@article{WallmannSperlichFroboese2014,
  author    = {Wallmann-Sperlich, Birgit and Froboese, Ingo},
  title     = {Physical Activity during Work, Transport and Leisure in Germany - Prevalence and Socio-Demographic Correlates},
  doi       = {10.1371/journal.pone.0112333},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-113648},
  year      = {2014},
  abstract  = {Background This study aimed 1) to provide data estimates concerning overall moderate- and vigorous-intensity physical activity (MVPA) as well as MVPA during work, transport and leisure in Germany and 2) to investigate MVPA and possible associations with socio-demographic correlates. Methods A cross-sectional telephone survey interviewed 2248 representative participants in the age of 18-65 years (1077 men; 42.4±13.4 years; body mass index: 25.3±4.5kg•m-2) regarding their self-reported physical activity across Germany. The Global Physical Activity Questionnaire was applied to investigate MVPA during work, transport and leisure and questions were answered concerning their demographics. MVPA was stratified by gender, age, body mass index, residential setting, educational and income level. To identify socio-demographic correlates of overall MVPA as well as in the domains, we used a series of linear regressions. Results 52.8\% of the sample achieved physical activity recommendations (53.7\% men/52.1\% women). Overall MVPA was highest in the age group 18-29 years (p<.05), in participants with 10 years of education (p<.05) and in participants with lowest income levels <1.500€ (p<.05). Regression analyses revealed that age, education and income were negatively associated with overall and work MVPA. Residential setting and education was positively correlated with transport MVPA, whereas income level was negatively associated with transport MVPA. Education was the only correlate for leisure MVPA with a positive association. Conclusions The present data underlines the importance of a comprehensive view on physical activity engagement according to the different physical activity domains and discloses a need for future physical activity interventions that consider socio-demographic variables, residential setting as well as the physical activity domain in Germany.},
  language  = {en}
}
@phdthesis{Staab2006,
  author    = {Staab, Charlotte},
  title     = {Pr{\"a}diktoren der Persistenz des ADHS},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-22424},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2006},
  abstract  = {Die vorliegende Studie hatte das Ziel pr{\"a}diktive Faktoren einer Persistenz von ADHS in das Erwachsenenalter ausfindig zu machen und den Einfluss von kindbezogenen, famili{\"a}ren und behandlungsbezogenen Eigenschaften auf den Verlauf und das Fortbestehen der ADHS-Symptomatik zu untersuchen. Das Untersuchungsgut bestand aus Patienten der Klinik und Poliklinik der Kinder- und Jugendpsychiatrie der Universit{\"a}t W{\"u}rzburg. Das Gesamtkollektiv bestand aus 146 Patienten, deren Akten wir auswerteten. 67 Patienten (46\%) konnten wir mittels WURS, DSM-IV-Kriterien, Anamnesebogen, SKID-I und SKID-II im Erwachsenenalter nachexplorieren. Der Katamnesezeitraum betrug ein Jahr, vom 04.11.2002 bis zum 03.11.2003. Die ehemaligen Patienten waren zum Katamnesezeitpunkt durchschnittlich 28 Jahre alt. Bei der Suche nach pr{\"a}diktiven Faktoren f{\"u}r eine Persistenz der ADHS-Symptomatik in das Erwachsenenalter konnten wir trotz der Studien, welche die Wichtigkeit ung{\"u}nstiger psychosozialer Faktoren f{\"u}r den Verlauf des ADHS belegen (Biederman et al 1996, Hart et al 1995, 1991c, Fischer et al 1993, Taylor et al 1991, Weiss und Hechtman 1986, Gittelman et al 1985, Hechtman et al 1984, Loney et al 1981), keine Pr{\"a}diktoren einer Persistenz der ADHS-Symptomatik finden. Unsere Ergebnisse lassen sich dahingehend erkl{\"a}ren, dass es sich beim ADHS um eine prim{\"a}r genetisch