@article{ThormannAhrensArmijosetal.2016, author = {Thormann, Birthe and Ahrens, Dirk and Armijos, Diego Mar{\´i}n and Peters, Marcell K. and Wagner, Thomas and W{\"a}gele, Johann W.}, title = {Exploring the Leaf Beetle Fauna (Coleoptera: Chrysomelidae) of an Ecuadorian Mountain Forest Using DNA Barcoding}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {2}, doi = {10.1371/journal.pone.0148268}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167253}, pages = {e0148268}, year = {2016}, abstract = {Background Tropical mountain forests are hotspots of biodiversity hosting a huge but little known diversity of insects that is endangered by habitat destruction and climate change. Therefore, rapid assessment approaches of insect diversity are urgently needed to complement slower traditional taxonomic approaches. We empirically compare different DNA-based species delimitation approaches for a rapid biodiversity assessment of hyperdiverse leaf beetle assemblages along an elevational gradient in southern Ecuador and explore their effect on species richness estimates. Methodology/Principal Findings Based on a COI barcode data set of 674 leaf beetle specimens (Coleoptera: Chrysomelidae) of 266 morphospecies from three sample sites in the Podocarpus National Park, we employed statistical parsimony analysis, distance-based clustering, GMYC- and PTP-modelling to delimit species-like units and compared them to morphology-based (parataxonomic) species identifications. The four different approaches for DNA-based species delimitation revealed highly similar numbers of molecular operational taxonomic units (MOTUs) (n = 284-289). Estimated total species richness was considerably higher than the sampled amount, 414 for morphospecies (Chao2) and 469-481 for the different MOTU types. Assemblages at different elevational levels (1000 vs. 2000 m) had similar species numbers but a very distinct species composition for all delimitation methods. Most species were found only at one elevation while this turnover pattern was even more pronounced for DNA-based delimitation. Conclusions/Significance Given the high congruence of DNA-based delimitation results, probably due to the sampling structure, our study suggests that when applied to species communities on a regionally limited level with high amount of rare species (i.e. ~50\% singletons), the choice of species delimitation method can be of minor relevance for assessing species numbers and turnover in tropical insect communities. Therefore, DNA-based species delimitation is confirmed as a valuable tool for evaluating biodiversity of hyperdiverse insect communities, especially when exact taxonomic identifications are missing.}, language = {en} } @article{LehnersTabatabaiPrifertetal.2016, author = {Lehners, Nicola and Tabatabai, Julia and Prifert, Christiane and Wedde, Marianne and Puthenparambil, Joe and Weissbrich, Benedikt and Biere, Barbara and Schweiger, Brunhilde and Egerer, Gerlinde and Schnitzler, Paul}, title = {Long-Term Shedding of Influenza Virus, Parainfluenza Virus, Respiratory Syncytial Virus and Nosocomial Epidemiology in Patients with Hematological Disorders}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {2}, doi = {10.1371/journal.pone.0148258}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167243}, pages = {e0148258}, year = {2016}, abstract = {Respiratory viruses are a cause of upper respiratory tract infections (URTI), but can be associated with severe lower respiratory tract infections (LRTI) in immunocompromised patients. The objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (RSV) and the duration of viral shedding in hematological patients. Nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and RSV on admission as well as on development of respiratory symptoms. Consecutive swabs were collected until viral clearance. Out of 672 tested patients, a total of 111 patients (17\%) were infected with one of the investigated viral agents: 40 with influenza, 13 with parainfluenza and 64 with RSV; six patients had influenza/RSV or parainfluenza/RSV co-infections. The majority of infected patients (n = 75/111) underwent stem cell transplantation (42 autologous, 48 allogeneic, 15 autologous and allogeneic). LRTI was observed in 48 patients, of whom 15 patients developed severe LRTI, and 13 patients with respiratory tract infection died. Phylogenetic analysis revealed a variety of influenza A(H1N1)pdm09, A(H3N2), influenza B, parainfluenza 3 and RSV A, B viruses. RSV A was detected in 54 patients, RSV B in ten patients. The newly emerging RSV A genotype ON1 predominated in the study cohort and was found in 48 (75\%) of 64 RSV-infected patients. Furthermore, two distinct clusters were detected for RSV A genotype ON1, identical RSV G gene sequences in these patients are consistent with nosocomial transmission. Long-term viral shedding for more than 30 days was significantly associated with prior allogeneic transplantation (p = 0.01) and was most pronounced in patients with RSV infection (n = 16) with a median duration of viral shedding for 80 days (range 35-334 days). Long-term shedding of respiratory viruses might be a catalyzer of nosocomial transmission and must be considered for efficient infection control in immunocompromised patients.