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Research Database

A research database is being implemented to inform about the on-going or closed research projects at Karl Landsteiner University of Health Sciences.

This database is in the status of work in progress.

Projects

  • Pseudomonas aeruginosa

    Development of an electrochemical sensor for the rapid detection of Pseudomonas aeruginosa in hospitals

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB)
    • Project Number: LSC17_015
    • Project Lead: Martin Brandl, Danube University Krems / Center for Integrated Sensor Systems
    • Project Partner: Karl Landsteiner University of Health Sciences / Institute of Hygiene and Microbiology (University Hospital St. Pölten)
    • Duration: 36 months starting from 01.01.2019

    Background

    Pseudomonas aeruginosa is a high-risk bacterial pathogen. Therefore, rapid detection and further identification are important targets in medicine, food industry and drinking water hygiene to ensure public health and safety. P. aeruginosa is a widely spread soil and water bacterium and is regarded as a major hospital germ. Infections with P. aeruginosa are a common cause of morbidity and mortality worldwide. Current methods for detection are often based on classical cultivation, microscopic and biochemical analyzes, and also molecular methods are increasingly used. However, all of these procedures are often time-consuming, expensive, require special equipment and trained personnel. An electrochemical methodology for a Pseudomonas detector is to be developed in the planned NFB project. This biosensor can facilitate the detection of P. aeruginosa as a "pretester" and as an early warning system accelerate the
    overall diagnosis of this bacterial pathogen. In the cultivation of the bacterium on cetrimide agar, the release of pyocyanin, a blue-green secondary metabolite, which is specifically produced by P. aeruginosa, results in colored colonies. However, pyocyanine also has redox-active properties and, therefore, can be used for a specific, electrochemical detection of these bacteria. The electroactive properties of pyocyanine can be determined with different voltametric and amperometric methods, e.g. cyclic voltammetry. This bacterial secondary metabolite serves as a starting point for the development of methods, which is carried out at the Danube University Krems, Center for Integrated Sensor Systems, Working Group "Water and Environmental Sensors". The developed procedure is then to be tested with hospital samples from the Clinic Institute for Hygiene and Microbiology, University Hospital St. Pölten. Finally, the results obtained from the detected infection exciter are to be evaluated by the novel sensor and the validated hospital analysis.

  • Vibrio Cholerae

    An innovative strategy for the quantification and prediction of toxigenic and non-toxigenic Vibrio cholerae in environmental water resources

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2017
    • Project Number: LSC17_007
    • Project Lead: Alexander Kirschner, Karl Landsteiner University of Health Sciences / Division Water Quality and Health
    • Project Partner: Technische Universität Wien / IFA Tulln Working Group Molecular Diagnostics, Lower Austrian Government / Department of Environmental Hygiene, Medical University of Vienna / Institute for Hygiene and Applied Immunology
    • Duration: 36 months starting from 01.01.2019

    Background

    Vibrio cholerae is a natural inhabitant of aquatic ecosystems and the causative agent of the devastating disease cholera. Cholera is caused by toxigenic strains belonging to the serogroups O1 and O139. However nontoxigenic V.cholerae (NTVC) cause several other kinds of infections with potential fatal outcome. In the past 20 years, NTVC infections have been significantly increasing in Europe in association with global warming. In Lower Austria, two extreme cases occurred for the first time in 2015. Both cases were associated with bathing activities during an extreme summer heatwave. To date, the decisive factors controlling NTVC occurrence in inland bathing waters are not clear. Such information and the availability of reliable NTVC quantification methods are prerequisite to enable prediction models and early warning systems of NTVC occurrence. Besides cultivation on microbiological media, molecular and cell-based methods have been developed. So far, cell-based detection combining fluorescence labelling (FISH) and solid phase cytometry (SPC) proved most successful for NTVC quantification. However, FISH/SPC does not differentiate V.cholerae from closely related species, and it is extremely labor intensive and expensive. In this project, an approach based on alternative molecular recognition molecules –APTAMERS– are proposed. Aptamers are short oligonucleotides that bind their target with high selectivity and affinity. They have proven equally efficient as antibodies in many applications. Once an aptamer is identified, unlimited amounts can be produced at low costs. To date, however, there are no aptamers available for V.cholerae. Two main goals shall be achieved. First, NTVC abundance shall be comprehensively monitored with state-of-the-art methods along environmental and spatiotemporal gradients in representative bathing waters, and second, a new cutting-edge aptamer technology shall be developed for tailored quantification of NTVC and V.cholerae O1/O139. Prediction models of NTVC abundance in bathing waters shall be delivered as tools for risk assessment and easy protocols for culture-independent quantification of V.cholerae. This will significantly contribute to improved disease preparedness and public health concerning NTVC in bathing waters and toxigenic V.cholerae in water resources. The resulting aptamer products, applications and intellectual property may be exploited in follow-up translational projects, in form of spin-off companies or transfer to local third-party enterprises. The proposal is directly contributing to the prioritised research area “Intelligent Indication Systems and Diagnostics” within the recent FTI strategy for Lower Austria. Sustainable collaborations will be stimulated between the project partners within the Interuniversity Cooperation Centre Water & Health, a research centre to pioneer cutting edge water quality research. Thus, the project will contribute in a sustainable manner to the welfare of Lower Austria.

  • Reproducing biological tissues

    Reproducing biological tissues in terms of their mechanical properties by means of 3D printing

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Science Call Dissertation 2017
    • Project Number: SC17_016
    • Project Lead: Dieter Pahr, Karl Landsteiner University of Health Sciences / Division Biomechanics
    • Duration: 36 months starting from 01.12.2018

    Background

    3D printing, also known as additive manufacturing (AM) or rapid prototyping, has become a highly versatile tool with a broad range of applications, such as manufacturing, art, design, and medicine. In the field of biomedical engineering AM has not only gained wide popularity in tissue engineering for printing scaffolds and in biomechanics for patient-specific prostheses, but it has also been proposed as an instrument for fabricating realistic 3D models. For example, individual modelling of patient-specific conditions via AM poses an excellent opportunity for surgeons to practice procedures beforehand. Studies have shown that in doing so operation time is reduced and the physician's confidence is increased, resulting in shorter times of radiation exposure and lower costs. Although 3D modelling approaches for pre-surgical planning have been reported previously, a closer look, concerning the mechanical properties of the printed materials, is still required. Currently, these models lack accurate representation of the tissue biomechanics. This demands a procedure for fine-tuning the mechanical properties of the 3D printed materials to closely match the in vivo conditions. In this project, 3D printing is applied to the task of producing materials that closely imitate biological tissues, and organ-like structures, in terms of their mechanical properties. The printed tissues can be patient-specific for pre-surgical planning, as well as standardized for applications in research dealing with advancing novel operating techniques, implant technology, and other medical devices. One of the incentives is to thereby limit the demand of donor organs and reduce variability of the organs used in research. Due to the fact that the capabilities of 3D printing are currently rapidly increasing, this research can also be seen as the groundwork for even more applications concerning printed organs that might be possible with future technology. The key objectives of this project are:
    the establishment of a testing protocol for acquiring characteristic biomechanical parameters of different tissues, the development of software tools for attaining these parameters in 3D printed structures (based on suitable material combinations and spatial distribution thereof, plus post-processing procedures), the printing of these tissue replicas alongside the validation of their mechanical properties via comparison with the actual tissue characteristics. All instructions for manufacturing these models are to be contained in a so-called “toolbox”.

  • Iron metabolism of the human placenta

    Iron metabolism of the human placenta – the key to understand iron transfer from the mother to the fetus

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2017
    • Project Number: LSC17_008
    • Project Lead: Hans Salzer, Karl Landsteiner University of Health Sciences / Division of Paediatrics (University Hospital Tulln)
    • Project Partner: Medical University of Vienna / Institute of Medical Genetics, Landesklinikum Mistelbach / Department of Pediatrics and Adolescent Medicine
    • Duration: 36 months starting from 05.11.2018

    Background

    Background:
    Iron is an essential trace element that is required by all cells, but toxic when present in excess. Iron deficiency is the most common form of micronutritional deficiency worldwide. Preterm infants as well as pregnant women are most likely to suffer from it. During pregnancy, the placenta is the major interface of nutritional exchange between mother and developing fetus. Although mammalian iron metabolism is in general very well characterized, surprisingly little is known about iron metabolism and transfer in the human placenta.
    Aims:
    Inspired by the substantial gaps of knowledge on human placental iron metabolism and by our preliminary data on human placenta, we aim to study:
    (1) The iron metabolism and transport in human placentas and appropriate cell models.
    (2) The iron status of healthy mother-child-pairs in relation to placental expression of proteins involved in iron metabolism as well as in relation to placental iron.
    Methods:
    In the proposed study, which is based on overall 105 healthy, non-anemic mother-child-pairs, iron status of pregnant women and neonates in relation to placental expression and localization of iron metabolising and transporting proteins is investigated. In vitro experiments with human placental cells (primary trophoblast cells, Hofbauer cells, primary placental endothelial cells, and the two placental cell lines BeWo and HUVEC) will be conducted to examine and confirm the involvement of TFR1, FPN1, ZIP8 and other (to be selected) candidate proteins in placental iron metabolism and transport.
    Innovation:
    The proposed study is the first, which combines iron status of mother-child-pairs with extensive basic research (protein expression, function, and localization) on human placentas. The key proteins involved in human placental iron metabolism and transport will be examined for the first time together. The study is based on a comparably large number of mother-child-pairs. With the proposed study we aim to add new knowledge on human placental iron metabolism and transfer. We expect long-term benefits arising from this innovative approach, which will enable us in the long run to optimize the therapy of maternal and preterm iron deficiency.

