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This study used confirmatory factor analyses and descriptive statistics on new data from 345 dual study graduates in Germany to further assess a newly developed and recently published self-report inventory of employability. The resulting 19-item inventory showed a good model fit and factorial validity, with small to medium interscale correlations. This provides a solid base for further research and a targeted tool for assessing dual study graduates’ employability. Limitations and future research scope are discussed.

Localized jawbone invasion is a milestone in the progression of oral squamous cell carcinoma (OSCC). The factors that promote this process are not well understood. Sclerostin is known to be involved in bone metabolism and there are preliminary reports of its involvement in bone tumors and bone metastasis. To identify a possible involvement of sclerostin in the bone invasion process of OSCC, sclerostin expression was analyzed in vitro in two different human OSCC tumor cell lines by quantitative real-time polymerase chain reaction (qRT-PCR), and the effect of recombinant human (rh)-sclerostin treatment on tumor cell capabilities was evaluated using proliferation, migration, and invasion assays. Undifferentiated human mesenchymal stem cells (hMSCs) were osteogenically differentiated and co-cultured with OSCC tumor cells to demonstrate potential interactions and migration characteristics. Sclerostin expression was evaluated in clinical cases by immunohistochemistry at the OSCC–jawbone interface in a cohort of 15 patients. Sclerostin expression was detected in both OSCC tumor cell lines in vitro and was also detected at the OSCC–jawbone interface in clinical cases. Tumor cell proliferation rate, migration and invasion ability were increased by rh-sclerostin treatment. The migration rate of tumor cells co-cultured with osteogenically differentiated hMSCs was increased. The results presented are the first data suggesting a possible involvement of sclerostin in the bone invasion process of OSCC, which deserves further investigation and may be a potential approach for drug-based tumor therapy.

Die Potenziale eines dualen Studiums führen zur Annahme, dass Absolventen und Absolventinnen über eine hohe Employability verfügen und sie damit gute Chancen bei der Erhaltung und Aufrechterhaltung einer Beschäftigung nach dem Studium haben. Um diese Annahme zu überprüfen, wurde ein Inventar entwickelt und mit Studierenden der Dualen Hochschule Baden-Württemberg erprobt. Zur Analyse der Daten wurden Hauptkomponentenanalysen, konfirmatorische Faktorenanalysen und ein Mann-Whitney-U-Test eingesetzt. In zwei Studien wurde ein reliables und valides Instrument entwickelt. Die Ergebnisse werden vor dem Hintergrund ihrer Anwendung in der Praxis diskutiert.

Additive manufacturing is well established for plastics and metals, and it gets more and more implemented in a variety of industrial processes. Beside these well-established material platforms, additive manufacturing processes are highly interesting for ceramics, especially regarding resource conservation and for the production of complex three-dimensional shapes and structures with specific feature sizes in the µm and mm range with high accuracy. The usage of ceramics in 3D printing is, however, just at the beginning of a technical implementation in a continuously and fast rising field of research and development. The flexible fabrication of highly complex and precise 3D structures by means of light-induced photopolymerization that are difficult to realize using traditional ceramic fabrication methods such as casting and machining is of high importance. Generally, slurry-based ceramic 3D printing technologies involve liquid or semi-liquid polymeric systems dispersed with ceramic particles as feedstock (inks or pastes), depending on the solid loading and viscosity of the system. This paper includes all types of photo-curable polymer-ceramic-mixtures (feedstock), while demonstrating our own work on 3D printed alumina toughened zirconia based ceramic slurries with light induced polymerization on the basis of two-photon absorption (TPA) for the first time. As a proven exemplary on cuboids with varying edge length and double pyramids in the µm-range we state that real 3D micro-stereolithographic fabrication of ceramic products will be generally possible in the near future by means of TPA. This technology enables the fabrication of 3D structures with high accuracy in comparison to ceramic technologies that apply single-photon excitation. In sum, our work is intended to contribute to the fundamental development of this technology for the representation of oxide-ceramic components (proof-of-principle) and helps to exploit the high potential of additive processes in the field of bio-ceramics in the medium to long-term future.

