@article{KollgaardUgurelBeckerIdornetal.2015,
  author    = {K{\o}llgaard, Tania and Ugurel-Becker, Selma and Idorn, Manja and Andersen, Mads Hald and Becker, J{\"u}rgen C. and Straten, Per thor},
  title     = {Pre-Vaccination Frequencies of Th17 Cells Correlate with Vaccine-Induced T-Cell Responses to Survivin-Derived Peptide Epitopes},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {7},
  doi       = {10.1371/journal.pone.0131934},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151509},
  pages     = {e0131934},
  year      = {2015},
  abstract  = {Various subsets of immune regulatory cells are suggested to influence the outcome of therapeutic antigen-specific anti-tumor vaccinations. We performed an exploratory analysis of a possible correlation of pre-vaccination Th17 cells, MDSCs, and Tregs with both vaccination-induced T-cell responses as well as clinical outcome in metastatic melanoma patients vaccinated with survivin-derived peptides. Notably, we observed dysfunctional Th1 and cytotoxic T cells, i.e. down-regulation of the CD3\(\zeta\)chain (p=0.001) and an impaired IFN\(\gamma\)-production (p=0.001) in patients compared to healthy donors, suggesting an altered activity of immune regulatory cells. Moreover, the frequencies of Th17 cells (p=0.03) and Tregs (p=0.02) were elevated as compared to healthy donors. IL-17-secreting CD4\(^{+}\) T cells displayed an impact on the immunological and clinical effects of vaccination: Patients characterized by high frequencies of Th17 cells at pre-vaccination were more likely to develop survivin-specific T-cell reactivity post-vaccination (p=0.03). Furthermore, the frequency of Th17 (p=0.09) and Th17/IFN\(\gamma\)\(^{+}\) (p=0.19) cells associated with patient survival after vaccination. In summary, our explorative, hypothesis-generating study demonstrated that immune regulatory cells, in particular Th17 cells, play a relevant role for generation of the vaccine-induced anti-tumor immunity in cancer patients, hence warranting further investigation to test for validity as predictive biomarkers.},
  language  = {en}
}
@article{MuellerStoetterKalluvyaetal.2015,
  author    = {Mueller, A. and Stoetter, L. and Kalluvya, S. and Stich, A. and Majinge, C. and Weissbrich, B. and Kasang, C.},
  title     = {Prevalence of hepatitis B virus infection among health care workers in a tertiary hospital in Tanzania},
  series = {BMC Infectious Diseases},
  volume    = {15},
  journal   = {BMC Infectious Diseases},
  number    = {386},
  doi       = {10.1186/s12879-015-1129-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141786},
  year      = {2015},
  abstract  = {Background: Sub-Saharan Africa has a high prevalence of hepatitis B virus (HBV) infections. Health care workers (HCWs) are at high risk of contracting HBV infection through their occupation. Vaccination of HCWs against HBV is standard practice in many countries, but is often not implemented in resource-poor settings. We aimed with this cross-sectional study to determine HBV prevalence, HCW vaccination status, and the risk factors for HCWs contracting HBV infection in Tanzania. Methods: We enrolled 600 HCWs from a tertiary Tanzanian hospital. Their demographics, medical histories, HBV vaccination details and risk factors for contracting blood-borne infections were collected using a standardized questionnaire. Serum samples were tested for HBV and hepatitis C virus (HCV) markers by ELISA techniques, PCR and an anti-HBs rapid test. HCWs were divided in two subgroups: those at risk of contracting HBV (rHCW 79.2 \%) via exposure to potentially infectious materials, and those considered not at risk of contracting HBV (nrHCW, 20.8 \%). Results: The overall prevalence of chronic HBV infection (HBsAg+, anti-HBc+, anti-HBs-) was 7.0 \% (42/598). Chronic HBV infection was found in 7.4 \% of rHCW versus 5.6 \% of nrHCW(p-value = 0.484). HCWs susceptible to HBV (HBsAg-, anti-HBc-, anti-HBs-) comprised 31.3 \%. HBV immunity achieved either by healed HBV infection (HBsAg-, anti-HBc+, anti-HBs+) or by vaccination (HBsAg-, anti-HBc-, anti-HBs+) comprised 36.5 \% and 20.2 \%, respectively. 4.8 \% of participants had indeterminate results (HBsAg-, anti-HBc+, anti-HBc-IgM-, anti-HBs-). Only 77.1 \% of HCWs who received a full vaccination course had an anti-HBs titer > 10 ml/U. An anti-HBs point-of-care test was 80.7 \% sensitive and 96.9 \% specific. There was a significantly higher risk for contracting HBV (anti-HBc+) among those HCW at occupational risk (rHCW) of older age (odds ratios (OR) in rHCW 3.297, p < 0.0001 vs. nrHCW 1.385, p = 0.606) and among those HCW being employed more than 11 years (OR 2.51, p < 0.0001***). HCV prevalence was low (HCV antibodies 1.2 \% and HCV-RNA 0.3 \%). Conclusions: Chronic HBV infection is common among Tanzanian HCWs. One third of HCWs were susceptible to HBV infection, highlighting the need for vaccination. Due to high prevalence of naturally acquired immunity against HBV pre-testing might be a useful tool to identify susceptible individuals.},
