@article{KippnichSchorscherKredeletal.2020, author = {Kippnich, Maximilian and Schorscher, Nora and Kredel, Markus and Markus, Christian and Eden, Lars and Gassenmaier, Tobias and Lock, Johann and Wurmb, Thomas}, title = {Dual‑room twin‑CT scanner in multiple trauma care: first results after implementation in a level one trauma centre}, series = {European Journal of Trauma and Emergency Surgery}, journal = {European Journal of Trauma and Emergency Surgery}, issn = {1863-9933}, doi = {10.1007/s00068-020-01374-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232390}, year = {2020}, abstract = {Purpose The trauma centre of the Wuerzburg University Hospital has integrated a pioneering dual-room twin-CT scanner in a multiple trauma pathway. For concurrent treatment of two trauma patients, two carbon CT examination and intervention tables are positioned head to head with one sliding CT-Gantry in the middle. The focus of this study is the process of trauma care with the time to CT (tCT) and the time to operation (tOR) as quality indicator. Methods All patients with suspected multiple trauma, who required emergency surgery and who were initially diagnosed by the CT trauma protocol between 05/2018 and 12/2018 were included. Data relating to time spans (tCT and tOR), severity of injury and outcome was obtained. Results 110 of the 589 screened trauma patients had surgery immediately after finishing primary assessment in the ER. The ISS was 17 (9-34) (median and interquartile range, IQR). tCT was 15 (11-19) minutes (median and IQR) and tOR was 96.5 (75-119) minutes (median and IQR). In the first 30 days, seven patients died (6.4\%) including two within the first 24 h (2\%). There were two ICU days (1-6) (median and IQR) and one (0-1) (median and IQR) ventilator day. Conclusion The twin-CT technology is a fascinating tool to organize high-quality trauma care for two multiple trauma patients simultaneously}, language = {en} } @article{OehlerKistnerMartinetal.2017, author = {Oehler, Beatrice and Kistner, Katrin and Martin, Corinna and Schiller, J{\"u}rgen and Mayer, Rafaela and Mohammadi, Milad and Sauer, Reine-Solange and Filipovic, Milos R. and Nieto, Francisco R. and Kloka, Jan and Pfl{\"u}cke, Diana and Hill, Kerstin and Schaefer, Michael and Malcangio, Marzia and Reeh, Peter W. and Brack, Alexander and Blum, Robert and Rittner, Heike L.}, title = {Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, number = {5447}, doi = {10.1038/s41598-017-05348-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158536}, year = {2017}, abstract = {Phospholipids occurring in cell membranes and lipoproteins are converted into oxidized phospholipids (OxPL) by oxidative stress promoting atherosclerotic plaque formation. Here, OxPL were characterized as novel targets in acute and chronic inflammatory pain. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) and its derivatives were identified in inflamed tissue by mass spectrometry and binding assays. They elicited calcium influx, hyperalgesia and induced pro-nociceptive peptide release. Genetic, pharmacological and mass spectrometric evidence in vivo as well as in vitro confirmed the role of transient receptor potential channels (TRPA1 and TRPV1) as OxPAPC targets. Treatment with the monoclonal antibody E06 or with apolipoprotein A-I mimetic peptide D-4F, capturing OxPAPC in atherosclerosis, prevented inflammatory hyperalgesia, and in vitro TRPA1 activation. Administration of D-4F or E06 to rats profoundly ameliorated mechanical hyperalgesia and inflammation in collagen-induced arthritis. These data reveal a clinically relevant role for OxPAPC in inflammation offering therapy for acute and chronic inflammatory pain treatment by scavenging OxPAPC.}, language = {en} } @article{KindlTeichmuellerEscolanoLozanoetal.2022, author = {Kindl, Gudrun and Teichm{\"u}ller, Karolin and Escolano-Lozano, Fabiola and Birklein, Frank and Rittner, Heike L.}, title = {Pain, disability, and lifestyle: Patients with complex regional pain syndrome compared to chronic musculoskeletal pain-A retrospective analysis}, series = {European Journal of Pain}, volume = {26}, journal = {European Journal of Pain}, number = {3}, doi = {10.1002/ejp.1900}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318200}, pages = {719 -- 728}, year = {2022}, abstract = {Background Complex regional pain syndrome (CRPS) is an orphan disease occurring as a complication after trauma. Due to its acute onset and the typical clinical presentation of the inflammatory and autonomous signs, it is an eye-catching chronic pain disease affecting also young and working people. In social media and the internet, high pain severity and the unfavourable prognosis are often empathized. Methods Here, we compared epidemiological, pain and lifestyle factors of 223 CPRS patients from the "ncRNAPain" cohort with 255 patients with chronic musculoskeletal pain (MSK). MSK patients were recruited at the beginning of a multimodal pain therapy programme. We