TY - JOUR A1 - Pereira, Ana Rita A1 - Lipphaus, Andreas A1 - Ergin, Mert A1 - Salehi, Sahar A1 - Gehweiler, Dominic A1 - Rudert, Maximilian A1 - Hansmann, Jan A1 - Herrmann, Marietta T1 - Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal Stem Cell−Extracellular Matrix Interactions JF - Materials N2 - In bone tissue engineering, the design of in vitro models able to recreate both the chemical composition, the structural architecture, and the overall mechanical environment of the native tissue is still often neglected. In this study, we apply a bioreactor system where human bone-marrow hMSCs are seeded in human femoral head-derived decellularized bone scaffolds and subjected to dynamic culture, i.e., shear stress induced by continuous cell culture medium perfusion at 1.7 mL/min flow rate and compressive stress by 10% uniaxial load at 1 Hz for 1 h per day. In silico modeling revealed that continuous medium flow generates a mean shear stress of 8.5 mPa sensed by hMSCs seeded on 3D bone scaffolds. Experimentally, both dynamic conditions improved cell repopulation within the scaffold and boosted ECM production compared with static controls. Early response of hMSCs to mechanical stimuli comprises evident cell shape changes and stronger integrin-mediated adhesion to the matrix. Stress-induced Col6 and SPP1 gene expression suggests an early hMSC commitment towards osteogenic lineage independent of Runx2 signaling. This study provides a foundation for exploring the early effects of external mechanical stimuli on hMSC behavior in a biologically meaningful in vitro environment, opening new opportunities to study bone development, remodeling, and pathologies. KW - bone tissue engineering KW - human trabecular bone decellularization KW - in vitro modeling KW - shear stress KW - compressive load KW - fluid simulation KW - cell-matrix interaction KW - mechanotransduction Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245012 SN - 1996-1944 VL - 14 IS - 16 ER - TY - JOUR A1 - Eisenhuth, Nicole A1 - Vellmer, Tim A1 - Rauh, Elisa T. A1 - Butter, Falk A1 - Janzen, Christian J. T1 - A DOT1B/Ribonuclease H2 Protein Complex Is Involved in R-Loop Processing, Genomic Integrity, and Antigenic Variation in Trypanosoma brucei JF - mbio N2 - The parasite Trypanosoma brucei periodically changes the expression of protective variant surface glycoproteins (VSGs) to evade its host's immune sys-tem in a process known as antigenic variation. One route to change VSG expres-sion is the transcriptional activation of a previously silent VSG expression site (ES), a subtelomeric region containing the VSG genes. Homologous recombination of a different VSG from a large reservoir into the active ES represents another route. The conserved histone methyltransferase DOT1B is involved in transcriptional silencing of inactive ES and influences ES switching kinetics. The molecular machin-ery that enables DOT1B to execute these regulatory functions remains elusive, however. To better understand DOT1B-mediated regulatory processes, we purified DOT1B-associated proteins using complementary biochemical approaches. We iden-tified several novel DOT1B interactors. One of these was the RNase H2 complex, previously shown to resolve RNA-DNA hybrids, maintain genome integrity, and play a role in antigenic variation. Our study revealed that DOT1B depletion results in an increase in RNA-DNA hybrids, accumulation of DNA damage, and ES switch-ing events. Surprisingly, a similar pattern of VSG deregulation was observed in RNase H2 mutants. We propose that both proteins act together in resolving R-loops to ensure genome integrity and contribute to the tightly regulated process of anti-genic variation. KW - DOT1B KW - R-loop KW - antigenic variation KW - chromatin structure KW - genomic integrity Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260698 VL - 12 IS - 6 ER - TY - JOUR A1 - Voelker, Johannes A1 - Voelker, Christine A1 - Engert, Jonas A1 - Goemann, Nikolas A1 - Hagen, Rudolf A1 - Rak, Kristen T1 - Spontaneous Calcium Oscillations through Differentiation: A Calcium Imaging Analysis of Rat Cochlear Nucleus Neural Stem Cells JF - Cells N2 - Causal therapies for the auditory-pathway and inner-ear diseases are still not yet available for clinical application. Regenerative medicine approaches are discussed and examined as possible therapy options. Neural stem cells could play a role in the regeneration of the auditory pathway. In recent years, neural stem and progenitor cells have been identified in the cochlear nucleus, the second nucleus of the auditory pathway. The current investigation aimed to analyze cell maturation concerning cellular calcium activity. Cochlear nuclei from PND9 CD rats were microscopically dissected and propagated as neurospheres in free-floating cultures in stem-cell medium (Neurobasal, B27, GlutaMAX, EGF, bFGF). After 30 days, the dissociation and plating of these cells took place under withdrawal of the growth factors and the addition of retinoic acid, which induces neural cell differentiation. Calcium imaging analysis with BAPTA-1/Oregon Green was carried out at different times during the differentiation phase. In addition, the influence of different voltage-dependent calcium channels was analyzed through the targeted application of inhibitors