TY - JOUR A1 - Heidenreich, Julius F. A1 - Weng, Andreas M. A1 - Donhauser, Julian A1 - Greiser, Andreas A1 - Chow, Kelvin A1 - Nordbeck, Peter A1 - Bley, Thorsten A. A1 - Köstler, Herbert T1 - T1- and ECV-mapping in clinical routine at 3 T: differences between MOLLI, ShMOLLI and SASHA JF - BMC Medical Imaging N2 - Background T1 mapping sequences such as MOLLI, ShMOLLI and SASHA make use of different technical approaches, bearing strengths and weaknesses. It is well known that obtained T1 relaxation times differ between the sequence techniques as well as between different hardware. Yet, T1 quantification is a promising tool for myocardial tissue characterization, disregarding the absence of established reference values. The purpose of this study was to evaluate the feasibility of native and post-contrast T1 mapping methods as well as ECV maps and its diagnostic benefits in a clinical environment when scanning patients with various cardiac diseases at 3 T. Methods Native and post-contrast T1 mapping data acquired on a 3 T full-body scanner using the three pulse sequences 5(3)3 MOLLI, ShMOLLI and SASHA in 19 patients with clinical indication for contrast enhanced MRI were compared. We analyzed global and segmental T1 relaxation times as well as respective extracellular volumes and compared the emerged differences between the used pulse sequences. Results T1 times acquired with MOLLI and ShMOLLI exhibited systematic T1 deviation compared to SASHA. Myocardial MOLLI T1 times were 19% lower and ShMOLLI T1 times 25% lower compared to SASHA. Native blood T1 times from MOLLI were 13% lower than SASHA, while post-contrast MOLLI T1-times were only 5% lower. ECV values exhibited comparably biased estimation with MOLLI and ShMOLLI compared to SASHA in good agreement with results reported in literature. Pathology-suspect segments were clearly differentiated from remote myocardium with all three sequences. Conclusion Myocardial T1 mapping yields systematically biased pre- and post-contrast T1 times depending on the applied pulse sequence. Additionally calculating ECV attenuates this bias, making MOLLI, ShMOLLI and SASHA better comparable. Therefore, myocardial T1 mapping is a powerful clinical tool for classification of soft tissue abnormalities in spite of the absence of established reference values. KW - T1 mapping KW - MOLLI KW - ShMOLLI KW - SASHA KW - Extracellular volume KW - 3 T Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201999 VL - 19 ER - TY - JOUR A1 - Streinzer, Martin A1 - Chakravorty, Jharna A1 - Neumayer, Johann A1 - Megu, Karsing A1 - Narah, Jaya A1 - Schmitt, Thomas A1 - Bharti, Himender A1 - Spaethe, Johannes A1 - Brockmann, Axel T1 - Species composition and elevational distribution of bumble bees (Hymenoptera, Apidae, Bombus Latreille) in the East Himalaya, Arunachal Pradesh, India JF - ZooKeys N2 - The East Himalaya is one of the world’s most biodiverse ecosystems. However, very little is known about the abundance and distribution of many plant and animal taxa in this region. Bumble bees are a group of cold-adapted and high elevation insects that fulfil an important ecological and economical function as pollinators of wild and agricultural flowering plants and crops. The Himalayan mountain range provides ample suitable habitats for bumble bees. Systematic study of Himalayan bumble bees began a few decades ago and the main focus has centred on the western region, while the eastern part of the mountain range has received little attention and only a few species have been verified. During a three-year survey, more than 700 bumble bee specimens of 21 species were collected in Arunachal Pradesh, the largest of the north-eastern states of India. The material included a range of species that were previously known from a limited number of collected specimens, which highlights the unique character of the East Himalayan ecosystem. Our results are an important first step towards a future assessment of species distribution, threat, and conservation. Clear elevation patterns of species diversity were observed, which raise important questions about the functional adaptations that allow bumble bees to thrive in this particularly moist region in the East Himalaya. KW - Alpine habitats KW - Apidae KW - conservation KW - global change KW - insect collection KW - pollination Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201937 VL - 851 ER - TY - JOUR A1 - Schuler, Michael A1 - Murauer, Kathrin A1 - Stangl, Stephanie A1 - Grau, Anna A1 - Gabriel, Katharina A1 - Podger, Lauren A1 - Heuschmann, Peter U. A1 - Faller, Hermann T1 - Pre-post changes in main outcomes of medical rehabilitation in Germany: protocol of a systematic review and meta-analysis of individual participant and aggregated data JF - BMJ Open N2 - Introduction Multidisciplinary, complex rehabilitation interventions are an important part of the treatment of chronic diseases. However, little is known about the effectiveness of routine rehabilitation interventions within the German healthcare system. Due to the nature of the social insurance system in Germany, randomised controlled trials examining the effects of rehabilitation interventions are challenging to implement and scarcely accessible. Consequently, alternative pre-post designs can be employed to assess pre-post effects of medical rehabilitation programmes. We present a protocol of systematic review and meta-analysis methods to assess the pre-post effects of rehabilitation interventions in Germany. Methods and analysis The respective study will be conducted within the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A systematic literature review will be conducted to identify studies reporting the pre-post effects (start of intervention