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Fibroblast specific protein 1 (FSP1)/S100A4 is a calcium binding protein which has been linked to epithelial-mesenchymal transition, tissue fibrosis, pulmonary vascular disease, metastatic tumour development, increased tumour cell motility and invasiveness. This protein is reported to be also expressed in newly formed and differentiated fibroblasts and has been used in various studies to demonstrate epithelial-mesenchymal transition (EMT). We aimed to characterize S100A4 positive cells in different human tissue compartments, with the focus on fibroblasts/myofibroblast. We found S100A4 expression in a wide range of cells. Fibroblasts/myofibroblasts showed a broad spectrum of staining intensity, ranging from negative to strong expression of S100A4, with the strongest expression in smooth muscle actin positive myofibroblasts. Cells of haematopoietic lineage, namely CD4 and CD8 positive T-lymphocytes, but not B-lymphocytes expressed S100A4. All investigated monocytes, macrophages and specialised histiocytes were positive for S100A4. Even some epithelial cells of the kidney and bladder were positive for S100A4. Expression was also found in the vasculature. Here, cells of the subendothelial space, tunica adventitia and some smooth muscle cells of the tunica media were positive for S100A4. In summary, S100A4 is expressed in various cell types of different lineage and is not, as originally believed, specific for fibroblasts (FSP). Results attained under the premise of specificity of FSP1/S100A4 for fibroblasts, like the founding research on EMT type 2 in kidney and liver, therefore need to be reinterpreted.

Der Menschenwürde kommt bei den körperbezogenen psychosozialen Tätigkeiten im Bereich des gehobenen Dienstes für Gesundheits- und Krankenpflege eine wichtige Rolle zu. Um willentlich gute angemessene Handlungen in der spezifischen Betreuungssituation zu entscheiden, bedarf es eines systematischen Nachdenkens. Die Pflegeethik wird nicht bloß als eine theoretisch-wissenschaftliche Methode, die unter anderem die etablierten Werte einer Gesellschaft zur Disposition stellt, sondern auch als eine zwischenmenschliche Praxis verstanden, die durch das interpretative, kontextuelle und hermeneutische Wissen über die Patient:innen eine situationsbezogene, assoziativ erspürte, erfahrungsgeleitete sowie ganzheitliche – würdevolle – Begleitung ermöglicht. Die Pflegeethik gewährt zudem eine kritische Standortreflexion und unterstützt den Professionalisierungsprozess der Pflege. Das arbeitsrechtliche Bundesgesetz der Gesundheits- und Krankenpflege (GuKG) determiniert die Pflegeinteraktion, indem es den Verhaltenskorridor durch die gesetzten Rahmenbedingungen einengt. Die Normen der Aus-, Fort- und Weiterbildungen, die gesetzlichen Bestimmungen bezüglich des Kompetenzbereichs der diplomierten Pflegekräfte und der normierte Gesundheits- und Krankenpflegebeirat beeinflussen die Menschenwürde in der Pflegearbeit maßgeblich. Lücken im Gesetz, wie bspw. die fehlende Verankerung der Pflegeethik oder unzureichende salutogenetische Maßnahmen für die Pflegekräfte, wirken sich hinderlich auf einen würdevollen Umgang aus., Human dignity has an important role in body-related psychosocial activities in the field of higher level health care and nursing. In order to make appropriate wise decisions in the specific care situation, systematic reflection is required. Nursing ethics is not only understood as a theoretical-scientific method that, among other things, provides established values of a society, but also as an interpersonal practice that, through interpretative, contextual and hermeneutic knowledge of the patient, enables situational, associatively sensed, experienceguided as well as holistic – dignified – care. Additionally, care ethics grants a critical location reflection and supports the professionalization process of the nursing sector in general. The federal law of health care and nursing (GuKG) determines the nursing interaction by narrowing the corridor of behavior through the set framework conditions. The standards of education and further trainings, the legal provisions regarding the scope of competence of certified nurses and the standardized health and nursing advisory board have a significant influence on human dignity in nursing work. Gaps in the law, such as the lack of anchoring of nursing ethics or insufficient salutogenetic measures for the nursing staff, have an obstructive effect on dignified treatment., Sabine Vogetseder, MA, in englischer Sprache, Abweichender Titel laut Übersetzung der Verfasserin/des Verfassers, Masterarbeit Universität Innsbruck, Universitätslehrgang Medizinrecht 2022

