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result(s) for
"Bergmann, B"
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sEH-derived metabolites of linoleic acid drive pathologic inflammation while impairing key innate immune cell function in burn injury
2022
Fatty acid composition in the Western diet has shifted from saturated to polyunsaturated fatty acids (PUFAs), and specifically to linoleic acid (LA, 18:2), which has gradually increased in the diet over the past 50 y to become the most abundant dietary fatty acid in human adipose tissue. PUFA-derived oxylipins regulate a variety of biological functions. The cytochrome P450 (CYP450)–formed epoxy fatty acid metabolites of LA (EpOMEs) are hydrolyzed by the soluble epoxide hydrolase enzyme (sEH) to dihydroxyoctadecenoic acids (DiHOMEs). DiHOMEs are considered cardioprotective at low concentrations but at higher levels have been implicated as vascular permeability and cytotoxic agents and are associated with acute respiratory distress syndrome in severe COVID-19 patients. High EpOME levels have also correlated with sepsis-related fatalities; however, those studies failed to monitor DiHOME levels. Considering the overlap of burn pathophysiology with these pathologies, the role of DiHOMEs in the immune response to burn injury was investigated. 12,13-DiHOME was found to facilitate the maturation and activation of stimulated neutrophils, while impeding monocyte and macrophage functionality and cytokine generation. In addition, DiHOME serum concentrations were significantly elevated in burn-injured mice and these increases were ablated by administration of 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a sEH inhibitor. TPPU also reduced necrosis of innate and adaptive immune cells in burned mice, in a dose-dependent manner. The findings suggest DiHOMEs are a key driver of immune cell dysfunction in severe burn injury through hyperinflammatory neutrophilic and impaired monocytic actions, and inhibition of sEH might be a promising therapeutic strategy to mitigate deleterious outcomes in burn patients.
Journal Article
Extended-Aperture Shape Measurements Using Spatially Partially Coherent Illumination (ExASPICE)
by
Falldorf, Claas
,
Agour, Mostafa
,
Bergmann, Ralf B.
in
Aperture
,
depth discrimination
,
Electronics industry
2024
We have recently demonstrated that the 3D shape of micro-parts can be measured using LED illumination based on speckle contrast evaluation in the recently developed SPICE profilometry (shape measurements based on imaging with spatially partially coherent illumination). The main advantage of SPICE is its improved robustness and measurement speed compared to confocal or white light interferometry. The limited spatial coherence of the LED illumination is used for depth discrimination. An electrically tunable lens in a 4f-configuration is used for fast depth scanning without mechanically moving parts. The approach is efficient, takes less than a second to capture required images, is eye-safe and offers a depth of focus of a few millimeters. However, SPICE’s main limitation is its assumption of a small illumination aperture. Such a small illumination aperture affects the axial scan resolution, which dominates the measurement uncertainty. In this paper, we propose a novel method to overcome the aperture angle limitation of SPICE by illuminating the object from different directions with several independent LED sources. This approach reduces the full width at half maximum of the contrast envelope to one-eighth, resulting in a twofold improvement in measurement accuracy. As a proof of concept, shape measurements of various metal objects are presented.
Journal Article
A Complementary Approach for Securing and Anti-Counterfeiting of Valuable Documents Based on Encryption of Computer-Generated Hologram
by
Khattab, Tawfik A.
,
Ahmed, Zakaria E.
,
Attia, Yasser A.
in
Algorithms
,
anti-counterfeiting
,
Bar codes
2025
We present a novel approach for securing valuable documents using a complementary approach based on the encryption of computer-generated holograms (CGHs). The proposed approach utilizes the well-known iterative Fourier transform algorithm (IFTA) to generate a phase-only CGH for valuable digital and/or physical documents. The generated CGH is then secured by binary phase randomization, which is implemented using the symmetric encryption technique, exclusive OR (XOR). The reconstruction process for the calculated secured CGHs varied slightly depending on whether the documents were digital or physical. For digital documents, reconstruction was performed using a symmetric decryption key followed by an inverse Fourier transform (IFFT). On the other hand, the reconstruction of the physical document involved two additional processes: printing and scanning. To evaluate the quality of the digital reconstruction, the speckle signal-to-noise ratio (SSNR) was estimated for both printed grayscale and binary CGHs. The security analysis of the XOR-encrypted CGH was quantitatively evaluated to ensure the level of protection against various cryptographic attacks such as plaintext and brute-force attacks. The results revealed that the combination of phase CGHs and the XOR encryption/decryption provides robust cryptographic protection for valuable documents, benefiting document security and anti-counterfeiting.
