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  • 1
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 22 ( 2021-11-17), p. 5349-
    Abstract: Selatogrel, a potent and reversible antagonist of the P2Y12 receptor, inhibited FeCl3-induced thrombosis in rats. Here, we report the anti-thrombotic effect of selatogrel after subcutaneous applications in guinea pigs and mice. Selatogrel inhibited platelet function only 10 min after subcutaneous application in mice. In addition, in a modified Folts thrombosis model in guinea pigs, selatogrel prevented a decrease in blood-flow, indicative of the inhibition of ongoing thrombosis, approximately 10 min after subcutaneous injection. Selatogrel fully normalised blood flow; therefore, we speculate that it may not only prevent, but also dissolve, platelet thrombi. Thrombus dissolution was investigated using real-time intravital microscopy in mice. The infusion of selatogrel during ongoing platelet thrombus formation stopped growth and induced the dissolution of the preformed platelet thrombus. In addition, platelet-rich thrombi were given 30 min to consolidate in vivo. The infusion of selatogrel dissolved the preformed and consolidated platelet thrombi. Dissolution was limited to the disintegration of the occluding part of the platelet thrombi, leaving small mural platelet aggregates to seal the blood vessel. Therefore, our experiments uncovered a novel advantage of selatogrel: the dissolution of pre-formed thrombi without the disintegration of haemostatic seals, suggesting a bipartite benefit of the early application of selatogrel in patients with acute thrombosis.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 2
    In: Materials, MDPI AG, Vol. 14, No. 9 ( 2021-04-23), p. 2157-
    Abstract: After conventional forming processes, the residual stress distribution in wires is frequently unfavorable for subsequent processes, such as bending operations. High tensile residual stresses typically occur near the wire surface and normally limit further processability of the material. Additional heat treatment operations or shot peening are often used to influence the residual stress distribution in the material after conventional manufacturing, which is time- and energy-consuming. This paper presents an approach for influencing the residual stress distribution by modifying the forming process, especially regarding die geometry. The aim is to reduce the resulting tensile stress levels near the surface. Specific forming elements are integrated into the dies to achieve this residual stress reduction. These modifications in the forming zone have a significant influence on process properties, such as plastic strain and deformation direction, but typically do not influence product geometry. This paper describes the theoretical approach and model setup, the FE simulation, and the results of the experimental tests. The characterization of the residual stress states in the specimen was carried out through X-ray diffraction using the sin2Ψ method.
    Type of Medium: Online Resource
    ISSN: 1996-1944
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2487261-1
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  • 3
    In: Nutrients, MDPI AG, Vol. 12, No. 4 ( 2020-03-30), p. 951-
    Abstract: Sodium butyrate (SoB) supplementation has been suggested to attenuate the development of non-alcoholic fatty liver disease (NAFLD). Here, we determined the therapeutic potential of SoB on NAFLD progression and molecular mechanism involved. Eight-week old C57BL/6J mice were pair-fed a fat-, fructose- and cholesterol-rich diet (FFC) or control diet (C). After 8 weeks, some mice received 0.6g SoB/kg bw in their respective diets (C+SoB; FFC+SoB) or were maintained on C or FFC for the next 5 weeks of feeding. Liver damage, markers of glucose metabolism, inflammation, intestinal barrier function and melatonin metabolism were determined. FFC-fed mice progressed from simple steatosis to early non-alcoholic steatohepatitis, along with significantly higher TNFα and IL-6 protein levels in the liver and impaired glucose tolerance. In FFC+SoB-fed mice, disease was limited to steatosis associated with protection against the induction of Tlr4 mRNA and iNOS protein levels in livers. SoB supplementation had no effect on FFC-induced loss of tight junction proteins in the small intestine but was associated with protection against alterations in melatonin synthesis and receptor expression in the small intestine and livers of FFC-fed animals. Our results suggest that the oral supplementation of SoB may attenuate the progression of simple steatosis to steatohepatitis.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2518386-2
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  • 4
    In: Children, MDPI AG, Vol. 9, No. 6 ( 2022-05-28), p. 794-
    Abstract: Low copeptin levels may indicate inadequate arginine-vasopressin release promoting arterial hypotension, whereas high copeptin concentrations may reflect disease severity. This single-center prospective non-randomized clinical trial analyzed the course of blood copeptin in critically ill normo- and hypotensive children and its association with disease severity. In 164 patients (median age 0.5 years (interquartile range 0.1, 2.9)), the mean copeptin concentration at baseline was 43.5 pmol/L. Though not significantly different after 61 h (primary outcome, mean individual change: −12%, p = 0.36, paired t-test), we detected 1.47-fold higher copeptin concentrations during arterial hypotension when compared to normotension (mixed-effect ANOVA, p = 0.01). In total, 8 out of 34 patients (23.5%) with low copeptin concentrations 〈 10 pmol/L were hypotensive. Copeptin was highest in the adjusted mixed-effect regression analysis within the first day (+20% at 14 h) and decreased significantly at 108 h (−27%) compared to baseline (p = 0.002). Moreover, we found a significant association with vasopressor-inotrope treatment intensity, infancy (1–12 months) and cardiopulmonary bypass (all p ≤ 0.001). In conclusion, high copeptin values were associated with arterial hypotension and severity of disease in critically ill children. This study does not support the hypothesis that low copeptin values might be indicative of arginine-vasopressin deficiency.
