@article{SunOrtegaTanetal.2018,
  author    = {Sun, Ping and Ortega, Gabriela and Tan, Yan and Hua, Qian and Riederer, Peter F. and Deckert, J{\"u}rgen and Schmitt-B{\"o}hrer, Angelika G.},
  title     = {Streptozotocin impairs proliferation and differentiation of adult hippocampal neural stem cells in vitro-correlation with alterations in the expression of proteins associated with the insulin system},
  series = {Frontiers in Aging Neuroscience},
  volume    = {10},
  journal   = {Frontiers in Aging Neuroscience},
  number    = {145},
  doi       = {10.3389/fnagi.2018.00145},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176741},
  year      = {2018},
  abstract  = {Rats intracerebroventricularily (icv) treated with streptozotocin (STZ), shown to generate an insulin resistant brain state, were used as an animal model for the sporadic form of Alzheimer's disease (sAD). Previously, we showed in an in vivo study that 3 months after STZ icv treatment hippocampal adult neurogenesis (AN) is impaired. In the present study, we examined the effects of STZ on isolated adult hippocampal neural stem cells (NSCs) using an in vitro approach. We revealed that 2.5 mM STZ inhibits the proliferation of NSCs as indicated by reduced number and size of neurospheres as well as by less BrdU-immunoreactive NSCs. Double immunofluorescence stainings of NSCs already being triggered to start with their differentiation showed that STZ primarily impairs the generation of new neurons, but not of astrocytes. For revealing mechanisms possibly involved in mediating STZ effects we analyzed expression levels of insulin/glucose system-related molecules such as the glucose transporter (GLUT) 1 and 3, the insulin receptor (IR) and the insulin-like growth factor (IGF) 1 receptor. Applying quantitative Real time-PCR (qRT-PCR) and immunofluorescence stainings we showed that STZ exerts its strongest effects on GLUT3 expression, as GLUT3 mRNA levels were found to be reduced in NSCs, and less GLUT3-immunoreactive NSCs as well as differentiating cells were detected after STZ treatment. These findings suggest that cultured NSCs are a good model for developing new strategies to treat nerve cell loss in AD and other degenerative disorders.},
  language  = {en}
}
@article{ZayatsJacobsenKleppeetal.2016,
  author    = {Zayats, T and Jacobsen, KK and Kleppe, R and Jacob, CP and Kittel-Schneider, S and Ribas{\´e}s, M and Ramos-Quiroga, JA and Richarte, V and Casas, M and Mota, NR and Grevet, EH and Klein, M and Corominas, J and Bralten, J and Galesloot, T and Vasquez, AA and Herms, S and Forstner, AJ and Larsson, H and Breen, G and Asherson, P and Gross-Lesch, S and Lesch, KP and Cichon, S and Gabrielsen, MB and Holmen, OL and Bau, CHD and Buitelaar, J and Kiemeney, L and Faraone, SV and Cormand, B and Franke, B and Reif, A and Haavik, J and Johansson, S},
  title     = {Exome chip analyses in adult attention deficit hyperactivity disorder},
  series = {Translational Psychiatry},
  volume    = {6},
  journal   = {Translational Psychiatry},
  number    = {e923},
  doi       = {10.1038/tp.2016.196},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168297},
  year      = {2016},
  abstract  = {Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. We performed an exome-wide scan of adult ADHD using the Illumina Human Exome Bead Chip, which interrogates over 250 000 common and rare variants. Participants were recruited by the International Multicenter persistent ADHD CollaboraTion (IMpACT). Statistical analyses were divided into 3 steps: (1) gene-level analysis of rare variants (minor allele frequency (MAF)<1\%); (2) single marker association tests of common variants (MAF⩾1\%), with replication of the top signals; and (3) pathway analyses. In total, 9365 individuals (1846 cases and 7519 controls) were examined. Replication of the most associated common variants was attempted in 9847 individuals (2077 cases and 7770 controls) using fixed-effects inverse variance meta-analysis. With a Bonferroni-corrected significance level of 1.82E-06, our analyses of rare coding variants revealed four study-wide significant loci: 6q22.1 locus (P=4.46E-08), where NT5DC1 and COL10A1 reside; the SEC23IP locus (P=6.47E-07); the PSD locus (P=7.58E-08) and ZCCHC4 locus (P=1.79E-06). No genome-wide significant association was observed among the common variants. The strongest signal was noted at rs9325032 in PPP2R2B (odds ratio=0.81, P=1.61E-05). Taken together, our data add to the growing evidence of general signal transduction molecules (NT5DC1, PSD, SEC23IP and ZCCHC4) having an important role in the etiology of ADHD. Although the biological implications of these findings need to be further explored, they highlight the possible role of cellular communication as a potential core component in the development of both adult and childhood forms of ADHD.},
  language  = {en}
}
@article{RemdeKranzMorelletal.2023,
  author    = {Remde, Hanna and Kranz, Stefanie and Morell, Sarah Maria and Altieri, Barbara and Kroiss, Matthias and Detomas, Mario and Fassnacht, Martin and Deutschbein, Timo},
  title     = {Clinical course of patients with adrenal incidentalomas and cortisol autonomy},
  series = {Frontiers in Endocrinology},
  volume    = {14},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2023.1123132},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-316793},
  year      = {2023},
  abstract  = {Background Adrenal incidentalomas with cortisol autonomy are associated with increased cardiovascular morbidity and mortality. Specific data on the clinical and biochemical course of affected patients are lacking. Methods Retrospective study from a tertiary referral centre in Germany. After exclusion of overt hormone excess, malignancy and glucocorticoid medication, patients with adrenal incidentalomas were stratified according to serum cortisol after 1 mg dexamethasone: autonomous cortisol secretion (ACS), >5.0; possible ACS (PACS), 1.9-5.0; non-functioning adenomas (NFA), ≤1.8 µg/dl. Results A total of 260 patients were enrolled (147 women (56.5\%), median follow-up 8.8 (2.0-20.8) years). At initial diagnosis, median age was 59.5 (20-82) years, and median tumour size was 27 (10-116) mm. Bilateral tumours were more prevalent in ACS (30.0\%) and PACS (21.9\%) than in NFA (8.1\%). Over time, 40/124 (32.3\%) patients had a shift of their hormonal secretion pattern (NFA to PACS/ACS, n=15/53; PACS to ACS, n=6/47; ACS to PACS, n=11/24; PACS to NFA, n=8/47). However, none of the patients developed overt Cushing's syndrome. Sixty-one patients underwent adrenalectomy (NFA, 17.9\%; PACS, 24.0\%; ACS, 