  • Knee Osteoarthritis

    Motor Learning in Knee Osteoarthritis Therapy - A New Rehabilitation Approach

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2017
    • Project Number: LSC17_014
    • Project Lead: Barbara Wondrasch, FH St. Pölten / Institute of Health Sciences
    • Project Partner: Orthopaedic Hospital Vienna-Speising, Danube University Krems / Faculty of Health and Medicine, Karl Landsteiner University of Health Sciences / Division of Trauma Surgery (University Hospital St. Pölten)
    • Duration: 36 months starting from 01.11.2018

    Background

    Background
    Osteoarthrosis (OA) is a disease of the joint originating from the articular cartilage, the joint capsule and the subchondral bone and is the most common joint disease worldwide. The knee joint is most commonly affected and in addition to the individual impairments due to pain, reduced joint function and restrictions in daily life as well as in sports activities, OA also leads to very high socio-economic burdens (pain medication, operations and rehabilitation stays, sick leave, early retirement). The literature shows that the conservative therapy, and especially the physiotherapy, wins increasingly significance, as it leads to a short-term reduction of symptoms and improvement of the symptoms. The focus of physiotherapy includes on the one hand passive measures for improvement of cartilage metabolism, on the other hand, a neuromuscular training to improve the joint function.
    In addition to the local changes in the joint structures in the knee joint, however, there are also changes in the central nervous system leading to altered movement behavior, which in turn increases the intra-articular load. Until now physiotherapy does not take have these central changes into account, maybe a reason for the unsatisfactory long-term results of the knee joint function.
    Objective and content:
    The local structural and central neuronal changes of VKB (anterior cruciate ligament insufficiency) patients and knee osteoarthritis patients are very similar; therefore, the aim of this project is to examine the influence of special feedback forms on the knee joint functions in patients with knee arthrosis.
    Method:
    A randomized clinical trial will be conducted with two groups of patients. The control group receives a standard physiotherapy program, while the intervention group with special physiotherapy program receives feedback techniques. The program is performed in the form of booster sessions, i.e. units over 3 months. For the evaluation, outcome parameters are used which are in line with the requirements of the international classification of Functioning, Disability and Health (ICF).

  • Digitisation as a chance for restoration and visualisation

    Digitisation as a chance for restoration and visualisation – A pilot study on the 30,000 year old double burial of newborns from Krems-Wachtberg

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), FTI Call 2017
    • Project Number: FTI17-010
    • Project Lead: Dieter Pahr, Karl Landsteiner University of Health Sciences / Division Biomechanics
    • Project Partner: Museum of Natural History Vienna / Department of Anthropology, Danube University Krems / Collection Studies and Management, Austrian Academy of Science / Institute for Oriental and European Archaeology
    • Duration: 24 months starting from 01.11.2018

    Background

    The discovery of the more than 30,000 years old ritual double burial of two neonates at the Krems-Wachtberg site in 2005 has evoked much attention not only by the media and the general public, but also from the international scientific community as findings of sub adults of ancient humans are, on a global scale, extremely rare occasions. After the discovery and exposure the ritual burial was carefully recovered as a block, and the fragile specimens were stored to keep its original excellent condition. In 2015 the recovered block was excavated, documenting each single step with state-of-the art methods.
    Digitisation is now aimed for to enable analyses, restoration and also visualisation. Currently, the only non-destructive way to make a digital copy and visualize the remains is high-resolution micro-computed tomography imaging. It allows 3D reconstruction of the surface as well as the inner micro-structure - making it possible to “uncover the invisible”. Such a device has been installed at the division for Biomechanics of KL University as part of the Core Facility at Campus Krems. This will overcome the current restrictions of analysis and allows a digitisation of the findings for future analysis.
    Together with the available light scanning data from the excavation the whole assembly can be reconstructed. Apart from 3-dimensional reconstruction it will be possible to restorate the chaîne operatoire of activities which were part of this burial process, as well as the post-sedimentary formation processes (4D = modelling the development through time).
    In addition to the reconstruction of the burial, up-to-date documentation and archiving of the data is of utmost importance to lay a basis for further research. Thus, one of the main objectives of this pilot project is to set up a catalogue of criteria for a long term, open-source data repository which provides access to all the data regarding the excavation and findings for larger groups of scientists beyond disciplinary borders.
    Digitisation of the Krems-Wachtberg double burial is challenging in all respects and requires a variety of experts to deal with the many aspects that are inherent in such a spectacular discovery. For the first time, it is possible to investigate this outstanding find from Krems-Wachtberg under the leadership of Lower Austrian research institutions. As one of its main targets, the proposed project will contribute to a further professionalization in Collection Management and Museology – one of the areas of Lower Austrian FTI strategy – and it will significantly improve the visibility of cultural heritage in Lower Austria by latest technical developments that allow for scientific exploitation on an international level.

  • HIPStar

    Obesity-specific joint center estimation in gait analysis

    • Funding Institution / Call: FWF Austrian Science Fund
    • Project Number: P 30923-B30
    • Project Lead: Brian Horsak, FH St. Pölten / Institute of Health Sciences
    • Project Partner: Karl Landsteiner University of Health Sciences / Division Biomechanics, Medical University of Vienna / Department of Pediatrics and Adolescent Medicine, Orthopaedic Hospital Vienna-Speising
    • Duration: 36 months starting from 01.10.2018

    Background

    Gait analysis aims at gathering quantitative information about the mechanics of the musculo-skeletal system during locomotion. Typically, in gait analysis, variables such as kinematics, joint moments, and powers are determined. This information is used to evaluate pathological gait patterns. Errors in locating the three-dimensional (3D) position of the hip joint center (HJC) can strongly affect the calculation of 3D gait analysis variables. This consequentially leads to incorrect interpretations. The problem of inaccuracy in HJC location increases significantly in patients where bony landmarks are difficult to identify, such as in overweight or obese populations. Nevertheless, gait analysis remains as the state of the art method for clinicians and for researchers. Often medical imaging-based methods are recommended to identify the 3D HJC localization. However, some of those methods expose patients to radiation or are expensive and time-consuming. Therefore, non-invasive predictive methods, based on experimental data, or functional models were introduced in recent years to estimate the position of the HJC. Researcher has attempted to evaluate which of these methods best determine the HJC most accurately in various populations. Among those, only a few studies recruited children or clinically diagnosed patients. Surprisingly, there is no study, which recruited overweight or obese children and adolescents. However, all currently non-invasive available methods are strongly affected by the amount of subcutaneous fat present (wobbling mass), which can introduce great inaccuracies. Therefore, a study to identify how well existing HJC estimation methods work for this very specific population is strongly recommended. In addition, new methods such as 3D free-hand ultrasound techniques (3DUS) may bear great potential for accurate and non-invasive estimation techniques. These methods, are still experimental and have not yet been tested in overweight populations.
    The primary aim of this study is to evaluate the accuracy of current non-invasive HJC estimation methods for clinical 3D gait analysis to magnetic resonance imaging (MRI) in a population of overweight or obese children and adolescents. Based on the results obtained in this study, we will (i) provide recommendations, for which methods serve best to estimate the HJC position; (ii) develop soft tissue compensation algorithms and strategies that allow for a more accurate estimation of the HJC; (iii) in addition, we will evaluate the use of 3DUS as a promising alternative in HJC estimation.

