Objective: Guidelines for the treatment of early-onset breast cancer have been proposed in several countries, but to date, their impact on outcomes is unverified. The objective of this study was to evaluate the association between guideline-adherent versus nonadherent treatment and recurrence-free survival (RFS) and overall survival (OAS) in early-onset breast cancer patients. Methods: A total of 1,778 patients were included in the study, of whom 111 were 35 years or younger and 1,667 were between 36 and 55 years. RFS and OAS were compared between the two groups, with respect to multiple parameters. All survival data were adjusted for tumor characteristics and analyzed with respect to guideline adherence according to the German Step 3 guidelines. Results: Statistically significant differences between the two groups (Conclusion: Guideline-adherent treatment for early-onset breast cancer patients significantly improves OAS and RFS and should therefore be demanded for all patients.

The objective of this study was to show differences between breast cancer patientsor =35 and35 years with regard to tumor characteristics and to present the patient-relevant outcomes overall survival (OAS) and recurrence-free survival (RFS).We analyzed data from 119 women aged 35 years or younger with breast cancer and compared multiple parameters against breast cancer patients between 36 and 55 (n = 1,097), all pre-menopausal. Data were adjusted for tumor characteristics and therapy.There was no statistically significant difference in tumor size, axillary lymph node involvement, and histological subtypes. On the contrary, grading lymphovascular invasion and receptor negativity showed statistically significant differences. Unadjusted hazard ratio are 2.11 (1.32-3.39) (OAS) and 1.92 (1.35-2.73) (RFS). Multi-adjusted hazard ratio are 2.97 (1.70-5.18) (OAS) and 2.11 (1.42-3.13) (RFS).In conclusion, young breast cancer patients still have a poor prognosis. Even after adjustment of the data, OAS and RFS showed a worse prognosis. Normal prognostic factors like tumor size, axillary lymph node involvement, and grading can therefore be not the explanation for the more aggressive disease progress within early onset breast cancer patients.

The objective of this research was to develop a non-invasive yield mapping system for sugar beets by applying ultra wideband (UWB) radar technology. Similar to radars used in geological engineering, these devices acquire data via electromagnetic waves. The basic idea was to use such data to identify sugar beets in agricultural soils. The initial research task was to distinguish sugar beets from the surrounding soil.