searched for factors predicting pain intensity. Results Both chronic pain diseases affected women in middle age. Patients with MSK were more obese, drank more alcohol, and were less educated (Pearson chi-square Test or Mann-Whitney/U-Test). Both groups smoked more than healthy people in the OECD (Organization for Economic Cooperation and Development). Mann-Whitney/U-Test confirmed that CRPS patients did not have more severe pain and did not suffer more from pain-related disability than patients with MSK. CRPS patients also had less psychiatric comorbidities. Multiple linear regression analysis revealed that group assignment, depressive characteristics, body mass index, average alcohol consumption and smoking predicted higher pain ratings, while disease duration, anxiety symptoms or gender had no influence on pain intensity. Conclusion In summary, our study supports a more optimistic view on pain in CRPS patients in comparison to MSK and identifies lifestyle factors that might contribute to the pathophysiology like smoking and drinking. Important next steps are the identification of CRPS patients at risk for chronification or—vice versa—with protective factors for pain resolution. Significance This study compares complex regional pain syndrome (CRPS) and chronic musculoskeletal pain and questions previously reported pain, disability and lifestyle factors associated with CRPS.}, language = {en} } @phdthesis{Hu2021, author = {Hu, Xiawei}, title = {Role of claudin-12 in neuronal barriers in painful murine and human neuropathy}, doi = {10.25972/OPUS-20806}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208065}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {In peripheral nervous system (PNS), the blood-nerve barrier (BNB) and myelin barrier (MB) are important physiological fences for maintaining the environment for axons, Schwann cells and other associated cells within peripheral nerves. The perineurium surrounding the nerves and endoneurial vessels nourishing the nerves compose the BNB. Schwann cells wrapping around neurons form the MB. Destruction or malfunction of the barriers has been postulated as an initial step in the development of pathologic conditions concerning human peripheral nerves, such as traumatic neuropathy and the disease of chronic inflammatory demyelination polyneuropathy (CIDP). Tight junction proteins (TJPs) are intercellular junctions building the microstructure of barriers. They play a key role in tightly connecting adjacent cells, controlling the passage of ions, water and other molecules via the paracellular pathway, and maintaining the cell polarity. Among the family of TJPs, claudins are the major structural components which form the backbone of TJs. Certain key TJPs [e.g. claudins (claudin-1, -5, -19, occludin, zona occludens (ZO-1)] have been identified in neural barriers and explored for therapeutic targets. The expression of Cldn12 gene has been documented in human/rodent tibial nerves, spinal cord and DRG. However, the role of claudin-12 in PNS is unknown. In the present study, we firstly found a loss of claudin-12 immunoreactivity (IR) in male or postmenopausal female patients with painful CIDP or non-inflammatory polyneuropathy (PNP). Then, we utilized male and female Cldn12-KO mice and the chronic constriction injury (CCI) model. Cldn12 mRNA and IR were reduced in WT mice after nerve injury. Deletion of Cldn12 via general knockout (KO) induced mechanical allodynia at baseline level and after CCI in time-dependent manner in male mice. KO of Cldn12 in males resulted in loss of small axons, perineurial barrier and MB breakdown, as well as TJP complex disruption with claudin-1, -19 and Pmp22 reduction. Moreover, local Cldn12 siRNA application mimicked mechanical allodynia and MB breakdown. In conclusion, claudin-12 deficiency is associated with painful CIDP/non-inflammatory PNP. Claudin-12 is a regulatory TJP crucial for mechanical nociception, perineurial barrier and MB integrity, and proper TJP composition in mice. Therefore, further investigating the functions of claudin-12 and its mechanism is important to prompt the development of new therapeutic approaches for painful neuropathies.}, language = {en} } @article{NagaiFoersterDote2022, author = {Nagai, Michiaki and F{\"o}rster, Carola Yvette and Dote, Keigo}, title = {Sex hormone-specific neuroanatomy of Takotsubo syndrome: is the insular cortex a moderator?}, series = {Biomolecules}, volume = {12}, journal = {Biomolecules}, number = {1}, issn = {2218-273X}, doi = {10.3390/biom12010110}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254776}, year = {2022}, abstract = {Takotsubo syndrome (TTS), a transient form of dysfunction in the heart's left ventricle, occurs predominantly in postmenopausal women who have emotional stress. Earlier studies support the concept that the human circulatory system is modulated by a cortical network (consisting of the anterior cingulate gyrus, amygdala, and insular cortex (Ic)) that plays a pivotal role in the central autonomic nervous system in relation to emotional stressors. The Ic plays a crucial role in the sympathovagal balance, and decreased levels of female sex hormones have been speculated to change functional cerebral asymmetry, with a possible link to autonomic instability. In this review, we focus on the Ic as an important moderator of the human brain-heart axis in association with sex hormones. We also summarize the current knowledge regarding the sex-specific neuroanatomy in TTS.