of the L-, N-, R- and T-type calcium channels. For this purpose, comparative examinations were performed on CN NSCs, and primary CN neurons. As the cells differentiated, a significant increase in spontaneous neuronal calcium activity was demonstrated. In the differentiation stage, specific frequencies of the spontaneous calcium oscillations were measured in different regions of the individual cells. Initially, the highest frequency of spontaneous calcium oscillations was ascertainable in the maturing somata. Over time, these were overtaken by calcium oscillations in the axons and dendrites. Additionally, in the area of the growth cones, an increasing activity was determined. By inhibiting voltage-dependent calcium channels, their expression and function in the differentiation process were confirmed. A comparable pattern of maturation of these channels was found in CN NSCs and primary CN neurons. The present results show that neural stem cells of the rat cochlear nucleus differentiated not only morphologically but also functionally. Spontaneous calcium activities are of great relevance in terms of neurogenesis and integration into existing neuronal structures. These functional aspects of neurogenesis within the auditory pathway could serve as future targets for the exogenous control of neuronal regeneration. KW - neurogenesis KW - neural stem cells KW - neuronal oscillations KW - neuronal maturation KW - auditory pathway KW - regenerative capacity Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248482 SN - 2073-4409 VL - 10 IS - 10 ER - TY - JOUR A1 - Seeger, Jennifer A1 - Lenhard, Wolfgang A1 - Wisniewski, Katrin T1 - Metakognitives Strategiewissen in sprachbezogenen Situationen : Interne Struktur und Validität des ScenEx JF - Diagnostica N2 - Studieren stellt hohe Anforderungen an selbstregulatorische Fähigkeiten und eigenverantwortlichen Umgang mit schwierigen Situationen. Aus den zusätzlichen sprachlichen Barrieren für ausländische Studierende erwachsen spezifische selbstregulatorische Aufgaben, wie der Umgang mit Verständnisproblemen in Vorlesungen. Da hierfür bisher kaum geeignete Erhebungsinstrumente existieren, versucht ScenEx diese Lücke zu schließen. Der Test erfasst das metakognitive Strategiewissen in sprachlich herausfordernden Situationen im Studienalltag. Anhand einer Stichprobe von 290 ausländischen Studierenden im ersten Fachsemester wird die psychometrische Qualität und interne Struktur des Instruments überprüft. ScenEx zeigt eine zufriedenstellende interne Konsistenz und gute Itemfit-Kennwerte, erwartungskonform liegen lokale stochastische Abhängigkeiten der Aufgaben innerhalb der Szenarien vor. Eine konfirmatorische Faktorenanalyse bestätigt die Grobstruktur der Szenarien und des Gesamtscores des Tests. Das Verfahren ist für die weitere Entwicklung der Sprachkompetenz über die anfängliche Sprachfähigkeit hinaus prädiktiv. ScenEx erweist sich insgesamt als ein reliables und valides Instrument zur Erfassung des Strategiewissens in schwierigen Situationen im Studium. N2 - Studying at a university requires a high degree of self-reliance. Self-regulatory skills and the ability to independently handle difficult situations are important for successfully completing a degree. In addition, foreign students are faced with language-based challenges demanding specific self-regulatory skills, such as dealing with comprehension problems in lectures. To date, assessing these skills has been difficult because of a lack of suitable instruments. The ScenEx Questionnaire purports to close this gap by measuring metacognitive strategic knowledge in everyday study situations by posing language-based challenges, presented as scenarios. Using a sample of 290 foreign students in their first semester, we assessed the psychometric quality of ScenEx. ScenEx shows a satisfactory internal consistency and good item fit. A confirmatory factor analysis confirms the structure of the scenarios and the overall score of the test. The procedure predicts the further development of language competence beyond the initial stage. ScenEx is a valid and reliable instrument for assessing strategic knowledge regarding linguistically difficult situations at the university. T2 - Metacognitive Strategic Knowledge in Language-Related Situations KW - Selbstregulation KW - Strategiewissen KW - Bildungsausländer KW - Studienerfolg KW - Deutsch als Fremdsprache KW - self-regulation KW - strategic knowledge KW - foreign students KW - academic success Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242375 SN - 0012-1924 SN - 2190-622X VL - 67 IS - 4 ER - TY - JOUR A1 - Plassmeier, Lars A1 - Hankir, Mohammed K. A1 - Seyfried, Florian T1 - Impact of Excess Body Weight on Postsurgical Complications JF - Visceral Medicine N2 - Background: Obesity is considered a risk factor for postoperative complications as it can limit exposure to the operation field, thereby significantly prolonging surgery time. Obesity-associated comorbidities, such as low-grade systemic inflammation, impaired functional status, and type 2 diabetes, are independent risk factors for impaired anastomotic wound healing and nonsurgical site infections. If obesity itself is an independent risk factor for surgical complications remains controversial, but the reason for this is largely