  language  = {en}
}
@article{ZinnerHauserBornetal.2015,
  author    = {Zinner, Christoph and Hauser, Anna and Born, Dennis-Peter and Wehrlin, Jon P. and Holmberg, Hans-Christer and Sperlich, Billy},
  title     = {Influence of Hypoxic Interval Training and Hyperoxic Recovery on Muscle Activation and Oxygenation in Connection with Double-Poling Exercise},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {10},
  doi       = {10.1371/journal.pone.0140616},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126299},
  pages     = {e0140616},
  year      = {2015},
  abstract  = {Here, we evaluated the influence of breathing oxygen at different partial pressures during recovery from exercise on performance at sea-level and a simulated altitude of 1800 m, as reflected in activation of different upper body muscles, and oxygenation of the m. triceps brachii. Ten well-trained, male endurance athletes (25.3±4.1 yrs; 179.2±4.5 cm; 74.2±3.4 kg) performed four test trials, each involving three 3-min sessions on a double-poling ergometer with 3-min intervals of recovery. One trial was conducted entirely under normoxic (No) and another under hypoxic conditions \((Ho; F_iO_2 = 0.165)\). In the third and fourth trials, the exercise was performed in normoxia and hypoxia, respectively, with hyperoxic recovery \((HOX; F_iO_2 = 1.00)\) in both cases. Arterial hemoglobin saturation was higher under the two HOX conditions than without HOX (p<0.05). Integrated muscle electrical activity was not influenced by the oxygen content (best d = 0.51). Furthermore, the only difference in tissue saturation index measured via near-infrared spectroscopy observed was between the recovery periods during the NoNo and HoHOX interventions (P<0.05, d = 0.93). In the case of HoHo the athletes' \(P_{mean}\) declined from the first to the third interval (P < 0.05), whereas Pmean was unaltered under the HoHOX, NoHOX and NoNo conditions. We conclude that the less pronounced decline in \(P_{mean}\) during 3 x 3-min double-poling sprints in normoxia and hypoxia with hyperoxic recovery is not related to changes in muscle activity or oxygenation. Moreover, we conclude that hyperoxia \((F_iO_2 = 1.00)\) used in conjunction with hypoxic or normoxic work intervals may serve as an effective aid when inhaled during the subsequent recovery intervals.},
  language  = {en}
}
@article{SchickBaarBrunoetal.2015,
  author    = {Schick, Martin Alexander and Baar, Wolfgang and Bruno, Raphael Romano and Wollborn, Jakob and Held, Christopher and Schneider, Reinhard and Flemming, Sven and Schlegel, Nicolas and Roewer, Norbert and Neuhaus, Winfried and Wunder, Christian},
  title     = {Balanced hydroxyethylstarch (HES 130/0.4) impairs kidney function in-vivo without inflammation},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {9},
  doi       = {10.1371/journal.pone.0137247},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126068},
  pages     = {e0137247},
  year      = {2015},
  abstract  = {Volume therapy is a standard procedure in daily perioperative care, and there is an ongoing discussion about the benefits of colloid resuscitation with hydroxyethylstarch (HES). In sepsis HES should be avoided due to a higher risk for acute kidney injury (AKI). Results of the usage of HES in patients without sepsis are controversial. Therefore we conducted an animal study to evaluate the impact of 6\% HES 130/0.4 on kidney integrity with sepsis or under healthy conditions Sepsis was induced by standardized Colon Ascendens Stent Peritonitis (sCASP). sCASP-group as well as control group (C) remained untreated for 24 h. After 18 h sCASP+HES group (sCASP+VOL) and control+HES (C+VOL) received 50 ml/KG balanced 6\% HES (VOL) 130/0.4 over 6h. After 24h kidney function was measured via Inulin- and PAH-Clearance in re-anesthetized rats, and serum urea, creatinine (crea), cystatin C and Neutrophil gelatinase-associated lipocalin (NGAL) as well as histopathology were analysed. In vitro human proximal tubule cells (PTC) were cultured +/- lipopolysaccharid (LPS) and with 0.1-4.0\% VOL. Cell viability was measured with XTT-, cell toxicity with LDH-test. sCASP induced severe septic AKI demonstrated divergent results regarding renal function by clearance or creatinine measure focusing on VOL. Soleley HES (C+VOL) deteriorated renal function without sCASP. Histopathology revealed significantly derangements in all HES groups compared to control. In vitro LPS did not worsen the HES induced reduction of cell viability in PTC cells. For the first time, we demonstrated, that application of 50 ml/KG 6\% HES 130/0.4 over 6 hours induced AKI without inflammation in vivo. Severity of sCASP induced septic AKI might be no longer susceptible to the way of volume expansion},