vs end of intervention or later) in German healthcare. Studies investigating the following disease groups will be included: orthopaedics, rheumatology, oncology, pulmonology, cardiology, endocrinology, gastroenterology and psychosomatics. The primary outcomes of interest are physical/mental quality of life, physical functioning and social participation for all disease groups as well as pain (orthopaedic and rheumatologic patients only), blood pressure (cardiac patients only), asthma control (patients with asthma only), dyspnoea (patients with chronic obstructive pulmonary disease only) and depression/anxiety (psychosomatic patients only). We will invite the principal investigators of the identified studies to provide additional individual patient data. We aim to perform the meta-analyses using individual patient data as well as aggregate data. We will examine the effects of both study-level and patient-level moderators by using a meta-regression method. Ethics and dissemination Only studies that have received institutional approval from an ethics committee and present anonymised individual patient data will be included in the meta-analysis. The results will be presented in a peer-reviewed publication and at research conferences. A declaration of no objection by the ethics committee of the University of Würzburg is available (number 20180411 01). KW - medical rehabilitation Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201929 VL - 9 IS - 5 ER - TY - JOUR A1 - Gräb, Patrick A1 - Geidel, Ekkehard T1 - Spectroscopic studies of food colorings JF - World Journal of Chemical Education N2 - In chemical education, it is often a challenge to understand the basic principles of spectroscopic techniques due to missing connections to the real world. Therefore, the present contribution offers context-based applications of UV/Vis spectroscopy for analytics of food colorings with which learners can improve their skills regarding this method. The spectroscopic determination of food colorings seems to be a promising approach due to the long tradition and omnipresence of dyes in supermarket products. The therefor-required spectral data for commonly used dyes are provided for educational usage. Qualitative and quantitative analytics of food colorings in four different lemonades and chocolate beans have been used to introduce learners to important analytical techniques like sample preparation or elimination of confounding factors. These analytics also display the limitations of the method in the visible range of light in the case of tartrazine and curcumin. By applying Lambert-Beer-Bouguer’s Law in different variations, typical calculations of concentrations can be studied in quantitative analyses. The studied food samples demonstrate the different usage of food colorings depending on the country of sale. Finally, a 3D-printable low-cost photometer suitable for the discussed quantitative analytics in educational contexts is presented. KW - UV/Vis spectroscopy KW - quantitative analysis KW - food colorings KW - context-based teaching KW - low-cost photometer Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201908 VL - 7 IS - 2 ER - TY - JOUR A1 - Kim, Brandon J. A1 - McDonagh, Maura A. A1 - Deng, Liwen A1 - Gastfriend, Benjamin D. A1 - Schubert-Unkmeir, Alexandra A1 - Doran, Kelly S. A1 - Shusta, Eric V. T1 - Streptococcus agalactiae disrupts P-glycoprotein function in brain endothelial cells JF - Fluids and Barriers of the CNS N2 - Bacterial meningitis is a serious life threatening infection of the CNS. To cause meningitis, blood–borne bacteria need to interact with and penetrate brain endothelial cells (BECs) that comprise the blood–brain barrier. BECs help maintain brain homeostasis and they possess an array of efflux transporters, such as P-glycoprotein (P-gp), that function to efflux potentially harmful compounds from the CNS back into the circulation. Oftentimes, efflux also serves to limit the brain uptake of therapeutic drugs, representing a major hurdle for CNS drug delivery. During meningitis, BEC barrier integrity is compromised; however, little is known about efflux transport perturbations during infection. Thus, understanding the impact of bacterial infection on P-gp function would be important for potential routes of therapeutic intervention. To this end, the meningeal bacterial pathogen, Streptococcus agalactiae, was found to inhibit P-gp activity in human induced pluripotent stem cell-derived BECs, and live bacteria were required for the observed inhibition. This observation was correlated to decreased P-gp expression both in vitro and during infection in vivo using a mouse model of bacterial meningitis. Given the impact of bacterial interactions on P-gp function, it will be important to incorporate these findings into analyses of drug delivery paradigms for bacterial infections of the CNS. KW - Group B Streptococcus KW - Streptococcus agalactiae KW - Brain endothelial cells KW - P-glycoprotein KW - Efflux transport KW - Meningitis KW - Stem cells KW - P-gp Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201895 VL - 16 ER - TY - JOUR A1 - Drayß, Maria A1 - Claus, Heike A1 - Hubert, Kerstin A1 - Thiel, Katrin A1 - Berger, Anja A1 - Sing, Andreas A1 - van der Linden, Mark A1 - Vogel, Ulrich A1 - Lâm, Thiên-Trí T1 - Asymptomatic carriage of Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, Group A Streptococcus and Staphylococcus aureus among adults aged 65 years and older JF - PLoS ONE N2 - Objective The aim of this study was to determine the prevalence of Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, group A Streptococcus (GAS), and Staphylococcus aureus in asymptomatic elderly people and to unravel risk factors leading to