determinierte St{\"o}rung handelt, welche in ihrem Verlauf von verschiedensten intervenierenden Faktoren beeinflusst wird. Es handelt sich um ein komplexes Zusammenspiel von zu Grunde liegenden biologischen Faktoren mit verschiedenen Gen-Umwelt-Interaktionen, ein Zusammenspiel von Individuum mit seiner Pers{\"o}nlichkeit und eigenen Coping-Strategien, sowie der Art des Umfeldes und deren Reaktion auf das Verhalten des Betroffenen. Daher besteht keine M{\"o}glichkeit den Verlauf von ADHS anhand von Eigenschaften, welche zu einem einzigen Zeitpunkt (bei Erstvorstellung) erfasst wurden vorherzusagen. In unserer Stichprobe wurde eine Achse-I-Diagnose bei der H{\"a}lfte der mit dem SKID-I-Interview nachuntersuchten Probanden gestellt. Entsprechend unserer Annahme, dass Erwachsene mit vielen Symptomen des ADHS einen ung{\"u}nstigeren Verlauf mit mehr Achse-I-St{\"o}rungen nehmen, fanden sich diese St{\"o}rungen zu etwa zwei Dritteln bei den Erwachsenen mit mehr als 6 fortbestehenden Symptomen des ADHS, w{\"a}hrend kein Erwachsener ohne Symptome des ADHS eine Achse-I-Diagnose hatte. Bei 61\% (n=36) der mit dem SKID-II-Interview nachexplorierten Patienten wurde die Diagnose einer Pers{\"o}nlichkeitsst{\"o}rung gestellt. Am h{\"a}ufigsten fanden sich die Diagnosen einer dissozialen (21\%), einer selbstunsicher-vermeidenden (21\%), einer negativistischen (18\%), einer narzisstischen (14\%) und einer emotional-instabilen Pers{\"o}nlichkeitsst{\"o}rung (9\%). Bemerkenswert ist, dass sich keiner der Erwachsenen unserer Studie aktuell in psychiatrischer Behandlung befand. Dies steht im Kontrast zu der meist fortbestehenden Restsymptomatik des ADHS und der hohen Rate komorbider Achse-I- und Achse-II-St{\"o}rungen, welche mit psychosozialen Beeintr{\"a}chtigungen einhergehen. Eine kontinuierliche, {\"u}ber das Kindesalter hinausreichende Betreuung von Patienten mit ADHS, sowie eine ausf{\"u}hrliche Aufkl{\"a}rung k{\"o}nnten einem solchen ung{\"u}nstigen Verlauf entgegenwirken. Eine ad{\"a}quate Behandlung Erwachsener mit ADHS ist nur m{\"o}glich, wenn Komorbidit{\"a}ten ber{\"u}cksichtigt und gleichzeitig mitbehandelt werden. Weitere epidemiologische und neurobiologische Studien mit einem gr{\"o}ßeren Kollektiv sind notwendig zum Auffinden von Einflussfaktoren auf den Verlauf des ADHS und zur Kl{\"a}rung der Komorbidit{\"a}tsbeziehungen des ADHS.},
  language  = {de}
}
@article{RamachandranSchirmerMuenstetal.2015,
  author    = {Ramachandran, Sarada Devi and Schirmer, Katharina and M{\"u}nst, Bernhard and Heinz, Stefan and Ghafoory, Shahrouz and W{\"o}lfl, Stefan and Simon-Keller, Katja and Marx, Alexander and {\O}ie, Cristina Ionica and Ebert, Matthias P. and Walles, Heike and Braspenning, Joris and Breitkopf-Heinlein, Katja},
  title     = {In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {10},
  doi       = {10.1371/journal.pone.0139345},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139552},
  pages     = {e0139345},
  year      = {2015},
  abstract  = {In this study we used differentiated adult human upcyte (R) cells for the in vitro generation of liver organoids. Upcyte (R) cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte (R) process). Proliferating upcyte (R) cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte (R) cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel\(^{TM}\), they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.},
  language  = {en}
}
@article{OkoroBarquistConnoretal.2015,
  author    = {Okoro, Chinyere K. and Barquist, Lars and Connor, Thomas R. and Harris, Simon R. and Clare, Simon and Stevens, Mark P. and Arends, Mark J. and Hale, Christine and Kane, Leanne and Pickard, Derek J. and Hill, Jennifer and Harcourt, Katherine and Parkhill, Julian and Dougan, Gordon and Kingsley, Robert A.},
  title     = {Signatures of adaptation in human invasive Salmonella Typhimurium ST313 populations from sub-Saharan Africa},
