Medical University of Vienna

Iron and manganese (Fe/Mn) often lead to aesthetic quality issues in water supply. Strong and problematic black-brown particle formation was persistently observed in an alluvial drinking water well, even though oxygen enrichment probes, intended for in situ i.e., subsurface iron/manganese removal, were installed. To investigate the cause of the problem, a comparative and multiparametric approach was undertaken at the problematic well, seven additional wells (with 0.3 to 70 km distance to the affected well) and all the adjacent surface waters. Via a time-series investigation of up to 2.5 years, microbiological analysis (high-throughput 16S rRNA gene amplicon sequencing, total cell count) and chemical analysis (high-resolution elemental analysis using inductively coupled mass spectrometry and others) of the water samples were performed. Results revealed previously unreported, extremely dynamic, and seasonally recurring patterns of genus Crenothrix (a sheathed, filamentous bacterial population) in water samples obtained from the particle-affected well. Crenothrix spp. dominated the microbial community in summer months (up to 82 % relative abundance), being virtually absent in winter. Explanatory models for the high dynamics and association with bio-geochemical processes were established. These included methane formation and manganese mobilization in relation to riverbank filtration in the summer months, as well as changing aerobic and anaerobic conditions in the aquifer. Dominance of Crenothrix spp. in the affected well, low abundance in weak particle-affected wells, and total absence in non-affected wells was observed. This led to the suggestion of Crenothrix spp. as a technical indicator for Fe/Mn treatment failure for alluvial groundwater (e.g., genetic marker quantification by q/dPCR), to be evaluated in future studies regarding their applicability across a broader geographic context. Despite being first described in association with drinking water deterioration 150 years ago, this is the first study reporting seasonally recurring dominant patterns of Crenothrix spp. in association with operational/aesthetic issues for drinking water production.

Otodectes cynotis (Acari: Psoroptidae) constitutes an obligate, non-burrowing ectoparasite and causes otodectic mange primarily in domestic and wild carnivores. Only few studies have described this parasite in herbivore hosts so far. In the current study, we report O. cynotis infestations in Southern pudus (Pudu puda), categorized in the IUCN red list as near threatened. Otodectes cynotis was detected in free-ranging animals in Chile (in situ), as well as in zoo-housed pudus at the Zoo Wuppertal, Germany (ex situ). During clinical work, two free-ranging pudus temporarily rehabilitated at the Centro de Rehabilitación de Fauna Silvestre (CEREFAS), Valdivia, Chile, were observed with low to moderate yellowish-brown secretions and encrustations inside the pinna and external auditory canal accompanied by an inflammatory Otitis externa. Analysis via light microscopy exhibited the presence of mange mites, which were identified as O. cynotis via morphological characteristics and molecular analysis. At the Zoo Wuppertal, ear mites were detected in 15 pudus between 2015 and 2024, however, a definite species identification (O. cynotis) was carried out in 4 animals within the current study between 2023 and 2024. Some affected pudus showed bald spots around the ears and the head and exhibited headshaking behavior, whilst others were asymptomatic. In some cases, mites were found as a secondary finding when clinical examination under general anesthesia was performed for other reasons. To the best of our knowledge, this signifies the first report of O. cynotis infestations in pudus by combining morphological and molecular identification. We here present clinical in situ and ex situ data and show that zoological gardens and widlife rehabilitation centers play an important role in research and monitoring of neglected wildlife diseases.

An overview is given on the range of direct and indirect treatment interventions for swallowing problems. The therapist’s role in planning dysphagia interventions, screening, assessment, behavioural treatment and evaluation is elucidated. With emphasis on the multidisciplinary team, tasks and responsibilities of the phoniatrician are described. Basic principles of drug treatment in dysphagia are introduced, addressing pharmacological intervention for swallowing problems in degenerative neurological diseases and medications that potentially affect swallowing function. Botulinum toxin is presented as a treatment option of isolated cricopharyngeal dysfunction or upper oesophageal sphincter spasm. Oral, enteral and parenteral nutrition management in dysphagic patients is introduced in two parts. After a short overview on oral, enteral and parenteral nutrition management in dysphagic patients, the refeeding syndrome is described. Challenges in the production of texture-modified food in oropharyngeal dysphagia are presented in detail. Indications for surgical procedures in dysphagia are introduced, addressing specific organ structures, severe aspiration, swallowing disorders after radio-chemotherapy and percutaneous endoscopic gastrostomy (PEG). Indications and contra-indications of PEG and ethical issues are discussed. Tracheal tube management is described with a stepwise approach to rehabilitation of voice and swallowing. Complications of tracheal cannula usage are described. Causes and predictors of dysphagia in non-surgically treated patients with head and neck cancer are introduced, addressing inter alia the toxicity of radiotherapy. The incidence of aspiration and aspiration pneumonia, dysphagia stages according to swallowing phases and the multidisciplinary management of swallowing in this patient group are given. Prognostic aspects are discussed, considering oropharyngeal dysphagia in neurological disorders, after radio-chemotherapy for, or primarily surgically treated, ENT malignancies and other disorders.