Journal Article
Utilizing predictive machine-learning modelling unveils feature-based risk assessment system for hyperinflammatory patterns and infectious outcomes in polytrauma
2023
Earlier research has identified several potentially predictive features including biomarkers associated with trauma, which can be used to assess the risk for harmful outcomes of polytraumatized patients. These features encompass various aspects such as the nature and severity of the injury, accompanying health conditions, immune and inflammatory markers, and blood parameters linked to organ functioning, however their applicability is limited. Numerous indicators relevant to the patients` outcome are routinely gathered in the intensive care unit (ICU) and recorded in electronic medical records, rendering them suitable predictors for risk assessment of polytraumatized patients.
317 polytraumatized patients were included, and the influence of 29 clinical and biological features on the complication patterns for systemic inflammatory response syndrome (SIRS), pneumonia and sepsis were analyzed with a machine learning workflow including clustering, classification and explainability using SHapley Additive exPlanations (SHAP) values. The predictive ability of the analyzed features within three days after admission to the hospital were compared based on patient-specific outcomes using receiver-operating characteristics.
A correlation and clustering analysis revealed that distinct patterns of injury and biomarker patterns were observed for the major complication classes. A k-means clustering suggested four different clusters based on the major complications SIRS, pneumonia and sepsis as well as a patient subgroup that developed no complications. For classification of the outcome groups with no complications, pneumonia and sepsis based on boosting ensemble classification, 90% were correctly classified as low-risk group (no complications). For the high-risk groups associated with development of pneumonia and sepsis, 80% of the patients were correctly identified. The explainability analysis with SHAP values identified the top-ranking features that had the largest impact on the development of adverse outcome patterns. For both investigated risk scenarios (infectious complications and long ICU stay) the most important features are SOFA score, Glasgow Coma Scale, lactate, GGT and hemoglobin blood concentration.
The machine learning-based identification of prognostic feature patterns in patients with traumatic injuries may improve tailoring personalized treatment modalities to mitigate the adverse outcomes in high-risk patient clusters.
Journal Article
Vascular impulse technology versus elevation for reducing the swelling of upper and lower extremity joint fractures
by
Swartman, Benedict
,
Baumann, Lukas
,
Bergmann, Moritz B.
in
692/308/2779/777
,
692/308/409
,
Edema
2023
Soft-tissue conditioning due to posttraumatic oedema after complicated joint fractures is a central therapeutic aspect both pre- and postoperatively. On average, 6–10 days pass until the patient is suitable for surgery. This study compares the decongestant effect of vascular impulse technology (VIT) with that of conventional elevation. In this monocentric RCT, 68 patients with joint fractures of the upper (n = 36) and lower (n = 32) extremity were included and randomized after consent in a 1:1 ratio. Variables were evaluated for all fractures together and additionally subdivided into upper or lower extremity for better clinical comparability. Primary endpoint was the time in days from hospital admission to operability. Secondary endpoints were total length of stay, oedema reduction, pain intensity, complications, and revisions. The time from admission until operability was reduced by 1.4 (95% CI − 0.4; 3.1) days in the mITT analysis (p = 0.120) and was statistically significant with 1.7 (95% CI 0.1; 3.3) days in the as-treated sensitivity analysis (p
AT
= 0.038). Significantly less pain and a faster oedema reduction were found in the intervention group. Due to rare occurrences, nothing can be concluded regarding complications and revisions. Administration of VIT therapy did not lead to a significant reduction in time until operability in the whole population but was superior to elevation for soft-tissue conditioning and pain reduction. However, there was a significant reduction by 2.5 days (95% CI 0.7; 4.3) in the subgroup of lower extremity fractures. VIT therapy therefore seems to be a helpful tool in the treatment of posttraumatic oedema after complex joint fractures of the lower and upper extremity, especially in tibial head and lower leg fractures.