Der Menschenwürde kommt bei den körperbezogenen psychosozialen Tätigkeiten im Bereich des gehobenen Dienstes für Gesundheits- und Krankenpflege eine wichtige Rolle zu. Um willentlich gute angemessene Handlungen in der spezifischen Betreuungssituation zu entscheiden, bedarf es eines systematischen Nachdenkens. Die Pflegeethik wird nicht bloß als eine theoretisch-wissenschaftliche Methode, die unter anderem die etablierten Werte einer Gesellschaft zur Disposition stellt, sondern auch als eine zwischenmenschliche Praxis verstanden, die durch das interpretative, kontextuelle und hermeneutische Wissen über die Patient:innen eine situationsbezogene, assoziativ erspürte, erfahrungsgeleitete sowie ganzheitliche – würdevolle – Begleitung ermöglicht. Die Pflegeethik gewährt zudem eine kritische Standortreflexion und unterstützt den Professionalisierungsprozess der Pflege. Das arbeitsrechtliche Bundesgesetz der Gesundheits- und Krankenpflege (GuKG) determiniert die Pflegeinteraktion, indem es den Verhaltenskorridor durch die gesetzten Rahmenbedingungen einengt. Die Normen der Aus-, Fort- und Weiterbildungen, die gesetzlichen Bestimmungen bezüglich des Kompetenzbereichs der diplomierten Pflegekräfte und der normierte Gesundheits- und Krankenpflegebeirat beeinflussen die Menschenwürde in der Pflegearbeit maßgeblich. Lücken im Gesetz, wie bspw. die fehlende Verankerung der Pflegeethik oder unzureichende salutogenetische Maßnahmen für die Pflegekräfte, wirken sich hinderlich auf einen würdevollen Umgang aus., Human dignity has an important role in body-related psychosocial activities in the field of higher level health care and nursing. In order to make appropriate wise decisions in the specific care situation, systematic reflection is required. Nursing ethics is not only understood as a theoretical-scientific method that, among other things, provides established values of a society, but also as an interpersonal practice that, through interpretative, contextual and hermeneutic knowledge of the patient, enables situational, associatively sensed, experienceguided as well as holistic – dignified – care. Additionally, care ethics grants a critical location reflection and supports the professionalization process of the nursing sector in general. The federal law of health care and nursing (GuKG) determines the nursing interaction by narrowing the corridor of behavior through the set framework conditions. The standards of education and further trainings, the legal provisions regarding the scope of competence of certified nurses and the standardized health and nursing advisory board have a significant influence on human dignity in nursing work. Gaps in the law, such as the lack of anchoring of nursing ethics or insufficient salutogenetic measures for the nursing staff, have an obstructive effect on dignified treatment., Sabine Vogetseder, MA, in englischer Sprache, Abweichender Titel laut Übersetzung der Verfasserin/des Verfassers, Masterarbeit Universität Innsbruck, Universitätslehrgang Medizinrecht 2022

Diagnosis of salivary gland neoplasms is often challenging due to their high morphological diversity and overlaps. Several recurrent molecular alterations have been described recently, which can serve as powerful diagnostic tools and potential therapeutic targets (e.g. NTRK or RET fusions). However, current sequential molecular testing can be expensive and time consuming. In order to facilitate the diagnosis of salivary gland neoplasms, we designed an all-in-one RNA-based next generation sequencing panel suitable for the detection of mutations, fusions and gene expression levels (including NR4A3) of 27 genes involved in salivary gland neoplasms. Here we present the validation of the "SalvGlandDx" panel on FFPE histological specimen including fine needle aspiration (FNA) cell block material, against the standard methods currently used at our institution. In a second part we describe selected unique cases in which the SalvGlandDx panel allowed proper diagnosis and new insights into special molecular characteristics of selected salivary gland tumors. We characterize a unique salivary gland adenocarcinoma harboring a ZCCHC7-NTRK2 fusion, a highly uncommon spindle cell and pseudoangiomatoid adenoid-cystic carcinoma with MYBL1-NFIB fusion, and a purely oncocytic mucoepidermoid carcinoma, whereas diagnosis could be made by detection of a CRTC3-MAML2 rearrangement on the cell block specimen of the FNA. Further, a rare case of a SS18-ZBTB7A rearranged low-grade adenocarcinoma previously described as potential spectrum of microsecretory adenocarcinoma, is reported. In addition, features of six cases within the spectrum of polymorphous adenocarcinoma / cribriform adenocarcinoma of salivary gland including PRKD1 p.E710D mutations and novel fusions involving PRKAR2A-PRKD1, SNX9-PRKD1 and ATL2-PRKD3, are described.