  language  = {en}
}
@article{PoppThielmanNieswandtetal.2015,
  author    = {Popp, Michael and Thielman, Ina and Nieswandt, Bernhard and Stegner, David},
  title     = {Normal Platelet Integrin Function in Mice Lacking Hydrogen Peroxide-Induced Clone-5 (Hic-5)},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {7},
  doi       = {10.1371/journal.pone.0133429},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125724},
  pages     = {e0133429},
  year      = {2015},
  abstract  = {Integrin αIIbβ3 plays a central role in the adhesion and aggregation of platelets and thus is essential for hemostasis and thrombosis. Integrin activation requires the transmission of a signal from the small cytoplasmic tails of the α or β subunit to the large extracellular domains resulting in conformational changes of the extracellular domains to enable ligand binding. Hydrogen peroxide-inducible clone-5 (Hic-5), a member of the paxillin family, serves as a focal adhesion adaptor protein associated with αIIbβ3 at its cytoplasmic tails. Previous studies suggested Hic-5 as a novel regulator of integrin αIIbβ3 activation and platelet aggregation in mice. To assess this in more detail, we generated Hic-5-null mice and analyzed activation and aggregation of their platelets in vitro and in vivo. Surprisingly, lack of Hic-5 had no detectable effect on platelet integrin activation and function in vitro and in vivo under all tested conditions. These results indicate that Hic-5 is dispensable for integrin αIIbβ3 activation and consequently for arterial thrombosis and hemostasis in mice.},
  language  = {en}
}
@article{TsonevaStritzkerBedenketal.2015,
  author    = {Tsoneva, Desislava and Stritzker, Jochen and Bedenk, Kristina and Zhang, Qian and Cappello, Joseph and Fischer, Utz and Szalay, Aladar A.},
  title     = {Drug-encoded Biomarkers for Monitoring Biological Therapies},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {9},
  doi       = {10.1371/journal.pone.0137573},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125265},
  pages     = {e0137573},
  year      = {2015},
  abstract  = {Blood tests are necessary, easy-to-perform and low-cost alternatives for monitoring of oncolytic virotherapy and other biological therapies in translational research. Here we assessed three candidate proteins with the potential to be used as biomarkers in biological fluids: two glucuronidases from E. coli (GusA) and Staphylococcus sp. RLH1 (GusPlus), and the luciferase from Gaussia princeps (GLuc). The three genes encoding these proteins were inserted individually into vaccinia virus GLV-1h68 genome under the control of an identical promoter. The three resulting recombinant viruses were used to infect tumor cells in cultures and human tumor xenografts in nude mice. In contrast to the actively secreted GLuc, the cytoplasmic glucuronidases GusA and GusPlus were released into the supernatants only as a result of virus-mediated oncolysis. GusPlus resulted in the most sensitive detection of enzyme activity under controlled assay conditions in samples containing as little as 1 pg/ml of GusPlus, followed by GusA (25 pg/ml) and GLuc (≥375 pg/ml). Unexpectedly, even though GusA had a lower specific activity compared to GusPlus, the substrate conversion in the serum of tumor-bearing mice injected with the GusA-encoding virus strains was substantially higher than that of GusPlus. This was attributed to a 3.2 fold and 16.2 fold longer half-life of GusA in the blood stream compared to GusPlus and GLuc respectively, thus a more sensitive monitor of virus replication than the other two enzymes. Due to the good correlation between enzymatic activity of expressed marker gene and virus titer, we conclude that the amount of the biomarker protein in the body fluid semiquantitatively represents the amount of virus in the infected tumors which was confirmed by low light imaging. We found GusA to be the most reliable biomarker for monitoring oncolytic virotherapy among the three tested markers.},
  language  = {en}
}