    Type of Medium: Online Resource
    ISSN: 2227-9067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2732685-8
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  • 5
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 13 ( 2023-06-23), p. 10564-
    Abstract: The Cuprizone mouse model is widely used in studies on de- and remyelination. In the hands of different experimenters, the Cuprizone concentrations that lead to comparable levels of demyelination differ considerably. The reasons for this variability are unknown. In this study, we tested whether different Cuprizone formulations from different vendors and manufacturers influenced Cuprizone-induced histopathological hallmarks. We intoxicated male C57BL/6 mice with six Cuprizone powders that differed in their manufacturer, vendor, and purity. After five weeks, we analyzed the body weight changes over the course of the experiment, as well as the demyelination, astrogliosis, microgliosis and axonal damage by histological LFB-PAS staining and immunohistochemical labelling of PLP, IBA1, GFAP and APP. All Cuprizone formulations induced demyelination, astrogliosis, microgliosis, axonal damage and a moderate drop in body weight at the beginning of the intoxication period. In a cumulative evaluation of all analyses, two Cuprizone formulations performed weaker than the other formulations. In conclusion, all tested formulations did work, but the choice of Cuprizone formulation may have been responsible for the considerable variability in the experimental outcomes.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 19 ( 2023-09-27), p. 6221-
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 19 ( 2023-09-27), p. 6221-
    Abstract: Background: The management of pelvic fractures is a significant challenge. Surgical site infection can result in the need for revision surgery, cause functional impairment, and lead to a prolonged length of stay and increased treatment costs. Although reports on fracture-related infection (FRI) after pelvic fracture fixation are sparsely reported in the literature, it is a serious complication. This study analysed patients with FRIs after pelvic fracture regarding patient characteristics, treatment strategies, and an evaluation of risk factors for FRI. Methods: In this retrospective single-centre study, FRI was diagnosed based on clinical symptoms of infection and a positive culture of a bacterial infection. Depending on the severity and acuteness of the infection, osseous stabilization was restored either via implant retention (stable implant, no osteolysis), exchange (loose implant or bony defect), or external fixation (recurrence of infection after prior implant retaining revision). Healing of infection was defined as no sign of recurring infection upon clinical, radiological, and laboratory examination in the last follow-up visit. Results: The FRI rate in our patient population was 7.5% (24/316). In 8/24 patients, the FRI occurred within the first three weeks after initial surgery (early) and 16/24 presented with a late onset of symptoms of FRI. A strategy of debridement, antibiotics, and implant retention (DAIR) was successful in 9/24 patients with FRI after pelvic fracture. A total of 10 patients required an exchange of osteo-synthetic implants, whereof three were exchanged to an external fixator. In five patients, we removed the implant because the fracture had already consolidated at the time of revision for infection. A total of 17/24 patients had a poly-microbial infection after a pelvic fracture and 3/24 patients died from post-traumatic multi-organ failure within the first 6 months after trauma. There were no cases of persistent infection within the remaining 21 patients. Conclusions: Although poly-microbial infection is common in FRI after pelvic fracture, the recurrence rate of infection is relatively low. A complex pelvic trauma with significant soft tissue injury is a risk factor for recurrent infection and multiple revisions. A strategy of DAIR can be successful in patients with a stable implant. In cases with recurrent infection or an unstable fracture site, the exchange of implants should be considered.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 7
    Online Resource
    Online Resource
    MDPI AG ; 2018
    In:  World Electric Vehicle Journal Vol. 9, No. 1 ( 2018-06-07), p. 8-
    In: World Electric Vehicle Journal, MDPI AG, Vol. 9, No. 1 ( 2018-06-07), p. 8-
    Abstract: To better evaluate the configuration of battery packs in electric vehicles (EV) in the early design phase, this paper proposes a mathematic model for the simulation of battery packs based on the elementwise calculations of matrices. This model is compatible with the different battery models and has a fast simulation speed. An experimental platform is built for the verification. Based on the proposed model and the statistic features of battery cells, the influence of the number of paralleled cells in a battery pack is evaluated in Monte-Carlo experiments. The simulation results obtained from Monte-Carlo experiments show that the parallel number is able to influence the total energy loss inside the cells, the energy loss caused by the balancing of the battery management system (BMS) and the degradation of the battery pack.