Journal Article
TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function
by
Wan, Debin
,
Gogolla, Falk
,
Goetzman, Holly
in
1-Phosphatidylinositol 3-kinase
,
631/250/127
,
631/250/24
2021
Oxylipins modulate the behavior of immune cells in inflammation. Soluble epoxide hydrolase (sEH) converts anti-inflammatory epoxyeicosatrienoic acid (EET) to dihydroxyeicosatrienoic acid (DHET). An sEH-inhibitor, TPPU, has been demonstrated to ameliorate lipopolysaccharide (LPS)- and sepsis-induced inflammation via EETs. The immunomodulatory role of DHET is not well characterized. We hypothesized that TPPU dampens inflammation and that sEH-derived DHET alters neutrophil functionality in burn induced inflammation. Outbred mice were treated with vehicle, TPPU or 14,15-DHET and immediately subjected to either sham or dorsal scald 28% total body surface area burn injury. After 6 and 24 h, interleukin 6 (IL-6) serum levels and neutrophil activation were analyzed. For in vitro analyses, bone marrow derived neutrophil functionality and mRNA expression were examined. In vivo, 14,15-DHET and IL-6 serum concentrations were decreased after burn injury with TPPU administration. In vitro, 14,15-DHET impaired neutrophil chemotaxis, acidification, CXCR1/CXCR2 expression and reactive oxygen species (ROS) production, the latter independent from p38MAPK and PI3K signaling. We conclude that TPPU administration decreases DHET post-burn. Furthermore, DHET downregulates key neutrophil immune functions and mRNA expression. Altogether, these data reveal that TPPU not only increases anti-inflammatory and inflammation resolving EET levels, but also prevents potential impairment of neutrophils by DHET in trauma.
Journal Article
Optical In-Process Measurement: Concepts for Precise, Fast and Robust Optical Metrology for Complex Measurement Situations
by
Falldorf, Claas
,
Bergmann, Ralf B.
,
Kalms, Michael
in
fringe projection
,
in situ measurement
,
in-process measurement
2021
Optical metrology is a key element for many areas of modern production. Preferably, measurements should take place within the production line (in-process) and keep pace with production speed, even if the parts have a complex geometry or are difficult to access. The challenge for modern optical in-process measurements is, therefore, how to simultaneously make optical metrology precise, fast, robust and capable of handling geometrical complexity. The potential of individual techniques to achieve these demands can be visualized by the tetrahedron of optical metrology. Depending on the application, techniques based on interferometry or geometrical optics may have to be preferred. The paper emphasizes complexity and robustness as prime areas of improvement. Concerning interferometric techniques, we report on fast acquisition as used in holography, tailoring of coherence properties and use of Multiple simultaneous Viewing direction holography (MultiView), self reference used in Computational Shear Interferometry (CoSI) and the simultaneous use of several light sources in Multiple Aperture Shear Interferometry (MArS) based on CoSI as these techniques have proven to be particularly effective. The use of advanced approaches based on CoSI requires a transition of the description of light from the use of the well-known wave field to the coherence function of light. Techniques based on geometric optics are generally comparatively robust against environmental disturbances, and Fringe Projection (FP) is shown to be especially useful in very demanding measurement conditions.
Journal Article
Potential Targets to Mitigate Trauma- or Sepsis-Induced Immune Suppression
by
Crisologo, Peter A.