}, language = {en} } @article{AcqualagnaBotrelVidaurreetal.2016, author = {Acqualagna, Laura and Botrel, Loic and Vidaurre, Carmen and K{\"u}bler, Andrea and Blankertz, Benjamin}, title = {Large-Scale Assessment of a Fully Automatic Co-Adaptive Motor Imagery-Based Brain Computer Interface}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {2}, doi = {10.1371/journal.pone.0148886}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167230}, pages = {e0148886}, year = {2016}, abstract = {In the last years Brain Computer Interface (BCI) technology has benefited from the development of sophisticated machine leaning methods that let the user operate the BCI after a few trials of calibration. One remarkable example is the recent development of co-adaptive techniques that proved to extend the use of BCIs also to people not able to achieve successful control with the standard BCI procedure. Especially for BCIs based on the modulation of the Sensorimotor Rhythm (SMR) these improvements are essential, since a not negligible percentage of users is unable to operate SMR-BCIs efficiently. In this study we evaluated for the first time a fully automatic co-adaptive BCI system on a large scale. A pool of 168 participants naive to BCIs operated the co-adaptive SMR-BCI in one single session. Different psychological interventions were performed prior the BCI session in order to investigate how motor coordination training and relaxation could influence BCI performance. A neurophysiological indicator based on the Power Spectral Density (PSD) was extracted by the recording of few minutes of resting state brain activity and tested as predictor of BCI performances. Results show that high accuracies in operating the BCI could be reached by the majority of the participants before the end of the session. BCI performances could be significantly predicted by the neurophysiological indicator, consolidating the validity of the model previously developed. Anyway, we still found about 22\% of users with performance significantly lower than the threshold of efficient BCI control at the end of the session. Being the inter-subject variability still the major problem of BCI technology, we pointed out crucial issues for those who did not achieve sufficient control. Finally, we propose valid developments to move a step forward to the applicability of the promising co-adaptive methods.}, language = {en} } @article{Hoelldobler2016, author = {H{\"o}lldobler, Bert}, title = {Queen Specific Exocrine Glands in Legionary Ants and Their Possible Function in Sexual Selection}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {3}, doi = {10.1371/journal.pone.0151604}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167057}, pages = {e0151604}, year = {2016}, abstract = {The colonies of army ants and some other legionary ant species have single, permanently wingless queens with massive post petioles and large gasters. Such highly modified queens are called dichthadiigynes. This paper presents the unusually rich exocrine gland endowment of dichthadiigynes, which is not found in queens of other ant species. It has been suggested these kinds of glands produce secretions that attract and maintain worker retinues around queens, especially during migration. However, large worker retinues also occur in non-legionary species whose queens do not have such an exuberance of exocrine glands. We argue and present evidence in support of our previously proposed hypothesis that the enormous outfit of exocrine glands found in dichthadiigynes is due to sexual selection mediated by workers as the main selecting agents}, language = {en} } @article{WeidnerRousseauPlauthetal.2016, author = {Weidner, Christopher and Rousseau, Morten and Plauth, Annabell and Wowro, Sylvia J. and Fischer, Cornelius and Abdel-Aziz, Heba and Sauer, Sascha}, title = {Iberis amara Extract Induces Intracellular Formation of Reactive Oxygen Species and Inhibits Colon Cancer}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0152398}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167044}, pages = {e0152398}, year = {2016}, abstract = {Massively increasing global incidences of colorectal cancer require efficient treatment and prevention strategies. Here, we report unexpected anticancerogenic effects of hydroethanolic Iberis amara extract (IAE), which is known as a widely used phytomedical product for treating gastrointestinal complaints. IAE significantly inhibited the proliferation of HT-29 and T84 colon carcinoma cells with an inhibitory concentration (IC\(_{50}\)) of 6 and 9 μg/ml, respectively, and further generated inhibitory effects in PC-3 prostate and MCF7 breast cancer cells. Inhibition of proliferation in HT-29 cells was associated with a G2/M phase cell cycle arrest including reduced expression of various regulatory marker proteins. Notably, in HT-29 cells IAE further induced apoptosis by intracellular formation of reactive oxygen species (ROS). Consistent with predictions derived from our in vitro experiments, bidaily oral gavage of 50 mg/kg of IAE over 4 weeks resulted in significant inhibition of tumor growth in a mouse HT-29 tumor xenograft model. Taken together, Iberis amara extracts could become useful alternatives for preventing and treating the progression of colon cancer.