Polyelectrolyte multilayers (PEM) are versatile tools used to investigate fundamental interactions between material-related parameters and the resulting performance in stem cell differentiation, respectively, in bone tissue engineering. In the present study, we investigate the suitability of PEMs with a varying collagen content for use as drug carriers for the human bone morphogenetic protein 2 (rhBMP-2). We use three different PEM systems consisting either of the positively charged poly-L-lysine or the glycoprotein collagen type I and the negatively charged glycosaminoglycan heparin. For a specific modification of the loading capacity and the release kinetics, the PEMs were stepwise cross-linked before loading with cytokine. We demonstrate the possibility of immobilizing significant amounts of rhBMP-2 in all multilayer systems and to specifically tune its release via cross-linking. Furthermore, we prove that the drug release of rhBMP-2 plays only a minor role in the differentiation of osteoprogenitor cells. We find a significantly higher influence of the immobilized rhBMP-2 within the collagen-rich coatings that obviously represent an excellent mimicry of the native extracellular matrix. The cytokine immobilized in its bioactive form was able to achieve an increase in orders of magnitude both in the early stages of differentiation and in late calcification compared to the unloaded layers.

The aim of the present study was to develop a collagen/heparin-based multilayer coating on titanium surfaces for retarded release of recombinant human bone morphogenic protein 2 (rhBMP2) to enhance the osteogenic activity of implant surfaces. Polyelectrolyte multilayer (PEM) coatings were constructed on sandblasted/acid-etched surfaces of titanium discs using heparin and collagen. PEM films of ten double layers were produced and overlayed with 200 µL of a rhBMP2 solution containing 15 µg rhBMP2. Subsequently, cross-linking of heparin molecules was performed using EDC/NHS chemistry to immobilize the incorporated rhBMP2. Release characteristics for 3 weeks, induction of Alkaline Phosphatase (ALP) in C2C12 cells and proliferation of human mesenchymal stem cells (hMSCs) were evaluated to analyze the osteogenic capacity of the surface. The coating incorporated 10.5 µg rhBMP2 on average per disc and did not change the surface morphology. The release profile showed a delivery of 14.5% of the incorporated growth factor during the first 24 h with a decline towards the end of the observation period with a total release of 31.3%. Cross-linking reduced the release with an almost complete suppression at 100% cross-linking. Alkaline Phosphatase was significantly increased on day 1 and day 21, indicating that the growth factor bound in the coating remains active and available after 3 weeks. Proliferation of hMSCs was significantly enhanced by the non-cross-linked PEM coating. Nanocoating using collagen/heparin-based PEMs can incorporate clinically relevant amounts of rhBMP2 on titanium surfaces with a retarded release and a sustained enhancement of osteogenic activity without changing the surface morphology.

The layer-by-layer (LbL) self-assembly technique is an effective method to immobilize components of the extracellular matrix (ECM) such as collagen and heparin onto, e.g., implant surfaces/medical devices with the aim of forming polyelectrolyte multilayers (PEMs). Increasing evidence even suggests that cross-linking influences the physicochemical character of PEM films since mechanical cues inherent to the substrate may be as important as its chemical nature to influence the cellular behavior. In this study, for the first-time different collagen/heparin films have been prepared and cross-linked with EDC/NHS chemistry. Quartz crystal microbalance, zeta potential analyzer, diffuse reflectance Fourier transform infrared spectroscopy, atomic force microscopy and ellipsometry were used to characterize film growth, stiffness, and topography of different film systems. The analysis of all data proves a nearly linear film growth for all PEM systems, the efficacy of cross-linking and the corresponding changes in the film rigidity after cross-linking and an appropriate surface topography. Furthermore, preliminary cell culture experiments illustrated those cellular processes correlate roughly with the quantity of newly created covalent amide bonds. This allows a precise adjustment of the physicochemical properties of the selected film architecture regarding the desired application and target cells. It could be shown that collagen improves the biocompatibility of heparin containing PEMs and due to their ECM-analogue nature both molecules are ideal candidates intended to be used for any biomedical application with a certain preference to improve the performance of bone implants or bone augmentation strategies.

Abstract Background Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related deaths worldwide and is primarily treated with radiation, surgery, and platinum-based drugs like cisplatin and carboplatin. The major challenge in the treatment of NSCLC patients is intrinsic or acquired resistance to chemotherapy. Molecular markers predicting the outcome of the patients are urgently needed. Methods Here, we employed patient-derived xenografts (PDXs) to detect predictive methylation biomarkers for platin-based therapies. We used MeDIP-Seq to generate genome-wide DNA methylation profiles of 22 PDXs, their parental primary NSCLC, and their corresponding normal tissues and complemented the data with gene expression analyses of the same tissues. Candidate biomarkers were validated with quantitative methylation-specific PCRs (qMSP) in an independent cohort. Results Comprehensive analyses revealed that differential methylation patterns are highly similar, enriched in PDXs and lung tumor-specific when comparing differences in methylation between PDXs versus primary NSCLC. We identified a set of 40 candidate regions with methylation correlated to carboplatin response and corresponding inverse gene expression pattern even before therapy. This analysis led to the identification of a promoter CpG island methylation of LDL receptor-related protein 12 (LRP12) associated with increased resistance to carboplatin. Validation in an independent patient cohort (n = 35) confirmed that LRP12 methylation status is predictive for therapeutic response of NSCLC patients to platin therapy with a sensitivity of 80% and a specificity of 84% (p

