TY - JOUR A1 - Elhfnawy, Ahmed Mohamed A1 - Elsalamawy, Doaa A1 - Abdelraouf, Mervat A1 - Schliesser, Mira A1 - Volkmann, Jens A1 - Fluri, Felix T1 - Red flags for a concomitant giant cell arteritis in patients with vertebrobasilar stroke: a cross-sectional study and systematic review JF - Acta Neurologica Belgica N2 - Giant cell arteritis (GCA) may affect the brain-supplying arteries, resulting in ischemic stroke, whereby the vertebrobasilar territory is most often involved. Since etiology is unknown in 25% of stroke patients and GCA is hardly considered as a cause, we examined in a pilot study, whether screening for GCA after vertebrobasilar stroke might unmask an otherwise missed disease. Consecutive patients with vertebrobasilar stroke were prospectively screened for GCA using erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin, and halo sign of the temporal and vertebral artery on ultrasound. Furthermore, we conducted a systematic literature review for relevant studies. Sixty-five patients were included, and two patients (3.1%) were diagnosed with GCA. Patients with GCA were older in age (median 85 versus 69 years, p = 0.02). ESR and CRP were significantly increased and hemoglobin was significantly lower in GCA patients compared to non-GCA patients (median, 75 versus 11 mm in 1 h, p = 0.001; 3.84 versus 0.25 mg/dl, p = 0.01, 10.4 versus 14.6 mg/dl, p = 0.003, respectively). Multiple stenoses/occlusions in the vertebrobasilar territory affected our two GCA patients (100%), but only five (7.9%) non-GCA patients (p = 0.01). Our literature review identified 13 articles with 136 stroke patients with concomitant GCA. Those were old in age. Headache, increased inflammatory markers, and anemia were frequently reported. Multiple stenoses/occlusions in the vertebrobasilar territory affected around 70% of stroke patients with GCA. Increased inflammatory markers, older age, anemia, and multiple stenoses/occlusions in the vertebrobasilar territory may be regarded as red flags for GCA among patients with vertebrobasilar stroke. KW - giant cell arteritis KW - vertebrobasilar stroke KW - blood sedimentation KW - C-reactive protein KW - hemoglobin KW - stenosis Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-315610 SN - 0300-9009 SN - 2240-2993 VL - 120 IS - 6 ER - TY - JOUR A1 - McNeill, Rhiannon V. A1 - Ziegler, Georg C. A1 - Radtke, Franziska A1 - Nieberler, Matthias A1 - Lesch, Klaus‑Peter A1 - Kittel‑Schneider, Sarah T1 - Mental health dished up — the use of iPSC models in neuropsychiatric research JF - Journal of Neural Transmission N2 - Genetic and molecular mechanisms that play a causal role in mental illnesses are challenging to elucidate, particularly as there is a lack of relevant in vitro and in vivo models. However, the advent of induced pluripotent stem cell (iPSC) technology has provided researchers with a novel toolbox. We conducted a systematic review using the PRISMA statement. A PubMed and Web of Science online search was performed (studies published between 2006–2020) using the following search strategy: hiPSC OR iPSC OR iPS OR stem cells AND schizophrenia disorder OR personality disorder OR antisocial personality disorder OR psychopathy OR bipolar disorder OR major depressive disorder OR obsessive compulsive disorder OR anxiety disorder OR substance use disorder OR alcohol use disorder OR nicotine use disorder OR opioid use disorder OR eating disorder OR anorexia nervosa OR attention-deficit/hyperactivity disorder OR gaming disorder. Using the above search criteria, a total of 3515 studies were found. After screening, a final total of 56 studies were deemed eligible for inclusion in our study. Using iPSC technology, psychiatric disease can be studied in the context of a patient’s own unique genetic background. This has allowed great strides to be made into uncovering the etiology of psychiatric disease, as well as providing a unique paradigm for drug testing. However, there is a lack of data for certain psychiatric disorders and several limitations to present iPSC-based studies, leading us to discuss how this field may progress in the next years to increase its utility in the battle to understand psychiatric disease. KW - hiPSC KW - iPSC KW - stem cells KW - mental disorders KW - affective disorders KW - ADHD Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235666 SN - 0300-9564 VL - 127 ER - TY - JOUR A1 - Endlich, Darius A1 - Richter, Tobias A1 - Marx, Peter A1 - Lenhard, Wolfgang A1 - Moll, Kristina A1 - Witzel, Björn A1 - Schulte-Körne, Gerd T1 - Spelling Error Detection : A Valid and Economical Task for Assessing Spelling Skills in Elementary-School Children JF - Zeitschrift für Entwicklungspsychologie und Pädagogische Psychologie N2 - The ability to spell words correctly is a key competence for educational and professional achievement. Economical procedures are essential to identifying children with spelling problems as early as possible. Given the strong evidence showing that reading and spelling are based on the same orthographic knowledge, error-detection tasks (EDTs) could be considered such an economical procedure. Although EDTs are widely used in English-speaking countries, the few studies in German-speaking countries investigated only pupils in secondary school. The present study investigated N = 1,513 children in elementary school. We predicted spelling competencies (measured by dictation or gap-fill dictation) based on an EDT via linear regression. Error-detection abilities significantly predicted spelling competencies (R² between .509 and .679), indicating a strong connection. Predictive values in identifying children with poor spelling abilities with an EDT proved to be sufficient. Error detection for the assessment of spelling skills is therefore a valid instrument for transparent languages as well. N2 - Rechtschreibung zählt zu den Schlüsselkompetenzen für schulischen und beruflichen Erfolg. Um Kinder mit Rechtschreibproblemen adäquat zu unterstützen, ist eine frühe, möglichst niederschwellige Diagnostik essenziell. Aufgaben, in denen Rechtschreibfehler in präsentierten Texten zu identifizieren sind, könnten derartige ökonomische Verfahren darstellen. Obgleich Fehleridentifikationstests im angloamerikanischen Sprachraum weit verbreitet sind, haben sich die wenigen Studien im deutschsprachigen Raum bisher ausschließlich mit Kindern der Sekundarstufe beschäftigt. Die vorliegende Arbeit untersuchte in vier unabhängigen Studien N = 1.513 Grundschulkinder. Mittels linearer Regressionen wurden Rechtschreibkompetenzen (erhoben durch Fließ- und Lückendiktate) durch Leistungen in Fehleridentifikationstests vorhergesagt. Leistungen im Fehleridentifikationstest sagten Rechtschreibkompetenzen in allen Studien signifikant voraus (R² zwischen .509 und .679), was eine starke Assoziation der beiden Maße belegt. Prädiktive Werte zur Identifikation von Kindern mit schwachen Rechtschreibleistungen durch den Fehleridentifikationstest waren gut. Fehleridentifikation als Maß für Rechtschreibkompetenzen ist damit ein valides Instrument nicht nur für den angloamerikanischen Sprachraum, sondern auch für transparente Sprachen. T2 - Fehleridentifikation: Ein valides und ökonomisches Verfahren zur Erfassung von Rechtschreibkompetenzen in der Grundschule KW - spelling KW - dictation KW - error detection KW - developmental dyslexia KW - diagnosis KW - Rechtschreibung KW - Diktat KW - Fehleridentifikation KW - Lese-Rechtschreibstörung KW - Diagnose Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244665 SN - 0049-8637 SN - 2190-6262 VL - 52 IS - 1-2 ER - TY - JOUR A1 - Andreska, Thomas A1 - Lüningschrör, Patrick A1 - Sendtner, Michael T1 - Regulation of TrkB cell surface expression — a mechanism for modulation of neuronal responsiveness to brain-derived neurotrophic factor JF - Cell and Tissue Research N2 - Neurotrophin signaling via receptor tyrosine kinases is essential for the development and function of the nervous system in vertebrates. TrkB activation and signaling show substantial differences to other receptor tyrosine kinases of the Trk family that mediate the responses to nerve growth factor and neurotrophin-3. Growing evidence suggests that TrkB cell surface expression is highly regulated and determines the sensitivity of neurons to brain-derived neurotrophic factor (BDNF). This translocation of TrkB depends on co-factors and modulators of cAMP levels, N-glycosylation, and receptor transactivation. This process can occur in very short time periods and the resulting rapid modulation of target cell sensitivity to BDNF could represent a mechanism for fine-tuning of synaptic plasticity and communication in complex neuronal networks. This review focuses on those modulatory mechanisms in neurons that regulate responsiveness to BDNF via control of TrkB surface expression. KW - BDNF KW - TrkB KW - subcellular trafficking KW - transactivation KW - synaptic plasticity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235055 VL - 382 ER - TY - JOUR A1 - Stengel, Felix A1 - Vulinovic, Franca A1 - Meier, Britta A1 - Grütz, Karen A1 - Klein, Christine A1 - Capetian, Philipp T1 - Impaired differentiation of human induced neural stem cells by TOR1A overexpression JF - Molecular Biology Reports N2 - DYT-TOR1A is the most common inherited dystonia caused by a three nucleotide (GAG) deletion (dE) in the TOR1A gene. Death early after birth and cortical anomalies of the full knockout in rodents underscore its developmental importance. We therefore explored the timed effects of TOR1A-wt and TOR1A-dE during differentiation in a human neural in vitro model. We used lentiviral tet-ON expression of TOR1A-wt and -dE in induced neural stem cells derived from healthy donors. Overexpression was induced during proliferation of neural precursors, during differentiation and after differentiation into mature neurons. Overexpression of both wildtype and mutated protein had no effect on the viability and cell number of neural precursors as well as mature neurons when initiated before or after differentiation. However, if induced during differentiation, overexpression of TOR1A-wt and -dE led to a pronounced reduction of mature neurons in a dose dependent manner. Our data underscores the importance of physiological expression levels of TOR1A as crucial for proper neuronal differentiation. We did not find evidence for a specific impact of the mutated TOR1A on neuronal maturation. KW - dystonia KW - DYT1 KW - torsinA KW - TOR1A KW - neuronal stem cells KW - neuronal differentiation KW - inducible expression Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241177 UR - https://doi.org/10.1007/s11033-020-05390-x VL - 47 ER - TY - JOUR A1 - Reiners, Christoph A1 - Drozd, Valentina A1 - Yamashita, Shunichi T1 - Hypothyroidism after radiation exposure: brief narrative review JF - Journal of Neural Transmission N2 - The thyroid gland is among the organs at the greatest risk of cancer from ionizing radiation. Epidemiological evidence from survivors of radiation therapy, atomic bombing, and the Chernobyl reactor accident, clearly shows that radiation exposure in childhood can cause thyroid cancer and benign thyroid nodules. Radiation exposure also may induce hypothyroidism and autoimmune reactions against the thyroid, but these effects are less well-documented. The literature includes only a few, methodologically weak animal studies regarding genetic/molecular mechanisms underlying hypothyroidism and thyroid autoimmunity after radiation exposure. Rather, evidence about radiation-induced hypothyroidism and thyroid autoimmunity derives mainly from follow-up studies in patients treated with external beam radiotherapy (EBRT) or iodine-131, and from epidemiological studies in the atomic bombing or nuclear accident survivors. Historically, hypothyroidism after external irradiation of the thyroid in adulthood was considered not to develop below a 10–20 Gy dose threshold. Newer data suggest a 10 Gy threshold after EBRT. By contrast, data from patients after iodine-131 “internal radiation therapy” of Graves´ disease indicate that hypothyroidism rarely occurs below thyroid doses of 50 Gy. Studies in children affected by the Chernobyl accident indicate that the dose threshold for hypothyroidism may be considerably lower, 3–5 Gy, aligning with observations in A-bomb survivors exposed as children. The reasons for these dose differences in radiosensitivity are not fully understood. Other important questions about the development of hypothyroidism after radiation exposure e.g., in utero, about the interaction between autoimmunity and hypofunction, and about the different effects of internal and external irradiation still must be answered. KW - thyroid KW - hypothyroidism KW - autoimmune thyroiditis KW - diagnostic medical radiation exposure KW - therapeutic medical radiation exposure (EBRT/ RAI) KW - other radiation exposure (atomic bombing/nuclear accidents) Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235653 SN - 0300-9564 VL - 127 ER - TY - JOUR A1 - Cao, Liyu A1 - Chen, Xinyu A1 - Haendel, Barbara F. T1 - Overground Walking Decreases Alpha Activity and Entrains Eye Movements in Humans JF - Frontiers in Human Neuroscience N2 - Experiments in animal models have shown that running increases neuronal activity in early visual areas in light as well as in darkness. This suggests that visual processing is influenced by locomotion independent of visual input. Combining mobile electroencephalography, motion- and eye-tracking, we investigated the influence of overground free walking on cortical alpha activity (~10 Hz) and eye movements in healthy humans. Alpha activity has been considered a valuable marker of inhibition of sensory processing and shown to negatively correlate with neuronal firing rates. We found that walking led to a decrease in alpha activity over occipital cortex compared to standing. This decrease was present during walking in darkness as well as during light. Importantly, eye movements could not explain the change in alpha activity. Nevertheless, we found that walking and eye related movements were linked. While the blink rate increased with increasing walking speed independent of light or darkness, saccade rate was only significantly linked to walking speed in the light. Pupil size, on the other hand, was larger during darkness than during light, but only showed a modulation by walking in darkness. Analyzing the effect of walking with respect to the stride cycle, we further found that blinks and saccades preferentially occurred during the double support phase of walking. Alpha power, as shown previously, was lower during the swing phase than during the double support phase. We however could exclude the possibility that the alpha modulation was introduced by a walking movement induced change in electrode impedance. Overall, our work indicates that the human visual system is influenced by the current locomotion state of the body. This influence affects eye movement pattern as well as neuronal activity in sensory areas and might form part of an implicit strategy to optimally extract sensory information during locomotion. KW - mobile EEG KW - alpha oscillations KW - blinks KW - saccades KW - locomotion KW - pupil size KW - walking phase KW - motor entrainment Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219872 SN - 1662-5161 VL - 14 ER - TY - JOUR A1 - Wertgen, Andreas G. A1 - Richter, Tobias T1 - Source credibility modulates the validation of implausible information JF - Memory & Cognition N2 - Validation of text information as a general mechanism for detecting inconsistent or false information is an integral part of text comprehension. This study examined how the credibility of the information source affects validation processes. Two experiments investigated combined effects of source credibility and plausibility of information during validation with explicit (ratings) and implicit (reading times) measurements. Participants read short stories with a high-credible versus low-credible person that stated a consistent or inconsistent assertion with general world knowledge. Ratings of plausibility and ratings of source credibility were lower when a credible source stated a world-knowledge inconsistent assertion compared with a low-credible source. Reading times on target sentences and on spillover sentences were slower when a credible source stated an assertion inconsistent with world knowledge compared with a low-credible source, suggesting that source information modulated the validation of implausible information. These results show that source credibility modulates validation and suggest a bidirectional relationship of perceived plausibility and source credibility in the reading process. KW - validation KW - plausibility KW - sourcing KW - credibility KW - text comprehension Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234825 SN - 0090-502X VL - 48 ER - TY - JOUR A1 - Lapuente, Juan A1 - Arandjelovic, Mimi A1 - Kühl, Hjalmar A1 - Dieguez, Paula A1 - Boesch, Christophe A1 - Linsenmair, K. Eduard T1 - Sustainable Peeling of Kapok Tree (Ceiba pentandra) Bark by the Chimpanzees (Pan troglodytes verus) of Comoé National Park, Ivory Coast JF - International Journal of Primatology N2 - Primates often consume either bark or cambium (inner bark) as a fallback food tocomplete their diet during periods of food scarcity. Wild chimpanzees exhibit greatbehavioral diversity across Africa, as studies of new populations frequently reveal.Since 2014, we have been using a combination of camera traps and indirect signs tostudy the ecology and behavior of wild chimpanzees (Pan troglodytes verus) in ComoéNational Park, Ivory Coast, to document and understand the behavioral adaptations thathelp them to survive in a savanna–forest mosaic landscape. We found that Comoéchimpanzees peel the bark of the buttresses of kapok tree (Ceiba pentandra) trees to eatthe cambium underneath. Individuals of all sex/age classes across at least six neigh-boring communities peeled the bark, but only during the late rainy season andbeginning of the dry season, when cambium may represent an important fallback food.Baboons (Papio anubis) also target the same trees but mainly eat the bark itself. Mostof the bark-peeling wounds onCeibatrees healed completely within 2 years, seeminglywithout any permanent damage. We recorded chimpanzees visiting trees in early stagesof wound recovery but leaving them unpeeled. Only 6% of peeled trees (N= 53) werereexploited after a year, suggesting that chimpanzees waited for the rest of the trees toregrow the bark fully before peeling them again, thus using them sustainably. Manyhuman groups of hunter-gatherers and herders exploited cambium sustainably in thepast. The observation that similar sustainable bark-peeling behavior evolved in bothchimpanzees and humans suggests that it has an important adaptive value in harshenvironments when other food sources become seasonally scarce, by avoiding thedepletion of the resource and keeping it available for periods of scarcity. KW - bark-peeling KW - ceiba pentandra KW - chimpanzee KW - Savanna–Forest mosaic KW - sustainable Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232581 SN - 0164-0291 VL - 41 ER - TY - JOUR A1 - Gesell, Nathalie A1 - Niklas, Frank A1 - Schmiedeler, Sandra A1 - Segerer, Robin T1 - Mindfulness and romantic relationship outcomes: the mediating role of conflict resolution styles and closeness JF - Mindfulness N2 - Objectives The association of mindfulness and romantic relationship outcomes such as partnership quality and satisfaction is well-established; however, the mechanisms of action are not yet clear. The current study tested conflict resolution styles and closeness as possible mediating factors. We hypothesized that trait mindfulness would increase the use of constructive conflict resolution styles (positive problem solving), decrease the use of destructive styles (conflict engagement, withdrawal, and compliance), and promote feelings of closeness between partners, which in turn would predict positive relationship outcomes (namely partnership quality, partnership satisfaction, and sexual satisfaction). Methods A total of 209 individuals (86% German, 76% female, mean age = 32 years) living in a relationship (31% married) participated in an online questionnaire. Results Mediation analyses revealed that positive problem solving mediated the association between mindfulness and partnership quality with b = .09 (95% CI = .03–.17), mindfulness and partnership satisfaction with b = .07 (95% CI = .02–.13), and mindfulness and sexual satisfaction with b = .04 (95% CI = .00–.10). Furthermore, a mediating role of withdrawal and closeness was shown for individual relationship outcomes. Conclusions Findings suggest that more positive problem solving, less withdrawal, and more closeness are mechanisms by which mindfulness is associated with positive relationship outcomes. The results of our study thus broaden our understanding of the processes that underlie fulfilling romantic relationships and, in turn, underline the positive effects of mindfulness. KW - mindfulness KW - trait mindfulness KW - romantic relationship KW - relationship satisfaction KW - closeness KW - conflict resolution Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235080 SN - 1868-8527 VL - 11 ER - TY - JOUR A1 - Güsgen, C. A1 - Anger, F. A1 - Hauer, T. A1 - Willms, A. A1 - Buhr, H. J. A1 - Germer, C.-T. A1 - Schwab, R. A1 - Lock, J. F. T1 - Fortbildung von Allgemein- und Viszeralchirurgen in der lebensrettenden Notfallchirurgie. Ergebnisse einer Umfrage unter Operationskursteilnehmern JF - Der Chirurg N2 - Hintergrund Die geringe Anzahl operativ zu versorgender Körperhöhlenverletzungen erfordert ein Umdenken in der chirurgischen Aus- und Weiterbildung. Ein entsprechendes Kursformat wird seit 2014 über die DGAV angeboten. Um Berechtigung, Bedarf, Nutzen und Erfolg eines solchen Kursformates zu erheben, erfolgte eine Evaluation durch die bisherigen Kursteilnehmer. Material und Methoden Kursevaluation und zusätzliche Onlinebefragung der bisherigen Kursteilnehmer hinsichtlich Alter, Geschlecht, Ausbildungsstand, Fachrichtung, Versorgungsstufe des Krankenhauses, notfallchirurgischer Erfahrungen, der Häufigkeit chirurgischer Notfallversorgungen, Teilnahme an anderen Kursformaten, Erfahrungen nach der Kursteilnahme, Einschätzung der aktuellen Fort- und Weiterbildungssituation und Finanzierung solcher Kurse. Ergebnisse Insgesamt 142 Kursteilnehmer evaluierten ihre Kursteilnahme, zusätzlich beantworteten 83 den Onlinefragebogen. Über 90 % berichteten von einem nachhaltigen positiven Einfluss des Kurses auf ihr notfallchirurgisches Handeln. Mehr als die Hälfte konnte von konkreten Notfallsituationen berichten, die sie aufgrund der Kursteilnahme besser bewältigen konnten. In der Notfallversorgung erfahrene Chirurgen bewerteten den eigenen Lernerfolg durch die Kursteilnahme signifikant häufiger positiv als ihre weniger erfahrenen Kollegen. Keinen Einfluss auf den Lernerfolg hatten eine Ober- oder Chefarztposition, die Versorgungsstufe des Krankenhauses, das Alter oder Geschlecht der Teilnehmer. Die Mehrheit der antwortenden Chirurgen befürwortet die Integration eines solchen Kursformates in die chirurgische Weiterbildung und fordert hierzu eine finanzielle Unterstützung. Schlussfolgerung Kursformate, in denen notfallchirurgische Strategien und Fähigkeiten vermittelt werden, sind etabliert und werden sehr positiv evaluiert. Die Fort- und Weiterbildung in notfallchirurgischen Fähigkeiten und Kenntnissen liegt im gesellschaftlichen Interesse und zumindest anteilig auch in ihrer Verantwortung. N2 - Background Due to a decreasing number of emergency procedures for body cavity injuries, surgical training is inadequate and current educational concepts must be reconsidered. The German Society for General and Visceral Surgery has set up a surgical training course in 2014 to overcome this shortage. In order to assess the eligibility, needs, benefits and success of such a training format, participants were asked to evaluate the program. Material and methods All participants evaluated the course during participation and were later asked to answer an online survey regarding their age, gender, level of surgical education, surgical discipline, level of care of the hospital, emergency surgical experience and frequency of performing emergency surgery, participation in other programs, experiences after participating in the course, rating of the current training curriculum and funding of such courses. Results Out of 142 participants 83 replied to the online survey. Over 90% reported a lasting positive influence of the course on emergency surgical skills. More than half of the responders remembered a clinical situation which they successfully managed due to the skills they gained during the course. Surgeons experienced in emergency treatment felt significantly more benefit than less experienced colleagues. A consultancy position, the level of care of the hospital, age and sex of the participants did not influence the overall benefits reported. The majority of responding surgeons were in favor of including such a training course in surgical education and stipulated public financial support. Conclusion Course formats that mediate emergency surgery strategies and skills are established and well accepted. Training of surgeons in life-saving emergency surgery is in the public interest and is also partly the responsibility of society. T2 - Advanced training of general and visceral surgeons in life-saving emergency surgery. Results of a survey among participants of a surgery course KW - Damage control surgery KW - Terroranschlagtrauma KW - Abdominaltrauma KW - Messerstichverletzung KW - Schussverletzung KW - damage control surgery KW - terror attack trauma KW - abdominal trauma KW - stab wounds KW - shooting injuries Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235246 SN - 0009-4722 VL - 91 ER - TY - JOUR A1 - Juergens, Lukas A1 - Bieniussa, Linda A1 - Voelker, Johannes A1 - Hagen, Rudolf A1 - Rak, Kristen T1 - Spatio-temporal