}, language = {en} } @article{WurmbScholtesKolibayetal.2020, author = {Wurmb, Thomas and Scholtes, Katja and Kolibay, Felix and Schorscher, Nora and Ertl, Georg and Ernestus, Ralf-Ingo and Vogel, Ulrich and Franke, Axel and Kowalzik, Barbara}, title = {Hospital preparedness for mass critical care during SARS-CoV-2 pandemic}, series = {Critical Care}, volume = {24}, journal = {Critical Care}, doi = {10.1186/s13054-020-03104-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230201}, year = {2020}, abstract = {Mass critical care caused by the severe acute respiratory syndrome corona virus 2 pandemic poses an extreme challenge to hospitals. The primary goal of hospital disaster preparedness and response is to maintain conventional or contingency care for as long as possible. Crisis care must be delayed as long as possible by appropriate measures. Increasing the intensive care unit (ICU) capacities is essential. In order to adjust surge capacity, the reduction of planned, elective patient care is an adequate response. However, this involves numerous problems that must be solved with a sense of proportion. This paper summarises preparedness and response measures recommended to acute care hospitals.}, language = {en} } @article{SchusterJohannsenIsbaryetal.2018, author = {Schuster, Frank and Johannsen, Stephan and Isbary, Susanne and T{\"u}rkmeneli, Ismail and Roewer, Norbert}, title = {In vitro effects of levosimendan on muscle of malignant hyperthermia susceptible and non-susceptible swine}, series = {BMC Anesthesiology}, volume = {18}, journal = {BMC Anesthesiology}, number = {182}, doi = {10.1186/s12871-018-0644-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176991}, year = {2018}, abstract = {Background: The calcium sensitizer levosimendan is increasingly used to improve hemodynamics in patients with acutely decompensated heart failure. By binding to cardiac troponin C the conformation of the calcium-troponin C complex is stabilized, which leads to acceleration of actin-myosin crossbrigde formation and increased force generating capacity of muscle fibers. Besides indications in cardiac failure, beneficial effects of levosimendan in skeletal muscle disorders are currently evaluated. The aim of this study was to investigate differential effects of levosimendan on skeletal muscle of pigs with and without susceptibility to malignant hyperthermia (MH) in order to identify possible risks of this emerging drug for patients with predisposition to MH. Methods: Muscle bundles of 17 pigs (9 MH susceptible (MHS); 8 MH non-susceptible (MHN)) were excised under general anesthesia and examined in the tissue bath with increasing concentrations of levosimendan (0.065; 0.125; 0.5; 1.0; 10 and 50 μg/ml). Baseline tension and twitch force were monitored continuously. Data are presented as median and interquartile range. Statistical evaluation was performed using D'Agostino \& Pearson test for normal distribution and student's t test and 2-way ANOVA for differences between the groups. P < 0.05 was considered significant. Results: There were no differences between the groups concerning length, weight, initial twitch force and pre-drug resting tension of the investigated muscle strips. After an initial decrease in both groups, twitch amplitude was significantly higher in MHN (- 3.0 [- 5.2-0.2] mN) compared to MHS (- 7.5 [- 10.8- -4.5] mN) (p = 0.0034) muscle at an applied levosimendan concentration of 50 μg/ml. A marked increase in resting tension was detected following levosimendan incubation with 50 μg/ml in MHS muscle bundles (3.3 [0.9-6.1] mN) compared to MHN (- 0.7 [- 1.3-0.0] mN) (p < 0.0001). Conclusions: This in vitro investigation revealed the development of significant contractures in muscle bundles of MHS pigs after incubation with levosimendan. However, the effect appeared only at supra-therapeutic concentrations and further research is needed to determine the impact of levosimendan on MHS individuals in vivo.