Die Tirol Kliniken haben sich vor dem Hintergrund der Klimaerwärmung und der endlichen Ressourcen dazu entschieden, einen Transformationsprozess zu mehr ökologischer, ökonomischer sowie sozialer Nachhaltigkeit zu vollziehen. In dieser großen multiperspektiven Organisation treffen differente Werte der psychischen sowie sozialen Systeme aufeinander, die sich für die Umsetzung der Nachhaltigkeitsziele als Hindernis erweisen. Diese Masterthesis erforscht die förderlichen Bedingungsverhältnisse auf dem Weg zu mehr Nachhaltigkeit mit Hilfe der soziologischen Systemtheorie. Dieses Konzept stellt die Multiperspektivität konsequent in den Vordergrund und ist aufgrund ihrer theoretischen Grundentscheidungen besonders geeignet, die durch die divergenten Perspektiven entstehenden Kommunikations-probleme herauszuarbeiten. Um das Identitätsmerkmal einer nachhaltigkeitsbewussten Organisation als ein Selbstverständnis in den Bereichen der Tirol Kliniken erfahrbar zu machen, müssen sich die Nachhaltigkeitsthemen zirkulär manifestieren. Das heißt, dass sich die Themen der Nachhaltigkeit sowohl durch die psychischen Systeme in Form von Führungspersonen sowie MitarbeiterInnen als auch durch die sozialen Systeme in Form von Funktions-, Organisations- sowie Interaktionssystemen wechselseitig ermöglichen müssen. Dabei bietet sich die Prozessethik als ein Instrument des gemeinsamen Lernens sowie Reflektierens rund um die Themen der Nachhaltigkeit an. Die differenten Systeme der Tirol Kliniken bilden durch dieses vermittelnde Verfahren eine Art Parlament der Funktionen und können so gemeinsam Lösungen für die komplexen Aufgabenstellungen entscheiden., The organization “Tirol Kliniken” decided in regard to the background of global climate change and the issue of ending resources to implement a transformation process to more ecological, economic, and social sustainability. This sizable, multiperspective organization embraces different values of various, inherently contrary, psychic, and social systems, which occurs to act as a barrier for the implementation of sustainability goals. This master thesis quests beneficial conditions as a base for achieving more sustainability, with the help of the sociological system theory. This concept emphasizes the multiperspectivity and their critical implementations and is thus eligible to solve resulting communication problems within the organization. For raising the tangibility of the criteria of a sustainability-conscious organization as a self-image within all divisions of “Tirol Kliniken”, sustainability subjects shall be manifested in a circular way, which means, that the psychic systems, like management stuff and employees, as well as the social systems, the functional, organizational and interactional systems, are set to reciprocally enable efforts of sustainability. A suitable instrument for achieving mutual learning and reflecting is a method named “processethics”. With this mediating method, the different systems of the organization “Tirol Kliniken” are enabled to form some kind of a “parliament of the functions” and are thus able to find mutual solutions for complex tasks., Sabine Vogetseder, Abweichender Titel laut Übersetzung der Verfasserin/des Verfassers, Universität Innsbruck, Masterarbeit, 2020, (VLID)5392796

Regulatory T cells (Tregs) represent a major population in the control of immune homeostasis and autoimmunity. Here we show that Fos-like 2 (Fosl2), a TCR-induced AP1 transcription factor, represses Treg development and controls autoimmunity. Mice overexpressing Fosl2 (Fosl2$^{tg}$) indeed show a systemic inflammatory phenotype, with immune infiltrates in multiple organs. This phenotype is absent in Fosl2$^{tg}$ × Rag2$^{-/-}$ mice lacking T and B cells, and Fosl2 induces T cell-intrinsic reduction of Treg development that is responsible for the inflammatory phenotype. Fosl2$^{tg}$ T cells can transfer inflammation, which is suppressed by the co-delivery of Tregs, while Fosl2 deficiency in T cells reduces the severity of autoimmunity in the EAE model. We find that Fosl2 could affect expression of FoxP3 and other Treg development genes. Our data highlight the importance of AP1 transcription factors, in particular Fosl2, during T cell development to determine Treg differentiation and control autoimmunity.

Zusammenfassung: Wir beschreiben einen testikulären primitiven neuroektodermalen Tumor (PNET) mit intratubulärer Keimzellneoplasie des angrenzenden Hodenparenchyms bei einem 25-jährigen Patienten. Testikuläre PNET sind selten. Ihre Entstehung wird auf eine maligne somatische Transformation in einem testikulären Keimzelltumor zurückgeführt. Morphologisch und molekularpathologisch ähneln diese Tumoren kindlichen zentralen PNET, die keine Rearrangierung des EWS-Gens auf Chromosom22 aufweisen. Auch im hier beschriebenen Fall konnte keine Translokation nachgewiesen werden