colonization. Methods A multi-centre cross-sectional study was conducted including 677 asymptomatic adults aged 65 years or more, living at home or in nursing homes. Study areas were Greater Aachen (North-Rhine-Westphalia) and Wuerzburg (Bavaria), both regions with medium to high population density. Nasal and oropharyngeal swabs as well as questionnaires were collected from October 2012 to May 2013. Statistical analysis included multiple logistic regression models. Results The carriage rate was 1.9% ([95%CI: 1.0–3.3%]; 13/677) for H. influenzae, 0.3% ([95%CI: 0–1.1%]; 2/677) for N. meningitidis and 0% ([95% CI: 0–0.5%]; 0/677) for S. pneumoniae and GAS. Staphylococcus aureus was harboured by 28.5% of the individuals ([95% CI: 25.1–32.1%]; 193/677) and 0.7% ([95% CI: 0.2–1.7%]; 5/677) were positive for methicillin-resistant S. aureus. Among elderly community-dwellers colonization with S. aureus was significantly associated with higher educational level (adjusted OR: 1.905 [95% CI: 1.248–2.908]; p = 0.003). Among nursing home residents colonization was associated with being married (adjusted OR: 3.367 [1.502–7.546]; p = 0.003). Conclusion The prevalence of N. meningitidis, H. influenzae, S. pneumoniae and GAS was low among older people in Germany. The S. aureus rate was expectedly high, while MRSA was found in less than 1% of the individuals. KW - Geriatric care KW - Geriatrics KW - Elderly KW - Staphylococcus aureus KW - Nursing homes KW - Haemophilus influenzae KW - Neisseria meningitidis KW - Methicillin-resistant Staphylococcus aureus Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201042 VL - 14 IS - 2 ER - TY - JOUR A1 - Thiem, Alexander A1 - Hesbacher, Sonja A1 - Kneitz, Hermann A1 - di Primio, Teresa A1 - Heppt, Markus V. A1 - Hermanns, Heike M. A1 - Goebeler, Matthias A1 - Meierjohann, Svenja A1 - Houben, Roland A1 - Schrama, David T1 - IFN-gamma-induced PD-L1 expression in melanoma depends on p53 expression JF - Journal of Experimental & Clinical Cancer Research N2 - Background Immune checkpoint inhibition and in particular anti-PD-1 immunotherapy have revolutionized the treatment of advanced melanoma. In this regard, higher tumoral PD-L1 protein (gene name: CD274) expression is associated with better clinical response and increased survival to anti-PD-1 therapy. Moreover, there is increasing evidence that tumor suppressor proteins are involved in immune regulation and are capable of modulating the expression of immune checkpoint proteins. Here, we determined the role of p53 protein (gene name: TP53) in the regulation of PD-L1 expression in melanoma. Methods We analyzed publicly available mRNA and protein expression data from the cancer genome/proteome atlas and performed immunohistochemistry on tumors with known TP53 status. Constitutive and IFN-ɣ-induced PD-L1 expression upon p53 knockdown in wildtype, TP53-mutated or JAK2-overexpressing melanoma cells or in cells, in which p53 was rendered transcriptionally inactive by CRISPR/Cas9, was determined by immunoblot or flow cytometry. Similarly, PD-L1 expression was investigated after overexpression of a transcriptionally-impaired p53 (L22Q, W23S) in TP53-wt or a TP53-knockout melanoma cell line. Immunoblot was applied to analyze the IFN-ɣ signaling pathway. Results For TP53-mutated tumors, an increased CD274 mRNA expression and a higher frequency of PD-L1 positivity was observed. Interestingly, positive correlations of IFNG mRNA and PD-L1 protein in both TP53-wt and -mutated samples and of p53 and PD-L1 protein suggest a non-transcriptional mode of action of p53. Indeed, cell line experiments revealed a diminished IFN-ɣ-induced PD-L1 expression upon p53 knockdown in both wildtype and TP53-mutated melanoma cells, which was not the case when p53 wildtype protein was rendered transcriptionally inactive or by ectopic expression of p53\(^{L22Q,W23S}\), a transcriptionally-impaired variant, in TP53-wt cells. Accordingly, expression of p53\(^{L22Q,W23S}\) in a TP53-knockout melanoma cell line boosted IFN-ɣ-induced PD-L1 expression. The impaired PD-L1-inducibility after p53 knockdown was associated with a reduced JAK2 expression in the cells and was almost abrogated by JAK2 overexpression. Conclusions While having only a small impact on basal PD-L1 expression, both wildtype and mutated p53 play an important positive role for IFN-ɣ-induced PD-L1 expression in melanoma cells by supporting JAK2 expression. Future studies should address, whether p53 expression levels might influence response to anti-PD-1 immunotherapy. KW - Melanoma KW - PD-L1 KW - CD274 KW - p53 KW - TP53 KW - JAK2 Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201016 VL - 38 ER - TY - JOUR A1 - Vadokas, Georg A1 - Koehler, Stefan A1 - Weiland, Judith A1 - Lilla, Nadine A1 - Stetter, Christian A1 - Westermaier, Thomas T1 - Early antiinflammatory therapy attenuates brain damage after SAH in rats JF - Translational Neuroscience N2 - Background Early inflammatory processes may play an important role in the development of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Experimental studies suggest that anti-inflammatory and membrane-stabilizing drugs might have beneficial effects, although the underlying mechanisms are not fully understood. The aim of this study was to investigate the effect of early treatment with methylprednisolone and minocycline on cerebral perfusion and EBI after experimental SAH. Methods Male Sprague-Dawley rats were subjected to SAH using the endovascular filament model. 