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Search Results: 1 - 10 of 402149 matches for " Nadja Müller "
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Cost-effectiveness analysis of cognitive behaviour therapy for treatment of minor or mild-major depression in elderly patients with type 2 diabetes: study protocol for the economic evaluation alongside the MIND-DIA randomized controlled trial (MIND-DIA CEA)
Nadja Chernyak, Frank Petrak, Kristin Plack, Martin Hautzinger, Matthias J Müller, Guido Giani, Andrea Icks
BMC Geriatrics , 2009, DOI: 10.1186/1471-2318-9-25
Abstract: Patients will be followed for 15 months. During this period data on health sector costs, patient costs and societal productivity/time costs will be collected in addition to clinical data. Person-years free of moderate/severe major depression, quality adjusted life years (QALYs), and cumulative costs will be estimated for each arm of the trial (CBT, TAU and SH). To determine cost-effectiveness of the CBT, differences in costs and effects between the CBT group and TAU/SH group will be calculated.CBT is a potentially effective treatment option to improve quality of life and to avoid the onset of a moderate/severe major depression in elderly patients with type 2 diabetes and minor or mild-major depression. This hypothesis will be evaluated in the MIND-DIA trial. Based on these results the associated economic evaluation will provide additional evidence on the cost-effectiveness of CBT in this target population. Methodological strengths and weaknesses of the planned economic evaluation are discussed.The MIND-DIA study has been registered at the Current Controlled Trials Register (ISRCTN58007098).Depression is a highly prevalent disorder with a substantial impact on quality of life and societal cost [1,2]. This applies in particular to patients with diabetes, since depression has been shown to be more prevalent among these patients as compared to those without diabetes [3-5]. Major depression and elevated depression symptoms were present, respectively, in 11 and 31% of individuals with diabetes according to a meta-analysis [4]. Previous research demonstrates that comorbid depression in patients with diabetes is associated with poor self care, i.e. adherence to medication, diet, exercise and smoking cessation [6-8], additive functional impairment and work disability [9], poorer glycaemic control [10], higher risk of microvascular and macrovascular complications [11,12], decreased quality of life [13], higher mortality [14,15], increased healthcare utilization and higher cos
SOX2-RNAi attenuates S-phase entry and induces RhoA-dependent switch to protease-independent amoeboid migration in human glioma cells
Felix Oppel, Nadja Müller, Gabriele Schackert, Sandy Hendruschk, Daniel Martin, Kathrin D Geiger, Achim Temme
Molecular Cancer , 2011, DOI: 10.1186/1476-4598-10-137
Abstract: Retroviral shRNA-vectors were utilized to stably knockdown SOX2 in U343-MG and U373-MG cells. The resulting phenotype was investigated by Western blot, migration/invasion assays, RhoA G-LISA, time lapse video imaging, and orthotopic xenograft experiments.SOX2 depletion results in pleiotropic effects including attenuated cell proliferation caused by decreased levels of cyclinD1. Also an increased TCF/LEF-signaling and concomitant decrease in Oct4 and Nestin expression was noted. Furthermore, down-regulation of focal adhesion kinase (FAK) signaling and of downstream proteins such as HEF1/NEDD9, matrix metalloproteinases pro-MMP-1 and -2 impaired invasive proteolysis-dependent migration. Yet, cells with knockdown of SOX2 switched to a RhoA-dependent amoeboid-like migration mode which could be blocked by the ROCK inhibitor Y27632 downstream of RhoA-signaling. Orthotopic xenograft experiments revealed a higher tumorigenicity of U343-MG glioma cells transduced with shRNA targeting SOX2 which was characterized by increased dissemination of glioma cells.Our findings suggest that SOX2 plays a role in the maintenance of a less differentiated glioma cell phenotype. In addition, the results indicate a critical role of SOX2 in adhesion and migration of malignant gliomas.Despite multimodal treatment the prognosis for glioblastoma (GBM), the most common and most malignant brain tumor remains poor, with the majority of patients dying within 1 year after diagnosis [1]. Glioblastomas, gliomas of WHO grade IV, diffusely spread into the surrounding brain and the invading tumor cells migrate along the white matter tracks and assemble satellites around neuron cell bodies, blood vessels and the subpial region [2,3]. Since glioblastoma cells infiltrate wide areas of the brain every resection of the bulk tumor is usually followed by a tumor re-initiation at the resection site or at another place in the brain [4,5]. The cellular origin of glioblastoma is still under investigation and it is h
Tumor Evasion from T Cell Surveillance
Katrin T pfer,Stefanie Kempe,Nadja Müller,Marc Schmitz,Michael Bachmann,Marc Cartellieri,Gabriele Schackert,Achim Temme
Journal of Biomedicine and Biotechnology , 2011, DOI: 10.1155/2011/918471
Abstract: An intact immune system is essential to prevent the development and progression of neoplastic cells in a process termed immune surveillance. During this process the innate and the adaptive immune systems closely cooperate and especially T cells play an important role to detect and eliminate tumor cells. Due to the mechanism of central tolerance the frequency of T cells displaying appropriate arranged tumor-peptide-specific-T-cell receptors is very low and their activation by professional antigen-presenting cells, such as dendritic cells, is frequently hampered by insufficient costimulation resulting in peripheral tolerance. In addition, inhibitory immune circuits can impair an efficient antitumoral response of reactive T cells. It also has been demonstrated that large tumor burden can promote a state of immunosuppression that in turn can facilitate neoplastic progression. Moreover, tumor cells, which mostly are genetically instable, can gain rescue mechanisms which further impair immune surveillance by T cells. Herein, we summarize the data on how tumor cells evade T-cell immune surveillance with the focus on solid tumors and describe approaches to improve anticancer capacity of T cells.