}, language = {en} } @article{ChenLotzRoeweretal.2018, author = {Chen, Shasha and Lotz, Christopher and Roewer, Norbert and Broscheit, Jens-Albert}, title = {Comparison of volatile anesthetic-induced preconditioning in cardiac and cerebral system: molecular mechanisms and clinical aspects}, series = {European Journal of Medical Research}, volume = {23}, journal = {European Journal of Medical Research}, number = {10}, doi = {10.1186/s40001-018-0308-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175509}, year = {2018}, abstract = {Volatile anesthetic-induced preconditioning ( APC) has shown to have cardiac and cerebral protective properties in both pre-clinical models and clinical trials. Interestingly, accumulating evidences demonstrate that, except from some specific characters, the underlying molecular mechanisms of APC-induced protective effects in myocytes and neurons are very similar; they share several major intracellular signaling pathways, including mediating mitochondrial function, release of inflammatory cytokines and cell apoptosis. Among all the experimental results, cortical spreading depolarization is a relative newly discovered cellular mechanism of APC, which, however, just exists in central nervous system. Applying volatile anesthetic preconditioning to clinical practice seems to be a promising cardio- and neuroprotective strategy. In this review, we also summarized and discussed the results of recent clinical research of APC. Despite all the positive experimental evidences, large-scale, long-term, more precisely controlled clinical trials focusing on the perioperative use of volatile anesthetics for organ protection are still needed.}, language = {en} } @article{HolzmannLittigFrankSchmadereretal.2022, author = {Holzmann-Littig, Christopher and Frank, Tamara and Schmaderer, Christoph and Braunisch, Matthias C. and Renders, Lutz and Kranke, Peter and Popp, Maria and Seeber, Christian and Fichtner, Falk and Littig, Bianca and Carbajo-Lozoya, Javier and Meerpohl, Joerg J. and Haller, Bernhard and Allwang, Christine}, title = {COVID-19 Vaccines: Fear of side effects among German health care workers}, series = {Vaccines}, volume = {10}, journal = {Vaccines}, number = {5}, issn = {2076-393X}, doi = {10.3390/vaccines10050689}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270561}, year = {2022}, abstract = {(1) Background: Health care workers (HCWs) play a key role in increasing anti-COVID vaccination rates. Fear of potential side effects is one of the main reasons for vaccine hesitancy. We investigated which side effects are of concern to HCWs and how these are associated with vaccine hesitancy. (2) Methods: Data were collected in an online survey in February 2021 among HCWs from across Germany with 4500 included participants. Free-text comments on previously experienced vaccination side effects, and fear of short- and long-term side effects of the COVID-19 vaccination were categorized and analyzed. (3) Results: Most feared short-term side effects were vaccination reactions, allergic reactions, and limitations in daily life. Most feared long-term side effects were (auto-) immune reactions, neurological side effects, and currently unknown long-term consequences. Concerns about serious vaccination side effects were associated with vaccination refusal. There was a clear association between refusal of COVID-19 vaccination in one's personal environment and fear of side effects. (4) Conclusions: Transparent information about vaccine side effects is needed, especially for HCW. Especially when the participants' acquaintances advised against vaccination, they were significantly more likely to fear side effects. Thus, further education of HCW is necessary to achieve good information transfer in clusters as well.}, language = {en} } @article{ShityakovBencurovaFoersteretal.2020, author = {Shityakov, Sergey and Bencurova, Elena and F{\"o}rster, Carola and Dandekar, Thomas}, title = {Modeling of shotgun sequencing of DNA plasmids using experimental and theoretical approaches}, series = {BMC Bioinformatics}, volume = {2020}, journal = {BMC Bioinformatics}, doi = {10.1186/s12859-020-3461-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229169}, year = {2020}, abstract = {Background Processing and analysis of DNA sequences obtained from next-generation sequencing (NGS) face some difficulties in terms of the correct prediction of DNA sequencing outcomes without the implementation of bioinformatics approaches. However, algorithms based on NGS perform inefficiently due to the generation of long DNA fragments, the difficulty of assembling them and the complexity of the used genomes. On the other hand, the Sanger DNA sequencing method is still considered to be the most reliable; it is a reliable choice for virtual modeling to build all possible consensus sequences from smaller DNA fragments. Results In silico and in vitro experiments were conducted: (1) to implement and test our novel sequencing algorithm, using the standard cloning vectors of different length and (2) to validate experimentally virtual shotgun sequencing using the PCR technique with the number of cycles from 1 to 9 for each reaction. Conclusions We applied a novel algorithm based on Sanger methodology to correctly predict and emphasize the performance of DNA sequencing techniques as well as in de novo DNA sequencing and its further application in synthetic biology. We demonstrate the statistical significance of our results.