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468 Publications visible to you, out of a total of 468
In-vivo Dynamics of the Human Hippocampus across the Menstrual Cycle.
LIFE Adult

Abstract (Expand)

Sex hormones fluctuate during the menstrual cycle. Evidence from animal studies suggests similar subtle fluctuations in hippocampal structure, predominantly linked to estrogen. Hippocampal abnormalities … have been observed in several neuropsychiatric pathologies with prominent sexual dimorphism. Yet, the potential impact of subtle sex-hormonal fluctuations on human hippocampal structure in health is unclear. We tested the feasibility of longitudinal neuroimaging in conjunction with rigorous menstrual cycle monitoring to evaluate potential changes in hippocampal microstructure associated with physiological sex-hormonal changes. Thirty longitudinal diffusion weighted imaging scans of a single healthy female subject were acquired across two full menstrual cycles. We calculated hippocampal fractional anisotropy (FA), a measure sensitive to changes in microstructural integrity, and investigated potential correlations with estrogen. We observed a significant positive correlation between FA values and estrogen in the hippocampus bilaterally, revealing a peak in FA closely paralleling ovulation. This exploratory, single-subject study demonstrates the feasibility of a longitudinal DWI scanning protocol across the menstrual cycle and is the first to link subtle endogenous hormonal fluctuations to changes in FA in vivo. In light of recent attempts to neurally phenotype single humans, our findings highlight menstrual cycle monitoring in parallel with highly sampled individual neuroimaging data to address fundamental questions about the dynamics of plasticity in the adult brain.

Authors: C. Barth, C. J. Steele, K. Mueller, V. P. Rekkas, K. Arelin, A. Pampel, I. Burmann, J. Kratzsch, A. Villringer, J. Sacher

Date Published: 7th Oct 2016

Publication Type: Not specified

Incidence of severe sepsis and septic shock in German intensive care units: the prospective, multicentre INSEP study.
SepNet - German Competence Network Sepsis

Abstract (Expand)

PURPOSE: To estimate the incidence density, point prevalence and outcome of severe sepsis and septic shock in German intensive care units (ICUs). METHODS: In a prospective, multicentre, longitudinal … observational study, all patients already on the ICU at 0:00 on 4 November 2013 and all patients admitted to a participating ICU between 0:00 on 4 November 2013 and 2359 hours on 1 December 2013 were included. The patients were followed up for the occurrence of severe sepsis or septic shock (SEPSIS-1 definitions) during their ICU stay. RESULTS: A total of 11,883 patients from 133 ICUs at 95 German hospitals were included in the study, of whom 1503 (12.6 %) were diagnosed with severe sepsis or septic shock. In 860 cases (57.2 %) the infections were of nosocomial origin. The point prevalence was 17.9 % (95 % CI 16.3-19.7).The calculated incidence rate of severe sepsis or septic shock was 11.64 (95 % CI 10.51-12.86) per 1000 ICU days. ICU mortality in patients with severe sepsis/septic shock was 34.3 %, compared with 6 % in those without sepsis. Total hospital mortality of patients with severe sepsis or septic shock was 40.4 %. Classification of the septic shock patients using the new SEPSIS-3 definitions showed higher ICU and hospital mortality (44.3 and 50.9 %). CONCLUSIONS: Severe sepsis and septic shock continue to be a frequent syndrome associated with high hospital mortality. Nosocomial infections play a major role in the development of sepsis. This study presents a pragmatic, affordable and feasible method for the surveillance of sepsis epidemiology. Implementation of the new SEPSIS-3 definitions may have a major effect on future epidemiological data.