During a study on the mTor pathway in the rat kidney we observed a striking increase of the phosphorylation of the S6 kinase in mitosis. In cryostat sections of perfusion-fixed tissue mitotic cells appeared as bright spots in immunofluorescence using an antibody specific for the phosphorylation site Thr421/Ser424. They were easily spotted in overviews with the objective 4× and 10×. Immunofluorescence was weak during the interphase. During the prophase it increased in both the nucleus and the cytoplasm and it remained bright during the subsequent phases of mitosis. All mitotic cells which were found in tubules and in the interstitium of the kidney using a chromatin stain displayed the bright immunofluorescence for phospho-S6 kinase. The same phenomenon was observed in rat liver and in mouse kidney as well as in a human cell line. Provided a rapid fixation, mitotic cells could be identified with the immunoperoxidase technique in paraffin sections of immersion-fixed tissue. This is the first report of phosphorylation of S6 kinase during mitosis in vivo. Thus, immunohistochemistry with anti-phospho-S6 kinase (Thr421/Ser424) appears to provide a convenient way to detect mitotic cells at low magnification

We searched for morphological evidence to support the hypothesis that stem cells are responsible for renal tubular cell proliferation. The rationale of the study was that if proliferation relies on progenitors, mitotically active cells should be less differentiated than their neighbors. As the retention of the thymidine analog BrdU has been the only approach employed to identify stem cells in the kidney up to now we additionally characterized BrdU-retaining cells. Rat kidneys were fixed by perfusion. Cycling cells identified by mitotic figures or the expression of the proliferating cell nuclear antigen (PCNA) were examined by light microscopy and electron microscopy as well as immunofluorescence for four differentiation markers. Newborn rats were injected with BrdU in order to detect label-retaining cells. After a period of 8, 14 and 35weeks the kidneys were examined for BrdU by immunofluorescence and the four differentiation markers mentioned above. All cycling cells showed the same degree of differentiation compared to non-cycling cells. Most of the detected label-retaining cells were differentiated. We conclude that cycling cells in tubules of the healthy kidney are differentiated and that the retention of label is not a criterion to identify stem cells in renal tubules

The eukaryotic translation initiation factor eIF3a is one of the core subunits of the translation initiation complex eIF3, responsible for ribosomal subunit joining and mRNA recruitment to the ribosome. It is known to play an important role in general translation initiation as well as in the specific translational regulation of various gene products, among which many influence tumour development, progression, and the therapeutically important pathways of DNA damage repair. Therefore, beyond its role in protein synthesis, eIF3a is emerging as regulator in tumour pathogenesis and therapy response and, therefore, a potential tumor marker. By means of a tissue microarray (TMA) for histopathological and statistical assessment, we here show eIF3a expression in 103 cases of squamous cell carcinoma of the oral cavity (OSCC), representing tissues from 103 independent patients. A subset of the study cohort was treated with platinum based therapy. Our results show that the 170 kDa protein is upregulated in OSCC and correlates with good overall survival. Overexpressing tumors respond better to platinum-based chemotherapy, suggesting eIF3a as a putative predictive as well as prognostic tumor marker in OSCC.

This thesis covers the analysis of sparse and irregular fuel consumption data of long distance haulage articulate trucks. It is shown that this kind of data is hard to analyse with multivariate as well as with functional methods. To be able to analyse the data, Principal Components Analysis through Conditional Expectation (PACE) is used, which enables the use of observations from many trucks to compensate for the sparsity of observations in order to get continuous results. The principal component scores generated by PACE, can then be used to get rough estimates of the trajectories for single trucks as well as to detect outliers. The data centric approach of PACE is very useful to enable functional analysis of sparse and irregular data. Functional analysis is desirable for this data to sidestep feature extraction and enabling a more natural view on the data.

This thesis covers the analysis of sparse and irregular fuel consumption data of long distance haulage articulate trucks. It is shown that this kind of data is hard to analyse with multivariate as well as with functional methods. To be able to analyse the data, Principal Components Analysis through Conditional Expectation (PACE) is used, which enables the use of observations from many trucks to compensate for the sparsity of observations in order to get continuous results. The principal component scores generated by PACE, can then be used to get rough estimates of the trajectories for single trucks as well as to detect outliers. The data centric approach of PACE is very useful to enable functional analysis of sparse and irregular data. Functional analysis is desirable for this data to sidestep feature extraction and enabling a more natural view on the data.

