TY  - JOUR
A1  - Gotru, Sanjeev Kiran
A1  - van Geffen, Johanna P.
A1  - Nagy, Magdolna
A1  - Mammadova-Bach, Elmina
A1  - Eilenberger, Julia
A1  - Volz, Julia
A1  - Manukjan, Georgi
A1  - Schulze, Harald
A1  - Wagner, Leonard
A1  - Eber, Stefan
A1  - Schambeck, Christian
A1  - Deppermann, Carsten
A1  - Brouns, Sanne
A1  - Nurden, Paquita
A1  - Greinacher, Andreas
A1  - Sachs, Ulrich
A1  - Nieswandt, Bernhard
A1  - Hermanns, Heike M.
A1  - Heemskerk, Johan W. M.
A1  - Braun, Attila
T1  - Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases
JF  - Scientific Reports
N2  - Zinc (Zn2+) can modulate platelet and coagulation activation pathways, including fibrin formation. Here, we studied the (patho)physiological consequences of abnormal platelet Zn2+ storage and release. To visualize Zn2+ storage in human and mouse platelets, the Zn2+ specific fluorescent dye FluoZin3 was used. In resting platelets, the dye transiently accumulated into distinct cytosolic puncta, which were lost upon platelet activation. Platelets isolated from Unc13d−/− mice, characterized by combined defects of α/δ granular release, showed a markedly impaired Zn2+ release upon activation. Platelets from Nbeal2−/− mice mimicking Gray platelet syndrome (GPS), characterized by primarily loss of the α-granule content, had strongly reduced Zn2+ levels, which was also confirmed in primary megakaryocytes. In human platelets isolated from patients with GPS, Hermansky-Pudlak Syndrome (HPS) and Storage Pool Disease (SPD) altered Zn2+ homeostasis was detected. In turbidity and flow based assays, platelet-dependent fibrin formation was impaired in both Nbeal2−/− and Unc13d−/− mice, and the impairment could be partially restored by extracellular Zn2+. Altogether, we conclude that the release of ionic Zn2+ store from secretory granules upon platelet activation contributes to the procoagulant role of Zn2+ in platelet-dependent fibrin formation.
KW  - coagulation system
KW  - metals
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227455
VL  - 9
ER  - 
TY  - JOUR
A1  - Regn, Michael
A1  - Laggerbauer, Bernhard
A1  - Jentzsch, Claudia
A1  - Ramanujam, Deepak
A1  - Ahles, Andrea
A1  - Sichler, Sonja
A1  - Calzada-Wack, Julia
A1  - Koenen, Rory R.
A1  - Braun, Attila
A1  - Nieswandt, Bernhard
A1  - Engelhardt, Stefan
T1  - Peptidase inhibitor 16 is a membrane-tethered regulator of chemerin processing in the myocardium
JF  - Journal of Molecular and Cellular Cardiology
N2  - A key response of the myocardium to stress is the secretion of factors with paracrine or endocrine function. Intriguing in this respect is peptidase inhibitor 16 (PI16), a member of the CAP family of proteins which we found to be highly upregulated in cardiac disease. Up to this point, the mechanism of action and physiological function of PI16 remained elusive. Here, we show that PI16 is predominantly expressed by cardiac fibroblasts, which expose PI16 to the interstitium via a glycophosphatidylinositol (-GPI) membrane anchor. Based on a reported genetic association of PI16 and plasma levels of the chemokine chemerin, we investigated whether PI16 regulates post-translational processing of its precursor pro-chemerin. PI16-deficient mice were engineered and found to generate higher levels of processed chemerin than wildtype mice. Purified recombinant PI16 efficiently inhibited cathepsin K, a chemerin-activating protease, in vitro. Moreover, we show that conditioned medium from PI16-overexpressing cells impaired the activation of pro-chemerin. Together, our data indicate that PI16 suppresses chemerin activation in the myocardium and suggest that this circuit may be part of the cardiac stress response.
