@article{MoremiClausVogeletal.2019, author = {Moremi, Nyambura and Claus, Heike and Vogel, Ulrich and Mshana, Stephen E.}, title = {The role of patients and healthcare workers Staphylococcus aureus nasal colonization in occurrence of surgical site infection among patients admitted in two centers in Tanzania}, series = {Antimicrobial Resistance \& Infection Control}, volume = {8}, journal = {Antimicrobial Resistance \& Infection Control}, doi = {10.1186/s13756-019-0554-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224185}, year = {2019}, abstract = {Background Colonization with Staphylococcus aureus has been identified as a risk for subsequent occurrence of infection. This study investigated the relationship between S. aureus colonization of patients and healthcare workers (HCWs), and subsequent surgical site infections (SSI). Methods Between December 2014 and September 2015, a total of 930 patients and 143 HCWs were enrolled from the Bugando Medical Centre and Sekou Toure hospital in Mwanza, Tanzania. On admission and discharge nasal swabs, with an additional of wound swab for those who developed SSI were collected from patients whereas HCWs were swabbed once. Identification and antimicrobial susceptibility testing were done by VITEK-MS and VITEK-2, respectively. Detection of Panton Valentine leukocidin (PVL) and mecA genes was done by PCR. S. aureus isolates were further characterized by spa typing and Multi-Locus Sequence Typing (MLST). Results Among 930 patients screened for S. aureus on admission, 129 (13.9\%) were positive of which 5.4\% (7/129) were methicillin-resistant S. aureus (MRSA). Amongst 363 patients rescreened on discharge, 301 patients had been tested negative on admission of whom 29 (9.6\%) turned positive after their hospital stay. Three (10.3\%) of the 29 acquired S. aureus were MRSA. Inducible Clindamycin resistance occurred more often among acquired S. aureus isolates than among isolates from admission [34.5\% (10/29) vs. 17.1\% (22/129), P = 0.018]. S. aureus contributed to 21.1\% (n = 12) of the 57 cases of investigated SSIs among 536 patients followed. Seven out of eight S. aureus carriage/infection pairs had the same spa and sequence types. The previously reported dominant PVL-positive ST88 MRSA strain with spa type t690 was detected in patients and HCW. Conclusion A significant proportion of patients acquired S. aureus during hospitalization. The finding of more than 90\% of S. aureus SSI to be of endogenous source underscores the need of improving infection prevention and control measures including screening and decolonization of high risk patients.}, language = {en} } @article{BrumbergBlazhenetsSchroeteretal.2019, author = {Brumberg, Joachim and Blazhenets, Ganna and Schr{\"o}ter, Nils and Frings, Lars and Jost, Wolfgang H. and Lapa, Constantin and Meyer, Philipp T.}, title = {Imaging cardiac sympathetic innervation with MIBG: linear conversion of the heart-to-mediastinum ratio between different collimators}, series = {EJNMMI Physics}, volume = {6}, journal = {EJNMMI Physics}, doi = {10.1186/s40658-019-0250-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221675}, year = {2019}, abstract = {Background The heart-to-mediastinum (H/M) ratio is a commonly used parameter to measure cardiac I-123 metaiodobenzylguanidine (MIBG) uptake. Since the H/M ratio is substantially influenced by the collimator type, we investigated whether an empirical linear conversion of H/M ratios between camera systems with low-energy (LE) and medium-energy (ME) collimator is possible. Methods We included 18 patients with parkinsonism who were referred to one of the two participating molecular imaging facilities for the evaluation of cardiac sympathetic innervation by MIBG scintigraphy. Two consecutive planar image datasets were acquired with LE and ME collimators at 4 h after MIBG administration. Linear regression analyses were performed to describe the association between the H/M ratios gained with both collimator settings, and the accuracy of a linear transfer of the H/M ratio between collimators and across centers was assessed using a leave-one-out procedure. Results H/M ratios acquired with LE and ME collimators showed a strong linear relationship both within each imaging facility (R\(^2\) = 0.99, p < 0.001 and R\(^2\) = 0.90, p < 0.001) and across centers (H/M-LE = 0.41 × H/M-ME + 0.63, R\(^2\) = 0.97, p < 0.001). A linear conversion of H/M ratios between collimators and across centers was estimated to be very accurate (mean absolute error 0.05 ± 0.04; mean relative absolute error 3.2 ± 2.6\%). Conclusions The present study demonstrates that a simple linear conversion of H/M ratios acquired with different collimators is possible with high accuracy. This should greatly facilitate the exchange of normative data between settings and pooling of data from different institutions.