  • AQUASCREEN

    Development of a pioneering water investigation procedure for the drinking water supply of tomorrow

    • Funding Institution / Call: WST3 (Land Niederösterreich, Abteilung Wirtschaft, Tourismus & Technologie)
    • Project Number: WST3-F-5031298/001-2017/K3-W-47/007-2017
    • Project Lead: Andreas Farnleitner, Karl Landsteiner University of Health Sciences / Division Water Quality and Health
    • Project Partner: EVN Wasser GmbH, University of Natural Resources and Life Sciences, Vienna / Department of Agrobiotechnology, IFA-Tulln
    • Duration: 24 months starting from 01.09.2018

    Background

    The biostability of water, i.e. the ability to store and distribute water without negative microbiological quality changes, is a crucial aspect in public water supply. Biostability is important for the esthetical characteristics of water (e.g. good taste and appearance) and it is essential to protect public health (i.e. conditions to not support the growth of facultative pathogens, such as Pseudomonas aeruginosa). The methods for the determination of biostability of water still suffer from major technical shortcomings and require significant future improvements.
    Due to a permanent increase of ground water temperature, caused by the global change (on average 0.05C° per year), growth of facultative pathogens is likely increasing in drinking water. The improved possibility to analyze and predict the growth potential of facultative pathogens in ground- and drinking water is thus becoming more important.
    This research project aims to develop and evaluate a new innovative approach to determine the biostability of ground- and drinking water by using up-to-date high-throughput DNA sequencing technology to screen and predict for bacterial population changes. To enable the tracking of biochemical key-processes in water supply, the possibility to combine the “basic module” with high-resolution chemical analysis will be determined as well. The main focus of AQUASCREEN is directed towards drinking water recourses which have significance in Lower Austria (i.e. well water, spring water, ground water).
    Milestone 1: Established experimental approach for the determination of the bacterial growth potential in ground- and drinking water based on flow cytometry and high-throughput DNA sequencing (“basic module”).
    Milestone 2: Analysis and evaluation of the new possibilities based on a case study with relevance for drinking water supply and comparison of results with traditional approaches.
    Milestone 3: Identified development needs to combine the “basic module” with high-resolution chemical analysis (advanced module “biogeochemistry”) and to detect and differentiate the growth potential of facultative pathogens, as detected by culture-based methods (advanced module “facultative pathogens”).
    The aim of this research proposal is to overcome the methodical limitations of the past and to successfully establish a new strategy supporting the reproducible and straightforward determination of biostability and its prediction in ground- and drinking water. Results of this research will support the development of new practical determination systems (prototypes).

  • REEgain

    Sustainable biological recycling of environmentally hazardous substances (Rare Earth Elements) from electronic waste and wastewater

    • Funding Institution / Call: INTERREG
    • Project Number: Interreg ATCZ172
    • Project Lead: Dominik Schild, IMC University of Applied Sciences Krems / Department of Life Sciences
    • Project Partner: Karl Landsteiner University of Health Sciences / Division Water Quality and Health, Mikrobiologický ústav AVČR, Zentrum ALGATECH, Danube University Krems / Center for Biomedical Technology, Saubermacher Dienstleistungs AG, Stark GmbH, Městská Vodohospodářská s.r.o.
    • Duration: 48 months starting from 01.07.2018

    Background

    Rare earths are used in electronic devices such as mobile phones, computers and energy-saving bulbs. However, they are scarce and cannot be recycled using eco-friendly methods. Complex and expensive mining, coupled with scarce supply, means that the prices of rare earths on the world market are rising steadily. Due to continuous technical advances, we can already predict that the supply situation for rare earths will become critical in future, which in turn could pose a threat to the development of innovative technologies.

    The project partners aim to counter this trend using a new technology. This involves an approach that has never been used before: recycling by means of microorganisms (bacteria and algae). The goal of the international project partner consortium is to develop a practicable recycling technology in collaboration with regional industry, with a view to reclaiming rare earths from electronic waste and subsequently making the technology available to businesses. The consortium liaises regularly with its strategic partners, which guarantees that market needs and the technological limitations of business are taken into account in the development process.

  • BEST MgAlloy

    Biocompatible elements - simulations and tests for Mg alloys

    • Funding Institution / Call: WST3 (Land Niederösterreich, Abteilung Wirtschaft, Tourismus & Technologie)
    • Project Number: KF3-F-639/004-2017
    • Project Lead: Rosemarie Gfatter, AIT Austrian Institute of Technology
    • Project Partner: Aerospace & Advanced Composites GmbH, FH Wiener Neustadt, AC2T research GmbH, Karl Landsteiner University of Health Sciences / Division Biomechanics
    • Duration: 36 months starting from 01.04.2018

    Background

    Biodegradable magnesium-based implants are increasingly coming into focus for temporary use in medical applications, such as plates, nails, pins or screws for osteosynthesis of broken bones. The great advantage of this is the elimination of a second operation for explanting any permanent metallic fixations.

  • Follow-up psychiatric patients

    Graded psychiatric care for patients with special care needs

    • Funding Institution / Call: NÖGUS
    • Project Lead: Friedrich Riffer, Psychosomatic Center Waldviertel - Eggenburg Clinic
    • Project Partner: Karl Landsteiner University of Health Sciences / Division of Psychiatry for Adults (University Hospital Tulln), Psychosomatic Center Waldviertel - Eggenburg Clinic
    • Duration: 24 months starting from 01.04.2018

    Background

    Patients being treated frequently and in different care facilities, also due to repeated treatment discontinuations, burden the care structures. The causes of the repeated treatment discontinuations and consequently readmissions, as well as the lack of reintegration are not restrictive known. It is therefore of great importance to investigate which factors are associated with potential readmissions and play a role in social reintegration. This project examines the benefits of patients with special aftercare needs. The goal is to optimize the graded care and reduce the readmissions. Basic knowledge will be gained on the benefit of patients with special care needs, who will contribute to the dismissal of the care system.
    Questions:
    1. Are there subgroups of patients with or without fundamental social and cognitive impairment among psychiatric patients with addiction (F1) or personality disorders (F6)?
    2. Is there a difference among the subgroups of psychiatric patients with or without cognitive thinking disorders regarding (re)admission r and cumulative length of stay, and social and professional reintegration

  • Medi3D Print

    3D print of biological materials

    • Funding Institution / Call: FFG, COMET
    • Project Lead: Nikolaus Dellantoni, ACMIT - Austrian Center for Medical Innovation and Technology
    • Project Partner: Karl Landsteiner University of Health Sciences / Division Biomechanics
    • Duration: 36 months starting from 01.01.2018

    Background

    3D printing is entering medicine and can help in many ways. In addition to accurately fitting implants and orthoses, 3D printing can be used in surgical preparation to gain a better understanding of the planned surgery. Increasingly, the printing of organs is becoming more important. In this research project materials are to be printed with the help of the Polyjet process which come as close as possible to real biological tissues from the haptic but also with regard to the biomechanical behavior. The printing technology developed in this way enables the production of patient-specific organ models based on CT and MRI data, which can be used for preoperative planning prior to complicated procedures. Furthermore, for the further development of surgical techniques and implants mechanically equivalent organs or specimens can be produced, which make dispensing with the use of body donations for these concerns. The printed organs are standardizable and have no undesirable variability, as is the case with body donation.

  • D.O.T.

    Die Offene Tür - Mental Health Project

    • Funding Institution / Call: Träger LBG GmbH
    • Project Number: LBG 01
    • Project Lead: Beate Schrank, Karl Landsteiner University of Health Sciences / D.O.T. - Die offene Tür (The Open Door)
    • Project Partner: Ludwig Boltzmann Gesellschaft
    • Duration: 48 months starting from 01.01.2018

    Background

    Social connectedness in adolescents is an important protective factor for health. Adolescent children of parents with mental illness (COPMI) are at risk of poor social connectedness, especially in periods of school transition. In COPMI and non-COPMI early adolescents, we seek to (i) understand mechanisms of social connectedness, (ii) improve social connectedness by enhancing social-emotional skills and appropriate peer connections through a digital hub, (iii) tailor the hub to maximise individuals’ gains, (iv) facilitate related positive outcomes, such as reductions in stigma via opportunity for positive COPMI-non-COPMI contact. Profound literature reviews and ongoing stakeholder and expert consultation will guide the design of a blended intervention comprising the online hub housing digital experiences and peer matching, and complementary school/service-based social wellbeing programmes. A pilot evaluation will test the intervention acceptability, feasibility and processes of changes; and explore the efficacy of the hub in two versions, i.e. standard and an individually adaptive mode.

  • Sepsis GEMMA

    Characterization of Blood Cell Derived Extracellular Vesicles with Nano Electrospray Gas-Phase Electrophoretic Mobility Molecular Analysis (nES-GEMMA)

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2016
    • Project Number: LSC16_018
    • Project Lead: Carla Tripisciano, Danube University Krems
    • Project Partner: Technische Universität Wien / Institute of Chemical Technologies and Analytics, Karl Landsteiner University of Health Sciences / Division of Anaesthesiology and Intensive Care (University Hospital St. Pölten), Danube University Krems / Department for Health Sciences and Biomedicine, Technische Universität Wien / Institute of Chemical Technologies and Analytics
    • Duration: 36 months starting from 01.01.2018

    Background

    Extracellular vesicles (EVs) are released by cells upon activation or stress and are present in all body fluids. They have recently emerged as versatile mediators of intercellular communication and as potentially rich reservoirs of clinical biomarkers. They are involved in a multiplicity of physiological processes, such as the regulation of the vascular function, and there is ample evidence for their roles in various pathological settings, such as cancer, inflammation and thrombosis. Channeling the properties of EVs towards therapeutic application and patient care is dependent on technological progress in analytical approaches. The complexity of biological fluids along with the heterogeneity of EVs challenges their isolation and characterization. The most commonly applied separation protocols, such as ultracentrifugation and density gradient centrifugation, are hampered by uncontrolled loss of vesicles and co-isolation of contaminants, such as cellular debris, protein aggregates, lipoproteins, or nucleic acids. Flow cytometry has found widespread application for the characterization of EVs, but EVs smaller than 200 nm, representing a high percentage of all vesicles present in blood, are not detectable with this approach. Other methods, such as nanoparticle tracking analysis are capable of detecting vesicles down to a size of 10 nm, but are not able to differentiate them from non-vesicular material, such as protein aggregates. Here, we will investigate the application of Nano Electrospray Gas-phase Electrophoretic Mobility Molecular Analysis (nES-GEMMA) for the characterization of extracellular vesicles, in particular exosomes, from complex biological matrices, such as human blood or plasma. We aim to set up standardized protocols for the isolation of highly pure EV fractions and their characterization with nES-GEMMA. We will apply nES GEMMA to quantify exosomes, which is superior to indirect quantification based on protein concentration as used to date, and we will assess for the first time whether protein and lipid content are qualitatively influenced by the size of extracellular vesicles by collecting size separated vesicles via an electrostatic nanometer aerosol sampler. Finally, we will monitor eventual modifications in the composition of vesicles obtained from physiological and different pathological settings. As a first application in clinical samples, nES-GEMMA will be used in combination with conventional flow cytometry and nanoparticle tracking analysis to quantify and characterize extracellular vesicles from the plasma of healthy donors and sepsis patients.