39.0\%). When non-operated patients with NFA were compared to PACS and ACS at last follow-up, arterial hypertension (65.3\% vs. 81.9\% and 92.0\%; p<0.05), diabetes (23.8\% vs. 35.6\% and 40.0\%; p<0.01), and thromboembolic events (PACS: HR 3.43, 95\%-CI 0.89-13.29; ACS: HR 5.96, 95\%-CI 1.33-26.63; p<0.05) were significantly less frequent, along with a trend towards a higher rate of cardiovascular events in case of cortisol autonomy (PACS: HR 2.23, 95\%-CI 0.94-5.32; ACS: HR 2.60, 95\%-CI 0.87-7.79; p=0.1). Twenty-five (12.6\%) of the non-operated patients died, with higher overall mortality in PACS (HR 2.6, 95\%-CI 1.0-4.7; p=0.083) and ACS (HR 4.7, 95\%-CI 1.6-13.3; p<0.005) compared to NFA. In operated patients, prevalence of arterial hypertension decreased significantly (77.0\% at diagnosis to 61.7\% at last follow-up; p<0.05). The prevalence of cardiovascular events and mortality did not differ significantly between operated and non-operated patients, whereas thromboembolic events were significantly less frequent in the surgical treatment group. Conclusion Our study confirms relevant cardiovascular morbidity in patients with adrenal incidentalomas (especially those with cortisol autonomy). These patients should therefore be monitored carefully, including adequate treatment of typical cardiovascular risk factors. Adrenalectomy was associated with a significantly decreased prevalence of hypertension. However, more than 30\% of patients required reclassification according to repeated dexamethasone suppression tests. Thus, cortisol autonomy should ideally be confirmed before making any relevant treatment decision (e.g. adrenalectomy).},
  language  = {en}
}
@article{WeismannSchneiderHoeybye2016,
  author    = {Weismann, Dirk and Schneider, Andreas and H{\"o}ybye, Charlotte},
  title     = {Clinical aspects of symptomatic hyponatremia},
  series = {Endocrine Connections},
  volume    = {5},
  journal   = {Endocrine Connections},
  number    = {5},
  doi       = {10.1530/EC-16-0046},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162936},
  pages     = {R35-R43},
  year      = {2016},
  abstract  = {Hyponatremia (HN) is a common condition, with a large number of etiologies and a complicated treatment. Although chronic HN has been shown to be a predictor of poor outcome, sodium-increasing treatments in chronic stable and asymptomatic HN have not proven to increase life expectancy. For symptomatic HN, in contrast, the necessity for urgent treatment has broadly been accepted to avoid the development of fatal cerebral edema. On the other hand, a too rapid increase of serum sodium in chronic HN may result in cerebral damage due to osmotic demyelinisation. Recently, administration of hypertonic saline bolus has been recommended as first-line treatment in patients with moderate-to-severe symptomatic HN. This approach is easy to memorize and holds the potential to greatly facilitate the initial treatment of symptomatic HN. First-line treatment of chronic HN is fluid restriction and if ineffective treatment with tolvaptan or in some patients other agents should be considered. A number of recommendations and guidelines have been published on HN. In the present review, the management of patients with HN in relation to everyday clinical practice is summarized with focus on the acute management.},
  language  = {en}
}
@article{VonaNandaShehataDieleretal.2017,
  author    = {Vona, Barbara and Nanda, Indrajit and Shehata-Dieler, Wafaa and Haaf, Thomas},
  title     = {Genetics of Tinnitus: Still in its Infancy},
  series = {Frontiers in Neuroscience},
  volume    = {11},
  journal   = {Frontiers in Neuroscience},
  number    = {236},
  doi       = {10.3389/fnins.2017.00236},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170926},
  year      = {2017},
  abstract  = {Tinnitus is the perception of a phantom sound that affects between 10 and 15\% of the general population. Despite this considerable prevalence, treatments for tinnitus are presently lacking. Tinnitus exhibits a diverse array of recognized risk factors and extreme clinical heterogeneity. Furthermore, it can involve an unknown number of auditory and non-auditory networks and molecular pathways. This complex combination has hampered advancements in the field. The identification of specific genetic factors has been at the forefront of several research investigations in the past decade. Nine studies have examined genes in a case-control association approach. Recently, a genome-wide association study has highlighted several potentially significant pathways that are implicated in tinnitus. Two twin studies have calculated a moderate heritability for tinnitus and disclosed a greater concordance rate in monozygotic twins compared to dizygotic twins. Despite the more recent data alluding to genetic factors in tinnitus, a strong association with any specific genetic locus is lacking and a genetic study with sufficient statistical power has yet to be designed. Future research endeavors must overcome the many inherent limitations in previous study designs. This review summarizes the previously embarked upon tinnitus genetic investigations and summarizes the hurdles that have been encountered. The identification of candidate genes responsible for tinnitus may afford gene based diagnostic approaches, effective therapy development, and personalized therapeutic intervention.},
  language  = {en}
}
@article{MuelekSeefriedGenestetal.2017,
  author    = {M{\"u}lek, Melanie and Seefried, Lothar and Genest, Franca and H{\"o}gger, Petra},
  title     = {Distribution of constituents and metabolites of maritime pine bark extract (Pycnogenol\(^{®}\)) into serum, blood cells, and synovial fluid of patients with severe osteoarthritis: a randomized controlled trial},
  series = {Nutrients},
  volume    = {9},
  journal   = {Nutrients},
  number    = {5},
  doi       = {10.3390/nu9050443},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159862},
  pages     = {443},
  year      = {2017},