Strategy for Sensitive and Specific Detection of Yersinia pestis in Skeletons of the Black Death Pandemic
Lisa Seifert, Michaela Harbeck, Astrid Thomas, Nadja Hoke, Lothar Z?ller, Ingrid Wiechmann, Gisela Grupe, Holger C. Scholz, Julia M. Riehm
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075742
Abstract: Yersinia pestis has been identified as the causative agent of the Black Death pandemic in the 14th century. However, retrospective diagnostics in human skeletons after more than 600 years are critical. We describe a strategy following a modern diagnostic algorithm and working under strict ancient DNA regime for the identification of medieval human plague victims. An initial screening and DNA quantification assay detected the Y. pestis specific pla gene of the high copy number plasmid pPCP1. Results were confirmed by conventional PCR and sequence analysis targeting both Y. pestis specific virulence plasmids pPCP1 and pMT1. All assays were meticulously validated according to human clinical diagnostics requirements (ISO 15189) regarding efficiency, sensitivity, specificity, and limit of detection (LOD). Assay specificity was 100% tested on 41 clinically relevant bacteria and 29 Y. pseudotuberculosis strains as well as for DNA of 22 Y. pestis strains and 30 previously confirmed clinical human plague samples. The optimized LOD was down to 4 gene copies. 29 individuals from three different multiple inhumations were initially assessed as possible victims of the Black Death pandemic. 7 samples (24%) were positive in the pPCP1 specific screening assay. Confirmation through second target pMT1 specific PCR was successful for 4 of the positive individuals (14%). A maximum of 700 and 560 copies per μl aDNA were quantified in two of the samples. Those were positive in all assays including all repetitions, and are candidates for future continuative investigations such as whole genome sequencing. We discuss that all precautions taken here for the work with aDNA are sufficient to prevent external sample contamination and fulfill the criteria of authenticity. With regard to retrospective diagnostics of a human pathogen and the uniqueness of ancient material we strongly recommend using a careful strategy and validated assays as presented in our study.
Alterations of White Matter Integrity Related to the Season of Birth in Schizophrenia: A DTI Study
Stéphanie Giezendanner, Sebastian Walther, Nadja Razavi, Claudia Van Swam, Melanie Sarah Fisler, Leila Maria Soravia, Jennifer Andreotti, Simon Schwab, Kay Jann, Roland Wiest, Helge Horn, Thomas J?rg Müller, Thomas Dierks, Andrea Federspiel
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075508
Abstract: In schizophrenia there is a consistent epidemiological finding of a birth excess in winter and spring. Season of birth is thought to act as a proxy indicator for harmful environmental factors during foetal maturation. There is evidence that prenatal exposure to harmful environmental factors may trigger pathologic processes in the neurodevelopment, which subsequently increase the risk of schizophrenia. Since brain white matter alterations have repeatedly been found in schizophrenia, the objective of this study was to investigate whether white matter integrity was related to the season of birth in patients with schizophrenia. Thirty-four patients with schizophrenia and 33 healthy controls underwent diffusion tensor imaging. Differences in the fractional anisotropy maps of schizophrenia patients and healthy controls born in different seasons were analysed with tract-based spatial statistics. A significant main effect of season of birth and an interaction of group and season of birth showed that patients born in summer had significantly lower fractional anisotropy in widespread white matter regions than those born in the remainder of the year. Additionally, later age of schizophrenia onset was found in patients born in winter months. The current findings indicate a relationship of season of birth and white matter alterations in schizophrenia and consequently support the neurodevelopmental hypothesis of early pathological mechanisms in schizophrenia.