}, language = {en} } @article{KlementChampOttoetal.2016, author = {Klement, Rainer J. and Champ, Colin E. and Otto, Christoph and K{\"a}mmerer, Ulrike}, title = {Anti-Tumor Effects of Ketogenic Diets in Mice: A Meta-Analysis}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0155050}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167036}, pages = {e0155050}, year = {2016}, abstract = {Background Currently ketogenic diets (KDs) are hyped as an anti-tumor intervention aimed at exploiting the metabolic abnormalities of cancer cells. However, while data in humans is sparse, translation of murine tumor models to the clinic is further hampered by small sample sizes, heterogeneous settings and mixed results concerning tumor growth retardation. The aim was therefore to synthesize the evidence for a growth inhibiting effect of KDs when used as a monotherapy in mice. Methods We conducted a Bayesian random effects meta-analysis on all studies assessing the survival (defined as the time to reach a pre-defined endpoint such as tumor volume) of mice on an unrestricted KD compared to a high carbohydrate standard diet (SD). For 12 studies meeting the inclusion criteria either a mean survival time ratio (MR) or hazard ratio (HR) between the KD and SD groups could be obtained. The posterior estimates for the MR and HR averaged over four priors on the between-study heterogeneity τ\(^{2}\) were MR = 0.85 (95\% highest posterior density interval (HPDI) = [0.73, 0.97]) and HR = 0.55 (95\% HPDI = [0.26, 0.87]), indicating a significant overall benefit of the KD in terms of prolonged mean survival times and reduced hazard rate. All studies that used a brain tumor model also chose a late starting point for the KD (at least one day after tumor initiation) which accounted for 26\% of the heterogeneity. In this subgroup the KD was less effective (MR = 0.89, 95\% HPDI = [0.76, 1.04]). Conclusions There was an overall tumor growth delaying effect of unrestricted KDs in mice. Future experiments should aim at differentiating the effects of KD timing versus tumor location, since external evidence is currently consistent with an influence of both of these factors.}, language = {en} } @article{VogtmannHuaZelleretal.2016, author = {Vogtmann, Emily and Hua, Xing and Zeller, Georg and Sunagawa, Shinichi and Voigt, Anita Y. and Hercog, Rajna and Goedert, James J. and Shi, Jianxin and Bork, Peer and Sinha, Rashmi}, title = {Colorectal Cancer and the Human Gut Microbiome: Reproducibility with Whole-Genome Shotgun Sequencing}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0155362}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166904}, pages = {e0155362}, year = {2016}, abstract = {Accumulating evidence indicates that the gut microbiota affects colorectal cancer development, but previous studies have varied in population, technical methods, and associations with cancer. Understanding these variations is needed for comparisons and for potential pooling across studies. Therefore, we performed whole-genome shotgun sequencing on fecal samples from 52 pre-treatment colorectal cancer cases and 52 matched controls from Washington, DC. We compared findings from a previously published 16S rRNA study to the metagenomics-derived taxonomy within the same population. In addition, metagenome-predicted genes, modules, and pathways in the Washington, DC cases and controls were compared to cases and controls recruited in France whose specimens were processed using the same platform. Associations between the presence of fecal Fusobacteria, Fusobacterium, and Porphyromonas with colorectal cancer detected by 16S rRNA were reproduced by metagenomics, whereas higher relative abundance of Clostridia in cancer cases based on 16S rRNA was merely borderline based on metagenomics. This demonstrated that within the same sample set, most, but not all taxonomic associations were seen with both methods. Considering significant cancer associations with the relative abundance of genes, modules, and pathways in a recently published French metagenomics dataset, statistically significant associations in the Washington, DC population were detected for four out of 10 genes, three out of nine modules, and seven out of 17 pathways. In total, colorectal cancer status in the Washington, DC study was associated with 39\% of the metagenome-predicted genes, modules, and pathways identified in the French study. More within and between population comparisons are needed to identify sources of variation and disease associations that can be reproduced despite these variations. Future studies should have larger sample sizes or pool data across studies to have sufficient power to detect associations that are reproducible and significant after correction for multiple testing.}, language = {en} } @article{StockPetrašMelteretal.2016, author = {Stock, Nina Katharina and Petr{\´a}š, Petr and Melter, Oto and Kapounov{\´a}, Gabriela and Vopalkov{\´a}, Petra and Kubele, Jan and Vaniš, V{\´a}clav and Tkadlec, Jan and Buk{\´a}čkov{\´a}, Eva and Machov{\´a}, Ivana and Jindr{\´a}k, Vlastimil}, title = {Importance of Multifaceted Approaches in Infection Control: A Practical Experience from an Outbreak Investigation}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0157981}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166891}, pages = {e0157981}, year = {2016}, abstract = {Background This study presents the results of a multidisciplinary, nosocomial MRSA outbreak investigation in an 8-bed medical intensive care unit (ICU). The identification of seven MRSA positive patients in the beginning of 2014 led to the closure of the ward for several weeks. A multidisciplinary, retrospective investigation was initiated in order to identify the reason and the source for the outbreak, describe MRSA transmission in the department and identify limitations in infection control. Methods The investigation comprised an epidemiological description of MRSA cases from 2012 to 2014 and a characterization of MRSA isolates, including phage-, spa- and PFGE-typing. Additionally, MRSA screening was performed from the hospital staff and the environment. To identify the reason