  abstract  = {The present randomized controlled study aimed to investigate the in vivo distribution of constituents or metabolites of the standardized maritime pine bark extract Pycnogenol\(^{®}\). Thirty-three patients with severe osteoarthritis scheduled for a knee arthroplasty were randomized to receive either 200 mg per day Pycnogenol\(^{®}\) (P+) or no treatment (Co) over three weeks before surgery. Serum, blood cells, and synovial fluid samples were analyzed using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization (LC-ESI/MS/MS). Considerable interindividual differences were observed indicating pronounced variability of the polyphenol pharmacokinetics. Notably, the highest polyphenol concentrations were not detected in serum. Catechin and taxifolin primarily resided within the blood cells while the microbial catechin metabolite δ-(3,4-dihydroxy-phenyl)-γ-valerolactone, ferulic, and caffeic acid were mainly present in synovial fluid samples. Taxifolin was detected in serum and synovial fluid exclusively in the P+ group. Likewise, no ferulic acid was found in serum samples of the Co group. Calculating ratios of analyte distribution in individual patients revealed a simultaneous presence of some polyphenols in serum, blood cells, and/or synovial fluid only in the P+ group. This is the first evidence that polyphenols distribute into the synovial fluid of patients with osteoarthritis which supports rationalizing the results of clinical efficacy studies.},
  language  = {en}
}
@article{LeeEyerFelgenhaueretal.2015,
  author    = {Lee, Marcel and Eyer, Florian and Felgenhauer, Norbert and Klinker, Hartwig H. F. and Spinner, Christoph D.},
  title     = {Overdose of dolutegravir in combination with tenofovir disaproxil fumarate/emtricitabine in suicide attempt in a 21-year old patient},
  series = {AIDS Research and Therapy},
  volume    = {12},
  journal   = {AIDS Research and Therapy},
  number    = {18},
  doi       = {10.1186/s12981-015-0054-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151994},
  year      = {2015},
  abstract  = {A 21 year old MSM patient with newly diagnosed HIV infection was hospitalized in our department after ingestion of an overdose of his antiretroviral therapy (ART) comprising dolutegravir (DTG - Tivicay\(^{®}\)) and tenofovir disaproxil fumarate/emtricitabine (Truvada\(^{®}\)) in suicidal intention. On admission, the patient did not show any clinical signs of intoxication and laboratory findings were unremarkable. After 6 hours of intensive care monitoring, the patient was referred to a psychiatric clinic. 5 days after the day of intoxication, serum creatinine levels increased to high normal values (1.2 mg/dl). However, levels never exceeded the upper threshold. 8 and 12 weeks later, serum creatinine normalized to levels measured prior to the intoxication. No other adverse events occurred, and the patient does not suffer from permanent impairments.},
  language  = {en}
}
@article{WeigandRonchiRizkRabinetal.2017,
  author    = {Weigand, Isabel and Ronchi, Cristina L. and Rizk-Rabin, Marthe and Dalmazi, Guido Di and Wild, Vanessa and Bathon, Kerstin and Rubin, Beatrice and Calebiro, Davide and Beuschlein, Felix and Bertherat, J{\´e}r{\^o}me and Fassnacht, Martin and Sbiera, Silviu},
  title     = {Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas},
  series = {Scientific Reports},
  volume    = {7},
  journal   = {Scientific Reports},
  number    = {49},
  doi       = {10.1038/s41598-017-00125-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157952},
  year      = {2017},
  abstract  = {Somatic mutations in protein kinase A catalytic α subunit (PRKACA) were found to be causative for 30-40\% of cortisol-producing adenomas (CPA) of the adrenal gland, rendering PKA signalling constitutively active. In its resting state, PKA is a stable and inactive heterotetramer, consisting of two catalytic and two regulatory subunits with the latter inhibiting PKA activity. The human genome encodes three different PKA catalytic subunits and four different regulatory subunits that are preferentially expressed in different organs. In normal adrenal glands all regulatory subunits are expressed, while CPA exhibit reduced protein levels of the regulatory subunit IIβ. In this study, we linked for the first time the loss of RIIβ protein levels to the PRKACA mutation status and found the down-regulation of RIIβ to arise post-transcriptionally. We further found the PKA subunit expression pattern of different tumours is also present in the zones of the normal adrenal cortex and demonstrate that the different PKA subunits have a differential expression pattern in each zone of the normal adrenal gland, indicating potential specific roles of these subunits in the regulation of different hormones secretion.},
  language  = {en}
}
@article{WangIpKlausKarikarietal.2017,
  author    = {Wang Ip, Chi and Klaus, Laura-Christin and Karikari, Akua A. and Visanji, Naomi P. and Brotchie, Jonathan M. and Lang, Anthony E. and Volkmann, Jens and Koprich, James B.},
  title     = {AAV1/2-induced overexpression of A53T-α-synuclein in the substantia nigra results in degeneration of the nigrostriatal system with Lewy-like pathology and motor impairment: a new mouse model for Parkinson's disease},
  series = {Acta Neuropathologica Communications},
  volume    = {5},
  journal   = {Acta Neuropathologica Communications},
  number    = {11},
  doi       = {10.1186/s40478-017-0416-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159429},
  year      = {2017},
  abstract  = {α-Synuclein is a protein implicated in the etiopathogenesis of Parkinson's disease (PD). AAV1/2-driven overexpression of human mutated A53T-α-synuclein in rat and monkey substantia nigra (SN) induces degeneration of nigral dopaminergic neurons and decreases striatal dopamine and tyrosine hydroxylase (TH). Given certain advantages of the mouse, especially it being amendable to genetic manipulation, translating the AAV1/2-A53T α-synuclein model to mice would be of significant value. AAV1/2-A53T α-synuclein or AAV1/2 empty vector (EV) at a concentration of 5.16 x 10\(^{12}\) gp/ml were unilaterally injected into the right SN of male adult C57BL/6 mice. Post-mortem examinations included immunohistochemistry to analyze nigral α-synuclein, Ser129 phosphorylated α-synuclein and TH expression, striatal dopamine transporter (DAT) levels by autoradiography and dopamine levels by high performance liquid chromatography. At 10 weeks, in AAV1/2-A53T α-synuclein mice there was a 33\% reduction in TH+ dopaminergic nigral neurons (P < 0.001), 29\% deficit in striatal DAT binding (P < 0.05), 38\% and 33\% reductions in dopamine (P < 0.001) and DOPAC (P < 0.01) levels and a 60\% increase in dopamine turnover (homovanilic acid/dopamine ratio; P < 0.001). Immunofluorescence showed that the AAV1/2-A53T α-synuclein injected mice had widespread nigral and striatal expression of vector-delivered A53T-α-synuclein. Concurrent staining with human PD SN samples using gold standard histological methodology for Lewy pathology detection by proteinase K digestion and application of specific antibody raised against human Lewy body α-synuclein (LB509) and Ser129 phosphorylated α-synuclein (81A) revealed insoluble α-synuclein aggregates in AAV1/2-A53T α-synuclein mice resembling Lewy-like neurites and bodies. In the cylinder test, we observed significant paw use asymmetry in the AAV1/2-A53T α-synuclein group when compared to EV controls at 5 and 9 weeks post injection (P < 0.001; P < 0.05). These data show that unilateral injection of AAV1/2-A53T α-synuclein into the mouse SN leads to persistent motor deficits, neurodegeneration of the nigrostriatal dopaminergic system and development of Lewy-like pathology, thereby reflecting clinical and pathological hallmarks of human PD.},
