TY - JOUR A1 - Gilbert, Fabian A1 - Klein, Detlef A1 - Weng, Andreas Max A1 - Köstler, Herbert A1 - Schmitz, Benedikt A1 - Schmalzl, Jonas A1 - Böhm, Dirk T1 - Supraspinatus muscle elasticity measured with real time shear wave ultrasound elastography correlates with MRI spectroscopic measured amount of fatty degeneration JF - BMC Muscoskeletal Disorders N2 - Background: Fatty Degeneration (FD) of the rotator cuff muscles influences functional and anatomical outcome after rotator cuff repair. The MRI based estimation of fatty degeneration is the gold standard. There is some evidence that Ultrasound elastography (EUS) can detect local differences of tissue stiffness in muscles and tendons. Shear-wave elastography (SWE) was evaluated to determine the extent to which shear wave velocity was associated with measures of fatty degeneration. MRI-spectroscopic fat measurement was used as a reference to quantify the amount of fat in the muscle belly. Methods: Forty-two patients underwent SWE of the supraspinatus muscles at its thickest diameter. After ultrasound evaluation an MRI-spectroscopic fat measurement of the supraspinatus muscle was performed using the SPLASH-technique. A gel filled capsule was used to locate the measured area in the MRI. The values of shear wave velocity (SWV) measured with SWE and spectroscopic fat measurement were correlated statistically using Pearson’s correlation test. Results: Correlation of the fat amount measured with MRI-spectroscopy and the SWV measured with SWE was ρ =0.82. Spectroscopic measured fat ratio of the supraspinatus muscle ranged from 0% to 77.41% and SWV from 1.59 m/s to 5.32 m/s. In 4 patients no sufficient SWE could be performed, these individuals showed a larger diameter of the overlying soft tissue. SWV measured with SWE showed a good correlation with MRI spectroscopic fat amount of the supraspinatus muscle. Conclusion: These preliminary data suggest that SWE may be a sufficient tool in detecting and estimating the amount of fatty degeneration in the supraspinatus muscle in real time. Large overlying soft tissue may be a limitation in performing sufficient EUS. KW - shoulder surgery KW - rotator cuff KW - MRI KW - ultrasound KW - fatty degeneration Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159378 VL - 18 IS - 549 ER - TY - JOUR A1 - Gil-Pulido, Jesus A1 - Cochain, Clement A1 - Lippert, Malte A. A1 - Schneider, Nicole A1 - Butt, Elke A1 - Amézaga, Núria A1 - Zernecke, Alma T1 - Deletion of Batf3-dependent antigen-presenting cells does not affect atherosclerotic lesion formation in mice JF - PLoS ONE N2 - Atherosclerosis is the main underlying cause for cardiovascular events such as myocardial infarction and stroke and its development might be influenced by immune cells. Dendritic cells (DCs) bridge innate and adaptive immune responses by presenting antigens to T cells and releasing a variety of cytokines. Several subsets of DCs can be discriminated that engage specific transcriptional pathways for their development. Basic leucine zipper transcription factor ATF-like 3 (Batf3) is required for the development of classical CD8α\(^{+}\) and CD103\(^{+}\) DCs. By crossing mice deficient in Batf3 with atherosclerosis-prone low density lipoprotein receptor (Ldlr\(^{−/-}\))-deficient mice we here aimed to further address the contribution of Batf3-dependent CD8α\(^{+}\) and CD103\(^{+}\) antigen-presenting cells to atherosclerosis. We demonstrate that deficiency in Batf3 entailed mild effects on the immune response in the spleen but did not alter atherosclerotic lesion formation in the aorta or aortic root, nor affected plaque phenotype in low density lipoprotein receptor-deficient mice fed a high fat diet. We thus provide evidence that Batf3-dependent antigen-presenting cells do not have a prominent role in atherosclerosis. KW - atherosclerosis KW - dendritic cells KW - Batf3 KW - deficiency Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170535 VL - 12 IS - 8 ER - TY - JOUR A1 - Giampaolo, Sabrina A1 - Wójcik, Gabriela A1 - Serfling, Edgar A1 - Patra, Amiya K. T1 - Interleukin-2-regulatory T cell axis critically regulates maintenance of hematopoietic stem cells JF - Oncotarget N2 - The role of IL-2 in HSC maintenance is unknown. Here we show that Il2\(^{−/-}\) mice develop severe anomalies in HSC maintenance leading to defective hematopoiesis. Whereas, lack of IL-2 signaling was detrimental for lympho- and erythropoiesis, myelopoiesis was enhanced in Il2\(^{−/-}\) mice. Investigation of the underlying mechanisms of dysregulated hematopoiesis in Il2\(^{−/-}\) mice shows that the IL-2-T\(_{reg}\) cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of T\(_{reg}\) activity resulted in increased IFN-γ production by activated T cells and an expansion