unexplored. Summary: A MEDLINE literature search was performed using the terms: “obesity,” “excess body weight,” and “surgical complications.” Out of 65,493 articles 432 meta-analyses were screened, of which 25 meta-analyses were on the subject. The vast majority of complex oncologic procedures in the field of visceral surgery have shown higher complication rates in obese patients. Meta-analyses from the last 10 to 15 years with high numbers of patients enrolled consistently have shown longer operation times, higher blood loss, longer hospital stay for colorectal procedures, oncologic upper gastrointestinal (GI) procedures, and pancreatic surgery. Interestingly, these negative effects seem not to affect the overall survival in oncologic patients, especially in esophageal resections. A selection bias in oncologic upper GI patients may have influenced the results with higher BMI in upper GI cancer to be a predictor for better nutritional and performance status. Key Messages: Contrary to bariatric surgery, only limited evidence indicated that site and type of surgery, the approach to the abdominal cavity (laparoscopic vs. open), institutional factors, and the type of perioperative care such as ERAS protocols may play a role in determining postsurgical complications in obese patients. The initial question remains therefore partially unanswered. Large nationwide register-based studies are necessary to better understand which aspects of obesity and its related comorbidities define it as a risk factor for surgical complications. KW - obesity KW - surgical complications KW - laparoscopy Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244890 SN - 2297-4725 SN - 2297-475X VL - 37 IS - 4 ER - TY - JOUR A1 - Ibebuchi, Chibuike Chiedozie T1 - Revisiting the 1992 severe drought episode in South Africa: the role of El Niño in the anomalies of atmospheric circulation types in Africa south of the equator JF - Theoretical and Applied Climatology N2 - During strong El Niño events, below-average rainfall is expected in large parts of southern Africa. The 1992 El Niño season was associated with one of the worst drought episodes in large parts of South Africa. Using reanalysis data set from NCEP-NCAR, this study examined circulation types (CTs) in Africa south of the equator that are statistically related to the El Niño signal in the southwest Indian Ocean and the implication of this relationship during the 1992 drought episode in South Africa. A statistically significant correlation was found between the above-average Nino 3.4 index and a CT that features widespread cyclonic activity in the tropical southwest Indian Ocean, coupled with a weaker state of the south Indian Ocean high-pressure. During the analysis period, it was found that the El Niño signal enhanced the amplitude of the aforementioned CT. The impacts of the El Niño signal on CTs in southern Africa, which could have contributed to the 1992 severe drought episode in South Africa, were reflected in (i) robust decrease in the frequency of occurrence of the austral summer climatology pattern of atmospheric circulation that favors southeasterly moisture fluxes, advected by the South Indian Ocean high-pressure; (ii) modulation of easterly moisture fluxes, advected by the South Atlantic Ocean high-pressure, ridging south of South Africa; (iii) and enhancement of the amplitude of CTs that both enhances subsidence over South Africa, and associated with the dominance of westerlies across the Agulhas current. Under the ssp585 scenario, the analyzed climate models suggested that the impact of radiative heating on the CT significantly related to El Niño might result in an anomalous increase in surface pressure at the eastern parts of South Africa. KW - South Africa KW - drought KW - El Niño Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-268569 SN - 1434-4483 VL - 146 IS - 1-2 ER - TY - JOUR A1 - Cao, Liyu A1 - Steinborn, Michael B. A1 - Haendel, Barbara F. T1 - Delusional thinking and action binding in healthy individuals JF - Scientific Reports N2 - Action binding is the effect that the perceived time of an action is shifted towards the action related feedback. A much larger action binding effect in schizophrenia compared to normal controls has been shown, which might be due to positive symptoms like delusions. Here we investigated the relationship between delusional thinking and action binding in healthy individuals, predicting a positive correlation between them. The action binding effect was evaluated by comparing the perceived time of a keypress between an operant (keypress triggering a sound) and a baseline condition (keypress alone), with a novel testing method that massively improved the precision of the subjective timing measurement. A positive correlation was found between the tendency of delusional thinking (measured by the 21-item Peters et al. delusions inventory) and action binding across participants after controlling for the effect of testing order between operant and baseline conditions. The results indicate that delusional thinking in particular influences action time perception and support the notion of a continuous distribution of schizotypal traits with normal controls at one end and clinical patients at the other end. KW - cognitive neuroscience KW - psychology Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-264707 VL - 11 IS - 1 ER - TY - JOUR A1 - Paudel, Rupesh A1 - Fusi, Lorenza A1 - Schmidt, Marc T1 - The MEK5/ERK5 pathway in health and disease JF - International Journal of Molecular Sciences N2 - The MEK5/ERK5 mitogen-activated protein kinases (MAPK) cascade is a unique signaling module activated by both mitogens and stress stimuli, including cytokines, fluid shear stress, high osmolarity, and oxidative stress. Physiologically, it is mainly known as a mechanoreceptive pathway in the endothelium, where it transduces the various vasoprotective effects of laminar blood flow. However, it also maintains integrity in other tissues exposed to mechanical stress, including bone, cartilage, and muscle, where it exerts a key function as a survival and differentiation pathway. Beyond its diverse physiological roles, the MEK5/ERK5 pathway has also been implicated in various diseases, including cancer, where it has recently emerged as a major escape route, sustaining tumor cell survival and proliferation under drug stress. In addition, MEK5/ERK5 dysfunction may foster cardiovascular diseases such as atherosclerosis. Here, we highlight the importance of the MEK5/ERK5 pathway in health and disease, focusing on its role as a protective cascade in mechanical stress-exposed healthy tissues and its function as a therapy resistance pathway in cancers. We discuss the perspective of targeting this cascade for cancer treatment and weigh its chances and potential risks when considering its emerging role as a protective stress response pathway. KW - atherosclerosis KW - bone KW - cartilage KW - endothelium KW - extracellular-regulated kinase 5 KW - Krüppel-like factor KW - mechanotransduction KW - mitogen-activated protein kinase KW - stress signaling KW - tumor Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261638 SN - 1422-0067 VL - 22 IS - 14 ER - TY - JOUR A1 - Bielmeier, Christina B. A1 - Roth, Saskia A1 - Schmitt, Sabrina I. A1 - Boneva, Stefaniya K. A1 - Schlecht, Anja A1 - Vallon, Mario A1 - Tamm, Ernst R. A1 - Ergün, Süleyman A1 - Neueder, Andreas A1 - Braunger, Barbara M. T1 - Transcriptional profiling identifies upregulation of neuroprotective pathways in retinitis pigmentosa JF - International Journal of Molecular Sciences N2 - Hereditary retinal degenerations like retinitis pigmentosa (RP) are among the leading causes of blindness in younger patients. To enable in vivo investigation of cellular and molecular mechanisms responsible for photoreceptor cell death and to allow testing of therapeutic strategies that could prevent retinal degeneration, animal models have been created. In this study, we deeply characterized the transcriptional profile of mice carrying the transgene rhodopsin V20G/P23H/P27L (VPP), which is a model for autosomal dominant RP. We examined the degree of photoreceptor degeneration and studied the impact of the VPP transgene-induced retinal degeneration on the transcriptome level of the retina using next generation RNA sequencing (RNASeq) analyses followed by weighted correlation network analysis (WGCNA). We furthermore identified cellular subpopulations responsible for some of the observed dysregulations using in situ hybridizations, immunofluorescence staining, and 3D reconstruction. Using RNASeq analysis, we identified 9256 dysregulated genes and six significantly associated gene modules in the subsequently performed WGCNA. Gene ontology enrichment showed, among others, dysregulation of genes involved in TGF-β regulated extracellular matrix organization, the (ocular) immune system/response, and cellular homeostasis. Moreover, heatmaps confirmed clustering of significantly dysregulated genes coding for components of the TGF-β, G-protein activated, and VEGF signaling pathway. 3D reconstructions of immunostained/in situ hybridized sections revealed retinal neurons and Müller cells as the major cellular population expressing representative components of these signaling pathways. The predominant effect of VPP-induced photoreceptor degeneration pointed towards induction of neuroinflammation and the upregulation of neuroprotective pathways like TGF-β, G-protein activated, and VEGF signaling. Thus, modulation of these processes and signaling pathways might represent new therapeutic options to delay the degeneration of photoreceptors in diseases like RP. KW - retinitis pigmentosa KW - VPP mouse model KW - in-situ hybridization KW - neurodegeneration KW - neuroinflammation KW - extracellular matrix disorganisation KW - neuroprotective pathways Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260769 SN - 1422-0067 VL - 22 IS - 12 ER - TY - JOUR A1 - Pernitzsch, Sandy R. A1 - Alzheimer, Mona A1 - Bremer, Belinda U. A1 - Robbe-Saule, Marie A1 - De Reuse, Hilde A1 - Sharma, Cynthia M. T1 - Small RNA mediated gradual control of lipopolysaccharide biosynthesis affects antibiotic resistance in Helicobacter pylori JF - Nature Communications N2 - The small, regulatory RNA RepG (Regulator of polymeric G-repeats) regulates the expression of the chemotaxis receptor TlpB in Helicobacter pylori by targeting a variable G-repeat in the tlpB mRNA leader. Here, we show that RepG additionally controls lipopolysaccharide (LPS) phase variation by also modulating the expression of