distribution of tubulin-binding cofactors and posttranslational modifications of tubulin in the cochlea of mice JF - Histochemistry and Cell Biology N2 - The five tubulin-binding cofactors (TBC) are involved in tubulin synthesis and the formation of microtubules. Their importance is highlighted by various diseases and syndromes caused by dysfunction or mutation of these proteins. Posttranslational modifications (PTMs) of tubulin promote different characteristics, including stability-creating subpopulations of tubulin. Cell- and time-specific distribution of PTMs has only been investigated in the organ of Corti in gerbils. The aim of the presented study was to investigate the cell type-specific and time-specific expression patterns of TBC proteins and PTMs for the first time in murine cochleae over several developmental stages. For this, murine cochleae were investigated at the postnatal (P) age P1, P7 and P14 by immunofluorescence analysis. The investigations revealed several profound interspecies differences in the distribution of PTMs between gerbil and mouse. Furthermore, this is the first study to describe the spatio-temporal distribution of TBCs in any tissue ever showing a volatile pattern of expression. The expression analysis of TBC proteins and PTMs of tubulin reveals that these proteins play a role in the physiological development of the cochlea and might be essential for hearing. KW - tubulin-binding cofactors KW - tubulin KW - development KW - cochlea KW - posttranslational modifications KW - hearing Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234852 SN - 0948-6143 VL - 154 ER - TY - BOOK A1 - Reuter, Oliver M. T1 - Erfahrungsverankerte Rezeption : Eine Methode zur Verzahnung von Produktion und Rezeption N2 - Eine Rezeption auf den von Kindern und Jugendlichen selbst gemachten Erfahrungen aufzubauen, ist das zentrale Anliegen der ausgeführten Methode zur Verschränkung von produktiven und rezeptiven Anteilen im Kunstunterricht. Indem vor der Rezeption eine bildnerische Praxis stattfindet, können Ideen und Vorstellungen selbständig und individuell entwickelt und in Bilder übersetzt werden. Bei der erfahrungsverankerten Vermittlung basiert die Rezeption auf einer Schnittmenge zwischen eigenen Handlungen im bildnerischen oder darstellenden Prozess und zentralen Aspekten des Werks. Solche Referenzpunkte zwischen der Produktion und der Rezeption können im Material, im Thema, in der Gattung, im bildnerischen Verfahren oder in einer künstlerischen Strategie ausfindig gemacht werden. Sie dienen dazu, Einsichten, Einstellungen, Kenntnisse und Wissen aus der Produktion in die Rezeption mitzunehmen. Somit ist die Methode der erfahrungsverankerten Rezeption gleichermaßen geeignet für die Vermittlung historischer wie für zeitgenössischer Kunst. Nach der Darlegung und Konturierung der Konzeption zeigt die Publikation Wege auf, die erfahrungsverankerte Rezeption in Unterricht zu überführen. Exemplarische Unterrichtsskizzen illustrieren die Umsetzung im Kunstunterricht. KW - Erfahrung KW - Kunsterziehung KW - Rezeption KW - Unterrichtsmethode KW - Kunstvermittlung KW - Unterrichtsvorbereitung KW - Bildnerisches Gestalten KW - Erfahrungsverankerte Rezeption KW - Ästhetische Praxis KW - Ästhetische Bildung Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-345281 UR - https://www.kopaed.de/kopaedshop/?pg=2_15&pid=1263 SN - 978-3-86736-580-2 N1 - Eine inhaltlich unveränderte, technisch korrigierte Version ist unter https://doi.org/10.25972/OPUS-34528 verfügbar. PB - kopaed ET - 1. Auflage ER - TY - JOUR A1 - Herrmann, Johannes A1 - Adam, Elisabeth Hannah A1 - Notz, Quirin A1 - Helmer, Philipp A1 - Sonntagbauer, Michael A1 - Ungemach-Papenberg, Peter A1 - Sanns, Andreas A1 - Zausig, York A1 - Steinfeldt, Thorsten A1 - Torje, Iuliu A1 - Schmid, Benedikt A1 - Schlesinger, Tobias A1 - Rolfes, Caroline A1 - Reyher, Christian A1 - Kredel, Markus A1 - Stumpner, Jan A1 - Brack, Alexander A1 - Wurmb, Thomas A1 - Gill-Schuster, Daniel A1 - Kranke, Peter A1 - Weismann, Dirk A1 - Klinker, Hartwig A1 - Heuschmann, Peter A1 - Rücker, Viktoria A1 - Frantz, Stefan A1 - Ertl, Georg A1 - Muellenbach, Ralf Michael A1 - Mutlak, Haitham A1 - Meybohm, Patrick A1 - Zacharowski, Kai A1 - Lotz, Christopher T1 - COVID-19 Induced Acute Respiratory Distress Syndrome — A Multicenter Observational Study JF - Frontiers in Medicine N2 - Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS). Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included. Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay. Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients. KW - COVID-19 KW - ARDS (acute respiratory distress syndrome) KW - intensive care medicine KW - pandemia KW - Germany Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219834 SN - 2296-858X VL - 7 ER - TY - JOUR A1 - Gabbert, Lydia A1 - Dilling, Christina A1 - Meybohm, Patrick A1 - Burek, Malgorzata T1 - Deletion of Protocadherin Gamma C3 Induces Phenotypic and Functional Changes in Brain Microvascular Endothelial Cells In Vitro JF - Frontiers in Pharmacology N2 - Inflammation of the central nervous system (CNS) is associated with diseases such as multiple sclerosis, stroke and neurodegenerative diseases. Compromised integrity of the blood-brain barrier (BBB) and increased migration of immune cells into the CNS are the main characteristics of brain inflammation. Clustered protocadherins (Pcdhs) belong to a large family of cadherin-related molecules. Pcdhs are highly expressed in the CNS in neurons, astrocytes, pericytes and epithelial cells of the choroid plexus and, as we have recently demonstrated, in brain microvascular endothelial cells (BMECs). Knockout of a member of the Pcdh subfamily, PcdhgC3, resulted in significant changes in the barrier integrity of BMECs. Here we characterized the endothelial PcdhgC3 knockout (KO) cells using paracellular permeability measurements, proliferation assay, wound healing assay, inhibition of signaling pathways, oxygen/glucose deprivation (OGD) and a pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) treatment. PcdhgC3 KO showed an increased paracellular permeability, a faster proliferation rate, an altered expression of efflux pumps, transporters, cellular receptors, signaling and inflammatory molecules. Serum starvation led to significantly higher phosphorylation of extracellular signal-regulated kinases (Erk) in KO cells, while no changes in phosphorylated Akt kinase levels were found. PcdhgC3 KO cells migrated faster in the wound healing assay and this migration was significantly inhibited by respective inhibitors of the MAPK-, β-catenin/Wnt-, mTOR- signaling pathways (SL327, XAV939, or Torin 2). PcdhgC3 KO cells responded stronger to OGD and TNFα by significantly higher induction of interleukin 6 mRNA than wild type cells. These results suggest that PcdhgC3 is involved in the regulation of major signaling pathways and the inflammatory response of BMECs. KW - blood-brain barrier KW - protocadherin gamma C3 KW - inflammation KW - oxygen/glucose deprivation KW - stroke KW - tumor necrosis factor-α KW - proliferation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219828 SN - 1663-9812 VL - 11 ER - TY - JOUR A1 - Lotz, C. A1 - Muellenbach, R. M. A1 - Meybohm, P. A1 - Rolfes, C. A1 - Reyher, C. T1 - Präklinisches Management bei Herz-Kreislauf-Stillstand – extrakorporale kardiopulmonale Reanimation JF - Der Anaesthesist N2 - Hintergrund Die Überlebenschancen nach präklinischem Herz-Kreislauf-Stillstand sind weiterhin sehr gering. Trotz intensiver Bemühungen bleibt das Outcome seit vielen Jahren weitestgehend konstant. Neue Technologien wie die extrakorporale kardiopulmonale Reanimation (eCPR) können in bestimmten Situationen möglicherweise das Überleben mit gutem neurologischen Outcome signifikant verbessern. Fragestellung Beeinflusst die sofortige Reperfusion und Reoxygenierung des Körpers mittels eCPR das Überleben nach Herz-Kreislauf-Stillstand? Bedarf es einer Erweiterung der „chain of survival“ um die eCPR? Material und Methoden Diskussion aktueller Studienergebnisse und Leitlinienempfehlungen. Ergebnisse Die Überlebensraten nach präklinischem Herz-Kreislauf-Stillstand sind weltweit seit vielen Jahren unverändert bei 10–30 %. Trotz geringer Fallzahlen zeigen neuere retrospektive Studien, dass durch die eCPR eine Verbesserung des Outcome erzielt werden kann. In selektionierten Patientenkollektiven ist ein Überleben mit gutem neurologischen Outcome von 38 % möglich. Schlussfolgerung Ob und mit welcher Lebensqualität ein Herz-Kreislauf-Stillstand überlebt werden kann, ist von vielen unterschiedlichen Faktoren abhängig. Der Faktor Zeit, also die Vermeidung einer „No-flow-Phase“ und die Reduktion der „Low-flow-Phase“, ist von zentraler Bedeutung. Durch die sofortige Wiederherstellung von Zirkulation und Sauerstoffversorgung kann durch die eCPR das Überleben signifikant verbessert werden. Große kontrollierte, randomisierte Studien hierzu fehlen jedoch bisher. N2 - Background The chances of surviving out-of-hospital cardiac arrest (OHCA) are still very low. Despite intensive efforts the outcome has remained relatively poor over many years. In specific situations, new technologies, such as extracorporeal cardiopulmonary resuscitation (eCPR) could significantly improve survival with a good neurological outcome. Objective Does the immediate restoration of circulation and reoxygenation via eCPR influence the survival rate after OHCA? Is eCPR the new link in the chain of survival? Material and methods Discussion of current study results and guideline recommendations. Results The overall survival rates after OHCA have remained at 10–30% over many years. Despite low case numbers more recent retrospective studies showed that an improved outcome can be achieved with eCPR. In selected patient collectives survival with a favorable neurological outcome is possible in 38% of the cases. Conclusion Survival after cardiac arrest and the subsequent quality of life dependent on many different factors. The time factor, i.e. the avoidance of a no-flow phase and reduction of the low-flow phase is of fundamental importance. The immediate restoration of the circulation and oxygen supply by eCPR can significantly improve survival; however, large randomized, controlled trials are currently not available. KW - Rettungskette KW - eCPR KW - Extrakorporale Membranoxygenierung KW - Wiederbelebung KW - Außerklinischer Herz-Kreislauf-Stillstand KW - chain-of-survival KW - eCPR KW - extracorporeal membrane oxygenation KW - resuscitation KW - out-of-hospital cardiac arrest Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232525 SN - 0003-2417 VL - 69 ER - TY - JOUR A1 - Lotz, Christopher A1 - Notz, Quirin A1 - Kranke, Peter A1 - Kredel, Markus A1 - Meybohm, Patrick T1 - Unconventional approaches to mechanical ventilation - step-by-step through the COVID-19 crisis JF - Critical Care N2 - No abstract available. KW - COVID 19 KW - mechanical ventilation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229868 VL - 24 ER - TY - JOUR A1 - Averdunk, Luisa A1 - Bernhagen, Jürgen A1 - Fehnle, Karl A1 - Surowy, Harald A1 - Lüdecke, Hermann-Josef A1 - Mucha, Sören A1 - Meybohm, Patrick A1 - Wieczorek, Dagmar A1 - Leng, Lin A1 - Marx, Gernot A1 - Leaf, David E. A1 - Zarbock, Alexander A1 - Zacharowski, Kai A1 - Bucala, Richard A1 - Stoppe, Christian T1 - The Macrophage Migration Inhibitory Factor (MIF) promoter polymorphisms (rs3063368, rs755622) predict acute kidney injury and death after cardiac surgery JF - Journal of Clinical Medicine N2 - Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT\(_{5–7}\) (rs5844572/rs3063368,“-794”) and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT\(_7\)) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs. 13%; OR 2.01 (1.40–2.88), p = 0.0001). Carriers of CATT\(_7\) were also at higher risk of death (1.8% vs. 0.4%; OR 5.12 (0.99–33.14), p = 0.026). The GC genotype was associated with AKI (20% vs. GG/CC:13%, OR 1.71 (1.20–2.43), p = 0.003). Multivariate analyses identified CATT\(_7\) predictive for AKI (OR 2.13 (1.46–3.09), p < 0.001) and death (OR 5.58 (1.29–24.04), p = 0.021). CATT\(_7\) was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT\(_7\) allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance. KW - acute kidney injury KW - genetic polymorphisms KW - risk prediction KW - (cardiac) surgery KW - inflammatory cytokines KW - clinical studies Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-213126 SN - 2077-0383 VL - 9 IS - 9 ER - TY - JOUR A1 - Curtaz, Carolin J. A1 - Schmitt, Constanze A1 - Herbert, Saskia-Laureen A1 - Feldheim, Jonas A1 - Schlegel, Nicolas A1 - Gosselet, Fabien A1 - Hagemann, Carsten A1 - Roewer, Norbert A1 - Meybohm, Patrick A1 - Wöckel, Achim A1 - Burek, Malgorzata T1 - Serum-derived factors of breast cancer patients with brain metastases alter permeability of a human blood-brain barrier model JF - Fluids and Barriers of the CNS N2 - Background The most threatening metastases in breast cancer are brain metastases, which correlate with