  series = {PLoS Neglected Tropical Diseases},
  volume    = {9},
  journal   = {PLoS Neglected Tropical Diseases},
  number    = {3},
  doi       = {10.1371/journal.pntd.0003611},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143779},
  pages     = {e0003611},
  year      = {2015},
  abstract  = {Two lineages of Salmonella enterica serovar Typhimurium (S. Typhimurium) of multi-locus sequence type ST313 have been linked with the emergence of invasive Salmonella disease across sub-Saharan Africa. The expansion of these lineages has a temporal association with the HIV pandemic and antibiotic usage. We analysed the whole genome sequence of 129 ST313 isolates representative of the two lineages and found evidence of lineage-specific genome degradation, with some similarities to that observed in S. Typhi. Individual ST313 S. Typhimurium isolates exhibit a distinct metabolic signature and modified enteropathogenesis in both a murine and cattle model of colitis, compared to S. Typhimurium outside of the ST313 lineages. These data define phenotypes that distinguish ST313 isolates from other S. Typhimurium and may represent adaptation to a distinct pathogenesis and lifestyle linked to an-immuno-compromised human population.},
  language  = {en}
}
@phdthesis{Kuhn2006,
  author    = {Kuhn, Jochen},
  title     = {Das Medulloblastom bei Erwachsenen : Prognostische Faktoren und histologische Besonderheiten einer seltenen Tumorentit{\"a}t : Vergleich einer adjuvanten mit einer neoadjuvanten Chemotherapie},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-21060},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2006},
  abstract  = {In dieser retrospektiven multizentrischen Analyse wurde bei 46 Beobachtungspatienten mit Medulloblastom im Alter von 16 bis 51 Jahren bei einem Median von 20,5 Jahren die Wirksamkeit und Vertr{\"a}glichkeit einer neoadjuvanten Chemotherapie, bestehend aus Procarbacin, Ifosfamid, Etoposid, Methotrexat, Cisplatin und Cytarabin mit einer Erhaltungschemotherapie mit Vincristin, CCNU und Cisplatin verglichen. Die progressionsfreie 4-Jahres{\"u}berlebensrate war bei der Erhaltungstherapie mit 86 \% tendenziell, jedoch nicht signifikant h{\"o}her als bei der Sandwichtherapie mit 61 \%. Die 4-Jahres-Gesamt{\"u}berlebensrate aller 46 Patienten lag bei 85 \% und das 4-Jahres-PFS aller Patienten bei 72 \%. Unter Erhaltungschemotherapie kam es h{\"a}ufiger zu relevanten Nebenwirkungen, so dass die Zytostatikadosis verringert oder die Chemotherapie abgebrochen werden musste. Bei der Erhaltungstherapie war dies bei 10 von 19 Patienten der Fall, bei neoadjuvanter Therapie bei 5 von 24 Patienten. Der Allgemeinzustand beurteilt mittels Karnofsky-Index mindestens ein Jahr nach Ende der Therapie war im Erhaltungstherapiearm signifikant schlechter als im Sandwichtherapiearm (p= 0,001). Im Vergleich zum Sandwichtherapiearm waren deutlich mehr Patienten, die eine Erhaltungstherapie erhalten hatten (5 von 15 vs. 0 von 14), nach {\"u}ber einem Jahr nach Ende der Therapie immer noch arbeitsunf{\"a}hig. Bei der histologischen Untersuchung trat die desmoplastische Variante gegen{\"u}ber der klassischen h{\"a}ufiger auf und war h{\"a}ufiger lateral im Kleinhirn lokalisiert als in vergleichbaren Studien bei Kindern. Folgende Faktoren wurden untersucht: Alter, Geschlecht, histologischer Typ, mediale oder laterale Tumorlokalisation, Resektionsgrad, Metastasierungsstadium, Vorhanden-sein eines Liquorshunts, geringere Bestrahlungsdosis sowie adjuvante oder neoadjuvante Chemotherapie. Abh{\"a}ngig vom Metastasierungsstadium zeigte sich ein starker Trend zu einer schlechteren {\"U}berlebenswahrscheinlichkeit (M2/3 Stadium 45 \% 4-J-PFS vs. 78 \% bei M0/1). Aufgrund der niedrigen Fallzahlen konnte aber in den Analysen kein Signifikanzniveau erreicht werden.},
  language  = {de}
}
@article{GlaserFehrholzCurstedtetal.2016,