Dysphagia is defined and distinguished from other swallowing disorders. Epidemiological data are presented. Symptomatic components of dysphagia, the rating of its severity, and indirect and direct symptoms are introduced. An overview is given about aetiological and pathogenetic backgrounds of dysphagia.

After discussion of general aspects of evaluation of verbal communication, specific assessment tools are presented to examine motor speech disorders highlighting informal and formal approaches. Issues to evaluate nonverbal communication are indicated. Elements of the Speech Motor Examination Protocol are introduced in detail as a precondition to developing an individual plan of clinical speech therapy and further therapeutic interventions. Concerning the evaluation of oral motor skills, an exemplary scale is displayed. Requirements to develop and apply objective analyses of speech are presented. Anatomical and sensorimotor examination of the structures involved in speech production, perceptual assessment, assessment levels, tasks and outcome measures in motor speech disorders are elucidated. Instrumental techniques are introduced. Elements of a comprehensive neurological evaluation and laboratory examinations are considered. Techniques of neuroradiological imaging are discussed in detail. Symptomatic aspects are presented in respect of various neurological diseases, useful for the differential diagnosis of the various causes of apraxia and dysarthria. Electromyography is elucidated by many examples of neurological vocal fold motor disorders. The interpretation of the results of logopaedic/SLP examination is defined as a synopsis with the further findings of the multi-disciplinary rehabilitation team. Items of occupational therapy are presented.

Frequently used tests for dysphagia screening and clinical swallowing evaluation are presented. The functional swallowing examination with flexible endoscopes is introduced, addressing the FEES protocol, innovations and technical advances. The technical background of fibre-optic endoscopic evaluation of swallowing (FEES) and digital workstation recording of FEES surveys is elucidated and technological items are explained. After displaying an assessment protocol, FEES scoring systems are presented. Indications, technical considerations, radiation dose, examination technique, interpretation and combined investigations of radiological diagnostic tools are introduced. Catheter-based technology and capsule-based pH-metry are presented as options of pharyngeal and oesophageal pH-metry, the evaluation of pH-measurements is explained. Concerning manometry, multichannel intraluminal impedance devices and high-resolution manometry (HRM) are introduced. To explain sonography of the tongue during swallowing and infant sucking, examination methods are displayed and examples of normal tongue motions are presented during these acts. Possible diagnostic applications of ultrasound of tongue movements are discussed and an overview is given about digital developments and advances. Health-related quality of life (HRQoL) questionnaires for swallowing disorders are introduced addressing generic QoL instruments, dysphagia-specific QoL questionnaires, paediatric dysphagia-related HRQoL measures, HRQoL in the elderly with dysphagia and questionnaires for primary diseases that often result in oropharyngeal dysphagia. Options to detect and to diagnose swallowing events by automatic digital recording are explained, and mobile devices are presented.

The current neuroscientific understanding of neural and mental functions is predominantly oriented towards the modular concepts of information technology. One aspect that is largely pushed into the background is the evaluation of brain function from an evolutionary point of view. The theoretical concepts of various scientific disciplines summarized in this book are largely based on evolutionary or hierarchical principles that can be applied to both neural and mental functions. The beginnings of this approach go back to the philosopher Herbert Spencer, who introduced an explanatory model for the phylogeny and pathologies of the brain with the concepts of evolution and dissolution. Hughlings Jackson found in the neurological symptoms of his patients Spencer´s principle of dissolution of the nervous system confirmed. From this point of view, cerebral lesions (dissolution) provide an insight into the phylogenetic development (evolution) of the brain. For Jackson, evolution represents a process from a state of the highest to the lowest organization, whereby he uses the term organization to describe the extent of the prefabricated automatic connections between the neural units. The validity of the hierarchical organization of the brain postulated by Jackson is largely confirmed by modern neurological research. Hierarchical principles of organization can be proven in the motor and somatosensory system, but also in the visual system.