  language  = {en}
}
@article{WilhelmSmetakReimeretal.2016,
  author    = {Wilhelm, M. and Smetak, M. and Reimer, P. and Geissinger, E. and Ruediger, T. and Metzner, B. and Schmitz, N. and Engert, A. and Schaefer-Eckart, K. and Birkmann, J.},
  title     = {First-line therapy of peripheral T-cell lymphoma: extension and long-term follow-up of a study investigating the role of autologous stem cell transplantation},
  series = {Blood Cancer Journal},
  volume    = {6},
  journal   = {Blood Cancer Journal},
  doi       = {10.1038/bcj.2016.63},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164506},
  pages     = {e452},
  year      = {2016},
  abstract  = {Current guidelines recommend consolidation with autologous stem cell transplantation (autoSCT) after induction chemotherapy for most patients with peripheral T-cell lymphoma (PTCL). This assumption is based on five prospective phase II studies, three of which included <50 patients with limited follow-up. Here we present the final analysis of the prospective German study. The treatment regimen consisted of four to six cycles of CHOP chemotherapy followed by mobilizing therapy and stem cell collection. Patients in complete remission (CR) or partial remission (PR) underwent myeloablative chemo(radio)therapy and autoSCT. From January 2001 to July 2010, 111 patients were enrolled in the study. The main subgroups were PTCL not specified (n=42) and angioimmunoblastic T-cell lymphoma (n=37). Seventy-five (68\%) of the 111 patients received transplantation. The main reason for not receiving autoSCT was progressive disease. In an intent-to-treat analysis, the complete response rate after myeloablative therapy was 59\%. The estimated 5-year overall survival, disease-free survival and progression-free survival rates were 44\%, 54\% and 39\%, respectively. The results of this study confirm that upfront autoSCT can result in long-term remissions in patients with all major subtypes of PTCL and therefore should be part of first-line therapy whenever possible.},
  language  = {en}
}
@article{WeigandBoosTasbihietal.2016,
  author    = {Weigand, Annika and Boos, Anja M. and Tasbihi, Kereshmeh and Beier, Justus P. and Dalton, Paul D. and Schrauder, Michael and Horch, Raymund E. and Beckmann, Matthias W. and Strissel, Pamela L. and Strick, Reiner},
  title     = {Selective isolation and characterization of primary cells from normal breast and tumors reveal plasticity of adipose derived stem cells},
  series = {Breast Cancer Research},
  volume    = {18},
  journal   = {Breast Cancer Research},
  number    = {32},
  doi       = {10.1186/s13058-016-0688-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164759},
  year      = {2016},
  abstract  = {Background There is a need to establish more cell lines from breast tumors in contrast to immortalized cell lines from metastatic effusions in order to represent the primary tumor and not principally metastatic biology of breast cancer. This investigation describes the simultaneous isolation, characterization, growth and function of primary mammary epithelial cells (MEC), mesenchymal cells (MES) and adipose derived stem cells (ADSC) from four normal breasts, one inflammatory and one triple-negative ductal breast tumors. Methods A total of 17 cell lines were established and gene expression was analyzed for MEC and MES (n = 42) and ADSC (n = 48) and MUC1, pan-KRT, CD90 and GATA-3 by immunofluorescence. DNA fingerprinting to track cell line identity was performed between original primary tissues and isolates. Functional studies included ADSC differentiation, tumor MES and MEC invasion co-cultured with ADSC-conditioned media (CM) and MES adhesion and growth on 3D-printed scaffolds. Results Comparative analysis showed higher gene expression of EPCAM, CD49f, CDH1 and KRTs for normal MEC lines; MES lines e.g. Vimentin, CD10, ACTA2 and MMP9; and ADSC lines e.g. CD105, CD90, CDH2 and CDH11. Compared to the mean of all four normal breast cell lines, both breast tumor cell lines demonstrated significantly lower ADSC marker gene expression, but higher expression of mesenchymal and invasion gene markers like SNAI1 and MMP2. When compared with four normal ADSC differentiated lineages, both tumor ADSC showed impaired osteogenic and chondrogenic but enhanced adipogenic differentiation and endothelial-like structures, possibly due to high PDGFRB and CD34. Addressing a functional role for overproduction of adipocytes, we initiated 3D-invasion studies including different cell types from the same patient. CM from ADSC differentiating into adipocytes induced tumor MEC 3D-invasion via EMT and amoeboid phenotypes. Normal MES breast cells adhered and proliferated on 3D-printed scaffolds containing 20 fibers, but not on 2.5D-printed scaffolds with single fiber layers, important for tissue engineering. Conclusion Expression analyses confirmed successful simultaneous cell isolations of three different phenotypes from normal and tumor primary breast tissues. Our cell culture studies support that breast-tumor environment differentially regulates tumor ADSC plasticity as well as cell invasion and demonstrates applications for regenerative medicine.},
  language  = {en}
}
@article{WunschZhangHansonetal.2015,
  author    = {Wunsch, Marie and Zhang, Wenji and Hanson, Jodi and Caspell, Richard and Karulin, Alexey Y. and Recks, Mascha S. and Kuerten, Stefanie and Sundararaman, Srividya and Lehmann, Paul V.},
  title     = {Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity},
  series = {Viruses},
  volume    = {7},
  journal   = {Viruses},
  doi       = {10.3390/v7082828},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151462},
  pages     = {4414 -- 4437},
  year      = {2015},