Following publication of the original article [1], we have been alerted to errors in Figs. 2 and 8. In Fig. 2B, the GAPDH loading control for Hec1A cells is shown twice in error (in Fig. 2B and Fig. 2C). In Fig. 8, in testis case 1 (first column) the MAGE-A4 staining panel was repeated and also appears as the NY-ESO-1 staining panel in error. The corrected versions of Fig. 2 and Fig. 8 are shown below. We apologize for this inconvenience.

Circulating cell-free DNA (cfDNA) released from cancerous tissues has been found to harbor tumor-associated alterations and to represent the molecular composition of the tumor. Recent advances in technologies, especially in next-generation sequencing, enable the analysis of low amounts of cfDNA from body fluids. We analyzed the exomes of tumor tissue and matched serum samples to investigate the molecular representation of the tumor exome in cfDNA. To this end, we implemented a workflow for sequencing of cfDNA from low serum volumes (200 μl) and performed whole-exome sequencing (WES) of serum and matched tumor tissue samples from six non-small cell lung cancer (NSCLC) patients and two control sera. Exomes, including untranslated regions (UTRs) of cfDNA were sequenced with an average coverage of 68.5x. Enrichment efficiency, target coverage, and sequencing depth of cfDNA reads were comparable to those from matched tissues. Discovered variants were compared between serum and tissue as well as to the COSMIC database of known mutations. Although not all tissue variants could be confirmed in the matched serum, up to 57% of the tumor variants were reflected in matched cfDNA with mutations in PIK3CA, ALK, and PTEN as well as variants at COSMIC annotated sites in all six patients analyzed. Moreover, cfDNA revealed a mutation in MTOR, which was not detected in the matched tissue, potentially from an untested region of the heterogeneous primary tumor or from a distant metastatic clone. WES of cfDNA may provide additional complementary molecular information about clinically relevant mutations and the clonal heterogeneity of the tumors.

BACKGROUND:Management of cardiac surgery patients is a very standardized procedure in respective local institutions. Yet only very limited evidence exists concerning optimal indication, safety and efficacy of hemodynamic monitoring catecholamine and fluid therapy. METHODS:Between April and May 2013, all 81 German anaesthesia departments involved in cardiac surgery care were asked to participate in a questionnaire addressing the institutional specific current practice in hemodynamic monitoring, catecholamine and volume therapy. RESULTS:51 (63%) questionnaires were completed and returned. All participating centers used basic hemodynamic monitoring (i.e. invasive arterial blood pressure and central venous pressure), supplemented by transesophageal echocardiography. Pulmonary arterial catheter and calibrated trend monitoring devices were also routinely available. In contrast, non-calibrated trend monitoring and esophageal doppler ultrasound devices were not commonly in use. Cerebral oximetry is increasingly emerging, but lacks clear indications. The majority of patients undergoing cardiac surgery, especially in university hospitals, required catecholamines during perioperative care, In case of low cardiac output syndrome, dobutamine (32%), epinephrine (30%) or phosphodiesterase inhibitors (8%) were first choice. In case of hypotension following vasoplegia, norepinephrine (96%) represented the most common catecholamine. 88% of the participating centers reported regular use of colloid fluids, with hydroxyethyl starches (HES) being first choice (64%). CONCLUSIONS:Choice of hemodynamic monitoring is homogenous throughout German centers treating cardiac surgery patients. Norepinephrine is the first line catecholamine in cases of decrease in peripheral vascular resistance. However, catecholamine choice for low cardiac output syndrome varies considerably. HES was the primary colloid used for fluid resuscitation. After conduct of this survey, HES use was restricted by European regulatory authorities in critically ill patients and should only be considered as second-line fluid in surgical patients without renal impairment or severe coagulopathy. Large clinical studies addressing catecholamine and fluid therapy in cardiac surgery patients are lacking.