  author    = {Glaser, Kirsten and Fehrholz, Markus and Curstedt, Tore and Kunzmann, Steffen and Speer, Christian P.},
  title     = {Effects of the New Generation Synthetic Reconstituted Surfactant CHF5633 on Pro- and Anti-Inflammatory Cytokine Expression in Native and LPS-Stimulated Adult CD14\(^{+}\) Monocytes},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {1},
  doi       = {10.1371/journal.pone.0146898},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180195},
  year      = {2016},
  abstract  = {Background Surfactant replacement therapy is the standard of care for the prevention and treatment of neonatal respiratory distress syndrome. New generation synthetic surfactants represent a promising alternative to animal-derived surfactants. CHF5633, a new generation reconstituted synthetic surfactant containing SP-B and SP-C analogs and two synthetic phospholipids has demonstrated biophysical effectiveness in vitro and in vivo. While several surfactant preparations have previously been ascribed immunomodulatory capacities, in vitro data on immunomodulation by CHF5633 are limited, so far. Our study aimed to investigate pro- and anti-inflammatory effects of CHF5633 on native and LPS-stimulated human adult monocytes. Methods Highly purified adult CD14\(^{+}\) cells, either native or simultaneously stimulated with LPS, were exposed to CHF5633, its components, or poractant alfa (Curosurf\(^{®}\)). Subsequent expression of TNF-α, IL-1β, IL-8 and IL-10 mRNA was quantified by real-time quantitative PCR, corresponding intracellular cytokine synthesis was analyzed by flow cytometry. Potential effects on TLR2 and TLR4 mRNA and protein expression were monitored by qPCR and flow cytometry. Results Neither CHF5633 nor any of its components induced inflammation or apoptosis in native adult CD14\(^{+}\) monocytes. Moreover, LPS-induced pro-inflammatory responses were not aggravated by simultaneous exposure of monocytes to CHF5633 or its components. In LPS-stimulated monocytes, exposure to CHF5633 led to a significant decrease in TNF-α mRNA (0.57 ± 0.23-fold, p = 0.043 at 4h; 0.56 ± 0.27-fold, p = 0.042 at 14h). Reduction of LPS-induced IL-1β mRNA expression was not significant (0.73 ± 0.16, p = 0.17 at 4h). LPS-induced IL-8 and IL-10 mRNA and protein expression were unaffected by CHF5633. For all cytokines, the observed CHF5633 effects paralleled a Curosurf®-induced modulation of cytokine response. TLR2 and TLR4 mRNA and protein expression were not affected by CHF5633 and Curosurf®, neither in native nor in LPS-stimulated adult monocytes. Conclusion The new generation reconstituted synthetic surfactant CHF5633 was tested for potential immunomodulation on native and LPS-activated adult human monocytes. Our data confirm that CHF5633 does not exert unintended pro-inflammatory effects in both settings. On the contrary, CHF5633 significantly suppressed TNF-α mRNA expression in LPS-stimulated adult monocytes, indicating potential anti-inflammatory effects.},
  language  = {en}
}
@article{BorgesO'ConnorPhillipsetal.2014,
  author    = {Borges, Alvaro H. and O'Connor, Jemma L. and Phillips, Andrew N. and Baker, Jason V. and Vjecha, Michael J. and Losso, Marcelo H. and Klinker, Hartwig and Lopardo, Gustavo and Williams, Ian and Lundgren, Jens D.},
  title     = {Factors Associated with D-Dimer Levels in HIV-Infected Individuals},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {3},
  doi       = {10.1371/journal.pone.0090978},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117094},
  pages     = {e90978},
  year      = {2014},
  abstract  = {Background: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. Methods: In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4(+) count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol. Results: Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels. Conclusions: D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels.},
  language  = {en}
}