for the outbreak, work-related, psychological and behavioral factors were investigated by impartial audits and staff interviews. Results Thirty-one MRSA cases were registered during the study period, and 36 isolates were investigated. Molecular typing determined the outbreak strain (phage type 54/812, PFGE type A4, spa type t003) and identified the probable index case. Nasal carriage in one employee and a high environmental contamination with the outbreak strain was documented. Important gaps in nursing procedures and general management were identified. Elevated stress levels and communication problems preceded the outbreak. Compliance with hand hygiene and isolation procedures was evaluated as appropriate. Conclusion This study demonstrates the complexity of controlling hospital-associated infections. The combined use of different typing methods is beneficial for outbreak investigations. Psychological, behavioral and other work-related factors have an important impact on the spread of nosocomial pathogens. These factors should be addressed and integrated in routine infection control practice.}, language = {en} } @article{KuntzenKuhnKuntzenetal.2016, author = {Kuntzen, Thomas and Kuhn, Sereina and Kuntzen, Daniela and Seifert, Burkhardt and M{\"u}llhaupt, Beat and Geier, Andreas}, title = {Influence of Ribavirin Serum Levels on Outcome of Antiviral Treatment and Anemia in Hepatitis C Virus Infection}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {7}, doi = {10.1371/journal.pone.0158512}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166888}, pages = {e0158512}, year = {2016}, abstract = {Background Ribavirin blood levels vary considerably between patients with standard weight-based dosing. Their impact on sustained virological response (SVR) with pegylated interferon and ribavirin is controversial, but has mostly been studied before the IL28b gene polymorphism as a possible confounder was discovered. Methods The impact of serum ribavirin trough levels at week 4, at the end of treatment and of mean levels across the entire antiviral treatment with pegylated interferon and ribavirin on relapse, SVR rates and anemia was retrospectively studied by univariate and multivariable logistic regression analyses in 214 patients with HCV genotype 1-4 infection, including 88 patients with available IL28b genotyping. Results Mean ribavirin levels varied between 0.68-5.65 mg/l and significantly differed between patients with or without SVR. By multivariable regression including age, sex, HCV viral load, HCV genotype, liver fibrosis stage, prior treatments, immunosuppression and IL28b genotype, ribavirin levels consistently displayed significant influence on SVR and relapse without indication for a specific importance of higher concentrations early or late in the treatment course. Although hemoglobin decline was on average more pronounced in patients with higher ribavirin levels, hemoglobin remained relatively stable in a significant proportion of these, indicating that ribavirin levels alone are insufficient to predict anemia. Conclusion While data are scarce to draw conclusions applicable for modern DAA therapies, these results support ribavirin treatment based on serum levels instead of purely weight-based dosing in combination with pegylated interferon.}, language = {en} } @article{VigoritoKuchenbaeckerBeesleyetal.2016, author = {Vigorito, Elena and Kuchenbaecker, Karoline B. and Beesley, Jonathan and Adlard, Julian and Agnarsson, Bjarni A. and Andrulis, Irene L. and Arun, Banu K. and Barjhoux, Laure and Belotti, Muriel and Benitez, Javier and Berger, Andreas and Bojesen, Anders and Bonanni, Bernardo and Brewer, Carole and Caldes, Trinidad and Caligo, Maria A. and Campbell, Ian and Chan, Salina B. and Claes, Kathleen B. M. and Cohn, David E. and Cook, Jackie and Daly, Mary B. and Damiola, Francesca and Davidson, Rosemarie and de Pauw, Antoine and Delnatte, Capucine and Diez, Orland and Domchek, Susan M. and Dumont, Martine and Durda, Katarzyna and Dworniczak, Bernd and Easton, Douglas F. and Eccles, Diana and Ardnor, Christina Edwinsdotter and Eeles, Ros and Ejlertsen, Bent and Ellis, Steve and Evans, D. Gareth and Feliubadalo, Lidia and Fostira, Florentia and Foulkes, William D. and Friedman, Eitan and Frost, Debra and Gaddam, Pragna and Ganz, Patricia A. and Garber, Judy and Garcia-Barberan, Vanesa and Gauthier-Villars, Marion and Gehrig, Andrea and Gerdes, Anne-Marie and Giraud, Sophie and Godwin, Andrew K. and Goldgar, David E. and Hake, Christopher R. and Hansen, Thomas V. O. and Healey, Sue and Hodgson, Shirley and Hogervorst, Frans B. L. and Houdayer, Claude and Hulick, Peter J. and Imyanitov, Evgeny N. and Isaacs, Claudine and Izatt, Louise and Izquierdo, Angel and Jacobs, Lauren and Jakubowska, Anna and Janavicius, Ramunas and Jaworska-Bieniek, Katarzyna and Jensen, Uffe Birk and John, Esther M. and Vijai, Joseph and Karlan, Beth Y. and Kast, Karin and Khan, Sofia and Kwong, Ava and Laitman, Yael and Lester, Jenny and Lesueur, Fabienne and Liljegren, Annelie and Lubinski, Jan and Mai, Phuong L. and Manoukian, Siranoush and Mazoyer, Sylvie and Meindl, Alfons and Mensenkamp, Arjen R. and Montagna, Marco and Nathanson, Katherine L. and Neuhausen, Susan L. and Nevanlinna, Heli and Niederacher, Dieter and Olah, Edith and Olopade, Olufunmilayo I. and Ong, Kai-ren and Osorio, Ana and Park, Sue Kyung and Paulsson-Karlsson, Ylva and Pedersen, Inge Sokilde and Peissel, Bernard and Peterlongo, Paolo and Pfeiler, Georg and Phelan, Catherine M. and Piedmonte, Marion and Poppe, Bruce and Pujana, Miquel