  • COMBIS

    Combinatory Bioactivity Screening

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2016
    • Project Number: LSC16_005
    • Project Lead: Martin Wagner, FFoQSI
    • Project Partner: Karl Landsteiner University of Health Sciences / Institute of Hygiene and Microbiology (University Hospital St. Pölten), University of Natural Resources and Life Sciences, Vienna / Institute for Applied Genetics and Cell Biology, University of Veterinary Medicine Vienna / Institute for Milk Hygiene
    • Duration: 36 months starting from 01.01.2018

    Background

    For decades virtually every easily cultivable microorganism has been investigated in pharmaceutical highthrough put screens (HTP) for natural bioactive compound production and after observation of a constantly increasing rediscovery rate of bioactive compounds the source was declared empty. As a consequence; large scale screening programs for natural bioactive compounds were mostly terminated. However, in recent years, the interest in natural bioactive compounds has been reignited based on mass sequencing results of microbial genomes predicting a much richer diversity of microbial metabolites than previously anticipated. These so called “cryptic” metabolites hold the potential for novel antibiotics, directly needed for the armsrace against the ever increasing incidence of pathogenic resistance. A promising approach to activate the production of “cryptic” metabolites is co-cultivation of competing microorganisms. For example fungi and bacteria are talented producers of natural compounds with potentially strong bioactive functions. In a previous work we could demonstrate that small chemical effectors induce or increase the production of otherwise repressed compounds in fungi which raises the chance of discovery of novel compounds. In addition it has been demonstrated that biotrophic conditions influence the production of bioactive compounds in fungi. Thus as innovative screening attempt we propose a high throughput assay combining small chemical effector treatment with combinatorial growth of fungi and bacteria under various biotrophic conditions. We will realize an automated HTP pipeline to co-cultivate 144 selected bacterial strains with 32 different fungi using 4 small chemical effectors under 4 biotrophic conditions. The 73728 so produced culture extracts will be screened for their ability to counteract microbial resistance in a direct approach for the presence of novel antibiotic compounds not susceptible to commonly found microbial resistances from human and veterinary sources in Lower Austria. Furthermore, in an indirect screening approach we will generate reporter strains primed for the presence of erm or cfr methylase mediated antibiotic resistance inhibitors. These resistance mechanisms are based on methylation of 16S rRNA which mediates resistance against several antibiotics at the same time and so far no in vivo active inhibitor has been discovered. The proposed project will deliver a co-cultivation HTP pipeline and a highly divers set of HTP assays for target driven screening attempts and has the potential to discover novel bioactive compounds.

  • Candida

    Exploitation of Candida-Lactobacillus interactions as potential probiotic targets

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2016
    • Project Number: LSC16_016
    • Project Lead: Christoph Schüller, University of Natural Resources and Life Sciences, Vienna
    • Project Partner: Karl Landsteiner University of Health Sciences / Institute of Hygiene and Microbiology (University Hospital St. Pölten)
    • Duration: 36 months starting from 01.11.2017

    Background

    Candida cells are common human commensals found on the skin and genitourinary tract. They cause mucosal infections which may progress to systemic candidosis. Of all cases of vulvo-vaginal candidosis (VVC) C. albicans and C. glabrata species occur in 90% and 8%, respectively. In the vaginal tract Candida cells compete with the commensal bacterial microflora. In healthy individuals bacteria and fungi co-exist in equilibrium. Treatment with antifungals aims at restoring the microbial balance. Here we propose to address current VVC treatment along three lines 1) to investigate the interactions that occur between Candida spp. and three abundant Lactobacillus species found in the vaginal tract to support the establishment of equilibrium; 2) to analyse local (eastern Austrian) candida strains for their genetic traits; and 3) to evaluate the efficacy of common probiotics and 4) find novel substances able to fight fungi and promote bacteria. The consortium combines clinical resources, molecular biology of Candida, cell culture, and robotic screening. Lactobacillus spp. restrict the progress of Candida in the vaginal tract by producing lactic and acetic acid and also by influencing in an undefined manner the nutrient availability, adherence to vaginal epithelium, biofilm formation, quorum sensing and stress resistance. The environmental and genetic factors triggering microbial imbalance in the vaginal tract constitute a complex host-microbe interaction system. We will address the Candida-Lactobacillus interaction in vitro in combinatorial co-culture on reconstituted human epithelium model system. We will especially focus on C. glabrata since it is harder to treat and much less explored compared to C. albicans. We will attempt to identify C. glabrata genetics and physiological responses involved in colonization of the vaginal tract. The physiological aspect covers the Candida-Lactobacillus interference on gene expression, adherence and biofilm formation properties. Genetic analysis will exploit and characterize lower Austria region clinical C. glabrata isolates. Furthermore, compounds will be screened in high throughput for their ability to foster the presence of different Lactobacillus strains and suppress the growth of Candida. We expect the identified novel targets to be useful for antifungal strategies against Candida to favour benign commensal populations. A considerable industry is selling probiotics for this purpose however with only partly documented efficacy. The projected work will seek novel alternative compounds to improve treatments in the future.

  • Endobone

    Developmental tissue engineering model of endochondral ossification for bone regeneration

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2016
    • Project Number: LSC16_024
    • Project Lead: Stefan Nehrer, Danube University Krems / Department of Regenerative Medicine
    • Project Partner: Karl Landsteiner University of Health Sciences / Division Biomechanics
    • Duration: 36 months starting from 01.10.2017

    Background

    Bone engraftment techniques to treat large bone defects involve implantation of allogenic bone grafts as a replacement tissue but are constrained on poor integration and functional anastomosis for ingrowth of vasculature from the host tissue. In proportionate many unresolved factors are to be addressed in advancing the clinical outcome for treating fracture non-unions, osteonecrosis, osteoporosis. Tissue engineering strategies hold promise in promoting bone regeneration. Nevertheless, the common approach in bone tissue engineering is by stimulating the osteogenesis route for regenerating bone which still remains an ineffective approach. Mimicking the natural process of bone formation through a developmental mechanism for formation of long bones called endochondral ossification has been envisioned from the commencement of research in the field of bone tissue engineering. In the current proposal, we propose a strategy for bone regeneration with naturally derived biomaterials incorporating extracellular matrix derived from cartilage (CD-ECM) as a template. We hypothesize that bone regeneration through a cartilaginous intermediate template onto solid biomaterials will produce a neotissue that mimics the native bone in its structure and functionality. To test this hypothesis we will compare bone regeneration from the proposed model to the gold-standard bone allografts used in clinics. CD-ECM incorporated biomaterials embedding hypertrophic chondrocytes are evaluated for their mineralized matrix formation in vitro with biochemical analysis and histological evaluation. Further, by non-destructive analysis micro-computed tomography (µCT) monitoring generated 3D segmented images and biomechanical testing of the scaffolds are evaluated together with computational finite element modelling simulations to determine the stiffness, strength of the engineered bone. The CD-ECM incorporated biomaterials are then implanted with or without hypertrophic chondrocytes ectopically in a mouse model for de novo mineralized matrix formation. The bone formation is further assessed by biochemical, µCT, biomechanical, computational modelling. This interdisciplinary approach would aid in a developmental engineering process instructing bioresponsive scaffolds to recapitulate native bone repair mechanisms.

  • WeRELaTE

    Advancing effective institutional models towards cohesive teaching, learning, research and writing development.

    • Funding Institution / Call: COST | European Cooperation in Science and Technology
    • Project Number: COST15221
    • Project Lead: Alison Farrell, Maynooth University
    • Project Partner: Karl Landsteiner University of Health Sciences / Research Management
    • Duration: 24 months starting from 04.09.2017

    Background

    This Action addresses the challenge of creating synergy among increasingly more specialised and centralised supports for four key higher education activities - research, writing, teaching and learning - which frequently fail to capitalise on their shared territories and common ground. In many institutions, central support for these four areas continues to grow, repeatedly in a reactive rather than strategic manner, in the form of sometimes overlapping programmes or activities, centres, institutes and other units. This responsive growth, often influenced by external forces, can result in the goals, structures and services of these central supports being less than optimal. Equally, what contributes to success, productivity and quality of outcomes, across research, writing, teaching and learning, can remain tacit, ill defined or indeed invisible. Our Action addresses the dearth of professional conversations and research around the shared territory of support for, and development of, these four areas. Such dialogue and research, across units and institutions, will illuminate intersections and contribute to institutional transformation based on complementary, coherent and integrated provision.