30 minutes after SAH, they were randomly assigned to receive an intravenous injection of methylprednisolone (16mg/kg body weight, n=10), minocycline (45mg/kg body weight, n=10) or saline (n=11). Mean arterial blood pressure (MABP), intracranial pressure (ICP) and local cerebral blood flow (LCBF) over both hemispheres were recorded continuously for three hours following SAH. Neurological assessment was performed after 24 hours. Hippocampal damage was analyzed by immunohistochemical staining (caspase 3). Results Treatment with methylprednisolone or minocycline did not result in a significant improvement of MABP, ICP or LCBF. Animals of both treatment groups showed a non-significant trend to better neurological recovery compared to animals of the control group. Mortality was reduced and hippocampal damage significantly attenuated in both methylprednisolone and minocycline treated animals. Conclusion The results of this study suggest that inflammatory processes may play an important role in the pathophysiology of EBI after SAH. Early treatment with the anti-inflammatory drugs methylprednisolone or minocycline in the acute phase of SAH has the potential to reduce brain damage and exert a neuroprotective effect. KW - subarachnoid hemorrhage KW - early brain injury KW - methylprednisolone KW - minocycline KW - neuroprotection Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201440 VL - 10 IS - 1 ER - TY - JOUR A1 - Huestegge, Lynn A1 - Herbort, Oliver A1 - Gosch, Nora A1 - Kunde, Wilfried A1 - Pieczykolan, Aleks T1 - Free-choice saccades and their underlying determinants: explorations of high-level voluntary oculomotor control JF - Journal of Vision N2 - Models of eye-movement control distinguish between different control levels, ranging from automatic (bottom-up, stimulus-driven selection) and automatized (based on well-learned routines) to voluntary (top-down, goal-driven selection, e.g., based on instructions). However, one type of voluntary control has yet only been examined in the manual and not in the oculomotor domain, namely free-choice selection among arbitrary targets, that is, targets that are of equal interest from both a bottom-up and top-down processing perspective. Here, we ask which features of targets (identity- or location-related) are used to determine such oculomotor free-choice behavior. In two experiments, participants executed a saccade to one of four peripheral targets in three different choice conditions: unconstrained free choice, constrained free choice based on target identity (color), and constrained free choice based on target location. The analysis of choice frequencies revealed that unconstrained free-choice selection closely resembled constrained choice based on target location. The results suggest that free-choice oculomotor control is mainly guided by spatial (location-based) target characteristics. We explain these results by assuming that participants tend to avoid less parsimonious recoding of target-identity representations into spatial codes, the latter being a necessary prerequisite to configure oculomotor commands. KW - Adolescent KW - Stimulation KW - Adult KW - Eye Movements/physiology KW - Female KW - Humans KW - Learning/physiology KW - Male KW - Oculomotor Muscles/physiology KW - Photic KW - Choice Behavior/physiology KW - Psychomotor Performance/physiology KW - Saccades/physiology KW - Young Adult KW - eye movement KW - saccades KW - free choice KW - top-down processing KW - bottom-up processing KW - control levels Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201493 VL - 19 IS - 3 ER - TY - JOUR A1 - Dietrich, Laura A1 - Meister, Julia A1 - Dietrich, Oliver A1 - Notroff, Jens A1 - Kiep, Janika A1 - Heeb, Julia A1 - Beuger, André A1 - Schütt, Brigitta T1 - Cereal processing at Early Neolithic Göbekli Tepe, southeastern Turkey JF - PLoS ONE N2 - We analyze the processing of cereals and its role at Early Neolithic Göbekli Tepe, southeastern Anatolia (10th / 9th millennium BC), a site that has aroused much debate in archaeological discourse. To date, only zooarchaeological evidence has been discussed in regard to the subsistence of its builders. Göbekli Tepe consists of monumental round to oval buildings, erected in an earlier phase, and smaller rectangular buildings, built around them in a partially contemporaneous and later phase. The monumental buildings are best known as they were in the focus of research. They are around 20 m in diameter and have stone pillars that are up to 5.5 m high and often richly decorated. The rectangular buildings are smaller and–in some cases–have up to 2 m high, mostly undecorated, pillars. Especially striking is the number of tools related to food processing, including grinding slabs/bowls, handstones, pestles, and mortars, which have not been studied before. We analyzed more than 7000 artifacts for the present contribution. The high frequency of artifacts is unusual for contemporary sites in the region. Using an integrated approach of formal, experimental, and macro- / microscopical use-wear analyses we show that Neolithic people at Göbekli Tepe have produced standardized and efficient grinding tools, most of which have been used for the processing of cereals. Additional phytolith analysis confirms the massive presence of cereals at the site, filling the gap left by the weakly preserved charred macro-rests. The organization of work and food supply has always been a central question of research into Göbekli Tepe, as the construction and maintenance of the monumental architecture would have necessitated a considerable work force. Contextual analyses of the distribution of the elements of the grinding kit on site highlight a clear link between plant food preparation and the rectangular buildings and indicate clear delimitations of working areas for food production on the terraces the structures lie on, surrounding the circular buildings. There is evidence for extensive plant food processing and archaeozoological data