}, language = {en} } @article{KienerChenKrebsetal.2019, author = {Kiener, Mirjam and Chen, Lanpeng and Krebs, Markus and Grosjean, Joȅl and Klima, Irena and Kalogirou, Charis and Riedmiller, Hubertus and Kneitz, Burkhard and Thalmann, George N. and Snaar-Jagalska, Ewa and Spahn, Martin and Kruithof-de Julio, Marianna and Zoni, Eugenio}, title = {miR-221-5p regulates proliferation and migration in human prostate cancer cells and reduces tumor growth in vivo}, series = {BMC Cancer}, volume = {19}, journal = {BMC Cancer}, doi = {10.1186/s12885-019-5819-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325762}, year = {2019}, abstract = {Background Despite latest advances in prostate cancer (PCa) therapy, PCa remains the third-leading cause of cancer-related death in European men. Dysregulation of microRNAs (miRNAs), small non-coding RNA molecules with gene expression regulatory function, has been reported in all types of epithelial and haematological cancers. In particular, miR-221-5p alterations have been reported in PCa. Methods miRNA expression data was retrieved from a comprehensive publicly available dataset of 218 PCa patients (GSE21036) and miR-221-5p expression levels were analysed. The functional role of miR-221-5p was characterised in androgen- dependent and androgen- independent PCa cell line models (C4-2 and PC-3M-Pro4 cells) by miR-221-5p overexpression and knock-down experiments. The metastatic potential of highly aggressive PC-3M-Pro4 cells overexpressing miR-221-5p was determined by studying extravasation in a zebrafish model. Finally, the effect of miR-221-5p overexpression on the growth of PC-3M-Pro4luc2 cells in vivo was studied by orthotopic implantation in male Balb/cByJ nude mice and assessment of tumor growth. Results Analysis of microRNA expression dataset for human primary and metastatic PCa samples and control normal adjacent benign prostate revealed miR-221-5p to be significantly downregulated in PCa compared to normal prostate tissue and in metastasis compared to primary PCa. Our in vitro data suggest that miR-221-5p overexpression reduced PCa cell proliferation and colony formation. Furthermore, miR-221-5p overexpression dramatically reduced migration of PCa cells, which was associated with differential expression of selected EMT markers. The functional changes of miR-221-5p overexpression were reversible by the loss of miR-221-5p levels, indicating that the tumor suppressive effects were specific to miR-221-5p. Additionally, miR-221-5p overexpression significantly reduced PC-3M-Pro4 cell extravasation and metastasis formation in a zebrafish model and decreased tumor burden in an orthotopic mouse model of PCa. Conclusions Together these data strongly support a tumor suppressive role of miR-221-5p in the context of PCa and its potential as therapeutic target.}, language = {en} } @article{KlementAbbasiSengerAdebahretal.2019, author = {Klement, Rainer J. and Abbasi-Senger, N. and Adebahr, S. and Alheid, H. and Allgaeuer, M. and Becker, G. and Blanck, O. and Boda-Heggemann, J. and Brunner, T. and Duma, M. and Eble, M. J. and Ernst, I. and Gerum, S. and Habermehl, D. and Hass, P. and Henkenberens, C. and Hildebrandt, G. and Imhoff, D. and Kahl, H. and Klass, N. D. and Krempien, R. and Lewitzki, V. and Lohaus, F. and Ostheimer, C. and Papachristofilou, A. and Petersen, C. and Rieber, J. and Schneider, T. and Schrade, E. and Semrau, R. and Wachter, S. and Wittig, A. and Guckenberger, M. and Andratschke, N.