  • Novel biomechanical test setup

    Development of a novel biomechanical test setup together with bone strength simulation models to improve the diagnoses and treatment of osteoporosis

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Science Call Dissertation 2016
    • Project Number: SC16_009
    • Project Lead: Dieter Pahr, Karl Landsteiner University of Health Sciences / Division Biomechanics
    • Duration: 36 months starting from 01.09.2017

    Background

    Osteoporosis (OP) is a silent bone disease resulting in loss of bone density, decreased bone strength and ultimately fracture. It is underrated, underdiagnosed and undertreated. Every third women and every fifth men over 50 are concerned. OP is responsible for more than 4 million fractures annually in the EU, with hip fracture as the most common type. This translates into more than €40 billions of health care costs, out of which less than 5% is spent on prevention. Beside diabetes, cardiovascular diseases, and cancer it’s one of the important health care challenges in the next decades. Especially in Lower Austria this puts an estimated €200 million of annual burden on the healthcare system only. The early diagnostics of OP is vital for fracture prevention. This in return increases the life quality of the patient, and decreases the healthcare and social costs. Bone density is used as predictor of osteoporotic fracture risk. It is measured with DEXA and diagnosed with a derived T-score. However, recent studies showed the inaccuracy and insufficiency of such densitometry measures. For example, more than 50% of OP fractures occur in the patients who are considered as “low risk” by this method, and 15% of patients are falsely treated for being at "high risk". An improvement of this situation needs (a) better screening techniques, (b) more screening, and (c) improved diagnosis scores. The goal of this project is to improve osteoporosis diagnostic tools. Bone fracture happens because of overloading and/or reduced resistance against loading due to bone loss. Finite element analysis (FEA) simulation is a non-invasive numerical method which is able to estimate individual bone strength in-vivo based on DEXA or Quantitative Computed Tomography (QCT) images. Geometrical, structural, and material properties are computed from images and combined with typical physiological loading conditions including the magnitude, direction, and frequency of the loading. The accuracy of the model is inherited from a good knowledge of all these parameters. FEA -based bone strength has the potential to effectively improve diagnosis, assessment, and monitoring of osteoporosis. But despite the significant progress made in the last decade, these predictions still need considerable improvements through enhancements in imaging, mechanical testing, and simulation techniques to justify their clinical use.

  • Irreducibility

    Irreducibility of the Subjective Experience

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Science Call Dissertation 2016
    • Project Number: SC16_025
    • Project Lead: Patrizia Giampieri-Deutsch, Karl Landsteiner University of Health Sciences / Division Psychodynamics
    • Duration: 36 months starting from 01.09.2017

    Background

    The dissertation project clarifies ontological questions in light of the mind-body problem providing a solid conceptual and philosophical framework that integrates a broad spectrum of different research results. Of key interest is the scientific understanding of the phenomenon of mental processes, which is difficult to explain within the causal structure of the physical world. Subsequently, it will be examined how mental processes realize their reference to other subjects, to intramental processes and to non-mental givens and processes. The focus is on the fundamentals of perception and the question of what makes an experience an experience in the first place, with special consideration of its qualitative and phenomenal aspects. The exploration of subjective experience, especially with regard to the therapeutic relationship, is thus placed on a sound foundation and opens up the possibility of new insights into basic research in medicine, the health sciences and the humanities.

  • Personalized Diagnostics

    Advanced personalized diagnostics to overcome severe side effects of protein therapeutics

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2016
    • Project Number: LSC16_008
    • Project Lead: Peter Allacher, IMC University of Applied Sciences Krems / Applied Bioanalytics & Drug Development
    • Project Partner: Karl Landsteiner University of Health Sciences / Division of Paediatrics (University Hospital St. Pölten)
    • Duration: 36 months starting from 01.09.2017

    Background

    Therapeutic protein drugs have been widely used to treat a variety of diseases including cancer, autoimmune diseases, neurological diseases, metabolic diseases, bleeding disorders and others. The global protein drug market reached nearly $174.7 billion in 2015 and should reach nearly $248.7 billion by 2020. Although most protein drugs offer a favourable benefit-risk ratio, one key hurdle for the maintenance of clinical efficacy and safety has been the development of unwanted immune responses against protein drugs, in particular the development of anti-drug antibodies. Some patients develop pathogenic antibodies which neutralize the biologic activity of the protein drug or cause devastating health problems such as anaphylaxis or autoimmune pathologies. Currently, there is no diagnostic tool which can predict and distinguish the development of harmless or pathogenic antibodies in an individual patient. Therefore, basic research efforts are required to better understand immune regulation and nature of harmless and pathogenic anti-drug antibodies and to create the scientific basis for the development of novel diagnostics. Early diagnosis of evolving pathogenic antibodies would provide a window of opportunity for early immune intervention which could prevent pathogenic immune responses. One prominent example of pathogenic anti-drug antibodies is the development of neutralizing antibodies against factor VIII (FVIII) following replacement therapy of hemophilia A patients with human FVIII products. The antibodies neutralize the biological activity of FVIII and render replacement therapies ineffective which can result in life-threatening bleeding complications. In this project application, we propose to close a major gap in current understanding of the nature and evolution of pathogenic antibodies against FVIII and their differentiation from non-pathogenic antibodies in patients with severe hemophilia A. We aim to generate novel data on the temporal association between epitope specificity (protein epitopes versus carbohydrate epitopes), affinity, isotype/IgG subclass profiles and functional activities of antibodies against FVIII which develop in patients following replacement therapy with FVIII products. The possibility to combine basic research with the analysis of longitudinal samples obtained from patients undergoing FVIII therapy will provide a unique opportunity to directly translate novel research findings into clinical application. The data coming out of this project will provide the scientific basis for the development of novel diagnostic tools, such as FVIII-specific microarrays, which will allow physicians to differentiate patient-specific characteristics and design personalized treatment approaches, and ultimately improve patient outcomes.

  • AQUASAFE

    Water Quality Monitoring of the Future - Genetic Fecal Markers for the Detection and Determination of Source of Fecal Traces

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Science Call Water 2015
    • Project Number: SC15_016
    • Project Lead: Andreas Farnleitner, Karl Landsteiner University of Health Sciences / Division Water Quality and Health
    • Project Partner: University of Natural Resources and Life Sciences, Vienna / Department of Agrobiotechnology, IFA-Tulln, Technische Universität Wien / Institute of Chemical Engineering, EVN Wasser GmbH
    • Duration: 36 months starting from 01.09.2017

    Background

    Molecular faecal pollution diagnostics, based on the detection of genetic faecal microbial source tracking (MST) markers, is about to revolutionise water quality testing. Such applications have been mainly focusing within the fields of recreational water quality monitoring, shellfish production, and maximum daily load monitoring. Scientific knowledge on the application of genetic faecal MST marker diagnostics, to support drinking water supply management and water safety planning, is hardly available yet. The proposed translational research project is going to establish the basic scientific knowledge needed to apply and further develop cutting edge genetic faecal marker diagnostics for quality testing to support water safety plans of drinking water supplies of tomorrow. Genetic faecal MST markers are supposed to extend current monitoring practices based on standard faecal indicator bacteria (SFIB) E. coli and enterococci in order to identify potential contamination sources for elimination or minimisation, and, to bridge the gap between traditional faecal pollution monitoring and microbial risk assessment. However, molecular diagnostics with adequate faecal-source specificity and faecal –source sensitivity is considered a key prerequisite for these applications. A new tiered application strategy for drinking water resources monitoring, based on the combination of bacterial and mitochondrial genetic faecal MST markers, is proposed. The new strategy will systematically be evaluated by means of relevant faecal pollution sources,
    representative water resources in Lower Austria, and important disinfection processes. To enable comparisons to traditional methods investigations will be complemented by SFIB and total cell count analysis. Chemical markers will be evaluated to support genetic MST diagnostics. The topic “Intelligent Indication Systems and Diagnostics” has been defined as prioritised research area within the recent FTI strategy (Programme for Research, Technology & Innovation for Lower Austria). The submitted research proposal is thus directly contributing to the adopted FTI strategy. The translational research project will stimulate sustainable collaborations between the Karl Landsteiner University, the well-established Center for Analytic Chemistry at IFA Tulln and the Interuniversity Cooperation Centre for Water and Health, a research centre to pioneer cutting edge water quality research. Furthermore, the project will directly collaborate with EVN Wasser GesmbH, the leading Lower Austrian drinking water supplier. The project will thus directly establish links between cutting edge water research and activities of a leading drinking water supplier to support the realization of water safety management of the future. Joint collaboration between these excellent partners in research and management will contribute to a further establishment of Lower Austria as a leading region in the water sector within the Danube and Central European Region.