    Type of Medium: Online Resource
    ISSN: 2032-6653
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2934699-X
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  • 8
    Online Resource
    Online Resource
    MDPI AG ; 2022
    In:  Aerospace Vol. 9, No. 2 ( 2022-01-20), p. 49-
    In: Aerospace, MDPI AG, Vol. 9, No. 2 ( 2022-01-20), p. 49-
    Abstract: Model-based predictive maintenance using high-frequency in-flight data requires digital twins that can model the dynamics of their physical twin with high precision. The models of the twins need to be fast and dynamically updatable. Machine learning offers the possibility to address these challenges in modeling the transient performance of aero engines. During transient operation, heat transferred between the engine’s structure and the annulus flow plays an important role. Diabatic performance modeling is demonstrated using non-dimensional transient heat transfer maps and transfer learning to extend turbomachinery transient modeling. The general form of such a map for a simple system similar to a pipe is reproduced by a Multilayer Perceptron neural network. It is trained using data from a finite element simulation. In a next step, the network is transferred using measurements to model the thermal transients of an aero engine. Only a limited number of parameters measured during selected transient maneuvers is needed to generate suitable non-dimensional transient heat transfer maps. With these additional steps, the extended performance model matches the engine thermal transients well.
    Type of Medium: Online Resource
    ISSN: 2226-4310
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2756091-0
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  • 9
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 18, No. 3 ( 2017-03-22), p. 679-
    Abstract: Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune-mediated demyelinating disease affecting mainly children and young adults. Differentiation to multiple sclerosis is not always possible, due to overlapping clinical symptoms and recurrent and multiphasic forms. Until now, immunoglobulins reactive to myelin oligodendrocyte glycoprotein (MOG antibodies) have been found in a subset of patients with ADEM. However, there are still patients lacking autoantibodies, necessitating the identification of new autoantibodies as biomarkers in those patients. Therefore, we aimed to identify novel autoantibody targets in ADEM patients. Sixteen ADEM patients (11 seronegative, 5 seropositive for MOG antibodies) were analysed for potential new biomarkers, using a protein microarray and immunohistochemistry on rat brain tissue to identify antibodies against intracellular and surface neuronal and glial antigens. Nine candidate antigens were identified in the protein microarray analysis in at least two patients per group. Immunohistochemistry on rat brain tissue did not reveal new target antigens. Although no new autoantibody targets could be found here, future studies should aim to identify new biomarkers for therapeutic and prognostic purposes. The microarray analysis and immunohistochemistry methods used here have several limitations, which should be considered in future searches for biomarkers.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2017
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 10
    In: Nutrients, MDPI AG, Vol. 14, No. 9 ( 2022-05-07), p. 1963-
    Abstract: Little is known about the (co-)occurrence of smoking, alcohol at-risk drinking, physical inactivity and overweight, and the motivation to change these behavioral health risk factors (HRFs) in older general hospital patients with cardiovascular disease. Between October and December 2016, all consecutively admitted patients aged 50 to 79 years were proactively recruited on 3 cardiology wards and asked to participate in a survey on HRFs and behavior change motivation. Of the eligible patients, 80.4% participated in the survey (n = 328). The mean age was 66.5 years (standard deviation 9.0), and 65.5% were male. At least 1 HRF was present in 91.8% (n = 280), at least 2 HRFs in 54.4% (n = 166), and 3 or 4 HRFs in 12.1% (n = 37) of participants. The proportion of older adults who contemplated or were changing or planning to change their behavior to meet health behavior recommendations ranged between 66.0% (smoking) and 93.2% (alcohol consumption). The results indicate a notable co-occurrence of behavioral HRFs in older patients with cardiovascular disease. The majority of older adults were at least considering changing the respective behavior. To prevent and treat diseases efficiently, hospitalization may be a suitable moment for systematic multiple HRF screening and intervention.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2518386-2
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