hint at large-scale hunting of gazelle between midsummer and autumn. As no large storage facilities have been identified, we argue for a production of food for immediate use and interpret these seasonal peaks in activity at the site as evidence for the organization of large work feasts. KW - Specimen grinding KW - Archaeology KW - Neolithic period KW - Sediment KW - Equipment KW - Stratigraphy KW - Limestone KW - Meat Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201504 VL - 14 IS - 5 ER - TY - JOUR A1 - Streng, Andrea A1 - Goettler, David A1 - Haerlein, Miriam A1 - Lehmann, Lisa A1 - Ulrich, Kristina A1 - Prifert, Christiane A1 - Krempl, Christine A1 - Weißbrich, Benedikt A1 - Liese, Johannes G. T1 - Spread and clinical severity of respiratory syncytial virus A genotype ON1 in Germany, 2011–2017 JF - BMC Infectious Diseases N2 - Background The Respiratory Syncytial Virus (RSV) A genotype ON1, which was first detected in Ontario (Canada) in 2010/11, appeared in Germany in 2011/12. Preliminary observations suggested a higher clinical severity in children infected with this new genotype. We investigated spread and disease severity of RSV-A ON1 in pediatric in- and outpatient settings. Methods During 2010/11 to 2016/17, clinical characteristics and respiratory samples from children with acute respiratory tract infections (RTI) were obtained from ongoing surveillance studies in 33 pediatric practices (PP), one pediatric hospital ward (PW) and 23 pediatric intensive care units (PICU) in Germany. RSV was detected in the respiratory samples by PCR; genotypes were identified by sequencing. Within each setting, clinical severity markers were compared between RSV-A ON1 and RSV-A non-ON1 genotypes. Results A total of 603 children with RSV-RTI were included (132 children in PP, 288 in PW, and 183 in PICU). Of these children, 341 (56.6%) were infected with RSV-A, 235 (39.0%) with RSV-B, and one child (0.2%) with both RSV-A and RSV-B; in 26 (4.3%) children, the subtype could not be identified. In the 341 RSV-A positive samples, genotype ON1 was detected in 247 (72.4%), NA1 in 92 (26.9%), and GA5 in 2 children (0.6%). RSV-A ON1, rarely observed in 2011/12, was the predominant RSV-A genotype in all settings by 2012/13 and remained predominant until 2016/17. Children in PP or PW infected with RSV-A ON1 did not show a more severe clinical course of disease compared with RSV-A non-ON1 infections. In the PICU group, hospital stay was one day longer (median 8 days, inter-quartile range (IQR) 7–12 vs. 7 days, IQR 5–9; p = 0.02) and duration of oxygen treatment two days longer (median 6 days, IQR 4–9 vs. 4 days, IQR 2–6; p = 0.03) for children infected with RSV-A ON1. Conclusions In children, RSV-A ON1 largely replaced RSV-A non-ON1 genotypes within two seasons and remained the predominant RSV-A genotype in Germany during subsequent seasons. A higher clinical severity of RSV-A ON1 was observed within the group of children receiving PICU treatment, whereas in other settings clinical severity of RSV-A ON1 and non-ON1 genotypes was largely similar. KW - Children KW - Respiratory tract infection KW - RSV-A ON1 KW - Epidemiology KW - Disease severity Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201516 VL - 19 ER - TY - JOUR A1 - Reichel, Thomas A1 - Rueckl, Kilian A1 - Fenwick, Annabel A1 - Vogt, Niklas A1 - Rudert, Maximilian A1 - Plumhoff, Piet T1 - Hibernoma of the upper extremity: complete case of a rare but benign soft tissue tumor JF - Case Reports in Orthopedics N2 - Hibernoma is a rare benign lipomatous tumor showing differentiation of brown fatty tissue. To the author’s best knowledge, there is no known case of malignant transformation or metastasis. Due to their slow, noninfiltrating growth hibernomas are often an incidental finding in the third or fourth decade of life. The vast majority are located in the thigh, neck, and periscapular region. A diagnostic workup includes ultrasound and contrast-enhanced MRI. Differential diagnosis is benign lipoma, well-differentiated liposarcoma, and rhabdomyoma. An incisional biopsy followed by marginal resection of the tumor is the standard of care, and recurrence after complete resection is not reported. The current paper presents diagnostic and intraoperative findings of a hibernoma of the upper arm and reviews similar reports in the current literature. KW - benige tumor Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201669 VL - 2019 ER - TY - JOUR A1 - Fayez, Shaimaa A1 - Feineis, Doris A1 - Aké Assi, Laurent A1 - Seo, Ean-Jeong A1 - Efferth, Thomas A1 - Bringmann, Gerhard T1 - Ancistrobreveines A–D and related dehydrogenated naphthylisoquinoline alkaloids with antiproliferative activities against leukemia cells, from the West African liana Ancistrocladus abbreviatus JF - RSC Advances N2 - A unique series of six biaryl natural products displaying four different coupling types (5,10 , 7,10 , 7,80 , and 5,80) were isolated from the roots of the West African liana Ancistrocladus abbreviatus (Ancistrocladaceae). Although at first sight structurally diverse, these secondary metabolites all have in common that they belong to the rare group of naphthylisoquinoline alkaloids with a fully dehydrogenated isoquinoline portion. Among the African Ancistrocladus species, A. abbreviatus is so far only the second one that was found to produce compounds with such a molecular entity. Here, we report on four new representatives, named ancistrobreveines A–D (12–14, and 6). They were identified along with the two known alkaloids 6-O-methylhamateine (4) and entdioncophylleine A (10). The two latter naphthylisoquinolines had so far only been detected in Ancistrocladus species from Southeast Asia. All of these fully dehydrogenated