Angel and Radice, Paolo and Rennert, Gad and Rodriguez, Gustavo C. and Rookus, Matti A. and Ross, Eric A. and Schmutzler, Rita Katharina and Simard, Jacques and Singer, Christian F. and Slavin, Thomas P. and Soucy, Penny and Southey, Melissa and Steinemann, Doris and Stoppa-Lyonnet, Dominique and Sukiennicki, Grzegorz and Sutter, Christian and Szabo, Csilla I. and Tea, Muy-Kheng and Teixeira, Manuel R. and Teo, Soo-Hwang and Terry, Mary Beth and Thomassen, Mads and Tibiletti, Maria Grazia and Tihomirova, Laima and Tognazzo, Silvia and van Rensburg, Elizabeth J. and Varesco, Liliana and Varon-Mateeva, Raymonda and Vratimos, Athanassios and Weitzel, Jeffrey N. and McGuffog, Lesley and Kirk, Judy and Toland, Amanda Ewart and Hamann, Ute and Lindor, Noralane and Ramus, Susan J. and Greene, Mark H. and Couch, Fergus J. and Offit, Kenneth and Pharoah, Paul D. P. and Chenevix-Trench, Georgia and Antoniou, Antonis C.}, title = {Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {7}, doi = {10.1371/journal.pone.0158801}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166869}, pages = {e0158801}, year = {2016}, abstract = {Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95\%CI: 0.68 to 0.79, p-value 2× 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95\%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.}, language = {en} } @article{HarksJockelSchneiderSchlagenhaufetal.2016, author = {Harks, Inga and Jockel-Schneider, Yvonne and Schlagenhauf, Ulrich and May, Theodor W. and Gravemeier, Martina and Prior, Karola and Petersilka, Gregor and Ehmke, Gregor}, title = {Impact of the Daily Use of a Microcrystal Hydroxyapatite Dentifrice on De Novo Plaque Formation and Clinical/Microbiological Parameters of Periodontal Health. A Randomized Trial}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {7}, doi = {10.1371/journal.pone.0160142}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166853}, pages = {e0160142}, year = {2016}, abstract = {Aim This 12-week prospective, randomized, double-blind, two-center trial evaluated the impact of a microcrystalline zinc hydroxyapatite (mHA) dentifrice on plaque formation rate (PFR) in chronic periodontitis patients. We hypothesized that mHA precipitates cause delayed plaque development when compared to a fluoridated control (AmF/SnF\(_{2}\)), and therefore would improve periodontal health. Material \& Methods At baseline and after 4 and 12 weeks, PFR and other clinical and microbiological parameters were recorded. Seventy periodontitis patients received a mHA or AmF/SnF\(_{2}\) dentifrice as daily oral care without hygiene instructions. Four weeks after baseline, participants received full mouth debridement and continued using the dentifrices for another 8 weeks. Results Primary outcome PFR did not change statistically significantly from baseline to weeks 4 and 12, neither in mHA (n = 33; 51.7±17.2\% vs. 48.5±16.65\% vs. 48.4±19.9\%) nor in AmF/SnF2-group (n = 34; 52.3±17.5\% vs. 52.5±21.3\% vs. 46.1±21.8\%). Secondary clinical parameters such as plaque control record, gingival index, bleeding on probing, and pocket probing depth improved, but between-group differences were not statistically significant. Microbiological analyses showed similar slight decreases in colony-forming units in both groups. Conclusion In patients with mild-to-moderate periodontitis, periodontal therapy and use of a mHA-or AmF/SnF\(_{2}\) dentifrice without instructions induced comparable improvements in periodontal health but did not significantly reduce the PFR.}, language = {en} } @article{HellenbrandClausSchinketal.2016, author = {Hellenbrand, Wiebke and Claus, Heike and Schink, Susanne and Marcus, Ulrich and Wichmann, Ole and Vogel, Ulrich}, title = {Risk of Invasive Meningococcal Disease in Men Who Have Sex with Men: Lessons Learned from an Outbreak in Germany, 2012-2013}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {8}, doi = {10.1371/journal.pone.0160126}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166842}, pages = {e0160126}, year = {2016}, abstract = {Background We undertook investigations in response to an invasive meningococcal disease (IMD) outbreak in men who have sex with men (MSM) in Berlin 2012-2013 to better understand meningococcal transmission and IMD risk in MSM. Methods We retrospectively searched for further IMD cases in MSM in Germany through local health departments and undertook exploratory interviews. We performed antigen sequence typing, characterized fHbp and aniA genes of strains with the outbreak finetype and reviewed epidemiologically or spatiotemporally linked cases from 2002-2014. Results Among the 148 IMD-cases notified from 01.01.2012-30.09.2013 in 18-59 year-old men we identified 13 MSM in 6 federal states: 11 serogroup C (MenC, all finetype C:P1.5-1,10-8:F3-6), 2 MenB. Interviews with 7 MSM revealed frequent meeting of multiple partners online or via mobile apps and illicit drug use as potential risk factors. MenC incidence was 13-fold higher in MSM than non-MSM. MenC isolates from 9/11 MSM had a novel fHbp allele 766. All C:P1.5-1,10-8:F3-6 strains from MSM versus 16/23 from non-MSM had intact aniA genes (p = 0.04). Although definitive evidence for transmission among MSM in epidemiological or spatiotemporal clusters in 2002-2014 was lacking, clusters were more frequent in men aged 20-49 years. Molecular analysis of C:P1.5-1,10-8:F3-6 strains revealed cases with intact aniA since 2007, mainly associated with fHbp361, fHbp766 and fHbp813, all involving one or more MSM. Conclusions MenC incidence was elevated in MSM during the study period. Multiple casual sexual contacts and illicit drug use were common in affected MSM. In all strains from MSM we detected an intact aniA gene coding for a nitrite reductase, which permits survival in microanaerobic environments and could play a role in meningococcal transmission in MSM through urogenital colonization. Furthermore, meningococcal transmission among MSM may be sustained over large areas and thus require modified spatiotemporal scanning algorithms for timely detection and control.