}, title = {The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases}, series = {BMC Cancer}, volume = {19}, journal = {BMC Cancer}, doi = {10.1186/s12885-019-5362-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325877}, year = {2019}, abstract = {Background The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. Methods The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. Results Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. Conclusion In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.}, language = {en} } @article{HoertererBaumbachLemperleetal.2019, author = {H{\"o}rterer, Hubert and Baumbach, Sebastian Felix and Lemperle, Stefan and Altenberger, Sebastian and Gottschalk, Oliver and Mehlhorn, Alexander Tobias and R{\"o}ser, Anke and Walther, Markus}, title = {Clinical outcome and concomitant injuries in operatively treated fractures of the lateral process of the talus}, series = {BMC Musculoskeletal Disorders}, volume = {20}, journal = {BMC Musculoskeletal Disorders}, doi = {10.1186/s12891-019-2603-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321207}, year = {2019}, abstract = {Background The aim of this study was to review the patient rated outcome (PROM) of surgically treated fractures to the lateral process of the talus (LPTF) and identify factors influencing the outcome. Methods Retrospective study with a current follow-up. Eligible were all patients treated surgically for a LPTF (n = 23) with a minimum follow-up of one year. Demographics, medical history, trauma mechanism, fracture characteristics, concomitant injuries, treatment details, complications, return to work and sports were assessed retrospectively. The current follow-up included the VAS FA, Karlsson Score, and SF-12. The primary outcome was the VAS FA. Secondary aim was the identification of parameters influencing the PROMs. Results 22 patients (96\% follow-up) with a mean age of 32 ± 9 (18 to 49) years were included. 73\% suffered a Hawkins Type 1, 23\% a Type 2, and one patient a Type 3 fracture. 82\% suffered concomitant injuries. 9\% suffered minor surgical side infections, 50\% developed symptomatic subtalar osteoarthritis. At final follow-up (44 ± 2 (12 to 97) months), the mean VAS FA Overall was 77 ± 21 (20 to 100), the Karlsson Score 72 ± 21 (34 to 97), and for the SF 12 the PCS 53 ± 8 (36 to 64) and the MCS 53 ± 7 (32 to 63). 50\% of patients returned to their previous level of sports. Hawkins Type 1 fractures resulted in better VAS FA Overall score than Type 2 fractures. Posttraumatic subtalar osteoarthritis was the independent factor associated to a poor patient rated outcome (VAS FA, Karlsson Score). Conclusion After a follow-up of over 3.5 years, surgically treated LPTF resulted in only moderate results. 50\% suffered posttraumatic symptomatic subtalar osteoarthritis, which was the primary independent parameter for a poor outcome following LPTF. Level of evidence Level III.}, language = {en} } @article{RichterKruppaMunzetal.2019, author = {Richter, Gesa M. and Kruppa, Jochen and Munz, Matthias and Wiehe, Ricarda and H{\"a}sler, Robert and Franke, Andre and Martins, Orlando and Jockel-Schneider, Yvonne and Bruckmann, Corinna and Dommisch, Henrik and Schaefer, Arne S.}, title = {A combined epigenome- and transcriptome-wide association study of the oral masticatory mucosa assigns CYP1B1 a central role for epithelial health in smokers}, series = {Clinical Epigenetics}, volume = {11}, journal = {Clinical Epigenetics}, doi = {10.1186/s13148-019-0697-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226175}, pages = {1-18}, year = {2019}, abstract = {Background The oral mucosa has an important role in maintaining barrier integrity at the gateway to the gastrointestinal and respiratory tracts. Smoking is a strong environmental risk factor for the common oral inflammatory disease periodontitis and oral cancer. Cigarette smoke affects gene methylation and expression in various tissues. This is the first epigenome-wide association study (EWAS) that aimed to identify biologically active methylation marks of the oral masticatory mucosa that are associated with smoking. Results Ex vivo biopsies of 18 current smokers and 21 never smokers were analysed with the Infinium Methylation EPICBeadChip and combined with whole transcriptome RNA sequencing (RNA-Seq; 16 mio reads per sample) of the same samples. We analysed the associations of CpG methylation values with cigarette