A hierarchical organization of instinctive actions has already been postulated by comparative behavioural research. However, these views require a corresponding hierarchical structural correlate in the brain. The field of evolutionary neuroethology tries to fathom these connections between specific behaviour and brain structure. According to Paul MacLean, the human brain is from an evolutionary point of view a “triune brain”, i.e. an evolutionary three-part neural system, which represents the phylogenetic heritage of reptiles as well as of lower- and higher-developed mammals. These associations form a unit, corresponding to a conglomerate of three brains, although they differ significantly in structure and neurochemistry, and—in evolutionary terms—are aeons apart. Although the associations are highly interconnected, there is also evidence of independent functioning. The findings of evolutionary neuroethology are also reflected in the ideas of evolutionary psychiatry, especially with regard to the genesis of psychopathological symptoms.

The observation of homologous behavioural patterns of related species, for example between humans and primates, provides insights into the evolutionary-hierarchical principles of brain development. Congenital behaviours in the form of instinctive movements, are found in humans in pure form almost exclusively in the newborn or infant, since early ontogenesis at least partially represents phylogenetic history. In the adult human being residuals of instinctive actions can still be observed in rudimentary form, for example in the greeting gestures, which can be assigned to the instinctive humility behaviour of many mammals. A further possibility to observe instinctive movements or actions in humans are—according to Jackson’s principle of dissolution—disease processes associated with focal or diffuse cerebral lesions. Depending on the severity of the brain dysfunction, these instinctive movements occur reflexive or automatically. In the dissolution of brain function thus phylogenetic and ontogenetic stages of development are exposed or repeated.

The theory of microgenesis is based on the assumption that every mental event is the result of an unfolding process that passes through the individual stages of evolution and ontogenesis. This process, which follows evolutionary neural hierarchical structures, is applicable to aspects of perception, action and consciousness. A disturbance of the microgenetic unfolding process, i.e. a neurological symptom produced by a brain lesion, is seen as a snapshot of a process that manifests prematurely, and thus in an incomplete form. The appearance of the symptom correlates with the height of the lesion. Microgenetic ideas are also represented in Gestalt therapy, a psychotherapeutic method whose theory is also based on the microgenetic unfolding process.

Sigmund Freud has been influenced as a neurologist by the work of Hughlings-Jackson and Herbert Spencer, thus the metapsychological theories of psychoanalysis also includes hierarchical aspects. In addition to the models of the psychic apparatus, the concepts of psychic functioning—the so-called primary and secondary process—or the phenomenon of regression are based on hierarchical principles. The onto- and phylogenetic references in psychoanalytical theory also contain hierarchical ideas. The research area of neuropsychoanalysis attempts to investigate and test metapsychological theories using neuroscientific methods. The data of evolutionary neuroethology provide numerous concepts that could be associated with psychoanalytical theory. MacLean’s concept of emotomentation and ratiomentation shows some striking parallels with the principles of primary and secondary process mentation discovered by Freud. Likewise, the pictorial and drive-determined contents of the dream event can be associated with the activity of the limbic system decoupled from the cortex.

Key message Plant-made PD1–Fc fusions engineered for optimized glycosylation and Fc-receptor engagement are highly efficient in blocking PD1/PDL1 interactions and can be cost-effective alternatives to antibody-based immune checkpoint inhibitors. Abstract Immune checkpoint inhibitors (ICIs) are antibodies to receptors that have pivotal roles during T-cell activation processes. The programmed cell death 1 (PD1) can be regarded as the primary immune checkpoint and antibodies targeting PD1 or its ligand PDL1 have revolutionized immunotherapy of cancer. However, the majority of patients fail to respond, and treatment resistance as well as immune-related adverse events are commonly associated with this therapy. Alternatives to antibody-based ICIs targeting the PD1 pathway may bear the potential to overcome some of these shortcomings. Here, we have used a plant expression platform based on the tobacco relative Nicotiana benthamiana to generate immunoglobulin fusion proteins harboring the wild type or an affinity-enhanced PD1 ectodomain. We have exploited the versatility of our system to generate variants that differed regarding their glycosylation profile as well as their capability to engage Fc-receptors. Unlike its wild-type counterpart, the affinity-enhanced versions showed strongly augmented capabilities to engage PDL1 in both protein- and cell-based assays. Moreover, in contrast with clinical antibodies, their binding is not affected by the glycosylation status of PDL1. Importantly, we could demonstrate that the plant-made PD1 fusion proteins are highly efficient in blocking inhibitory PD1 signaling in a T cell reporter assay. Taken together, our study highlights the utility of our plant-based protein expression platform to generate biologics with therapeutic potential. Targeting PDL1 with plant derived affinity-enhanced PD1 immunoglobulin fusion proteins may reduce overstimulation associated with antibody-based therapies while retaining favorable features of ICIs such as long serum half-life.