}, language = {en} } @article{MaaroufNeudorferElMajdoubetal.2016, author = {Maarouf, Mohammad and Neudorfer, Clemens and El Majdoub, Faycal and Lenartz, Doris and Kuhn, Jens and Sturm, Volker}, title = {Deep Brain Stimulation of Medial Dorsal and Ventral Anterior Nucleus of the Thalamus in OCD: A Retrospective Case Series}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {8}, doi = {10.1371/journal.pone.0160750}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166830}, pages = {e0160750}, year = {2016}, abstract = {Background The current notion that cortico-striato-thalamo-cortical circuits are involved in the pathophysiology of obsessive-compulsive disorder (OCD) has instigated the search for the most suitable target for deep brain stimulation (DBS). However, despite extensive research, uncertainty about the ideal target remains with many structures being underexplored. The aim of this report is to address a new target for DBS, the medial dorsal (MD) and the ventral anterior (VA) nucleus of the thalamus, which has thus far received little attention in the treatment of OCD. Methods In this retrospective trial, four patients (three female, one male) aged 31-48 years, suffering from therapy-refractory OCD underwent high-frequency DBS of the MD and VA. In two patients (de novo group) the thalamus was chosen as a primary target for DBS, whereas in two patients (rescue DBS group) lead implantation was performed in a rescue DBS attempt following unsuccessful primary stimulation. Results Continuous thalamic stimulation yielded no significant improvement in OCD symptom severity. Over the course of thalamic DBS symptoms improved in only one patient who showed "partial response" on the Yale-Brown Obsessive Compulsive (Y-BOCS) Scale. Beck Depression Inventory scores dropped by around 46\% in the de novo group; anxiety symptoms improved by up to 34\%. In the de novo DBS group no effect of DBS on anxiety and mood was observable. Conclusion MD/VA-DBS yielded no adequate alleviation of therapy-refractory OCD, the overall strategy in targeting MD/VA as described in this paper can thus not be recommended in DBS for OCD. The magnocellular portion of MD (MDMC), however, might prove a promising target in the treatment of mood related and anxiety disorders.}, language = {en} } @article{HeurichZeisKuechenhoffetal.2016, author = {Heurich, Marco and Zeis, Klara and K{\"u}chenhoff, Helmut and M{\"u}ller, J{\"o}rg and Belotti, Elisa and Bufka, Luděk and Woelfing, Benno}, title = {Selective Predation of a Stalking Predator on Ungulate Prey}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {8}, doi = {10.1371/journal.pone.0158449}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166827}, pages = {e0158449}, year = {2016}, abstract = {Prey selection is a key factor shaping animal populations and evolutionary dynamics. An optimal forager should target prey that offers the highest benefits in terms of energy content at the lowest costs. Predators are therefore expected to select for prey of optimal size. Stalking predators do not pursue their prey long, which may lead to a more random choice of prey individuals. Due to difficulties in assessing the composition of available prey populations, data on prey selection of stalking carnivores are still scarce. We show how the stalking predator Eurasian lynx (Lynx lynx) selects prey individuals based on species identity, age, sex and individual behaviour. To address the difficulties in assessing prey population structure, we confirm inferred selection patterns by using two independent data sets: (1) data of 387 documented kills of radio-collared lynx were compared to the prey population structure retrieved from systematic camera trapping using Manly's standardized selection ratio alpha and (2) data on 120 radio-collared roe deer were analysed using a Cox proportional hazards model. Among the larger red deer prey, lynx selected against adult males—the largest and potentially most dangerous prey individuals. In roe deer lynx preyed selectively on males and did not select for a specific age class. Activity during high risk periods reduced the risk of falling victim to a lynx attack. Our results suggest that the stalking predator lynx actively selects for size, while prey behaviour induces selection by encounter and stalking success rates.}, language = {en} } @article{SchererBauerSchmausetal.2016, author = {Scherer, Sandra D. and Bauer, Jochen and Schmaus, Anja and Neumaier, Christian and Herskind, Carsten and Veldwijk, Marlon R. and Wenz, Frederik and Sleeman, Jonathan P.