  abstract  = {Most humans become infected with human cytomegalovirus (HCMV). Typically, the immune system controls the infection, but the virus persists and can reactivate in states of immunodeficiency. While substantial information is available on the contribution of CD8 T cells and antibodies to anti-HCMV immunity, studies of the T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 subsets have been limited by the low frequency of HCMV-specific CD4 T cells in peripheral blood mononuclear cell (PBMC). Using the enzyme-linked Immunospot\(^{®}\) assay (ELISPOT) that excels in low frequency measurements, we have established these in a sizable cohort of healthy HCMV controllers. Cytokine recall responses were seen in all seropositive donors. Specifically, interferon (IFN)-\({\gamma}\) and/or interleukin (IL)-17 were seen in isolation or with IL-4 in all test subjects. IL-4 recall did not occur in isolation. While the ratios of T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 cells exhibited substantial variations between different individuals these ratios and the frequencies were relatively stable when tested in samples drawn up to five years apart. IFN-\({\gamma}\) and IL-2 co-expressing polyfunctional cells were seen in most subjects. Around half of the HCMV-specific CD4 cells were in a reversible state of exhaustion. The data provided here established the T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 characteristic of the CD4 cells that convey immune protection for successful immune surveillance against which reactivity can be compared when the immune surveillance of HCMV fails.},
  language  = {en}
}
@article{BiernackaSangkuhlJenkinsetal.2015,
  author    = {Biernacka, J. M. and Sangkuhl, K. and Jenkins, G. and Whaley, R. M. and Barman, P. and Batzler, A. and Altman, R. B. and Arolt, V. and Brockm{\"o}ller, J. and Chen, C. H. and Domschke, K. and Hall-Flavin, D. K. and Hong, C. J. and Illi, A. and Ji, Y. and Kampman, O. and Kinoshita, T. and Leinonen, E. and Liou, Y. J. and Mushiroda, T. and Nonen, S. and Skime, M. K. and Wang, L. and Baune, B. T. and Kato, M. and Liu, Y. L. and Praphanphoj, V. and Stingl, J. C. and Tsai, S. J. and Kubo, M. and Klein, T. E. and Weinshilboum, R.},
  title     = {The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response},
  series = {Translational Psychiatry},
  volume    = {5},
  journal   = {Translational Psychiatry},
  number    = {e553},
  doi       = {10.1038/tp.2015.47},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143223},
  year      = {2015},
  abstract  = {Response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably between patients. The International SSRI Pharmacogenomics Consortium (ISPC) was formed with the primary goal of identifying genetic variation that may contribute to response to SSRI treatment of major depressive disorder. A genome-wide association study of 4-week treatment outcomes, measured using the 17-item Hamilton Rating Scale for Depression (HRSD-17), was performed using data from 865 subjects from seven sites. The primary outcomes were percent change in HRSD-17 score and response, defined as at least 50\% reduction in HRSD-17. Data from two prior studies, the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study (PGRN-AMPS) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, were used for replication, and a meta-analysis of the three studies was performed (N = 2394). Although many top association signals in the ISPC analysis map to interesting candidate genes, none were significant at the genome-wide level and the associations were not replicated using PGRN-AMPS and STAR*D data. Top association results in the meta-analysis of response included single-nucleotide polymorphisms (SNPs) in the HPRTP4 (hypoxanthine phosphoribosyltransferase pseudogene 4)/VSTM5 (V-set and transmembrane domain containing 5) region, which approached genome-wide significance (P = 5.03E - 08) and SNPs 5' upstream of the neuregulin-1 gene, NRG1 (P = 1.20E - 06). NRG1 is involved in many aspects of brain development, including neuronal maturation and variations in this gene have been shown to be associated with increased risk for mental disorders, particularly schizophrenia. Replication and functional studies of these findings are warranted.},
  language  = {en}
}
@article{BoesSpiegelVoepeletal.2015,
  author    = {Boes, Alexander and Spiegel, Holger and Voepel, Nadja and Edgue, Gueven and Beiss, Veronique and Kapelski, Stephanie and Fendel, Rolf and Scheuermayer, Matthias and Pradel, Gabriele and Bolscher, Judith M. and Behet, Marije C. and Dechering, Koen J. and Hermsen, Cornelus C. and Sauerwein, Robert W. and Schillberg, Stefan and Reimann, Andreas and Fischer, Rainer},
  title     = {Analysis of a multi-component multi-stage malaria vaccine candidate—tackling the cocktail challenge},
  series = {PLoS ONE},
  volume    = {10},
  journal   = {PLoS ONE},
  number    = {7},
  doi       = {10.1371/journal.pone.0131456},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173092},
  pages     = {e0131456},
  year      = {2015},
  abstract  = {Combining key antigens from the different stages of the P. falciparum life cycle in the context of a multi-stage-specific cocktail offers a promising approach towards the development of a malaria vaccine ideally capable of preventing initial infection, the clinical manifestation as well as the transmission of the disease. To investigate the potential of such an approach we combined proteins and domains (11 in total) from the pre-erythrocytic, blood and sexual stages of P. falciparum into a cocktail of four different components recombinantly produced in plants. After immunization of rabbits we determined the domain-specific antibody titers as well as component-specific antibody concentrations and correlated them with stage specific in vitro efficacy. Using purified rabbit immune IgG we observed strong inhibition in functional in vitro assays addressing the pre-erythrocytic (up to 80\%), blood (up to 90\%) and sexual parasite stages (100\%). Based on the component-specific antibody concentrations we calculated the IC50 values for the pre-erythrocytic stage (17-25 μg/ml), the blood stage (40-60 μg/ml) and the sexual stage (1.75 μg/ml). While the results underline the feasibility of a multi-stage vaccine cocktail, the analysis of component-specific efficacy indicates significant differences in IC50 requirements for stage-specific antibody concentrations providing valuable insights into this complex scenario and will thereby improve future approaches towards malaria vaccine cocktail development regarding the selection of suitable antigens and the ratios of components, to fine tune overall and stage-specific efficacy.},
  language  = {en}
}
@article{DipaolaPavanCattaneoetal.2016,
  author    = {Dipaola, Mariangela and Pavan, Esteban E. and Cattaneo, Andrea and Frazzitta, Giuseppe and Pezzoli, Gianni and Cavallari, Paolo and Frigo, Carlo A. and Isaias, Ioannis U.},