KW  - Cells
KW  - Activation
KW  - Purification
KW  - Protein
KW  - Peptidase inhibitor 16 (PI16)
KW  - Identification
KW  - Inflammation
KW  - Adipokine
KW  - Metabolism
KW  - Heart
KW  - Mice
KW  - Chemerin
KW  - RARRES2
KW  - TIG2
KW  - Protease inhibition
KW  - Chemerin processing
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187039
VL  - 99
ER  - 
TY  - JOUR
A1  - Brecht, Isabel
A1  - Weissbrich, Benedikt
A1  - Braun, Julia
A1  - Toyka, Klaus Viktor
A1  - Weishaupt, Andreas
A1  - Buttmann, Mathias
T1  - Intrathecal, Polyspecific Antiviral Immune Response in Oligoclonal Band Negative Multiple Sclerosis
JF  - PLoS One
N2  - Background: Oligoclonal bands (OCB) are detected in the cerebrospinal fluid (CSF) in more than 95% of patients with multiple sclerosis (MS) in the Western hemisphere. Here we evaluated the intrathecal, polyspecific antiviral immune response as a potential diagnostic CSF marker for OCB-negative MS patients. 
Methodology/Principal Findings: We tested 46 OCB-negative German patients with paraclinically well defined, definite MS. Sixteen OCB-negative patients with a clear diagnosis of other autoimmune CNS disorders and 37 neurological patients without evidence for autoimmune CNS inflammation served as control groups. Antibodies against measles, rubella, varicella zoster and herpes simplex virus in paired serum and CSF samples were determined by ELISA, and virus-specific immunoglobulin G antibody indices were calculated. An intrathecal antibody synthesis against at least one neurotropic virus was detected in 8 of 26 (31%) patients with relapsing-remitting MS, 8 of 12 (67%) with secondary progressive MS and 5 of 8 (63%) with primary progressive MS, in 3 of 16 (19%) CNS autoimmune and 3 of 37 (8%) non-autoimmune control patients. Antibody synthesis against two or more viruses was found in 11 of 46 (24%) MS patients but in neither of the two control groups. On average, MS patients with a positive antiviral immune response were older and had a longer disease duration than those without. 
Conclusion: Determination of the intrathecal, polyspecific antiviral immune response may allow to establish a CSF-supported diagnosis of MS in OCB-negative patients when two or more of the four virus antibody indices are elevated.
KW  - MS
KW  - cerebrospinal fluid
KW  - differential diagnosis
KW  - nervous-system
KW  - criteria
KW  - serum
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134426
VL  - 7
IS  - 7
ER  - 
TY  - JOUR
A1  - Schweiger, Giovanna
A1  - Malorgio, Amos
A1  - Henckert, David
A1  - Braun, Julia
A1  - Meybohm, Patrick
A1  - Hottenrott, Sebastian
A1  - Froehlich, Corinna
A1  - Zacharowski, Kai
A1  - Raimann, Florian J.
A1  - Piekarski, Florian
A1  - Noethiger, Christoph B.
A1  - Spahn, Donat R.
A1  - Tscholl, David W.
A1  - Roche, Tadzio R.