}, title = {TGF-β1 Is Present at High Levels in Wound Fluid from Breast Cancer Patients Immediately Post-Surgery, and Is Not Increased by Intraoperative Radiation Therapy (IORT)}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {9}, doi = {10.1371/journal.pone.0162221}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166811}, pages = {e0162221}, year = {2016}, abstract = {In patients with low-risk breast cancer, intraoperative radiotherapy (IORT) during breast-conserving surgery is a novel and convenient treatment option for delivering a single high dose of irradiation directly to the tumour bed. However, edema and fibrosis can develop after surgery and radiotherapy, which can subsequently impair quality of life. TGF-β is a strong inducer of the extracellular matrix component hyaluronan (HA). TGF-β expression and HA metabolism can be modulated by irradiation experimentally, and are involved in edema and fibrosis. We therefore hypothesized that IORT may regulate these factors.Wound fluid (WF) draining from breast lumpectomy sites was collected and levels of TGF-β1 and HA were determined by ELISA. Proliferation and marker expression was analyzed in primary lymphatic endothelial cells (LECs) treated with recombinant TGF-β or WF. Our results show that IORT does not change TGF-β1 or HA levels in wound fluid draining from breast lumpectomy sites, and does not lead to accumulation of sHA oligosaccharides. Nevertheless, concentrations of TGF-β1 were high in WF from patients regardless of IORT, at concentrations well above those associated with fibrosis and the suppression of LEC identity. Consistently, we found that TGF-β in WF is active and inhibits LEC proliferation. Furthermore, all three TGF-β isoforms inhibited LEC proliferation and suppressed LEC marker expression at pathophysiologically relevant concentrations. Given that TGF-β contributes to edema and plays a role in the regulation of LEC identity, we suggest that inhibition of TGF-β directly after surgery might prevent the development of side effects such as edema and fibrosis.}, language = {en} } @article{RueckerKeilFitzgeraldetal.2016, author = {R{\"u}cker, Viktoria and Keil, Ulrich and Fitzgerald, Anthony P and Malzahn, Uwe and Prugger, Christof and Ertl, Georg and Heuschmann, Peter U and Neuhauser, Hannelore}, title = {Predicting 10-Year Risk of Fatal Cardiovascular Disease in Germany: An Update Based on the SCORE-Deutschland Risk Charts}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {9}, doi = {10.1371/journal.pone.0162188}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166804}, pages = {e0162188}, year = {2016}, abstract = {Estimation of absolute risk of cardiovascular disease (CVD), preferably with population-specific risk charts, has become a cornerstone of CVD primary prevention. Regular recalibration of risk charts may be necessary due to decreasing CVD rates and CVD risk factor levels. The SCORE risk charts for fatal CVD risk assessment were first calibrated for Germany with 1998 risk factor level data and 1999 mortality statistics. We present an update of these risk charts based on the SCORE methodology including estimates of relative risks from SCORE, risk factor levels from the German Health Interview and Examination Survey for Adults 2008-11 (DEGS1) and official mortality statistics from 2012. Competing risks methods were applied and estimates were independently validated. Updated risk charts were calculated based on cholesterol, smoking, systolic blood pressure risk factor levels, sex and 5-year age-groups. The absolute 10-year risk estimates of fatal CVD were lower according to the updated risk charts compared to the first calibration for Germany. In a nationwide sample of 3062 adults aged 40-65 years free of major CVD from DEGS1, the mean 10-year risk of fatal CVD estimated by the updated charts was lower by 29\% and the estimated proportion of high risk people (10-year risk > = 5\%) by 50\% compared to the older risk charts. This recalibration shows a need for regular updates of risk charts according to changes in mortality and risk factor levels in order to sustain the identification of people with a high CVD risk.}, language = {en} } @article{LoCascioGoetzeLatshangetal.2016, author = {Lo Cascio, Christian M. and Goetze, Oliver and Latshang, Tsogyal D. and Bluemel, Sena and Frauenfelder, Thomas and Bloch, Konrad E.}, title = {Gastrointestinal Dysfunction in Patients with Duchenne Muscular Dystrophy}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {10}, doi = {10.1371/journal.pone.0163779}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166793}, pages = {e0163779}, year = {2016}, abstract = {Background In adult patients with Duchenne muscular dystrophy (DMD) life-threatening constipation has been reported. Since gastrointestinal function in DMD has not been rigorously studied we investigated objective and subjective manifestations of gastrointestinal disturbances in DMD patients. Methods In 33 patients with DMD, age 12-41 years, eating behavior and gastrointestinal symptoms were evaluated by questionnaires. Gastric emptying half time (T\(_{1/2}\)) and oro-cecal transit time (OCTT) were evaluated by analyzing \(^{13}\)CO\(_{2}\) exhalation curves after ingestion of \(^{13}\)C labeled test meals. Colonic transit time (CTT) was measured by abdominal radiography following ingestion of radiopaque markers. Results The median (quartiles) T\(_{1/2}\) was 187 (168, 220) minutes, the OCTT was 6.3 (5.0, 7.9) hours, both substantially longer than normal data (Goetze 2005, T\(_{1/2}\): 107±10; Geypens 1999, OCTT 4.3±0.1 hours). The median CTT was 60 (48, 82) hours despite extensive use of laxative measures (Meier 1995, upper limit of normal: 60 hours). T\(_{1/2}\) and OCTT did not correlate with symptoms evaluated by the Gastroparesis Cardinal Symptom Index (GCSI) (Spearman r = -0.3, p = 0.1; and r = -0.15, p = 0.4, respectively). CTT was not correlated with symptoms of constipation assessed by ROME III criteria (r = 0.12, p = 0.5). Conclusions DMD patients have a markedly disturbed gastrointestinal motor function. Since objective measures of impaired gastrointestinal transport are not correlated with symptoms of gastroparesis or constipation our findings suggest that measures assuring adequate intestinal transport should be taken independent of the patient's perception in order to prevent potentially life threatening constipation, particularly in older DMD patients.