  • MFSD1 Transporter

    Investigationg the role of the novel major superfamily facilitator transporter

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2016
    • Project Number: LSC16_021
    • Project Lead: Daria Siekhaus, IST Austria
    • Project Partner: Karl Landsteiner University of Health Sciences / Division of Internal Medicine 1 (University Hospital St. Pölten)
    • Duration: 36 months starting from 01.08.2017

    Background

    Metastatic spread causes 90% of all tumor related fatalities and thus represents the greatest challenge for cancer patient survival. Tumor cells need to become motile and cross vascular barriers for metastatic spread. How these processes are controlled is not yet fully understood. The laboratory of Dr. Daria Siekhaus has identified a novel transporter, CG8602, required for Drosophila macrophages to invasively migrate into the tissues of the embryonic germband. Data from the Siekhaus lab point towards a role for CG8602 in regulating the glycosylation and stability of proteins that limit tissue entry. CG8602 appears necessary for the increased level of T antigen present on the surface of macrophages invading the tissue of the germband. Intriguingly, increased levels of T antigen have been found in metastatic cancer and antibodies against T antigen can reduce metastasis. This raised our interest in translating our findings into vertebrates, and Dr. Siekhaus recruited a post-doctoral fellow, Dr. Marko Roblek, with extensive experience in studying metastasis in mice back to Austria from Switzerland. This fellowship will help pay for his salary and material costs and thus enable him to conduct the work that will form the foundation for establishing his own independent lab. The mammalian ortholog of the CG8602 transporter, called MFSD1, is highly conserved, and belongs to the solute carrier superfamily (SLC). Yet its functions remain unknown due to a lack of prior studies. We seek to examine the role of MFSD1 in tumor cells during mouse metastatic initiation, We also will examine whether and how MFSD1 is involved in regulating protein glycosylation, protein stability, and how these potential changes affect the regulation of invasive tumor migration. By analyzing the function of MFSD1 and its interaction partners we aim to uncover the mechanism from aberrant glycosylation to the invasive migration phenotype observed during metastatic spread of tumors. This will include analysis of cell surface proteins, signaling cascades, and transcriptional regulation of cell migration. To test the relevance of these findings for the clinic, we are partnering with Dr. Wiesholzer and Dr. Kitzwoegerer at the Clinical Division for Internal Medicine, KLU University St Poelten. By analyzing resected tumor tissue from patients we will determine whether the level or localization of MFSD1 can be correlated with disease prognosis. We are eager to transfer findings from Drosophila to the vertebrate system in the context of metastasis research. Our prior data leads us to believe that this will lead to the description of an evolutionarily conserved mechanism that regulates invasive migration regulation from fly to vertebrates. This work can lay the ground work for
    understanding the basic biology of a novel vertebrate gene involved in regulating invasion and metastasis, and thus for the eventual development of a new therapeutic target and diagnostic biomarker for the clinic.

  • Biomarker for the early detection of melanoma

    Compartment specific in depth analysis of blood plasma nucleic acids for highly sensitive detection of early metastic events in melanoma disease

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2015
    • Project Number: LSC15_020
    • Project Lead: Jörg Burgstaller, University of Veterinary Medicine Vienna / Department of Agrobiotechnology, IFA-Tulln
    • Project Partner: Karl Landsteiner University of Health Sciences / Division of Dermatology and Venereal Diseases (University Hospital St. Pölten), University of Veterinary Medicine Vienna / Institute for Milk Hygiene
    • Duration: 36 months starting from 01.05.2017

    Background

    Biomarkers as indicators for therapeutic mode, onset, and response to treatment are rapidly gaining importance in clinical cancer management. Cancer biomarkers are tumour- or patient-related factors, which reflect the biological behaviour of a tumour and thus constitute a prognostic tool. Cutaneous malignant melanoma is a highly aggressive and metastatic tumour arising from cutaneous pigment cells termed melanocytes. Although incidence of melanoma and related mortality are continuously increasing, it is still impossible to predict the metastatic behaviour of melanoma in individual patients.
    In the past five years, the field of "liquid biopsies", i.e. the gain of important information on tumour development via nucleic acid (NA)-based analysis of blood samples, has tremendously progressed. It is now evident that in the blood, tumour-cell derived NAs reside in three different compartments, i.e. (i) intracellular NAs in circulating tumour cells, (ii) NAs in extracellular vesicles, and (iii) freely circulating protein-bound DNA in the plasma. Importantly, extracellular NAs are more abundant in blood, and therefore more accessible.Currently, the clinical applicability of blood-based tumour detection and monitoring methods is still limited to patients with progressive (metastatic) disease. Based on the hypothesis that a compartment-specific NA analysis will considerably aid in improving blood test sensitivity in comparison to holistic approaches, the overall objective of the herein presented study is to exploit the compartmentalization of tumour-derived blood NAs in order to establish a novel strategy for highly sensitive blood-based detection and monitoring of early stage human melanoma disease and metastasis. The applicant and cooperation partners aim at achieving this goal by (i) addressing the amount and composition of extracellular vesicular nucleic acids and circulating free DNA in vitro in order to comparatively evaluate vesicles as a reservoir of potential NA-type biomarkers, (ii) addressing the presence and amount of tumour-derived NA per compartment and possible changes of these parameters over time in a clinical study involving late stage melanoma patients, and by (iii) addressing the presence and amount of the most promising tumour-derived NAs identified in (ii) in a clinical study involving patients with high risk of melanoma recurrence as to achieve earliest possible detection of disease recurrence.

  • M3dRES

    Additive Manufacturing for Medical Research

    • Funding Institution / Call: FFG
    • Project Number: FFG858060
    • Project Lead: Francesco Moscato, Medical University of Vienna / Center for Medical Physics and Biomedical Engineering
    • Project Partner: ACMIT - Austrian Center for Medical Innovation and Technology, Karl Landsteiner University of Health Sciences / Division Biomechanics
    • Duration: 36 months starting from 01.05.2017

    Background

    The M3dRES project aims at establishing a unique infrastructure devoted to 3d-printing for medical research in a strongly interdisciplinary environment.
    M3dRES provides essential tools for the personalized patient treatment, for the enhancement of medical imaging, for the acceleration of tissue engineering and regenerative medicine, and for the modernization of current medical education.

  • Toxicokinetics of mercury in the placenta

    The toxicokinetics of mercury in the human placenta: correlation between genotype and phenotype in healthy and diseased placentas

    • Project Number: LSC15_014
    • Project Lead: Hans Salzer, Karl Landsteiner University of Health Sciences / Division of Paediatrics (University Hospital Tulln)
    • Project Partner: Medical University of Vienna / Institute of Medical Genetics, Karl Landsteiner University of Health Sciences / Division of Paediatrics (University Hospital St. Pölten)
    • Duration: 36 months starting from 01.12.2016

    Background

    Normal function of the placenta is pivotal for optimal fetal growth and development. The etiology of placental dysfunction is multifactorial with abundant gene and environment interactions. Placental dysfunctions are implicated in pregnancy complications such as gestational diabetes (GDM), pre-eclampsia (PE) and intrauterine growth restriction (IUGR). We intend to examine a certain aspect of reproductive toxicology, the mercury toxicokinetics in the healthy and diseased (GDM, PE, IUGR) human placenta. Based on the available data on the involved genes/proteins in mercury toxicokinetics from the healthy placenta, we now aim to compare their role and function in healthy and diseased placentas. We are interested whether mercury toxicokinetics are altered in dysfunctional placentas, which is a relevant issue in reproduction toxicology and individualized pregnancy care. We observed variable expression levels of placental proteins involved in mercury toxicokinetics. Our hypotheses are that 1) sequence variations in the candidate genes contribute to altered placental protein expression and as a consequence to altered toxicokinetics in the placenta, and 2) that the genetic background for mercury toxicokinetics is different between healthy and diseased placentae (GDM, PE, IUGR). The placenta is a unique organ for investigating genotype-phenotype relationship because the organ is accessible, protein levels and functions can relatively easy be determined, and also primary cells can be obtained. Methyl mercury (MeHg) is regarded as a model substrate because various amino acids, hormones, cancer drugs, and xenobiotics use at least in part the same transporter and metabolizing/detoxifying systems as the metal species. Studying transport and metabolisation/detoxification of MeHg in healthy and diseased placentas provides valuable data not only for the field of reproductive toxicology. Three groups of proteins related to mercury toxikokinetics are involved in placental (dys)function. There is evidence that amino acid transporter levels are altered in both IUGR and fetal overgrowth and that PE goes along with an altered oxidative defense in the placenta. There is some evidence that also ABC transporters are involved in PE and IUGR. We suggest six proteins, i.e., amino acid transporters LAT1 and b0,+, GSH system related enzymes GGT1 and GSTA1 and ABC transporters MRP1 and MRP3 to be examined in the healthy and diseased placenta. In the proposed study we aim to confirm (1) whether the protein specific effects on mercury toxicokinetics observed in previous experiments are direct effects. Based on the knowledge which proteins are directly related to mercury toxicokinetics, we will determine (2) which known functional genetic variants are related to placental protein expression and mercury contents by comparing healthy and diseased (GDM, PE, IUGR) placentas.