Cytotoxicity of Tumor Antigen Specific Human T Cells Is Unimpaired by Arginine Depletion
Markus Munder, Melanie Engelhardt, Diana Knies, Sergej Medenhoff, Guido Wabnitz, Claudia Luckner-Minden, Nadja Feldmeyer, Ralf-Holger Voss, Pascale Kropf, Ingrid Müller, Roland Conradi, Yvonne Samstag, Matthias Theobald, Anthony D. Ho, Hartmut Goldschmidt, Michael Hundemer
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0063521
Abstract: Tumor-growth is often associated with the expansion of myeloid derived suppressor cells that lead to local or systemic arginine depletion via the enzyme arginase. It is generally assumed that this arginine deficiency induces a global shut-down of T cell activation with ensuing tumor immune escape. While the impact of arginine depletion on polyclonal T cell proliferation and cytokine secretion is well documented, its influence on chemotaxis, cytotoxicity and antigen specific activation of human T cells has not been demonstrated so far. We show here that chemotaxis and early calcium signaling of human T cells are unimpaired in the absence of arginine. We then analyzed CD8+ T cell activation in a tumor peptide as well as a viral peptide antigen specific system: (i) CD8+ T cells with specificity against the MART-1aa26–35*A27L tumor antigen expanded with in vitro generated dendritic cells, and (ii) clonal CMV pp65aa495–503 specific T cells and T cells retrovirally transduced with a CMV pp65aa495–503 specific T cell receptor were analyzed. Our data demonstrate that human CD8+ T cell antigen specific cytotoxicity and perforin secretion are completely preserved in the absence of arginine, while antigen specific proliferation as well as IFN-γ and granzyme B secretion are severely compromised. These novel results highlight the complexity of antigen specific T cell activation and demonstrate that human T cells can preserve important activation-induced effector functions in the context of arginine deficiency.
Our Economy  [PDF]
Christian Müller*
Modern Economy (ME) , 2011, DOI: 10.4236/me.2011.24063
Abstract: I discuss the strengths and weaknesses of the current predominant approach to macroeconomic modelling of asset prices and suggest an alternative perspective. This alternative rests on the insight that the economy is the result of individual decisions. The industry standard has it, however, that individual action is ruled by objective, general laws instead. Changing the point of view allows to reconcile numerous puzzles and paves the way for a promising new research agenda.
Improved Variance Reduced Monte-Carlo Simulation of in-the-Money Options  [PDF]
Armin Müller
Journal of Mathematical Finance (JMF) , 2016, DOI: 10.4236/jmf.2016.63029
Abstract: Pricing derivatives with Monte-Carlo simulations involve standard errors that typically decrease at a rate proportional to\"\" where N is the sample size. Several approaches have been discussed to reduce the empirical variance for a given sample size. This article analyzes the joint application of the put-call-parity approach and importance sampling to variance reduced option pricing. For this purpose, we examine non-path-dependent and path-dependent options. For European options, we observe dramatic variance reduction, especially for in-the-money options. Also for arithmetic Asian options, a significant variance reduction is achieved.
Methodologies of Biophysical Wound Healing Therapies  [PDF]
Jacquelyn Dawn Parente, Margareta Müller, Knut Mller
Journal of Biomedical Science and Engineering (JBiSE) , 2016, DOI: 10.4236/jbise.2016.910B022
Abstract:
Purpose: To evaluate the effects of methodological variation of biophysical therapies on wound healing outcomes, as a preliminary study to develop a composite wound healing device. Methods: A literature search was focused on the variable devices, sys-tem configurations, input parameters, and treatment durations of negative pressure wound therapy (NPWT), electrical stimulation (ES), and low-level light therapy (LLLT) from 2011 to July 2016. Results: In NPWT, lower vacuum pressures of ?50 and ?80 mmHg achieved similar tissue perfusion outcomes as earlier recommendations of ?125 mmHg, while there is no established regimen with respect to continuous, square wave, or triangular NP waveform due to inconsistent results. Use of wound filler may contribute to improved tissue granulation when compared to topical NP. An ES configuration of high-voltage pulsed current with the stimulation electrode placed in the wound bed best resembles the endogenous skin current, which guides cellular migration. However, no studies have established optimal stimulation parameters. For LLLT, laser and LED proved similarly effective. Although red light has been almost exclusively used in human pressure ulcer treatment, studies comparing blue, green, and red wavelengths more consistently show biological effects using green light. Conclu-sions: Variation in the application of mechanical, electrical, and radiant energies may be used to modulate wound healing pathways. To 2012, no studies have examined use of these biophysical modalities in combination. Further methodological studies with a systems approach would help define optimal treatment protocols for improved wound healing outcomes in clinical practice.
Diphenyl methane laxatives do not induce electrolyte imbalance  [PDF]
Stefan Müller-Lissner
Open Journal of Gastroenterology (OJGas) , 2013, DOI: 10.4236/ojgas.2013.35046
Abstract: Aim: To analyse whether there are changes in sodium and potassium serum levels during chronic treatment with the diphenyl methanes bisacodyl and sodium picosulfate. Methods: A literature search was done using PubMed, and the reference lists of pertinent papers were screened for additional studies. Only studies of at least 4 weeks duration were considered for further analysis. Results: Four relevant studies were identified. In three randomised controlled trials with 5 to 10 mg daily of bisacodyl or sodium picosulfate, respectively, over four weeks no electrolyte losses were found. Hypokalemia was also not a problem in a group of patients with paraplegia using bisacodyl suppositories for 2 to 34 years. Conclusions: Electrolyte losses, particularly hypokalemia, are not a problem when bisacodyl or sodium picosulfate are used long-term.
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