of the HSCs in the bone marrow (BM). Though, restoring T\(_{reg}\) population successfully rescued HSC maintenance in Il2\(^{-/-}\) mice, preventing IFN-γ activity could do the same even in the absence of T\(_{reg}\) cells. Our study suggests that equilibrium in IL-2 and IFN-γ activity is critical for steady state hematopoiesis, and in clinical conditions of BM failure, IL-2 or anti-IFN-γ treatment might help to restore hematopoiesis. KW - immunity KW - hematopoietic stem cells KW - IL-2 KW - treg cells KW - IL-10 KW - IFN-γ KW - immunology and microbiology section KW - immune response Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170947 VL - 8 IS - 18 ER - TY - JOUR A1 - Ghosh, Sujal A1 - Hönscheid, Andrea A1 - Dückers, Gregor A1 - Ginzel, Sebastian A1 - Gohlke, Holger A1 - Gombert, Michael A1 - Kempkes, Bettina A1 - Klapper, Wolfram A1 - Kuhlen, Michaela A1 - Laws, Hans-Jürgen A1 - Linka, René Martin A1 - Meisel, Roland A1 - Mielke, Christian A1 - Niehues, Tim A1 - Schindler, Detlev A1 - Schneider, Dominik A1 - Schuster, Friedhelm R. A1 - Speckmann, Carsten A1 - Borkhardt, Arndt T1 - Human RAD52 - a novel player in DNA repair in cancer and immunodeficiency JF - Haematologica N2 - No abstract available. KW - human medicine KW - DNA-Repair KW - cancer KW - immunodeficiency KW - RAD52 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180862 VL - 102 IS - 2 ER - TY - JOUR A1 - Genheimer, Hannah A1 - Andreatta, Marta A1 - Asan, Esther A1 - Pauli, Paul T1 - Reinstatement of contextual conditioned anxiety in virtual reality and the effects of transcutaneous vagus nerve stimulation in humans JF - Scientific Reports N2 - Since exposure therapy for anxiety disorders incorporates extinction of contextual anxiety, relapses may be due to reinstatement processes. Animal research demonstrated more stable extinction memory and less anxiety relapse due to vagus nerve stimulation (VNS). We report a valid human three-day context conditioning, extinction and return of anxiety protocol, which we used to examine effects of transcutaneous VNS (tVNS). Seventy-five healthy participants received electric stimuli (unconditioned stimuli, US) during acquisition (Day1) when guided through one virtual office (anxiety context, CTX+) but never in another (safety context, CTX−). During extinction (Day2), participants received tVNS, sham, or no stimulation and revisited both contexts without US delivery. On Day3, participants received three USs for reinstatement followed by a test phase. Successful acquisition, i.e. startle potentiation, lower valence, higher arousal, anxiety and contingency ratings in CTX+ versus CTX−, the disappearance of these effects during extinction, and successful reinstatement indicate validity of this paradigm. Interestingly, we found generalized reinstatement in startle responses and differential reinstatement in valence ratings. Altogether, our protocol serves as valid conditioning paradigm. Reinstatement effects indicate different anxiety networks underlying physiological versus verbal responses. However, tVNS did neither affect extinction nor reinstatement, which asks for validation and improvement of the stimulation protocol. KW - psychology KW - vagus nerve stimulation KW - contextual anxiety KW - fear conditioning KW - extinction Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169892 VL - 7 IS - 17886 ER - TY - JOUR A1 - Geiger, Julia A1 - Hirtler, Daniel A1 - Gottfried, Kristina A1 - Rahman, Ozair A1 - Bollache, Emilie A1 - Barker, Alex J. A1 - Markl, Michael A1 - Stiller, Brigitte T1 - Longitudinal Evaluation of Aortic Hemodynamics in Marfan Syndrome: New Insights from a 4D Flow Cardiovascular Magnetic Resonance Multi-Year Follow-Up Study JF - Journal of Cardiovascular Magnetic Resonance N2 - Background The aim of this 4D flow cardiovascular magnetic resonance (CMR) follow-up study was to investigate longitudinal changes in aortic hemodynamics in adolescent patients with Marfan syndrome (MFS). Methods 4D flow CMR for the assessment of in-vivo 3D blood flow with full coverage of the thoracic aorta was performed twice (baseline scan t1/follow-up scan t2) in 19 adolescent MFS patients (age at t1: 12.7 ± 3.6 years, t2: 16.2 ± 4.3 years) with a mean follow-up duration of 3.5 ± 1.2 years. Ten healthy volunteers (24 ± 3.8 years) served as a control group. Data analysis included aortic blood flow visualization by color-coded 3D pathlines, and grading of flow patterns (helices/vortices) on a 3-point scale (none, moderate, severe; blinded reading, 2 observers). Regional aortic peak systolic velocities and systolic 3D wall shear stress (WSS) along the entire aortic wall were quantified. Z-Scores of the aortic root and proximal descending aorta (DAo) were assessed. Results Regional