alkaloids have in common being optically active despite the absence of stereogenic centers, due to the presence of the rotationally hindered biaryl axis as the only element of chirality. Except for ent-dioncophylleine A (10), which lacks an oxygen function at C-6, the ancistrobreveines A–D (12–14, and 6) and 6-O-methylhamateine (4) are 6-oxygenated alkaloids, and are, thus, typical ‘Ancistrocladaceae-type’ compounds. Ancistrobreveine C (14), is the first – and so far only – example of a 7,80-linked fully dehydrogenated naphthylisoquinoline discovered in nature that is configurationally stable at the biaryl axis. The stereostructures of the new alkaloids were established by spectroscopic (in particular HRESIMS, 1D and 2D NMR) and chiroptical (electronic circular dichroism) methods. Ancistrobreveine C (14) and 6-O-methylhamateine (4) exhibited strong antiproliferative activities against drug-sensitive acute lymphoblastic CCRF-CEM leukemia cells and their multidrugresistant subline, CEM/ADR5000. KW - chemistry Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201686 VL - 9 IS - 28 ER - TY - JOUR A1 - Schmidt, Karsten A1 - Jakubietz, Michael Gregor A1 - Gilbert, Fabian A1 - Hausknecht, Franca A1 - Meffert, Rainer Heribert A1 - Jakubietz, Rafael Gregor T1 - Quality of life after flap reconstruction of the distal lower extremity: is there a difference between a pedicled suralis flap and a free anterior lateral thigh flap? JF - Plastic and Reconstructive Surgery - Global Open N2 - Background: Flap reconstruction of the distal lower extremity is challenging. Especially, the concept of perforator surgery has increased available surgical options. Although results are generally judged in terms of objective facts, patients-perceived quality of life has largely remained unexamined. The aim of the study was to compare quality of life after lower extremity reconstruction with pedicled and free flaps. Methods: Patients were evaluated retrospectively after reconstruction of defects of the distal lower extremity either with distally based adipofascial sural flap (pedicled reverse sural flap) or an anterior lateral thigh (ALT) flap. A specific questionnaire was developed to measure the patient’s quality of life, based on short form health survey-12, Dresden Body Image Score-35, Patient Health Questionnaire-4, and XSMFA questionnaires with additional specific questions. Furthermore, results, secondary surgeries, and complications were analyzed. Results: Thirty-seven patients with reconstruction of lower limb defects treated with a pedicled reverse sural flap and 34 patients treated with an ALT flap were included in the study. There was no statistical significant difference in the overall satisfaction with the procedure in the long-term follow-up between both groups, but patients with ALT showed a higher satisfaction with the treatment in the initial postoperative period. Both groups demonstrated approximately similar results in the long term for self-acceptance and vitality. Conclusions: Although anatomic situation may dictate flap choice coverage with free flaps, a less-complicated flap is by no means regarded as an inferior treatment option in patient’s estimation. Despite the intuitive speculation that patients with more advanced reconstruction methods should have better function and subsequently higher quality of life, this assumption was clearly not supported by data in this study. KW - reconstructive surgery Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203940 VL - 7 IS - 4 ER - TY - JOUR A1 - Reichel, Thomas A1 - Mitnacht, Martin A1 - Fenwick, Annabel A1 - Meffert, Rainer A1 - Hoos, Olaf A1 - Fehske, Kai T1 - Incidence and characteristics of acute andoveruse injuries in elite powerlifters JF - Cogent Medicine N2 - Abstract: The aim of this study was the analysis of incidence and type of injury in German elite powerlifters. A total of n = 57 competitive athletes of the German powerlifting federation completed a retrospective survey regarding acute andoveruse injuries. With 224 total injuries, a mean incidence of 1.51 per 1.000 h or 0.49 per year was calculated. Most injuries affected the lower back (20.5%), elbow (11.2%), pelvic region (10.3) and the shoulder (9.8%). Regarding the type of injury acute inflammation (25.9%), muscle strains/sprains (20.5%) and skin lesions (13%) dominated. The mean incidence significantly declined with increasing age and training experience of the athlete. Athletes using a bench press shirt and various regenerative methods like sauna or swimming also showed decreased injury rates. There was no significant correlation between body weight, height or gender and injury incidence. Compared to other sports, the incidence of injuries and overuse syndromes is still low in powerlifting. Nonetheless, appropriate strategies in training, equipment, prevention and regeneration should be employed to protect the athlete from injury. KW - powerlifting KW - weightlifting KW - bench press KW - injury KW - overuse injury KW - strength training Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204005 VL - 6 ER - TY - JOUR A1 - Glutsch, Valerie A1 - Grän, Franziska A1 - Weber, Judith A1 - Gesierich, Anja A1 - Goebeler, Matthias A1 - Schilling, Bastian T1 - Response to combined ipilimumab and nivolumab after development of a nephrotic syndrome related to PD-1 monotherapy JF - Journal for ImmunoTherapy of Cancer N2 - Background High response rates of metastatic melanoma have been reported upon immune checkpoint inhibition by PD-1 blockade alone or in combination with CTLA-4 inhibitors. However, the majority of patients with a primary resistance to anti-PD-1 monotherapy is also refractory to a subsequent combined checkpoint inhibition. In BRAF wildtype