  title     = {Mechanical Energy Recovery during Walking in Patients with Parkinson Disease},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {6},
  doi       = {10.1371/journal.pone.0156420},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179739},
  year      = {2016},
  abstract  = {The mechanisms of mechanical energy recovery during gait have been thoroughly investigated in healthy subjects, but never described in patients with Parkinson disease (PD). The aim of this study was to investigate whether such mechanisms are preserved in PD patients despite an altered pattern of locomotion. We consecutively enrolled 23 PD patients (mean age 64±9 years) with bilateral symptoms (H\&Y ≥II) if able to walk unassisted in medication-off condition (overnight suspension of all dopaminergic drugs). Ten healthy subjects (mean age 62±3 years) walked both at their 'preferred' and 'slow' speeds, to match the whole range of PD velocities. Kinematic data were recorded by means of an optoelectronic motion analyzer. For each stride we computed spatio-temporal parameters, time-course and range of motion (ROM) of hip, knee and ankle joint angles. We also measured kinetic (Wk), potential (W\(_{p}\)), total (W\(_{totCM}\)) energy variations and the energy recovery index (ER). Along with PD progression, we found a significant correlation of W\(_{totCM}\) and W\(_{p}\) with knee ROM and in particular with knee extension in terminal stance phase. W\(_{k}\) and ER were instead mainly related to gait velocity. In PD subjects, the reduction of knee ROM significantly diminished both W\(_{p}\) and W\(_{totCM}\). Rehabilitation treatments should possibly integrate passive and active mobilization of knee to prevent a reduction of gait-related energetic components.},
  language  = {en}
}
@article{KredelKunzmannSchlegeletal.2017,
  author    = {Kredel, Markus and Kunzmann, Steffen and Schlegel, Paul-Gerhardt and W{\"o}lfl, Matthias and Nordbeck, Peter and B{\"u}hler, Christoph and Lotz, Christopher and Lepper, Philipp M. and Wirbelauer, Johannes and Roewer, Norbert and Muellenbach, Ralf M.},
  title     = {Double Peripheral Venous and Arterial Cannulation for Extracorporeal Membrane Oxygenation in Combined Septic and Cardiogenic Shock},
  series = {American Journal of Case Reports},
  volume    = {18},
  journal   = {American Journal of Case Reports},
  doi       = {10.12659/AJCR.902485},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158193},
  pages     = {723-727},
  year      = {2017},
  abstract  = {Background: The use of venoarterial extracorporeal membrane oxygenation (va-ECMO) via peripheral cannulation for septic shock is limited by blood flow and increased afterload for the left ventricle. Case Report: A 15-year-old girl with acute myelogenous leukemia, suffering from severe septic and cardiogenic shock, was treated by venoarterial extracorporeal membrane oxygenation (va-ECMO). Sufficient extracorporeal blood flow matching the required oxygen demand could only be achieved by peripheral cannulation of both femoral arteries. Venous drainage was performed with a bicaval cannula inserted via the left V. femoralis. To accomplish left ventricular unloading, an additional drainage cannula was placed in the left atrium via percutaneous atrioseptostomy (va-va-ECMO). Cardiac function recovered and the girl was weaned from the ECMO on day 6. Successful allogenic stem cell transplantation took place 2 months later. Conclusions: In patients with vasoplegic septic shock and impaired cardiac contractility, double peripheral venoarterial extracorporeal membrane oxygenation (va-va-ECMO) with transseptal left atrial venting can by a lifesaving option.},
  language  = {en}
}
@article{BaurBuentemeyerMegerleetal.2017,
  author    = {Baur, Johannes and B{\"u}ntemeyer, Tjark-Ole and Megerle, Felix and Deutschbein, Timo and Spitzweg, Christine and Quinkler, Marcus and Nawroth, Peter and Kroiss, Matthias and Germer, Christoph-Thomas and Fassnacht, Martin and Steger, Ulrich},
  title     = {Outcome after resection of Adrenocortical Carcinoma liver metastases: a retrospective study},
  series = {BMC Cancer},
  volume    = {17},
  journal   = {BMC Cancer},
  number    = {522},
  doi       = {10.1186/s12885-017-3506-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159409},
  year      = {2017},
  abstract  = {Background: Metastatic Adrenocortical Carcinoma (ACC) is a rare malignancy with a poor 5-year-survival rate (<15\%). A surgical approach is recommended in selected patients if complete resection of distant metastasis can be achieved. To date there are only limited data on the outcome after surgical resection of hepatic metastases of ACC. Methods: A retrospective analysis of the German Adrenocortical Carcinoma Registry was conducted. Patients with liver metastases of ACC but without extrahepatic metastases or incomplete tumour resection were included. Results: Seventy-seven patients fulfilled these criteria. Forty-three patients underwent resection of liver metastases of ACC. Complete tumour resection (R0) could be achieved in 30 (69.8\%). Median overall survival after liver resection was 76.1 months in comparison to 10.1 months in the 34 remaining patients with unresected liver metastases (p < 0.001). However, disease free survival after liver resection was only 9.1 months. Neither resection status (R0/R1) nor extent of liver resection were significant predictive factors for overall survival. Patients with a time interval to the first metastasis/recurrence (TTFR) of greater than 12 months or solitary liver metastases showed significantly prolonged survival. Conclusions: Liver resection in the case of ACC liver metastases can achieve long term survival with a median overall survival of more than 5 years, but disease free survival is short despite metastasectomy. Time to recurrence and single versus multiple metastases are predictive factors for the outcome.},
  language  = {en}
}
@article{WagnerWannerSchichetal.2017,
  author    = {Wagner, Martin and Wanner, Christoph and Schich, Martin and Kotseva, Kornelia and Wood, David and Hartmann, Katrin and Fette, Georg and R{\"u}cker, Viktoria and Oezkur, Mehmet and St{\"o}rk, Stefan and Heuschmann, Peter U.},
  title     = {Patient's and physician's awareness of kidney disease in coronary heart disease patients - a cross-sectional analysis of the German subset of the EUROASPIRE IV survey},
  series = {BMC Nephrology},
  volume    = {18},
  journal   = {BMC Nephrology},
  number    = {321},