a gene (hp0102) that is co-transcribed with tlpB. The hp0102 gene encodes a glycosyltransferase required for LPS O-chain biosynthesis and in vivo colonization of the mouse stomach. The G-repeat length defines a gradual (rather than ON/OFF) control of LPS biosynthesis by RepG, and leads to gradual resistance to a membrane-targeting antibiotic. Thus, RepG-mediated modulation of LPS structure might impact host immune recognition and antibiotic sensitivity, thereby helping H. pylori to adapt and persist in the host. The small RNA RepG modulates expression of chemotaxis receptor TlpB in Helicobacter pylori by targeting a length-variable G-repeat in the tlpB mRNA. Here, Pernitzsch et al. show that RepG also gradually controls lipopolysaccharide biosynthesis, antibiotic susceptibility, and in-vivo colonization of the stomach, by regulating a gene that is co-transcribed with tlpB. KW - bacterial genetics KW - bacterial immune evasion KW - pathogens KW - small RNAs Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261536 VL - 12 IS - 1 ER - TY - JOUR A1 - Frings, Verena Gerlinde A1 - Schöffski, Oliver A1 - Goebeler, Matthias A1 - Presser, Dagmar T1 - Economic analysis of the costs associated with Hidradenitis suppurativa at a German University Hospital JF - PLoS One N2 - Background and objectives Hidradenitis suppurativa (HS) significantly affects the patient`s quality of life and leads to multiple medical consultations. Aim of this study was to assess the utilization of medical care of HS patients. Patients and methods All patients presenting in 2017 for an outpatient, day patient and / or inpatient treatment with leading claim type HS at the Department of Dermatology, University Hospital Würzburg, were included. Primary outcome was the economic burden of HS patients, measured by resource utilization in €. Results The largest share of the direct medical costs for HS were the inpatient costs with a leading surgical diagnosis-related group (DRG). Antiseptics were the predominant topical prescription. While doxycycline was the most frequently prescribed systemic therapy, adalimumab was the main cost driver. The difference between in-patient (€ 110.25) and outpatient (€ 26.34) direct non-medical costs was statistically significant (p < 0.001). With regards to indirect medical costs, a statistically significantly higher loss of gross value added (inpatient mean € 1,827.00; outpatient mean € 203.00) and loss of production (inpatient mean € 1,026.00; outpatient mean € 228.00) could be noted (p < 0.001), respectively. Conclusions The present study on disease-specific costs of HS confirms that the hospital care of patients with this disease is cost-intensive. However, the primary goal of physicians is not and should not be to save costs regarding their patients`treatment, but rather the premise to utilize the existing resources as efficient as possible. Reducing the use of costly therapeutics and inpatient stays therefore requires more effective therapy options with an improved cost-benefit profile. KW - inpatients KW - outpatients KW - health insurance KW - dermatology KW - surgical and invasive medical procedures KW - health economics KW - psoriasis KW - indirect costs Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261668 VL - 16 IS - 8 ER - TY - JOUR A1 - Seefried, L. A1 - Rak, D. A1 - Petryk, A. A1 - Genest, F. T1 - Bone turnover and mineral metabolism in adult patients with hypophosphatasia treated with asfotase alfa JF - Osteoporosis International N2 - Summary There is limited understanding of how asfotase alfa affects mineral metabolism and bone turnover in adults with pediatric-onset hypophosphatasia. This study showed that adults with hypophosphatasia treated with asfotase alfa experienced significant changes in biochemical markers of bone and mineral metabolism, possibly reflecting enhanced bone remodeling of previously osteomalacic bone. Introduction Hypophosphatasia (HPP), due to a tissue nonspecific alkaline phosphatase (TNSALP) deficiency, can cause impaired bone mineralization and turnover. Although HPP may be treated with asfotase alfa, an enzyme replacement therapy, limited data are available on how treatment with asfotase alfa affects mineral metabolism and bone turnover in adults with HPP. Methods ALP substrates, bone turnover and mineral metabolism markers, and bone mineral density (BMD) data from EmPATHY, a single-center, observational study of adults (≥ 18 years) with pediatric-onset HPP treated with asfotase alfa (NCT03418389), were collected during routine clinical care and analyzed from baseline through 24 months of treatment. Results Data from 21 patients showed significantly increased ALP activity and reduced urine phosphoethanolamine (PEA)/creatinine (Cr) ratios after baseline through 24 months of asfotase alfa treatment. There were significant transient increases in parathyroid hormone 1-84 (PTH), osteocalcin, and procollagen type 1 N-propeptide (P1NP) levels at 3 and 6 months and in tartrate-resistant acid phosphatase 5b (TRAP5b) levels at 3 months, with a significant decrease in N-terminal telopeptide of type 1 collagen (NTX) levels at 24 months. Lumbar spine BMD T scores continuously increased during treatment. Conclusion Significant changes in bone turnover and mineral metabolism markers after