Introduction Fractures of the odontoid process are associated with high non-union rates, challenging treatment, and high incidence of screw-related complications. The aim of this study was to compare the biomechanical competence of a single biointegrative bone allograft screw versus two conventional cannulated screws for odontoid fracture fixation. Materials and methods The odontoid process of intact C2 vertebral specimens was subjected to quasi-static loading until fracture. Specimens with an Anderson and d’Alonzo type II or III fracture (n = 47) were fixated with either two conventional cannulated screws or with a single bone allograft screw. The constructs were biomechanically tested to failure in the same fashion as in their intact state. Stiffness, yield, and ultimate load were evaluated. The results were adjusted by age, sex, volumetric bone mineral density (vBMD), and the cross-sectional area ratio of cortical bone to total bone measured at the junction of the odontoid process with the vertebral body (Ct.Ar/Tt.Ar). Results Stiffness, yield and ultimate load were restored in the cannulated screws group by 44 ± 10%, 46 ± 7%, and 46 ± 5% and in the bone allograft group by 50 ± 12%, 30 ± 9%, and 34 ± 6% (mean ± SE). There were no significant differences between the groups regarding the three mechanical outcomes (0.104 ≤ p ≤ 0.223). Positive significant relation was found between vBMD and stiffness in each group (0.248 ≤ R²≤0.273, 0.018 ≤ p ≤ 0.038), as well as between Ct.Ar/Tt.Ar and stiffness (R²=0.218, p = 0.033), vBMD and ultimate load (R²=0.430, p = 0.001) and ultimate loadand vBMD (R²=0.315, p = 0.010) in the cannulated screws group. Conclusions The primary stability of odontoid fracture fixation is determined mainly by the quality of the local bone and independent of the fixation technique. From the biomechanical perspective, the lower mean values for the yield and ultimate load restored in the bone allograft group compared to the cannulated screws group should be compensated by lower peak load during the patient’s rehabilitation process.

Die Digitalisierung von (multimodalen) Texten hat nicht nur zu einer Bandbreite an Lesemedien geführt, sondern über neue Formen der Textdarstellung auf Smartphones, Tablets oder Computern auch zu neuen Formen des Lesens. Über die Frage hinaus, ob sich die Rezeptionsprozesse bei digitalisierten Texten von jenen einer gedruckten Lektüre unterscheiden, gilt es, die Medialität des Lesens in der multimedialen Medienkultur stets aufs Neue zu bestimmen. Der Beitrag unternimmt eine Verknüpfung theoretischer Ansätze der Medien des Lesens mit empirischen Bestandsaufnahmen von Lesepraktiken, um die Bedeutung der Medialität des Lesens im digitalen Zeitalter zu begreifen. Im Zentrum der Analyse stehen die Möglichkeiten und Konsequenzen des Lesens von Schrift-Bild-Kombinationen in Texten, welche die für das gedruckte Buch bestimmende Einheit von Speichern, Prozessieren und Übertragen überwunden haben, nicht mehr an einem festgelegten Ort existieren und sich in der multimodalen Umgebung laufend bewegen können.