  doi       = {10.1186/s12882-017-0730-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158387},
  year      = {2017},
  abstract  = {Background Chronic kidney disease (CKD) is a common comorbid condition in coronary heart disease (CHD). CKD predisposes the patient to acute kidney injury (AKI) during hospitalization. Data on awareness of kidney dysfunction among CHD patients and their treating physicians are lacking. In the current cross-sectional analysis of the German EUROASPIRE IV sample we aimed to investigate the physician's awareness of kidney disease of patients hospitalized for CHD and also the patient's awareness of CKD in a study visit following hospital discharge. Methods All serum creatinine (SCr) values measured during the hospital stay were used to describe impaired kidney function (eGFR\(_{CKD-EPI}\) < 60 ml/min/1.73m2) at admission, discharge and episodes of AKI (KDIGO definition). Information extracted from hospital discharge letters and correct ICD coding for kidney disease was studied as a surrogate of physician's awareness of kidney disease. All patients were interrogated 0.5 to 3 years after hospital discharge, whether they had ever been told about kidney disease by a physician. Results Of the 536 patients, 32\% had evidence for acute or chronic kidney disease during the index hospital stay. Either condition was mentioned in the discharge letter in 22\%, and 72\% were correctly coded according to ICD-10. At the study visit in the outpatient setting 35\% had impaired kidney function. Of 158 patients with kidney disease, 54 (34\%) were aware of CKD. Determinants of patient's awareness were severity of CKD (OR\(_{eGFR}\) 0.94; 95\%CI 0.92-0.96), obesity (OR 1.97; 1.07-3.64), history of heart failure (OR 1.99; 1.00-3.97), and mentioning of kidney disease in the index event's hospital discharge letter (OR 5.51; 2.35-12.9). Conclusions Although CKD is frequent in CHD, only one third of patients is aware of this condition. Patient's awareness was associated with kidney disease being mentioned in the hospital discharge letter. Future studies should examine how raising physician's awareness for kidney dysfunction may improve patient's awareness of CKD.},
  language  = {en}
}
@article{LotzSchmidRossietal.2016,
  author    = {Lotz, Christian and Schmid, Freia F. and Rossi, Angela and Kurdyn, Szymon and Kampik, Daniel and De Wever, Bart and Walles, Heike and Groeber, Florian K.},
  title     = {Alternative Methods for the Replacement of Eye Irritation Testing},
  series = {ALTEX - Alternatives to Animal Experimentation},
  volume    = {33},
  journal   = {ALTEX - Alternatives to Animal Experimentation},
  number    = {1},
  doi       = {10.14573/altex.1508241},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164444},
  pages     = {55-67},
  year      = {2016},
  abstract  = {In the last decades significant regulatory attempts were made to replace, refine and reduce animal testing to assess the risk of consumer products for the human eye. As the original in vivo Draize eye test is criticized for limited predictivity, costs and ethical issues, several animal-free test methods have been developed to categorize substances according to the global harmonized system (GHS) for eye irritation. This review summarizes the progress of alternative test methods for the assessment of eye irritation. Based on the corneal anatomy and current knowledge of the mechanisms causing eye irritation, different ex vivo and in vitro methods will be presented and discussed with regard to possible limitations and status of regulatory acceptance. In addition to established in vitro models, this review will also highlight emerging, full thickness cornea models that might be suited to predict all GHS categories.},
  language  = {en}
}
@article{HillmannWiedmannRueckeretal.2017,
  author    = {Hillmann, Steffi and Wiedmann, Silke and R{\"u}cker, Viktoria and Berger, Klaus and Nabavi, Darius and Bruder, Ingo and Koennecke, Hans-Christian and Seidel, G{\"u}nter and Misselwitz, Bj{\"o}rn and Janssen, Alfred and Burmeister, Christoph and Matthis, Christine and Busse, Otto and Hermanek, Peter and Heuschmann, Peter Ulrich},
  title     = {Stroke unit care in Germany: the German stroke registers study group (ADSR)},
  series = {BMC Neurology},
  volume    = {17},
  journal   = {BMC Neurology},
  number    = {49},
  doi       = {10.1186/s12883-017-0819-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159447},
  year      = {2017},
  abstract  = {Background: Factors influencing access to stroke unit (SU) care and data on quality of SU care in Germany are scarce. We investigated characteristics of patients directly admitted to a SU as well as patient-related and structural factors influencing adherence to predefined indicators of quality of acute stroke care across hospitals providing SU care. Methods: Data were derived from the German Stroke Registers Study Group (ADSR), a voluntary network of 9 regional registers for monitoring quality of acute stroke care in Germany. Multivariable logistic regression analyses were performed to investigate characteristics influencing direct admission to SU. Generalized Linear Mixed Models (GLMM) were used to estimate the influence of structural hospital characteristics (percentage of patients admitted to SU, year of SU-certification, and number of stroke and TIA patients treated per year) on adherence to predefined quality indicators. Results: In 2012 180,887 patients were treated in 255 hospitals providing certified SU care participating within the ADSR were included in the analysis; of those 82.4\% were directly admitted to a SU. Ischemic stroke patients without disturbances of consciousness (p < .0001), an interval onset to admission time ≤3 h (p < .0001), and weekend admission (p < .0001) were more likely to be directly admitted to a SU. A higher proportion of quality indicators within predefined target ranges were achieved in hospitals with a higher proportion of SU admission (p = 0.0002). Quality of stroke care could be maintained even if certification was several years ago. Conclusions: Differences in demographical and clinical characteristics regarding the probability of SU admission were observed. The influence of structural characteristics on adherence to evidence-based quality indicators was low.},
  language  = {en}
}
@article{LillaFuellgrafStetteretal.2017,
  author    = {Lilla, Nadine and F{\"u}llgraf, Hannah and Stetter, Christian and K{\"o}hler, Stefan and Ernestus, Ralf-Ingo and Westermaier, Thomas},
  title     = {First Description of Reduced Pyruvate Dehydrogenase Enzyme Activity Following Subarachnoid Hemorrhage (SAH)},