}, language = {en} } @article{WeibelPoppReisetal.2023, author = {Weibel, Stephanie and Popp, Maria and Reis, Stefanie and Skoetz, Nicole and Garner, Paul and Sydenham, Emma}, title = {Identifying and managing problematic trials: A research integrity assessment tool for randomized controlled trials in evidence synthesis}, series = {Research Synthesis Methods}, volume = {14}, journal = {Research Synthesis Methods}, number = {3}, doi = {10.1002/jrsm.1599}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318236}, pages = {357 -- 369}, year = {2023}, abstract = {Evidence synthesis findings depend on the assumption that the included studies follow good clinical practice and results are not fabricated or false. Studies which are problematic due to scientific misconduct, poor research practice, or honest error may distort evidence synthesis findings. Authors of evidence synthesis need transparent mechanisms to identify and manage problematic studies to avoid misleading findings. As evidence synthesis authors of the Cochrane COVID-19 review on ivermectin, we identified many problematic studies in terms of research integrity and regulatory compliance. Through iterative discussion, we developed a research integrity assessment (RIA) tool for randomized controlled trials for the update of this Cochrane review. In this paper, we explain the rationale and application of the RIA tool in this case study. RIA assesses six study criteria: study retraction, prospective trial registration, adequate ethics approval, author group, plausibility of methods (e.g., randomization), and plausibility of study results. RIA was used in the Cochrane review as part of the eligibility check during screening of potentially eligible studies. Problematic studies were excluded and studies with open questions were held in awaiting classification until clarified. RIA decisions were made independently by two authors and reported transparently. Using the RIA tool resulted in the exclusion of >40\% of studies in the first update of the review. RIA is a complementary tool prior to assessing "Risk of Bias" aiming to establish the integrity and authenticity of studies. RIA provides a platform for urgent development of a standard approach to identifying and managing problematic studies.}, 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{KurrekMorganHowardetal.2015, author = {Kurrek, Matt M. and Morgan, Pamela and Howard, Steven and Kranke, Peter and Calhoun, Aaron and Hui, Joshua and Kiss, Alex}, title = {Simulation as a New Tool to Establish Benchmark Outcome Measures in Obstetrics}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0131064}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151646}, pages = {e0131064}, year = {2015}, abstract = {Background There are not enough clinical data from rare critical events to calculate statistics to decide if the management of actual events might be below what could reasonably be expected (i.e. was an outlier). Objectives In this project we used simulation to describe the distribution of management times as an approach to decide if the management of a simulated obstetrical crisis scenario could be considered an outlier. Design Twelve obstetrical teams managed 4 scenarios that were previously developed. Relevant outcome variables were defined by expert consensus. The distribution of the response times from the teams who performed the respective intervention was graphically displayed and median and quartiles calculated using rank order statistics. Results Only 7 of the 12 teams performed chest compressions during the arrest following the 'cannot intubate/cannot ventilate' scenario. All other outcome measures were performed by at least 11 of the 12 teams. Calculation of medians and quartiles with 95\% CI was possible for all outcomes. Confidence intervals, given the small sample size, were large. Conclusion We demonstrated the use of simulation to calculate quantiles for management times of critical event. This approach could assist in deciding if a given performance could be considered normal and also point to aspects of care that seem to pose particular challenges as evidenced by a large number of teams not performing the expected maneuver. However sufficiently large sample sizes (i.e. from a national data base) will be required to calculate acceptable confidence intervals and to establish actual tolerance limits.