Tetraploidisation plays a crucial role in evolution, development, stress adaptation, and disease, but its beneficial or pathological effects in different tissues remain unclear. This study aims to compare physiological and unphysiological tetraploidy in eight steps: 1) mechanisms of diploidy-to-tetraploidy transition, 2) induction and elimination of unphysiological tetraploidy, 3) tetraploid cell characteristics, 4) stress-induced unphysiological tetraploidy, 5) comparison of physiological vs. unphysiological tetraploidy, 6) consequences of unphysiological stress-induced tetraploidy, 7) nutritional or pharmacological prevention strategies of tetraploidisation, and 8) knowledge gaps and future perspectives. Unphysiological tetraploidy is an adaptive stress response at a given threshold, often involving mitotic slippage. If tetraploid cells evade elimination through apoptosis or immune surveillance, they may re-enter the cell cycle, causing genetic instability, micronuclei formation, aneuploidy, modification of the epigenome and the development of diseases. The potential contributions of unphysiological tetraploidy to neurodegenerative, cardiovascular and diabetes related diseases are summarized in schematic figures and contrasted with its role in cancer development. The mechanisms responsible for the transition from physiological to unphysiological tetraploidy and the tolerance to tetraploidisation in unphysiological tetraploidy are not fully understood. Understanding these mechanisms is of critical importance to allow the development of targeted nutritional and pharmacological prevention strategies and therapies.

Objective: Implantable ventricular assist devices to support pediatric patients with left ventricular failure remain an unmet medical need. The aim of this work was to assess the feasibility of a miniaturized two-stage pump concept as a left ventricular assist device (LVAD) intended for small pediatric patients. Methods: The pump leverages a two-stage design with a back-to-back impeller configuration. Computational fluid dynamics (CFD) alongside finite element method (FEM) analysis were utilized to design the pump and its actuation. The magnetic and hydrodynamic properties of the axial and radial bearing were designed and analyzed considering the motor characteristics. The hydraulic performance was validated in a flow loop, and hemocompatibility parameters were numerically assessed and compared to the HeartMate 3. Results: At design condition of 1.5 L/min and 6400 rpm, the Two-Stage Pump builds up a pressure of 58 mmHg. The dynamic analysis of the radial hydrodynamic journal bearing demonstrated that an impeller equilibrium position can be achieved by introducing an additional radial load to balance the forces. The axial reluctance force of the motor is shown to be sufficient to balance the axial forces. The motor losses of 0.18 W result in a local temperature increase of 0.4 K. Compared to the Heartmate 3, the Two-Stage Pump demonstrates similar or even superior hemocompatibility results for pediatric use at a reduced circumferential velocity of 3.7 m/s. Conclusion and significance: The concept of the Two-Stage Pump demonstratesfeasibility and presents compelling results to address the medical challenge of an implantable LVAD for pediatric patients.

Ensuring comprehensive quality control of breast imaging systems involving ionizing radiation like mammography and tomosynthesis is crucial for high diagnostic confidence and maintaining an acceptable patient dose. This requires accurate dosimetric measurements, including air kerma, half-value layer (HVL), and tube voltage as key quantities. Ionization chambers or semiconductor-based X-ray multimeters (XMMs) are used to measure these parameters, with XMMs also displaying tube voltage in one exposure in addition to numerous other parameters. To correct for the influence of slight changes in the X-ray spectra on the response of XMMs, dedicated algorithms are implemented in the XMMs’ software. They often require manual selection of anode/filter combinations prior the measurements. However, to ensure comparability, consistency, and traceability, measurement equipment must be calibrated for each specific measurement quantity. National dosimetry laboratories may have limited options for calibration, and errors can occur if the wrong combination is selected in the XMM software. This study investigates the hypothesis that the selection of the anode/filter combination in XMM software influences the readings. The primary objective is to evaluate the impact of different anode/filter combinations selected in the software on the measurement of air kerma, half-value layer (HVL), and tube voltage. Additionally, the study assesses the feasibility of performing quality assurance for XMMs using a limited range of anode/filter combinations. The readings of eight commercially available XMMs for air kerma rate, HVL and tube voltage were compared with the reference values realized in the IAEA secondary standards dosimetry laboratory for five anode/filter combinations and tube voltages ranging from 25 to 35 kV. The deviation of XMMs readings with different selections of anode/filter combinations in the software was studied. The maximum deviation when anode/filter combination selected in the XMM software matched the anode/filter combination of the X-ray beam was 19% for air kerma, 9% for tube voltage and 10% for HVL. When the selected anode/filter combination set differed from the one used, maximum deviation increased up to 31% for air kerma, 44% for tube voltage and 45% for HVL. Appropriate selection of the anode/filter combination in the XMM software is crucial for obtaining reliable measurement results. Interpolation of calibration coefficients between different radiation qualities and selections is not recommended.