Editor:

Date Published: 1st Oct 2016

Publication Type: Journal article

Human Diseases: disease by infectious agent

CNS International Prognostic Index: A Risk Model for CNS Relapse in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP.
GLA - German Lymphoma Alliance

Abstract (Expand)

PURPOSE: To develop and validate a risk score for relapse in the CNS in patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: A total of 2,164 patients (18 to 80 years old) with … aggressive B-cell lymphomas (80% DLBCL) treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like chemotherapy, who were enrolled in studies from the German High-Grade Non-Hodgkin Lymphoma Study Group and the MabThera International Trial, were analyzed for occurrence of relapse/progression in the CNS. The resulting risk model was validated in an independent data set of 1,597 patients with DLBCL identified in the British Columbia Cancer Agency Lymphoid Cancer database. RESULTS: The risk model consists of the International Prognostic Index (IPI) factors in addition to involvement of kidneys and/or adrenal glands (CNS-IPI). In a three-risk group model, the low-risk group (46% of all patients analyzed), the intermediate-risk group (41%), and the high-risk group (12%) showed 2-year rates of CNS disease of 0.6% (CI, 0% to 1.2%), 3.4% (CI, 2.2% to 4.4%), and 10.2% (CI, 6.3% to 14.1%), respectively. Patients from the validation British Columbia Cancer Agency data set showed similar rates of CNS disease for low-risk (0.8%; CI, 0.0% to 1.6%), intermediate-risk (3.9%; CI, 2.3% to 5.5%), and high-risk (12.0%; CI, 7.9% to 16.1%) groups. CONCLUSION: The CNS-IPI is a robust, highly reproducible tool that can be used to estimate the risk of CNS relapse/progression in patients with DLBCL treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Close to 90% of patients with DLBCL belong to the low- and intermediate-risk groups and have a CNS relapse risk < 5%; they may be spared any diagnostic and therapeutic intervention. In contrast, those in the high-risk group have a > 10% risk of CNS relapse and should be considered for CNS-directed investigations and prophylactic interventions.

Authors: N. Schmitz, S. Zeynalova, M. Nickelsen, R. Kansara, D. Villa, L. H. Sehn, B. Glass, D. W. Scott, R. D. Gascoyne, J. M. Connors, M. Ziepert, M. Pfreundschuh, M. Loeffler, K. J. Savage

Date Published: 10th Sep 2016

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

THE COGNITIVE FUNCTIONING OF SOCIALLY ISOLATED INDIVIDUALS MAY PROFIT FROM HIGH MENTAL WORK DEMANDS
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Background: Previous studies have shown that individuals with poor social relationships have an increased risk for dementia. Dementia risk, however, can also be positively influenced by lifestyle factors … such as high mental demands at work (in particular as the work environment affects a very long lifetime period). Thus, our objective was to investigate whether the cognitive functioning of socially isolated individuals may profit from high mental work demands. Methods: Analyses were based on n=10,000 participants (aged 40-80 years) of the population-based German LIFE-Adult-Study. All participants underwent medical examinations and filled out standardized questionnaires. Cognitive functioning was assessed via the Verbal Fluency Test (VFT) and the Trail-Making Test (TMT). Social relationships were assessed via the Lubben Social Network Scale (LSNS-6). Results: The difference in cognitive func- tioning between high and low mental work demand conditions was larger in socially isolated individuals (VFT: 2.7 words, TMT-B: 26 seconds) compared to socially well integrated individuals (VFT: 2.1 words, TMT-B: 9 seconds). Multivariate regression analyses – adjusted for age, gender, and education – indicated that both mental work demands as well as social relationships are significantly asso- ciated with the level of cognitive functioning

Authors: F. S. Then, M. L. Schroeter, A. V. Witte, Christoph Engel, Markus Löffler, J. Thiery, A. Villringer, T. Luck, S. G. Riedel-Heller

Date Published: 1st Sep 2016

Publication Type: Not specified

Human Diseases: cognitive disorder

Response to the letter on 'Validating new diagnostic imaging criteria for primary progressive aphasia via anatomical likelihood estimation meta-analyses'.
LIFE Adult

Abstract

Not specified

Authors: S. Bisenius, J. Neumann, M. L. Schroeter

Date Published: 20th Jul 2016

Publication Type: Not specified

Human Diseases: dementia, aphasia

USP9X stabilizes XIAP to regulate mitotic cell death and chemoresistance in aggressive B-cell lymphoma.
GLA - German Lymphoma Alliance