a very poor overall survival, but also a limited quality of life. A key event for the metastatic progression of breast cancer into the brain is the migration of cancer cells across the blood-brain barrier (BBB). Methods We adapted and validated the CD34\(^+\) cells-derived human in vitro BBB model (brain-like endothelial cells, BLECs) to analyse the effects of patient serum on BBB properties. We collected serum samples from healthy donors, breast cancer patients with primary cancer, and breast cancer patients with, bone, visceral or cerebral metastases. We analysed cytokine levels in these sera utilizing immunoassays and correlated them with clinical data. We used paracellular permeability measurements, immunofluorescence staining, Western blot and mRNA analysis to examine the effects of patient sera on the properties of BBB in vitro. Results The BLECs cultured together with brain pericytes in transwells developed a tight monolayer with a correct localization of claudin-5 at the tight junctions (TJ). Several BBB marker proteins such as the TJ proteins claudin-5 and occludin, the glucose transporter GLUT-1 or the efflux pumps PG-P and BCRP were upregulated in these cultures. This was accompanied by a reduced paracellular permeability for fluorescein (400 Da). We then used this model for the treatment with the patient sera. Only the sera of breast cancer patients with cerebral metastases had significantly increased levels of the cytokines fractalkine (CX3CL1) and BCA-1 (CXCL13). The increased levels of fractalkine were associated with the estrogen/progesterone receptor status of the tumour. The treatment of BLECs with these sera selectively increased the expression of CXCL13 and TJ protein occludin. In addition, the permeability of fluorescein was increased after serum treatment. Conclusion We demonstrate that the CD34\(^+\) cell-derived human in vitro BBB model can be used as a tool to study the molecular mechanisms underlying cerebrovascular pathologies. We showed that serum from patients with cerebral metastases may affect the integrity of the BBB in vitro, associated with elevated concentrations of specific cytokines such as CX3CL1 and CXCL13. KW - Metastatic breast cancer KW - Blood–brain barrier KW - In vitro models KW - CX3CL1 KW - CXCL13 Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229940 VL - 17 ER - TY - JOUR A1 - Schlesinger, Tobias A1 - Weißbrich, Benedikt A1 - Wedekink, Florian A1 - Notz, Quirin A1 - Herrmann, Johannes A1 - Krone, Manuel A1 - Sitter, Magdalena A1 - Schmid, Benedikt A1 - Kredel, Markus A1 - Stumpner, Jan A1 - Dölken, Lars A1 - Wischhusen, Jörg A1 - Kranke, Peter A1 - Meybohm, Patrick A1 - Lotz, Christpher T1 - Biodistribution and serologic response in SARS-CoV-2 induced ARDS: A cohort study JF - PLoS One N2 - Background The viral load and tissue distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain important questions. The current study investigated SARS-CoV-2 viral load, biodistribution and anti-SARS-CoV-2 antibody formation in patients suffering from severe corona virus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). Methods This is a retrospective single-center study in 23 patients with COVID-19-induced ARDS. Data were collected within routine intensive care. SARS-CoV-2 viral load was assessed via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Overall, 478 virology samples were taken. Anti-SARS-CoV-2-Spike-receptor binding domain (RBD) antibody detection of blood samples was performed with an enzyme-linked immunosorbent assay. Results Most patients (91%) suffered from severe ARDS during ICU treatment with a 30-day mortality of 30%. None of the patients received antiviral treatment. Tracheal aspirates tested positive for SARS-CoV-2 in 100% of the cases, oropharyngeal swabs only in 77%. Blood samples were positive in 26% of the patients. No difference of viral load was found in tracheal or blood samples with regard to 30-day survival or disease severity. SARS-CoV-2 was never found in dialysate. Serologic testing revealed significantly lower concentrations of SARS-CoV-2 neutralizing IgM and IgA antibodies in survivors compared to non-survivors (p = 0.009). Conclusions COVID-19 induced ARDS is accompanied by a high viral load of SARS-CoV-2 in tracheal aspirates, which remained detectable in the majority throughout intensive care treatment. Remarkably, SARS-CoV-2 RNA was never detected in dialysate even in patients with RNAemia. Viral load or the buildup of neutralizing antibodies was not associated with 30-day survival or disease severity. KW - viral load Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231348 VL - 15, 2020 IS - 11 ER - TY - JOUR A1 - Flemming, S. A1 - Hankir, M. A1 - Ernestus, R.-I. A1 - Seyfried, F. A1 - Germer, C.-T. A1 - Meybohm, P. A1 - Wurmb, T. A1 - Vogel, U. A1 - Wiegering, A. T1 - Surgery in times of COVID-19 — recommendations for hospital and patient management JF - Langenbeck's Archives of Surgery N2 - Background The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has escalated rapidly to a global pandemic stretching healthcare systems worldwide to their limits. Surgeonshave had to immediately react to this unprecedented clinical challenge by systematically repurposing surgical wards. Purpose To provide a detailed set of guidelines developed in a surgical ward at University Hospital Wuerzburg to safelyaccommodate the exponentially rising cases of SARS-CoV-2 infected patients without compromising the care of emergencysurgery and oncological patients or jeopardizing the well-being of hospital staff. Conclusions The dynamic prioritization of SARS-CoV-2 infected and surgical patient groups is key to preserving life whilemaintaining high surgical standards. Strictly segregating patient groups in emergency rooms, non-intensive care wards andoperating areas prevents viral spread while adequately training and carefully selecting hospital staff allow them to confidentlyand successfully undertake their respective clinical duties. KW - SARS-CoV-2 KW - COVID-19 KW - Surgery Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231766 SN - 1435-2443 VL - 405 ER - TY - JOUR A1 - Notz, Quirin A1 - Schmalzing, Marc A1 - Wedekink, Florian A1 - Schlesinger, Tobias A1 - Gernert, Michael A1 - Herrmann, Johannes A1 - Sorger, Lena A1 - Weismann, Dirk A1 - Schmid, Benedikt A1 - Sitter, Magdalena A1 - Schlegel, Nicolas A1 - Kranke, Peter A1 - Wischhusen, Jörg A1 - Meybohm, Patrick A1 - Lotz, Christopher T1 - Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study JF - Frontiers in Immunology N2 - Objectives The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and function. However, interactions of pro- and anti-inflammatory mechanisms remain elusive. In the current study we characterized the immune responses in patients suffering from severe COVID-19-induced acute respiratory distress syndrome (ARDS). Methods This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14th and May 28th 2020 (n = 39). Longitudinal data were collected within routine clinical care, including flow-cytometry of lymphocyte subsets, cytokine analysis and growth differentiation factor 15 (GDF-15). Antibody responses against the receptor binding domain (RBD) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein were analyzed. Results All patients suffered from severe ARDS, 30.8% died. Interleukin (IL)-6 was massively elevated at every time-point. The anti-inflammatory cytokine IL-10 was concomitantly upregulated with IL-6. The cellular response was characterized by lymphocytopenia with low counts of CD8+ T cells, natural killer (NK) and naïve T helper cells. CD8+ T and NK cells recovered after 8 to 14 days. The B cell system was largely unimpeded. This coincided with a slight increase in anti-SARS-CoV-2-Spike-RBD immunoglobulin (Ig) G and a decrease in anti-SARS-CoV-2-Spike-RBD IgM. GDF-15 levels were elevated throughout ICU treatment. Conclusions Massively elevated levels of IL-6 and a delayed cytotoxic immune defense characterized severe COVID-19-induced ARDS. The B cell response and antibody production were largely unimpeded. No obvious imbalance of pro- and anti-inflammatory mechanisms was observed, with elevated GDF-15 levels suggesting increased tissue resilience. KW - Coronavirus Disease 2019 KW - acute respiratory distress syndrome KW - Severe Acute Respiratory Syndrome Coronavirus 2 KW - cytokines KW - inflammation KW - growth differentiation factor 15 KW - immune response Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212815 SN - 1664-3224 VL - 11 ER - TY - JOUR A1 - Hottenrott, Sebastian A1 - Schlesinger, Tobias A1 - Helmer, Philipp A1 - Meybohm, Patrick A1 - Alkatout, Ibrahim A1 - Kranke, Peter T1 - Do small incisions need only minimal anesthesia? — anesthetic management in laparoscopic and robotic surgery JF - Journal of Clinical Medicine N2 - Laparoscopic techniques have established themselves as a major part of modern surgery. Their implementation in every surgical discipline has played a vital part in the reduction of perioperative morbidity and mortality. Precise robotic surgery, as an evolution of this, is shaping the present and future operating theatre that an anesthetist is facing. While incisions get smaller and the impact on the organism seems to dwindle, challenges for anesthetists do not lessen and could even become more demanding than in open procedures. This review focuses on the pathophysiological effects of contemporary laparoscopic and robotic procedures and summarizes anesthetic challenges and strategies for perioperative management. KW - general anesthesia KW - anesthetics KW - perioperative care KW - minimally invasive surgery KW - laparoscopic surgery KW - robotic surgery Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220039 SN - 2077-0383 VL - 9 IS - 12 ER - TY - JOUR A1 - Neef, Vanessa A1 - Meisenzahl, David A1 - Kessler, Paul A1 - Raimann, Florian J. A1 - Piekarski, Florian A1 - Choorapoikayil, Suma A1 - Fleege, Christoph A1 - Zacharowski, Kai D. A1 - Meybohm, Patrick A1 - Meurer, Andrea T1 - Implementation of an anaemia walk‐in clinic: Feasibility and preliminary data from the Orthopedic University Hospital JF - Transfusion Medicine N2 - Background Approximately one in three patients suffers from preoperative anaemia. Even though haemoglobin is measured before surgery, anaemia management is not implemented in every hospital. Objective Here, we demonstrate the implementation of an anaemia walk‐in clinic at an Orthopedic University Hospital. To improve the diagnosis of iron deficiency (ID), we examined whether reticulocyte haemoglobin (Ret‐He) could be a useful additional parameter. Material and Methods In August 2019, an anaemia walk‐in clinic was established. Between September and December 2019, major orthopaedic surgical patients were screened for preoperative anaemia. The primary endpoint was the incidence of preoperative anaemia. Secondary endpoints included Ret‐He level, red blood cell (RBC) transfusion rate, in‐hospital length of stay and anaemia at hospital discharge. Results A total of 104 patients were screened for anaemia. Preoperative anaemia rate was 20.6%. Intravenous iron was supplemented in 23 patients. Transfusion of RBC units per patient (1.7 ± 1.2 vs. 0.2 ± 0.9; p = 0.004) and hospital length of stay (13.1 ± 4.8 days vs. 10.6 ± 5.1 days; p = 0.068) was increased in anaemic patients compared to non‐anaemic patients. Ret‐He values were significantly lower in patients with ID anaemia (33.3 pg [28.6–40.2 pg]) compared to patients with ID (35.3 pg [28.9–38.6 pg]; p = 0.015) or patients without anaemia (35.4 pg [30.2–39.4 pg]; p = 0.001). Conclusion Preoperative anaemia is common in orthopaedic patients. Our results proved the feasibility of an anaemia walk‐in clinic to manage preoperative anaemia. Furthermore, our analysis supports the use of Ret‐He as an additional parameter for the diagnosis of ID in surgical patients. KW - anaemia walk‐in clinic KW - blood transfusion KW - iron deficiency KW - orthopaedic patients KW - patient blood management KW - reticulocyte haemoglobin Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224594 VL - 30 IS - 6 SP - 467 EP - 474 ER - TY - JOUR A1 - Geiger, Dietmar T1 - Plant glucose transporter structure and function JF - Pflügers Archiv - European Journal of Physiology N2 - The carbohydrate D-glucose is the main source of energy in living organisms. In contrast to animals, as well as most fungi, bacteria, and archaea, plants are capable to synthesize a surplus of sugars characterizing them as autothrophic organisms. Thus, plants are de facto the source of all food on earth, either directly or indirectly via feed to livestock. Glucose is stored as polymeric glucan, in animals as glycogen and in plants as starch. Despite serving a general source for metabolic energy and energy storage, glucose is the main building block for cellulose synthesis and represents the metabolic starting point of carboxylate- and amino acid synthesis. Finally yet importantly, glucose functions as signalling molecule conveying the plant metabolic