  series = {Frontiers in Neuroscience},
  volume    = {11},
  journal   = {Frontiers in Neuroscience},
  number    = {37},
  doi       = {10.3389/fnins.2017.00037},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157636},
  year      = {2017},
  abstract  = {Object: Several previous studies reported metabolic derangements and an accumulation of metabolic products in the early phase of experimental subarachnoid hemorrhage (SAH), which may contribute to secondary brain damage. This may be a result of deranged oxygen utilization due to enzymatic dysfunction in aerobic glucose metabolism. This study was performed to investigate, if pyruvate dehydrogenase enzyme (PDH) is affected in its activity giving further hints for a derangement of oxidative metabolism. Methods: Eighteen male Sprague-Dawley rats were randomly assigned to one of two experimental groups (n = 9): (1) SAH induced by the endovascular filament model and (2) sham-operated controls. Mean arterial blood pressure (MABP), intracranial pressure (ICP), and local cerebral blood flow (LCBF; laser-Doppler flowmetry) were continuously monitored from 30 min before until 3 h after SAH. Thereafter, the animals were sacrificed and PDH activity was measured by ELISA. Results: PDH activity was significantly reduced in animals subjected to SAH compared to controls. Conclusion: The results of this study demonstrate for the first time a reduction of PDH activity following SAH, independent of supply of substrates and may be an independent factor contributing to a derangement of oxidative metabolism, failure of oxygen utilization, and secondary brain damage.},
  language  = {en}
}
@article{WollbornWunderStixetal.2015,
  author    = {Wollborn, Jakob and Wunder, Christian and Stix, Jana and Neuhaus, Winfried and Bruno, Rapahel R. and Baar, Wolfgang and Flemming, Sven and Roewer, Norbert and Schlegel, Nicolas and Schick, Martin A.},
  title     = {Phosphodiesterase-4 inhibition with rolipram attenuates hepatocellular injury in hyperinflammation in vivo and in vitro without influencing inflammation and HO-1 expression},
  series = {Journal of Pharmacology and Pharmacotherapeutics},
  volume    = {6},
  journal   = {Journal of Pharmacology and Pharmacotherapeutics},
  number    = {1},
  doi       = {10.4103/0976-500X.149138},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149336},
  pages     = {13-23},
  year      = {2015},
  abstract  = {Objective: To investigate the impact of the phophodiesterase-4 inhibition (PD-4-I) with rolipram on hepatic integrity in lipopolysaccharide (LPS) induced hyperinflammation. Materials and Methods: Liver microcirculation in rats was obtained using intravital microscopy. Macrohemodynamic parameters, blood assays, and organs were harvested to determine organ function and injury. Hyperinflammation was induced by LPS and PD-4-I rolipram was administered intravenously one hour after LPS application. Cell viability of HepG2 cells was measured by EZ4U-kit based on the dye XTT. Experiments were carried out assessing the influence of different concentrations of tumor necrosis factor alpha (TNF-α) and LPS with or without PD-4-I. Results: Untreated LPS-induced rats showed significantly decreased liver microcirculation and increased hepatic cell death, whereas LPS + PD-4-I treatment could improve hepatic volumetric flow and cell death to control level whithout influencing the inflammatory impact. In HepG2 cells TNF-α and LPS significantly reduced cell viability. Coincubation with PD-4-I increased HepG2 viability to control levels. The heme oxygenase 1 (HO-1) pathway did not induce the protective effect of PD-4-I. Conclusion: Intravenous PD-4-I treatment was effective in improving hepatic microcirculation and hepatic integrity, while it had a direct protective effect on HepG2 viability during inflammation.},
  language  = {en}
}
@article{HagemannStrengKraemeretal.2017,
  author    = {Hagemann, Christine and Streng, Andrea and Kraemer, Alexander and Liese, Johannes G.},
  title     = {Heterogeneity in coverage for measles and varicella vaccination in toddlers - analysis of factors influencing parental acceptance},
  series = {BMC Public Health},
  volume    = {17},
  journal   = {BMC Public Health},
  number    = {724},
  doi       = {10.1186/s12889-017-4725-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157827},
  year      = {2017},
  abstract  = {Background: In 2004, routine varicella vaccination was introduced in Germany for children aged 11-14 months. Routine measles vaccination had already been introduced in 1973 for the same age group, but coverage is still too low (<95\%) in some areas to eliminate measles. The present study assessed varicella and measles vaccination coverage and determinants of parental acceptance in two study regions, situated in Northern and Southern Bavaria (Germany). Methods: From 2009 to 2011, annual cross-sectional parent surveys were performed on random samples of 600 children aged 18-36 months in the Bavarian regions of both Munich and W{\"u}rzburg. Logistic regression models were used to identify factors associated with varicella and measles vaccination. Results: In 2009, 2010 and 2011, vaccination coverage was lower in Munich than in W{\"u}rzburg, for both varicella (Munich 53\%, 67\%, 69\% vs. W{\"u}rzburg 72\%, 81\%, 83\%) and for measles (Munich 88\%, 89\%, 91\% vs. W{\"u}rzburg 92\%, 93\%, 95\%). Recommendation by the physician was the main independent factor associated with varicella vaccination in both regions (adjusted odd ratios (OR) with 95\% confidence interval (CI): Munich OR 19.7, CI 13.6-28.6; W{\"u}rzburg OR 34.7, CI 22.6-53.2). Attendance at a childcare unit was positively associated with a higher acceptance of varicella vaccination in Munich (OR 1.5, CI 1.1-2.2). Regarding measles vaccination, attendance at a childcare unit was positively associated in both regions (Munich OR 2.0; CI 1.3-3.0; W{\"u}rzburg OR 1.8; CI 1.1-3.1), and a higher level of parental school education was negatively associated in W{\"u}rzburg (OR 0.5, CI 0.3-0.9). Conclusions: Vaccination rates differed between regions, with rates constantly higher in W{\"u}rzburg. Within each region, vaccination rates were lower for varicella than for measles. Measles vaccination status was mainly dependent upon socio-demographic factors (attendance at a childcare unit, parental school education), whereas for the more recently introduced varicella vaccination recommendation by the physician had the strongest impact. Hence, different strategies are needed to further improve vaccination rates for both diseases.},
  language  = {en}
}