systolic WSS was stable over the follow-up duration, except for a significant decrease in the proximal inner DAo segment (p = 0.02) between t1 and t2. MFS patients revealed significant lower mean systolic WSS in the proximal inner DAo compared with volunteers (0.78 ± 0.15 N/m\(^{2}\)) at baseline t1 (0.60 ± 0.18 N/m\(^{2}\); p = 0.01) and follow-up t2 (0.55 ± 0.16 N/m\(^{2}\); p = 0.001). There were significant relationships (p < 0.01) between the segmental WSS in the proximal inner DAo, DAo Z-scores (r = −0.64) and helix/vortex pattern grading (r = −0.55) at both t1 and t2. The interobserver agreement for secondary flow patterns assessment was excellent (Cohen’s k = 0.71). Conclusions MFS patients have lower segmental WSS in the inner proximal DAo segment which correlates with increased localized aberrant vortex/helix flow patterns and an enlarged diameter at one of the most critical sites for aortic dissection. General aortic hemodynamics are stable but these subtle localized DAo changes are already present at young age and tend to be more pronounced in the course of time. KW - Marfan syndrome KW - wall shear stress KW - hemodynamics KW - 4D flow cardiovascular magnetic resonance KW - follow-up KW - aorta Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171119 VL - 19 IS - 33 ER - TY - JOUR A1 - Gathungu, Duncan Kioi A1 - Borzì, Alfio T1 - Multigrid Solution of an Elliptic Fredholm Partial Integro-Differential Equation with a Hilbert-Schmidt Integral Operator JF - Applied Mathematics N2 - An efficient multigrid finite-differences scheme for solving elliptic Fredholm partial integro-differential equations (PIDE) is discussed. This scheme combines a second-order accurate finite difference discretization of the PIDE problem with a multigrid scheme that includes a fast multilevel integration of the Fredholm operator allowing the fast solution of the PIDE problem. Theoretical estimates of second-order accuracy and results of local Fourier analysis of convergence of the proposed multigrid scheme are presented. Results of numerical experiments validate these estimates and demonstrate optimal computational complexity of the proposed framework. KW - elliptic problems KW - finite differences KW - fredholm operator KW - multigrid schemes KW - numerical analysis Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158525 VL - 8 IS - 7 ER - TY - JOUR A1 - García-Betancur, Juan-Carlos A1 - Goñi-Moreno, Angel A1 - Horger, Thomas A1 - Schott, Melanie A1 - Sharan, Malvika A1 - Eikmeier, Julian A1 - Wohlmuth, Barbara A1 - Zernecke, Alma A1 - Ohlsen, Knut A1 - Kuttler, Christina A1 - Lopez, Daniel T1 - Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus JF - eLife N2 - A central question to biology is how pathogenic bacteria initiate acute or chronic infections. Here we describe a genetic program for cell-fate decision in the opportunistic human pathogen Staphylococcus aureus, which generates the phenotypic bifurcation of the cells into two genetically identical but different cell types during the course of an infection. Whereas one cell type promotes the formation of biofilms that contribute to chronic infections, the second type is planktonic and produces the toxins that contribute to acute bacteremia. We identified a bimodal switch in the agr quorum sensing system that antagonistically regulates the differentiation of these two physiologically distinct cell types. We found that extracellular signals affect the behavior of the agr bimodal switch and modify the size of the specialized subpopulations in specific colonization niches. For instance, magnesium-enriched colonization niches causes magnesium binding to S. aureusteichoic acids and increases bacterial cell wall rigidity. This signal triggers a genetic program that ultimately downregulates the agr bimodal switch. Colonization niches with different magnesium concentrations influence the bimodal system activity, which defines a distinct ratio between these subpopulations; this in turn leads to distinct infection outcomes in vitro and in an in vivo murine infection model. Cell differentiation generates physiological heterogeneity in clonal bacterial infections and helps to determine the distinct infection types. KW - Staphylococcus aureus KW - infection KW - cell differentiation KW - pathogenic bacteria Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170346 VL - 6 IS - e28023 ER - TY - JOUR A1 - Garcia-Larsen, Vanessa A1 - Arthur, Rhonda A1 - Potts, James F. A1 - Howarth, Peter H. A1 - Ahlström, Matti A1 - Haahtela, Tari A1 - Loureiro, Carlos A1 - Bom, Ana Todo A1 - Brożek, Grzegorz A1 - Makowska, Joanna A1 - Kowalski, Marek L. A1 - Thilsing, Trine A1 - Keil, Thomas A1 - Matricardi, Paolo M. A1 - Torén, Kjell A1 - van Zele, Thibaut A1 - Bachert, Claus