smoking and smoke pack year (SPY) levels in an analysis of covariance (ANCOVA). Nine CpGs were significantly associated with smoking status, with three CpGs mapping to the genetic region of CYP1B1 (cytochrome P450 family 1 subfamily B member 1;best p=5.5x10(-8)) and two mapping to AHRR (aryl-hydrocarbon receptor repressor; best p=5.9x10(-9)). In the SPY analysis, 61 CpG sites at 52 loci showed significant associations of the quantity of smoking with changes in methylation values. Here, the most significant association located to the gene CYP1B1, with p=4.0x10(-10). RNA-Seq data showed significantly increased expression of CYP1B1 in smokers compared to non-smokers (p=2.2x10(-14)), together with 13 significantly upregulated transcripts. Six transcripts were significantly downregulated. No differential expression was observed for AHRR. In vitro studies with gingival fibroblasts showed that cigarette smoke extract directly upregulated the expression of CYP1B1. Conclusion This study validated the established role of CYP1B1 and AHRR in xenobiotic metabolism of tobacco smoke and highlights the importance of epigenetic regulation for these genes. For the first time, we give evidence of this role for the oral masticatory mucosa.}, subject = {AHRR}, language = {en} } @article{WagnerKunzChowdhuryetal.2019, author = {Wagner, Fabienne and Kunz, Tobias C. and Chowdhury, Suvagata R. and Thiede, Bernd and Fraunholz, Martin and Eger, Debora and Kozjak-Pavlovic, Vera}, title = {Armadillo repeat-containing protein 1 is a dual localization protein associated with mitochondrial intermembrane space bridging complex}, series = {PLoS ONE}, volume = {14}, journal = {PLoS ONE}, number = {10}, doi = {10.1371/journal.pone.0218303}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202670}, pages = {e0218303}, year = {2019}, abstract = {Cristae architecture is important for the function of mitochondria, the organelles that play the central role in many cellular processes. The mitochondrial contact site and cristae organizing system (MICOS) together with the sorting and assembly machinery (SAM) forms the mitochondrial intermembrane space bridging complex (MIB), a large protein complex present in mammalian mitochondria that partakes in the formation and maintenance of cristae. We report here a new subunit of the mammalian MICOS/MIB complex, an armadillo repeat-containing protein 1 (ArmC1). ArmC1 localizes both to cytosol and mitochondria, where it associates with the outer mitochondrial membrane through its carboxy-terminus. ArmC1 interacts with other constituents of the MICOS/MIB complex and its amounts are reduced upon MICOS/MIB complex depletion. Mitochondria lacking ArmC1 do not show defects in cristae structure, respiration or protein content, but appear fragmented and with reduced motility. ArmC1 represents therefore a peripheral MICOS/MIB component that appears to play a role in mitochondrial distribution in the cell.}, language = {en} } @article{BelkaNickelKurth2019, author = {Belka, Janina and Nickel, Joachim and Kurth, Dirk G.}, title = {Growth on metallo-supramolecular coordination polyelectrolyte (MEPE) stimulates osteogenic differentiation of human osteosarcoma cells (MG63) and human bone marrow derived mesenchymal stem cells}, series = {Polymers}, volume = {11}, journal = {Polymers}, number = {7}, issn = {2073-4360}, doi = {10.3390/polym11071090}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197264}, pages = {1090}, year = {2019}, abstract = {Background: Culturing of cells is typically performed on standard tissue culture plates generating growth conditions, which in general do not reflect the native three-dimensional cellular environment. Recent investigations provide insights in parameters, which strongly affect the general cellular behavior triggering essential processes such as cell differentiation. The physical properties of the used material, such as stiffness, roughness, or topology, as well as the chemical composition of the cell-surface interface are shown to play a key role in the initiation of particular cellular responses. Methods: We extended our previous research, which identified thin films of metallo-supramolecular coordination polyelectrolytes (MEPEs) as substrate to trigger the