}, language = {en} } @article{WurmbSchorscherJusticeetal.2018, author = {Wurmb, T and Schorscher, N and Justice, P and Dietz, S and Schua, R and Jarausch, T and Kinstle, U and Greiner, J and M{\"o}ldner, G and M{\"u}ller, J and Kraus, M and Simon, S and Wagenh{\"a}user, U and Hemm, J and Roewer, N and Helm, M}, title = {Structured analysis, evaluation and report of the emergency response to a terrorist attack in Wuerzburg, Germany using a new template of standardised quality indicators}, series = {Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine}, volume = {26}, journal = {Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine}, number = {87}, doi = {10.1186/s13049-018-0555-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177054}, year = {2018}, abstract = {Background: Until now there has been a reported lack of systematic reports and scientific evaluations of rescue missions during terror attacks. This however is urgently required in order to improve the performance of emergency medical services and to be able to compare different missions with each other. Aim of the presented work was to report the systematic evaluation and the lessons learned from the response to a terror attack that happened in Wuerzburg, Germany in 2016. Methods: A team of 14 experts developed a template of quality indicators and operational characteristics, which allow for the description, assessment and comparison of civil emergency rescue missions during mass killing incidents. The entire systematic evaluation process consisted of three main steps. The first step was the systematic data collection according to the quality indicators and operational characteristics. Second was the systematic stratification and assessment of the data. The last step was the prioritisation of the identified weaknesses and the definition of the lessons learned. Results: Five important "lessons learned" have been defined. First of all, a comprehensive concept for rescue missions during terror attacks is essential. Furthermore, the establishment of a defined high priority communication infrastructure between the different dispatch centres ("red phone") is vital. The goal is to secure the continuity of information between a few well-defined individuals. Thirdly, the organization of the incident scene needs to be commonly decided and communicated between police, medical services and fire services during the mission. A successful mission tactic requires continuous flux of reports to the on-site command post. Therefore, a predefined and common communication infrastructure for all operational forces is a crucial point. Finally, all strategies need to be extensively trained before the real life scenario hits. Conclusion: According to a systematic evaluation, we defined the lessons learned from a terror attack in 2016. Further systematic reports and academic work surrounding life threatening rescue missions and mass killing incidents are needed in order to ultimately improve such mission outcomes. In the future, a close international collaboration might help to find the best database to report and evaluate major incidents but also mass killing events.}, language = {en} } @article{SchulteBlum2022, author = {Schulte, Annemarie and Blum, Robert}, title = {Shaped by leaky ER: Homeostatic Ca\(^{2+}\) fluxes}, series = {Frontiers in Physiology}, volume = {13}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2022.972104}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287102}, year = {2022}, abstract = {At any moment in time, cells coordinate and balance their calcium ion (Ca\(^{2+}\)) fluxes. The term 'Ca\(^{2+}\) homeostasis' suggests that balancing resting Ca2+ levels is a rather static process. However, direct ER Ca\(^{2+}\) imaging shows that resting Ca\(^{2+}\) levels are maintained by surprisingly dynamic Ca\(^{2+}\) fluxes between the ER Ca\(^{2+}\) store, the cytosol, and the extracellular space. The data show that the ER Ca\(^{2+}\) leak, continuously fed by the high-energy consuming SERCA, is a fundamental driver of resting Ca\(^{2+}\) dynamics. Based on simplistic Ca\(^{2+}\) toolkit models, we discuss how the ER Ca\(^{2+}\) leak could contribute to evolutionarily conserved Ca\(^{2+}\) phenomena such as Ca\(^{2+}\) entry, ER Ca\(^{2+}\) release, and Ca\(^{2+}\) oscillations.}, language = {en} } @article{DresenPimientoPateletal.2023, author = {Dresen, Ellen and Pimiento, Jose M. and Patel, Jayshil J. and Heyland, Daren K. and Rice, Todd W. and Stoppe, Christian}, title = {Overview of oxidative stress and the role of micronutrients in critical illness}, series = {Journal of Parenteral and Enteral Nutrition}, volume = {47}, journal = {Journal of Parenteral and Enteral Nutrition}, doi = {10.1002/jpen.2421}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318186}, pages = {S38 -- S49}, year = {2023}, abstract = {Inflammation and oxidative stress represent physiological response mechanisms to different types of stimuli and injury during critical illness. Its proper regulation is fundamental to cellular and organismal survival and are paramount to outcomes and recovery from critical illness. A proper maintenance of the delicate balance between inflammation, oxidative stress, and immune response is crucial for resolution from critical illness with important implications for patient outcome. The extent of inflammation and oxidative stress under normal conditions is limited by the antioxidant defense system of the human body, whereas the antioxidant capacity is commonly significantly compromised, and serum levels of micronutrients and vitamins significantly depleted in patients who are