status for adjustment of growth, development, and survival. Therefore, cell-to-cell and long-distance transport of photoassimilates/sugars throughout the plant body require the fine-tuned activity of sugar transporters facilitating the transport across membranes. The functional plant counterparts of the animal sodium/glucose transporters (SGLTs) are represented by the proton-coupled sugar transport proteins (STPs) of the plant monosaccharide transporter(-like) family (MST). In the framework of this special issue on “Glucose Transporters in Health and Disease,” this review gives an overview of the function and structure of plant STPs in comparison to the respective knowledge obtained with the animal Na+-coupled glucose transporters (SGLTs). KW - STP KW - sugar transport protein KW - glucose transport KW - plant photoassimilate partitioning Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-280643 VL - 472 IS - 9 ER - TY - JOUR A1 - Riederer, Peter A1 - ter Meulen, Volker T1 - Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses JF - Journal of Neural Transmission N2 - While there is abounding literature on virus-induced pathology in general and coronavirus in particular, recent evidence accumulates showing distinct and deleterious brain affection. As the respiratory tract connects to the brain without protection of the blood–brain barrier, SARS-CoV-2 might in the early invasive phase attack the cardiorespiratory centres located in the medulla/pons areas, giving rise to disturbances of respiration and cardiac problems. Furthermore, brainstem regions are at risk to lose their functional integrity. Therefore, long-term neurological as well as psychiatric symptomatology and eventual respective disorders cannot be excluded as evidenced from influenza-A triggered post-encephalitic Parkinsonism and HIV-1 triggered AIDS–dementia complex. From the available evidences for coronavirus-induced brain pathology, this review concludes a number of unmet needs for further research strategies like human postmortem brain analyses. SARS-CoV-2 mirroring experimental animal brain studies, characterization of time-dependent and region-dependent spreading behaviours of coronaviruses, enlightening of pathological mechanisms after coronavirus infection using long-term animal models and clinical observations of patients having had COVID-19 infection are calling to develop both protective strategies and drug discoveries to avoid early and late coronavirus-induced functional brain disturbances, symptoms and eventually disorders. To fight SARS-CoV-2, it is an urgent need to enforce clinical, molecular biological, neurochemical and genetic research including brain-related studies on a worldwide harmonized basis. KW - coronavirus KW - COVID-19 KW - SARS-CoV-2 brain disorders KW - cardiorespiratory centre KW - brain pathology KW - neurological symptoms/disorders KW - brain stem KW - Parkinson’s disease KW - Parkinsonism KW - Alzheimer’s disease KW - multiple sclerosis KW - movement disorders KW - neuroinvasion KW - therapy KW - neuroprotection KW - depression KW - cognitive dysfunction KW - brain bank KW - postmortem studies Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-314637 SN - 0300-9564 SN - 1435-1463 VL - 127 IS - 9 ER - TY - JOUR A1 - Dashkovskiy, Sergey A1 - Kapustyan, Oleksiy A1 - Schmid, Jochen T1 - A local input-to-state stability result w.r.t. attractors of nonlinear reaction–diffusion equations JF - Mathematics of Control, Signals, and Systems N2 - We establish the local input-to-state stability of a large class of disturbed nonlinear reaction–diffusion equations w.r.t. the global attractor of the respective undisturbed system. KW - local input-to-state stability KW - global attractor KW - lonlinear reaction-diffusion equations Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281099 VL - 32 IS - 3 ER - TY - JOUR A1 - Steinhardt, M. J. A1 - Wiercinska, E. A1 - Pham, M. A1 - Grigoleit, G. U. A1 - Mazzoni, A. A1 - Da-Via, M. A1 - Zhou, X. A1 - Meckel, K. A1 - Nickel, K. A1 - Duell, J. A1 - Krummenast, F. C. A1 - Kraus, S. A1 - Hopkinson, C. A1 - Weissbrich, B. A1 - Müllges, W. A1 - Stoll, G. A1 - Kortüm, K. M. A1 - Einsele, H. A1 - Bonig, H. A1 - Rasche, L. T1 - Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes JF - Journal of Translational Medicine N2 - Background Progressive multifocal leukoencephalopathy is a demyelinating CNS disorder. Reactivation of John Cunningham virus leads to oligodendrocyte infection with lysis and consequent axonal loss due to demyelination. Patients usually present with confusion and seizures. Late diagnosis and lack of adequate therapy options persistently result in permanent impairment of brain functions. Due to profound T cell depletion, impairment of T-cell function and potent immunosuppressive factors, allogeneic hematopoietic cell transplantation recipients are at high risk for JCV reactivation. To date, PML is almost universally fatal when occurring after allo-HCT. Methods To optimize therapy specificity, we enriched JCV specific T-cells out of the donor T-cell repertoire from the HLA-identical, anti-JCV-antibody positive family stem cell donor by unstimulated peripheral apheresis [1]. For this, we selected T cells responsive to five JCV peptide libraries via the Cytokine Capture System technology. It enables the enrichment of JCV specific T cells via identification of stimulus-induced interferon gamma secretion. Results Despite low frequencies of responsive T cells, we succeeded in generating a product containing 20 000 JCV reactive T cells ready for patient infusion. The adoptive cell transfer was performed without complication. Consequently, the clinical course stabilized and the patient slowly went into remission of PML with JCV negative CSF and containment of PML lesion expansion. Conclusion We report for the first time feasibility of generating T cells with possible anti-JCV activity from a seropositive family donor, a variation of virus specific T-cell therapies suitable for the post allo transplant setting. We also present the unusual case for successful treatment of PML after allo-HCT via virus specific T-cell therapy. KW - Myeloma KW - JCV KW - Prodigy KW - CCS KW - PML KW - Donor lymphocytes KW - Adaptive cell transfer Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229307 VL - 18 ER - TY - JOUR A1 - Stelzner, Kathrin A1 - Winkler, Ann-Cathrin A1 - Liang, Chunguang A1 - Boyny, Aziza A1 - Ade, Carsten P. A1 - Dandekar, Thomas A1 - Fraunholz, Martin J. A1 - Rudel, Thomas T1 - Intracellular Staphylococcus aureus Perturbs the Host Cell Ca\(^{2+}\) Homeostasis To Promote Cell Death JF - mBio N2 - The opportunistic human pathogen Staphylococcus aureus causes serious infectious diseases that range from superficial skin and soft tissue infections to necrotizing pneumonia and sepsis. While classically regarded as an extracellular pathogen, S. aureus is able to invade and survive within human cells. Host cell exit is associated with cell death, tissue destruction, and the spread of infection. The exact molecular mechanism employed by S. aureus to escape the host cell is still unclear. In this study, we performed a genome-wide small hairpin RNA (shRNA) screen and identified the calcium signaling pathway as being involved in intracellular infection. S. aureus induced a massive cytosolic Ca\(^{2+}\) increase in epithelial host cells after invasion and intracellular replication of the pathogen. This was paralleled by a decrease in endoplasmic reticulum Ca\(^{2+}\) concentration. Additionally, calcium ions from the extracellular space contributed to the cytosolic Ca2+ increase. As a consequence, we observed that the cytoplasmic Ca\(^{2+}\) rise led to an increase in mitochondrial Ca\(^{2+}\) concentration, the activation of calpains and caspases, and eventually to cell lysis of S. aureus-infected cells. Our study therefore suggests that intracellular S. aureus disturbs the host cell Ca\(^{2+}\) homeostasis and induces cytoplasmic Ca\(^{2+}\) overload, which results in both apoptotic and necrotic cell death in parallel or succession. IMPORTANCE Despite being regarded as an extracellular bacterium, the pathogen Staphylococcus aureus can invade and survive within human cells. The intracellular niche is considered a hideout from the host immune system and antibiotic treatment and allows bacterial proliferation. Subsequently, the intracellular bacterium induces host cell death, which may facilitate the spread of infection and tissue destruction. So far, host cell factors exploited by intracellular S. aureus to promote cell death are only poorly characterized. We performed a genome-wide screen and found the calcium signaling pathway to play a role in S. aureus invasion and cytotoxicity. The intracellular bacterium induces a cytoplasmic and mitochondrial Ca\(^{2+}\) overload, which results in host cell death. Thus, this study first showed how an intracellular bacterium perturbs the host cell Ca\(^{2+}\) homeostasis." KW - Staphylococcus aureus KW - calcium signaling pathway KW - cell death KW - facultatively intracellular pathogens Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231448 VL - 11 ER - TY - JOUR A1 - Kunz, Viktoria A1 - Bommert, Kathryn S. A1 - Kruk, Jessica A1 - Schwinning, Daniel A1 - Chatterjee, Manik A1 - Stühmer, Thorsten A1 - Bargou, Ralf A1 - Bommert, Kurt T1 - Targeting of the E3 ubiquitin-protein ligase HUWE1 impairs DNA repair capacity and tumor growth in preclinical multiple myeloma models JF - Scientific Reports N2 - Experimental evidence suggests that ubiquitin-protein ligases regulate a number of cellular processes involved in tumorigenesis. We analysed the role of the E3 ubiquitin-protein ligase HUWE1 for pathobiology of multiple myeloma (MM), a still incurable blood cancer. mRNA expression analysis indicates an increase in HUWE1 expression levels correlated with advanced stages of myeloma. Pharmacologic as well as RNAi-mediated HUWE1 inhibition caused anti-proliferative effects in MM cell lines in vitro and in an MM1.S xenotransplantation mouse model. Cell cycle analysis upon HUWE1 inhibition revealed decreased S phase cell fractions. Analyses of potential HUWE1-dependent molecular functions did not show involvement in MYC-dependent gene regulation. However, HUWE1 depleted MM cells displayed increased DNA tail length by comet assay, as well as changes in the levels of DNA damage response mediators such as pBRCA1, DNA-polymerase beta, gamma H2AX and Mcl-1. Our finding that HUWE1 might thus be involved in endogenous DNA repair is further supported by strongly enhanced apoptotic effects of the DNA-damaging agent melphalan in HUWE1 depleted cells in vitro and in vivo. These data suggest that HUWE1 might contribute to tumour growth by endogenous repair of DNA, and could therefore potentially be exploitable in future treatment developments. KW - MYC KW - interacts KW - gene Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230632 VL - 10 ER - TY - JOUR A1 - Sarukhanyan, Edita A1 - Shityakov, Sergey A1 - Dandekar, Thomas T1 - Rational drug design of Axl tyrosine kinase type I inhibitors as promising candidates against cancer JF - Frontiers in Chemistry N2 - The high level of Axl tyrosine kinase expression in various cancer cell lines makes it an attractive target for the development of anti-cancer drugs. In this study, we carried out several sets of in silico screening for the ATP-competitive Axl kinase inhibitors based on different molecular docking protocols. The best drug-like candidates were identified, after parental structure modifications, by their highest affinity to the target protein. We found that our newly designed compound R5, a derivative of the R428 patented analog, is the most promising inhibitor of the Axl kinase according to the three molecular docking algorithms applied in the study. The molecular docking results are in agreement with the molecular dynamics simulations using the MM-PBSA/GBSA implicit solvation models, which confirm the high affinity of R5 toward the protein receptor. Additionally, the selectivity test against other kinases also reveals a high affinity of R5 toward ABL1 and Tyro3 kinases, emphasizing its promising potential for the treatment of malignant tumors. KW - Axl tyrosine kinase KW - anti-cancer drug-like molecules KW - rational drug design KW - molecular docking KW - molecular dynamics Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199505 SN - 2296-2646 VL - 7 IS - 920 ER - TY - JOUR A1 - Altieri, Barbara A1 - Sbiera, Silviu A1 - Herterich, Sabine A1 - De Francia, Silvia A1 - Della Casa, Silvia A1 - Calabrese, Anna A1 - Pontecorvi, Alfredo A1 - Quinkler, Marcus A1 - Kienitz, Tina A1 - Mannelli, Massimo A1 - Canu, Letizia A1 - Angelousi, Anna A1 - Chortis, Vasileios A1 - Kroiss, Matthias A1 - Terzolo, Massimo A1 - Fassnacht, Martin A1 - Ronchi, Cristina L. T1 - Effects of Germline CYP2W1*6 and CYP2B6*6 Single Nucleotide Polymorphisms on Mitotane Treatment in Adrenocortical Carcinoma: A Multicenter ENSAT Study JF - Cancers N2 - Mitotane is the only approved