differentiation of muscular precursor cells. Results: Here, we show that the same MEPEs similarly stimulate the osteogenic differentiation of pre-osteoblasts. Remarkably, MEPE modified surfaces also trigger the differentiation of primary bone derived mesenchymal stem cells (BMSCs) towards the osteogenic lineage. Conclusion: This result leads to the conclusion that these surfaces individually support the specification of cell differentiation toward lineages that correspond to the natural commitment of the particular cell types. We, therefore, propose that Fe-MEPEs may be used as scaffold for the treatment of defects at least in muscular or bone tissue.}, language = {en} } @article{ReuschHolzmeierGerlachetal.2019, author = {Reusch, Engelbert and Holzmeier, Fabian and Gerlach, Marius and Fischer, Ingo and Hemberger, Patrick}, title = {Decomposition of Picolyl Radicals at High Temperature: A Mass Selective Threshold Photoelectron Spectroscopy Study}, series = {Chemistry - A European Journal}, volume = {25}, journal = {Chemistry - A European Journal}, number = {72}, doi = {10.1002/chem.201903937}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208132}, pages = {16652-16659}, year = {2019}, abstract = {The reaction products of the picolyl radicals at high temperature were characterized by mass-selective threshold photoelectron spectroscopy in the gas phase. Aminomethylpyridines were pyrolyzed to initially produce picolyl radicals (m /z =92). At higher temperatures further thermal reaction products are generated in the pyrolysis reactor. All compounds were identified by mass-selected threshold photoelectron spectroscopy and several hitherto unexplored reactive molecules were characterized. The mechanism for several dissociation pathways was outlined in computations. The spectrum of m /z =91, resulting from hydrogen loss of picolyl, shows four isomers, two ethynyl pyrroles with adiabatic ionization energies (IE\(_{ad}\)) of 7.99 eV (2-ethynyl-1H -pyrrole) and 8.12 eV (3-ethynyl-1H -pyrrole), and two cyclopentadiene carbonitriles with IE′s of 9.14 eV (cyclopenta-1,3-diene-1-carbonitrile) and 9.25 eV (cyclopenta-1,4-diene-1-carbonitrile). A second consecutive hydrogen loss forms the cyanocyclopentadienyl radical with IE′s of 9.07 eV (T\(_0\)) and 9.21 eV (S\(_1\)). This compound dissociates further to acetylene and the cyanopropynyl radical (IE=9.35 eV). Furthermore, the cyclopentadienyl radical, penta-1,3-diyne, cyclopentadiene and propargyl were identified in the spectra. Computations indicate that dissociation of picolyl proceeds initially via a resonance-stabilized seven-membered ring.}, language = {en} } @article{RuizDiefenbacherNelsonetal.2019, author = {Ruiz, E. Josue and Diefenbacher, Markus E. and Nelson, Jessica K. and Sancho, Rocio and Pucci, Fabio and Chakraborty, Atanu and Moreno, Paula and Annibaldi, Alessandro and Liccardi, Gianmaria and Encheva, Vesela and Mitter, Richard and Rosenfeldt, Mathias and Snijders, Ambrosius P. and Meier, Pascal and Calzado, Marco A. and Behrens, Axel}, title = {LUBAC determines chemotherapy resistance in squamous cell lung cancer}, series = {Journal of Experimental Medicine}, volume = {216}, journal = {Journal of Experimental Medicine}, number = {2}, doi = {10.1084/jem.20180742}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227146}, pages = {450-465}, year = {2019}, abstract = {Lung squamous cell carcinoma (LSCC) and adenocarcinoma (LADC) are the most common lung cancer subtypes. Molecular targeted treatments have improved LADC patient survival but are largely ineffective in LSCC. The tumor suppressor FBW7 is commonly mutated or down-regulated in human LSCC, and oncogenic KRasG12D activation combined with Fbxw7 inactivation in mice (KF model) caused both LSCC and LADC. Lineage-tracing experiments showed that CC10(+), but not basal, cells are the cells of origin of LSCC in KF mice. KF LSCC tumors recapitulated human LSCC resistance to cisplatin-based chemotherapy, and we identified LUBAC-mediated NF-kappa B signaling as a determinant of chemotherapy resistance in human and mouse. Inhibition of NF-kappa B activation using TAK1 or LUBAC inhibitors resensitized LSCC tumors to cisplatin, suggesting a future avenue for LSCC patient treatment.}, language = {en} }