asfotase alfa treatment suggest that treatment-mediated mineralization may enable remodeling and bone turnover on previously unmineralized surfaces. Urine PEA/Cr ratios may be a useful parameter in monitoring treatment during routine care. KW - bone mineral density KW - bone turnover KW - hypophosphatasia KW - enzyme replacement therapy KW - alkaline phosphatase Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265310 VL - 32 IS - 12 ER - TY - JOUR A1 - Becht, Alexander A1 - Schollmayer, Curd A1 - Monakhova, Yulia A1 - Holzgrabe, Ulrike T1 - Tracing the origin of paracetamol tablets by near-infrared, mid-infrared, and nuclear magnetic resonance spectroscopy using principal component analysis and linear discriminant analysis JF - Analytical and Bioanalytical Chemistry N2 - Most drugs are no longer produced in their own countries by the pharmaceutical companies, but by contract manufacturers or at manufacturing sites in countries that can produce more cheaply. This not only makes it difficult to trace them back but also leaves room for criminal organizations to fake them unnoticed. For these reasons, it is becoming increasingly difficult to determine the exact origin of drugs. The goal of this work was to investigate how exactly this is possible by using different spectroscopic methods like nuclear magnetic resonance and near- and mid-infrared spectroscopy in combination with multivariate data analysis. As an example, 56 out of 64 different paracetamol preparations, collected from 19 countries around the world, were chosen to investigate whether it is possible to determine the pharmaceutical company, manufacturing site, or country of origin. By means of suitable pre-processing of the spectra and the different information contained in each method, principal component analysis was able to evaluate manufacturing relationships between individual companies and to differentiate between production sites or formulations. Linear discriminant analysis showed different results depending on the spectral method and purpose. For all spectroscopic methods, it was found that the classification of the preparations to their manufacturer achieves better results than the classification to their pharmaceutical company. The best results were obtained with nuclear magnetic resonance and near-infrared data, with 94.6%/99.6% and 98.7/100% of the spectra of the preparations correctly assigned to their pharmaceutical company or manufacturer. KW - \(^{1}\)HNMR KW - IR KW - manufacturer KW - linear discriminant analysis KW - principal component analysis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265400 VL - 413 IS - 11 ER - TY - JOUR A1 - von Lukowicz, Hannah A1 - Schlegel, Paul-Gerhardt A1 - Härtel, Christoph A1 - Morbach, Henner A1 - Haubitz, Imme A1 - Wiegering, Verena T1 - ESPED survey on newly diagnosed immune thrombocytopenia in childhood: how much treatment do we give? JF - Molecular and Cellular Pediatrics N2 - Background Immune thrombocytopenia (ITP) is an autoimmune disease associated with isolated thrombocytopenia, which is caused by an imbalance between platelet production and platelet destruction. Petechial and mucous membrane hemorrhages are characteristic of ITP, but life-threatening bleeding rarely occurs. Depending on the bleeding symptoms, ITP can be treated with glucocorticoids (GC), intravenous immunoglobulins (IVIG), or in severe cases, platelet transfusions. Mild bleeding does not necessarily require therapy. Using the German Surveillance Unit for rare Pediatric Diseases (ESPED) we conducted a prospective survey on ITP patients in all German Children's Hospitals between September 2018 and August 2019. We collected data on ITP, including the clinical course, therapy implementation recommendations (according to the Association of German Scientific Medical Societies guidelines), outcome, and influence of treatment regimens depending on the treating physician´s experience with ITP patients. Results Of the 287 recorded cases of children with ITP, 268 questionnaires were sent to the authors. Two hundred seventeen of the questionnaires fulfilled the inclusion criteria. ITP affected boys and girls similarly, and the median age of manifestation was 3.5 years. The main reasons for hospitalization were thrombocytopenia, bleeding signs, hematomas, and/or petechiae. Bleeding scores were ≤ 3 in 96% of children, which corresponded to a low-to-moderately low risk of bleeding. No life-threatening bleeding was documented. The most common therapies were IVIG (n = 59), GC (n = 33), or a combination of these (n = 17). Blood products (i.e., red blood cells, platelet concentrate, and fresh frozen plasma) were given to 13 patients. Compared to the established guidelines, 67 patients were over-treated, and 2 patients were under-treated. Conclusions Adherence to German ITP treatment guidelines is currently limited. To improve patient safety and medical care, better medical training and dissemination of the guidelines are required in line with targeted analyses of patients with serious bleeding events to identify potential risk constellations. KW - pediatric immune thrombocytopenia KW - acute ITP KW - newly diagnosed ITP KW - ESPED KW - autoimmunity KW - treatment guidelines KW - intravenous immunoglobulins KW - bleeding score KW - children Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261832 VL - 8 ER - TY - JOUR A1 - Riechelmann, Eva A1 - Gamer, Matthias A1 - Böckler, Anna A1 - Huestegge, Lynn T1 - How ubiquitous is the direct-gaze advantage? Evidence for an averted-gaze advantage in a gaze-discrimination task JF - Attention, Perception, & Psychophysics N2 - Human eye gaze conveys an enormous amount of socially relevant information, and the rapid assessment of gaze direction is of particular relevance in order to adapt behavior accordingly. Specifically, previous research demonstrated evidence for an advantage of processing direct (vs. averted) gaze. The present study examined discrimination performance for gaze direction (direct vs. averted) under controlled presentation conditions: Using a backward-masking gaze-discrimination task, photographs of faces with direct and averted gaze were briefly presented, followed by a mask stimulus. Additionally, effects of facial context on gaze discrimination were assessed by either presenting gaze direction in isolation (i.e., by only showing the eye region) or in the context of an upright or inverted face. Across three experiments, we consistently observed a facial context effect with highest discrimination performance for faces presented in upright position, lower performance for inverted faces, and lowest performance for eyes presented in isolation. Additionally, averted gaze was generally responded to faster and with higher accuracy than direct gaze, indicating an averted-gaze advantage. Overall, the results suggest that direct gaze is not generally associated with processing advantages, thereby highlighting the important role of presentation conditions and task demands in gaze perception. KW - social cognition KW - gaze processing KW - averted gaze KW - direct gaze KW - gaze discrimination Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235268 SN - 1943-3921 VL - 83 ER - TY - JOUR A1 - Böckler, Anne A1 - Rennert, Annika A1 - Raettig, Tim T1 - Stranger, Lover, Friend? BT - The Pain of Rejection Does Not Depend JF - Social Psychology N2 - Social exclusion, even from minimal game-based interactions, induces negative consequences. We investigated whether the nature of the relationship with the excluder modulates the effects of ostracism. Participants played a virtual ball-tossing game with a stranger and a friend (friend condition) or a stranger and their romantic partner (partner condition) while being fully included, fully excluded, excluded only by the stranger, or excluded only by their close other. Replicating previous findings, full exclusion impaired participants’ basic-need satisfaction and relationship evaluation most severely. While the degree of exclusion mattered, the relationship to the excluder did not: Classic null hypothesis testing and Bayesian statistics showed no modulation of ostracism effects depending on whether participants were excluded by a stranger, a friend, or their partner. KW - interpersonal relationships KW - ostracism KW - rejection KW - social exclusion KW - social interaction Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238721 SN - 1864-9335 SN - 2151-2590 VL - 52 IS - 3 ER - TY - JOUR A1 - Engert, Jonas A1 - Rak, Kristen A1 - Bieniussa, Linsa A1 - Scholl, Miriam A1 - Hagen, Rudolf A1 - Völker, Johannes T1 - Evaluation of the Neurogenic Potential in the Rat Inferior Colliculus from Early Postnatal Days Until Adulthood JF - Molecular Neurobiology N2 - Neural stem cells (NSCs) have been recently identified in the inferior colliculus (IC). These cells are of particular interest, as no casual therapeutic options for impaired neural structures exist. This research project aims to evaluate the neurogenic potential in the rat IC from early postnatal days until adulthood. The IC of rats from postnatal day 6 up to 48 was examined by neurosphere assays and histological sections. In free-floating IC cell cultures, neurospheres formed from animals from early postnatal to adulthood. The amount of generated neurospheres decreased in older ages and increased with the number of cell line passages. Cells in the neurospheres and the histological sections stained positively with NSC markers (Doublecortin, Sox-2, Musashi-1, Nestin, and Atoh1). Dissociated single cells from the neurospheres differentiated and were stained positively for the neural lineage markers β-III-tubulin, glial fibrillary acidic protein, and myelin basic protein. In addition, NSC markers (Doublecortin, Sox-2, CDK5R1, and Ascl-1) were investigated by qRT-PCR. In conclusion, a neurogenic potential in the rat IC was detected and evaluated from early postnatal days until adulthood. The identification of NSCs in the rat IC and their age-specific characteristics contribute to a better understanding of the development and the plasticity of the auditory pathway and might be activated for therapeutic use. KW - central auditory pathway KW - inferior colliculus KW - neural progenitor cells KW - neural stem cells KW - neurosphere Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235811 SN - 0893-7648 VL - 58 ER - TY - JOUR A1 - Piselli, Claudio A1 - Benz, Roland T1 - Fosmidomycin transport through the phosphate‐specific porins OprO and OprP of Pseudomonas aeruginosa JF - Molecular Microbiology N2 - The