patients with a primary resistance to PD-1 inhibitors, therapeutic options are therefore limited and immune-related adverse events (irAE) have to be taken into consideration when discussing a subsequent immunotherapy. Case presentation We report the case of a 68-year-old male patient with metastatic melanoma who experienced an acute renal failure with nephrotic syndrome due to a minimal change disease developing after a single dose of the anti-PD-1 antibody pembrolizumab. A kidney biopsy revealed a podocytopathy without signs of interstitial nephritis. Renal function recovered to almost normal creatinine and total urine protein levels upon treatment with oral steroids and diuretics. Unfortunately, a disease progression (PD, RECIST 1.1) was observed in a CT scan after resolution of the irAE. In a grand round, re-exposure to a PD-1-containing regime was recommended. Consensually, a combined immunotherapy with ipilimumab and nivolumab was initiated. Nephrotoxicity was tolerable during combined immunotherapy and a CT scan of chest and abdomen showed a deep partial remission (RECIST 1.1) after three doses of ipilimumab (3 mg/kg) and nivolumab (1 mg/kg). Conclusion This case illustrates that a fulminant response to combined checkpoint inhibition is possible after progression after anti-PD-1 monotherapy and a severe irAE. KW - PD-1 KW - Immune-related adverse event KW - Minimal change disease KW - Ipilimumab KW - Nivolumab Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201214 VL - 7 ER - TY - JOUR A1 - Haring, Bernhard A1 - Crandall, Carolyn J A1 - Carbone, Laura A1 - Liu, Simin A1 - Li, Wenjun A1 - Johnson, Karen C A1 - Wactawski-Wende, Jean A1 - Shadyab, Aladdin H A1 - Gass, Margery L A1 - Kamensky, Victor A1 - Cauley, Jane A A1 - Wassertheil-Smoller, Sylvia T1 - Lipoprotein(a) plasma levels, bone mineral density and risk of hip fracture: a post hoc analysis of the Women’s Health Initiative, USA JF - BMJ Open N2 - Objectives Elevated Lipoprotein(a) (Lp[a]) is a well-known risk factor for cardiovascular disease. However, its roles in bone metabolism and fracture risk are unclear. We therefore investigated whether plasma Lp(a) levels were associated with bone mineral density (BMD) and incident hip fractures in a large cohort of postmenopausal women. Design Post hoc analysis of data from the Women’s Health Initiative (WHI), USA. Setting 40 clinical centres in the USA. Participants The current analytical cohort consisted of 9698 white, postmenopausal women enrolled in the WHI, a national prospective study investigating determinants of chronic diseases including heart disease, breast and colorectal cancers and osteoporotic fractures among postmenopausal women. Recruitment for WHI took place from 1 October 1993 to 31 December 1998. Exposures Plasma Lp(a) levels were measured at baseline. Outcome measures Incident hip fractures were ascertained annually and confirmed by medical records with follow-up through 29 August 2014. BMD at the femoral neck was measured by dual X-ray absorptiometry in a subset of participants at baseline. Statistical analyses Cox proportional hazards and logistic regression models were used to evaluate associations of quartiles of plasma Lp(a) levels with hip fracture events and hip BMD T-score, respectively. Results During a mean follow-up of 13.8 years, 454 incident cases of hip fracture were observed. In analyses adjusting for confounding variables including age, body mass index, history of hysterectomy, smoking, physical activity, diabetes mellitus, general health status, cardiovascular disease, use of menopausal hormone therapy, use of bisphosphonates, calcitonin or selective-oestrogen receptor modulators, baseline dietary and supplemental calcium and vitamin D intake and history of fracture, no significant association of plasma Lp(a) levels with low hip BMD T-score or hip fracture risk was detected. Conclusions These findings suggest that plasma Lp(a) levels are not related to hip BMD T-score or hip fracture events in postmenopausal women. KW - hip fracture Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201139 VL - 9 ER - TY - JOUR A1 - Gernert, Michael A1 - Tony, Hans-Peter A1 - Schwaneck, Eva Christina A1 - Gadeholt, Ottar A1 - Schmalzing, Marc T1 - Autologous hematopoietic stem cell transplantation in systemic sclerosis induces long-lasting changes in B cell homeostasis toward an anti-inflammatory B cell cytokine pattern JF - Arthritis Research & Therapy N2 - Background Autologous hematopoietic stem cell transplantation (aHSCT) is performed in patients with aggressive forms of systemic sclerosis (SSc). The profile of B cell reconstitution after aHSCT is not fully understood. The aim of this study was to investigate changes of B cell subsets and cytokine production of B cells in patients with SSc after aHSCT. Methods Peripheral blood of six patients with SSc was collected at defined intervals up to 16 months after aHSCT. Immunophenotyping was performed, and B cell function was determined by measuring cytokine secretion in supernatants of stimulated B cell cultures. Results Within 1 month after aHSCT, a peak in the percentage of CD38\(^{++}\)/CD10\(^+\)/IgD\(^+\) transitional B cells and CD38\(^{++}\)/CD27\(^{++}\)/IgD\(^−\) plasmablasts was detected. Long-term changes persisted up to 14 months after aHSCT and showed an increased percentage of total B cells; the absolute B cell number did not change significantly. Within the B cell compartment, an increased CD27/IgD\(^+\) naïve B cell percentage was found whereas decreased percentages of CD27\(^+\)/IgD\(^+\) pre-switched memory, CD27\(^+\)/IgD\(^−\) post-switched memory, and CD27\(^−\) /IgD\(^−\) double-negative B cells were seen after aHSCT. Cytokine secretion in B cell