}, language = {en} } @article{HoltfrerichSchwarzSprengeretal.2016, author = {Holtfrerich, Sarah K. C. and Schwarz, Katharina A. and Sprenger, Christian and Reimers, Luise and Diekhof, Esther K.}, title = {Endogenous Testosterone and Exogenous Oxytocin Modulate Attentional Processing of Infant Faces}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {11}, doi = {10.1371/journal.pone.0166617}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166783}, pages = {e0166617}, year = {2016}, abstract = {Evidence indicates that hormones modulate the intensity of maternal care. Oxytocin is known for its positive influence on maternal behavior and its important role for childbirth. In contrast, testosterone promotes egocentric choices and reduces empathy. Further, testosterone decreases during parenthood which could be an adaptation to increased parental investment. The present study investigated the interaction between testosterone and oxytocin in attentional control and their influence on attention to baby schema in women. Higher endogenous testosterone was expected to decrease selective attention to child portraits in a face-in-the-crowd-paradigm, while oxytocin was expected to counteract this effect. As predicted, women with higher salivary testosterone were slower in orienting attention to infant targets in the context of adult distractors. Interestingly, reaction times to infant and adult stimuli decreased after oxytocin administration, but only in women with high endogenous testosterone. These results suggest that oxytocin may counteract the adverse effects of testosterone on a central aspect of social behavior and maternal caretaking.}, language = {en} } @article{DreschersSauppHornefetal.2016, author = {Dreschers, Stephan and Saupp, Peter and Hornef, Mathias and Prehn, Andrea and Platen, Christopher and Morschh{\"a}user, Joachim and Orlikowsky, Thorsten W.}, title = {Reduced PICD in Monocytes Mounts Altered Neonate Immune Response to Candida albicans}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {11}, doi = {10.1371/journal.pone.0166648}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166778}, pages = {e0166648}, year = {2016}, abstract = {Background Invasive fungal infections with Candida albicans (C. albicans) occur frequently in extremely low birthweight (ELBW) infants and are associated with poor outcome. Phagocytosis of C.albicans initializes apoptosis in monocytes (phagocytosis induced cell death, PICD). PICD is reduced in neonatal cord blood monocytes (CBMO). Hypothesis Phagocytosis of C. albicans causes PICD which differs between neonatal monocytes (CBMO) and adult peripheral blood monocytes (PBMO) due to lower stimulation of TLR-mediated immune responses. Methods The ability to phagocytose C. albicans, expression of TLRs, the induction of apoptosis (assessment of sub-G1 and nick-strand breaks) were analyzed by FACS. TLR signalling was induced by agonists such as lipopolysaccharide (LPS), Pam3Cys, FSL-1 and Zymosan and blocked (neutralizing TLR2 antibodies and MYD88 inhibitor). Results Phagocytic indices of PBMO and CBMO were similar. Following stimulation with agonists and C. albicans induced up-regulation of TLR2 and consecutive phosphorylation of MAP kinase P38 and expression of TNF-α, which were stronger on PBMO compared to CBMO (p < 0.005). Downstream, TLR2 signalling initiated caspase-3-dependent PICD which was found reduced in CBMO (p < 0.05 vs PBMO). Conclusion Our data suggest direct involvement of TLR2-signalling in C. albicans-induced PICD in monocytes and an alteration of this pathway in CBMO.}, language = {en} } @article{XuHeKaiseretal.2016, author = {Xu, Li and He, Jianzheng and Kaiser, Andrea and Gr{\"a}ber, Nikolas and Schl{\"a}ger, Laura and Ritze, Yvonne and Scholz, Henrike}, title = {A Single Pair of Serotonergic Neurons Counteracts Serotonergic Inhibition of Ethanol Attraction in Drosophila}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {12}, doi = {10.1371/journal.pone.0167518}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166762}, pages = {e0167518}, year = {2016}, abstract = {Attraction to ethanol is common in both flies and humans, but the neuromodulatory mechanisms underlying this innate attraction are not well understood. Here, we dissect the function of the key regulator of serotonin signaling—the serotonin transporter-in innate olfactory attraction to ethanol in Drosophila melanogaster. We generated a mutated version of the serotonin transporter that prolongs serotonin signaling in the synaptic cleft and is targeted via the Gal4 system to different sets of serotonergic neurons. We identified four serotonergic neurons that inhibit the olfactory attraction to ethanol and two additional neurons that counteract this inhibition by strengthening olfactory information. Our results reveal that compensation can occur on the circuit level and that serotonin has a bidirectional function in modulating the innate attraction to ethanol. Given the evolutionarily conserved nature of the serotonin transporter and serotonin, the bidirectional serotonergic mechanisms delineate a basic principle for how random behavior is switched into targeted approach behavior.}, language = {en} }