drug for advanced adrenocortical carcinoma (ACC) and no biomarkers are available to predict attainment of therapeutic plasma concentrations and clinical response. Aim of the study was to evaluate the suitability of cytochrome P450(CYP)2W1 and CYP2B6 single nucleotide polymorphisms (SNPs) as biomarkers. A multicenter cohort study including 182 ACC patients (F/M = 121/61) treated with mitotane monotherapy after radical resection (group A, n = 103) or in not completely resectable, recurrent or advanced disease (group B, n = 79) was performed. CYP2W1*2, CYP2W1*6, CYP2B6*6 and CYP2B6 rs4803419 were genotyped in germline DNA. Mitotane blood levels were measured regularly. Response to therapy was evaluated as time to progression (TTP) and disease control rate (DCR). Among investigated SNPs, CYP2W1*6 and CYP2B6*6 correlated with mitotane treatment only in group B. Patients with CYP2W1*6 (n = 21) achieved less frequently therapeutic mitotane levels (>14 mg/L) than those with wild type (WT) allele (76.2% vs 51.7%, p = 0.051) and experienced shorter TTP (HR = 2.10, p = 0.019) and lower DCR (chi-square = 6.948, p = 0.008). By contrast, 55% of patients with CYP2B6*6 vs. 28.2% WT (p = 0.016) achieved therapeutic range. Combined, a higher rate of patients with CYP2W1*6WT+CYP2B6*6 (60.6%) achieved mitotane therapeutic range (p = 0.034). In not completely resectable, recurrent or advanced ACC, CYP2W1*6 SNP was associated with a reduced probability to reach mitotane therapeutic range and lower response rates, whereas CYP2B6*6 correlated with higher mitotane levels. The association of these SNPs may predict individual response to mitotane. KW - adrenocortical carcinoma KW - mitotane KW - CYP2W1 KW - CYP2B6 KW - SNP KW - biomarker KW - predictive marker Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200565 SN - 2072-6694 VL - 12 IS - 2 ER - TY - JOUR A1 - Fukushima, Kenji A1 - Pollock, David D. T1 - Amalgamated cross-species transcriptomes reveal organ-specific propensity in gene expression evolution JF - Nature Communications N2 - The origins of multicellular physiology are tied to evolution of gene expression. Genes can shift expression as organisms evolve, but how ancestral expression influences altered descendant expression is not well understood. To examine this, we amalgamate 1,903 RNA-seq datasets from 182 research projects, including 6 organs in 21 vertebrate species. Quality control eliminates project-specific biases, and expression shifts are reconstructed using gene-family-wise phylogenetic Ornstein-Uhlenbeck models. Expression shifts following gene duplication result in more drastic changes in expression properties than shifts without gene duplication. The expression properties are tightly coupled with protein evolutionary rate, depending on whether and how gene duplication occurred. Fluxes in expression patterns among organs are nonrandom, forming modular connections that are reshaped by gene duplication. Thus, if expression shifts, ancestral expression in some organs induces a strong propensity for expression in particular organs in descendants. Regardless of whether the shifts are adaptive or not, this supports a major role for what might be termed preadaptive pathways of gene expression evolution. KW - phylogenetic trees KW - adaptive conflict KW - divergence times KW - duplicate genes KW - recent origin KW - package KW - selection KW - alignmen KW - rates KW - biology Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230468 VL - 11, ER - TY - JOUR A1 - Römer, Daniela A1 - Cosarinsky, Marcela I. A1 - Roces, Flavio T1 - Selection and spatial arrangement of building materials during the construction of nest turrets by grass-cutting ants JF - Royal Society Open Science N2 - Ants build complex nest structures by reacting to simple, local stimuli. While underground nests result from the space generated by digging, some leaf- and grass-cutting ants also construct conspicuous aboveground turrets around nest openings. We investigated whether the selection of specific building materials occurs during turret construction in Acromyrmex fracticornis grass-cutting ants, and asked whether single building decisions at the beginning can modify the final turret architecture. To quantify workers' material selection, the original nest turret was removed and a choice between two artificial building materials, thin and thick sticks, was offered for rebuilding. Workers preferred thick sticks at the very beginning of turret construction, showed varying preferences thereafter, and changed to prefer thin sticks for the upper, final part of the turret, indicating that they selected different building materials over time to create a stable structure. The impact of a single building choice on turret architecture was evaluated by placing artificial beams that divided a colony's nest entrance at the beginning of turret rebuilding. Splitting the nest entrance led to the self-organized construction of turrets with branched galleries ending in multiple openings, showing that the spatial location of a single building material can strongly influence turret morphology. KW - collective building KW - behavioural plasticity KW - Acromyrmex fracticornis KW - quantitative stigmergy KW - self-organization KW - leaf-cutting ants Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230458 VL - 7 ER - TY - JOUR A1 - Schneider, Michael A1 - Tschöpe, André A1 - Hanselmann, Doris A1 - Ballweg, Thomas A1 - Gellermann, Carsten A1 - Franzreb, Matthias A1 - Mandel, Karl T1 - Adsorber Particles with Magnetically‐Supported Improved Electrochemical Conversion Behavior for Waste Water Treatment Processes JF - Particle & Particle Systems Characterization N2 - Micron‐sized supraparticles, consisting of a plurality of discrete nano‐ and microscale functional units, are assembled and fused by means of a droplet extrusion process. By combining nano magnetite, activated carbon, and conductive carbon with a polymeric binder matrix, particles are obtained which unite good magnetic properties, electrical conductivity, and adsorber activity through the high accessible surface area of the incorporated activated carbon of about 570 m\(^{2}\) g\(^{-1}\), thereby enabling a new approach toward sustainable water treatment processes. Due to the interplay of the components, it is possible to adsorb target substances, dissolved in the water which is demonstrated by the adsorption of the model dye methylene blue. A very fast adsorption kinetic and an adsorption capacity of about 400 mg g\(^{-1}\) is determined. By using the developed composite particles, it is also possible to electrochemically alter substances flowing through a magnetically‐stabilized fluidized‐bed reactor by electrochemically charging/discharging, significantly supported by the magnetic field enabling alternatingly optimum mobility/adsorption phases with contact/charging intervals. The electrochemical conversion can be increased up to 151% depending on the applied flow‐rate and electrical voltage. By applying an external magnetic field, a further increase of electrochemical conversion of up to 70% can be observed. KW - composite supraparticles KW - dye adsorption KW - electrochemical conversion KW - magnetic particles KW - water purification Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214738 VL - 37 IS - 2 ER - TY - JOUR A1 - Lohr, David A1 - Terekhov, Maxim A1 - Veit, Franziska A1 - Schreiber, Laura Maria T1 - Longitudinal assessment of tissue properties and cardiac diffusion metrics of the ex vivo porcine heart at 7 T: Impact of continuous tissue fixation using formalin JF - NMR in Biomedicine N2 - In this study we aimed to assess the effects of continuous formalin fixation on diffusion and relaxation metrics of the ex vivo porcine heart at 7 T. Magnetic resonance imaging was performed on eight piglet hearts using a 7 T whole body system. Hearts were measured fresh within 3 hours of cardiac arrest followed by immersion in 10% neutral buffered formalin. T\(_{2}\)* and T\(_{2}\) were assessed using a gradient multi‐echo and multi‐echo spin echo sequence, respectively. A spin echo and a custom stimulated echo sequence were employed to assess diffusion time‐dependent changes in metrics of cardiac diffusion tensor imaging. SNR was determined for b = 0 images. Scans were performed for 5 mm thick apical, midcavity and basal slices (in‐plane resolution: 1 mm) and repeated 7, 15, 50, 100 and 200 days postfixation. Eigenvalues of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) decreased significantly (P < 0.05) following fixation. Relative to fresh hearts, FA values 7 and 200 days postfixation were 90% and 80%, while respective relative ADC values at those fixation stages were 78% and 92%. Statistical helix and sheetlet angle distributions as well as respective mean and median values showed no systematic influence of continuous formalin fixation. Similar to changes in the ADC, values for T\(_{2}\), T\(_{2}\)* and SNR dropped initially postfixation. Respective relative values compared with fresh hearts at day 7 were 64%, 79% and 68%, whereas continuous fixation restored T\(_{2}\), T\(_{2}\)* and SNR leading to relative values of 74%, 100%, and 81% at day 200, respectively. Relaxation parameters and diffusion metrics are significantly altered by continuous formalin fixation. The preservation of microstructure metrics following prolonged fixation is a key finding that may enable future studies of ventricular remodeling in cardiac pathologies. KW - cardiovascular MR methods KW - diffusion tensor imaging KW - heart structure KW - relaxometry Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215536 VL - 33 IS - 7 ER - TY - JOUR A1 - Vogel, Jörg T1 - An RNA biology perspective on species‐specific programmable RNA antibiotics JF - Molecular Microbiology N2 - Our body is colonized by a vast array of bacteria the sum of which forms our microbiota. The gut alone harbors >1,000 bacterial species. An understanding of their individual or synergistic contributions to human health and disease demands means to interfere with their functions on the species level. Most of the currently available antibiotics are broad‐spectrum, thus too unspecific for a selective depletion of a single species of interest from the microbiota. Programmable RNA antibiotics in the form of short antisense oligonucleotides (ASOs) promise to achieve precision manipulation of bacterial communities. These ASOs are coupled to small peptides that carry them inside the bacteria to silence mRNAs of essential genes, for example, to target antibiotic‐resistant pathogens as an alternative to standard antibiotics. There is already proof‐of‐principle with diverse bacteria, but many open questions remain with respect to true species specificity, potential off‐targeting, choice of peptides for delivery, bacterial resistance mechanisms and the host response. While there is unlikely a one‐fits‐all solution for all microbiome species, I will discuss how recent progress in bacterial RNA biology may help to accelerate the development of programmable RNA antibiotics for microbiome editing and other applications. KW - antibiotic KW - microbiome KW - RNA-seq KW - small RNA Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214869 VL - 113 IS - 3 SP - 550 EP - 559 ER - TY - JOUR A1 - Wurmb, Thomas A1 - Franke, Axel A1 - Schorscher, Nora A1 - Kowalzik, Barbara A1 - Helm, Matthias A1 - Bohnen, Renate A1 - Helmerichs, Jutta A1 - Grueneisen, Ulrich A1 - Cwojdzinski, Detlef A1 - Jung, Georg A1 - Lücking, Gesa A1 - Weber, Martin T1 - Emergency response to terrorist attacks: results of the federal-conducted evaluation process in Germany JF - European Journal of Trauma and Emergency Surgery N2 - Purpose Rescue missions during terrorist attacks are extremely challenging for all rescue forces (police as well as non-police forces) involved. To improve the quality and safety of the rescue missions during an active killing event, it is obligatory to adapt common rescue mission goals and strategies. Methods After the recent attacks in Europe, the Federal Office of Civil Protection and Disaster Assistance started an evaluation process on behalf of the Federal Ministry of the Interior and the Federal Ministry of Health. This was done to identify weaknesses, lessons learned and to formulate new adapted guidelines. Results The presented bullet point recommendations summarise the basic and most important results of the ongoing evaluation process for the Federal Republic of Germany. The safety of all the rescue forces and survival of the greatest possible number of casualties are the priority goals. Furthermore, the preservation and re-establishment of the socio-political integrity are the overarching goals of the management of active killing events. Strategic incident priorities are to stop the killing and to save as much lives as possible. The early identification and prioritised transportation of casualties with life-threatening non-controllable bleeding are major tasks and the shortest possible on-scene time is an important requirement