  • Chondroitin Sulfate

    The role of chondroitin sulfate proteoglycan in the development of multidrug tolerance in melanoma cells

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2015
    • Project Number: LSC15_007
    • Project Lead: Christine Hafner, Karl Landsteiner University of Health Sciences / Division of Dermatology and Venereal Diseases (University Hospital St. Pölten)
    • Project Partner: Karl Landsteiner University of Health Sciences / Institute of Pathology (University Hospital St. Pölten), Karl Landsteiner University of Health Sciences / Institute of Pathology (University Hospital Krems), Medical University of Vienna / Institute of Pathophysiology and Allergy Research, University of Queensland / Dermatology Research Centre
    • Duration: 36 months starting from 01.11.2016

    Background

    Malignant melanoma is the most frequent cause of skin cancer-related deaths. Despite the progress in understanding the biology of this disease, it still remains a significant clinical problem. Melanoma is often associated with activating mutations in the BRAF gene at the amino acid position 600, which results in an uncontrolled activation of the MAP-kinase pathway and - as a consequence - leads to increased cell proliferation and migration. Although several BRAF inhibitors, such as vemurafenib, have been proven to be highly effective in inhibiting BRAFV600 mutated melanomas, resistant-associated secondary mutations, which reactivate alternative survival pathways, often occur. We have recently reported on the response of chondroitin sulfate proteoglycan 4 (CSPG4)-specific Abs to enhance the anti-proliferative effects of vemurafenib. These data implied that the microenvironment is important in determining the effect of targeting CSPG4 on cell migration and invasion and suggest a role for CSPG4 in the phenotypic plasticity of melanoma cells and the emergence of a transient drug-resistant state. Central to the model of stress-induced drug tolerance resulting in multi-drug resistant cancer cells called induced-drug tolerant cells (IDTCs) is their propensity to develop colonies for which cell adhesion is crucial. Based on these findings of cell adhesion and cell motility being crucial for early drug resistance we propose that anti-CSPG4 antibodies, which have shown promising results in two different animal models, prevent or delay IDTC formation in mutant BRAF melanoma cells if combined with standard treatment modalities such as BRAF and MEK inhibitors. During this project we will validate this hypothesis with in vitro and in vivo models of melanoma, we will analyse changes on protein and gene expression levels induced by these treatment modalities and we will validate these experimental data on patients´-derived melanoma samples. Targeting IDTCs with anti-CSPG4 antibodies could be a crucial step for the prevention of acquired drug resistance.

  • PHAGE

    The importance of phage-induced transduction for the acquisition and persistence of antibiotic resistance

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2014
    • Project Number: LSC14_006
    • Project Lead: Friederike Hilbert, University of Veterinary Medicine Vienna / Institute for Milk Hygiene
    • Project Partner: Karl Landsteiner University of Health Sciences / Institute of Hygiene and Microbiology (University Hospital St. Pölten)
    • Duration: 42 months starting from 01.03.2016

    Background

    Hospital-acquired-infections caused by antibiotic resistant pathogens is a global concern to public health. Even the Obama Administration has recently acknowledged the need for innovative research to slow down the public health threat of antibiotic resistant bacteria with a National Strategy for Combating Antibiotic Resistant Bacteria (CARB). The increasing prevalence of antibiotic resistant and multi-drug-resistant pathogens has been shown to considerably expand the burden of disease, despite numerous infection control measures and modern hospital epidemiology. Thus,antimicrobial resistance in microbes is considered to be one of the major threats in medicine and public health worldwide. The horizontal spread of antimicrobial resistance between bacteria is a critical step in the development of resistance during therapy, the dissemination of resistance between different bacterial species, the acquisition of resistance from environmental sources, and the evolution of the bacterial host. An understanding of the mechanisms of horizontal transfer of antimicrobial resistance genes between microorganisms inside and outside of the host is essential to finding strategies to combat their spread. Current knowledge is that the transfer of resistance factors is largely due to conjugative plasmids or transposons and only to a minor extent transduction via bacteriophages. However, based on whole genome sequencing it has been hypothesized that the latter mechanism might play a substantially more important role in the transfer of antimicrobial resistance than is currently accepted. Recently we were able to show that phage transduction is of primary importance in the acquisition of therapeutically important resistance genes in Escherichia coli found on food. We reported that chicken meat carries a number of coli-phages capable of transferring antimicrobial resistance. High numbers of randomly tested phages were able to transduce one or more antimicrobial resistances. Phage transduction of specific resistance elements appears to be widely distributed. This mechanism of transfer may explain unanswered questions regarding the emergence and spread of antimicrobial resistant pathogens. In this proposal we hypothesize that transduction of antibiotic resistance by phages in the medical environment takes place and has important consequences for human health. Thus, the development of new control strategies to cope with phage persistence and transduction need to be found. Thus, we propose to investigate the significance of transduction in the medical environment for hospital-associated pathogens causing major problems by means of antibiotic resistance like Escherichia coli and Staphylococcus aureus. We will isolate and characterize antimicrobial resistance transferring phages, clarify the mechanisms of transfer, analyse the therapeutic importance and finally explore the transduced bacterial host for phage transmission and virulence.

  • NRF2 Melanoma

    The role of NRF2 for Melanoma Progression - Insights into the mechanimsm of metastasis

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2014
    • Project Number: LSC14_007
    • Project Lead: Harald Hundsberger, IMC University of Applied Sciences Krems
    • Project Partner: Karl Landsteiner University of Health Sciences / Division of Dermatology and Venereal Diseases (University Hospital St. Pölten), Medical University of Vienna / Institute of Medical Genetics
    • Duration: 36 months starting from 01.03.2016

    Background

    Melanoma is one of the most frequent tumors in young adults and despite it only accounts for 4% of all cases of skin cancer, melanoma is responsible for 79% of all skin cancer related deaths. Despite progress has been achieved in treatment of Melanoma (e.g with B-raf inhibitors), finally patients succumb due to resistance mechanisms acquired by the tumor. Many lines of evidence have shown that especially metastatic melanoma exhibits a strong metabolic turnover, which is needed to fuel cell proliferation and anabolic pathways. This increased cellular turnover also results in an increased demand to maintain the redox homeostasis. Here we propose to analyze this high metabolic and therefore also ROS (Reactive Oxigen Species) generating stress as a possible Achilles heel of melanoma. One of the major regulators of stress response in cancer is NRF2. It plays a central role in protection of cells against oxidative and xenobiotic stresses. Therefore the inhibition of NRF2 or its target genes might re-establish the sensitivity of melanoma to apoptosis driven by ROS. Furthermore this mechanism could prevent resistance mechanisms frequently observed in metastatic melanoma and it might abolish the frequently observed activation of endothelial cells, which surround tumor cells. It is highly likely that a combination of state of the art melanoma treatment with compounds that inhibit the generation of ROS scavengers, potentiates the effectiveness of the current treatment regiments. We will use CRISPR based methods as well as pharmacological inhibition to elucidate the mechanistic role of NRF2 in melanoma cells and on endothelial cells. Furthermore we will transfer knowledge gained from our model by closely cooperating with clinicians, who routinely care for melanoma patients. Concluding, we propose that abolishing the antioxidative response by suppressing NRF2 directly or its targets will be an effective contribution in the battle to fight metastatic melanoma.

  • Tumor Cachexia

    Metabolic characterization of chronic inflammatory conditions such as metabolic syndrome and tumor cachexia

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2014
    • Project Number: LSC14_021
    • Project Lead: Martin Pecherstorfer, Karl Landsteiner University of Health Sciences / Division of Internal Medicine 2 (University Hospital St. Pölten)
    • Project Partner: IMC University of Applied Sciences Krems / Applied Bioanalytics & Drug Development, University of Vienna / Department of Analytical Chemistry, Medical University Graz / Core Facility Mass Spectrometry, Medical University of Vienna / Institute of Medical Statistics, Rudolfstiftung Hospital / Karl Landsteiner Institute for Obesity and Metabolic Diseases
    • Duration: 42 months starting from 01.02.2016

    Background

    The clinical picture of the metabolic syndrome (MeS) is characterized by obesity, hypertension, insulin resistance and pathological blood lipid levels. Furthermore, the existence of a chronic inflammatory state in the adipose tissue leads to changes in the lipid metabolism of the fat cells. As a result, this leads to a disturbed uptake, deposition and release of lipids and free fatty acids. Interestingly, in the blood plasma of patients with tumor cachexia (CaC), lipid and inflammatory markers are similar to those of the metabolic syndrome. Tumor cachexia (CaC) is the term for a metabolic disorder that occurs as a result of cancer. This disorder leads to cachexia of the patient and emaciation.
    For research, this raises two important questions: What are the pathophysiological processes in the metabolic syndrome and the tumor syndrome cachexia? Is there a common biological marker for the pathophysiological processes in metabolic syndrome and tumor cachexia?