T1  - Visual Blood, a 3D animated computer model to optimize the interpretation of blood gas analysis
JF  - Bioengineering
N2  - Acid–base homeostasis is crucial for all physiological processes in the body and is evaluated using arterial blood gas (ABG) analysis. Screens or printouts of ABG results require the interpretation of many textual elements and numbers, which may delay intuitive comprehension. To optimise the presentation of the results for the specific strengths of human perception, we developed Visual Blood, an animated virtual model of ABG results. In this study, we compared its performance with a conventional result printout. Seventy physicians from three European university hospitals participated in a computer-based simulation study. Initially, after an educational video, we tested the participants’ ability to assign individual Visual Blood visualisations to their corresponding ABG parameters. As the primary outcome, we tested caregivers’ ability to correctly diagnose simulated clinical ABG scenarios with Visual Blood or conventional ABG printouts. For user feedback, participants rated their agreement with statements at the end of the study. Physicians correctly assigned 90% of the individual Visual Blood visualisations. Regarding the primary outcome, the participants made the correct diagnosis 86% of the time when using Visual Blood, compared to 68% when using the conventional ABG printout. A mixed logistic regression model showed an odds ratio for correct diagnosis of 3.4 (95%CI 2.00–5.79, p < 0.001) and an odds ratio for perceived diagnostic confidence of 1.88 (95%CI 1.67–2.11, p < 0.001) in favour of Visual Blood. A linear mixed model showed a coefficient for perceived workload of −3.2 (95%CI −3.77 to −2.64) in favour of Visual Blood. Fifty-one of seventy (73%) participants agreed or strongly agreed that Visual Blood was easy to use, and fifty-five of seventy (79%) agreed that it was fun to use. In conclusion, Visual Blood improved physicians’ ability to diagnose ABG results. It also increased perceived diagnostic confidence and reduced perceived workload. This study adds to the growing body of research showing that decision-support tools developed around human cognitive abilities can streamline caregivers’ decision-making and may improve patient care.
KW  - blood gas analysis
KW  - medical devices
KW  - point-of-care-testing
KW  - situational awareness
KW  - technology
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304150
SN  - 2306-5354
VL  - 10
IS  - 3
ER  - 
TY  - JOUR
A1  - Bergauer, Lisa
A1  - Akbas, Samira
A1  - Braun, Julia
A1  - Ganter, Michael T.
A1  - Meybohm, Patrick
A1  - Hottenrott, Sebastian
A1  - Zacharowski, Kai
A1  - Raimann, Florian J.
A1  - Rivas, Eva
A1  - López-Baamonde, Manuel
A1  - Spahn, Donat R.
A1  - Noethiger, Christoph B.
A1  - Tscholl, David W.
A1  - Roche, Tadzio R.
T1  - Visual Blood, visualisation of blood gas analysis in virtual reality, leads to more correct diagnoses: a computer-based, multicentre, simulation study
JF  - Bioengineering
N2  - Interpreting blood gas analysis results can be challenging for the clinician, especially in stressful situations under time pressure. To foster fast and correct interpretation of blood gas results, we developed Visual Blood. This computer-based, multicentre, noninferiority study compared Visual Blood and conventional arterial blood gas (ABG) printouts. We presented six scenarios to anaesthesiologists, once with Visual Blood and once with the conventional ABG printout. The primary outcome was ABG parameter perception. The secondary outcomes included correct clinical diagnoses, perceived diagnostic confidence, and perceived workload. To analyse the results, we used mixed models and matched odds ratios. Analysing 300 within-subject cases, we showed noninferiority of Visual Blood compared to ABG printouts concerning the rate of correctly perceived ABG parameters (rate ratio, 0.96; 95% CI, 0.92–1.00; p = 0.06). Additionally, the study revealed two times higher odds of making the correct clinical diagnosis using Visual Blood (OR, 2.16; 95% CI, 1.42–3.29; p < 0.001) than using ABG printouts. There was no or, respectively, weak evidence for a difference in diagnostic confidence (OR, 0.84; 95% CI, 0.58–1.21; p = 0.34) and perceived workload (Coefficient, 2.44; 95% CI, −0.09–4.98; p = 0.06). This study showed that participants did not perceive the ABG parameters better, but using Visual Blood resulted in more correct clinical diagnoses than using conventional ABG printouts. This suggests that Visual Blood allows for a higher level of situation awareness beyond individual parameters’ perception. However, the study also highlighted the limitations of today’s virtual reality headsets and Visual Blood.
KW  - virtual reality
KW  - blood gas analysis
KW  - data display
KW  - point-of-care
KW  - situation awareness
KW  - user-centred design
KW  - diagnostic correctness
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-310979
SN  - 2306-5354
VL  - 10
IS  - 3
ER  -