Gram‐negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen, responsible for many hospital‐acquired infections. The bacterium is quite resistant toward many antibiotics, in particular because of the fine‐tuned permeability of its outer membrane (OM). General diffusion outer membrane pores are quite rare in this organism. Instead, its OM contains many substrate‐specific porins. Their expression is varying according to growth conditions and virulence. Phosphate limitations, as well as pathogenicity factors, result in the induction of the two mono‐ and polyphosphate‐specific porins, OprP and OprO, respectively, together with an inner membrane uptake mechanism and a periplasmic binding protein. These outer membrane channels could serve as outer membrane pathways for the uptake of phosphonates. Among them are not only herbicides, but also potent antibiotics, such as fosfomycin and fosmidomycin. In this study, we investigated the interaction between OprP and OprO and fosmidomycin in detail. We could demonstrate that fosmidomycin is able to bind to the phosphate‐specific binding site inside the two porins. The inhibition of chloride conductance of OprP and OprO by fosmidomycin is considerably less than that of phosphate or diphosphate, but it can be measured in titration experiments of chloride conductance and also in single‐channel experiments. The results suggest that fosmidomycin transport across the OM of P. aeruginosa occurs through OprP and OprO. Our data with the ones already known in the literature show that phosphonic acid‐containing antibiotics are in general good candidates to treat the infections of P. aeruginosa at the very beginning through a favorable OM transport system. KW - fosmidomycin KW - lipid bilayer membrane KW - OprO KW - OprP KW - porin Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238905 VL - 116 IS - 1 SP - 97 EP - 108 ER - TY - JOUR A1 - Wittkowski, Joachim A1 - Scheuchenpflug, Rainer T1 - Evidence on the Conceptual Distinctness of Normal Grief From Depression BT - A Multi-Faceted Analysis of Differential Validity JF - European Journal of Health Psychology N2 - Background: The distinctness of grief from depression has been the subject of a long scholarly debate, even influencing definitions of diagnostic criteria. Aims: This study aims at clarifying the issue by a multifaceted analysis of data from a large German sample. Method: A community sample of 406 bereaved persons answered the Wuerzburg Grief Inventory (WGI), a multidimensional grief questionnaire designed to measure normal grief in the German language, and the General Depression Scale – Short Version (GDS-S), a self-report depression scale. Data were analyzed by factor analysis to identify structural (dis-)similarities of the constructs, and analysis of variance (ANOVA) to identify the influence of the factors relationship to the deceased, type of death, and time since loss on grief measures and depression scores. Results: Factor analysis clustered items referring to grief-related impairments and depression into one factor, items referring to other dimensions of grief on separate factors, however. Relationship to the deceased influenced the grief measures impairments and nearness to the deceased, but not depression scores if controlled for impairments. Type of death showed specific effects on grief scores, but not on depression scores. Time since loss influenced grief scores, but not depression scores. Limitations: The analysis is based on a self-selected community sample of grieving persons, self-report measures, and in part, on cross-sectional data. Conclusion: Factor analysis and objective data show a clear distinction of dimensions of grief and depression. The human experience of grief contains a sense of nearness to the lost person, feelings of guilt, and positive aspects of the loss experience in addition to components resembling depression. KW - depression KW - grief KW - time since loss KW - type of death KW - Wuerzburg Grief Inventory (WGI) Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236531 SN - 2512-8442 SN - 2512-8450 VL - 28 IS - 3 SP - 101-110 ER - TY - JOUR A1 - Wannagat, Wienke A1 - Waizenegger, Gesine A1 - Niedling, Gerhild T1 - Coherence formation during narrative text processing: a comparison between auditory and audiovisual text presentation in 9- to 12-year-old children JF - Cognitive Processing N2 - In an experiment with 114 children aged 9–12 years, we compared the ability to establish local and global coherence of narrative texts between auditory and audiovisual (auditory text and pictures) presentation. The participants listened to a series of short narrative texts, in each of which a protagonist pursued a goal. Following each text, we collected the response time to a query word that was either associated with a near or a distant causal antecedent of the final sentence. Analysis of these response times indicated that audiovisual presentation has advantages over auditory presentation for accessing information relevant for establishing both local and global coherence, but there are indications that this effect may be slightly more pronounced for global coherence. KW - text comprehension KW - multimodal narratives KW - coherence KW - children Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235744 SN - 1612-4782 VL - 22 ER -