  • Future of Hearing

    Future of Hearing

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2014
    • Project Number: LSC14_027
    • Project Lead: Georg Mathias Sprinzl, Karl Landsteiner University of Health Sciences / Division of Otorhinolaryngology (University Hospital St. Pölten)
    • Project Partner: Hannover Medical School / Biomaterial Engineering, CEST
    • Duration: 37 months starting from 01.02.2016

    Background

    Severe deafness (1.7% of the total population) leads to social isolation, disability and early dementia. Hearing aids and cochlear implants (CI) bring help here, but eliminate the socio-economic effects only partially. The reason lies in the failure of the so-called "Cocktail Party Ability", where with a healthy hearing one can focus on a single conversation in a noisy room.
    This data processing is not found in the cortex, but the latter actively controls a filtering in the auditory organ (cochlea) via a down-going multilevel, efferent control. Despite all signal processing in hearing aids and CI, this unconscious regulation is difficult to imitate and their regulation by patients remains almost unused because of inconvenience. What is missing is the technical closing of the extended loop consisting of cochlea, cortex and hearing aid / CI.
    With Brain Computer Interfaces (BCI), the connection of the cortex or underlying stations of auditory efference to hearing aids could be possible in the future, albeit to a large extent cooperation of audiologists, neurosurgeons, electrophysiologists, electrode developers, modeling neuro- and cognitive scientists is needed. The University Hospital St. Pölten (UKStP) of the Karl Landsteiner Private University for Health Sciences recommends itself as the initiator of a roadmap, which incorporates the state of knowledge into teaching, evaluates the application focus and communicates a consensus on challenges and milestones.
    In addition to this long-term approach, in the first, smaller experiments it will be tested if efferent control can work. These experiments as part of ongoing animal experiments and CI patients allow easier access to the efferent auditory system to test (compound action potential CAP, tonotopic action potentials in sensing CI mode and EEG leads). A success would be a tentative conclusion of efferent regulation allowing patients to learn to use the efference - possibly as intuitive as BCI-controlled limbs *. (* Collinger JL et al, J. Clin. Trans. Science (2014) 7, 1, 1752-8062)

  • OsteoSim

    Computer simulation models for the early detection of osteoporosis

    • Funding Institution / Call: FFG, Basisprogramme BRIDGE 1
    • Project Number: FFG850746
    • Project Lead: Dieter Pahr, Karl Landsteiner University of Health Sciences / Division Biomechanics
    • Project Partner: Danube University Krems / Department of Regenerative Medicine, Braincon GmbH&CoKG, Technische Universität Wien / Institute for Lightweight Design and Structural Biomechanics
    • Duration: 36 months starting from 01.12.2015

    Background

    Osteoporosis is a common age disease of the bone. The cause of osteoporosis is usually a hormonal change. Older women are predominantly affected, but men are also increasingly suffering from this disease. The widespread of osteoporosis is gradually becoming a health economic problem. Osteoporosis gradually reduces bone density. As a result, the entire skeleton is weakened biomechanically and it is more likely to suffer from bone fractures. In clinical practice, the diagnosis of osteoporosis or, in general, the estimation of a fracture risk on the basis of bone density measurement (BMD measurement) is carried out. According to WHO, a T <-2.5 standard deviation is the critical threshold for the diagnosis of osteoporosis. Unfortunately, results of studies (eg, Rotterdam study3) show that in a group with non-vertebral fractures, only 44 percent of women and 21 percent of men had a value below -2.5. The final goal is to combine both medical reports from osteoporosis and osteoarthrosis together with new, validated assessment models, which gives better results than the T-score. As a secondary goal, relationships and possible interactions of both diseases are shown. This is to be achieved by four research tasks: new models of osteoporosis, standardization of radiographs, combined findings - correlations osteoporosis and osteoarthrosis, validation of new osteoporosis assessment models.

  • TIFOS

    Totally implantable fiber-optic sound sensing system for cochlear- and middle-ear hearing aids

    • Funding Institution / Call: NÖ Forschung & Bildung (NFB), Life Science Call 2014
    • Project Number: LSC14_026
    • Project Lead: Nikolaus Dellantoni, ACMIT - Austrian Center for Medical Innovation and Technology
    • Project Partner: Karl Landsteiner University of Health Sciences / Division of Otorhinolaryngology (University Hospital St. Pölten), Resident Specialist
    • Duration: 36 months starting from 01.11.2015

    Background

    Implantable hearing aids are in clinical use since more than 25 years. These include cochlear implants (CI), auditory brainstem implants (ABIs), bone-anchored hearing aids (BAHA) and implantable middle-ear implants (MEI). The main challenge for all these implantable devices is a lack of reliability of the implantable microphone due to a constant decrease of the initial sensitivity after exploitation. In this project we propose a contactless fiber-optic sensing technique based on low-coherence interferometry for amplitude measurement of the hearing ossicles, e.g. incus or malleus. Our approach is physiologically fully justified because sound transmission to the inner ear can be realized without any obstacles, taking advantage of the natural amplification properties of the outer ear and the ear drum. There is no feedback noise and signal distortion due to decoupling the microphone from the actuator. The contactless method does not change the original properties of the acoustic signal at all and the ossicle chain stays intact. The distance of about 5 mm between the sensing fiber and ossicle is large enough to prevent scarring. This also allows to use the device in case of small quasi-static long-term movements of ossicle in the middle-ear, that usually occur during the children growth, or rather large quasi-static short-term movements in case of alternation of atmospheric pressure or chewing. The current prototype of the device can reach sensitivity of about 40db SPL and about 70db SPL in audio frequency range which now should be further improved to around 30 dB SPL by increasing the signal-to-noise-ratio (SNR) of the system, accomplished by noise suppression of some individual parts of the system, like light source, fiber-optic link, photo receiver, or overall sensing configuration. Additionally, a more effective algorithm will be developed and embedded in a low-consumption DSP. The results will be verified by pre-clinical ex-vivo examination

  • DrinkingWATER@building

    Knowledge transfer and exchange of experience on drinking water quality in buildings

    • Funding Institution / Call: FFG
    • Project Number: FFG4952809
    • Project Lead: Thomas Czerny, FH Campus Vienna
    • Project Partner: AIT Austrian Institute of Technology, Karl Landsteiner University of Health Sciences / Division Water Quality and Health, OFI - Austrian Research Institute, Ecoplus. The Business Agency of Lower Austria
    • Duration: 6 months starting from 13.10.2014

Publications

The scientific staff of Karl Landsteiner University of Health Sciences as well as from our university hospitals are constantly publishing in internationally recognised journals.

 

Find here a selection of recently published articles:

Lymphocyte-to-monocyte ratio and neutrophil-to-lymphocyte ratio as biomarkers for predicting lymph node metastasis and survival in patients treated with radical cystectomy.D`Andrea, D et.al.J Surg Oncol, 2017
Cold Thermal Irrigation Decreases the Ipsilateral Gain of the Vestibulo-Ocular Reflex.Tamás, LT et al.Ear Hear, 2016
Chronic Paracoccidioidomycosis with adrenal involvement mimicking tuberculosis - A case report from Austria.Wagner, G et al.Med Mycol Case Rep, 2016
Canine olfaction as an alternative to analytical instruments for disease diagnosis: understanding 'dog personality' to achieve reproducible resultsHackner K; Pleil J;Journal of Breath Research, 2017
Randomized Trial of Bilateral versus Single
Internal-Thoracic-Artery Grafts
Taggart, D;NEJM, 2016
Normalised time-to-peak-distribution curves correlate with cerebral white matter hyperintensities - Could this improve early diagnosis?Nasel, C et al.J Cereb Blood Flow Metab, 2017
Vaccine hesitancy in AustriaSandhofer, M et al.Wr. Klinische Wochenschrift, 2017
Intraoperative MR imaging of cerebral oxygen metabolism during resection of brain lesionsStadlbauer, A. et alWorld Neurosurgery, 2017
Magnetic resonance imaging biomarkers for clinical routine assessment of microvascular architecture in gliomaStadlbauer, A. et alJ cerebral blood flow and metabolism, 2016
Short-term clinical outcomes for intermittent cold versus intermittent warm blood cardioplegia in 2200 adult cardiac surgery patientsTrescher, K et alJ Cardiovasc Surg (Torino), 2017
Compatibility of Meropenem with Different Commercial Peritoneal Dialysis SolutionsWiesholzer, M. et al.Perit Dial Int, 2016
A single-center retrospective analysis of first-line therapy of multiple myeloma with bendamustine-bortezomib-dexamethasoneZwickl, H. et al.Leuk Lymphoma, 2016

Events

  1. 18 Jan

    Master and More - Bildungsmesse München

    18. January 2019, 09:00 - 16:00
    MVG Museum München, Ständlerstr. 20, D-81549 München
  2. 09 Feb

    Horizon Stuttgart

    09. February 2019, 10:00 - 10. February 2019, 16:00
    Hanns-Martin-Schleyer-Halle, Mercedesstraße 69, D-70372 Stuttgart
  3. 22 Feb

    Einstieg Hamburg

    22. February 2019, 09:00 - 23. February 2019, 16:00
    Messe Hamburg / Halle B6 (Eingang Süd)