,
Hanschen, Marc
,
Beckmann, Nadine
in
Apoptosis
,
chronic critical illness
,
Clinical trials
2021
In sepsis and trauma, pathogens and injured tissue provoke a systemic inflammatory reaction which can lead to overwhelming inflammation. Concurrent with the innate hyperinflammatory response is adaptive immune suppression that can become chronic. A current key issue today is that patients who undergo intensive medical care after sepsis or trauma have a high mortality rate after being discharged. This high mortality is thought to be associated with persistent immunosuppression. Knowledge about the pathophysiology leading to this state remains fragmented. Immunosuppressive cytokines play an essential role in mediating and upholding immunosuppression in these patients. Specifically, the cytokines Interleukin-10 (IL-10), Transforming Growth Factor-β (TGF-β) and Thymic stromal lymphopoietin (TSLP) are reported to have potent immunosuppressive capacities. Here, we review their ability to suppress inflammation, their dynamics in sepsis and trauma and what drives the pathologic release of these cytokines. They do exert paradoxical effects under certain conditions, which makes it necessary to evaluate their functions in the context of dynamic changes post-sepsis and trauma. Several drugs modulating their functions are currently in clinical trials in the treatment of other pathologies. We provide an overview of the current literature on the effects of IL-10, TGF-β and TSLP in sepsis and trauma and suggest therapeutic approaches for their modulation.
Journal Article
High Resolution Imaging Using Micro-Objectives Fabricated by 2-Photon-Polymerization
by
Agour, Mostafa
,
Falldorf, Claas
,
Bergmann, Ralf B.
in
2-photon-polymerization
,
Aperture
,
Computer aided design
2025
We experimentally demonstrate high-resolution imaging using micro-objectives fabricated by two-photon polymerization (2PP) lithography, highlighting its potential as a flexible and precise fabrication method. The 2PP manufacturing process offers the ability to develop micro-optics with customized geometries and material properties, including tailored refractive indices. This flexibility introduces new degrees of freedom in optical system design and expands the applicability of micro-optics to advanced imaging tasks where other materials and fabrication methods are insufficient. For our study, bi-convex micro-optics with different geometries with radii of curvature of <15 μm and minimized contact areas (<1 μm2) to ensure easy release from the substrate were fabricated with 2PP and investigated for their optical performance. With these micro-optics, the tracks with a pitch of 320 nm and the pits and lands as small as 130 nm were successfully resolved on a BluRay disc surface, demonstrating for the first time the high-resolution imaging capabilities of bi-convex spherical micro lenses.
Journal Article
Diagnostic utility of IL-18 plasma levels in distinguishing abdominal from non-abdominal sepsis
2025
Abdominal sepsis is a critical and high-risk condition in intensive care, characterized by diagnostic challenges, complex treatment, and high mortality. Non-specific symptoms and the difficulty of discriminating harmful bacteria from the normal flora complicate a timely diagnosis and treatment. Although timely interventions are crucial, the best timing of surgery remains uncertain, especially in unstable patients. Diagnostic markers like C-reactive protein, procalcitonin, and interleukins help guide diagnosis but often lack specificity of an abdominal focus. This study aims to identify possible additional markers for earlier detection of abdominal sepsis.
Plasma samples were collected from 47 sepsis patients at the day of sepsis diagnosis, and from 10 healthy controls. Patients were retrospectively categorized into those with abdominal (n=23) and those with non-abdominal (n=24) sepsis. Patient`s characteristics, clinical outcomes, physiological and laboratory parameters, and cytokine levels were assessed. Receiver operating characteristic curves and Spearman correlation analyses were conducted.
Age and sex proportions were comparable across the sepsis groups, as were the chronic disease prevalence, the severity of illness and mortality rates. Patients with abdominal sepsis were more likely to undergo emergency surgeries. Pro-inflammatory cytokines like IL-6, MCP-1, and IL-18 were elevated, as was the anti-inflammatory IL-10 in both sepsis cohorts compared to healthy controls. IL-18 was particularly associated with a more severe inflammatory response in non-abdominal sepsis. IL-18 levels below 1892.00 pg/mL showed 82.6% sensitivity and 56.5% specificity for identifying patients with abdominal sepsis, with a significant diagnostic accuracy (AUC 0.68, p = 0.034). This suggests IL-18 as a useful additional moderate predictor for critical cases.
The results demonstrate that IL-18, IL-6, MCP-1, and IL-10 are increased in sepsis, while IL-18 may serve as an additional biomarker for distinguishing abdominal from non-abdominal sepsis.
Journal Article