critically ill. Hence, the provision of antioxidants and anti-inflammatory nutrients may help to reduce the extent of oxidative stress and therefore improve clinical outcomes in patients who are critically ill. As existing evidence of the beneficial effects of antioxidant supplementation in patients who are critically ill is still unclear, actual findings about the most promising anti-inflammatory and antioxidative candidates selenium, vitamin C, zinc, and vitamin D will be discussed in this narrative review. The existing evidence provided so far demonstrates that several factors need to be considered to determine the efficacy of an antioxidant supplementation strategy in patients who are critically ill and indicates the need for adequately designed multicenter prospective randomized control trials to evaluate the clinical significance of different types and doses of micronutrients and vitamins in selected groups of patients with different types of critical illness.}, language = {en} } @article{SarukhanyanShityakovDandekar2020, author = {Sarukhanyan, Edita and Shityakov, Sergey and Dandekar, Thomas}, title = {Rational drug design of Axl tyrosine kinase type I inhibitors as promising candidates against cancer}, series = {Frontiers in Chemistry}, volume = {7}, journal = {Frontiers in Chemistry}, number = {920}, issn = {2296-2646}, doi = {10.3389/fchem.2019.00920}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199505}, year = {2020}, abstract = {The high level of Axl tyrosine kinase expression in various cancer cell lines makes it an attractive target for the development of anti-cancer drugs. In this study, we carried out several sets of in silico screening for the ATP-competitive Axl kinase inhibitors based on different molecular docking protocols. The best drug-like candidates were identified, after parental structure modifications, by their highest affinity to the target protein. We found that our newly designed compound R5, a derivative of the R428 patented analog, is the most promising inhibitor of the Axl kinase according to the three molecular docking algorithms applied in the study. The molecular docking results are in agreement with the molecular dynamics simulations using the MM-PBSA/GBSA implicit solvation models, which confirm the high affinity of R5 toward the protein receptor. Additionally, the selectivity test against other kinases also reveals a high affinity of R5 toward ABL1 and Tyro3 kinases, emphasizing its promising potential for the treatment of malignant tumors.}, language = {en} } @article{WurmbFrankeSchorscheretal.2020, author = {Wurmb, Thomas and Franke, Axel and Schorscher, Nora and Kowalzik, Barbara and Helm, Matthias and Bohnen, Renate and Helmerichs, Jutta and Grueneisen, Ulrich and Cwojdzinski, Detlef and Jung, Georg and L{\"u}cking, Gesa and Weber, Martin}, title = {Emergency response to terrorist attacks: results of the federal-conducted evaluation process in Germany}, series = {European Journal of Trauma and Emergency Surgery}, volume = {46}, journal = {European Journal of Trauma and Emergency Surgery}, issn = {1863-9933}, doi = {10.1007/s00068-020-01347-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231777}, pages = {725-730}, year = {2020}, abstract = {Purpose Rescue missions during terrorist attacks are extremely challenging for all rescue forces (police as well as non-police forces) involved. To improve the quality and safety of the rescue missions during an active killing event, it is obligatory to adapt common rescue mission goals and strategies. Methods After the recent attacks in Europe, the Federal Office of Civil Protection and Disaster Assistance started an evaluation process on behalf of the Federal Ministry of the Interior and the Federal Ministry of Health. This was done to identify weaknesses, lessons learned and to formulate new adapted guidelines. Results The presented bullet point recommendations summarise the basic and most important results of the ongoing evaluation process for the Federal Republic of Germany. The safety of all the rescue forces and survival of the greatest possible number of casualties are the priority goals. Furthermore, the preservation and re-establishment of the socio-political integrity are the overarching goals of the management of active killing events. Strategic incident priorities are to stop the killing and to save as much lives as possible. The early identification and prioritised transportation of casualties with life-threatening non-controllable bleeding are major tasks and the shortest possible on-scene time is an important requirement with respect to safety issues. Conclusion With respect to hazard prevention tactics within Germany, we attributed the highest priority impact to the bullet points. The focus of the process has now shifted to intense work about possible solutions for the identified deficits and implementation strategies of such solutions during mass killing incidents.