with respect to safety issues. Conclusion With respect to hazard prevention tactics within Germany, we attributed the highest priority impact to the bullet points. The focus of the process has now shifted to intense work about possible solutions for the identified deficits and implementation strategies of such solutions during mass killing incidents. KW - terror attack KW - mission strategies KW - lessons learned KW - first responders KW - safety Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231777 SN - 1863-9933 VL - 46 ER - TY - JOUR A1 - Markert, Sebastian M. A1 - Skoruppa, Michael A1 - Yu, Bin A1 - Mulcahy, Ben A1 - Zhen, Mai A1 - Gao, Shangbang A1 - Sendtner, Michael A1 - Stigloher, Christian T1 - Overexpression of an ALS-associated FUS mutation in C. elegans disrupts NMJ morphology and leads to defective neuromuscular transmission JF - Biology Open N2 - The amyotrophic lateral sclerosis (ALS) neurodegenerative disorder has been associated with multiple genetic lesions, including mutations in the gene for fused in sarcoma (FUS), a nuclear-localized RNA/DNA-binding protein. Neuronal expression of the pathological form of FUS proteins in Caenorhabditis elegans results in mislocalization and aggregation of FUS in the cytoplasm, and leads to impairment of motility. However, the mechanisms by which the mutant FUS disrupts neuronal health and function remain unclear. Here we investigated the impact of ALS-associated FUS on motor neuron health using correlative light and electron microscopy, electron tomography, and electrophysiology. We show that ectopic expression of wild-type or ALS-associated human FUS impairs synaptic vesicle docking at neuromuscular junctions. ALS-associated FUS led to the emergence of a population of large, electron-dense, and filament-filled endosomes. Electrophysiological recording revealed reduced transmission from motor neurons to muscles. Together, these results suggest a pathological effect of ALS-causing FUS at synaptic structure and function organization. KW - C. elegans KW - fused in sarcoma KW - amyotrophic lateral sclerosis KW - uper-resolution array tomography KW - electron tomography KW - neuromuscular junction Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230662 VL - 9 ER - TY - JOUR A1 - Hedrich, Christian M. A1 - Morbach, Henner A1 - Reiser, Christiane A1 - Girschick, Hermann J. T1 - New Insights into Adult and Paediatric Chronic Non-bacterial Osteomyelitis CNO JF - Current Rheumatology Reports N2 - Purpose of Review To describe in detail the clinical synopsis and pathophysiology of chronic non-bacterial osteomyelitis and SAPHO syndrome. Recent Findings Chronic non-bacterial osteomyelitis (CNO) has been identified as a disease entity for almost 50 years. This inflammatory bone disorder is characterized by osteolytic as well as hyperostotic/osteosclerotic lesions. It is chronic in nature, but it can present with episodic flairs and phases of remission, which have led to the denomination “chronic recurrent osteomyelitis”, with its severe multifocal form “chronic recurrent multifocal osteomyelitis” (CRMO). For almost three decades, an infectious aetiology had been considered, since especially Propionibacterium acnes had been isolated from bone lesions of individual patients. However, this concept has been challenged since long-term antibiotic therapy did not alter the course of disease and modern microbiological techniques (including PCR) failed to confirm bone infection as an underlying cause. Over recent years, a profound dysregulation of cytokine expression profiles has been demonstrated in innate immune cells of CNO patients. A hallmark of monocytes from CNO patients is the failure to produce immune regulatory cytokines interleukin-10 (IL-10) and IL-19, which have been linked with genetic and epigenetic alterations. Subsequently, a significant upregulation of pro-inflammatory, NLRP3 inflammasome-dependent cytokines (IL-1β and TNF-α), has been demonstrated. Summary The current knowledge on CNO, the underlying molecular pathophysiology, and modern imaging strategies are summarized; differential diagnoses, treatment options, outcome measures, as well as quality of life studies are discussed. KW - chronic non-bacterial osteomyelitis KW - chronic recurrent multifocal osteomyelitis KW - bone autoinflammation KW - lymphoplasmacellular osteomyelitis Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232636 SN - 1523-3774 VL - 22 ER - TY - JOUR A1 - Volpp, Linda A1 - Ferianec, Vladimír A1 - Ježovičová, Miriam A1 - Ďuračková, Zdeňka A1 - Scherf-Clavel, Oliver A1 - Högger, Petra T1 - Constituents and Metabolites of a French Oak Wood Extract (Robuvit®) in Serum and Blood Cell Samples of Women Undergoing Hysterectomy JF - Frontiers in Pharmacology N2 - Ellagitannins are signature constituents of oak wood and their consumption has been associated with various health benefits. In vivo, they undergo metabolic degradation including gut microbial metabolism yielding urolithins. Only limited data is available about compounds being present in blood after intake of an extract from French oak wood, Robuvit®. In the course of a randomized, double-blind, controlled clinical investigation, 66 patients undergoing hysterectomy received placebo or 300 mg Robuvit® per day before and over 8 weeks after surgery. Serum and blood cell samples were analyzed by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The number of urolithin producers and the urolithin levels increased after intake of Robuvit®. In serum samples, the median concentration of urolithin A was 14.0 ng/ml [interquartile range (IQR) 57.4] after 8 weeks. Urolithin B was determined at 22.3 ng/ml (IQR 12.6), urolithin C at 2.66 ng/ml (IQR 2.08). In blood cells, lower concentrations and only urolithins A and B were detected. A statistically significant association of lower post-surgical pain scores with metabotype A was detected (p < 0.05). To conclude, supplementation with French oak wood extract raised urolithin generation in patients and suggested health advantages for urolithin-producers. KW - polyphenols KW - urolithins KW - oak wood KW - post-surgery recovery KW - human KW - liquid chromatography electrospray ionization tandem mass spectrometry Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200105 SN - 1663-9812 VL - 11 IS - 74 ER - TY - JOUR A1 - Rösing, Nils A1 - Salvador, Ellaine A1 - Güntzel, Paul A1 - Kempe, Christoph A1 - Burek, Malgorzata A1 - Holzgrabe, Ulrike A1 - Soukhoroukov, Vladimir A1 - Wunder, Christian A1 - Förster, Carola T1 - Neuroprotective Effects of Isosteviol Sodium in Murine Brain Capillary Cerebellar Endothelial Cells (cerebEND) After Hypoxia JF - Frontiers in Cellular Neuroscience N2 - Ischemic stroke is one of the leading causes of death worldwide. It damages neurons and other supporting cellular elements in the brain. However, the impairment is not only confined to the region of assault but the surrounding area as well. Besides, it also brings about damage to the blood-brain barrier (BBB) which in turn leads to microvascular failure and edema. Hence, this necessitates an on-going, continuous search for intervention strategies and effective treatment. Of late, the natural sweetener stevioside proved to exhibit neuroprotective effects and therapeutic benefits against cerebral ischemia-induced injury. Its injectable formulation, isosteviol sodium (STVNA) also demonstrated favorable results. Nonetheless, its effects on the BBB have not yet been investigated to date. As such, this present study was designed to assess the effects of STVNA in our in vitro stroke model of the BBB.The integrity and permeability of the BBB are governed and maintained by tight junction proteins (TJPs) such as claudin-5 and occludin. Our data show increased claudin-5 and occludin expression in oxygen and glucose (OGD)-deprived murine brain capillary cerebellar endothelial cells (cerebEND) after STVNa treatment. Likewise, the upregulation of the transmembrane protein integrin-αv was also observed. Finally, cell volume was reduced with the simultaneous administration of STVNA and OGD in cerebEND cells. In neuropathologies such as stroke, the failure of cell volume control is a major feature leading to loss of cells in the penumbra as well as adverse outcomes. Our initial findings, therefore, point to the neuroprotective effects of STVNA at the BBB in vitro, which warrant further investigation for a possible future clinical intervention. KW - isosteviol sodium KW - hypoxia KW - cerebEND cells KW - blood brain barrier KW - neuroprotection Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215013 SN - 1662-5102 VL - 14 ER - TY - JOUR A1 - Eder, Andreas B. A1 - Mitschke, Vanessa A1 - Gollwitzer, Mario T1 - What stops revenge taking? Effects of observed emotional reactions on revenge seeking JF - Aggressive Behavior N2 - What reaction stops revenge taking? Four experiments (total N = 191) examined this question where the victim of an interpersonal transgression could observe the offender's reaction (anger, sadness, pain, or calm) to a retributive noise punishment. We compared the punishment intensity selected by the participant before and after seeing the offender's reaction. Seeing the opponent in pain reduced subsequent punishment most strongly, while displays of sadness and verbal indications of suffering had no appeasing effect. Expression of anger about a retributive punishment did not increase revenge seeking relative to a calm reaction, even when the anger response was disambiguated as being angry with the punisher. It is concluded that the expression of pain is the most effective emotional display for the reduction of retaliatory aggression. The findings are discussed in light of recent research on reactive aggression and retributive justice. KW - aggression KW - emotion display KW - retaliation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214686 VL - 46 IS - 4 SP - 305 EP - 316 ER - TY - JOUR A1 - Memmel, Simon A1 - Sisario, Dmitri A1 - Zimmermann, Heiko A1 - Sauer, Markus A1 - Sukhorukov, Vladimir L. A1 - Djuzenova, Cholpon S. A1 - Flentje, Michael T1 - FocAn: automated 3D analysis of DNA repair foci in image stacks acquired by confocal fluorescence microscopy JF - BMC Bioinformatics N2 - Background Phosphorylated histone H2AX, also known as gamma H2AX, forms mu m-sized nuclear foci at the sites of DNA double-strand breaks (DSBs) induced by ionizing radiation and other agents. Due to their specificity and sensitivity, gamma H2AX immunoassays have become the gold standard for studying DSB induction and repair. One of these assays relies on the immunofluorescent staining of gamma H2AX followed by microscopic imaging and foci counting. During the last years, semi- and fully automated image analysis, capable of fast detection and quantification of gamma H2AX foci in large datasets of fluorescence images, are gradually replacing the traditional method of manual foci counting. A major drawback of the non-commercial software for foci counting (available so far) is that they are restricted to 2D-image data. In practice, these algorithms are useful for counting the foci located close to the midsection plane of the nucleus, while the out-of-plane foci are neglected. Results To overcome the limitations of 2D foci counting, we present a freely available ImageJ-based plugin (FocAn) for automated 3D analysis of gamma H2AX foci in z-image stacks acquired by confocal fluorescence microscopy. The image-stack processing algorithm implemented in FocAn is capable of automatic 3D recognition of individual cell nuclei and gamma H2AX foci, as well as evaluation of the total foci number per cell nucleus. The FocAn algorithm consists of two parts: nucleus identification and foci detection, each employing specific sequences of auto local thresholding in combination with watershed segmentation techniques. We validated the FocAn algorithm using fluorescence-labeled gamma H2AX in two glioblastoma cell lines, irradiated with 2 Gy and given up to 24 h post-irradiation for repair. We found that the data obtained with FocAn agreed well with those obtained with an already available software (FoCo) and manual counting. Moreover, FocAn was capable of identifying overlapping foci in 3D space, which ensured accurate foci counting even at high DSB density of up to similar to 200 DSB/nucleus. Conclusions FocAn is freely available an open-source 3D foci analyzer. The user-friendly algorithm FocAn requires little supervision and can automatically count the amount of DNA-DSBs, i.e. fluorescence-labeled gamma H2AX foci, in 3D image stacks acquired by laser-scanning microscopes without additional nuclei staining. KW - DNA double-strand breaks KW - ImageJ plugin KW - gamma H2AX-foci KW - Automated analysis KW - Ionizing radiation KW - Open-source tool KW - Radiation biology Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229023 VL - 21 ER - TY - JOUR A1 - Hartmannsberger, Beate A1 - Doppler, Kathrin A1 - Stauber, Julia A1 - Schlotter-Weigel, Beate A1 - Young, Peter A1 - Sereda, Michael W. A1 - Sommer, Claudia T1 - Intraepidermal nerve fiber density as biomarker in Charcot-Marie-Tooth disease 1A JF - Brain Communications N2 - Charcot–Marie–Tooth disease type 1A, caused by a duplication of the gene peripheral myelin protein 22 kDa, is the most frequent subtype of hereditary peripheral neuropathy with an estimated prevalence of 1:5000. Patients suffer from sensory deficits, muscle weakness and foot deformities. There is no treatment approved for this disease. Outcome measures in clinical trials were based mainly on clinical features but did not evaluate the actual nerve damage. In our case–control study, we aimed to provide objective and reproducible outcome measures for future clinical trials. We collected skin samples from 48 patients with Charcot–Marie–Tooth type 1A, 7 patients with chronic inflammatory demyelinating polyneuropathy, 16 patients with small fibre neuropathy and 45 healthy controls. To analyse skin innervation, 40-µm cryosections of glabrous skin taken from the lateral index finger were double-labelled by immunofluorescence. The disease severity of patients with Charcot–Marie–Tooth type 1A was assessed by the Charcot–Marie–Tooth neuropathy version 2 score, which ranged from 3 (mild) to 27 (severe) and correlated with age (P < 0.01, R = 0.4). Intraepidermal nerve fibre density was reduced in patients with Charcot–Marie–Tooth type 1A compared with the healthy control group (P < 0.01) and negatively correlated with disease severity (P < 0.05, R = −0.293). Meissner corpuscle (MC) density correlated negatively with age in patients with Charcot–Marie–Tooth type 1A (P < 0.01, R = −0.45) but not in healthy controls (P = 0.07, R = 0.28). The density of Merkel cells was reduced in patients with Charcot–Marie–Tooth type 1A compared with healthy controls (P < 0.05). Furthermore, in patients with Charcot–Marie–Tooth type 1A, the fraction of denervated Merkel cells was highly increased and correlated with age (P < 0.05, R = 0.37). Analysis of nodes of Ranvier revealed shortened paranodes and a reduced fraction of long nodes in patients compared with healthy controls (both P < 0.001). Langerhans cell density was increased in chronic inflammatory demyelinating polyneuropathy, but not different in Charcot–Marie–Tooth type 1A compared with healthy controls. Our data suggest that intraepidermal nerve fibre density might be used as an outcome measure in Charcot–Marie–Tooth type 1A disease, as it correlates with disease severity. The densities of Meissner corpuscles and Merkel cells might be an additional tool for the evaluation of the disease progression. Analysis of follow-up biopsies will clarify the effects of Charcot–Marie–Tooth type 1A disease progression on cutaneous innervation. KW - Charcot–Marie–Tooth disease type 1A KW - skin punch biopsy KW - intraepidermal nerve fibre density KW - Merkel cell density KW - reproducible outcome measure Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229538 VL - 2 IS - 1 ER - TY - JOUR A1 - Lepa, Carolin A1 - Möller‐Kerutt, Annika A1 - Stölting, Miriam A1 - Picciotto, Cara A1 - Eddy, Mee‐Ling A1 - Butt, Elke A1 - Kerjaschki, Dontscho A1 - Korb‐Pap, Adelheid A1 - Vollenbröker, Beate A1 - Weide, Thomas A1 - George, Britta A1 - Kremerskothen, Joachim A1 - Pavenstädt, Hermann T1 - LIM and SH3 protein 1 (LASP‐1): A novel link between the slit membrane and actin cytoskeleton dynamics in podocytes JF - The FASEB Journal N2 - The foot processes of podocytes exhibit a dynamic actin cytoskeleton, which maintains their complex cell structure and antagonizes the elastic forces of the glomerular capillary. Interdigitating secondary foot processes form a highly selective filter for proteins in the kidney, the slit membrane. Knockdown of slit membrane components such as Nephrin or Neph1 and cytoskeletal adaptor proteins such as CD2AP in mice leads to breakdown of the filtration barrier with foot process effacement, proteinuria, and early death of the mice. Less is known about the crosstalk between the slit membrane‐associated proteins and cytoskeletal components inside the podocyte foot processes. Our study shows that LASP‐1, an actin‐binding protein, is highly expressed in podocytes. Electron microscopy studies demonstrate that LASP‐1 is found at the slit membrane suggesting a role in anchoring slit membrane components to the actin cytoskeleton. Live cell imaging experiments with transfected podocytes reveal that LASP‐1 is either part of a highly dynamic granular complex or a static, actin cytoskeleton‐bound protein. We identify CD2AP as a novel LASP‐1 binding partner that regulates its association with the actin cytoskeleton. Activation of the renin‐angiotensin‐aldosterone system, which is crucial for podocyte function, leads to phosphorylation and altered localization of LASP‐1. In vivo studies using the Drosophila nephrocyte model indicate that Lasp is necessary for the slit membrane integrity and functional filtration. KW - actin cytoskeleton KW - angiotensin KW - CD2AP KW - nephrocyte KW - slit membrane Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215522 VL - 34 IS - 4 SP - 5453 EP - 5464 ER - TY - JOUR A1 - Elhfnawy, Ahmed Mohamed A1 - Abd El‐Raouf, Mervat A1 - Volkmann, Jens A1 - Fluri, Felix A1 - Elsalamawy, Doaa T1 - Relation of infarction location and volume to vertigo in vertebrobasilar stroke JF - Brain and Behavior N2 - Objective Vertigo is a common presentation of vertebrobasilar stroke. Anecdotal reports have shown that vertigo occurs more often in multiple than in single brainstem or cerebellar infarctions. We examined the relation between the location and volume of infarction and vertigo in patients with vertebrobasilar stroke. Methods Consecutive patients with vertebrobasilar stroke were prospectively recruited. The infarction location and volume were assessed in the diffusion‐weighted magnetic resonance imaging. Results Fifty‐nine patients were included, 32 (54.2%) with vertigo and 27 (45.8%) without vertigo. The infarction volume did not correlate with National Institute of Health Stroke Scale (NIHSS) score on admission (Spearman ρ = .077, p = .56) but correlated with modified Rankin Scale (ρ = .37, p = .004) on discharge. In the vertigo group, the proportion of men was lower (53.1% vs. 77.8%, p = .049), fewer patients had focal neurological deficits (65.6% vs. 96.3%, p = .004), patients tended to present later (median [IQR] was 7.5 [4–46] vs. 4 [2–12] hours, p = .052), numerically fewer patients received intravenous thrombolysis (15.6% vs. 37%, p = .06), and the total infarction volume was larger (5.6 vs. 0.42 cm3, p = .008) than in nonvertigo group. In multivariate logistic regression, infarction location either in the cerebellum or in the dorsal brainstem (odds ratio [OR] 16.97, 95% CI 3.1–92.95, p = .001) and a total infarction volume of >0.48 cm3 (OR 4.4, 95% CI 1.05–18.58, p = .043) were related to vertigo. In another multivariate logistic regression, after adjusting for age, sex, intravenous thrombolysis, serum level of white blood cells, and atrial fibrillation, vertigo independently predicted a total infarction volume of >0.48 cm3 (OR 5.75, 95% CI 1.43–23.08, p = .01). Conclusion Infarction location in the cerebellum and/or dorsal brainstem is an independent predictor of vertigo. Furthermore, larger infarction volume in these structures is associated with vertigo. A considerable proportion of patients with vascular vertigo present without focal neurological deficits posing a diagnostic challenge. National Institute of Health Stroke Scale is not sensitive for vertebrobasilar stroke. KW - brain stem KW - cerebellum KW - infarction volume KW - stroke KW - vertebrobasilar insufficiency KW - vertigo Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218047 VL - 10 IS - 3 ER - TY - JOUR A1 - Jung‐König, Mona A1 - Füllenbach, Christoph A1 - Murphy, Michael F. A1 - Manzini, Paola A1 - Laspina, Stefan A1 - Pendry, Kate A1 - Mühling, Jörg A1 - Wikman, Agneta A1 - Humbrecht, Catherine A1 - Rigal, Jean‐Christophe A1 - Lasocki, Sigismond A1 - Folléa, Gilles A1 - Seifried, Erhard A1 - Müller, Markus M. A1 - Geisen, Christof A1 - Aranko, Kari A1 - Zacharowski, Kai A1 - Meybohm, Patrick T1 - Programmes for the management of preoperative anaemia: audit in ten European hospitals within the PaBloE (Patient Blood Management in Europe) working group JF - Vox Sanguinis N2 - Background and objectives Preoperative anaemia is an independent risk factor for a higher morbidity and mortality, a longer hospitalization and increased perioperative transfusion rates. Managing preoperative anaemia is the first of three pillars of Patient Blood Management (PBM), a multidisciplinary concept to improve patient safety. While various studies provide medical information on (successful) anaemia treatment pathways, knowledge of organizational details of diagnosis and management of preoperative anaemia across Europe is scarce. Materials and methods To gain information on various aspects of preoperative anaemia management including organization, financing, diagnostics and treatment, we conducted a survey (74 questions) in ten hospitals from seven European nations within the PaBloE (Patient Blood Management in Europe) working group covering the year 2016. Results Organization and activity in the field of preoperative anaemia management were heterogeneous in the participating hospitals. Almost all hospitals had pathways for managing preoperative anaemia in place, however, only two nations had national guidelines. In six of the ten participating hospitals, preoperative anaemia management was organized by anaesthetists. Diagnostics and treatment focused on iron deficiency anaemia which, in most hospitals, was corrected with intravenous iron. Conclusion Implementation and approaches of preoperative anaemia management vary across Europe with a primary focus on treating iron deficiency anaemia. Findings of this survey motivated the hospitals involved to critically evaluate their practice and may also help other hospitals interested in PBM to develop action plans for diagnosis and management of preoperative anaemia. KW - iron deficiency KW - patient blood management KW - preoperative anaemia management Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214049 VL - 115 IS - 3 SP - 182 EP - 191 ER - TY - JOUR A1 - Haspert, Valentina A1 - Wieser, Matthias J. A1 - Pauli, Paul A1 - Reicherts, Philipp T1 - Acceptance-Based Emotion Regulation Reduces Subjective and Physiological Pain Responses JF - Frontiers in Psychology N2 - Acceptance-based regulation of pain, which focuses on the allowing of pain and pain related thoughts and emotions, was found to modulate pain. However, results so far are inconsistent regarding different pain modalities and indices. Moreover, studies so far often lack a suitable control condition, focus on behavioral pain measures rather than physiological correlates, and often use between-subject designs, which potentially impede the evaluation of the effectiveness of the strategies. Therefore, we investigated whether acceptance-based strategies can reduce subjective and physiological markers of acute pain in comparison to a control condition in a within-subject design. To this end, participants (N = 30) completed 24 trials comprising 10 s of heat pain stimulation. Each trial started with a cue instructing participants to welcome and experience pain (acceptance trials) or to react to the pain as it is without employing any regulation strategies (control trials). In addition to pain intensity and unpleasantness ratings, heart rate (HR) and skin conductance (SC) were recorded. Results showed significantly decreased pain intensity and unpleasantness ratings for acceptance compared to control trials. Additionally, HR was significantly lower during acceptance compared to control trials, whereas SC revealed no significant differences. These results demonstrate the effectiveness of acceptance-based strategies in reducing subjective and physiological pain responses relative to a control condition, even after short training. Therefore, the systematic investigation of acceptance in different pain modalities in healthy and chronic pain patients is warranted. KW - pain regulation KW - emotion regulation KW - acceptance KW - cognitive strategies KW - acute pain KW - acceptance-based strategy KW - psychological modulation of pain KW - pain ratings Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207220 SN - 1664-1078 VL - 11 ER - TY - JOUR A1 - Zamò, Alberto A1 - Johnston, Peter A1 - Attygalle, Ayoma D A1 - Laurent, Camille A1 - Arber, Daniel A A1 - Fend, Falko T1 - Aggressive B‐cell lymphomas with a primary bone marrow presentation JF - Histopathology KW - aggressive B‐cell lymphoma KW - bone marrow biopsy KW - bone marrow–spleen–liver large B‐cell lymphoma KW - diffuse large B‐cell lymphoma KW - EAHP/SH bone marrow workshop KW - high‐grade B‐cell lymphoma KW - intravascular large B‐cell lymphoma KW - primary bone marrow presentation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218327 VL - 77 IS - 3 SP - 369 EP - 379 ER -