We investigated the proliferative capacity of renal proximal tubular cells in healthy rats. Previously, we observed that tubular cells originate from differentiated cells. We now found 1) by application of bromo-deoxyuridine (BrdU) for 14 days and costaining for BrdU, and the G(1)-phase marker cyclin D1 that the bulk of cells in the S3 segment of juvenile rats were involved in proliferation; 2) that although the proliferation rate was about 10-fold higher in juvenile rats compared with adult rats, roughly 40% of S3 cells were in G(1) in both groups; 3) that after a strong mitotic stimulus (lead acetate), proliferation was similar in juveniles and adults; 4) that there was a high incidence of cyclin D1-positive cells also in the healthy human kidney; and 5) by labeling dividing cells with BrdU for 2 days before the application of lead acetate and subsequent costaining for BrdU and cell cycle markers, that, although a strong mitotic stimulus does not abolish the period of quiescence following division, it shortens it markedly. Thus the capacity of the proximal tubule to rapidly recruit cells into division relies on a large reserve pool of cells in G(1) and on the shortening of the obligatory period of quiescence that follows division.

We searched for morphological evidence to support the hypothesis that stem cells are responsible for renal tubular cell proliferation. The rationale of the study was that if proliferation relies on progenitors, mitotically active cells should be less differentiated than their neighbors. As the retention of the thymidine analog BrdU has been the only approach employed to identify stem cells in the kidney up to now we additionally characterized BrdU-retaining cells. Rat kidneys were fixed by perfusion. Cycling cells identified by mitotic figures or the expression of the proliferating cell nuclear antigen (PCNA) were examined by light microscopy and electron microscopy as well as immunofluorescence for four differentiation markers. Newborn rats were injected with BrdU in order to detect label-retaining cells. After a period of 8, 14 and 35weeks the kidneys were examined for BrdU by immunofluorescence and the four differentiation markers mentioned above. All cycling cells showed the same degree of differentiation compared to non-cycling cells. Most of the detected label-retaining cells were differentiated. We conclude that cycling cells in tubules of the healthy kidney are differentiated and that the retention of label is not a criterion to identify stem cells in renal tubules

Zusammenfassung: Wir beschreiben einen testikulären primitiven neuroektodermalen Tumor (PNET) mit intratubulärer Keimzellneoplasie des angrenzenden Hodenparenchyms bei einem 25-jährigen Patienten. Testikuläre PNET sind selten. Ihre Entstehung wird auf eine maligne somatische Transformation in einem testikulären Keimzelltumor zurückgeführt. Morphologisch und molekularpathologisch ähneln diese Tumoren kindlichen zentralen PNET, die keine Rearrangierung des EWS-Gens auf Chromosom22 aufweisen. Auch im hier beschriebenen Fall konnte keine Translokation nachgewiesen werden

During a study on the mTor pathway in the rat kidney we observed a striking increase of the phosphorylation of the S6 kinase in mitosis. In cryostat sections of perfusion-fixed tissue mitotic cells appeared as bright spots in immunofluorescence using an antibody specific for the phosphorylation site Thr421/Ser424. They were easily spotted in overviews with the objective 4× and 10×. Immunofluorescence was weak during the interphase. During the prophase it increased in both the nucleus and the cytoplasm and it remained bright during the subsequent phases of mitosis. All mitotic cells which were found in tubules and in the interstitium of the kidney using a chromatin stain displayed the bright immunofluorescence for phospho-S6 kinase. The same phenomenon was observed in rat liver and in mouse kidney as well as in a human cell line. Provided a rapid fixation, mitotic cells could be identified with the immunoperoxidase technique in paraffin sections of immersion-fixed tissue. This is the first report of phosphorylation of S6 kinase during mitosis in vivo. Thus, immunohistochemistry with anti-phospho-S6 kinase (Thr421/Ser424) appears to provide a convenient way to detect mitotic cells at low magnification

We searched for morphological evidence to support the hypothesis that stem cells are responsible for renal tubular cell proliferation. The rationale of the study was that if proliferation relies on progenitors, mitotically active cells should be less differentiated than their neighbors. As the retention of the thymidine analog BrdU has been the only approach employed to identify stem cells in the kidney up to now we additionally characterized BrdU-retaining cells. Rat kidneys were fixed by perfusion. Cycling cells identified by mitotic figures or the expression of the proliferating cell nuclear antigen (PCNA) were examined by light microscopy and electron microscopy as well as immunofluorescence for four differentiation markers. Newborn rats were injected with BrdU in order to detect label-retaining cells. After a period of 8, 14 and 35weeks the kidneys were examined for BrdU by immunofluorescence and the four differentiation markers mentioned above. All cycling cells showed the same degree of differentiation compared to non-cycling cells. Most of the detected label-retaining cells were differentiated. We conclude that cycling cells in tubules of the healthy kidney are differentiated and that the retention of label is not a criterion to identify stem cells in renal tubules