}, language = {en} } @article{RoesingSalvadorGuentzeletal.2020, author = {R{\"o}sing, Nils and Salvador, Ellaine and G{\"u}ntzel, Paul and Kempe, Christoph and Burek, Malgorzata and Holzgrabe, Ulrike and Soukhoroukov, Vladimir and Wunder, Christian and F{\"o}rster, Carola}, title = {Neuroprotective Effects of Isosteviol Sodium in Murine Brain Capillary Cerebellar Endothelial Cells (cerebEND) After Hypoxia}, series = {Frontiers in Cellular Neuroscience}, volume = {14}, journal = {Frontiers in Cellular Neuroscience}, issn = {1662-5102}, doi = {10.3389/fncel.2020.573950}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215013}, year = {2020}, abstract = {Ischemic stroke is one of the leading causes of death worldwide. It damages neurons and other supporting cellular elements in the brain. However, the impairment is not only confined to the region of assault but the surrounding area as well. Besides, it also brings about damage to the blood-brain barrier (BBB) which in turn leads to microvascular failure and edema. Hence, this necessitates an on-going, continuous search for intervention strategies and effective treatment. Of late, the natural sweetener stevioside proved to exhibit neuroprotective effects and therapeutic benefits against cerebral ischemia-induced injury. Its injectable formulation, isosteviol sodium (STVNA) also demonstrated favorable results. Nonetheless, its effects on the BBB have not yet been investigated to date. As such, this present study was designed to assess the effects of STVNA in our in vitro stroke model of the BBB.The integrity and permeability of the BBB are governed and maintained by tight junction proteins (TJPs) such as claudin-5 and occludin. Our data show increased claudin-5 and occludin expression in oxygen and glucose (OGD)-deprived murine brain capillary cerebellar endothelial cells (cerebEND) after STVNa treatment. Likewise, the upregulation of the transmembrane protein integrin-αv was also observed. Finally, cell volume was reduced with the simultaneous administration of STVNA and OGD in cerebEND cells. In neuropathologies such as stroke, the failure of cell volume control is a major feature leading to loss of cells in the penumbra as well as adverse outcomes. Our initial findings, therefore, point to the neuroprotective effects of STVNA at the BBB in vitro, which warrant further investigation for a possible future clinical intervention.}, language = {en} } @article{Jung‐KoenigFuellenbachMurphyetal.2020, author = {Jung-K{\"o}nig, Mona and F{\"u}llenbach, Christoph and Murphy, Michael F. and Manzini, Paola and Laspina, Stefan and Pendry, Kate and M{\"u}hling, J{\"o}rg and Wikman, Agneta and Humbrecht, Catherine and Rigal, Jean-Christophe and Lasocki, Sigismond and Foll{\´e}a, Gilles and Seifried, Erhard and M{\"u}ller, Markus M. and Geisen, Christof and Aranko, Kari and Zacharowski, Kai and Meybohm, Patrick}, title = {Programmes for the management of preoperative anaemia: audit in ten European hospitals within the PaBloE (Patient Blood Management in Europe) working group}, series = {Vox Sanguinis}, volume = {115}, journal = {Vox Sanguinis}, number = {3}, doi = {10.1111/vox.12872}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214049}, pages = {182 -- 191}, year = {2020}, abstract = {Background and objectives Preoperative anaemia is an independent risk factor for a higher morbidity and mortality, a longer hospitalization and increased perioperative transfusion rates. Managing preoperative anaemia is the first of three pillars of Patient Blood Management (PBM), a multidisciplinary concept to improve patient safety. While various studies provide medical information on (successful) anaemia treatment pathways, knowledge of organizational details of diagnosis and management of preoperative anaemia across Europe is scarce. Materials and methods To gain information on various aspects of preoperative anaemia management including organization, financing, diagnostics and treatment, we conducted a survey (74 questions) in ten hospitals from seven European nations within the PaBloE (Patient Blood Management in Europe) working group covering the year 2016. Results Organization and activity in the field of preoperative anaemia management were heterogeneous in the participating hospitals. Almost all hospitals had pathways for managing preoperative anaemia in place, however, only two nations had national guidelines. In six of the ten participating hospitals, preoperative anaemia management was organized by anaesthetists. Diagnostics and treatment focused on iron deficiency anaemia which, in most hospitals, was corrected with intravenous iron. Conclusion Implementation and approaches of preoperative anaemia management vary across Europe with a primary focus on treating iron deficiency anaemia. Findings of this survey motivated the hospitals involved to critically evaluate their practice and may also help other hospitals interested in PBM to develop action plans for diagnosis and management of preoperative anaemia.}, language = {en} }