Abstract (Expand)

The mitotic spindle assembly checkpoint (SAC) maintains genome stability and marks an important target for antineoplastic therapies. However, it has remained unclear how cells execute cell fate decisions … under conditions of SAC-induced mitotic arrest. Here, we identify USP9X as the mitotic deubiquitinase of the X-linked inhibitor of apoptosis protein (XIAP) and demonstrate that deubiquitylation and stabilization of XIAP by USP9X lead to increased resistance toward mitotic spindle poisons. We find that primary human aggressive B-cell lymphoma samples exhibit high USP9X expression that correlate with XIAP overexpression. We show that high USP9X/XIAP expression is associated with shorter event-free survival in patients treated with spindle poison-containing chemotherapy. Accordingly, aggressive B-cell lymphoma lines with USP9X and associated XIAP overexpression exhibit increased chemoresistance, reversed by specific inhibition of either USP9X or XIAP. Moreover, knockdown of USP9X or XIAP significantly delays lymphoma development and increases sensitivity to spindle poisons in a murine Emu-Myc lymphoma model. Together, we specify the USP9X-XIAP axis as a regulator of the mitotic cell fate decision and propose that USP9X and XIAP are potential prognostic biomarkers and therapeutic targets in aggressive B-cell lymphoma.

Authors: K. Engel, M. Rudelius, J. Slawska, L. Jacobs, B. Ahangarian Abhari, B. Altmann, J. Kurutz, A. Rathakrishnan, V. Fernandez-Saiz, A. Brunner, B. S. Targosz, F. Loewecke, C. J. Gloeckner, M. Ueffing, S. Fulda, M. Pfreundschuh, L. Trumper, W. Klapper, U. Keller, P. J. Jost, A. Rosenwald, C. Peschel, F. Bassermann

Date Published: 19th Jun 2016

Publication Type: Not specified

Human Diseases: B-cell lymphoma

Limited role for transforming growth factor-beta pathway activation-mediated escape from VEGF inhibition in murine glioma models.
GGN - German Glioma Network

Abstract (Expand)

BACKGROUND: The vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta pathways regulate key biological features of glioblastoma. Here we explore whether the TGF-beta … pathway, which promotes angiogenesis, invasiveness, and immunosuppression, acts as an escape pathway from VEGF inhibition. METHODS: The role of the TGF-beta pathway in escape from VEGF inhibition was assessed in vitro and in vivo and by gene expression profiling in syngeneic mouse glioma models. RESULTS: We found that TGF-beta is an upstream regulator of VEGF, whereas VEGF pathway activity does not alter the TGF-beta pathway in vitro. In vivo, single-agent activity was observed for the VEGF antibody B20-4.1.1 in 3 and for the TGF-beta receptor 1 antagonist LY2157299 in 2 of 4 models. Reduction of tumor volume and blood vessel density, but not induction of hypoxia, correlated with benefit from B20-4.1.1. Reduction of phosphorylated (p)SMAD2 by LY2157299 was seen in all models but did not predict survival. Resistance to B20 was associated with anti-angiogenesis escape pathway gene expression, whereas resistance to LY2157299 was associated with different immune response gene signatures in SMA-497 and GL-261 on transcriptomic profiling. The combination of B20 with LY2157299 was ineffective in SMA-497 but provided prolongation of survival in GL-261, associated with early suppression of pSMAD2 in tumor and host immune cells, prolonged suppression of angiogenesis, and delayed accumulation of tumor infiltrating microglia/macrophages. CONCLUSIONS: Our study highlights the biological heterogeneity of murine glioma models and illustrates that cotargeting of the VEGF and TGF-beta pathways might lead to improved tumor control only in subsets of glioblastoma.

Authors: D. Mangani, M. Weller, E. Seyed Sadr, E. Willscher, K. Seystahl, G. Reifenberger, G. Tabatabai, H. Binder, H. Schneider

Date Published: 12th Jun 2016

Publication Type: Not specified

Human Diseases: glioblastoma multiforme

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