A1 - Rymarczyk, Barbara A1 - Janson, Christer A1 - Forsberg, Bertil A1 - Niżankowska-Mogilnicka, Ewa A1 - Burney, Peter G. J. T1 - Is fruit and vegetable intake associated with asthma or chronic rhino-sinusitis in European adults? Results from the Global Allergy and Asthma Network of Excellence (GA\(^2\)LEN) Survey JF - Clinical and Translational Allergy N2 - Background: Fruits and vegetables are rich in compounds with proposed antioxidant, anti-allergic and anti-inflammatory properties, which could contribute to reduce the prevalence of asthma and allergic diseases. Objective: We investigated the association between asthma, and chronic rhino-sinusitis (CRS) with intake of fruits and vegetables in European adults. Methods: A stratified random sample was drawn from the Global Allergy and Asthma Network of Excellence (GA\(^2\)LEN) screening survey, in which 55,000 adults aged 15–75 answered a questionnaire on respiratory symptoms. Asthma score (derived from self-reported asthma symptoms) and CRS were the outcomes of interest. Dietary intake of 22 subgroups of fruits and vegetables was ascertained using the internationally validated GA\(^2\)LEN Food Frequency Questionnaire. Adjusted associations were examined with negative binomial and multiple regressions. Simes procedure was used to control for multiple testing. Results: A total of 3206 individuals had valid data on asthma and dietary exposures of interest. 22.8% reported having at least 1 asthma symptom (asthma score ≥1), whilst 19.5% had CRS. After adjustment for potential confounders, asthma score was negatively associated with intake of dried fruits (β-coefficient −2.34; 95% confidence interval [CI] −4.09, −0.59), whilst CRS was statistically negatively associated with total intake of fruits (OR 0.73; 95% CI 0.55, 0.97). Conversely, a positive association was observed between asthma score and alliums vegetables (adjusted β-coefficient 0.23; 95% CI 0.06, 0.40). None of these associations remained statistically significant after controlling for multiple testing. Conclusion and clinical relevance: There was no consistent evidence for an association of asthma or CRS with fruit and vegetable intake in this representative sample of European adults. KW - Fruits KW - Vegetables KW - Asthma KW - Chronic rhino‑sinusitis KW - Adults KW - Europe KW - Meta‑analysis KW - GA\(^2\)LEN Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180887 VL - 7 ER - TY - JOUR A1 - Fröhlich, M. A1 - Pinart, M. A1 - Keller, T. A1 - Reich, A. A1 - Cabieses, B. A1 - Hohmann, C. A1 - Postma, D. S. A1 - Bousquet, J. A1 - Antó, J. M. A1 - Keil, T. A1 - Roll, S. T1 - Is there a sex-shift in prevalence of allergic rhinitis and comorbid asthma from childhood to adulthood? A meta-analysis JF - Clinical and Translational Allergy N2 - Background: Allergic rhinitis and asthma as single entities affect more boys than girls in childhood but more females in adulthood. However, it is unclear if this prevalence sex-shift also occurs in allergic rhinitis and concurrent asthma. Thus, our aim was to compare sex-specifc differences in the prevalence of coexisting allergic rhinitis and asthma in childhood, adolescence and adulthood. Methods: Post-hoc analysis of systematic review with meta-analysis concerning sex-specific prevalence of allergic rhinitis. Using random-effects meta-analysis, we assessed male–female ratios for coexisting allergic rhinitis and asthma in children (0–10 years), adolescents (11–17) and adults (> 17). Electronic searches were performed using MEDLINE and EMBASE for the time period 2000–2014. We included population-based observational studies, reporting coexisting allergic rhinitis and asthma as outcome stratifed by sex. We excluded non-original or non-population-based studies, studies with only male or female participants or selective patient collectives. Results: From a total of 6539 citations, 10 studies with a total of 93,483 participants met the inclusion criteria. The male–female ratios (95% CI) for coexisting allergic rhinitis and asthma were 1.65 (1.52; 1.78) in children (N = 6 studies), 0.61 (0.51; 0.72) in adolescents (N = 2) and 1.03 (0.79; 1.35) in adults (N = 2). Male–female ratios for allergic rhinitis only were 1.25 (1.19; 1.32, N = 5) in children, 0.80 (0.71; 0.89, N = 2) in adolescents and 0.98 (0.74; 1.30, N = 2) in adults, respectively. Conclusions: The prevalence of coexisting allergic rhinitis and asthma shows a clear male predominance in childhood and seems to switch to a female predominance in adolescents. This switch was less pronounced for allergic rhinitis only. KW - Medicine KW - Allergic rhinitis KW - Asthma KW - Multimorbidity KW - Prevalence KW - Systematic review Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172508 VL - 7 ER -