cultures showed significantly increased IL-10 concentrations 13 to 16 months after aHSCT. Conclusion A changed composition of the B cell compartment is present for up to 14 months after aHSCT indicating positive persisting effects of aHSCT on B cell homeostasis. The cytokine secretion profile of B cells changes in the long term and shows an increased production of the immune regulatory cytokine IL-10 after aHSCT. These findings might promote the clinical improvements after aHSCT in SSc patients. KW - Systemic sclerosis KW - B cells KW - Memory B cells KW - naïve B cells KW - Autologous hematopoietic stem cell transplantation KW - Interleukin-10 Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201004 VL - 21 ER - TY - JOUR A1 - Ruf, Katharina A1 - Beer, Meinrad A1 - Köstler, Herbert A1 - Weng, Andreas Max A1 - Neubauer, Henning A1 - Klein, Alexander A1 - Platek, Kathleen A1 - Roth, Kristina A1 - Beneke, Ralph A1 - Hebestreit, Helge T1 - Size-adjusted muscle power and muscle metabolism in patients with cystic fibrosis are equal to healthy controls – a case control study JF - BMC Pulmonary Medicine N2 - Background Skeletal muscle function dysfunction has been reported in patients with cystic fibrosis (CF). Studies so far showed inconclusive data whether reduced exercise capacity is related to intrinsic muscle dysfunction in CF. Methods Twenty patients with CF and 23 age-matched controls completed an incremental cardiopulmonary cycling test. Further, a Wingate anaerobic test to assess muscle power was performed. In addition, all participants completed an incremental knee-extension test with 31P magnetic resonance spectroscopy to assess muscle metabolism (inorganic phosphate (Pi) and phosphocreatinine (PCr) as well as intracellular pH). In the MRI, muscle cross-sectional area of the M. quadriceps (qCSA) was also measured. A subgroup of 15 participants (5 CF, 10 control) additionally completed a continuous high-intensity, high-frequency knee-extension exercise task during 31P magnetic resonance spectroscopy to assess muscle metabolism. Results Patients with CF showed a reduced exercise capacity in the incremental cardiopulmonary cycling test (VO2peak: CF 77.8 ± 16.2%predicted (36.5 ± 7.4 ml/qCSA/min), control 100.6 ± 18.8%predicted (49.1 ± 11.4 ml/qCSA/min); p < 0.001), and deficits in anaerobic capacity reflected by the Wingate test (peak power: CF 537 ± 180 W, control 727 ± 186 W; mean power: CF 378 ± 127 W, control 486 ± 126 W; power drop CF 12 ± 5 W, control 8 ± 4 W. all: p < 0.001). In the knee-extension task, patients with CF achieved a significantly lower workload (p < 0.05). However, in a linear model analysing maximal work load of the incremental knee-extension task and results of the Wingate test, respectively, only muscle size and height, but not disease status (CF or not) contributed to explaining variance. In line with this finding, no differences were found in muscle metabolism reflected by intracellular pH and the ratio of Pi/PCr at submaximal stages and peak exercise measured through MRI spectroscopy. Conclusions The lower absolute muscle power in patients with CF compared to controls is exclusively explained by the reduced muscle size in this study. No evidence was found for an intrinsic skeletal muscle dysfunction due to primary alterations of muscle metabolism. KW - Cystic fibrosis KW - Exercise capacity KW - MRI spectroscopy KW - Muscle power KW - Phosphorylation KW - Lung disease, KW - Muscle function Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200981 VL - 19 ER - TY - JOUR A1 - Popp, Christina A1 - Ramírez-Zavala, Bernardo A1 - Schwanfelder, Sonja A1 - Krüger, Ines A1 - Morschhäuser, Joachim T1 - Evolution of fluconazole-resistant Candida albicans strains by drug-induced mating competence and parasexual recombination JF - mBio N2 - The clonal population structure of Candida albicans suggests that (para)sexual recombination does not play an important role in the lifestyle of this opportunistic fungal pathogen, an assumption that is strengthened by the fact that most C. albicans strains are heterozygous at the mating type locus (MTL) and therefore mating-incompetent. On the other hand, mating might occur within clonal populations and allow the combination of advantageous traits that were acquired by individual cells to adapt to adverse conditions. We have investigated if parasexual recombination may be involved in the evolution of highly drug-resistant strains exhibiting multiple resistance mechanisms against fluconazole, an antifungal drug that is commonly used to treat infections by C. albicans. Growth of strains that were heterozygous for MTL and different fluconazole resistance mutations in the presence of the drug resulted in the emergence of derivatives that had become homozygous for the mutated allele and the mating type locus and exhibited increased drug resistance. When MTLa/a and MTLα/α cells of these strains were mixed in all possible combinations, we could isolate mating products containing the genetic material from both parents. The initial mating products did not exhibit higher drug resistance than their parental strains, but further propagation under selective pressure resulted in the loss of the wild-type alleles and increased fluconazole resistance. Therefore, fluconazole treatment not only selects for resistance mutations but also promotes genomic alterations that confer mating competence, which allows cells in an originally clonal population to exchange individually acquired resistance mechanisms and generate highly drug-resistant progeny. KW - Candida albicans KW - drug resistance evolution KW - mating KW - parasexual recombination Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200901 VL - 10 IS - 1 ER -