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  • 1
    Online Resource
    Online Resource
    Use of Competition ELISA for Monitoring of West Nile Virus Infections in Horses in Germany
    MDPI AG ; 2013
    In:  International Journal of Environmental Research and Public Health Vol. 10, No. 8 ( 2013-07-24), p. 3112-3120
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 10, No. 8 ( 2013-07-24), p. 3112-3120
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph10083112
    Language: English
    Publisher: MDPI AG
    Publication Date: 2013
    detail.hit.zdb_id: 2175195-X
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  • 2
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    Structural and Biophysical Insights into SPINK1 Bound to Human Cationic Trypsin
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 7 ( 2022-03-23), p. 3468-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 7 ( 2022-03-23), p. 3468-
    Abstract: (1) The serine protease inhibitor Kazal type 1 (SPINK1) inhibits trypsin activity in zymogen granules of pancreatic acinar cells. Several mutations in the SPINK1 gene are associated with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). The most common variant is SPINK1 p.N34S. Although this mutation was identified two decades ago, the mechanism of action has remained elusive. (2) SPINK1 and human cationic trypsin (TRY1) were expressed in E. coli, and inhibitory activities were determined. Crystals of SPINK1–TRY1 complexes were grown by using the hanging-drop method, and phases were solved by molecular replacement. (3) Both SPINK1 variants show similar inhibitory behavior toward TRY1. The crystal structures are almost identical, with minor differences in the mutated loop. Both complexes show an unexpected rotamer conformation of the His63 residue in TRY1, which is a member of the catalytic triad. (4) The SPINK1 p.N34S mutation does not affect the inhibitory behavior or the overall structure of the protein. Therefore, the pathophysiological mechanism of action of the p.N34S variant cannot be explained mechanistically or structurally at the protein level. The observed histidine conformation is part of a mechanism for SPINK1 that can explain the exceptional proteolytic stability of this inhibitor.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23073468
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
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    Safety and Healthcare Resource Utilization in Patients Undergoing Left Atrial Appendage Closure—A Nationwide Analysis
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 14 ( 2023-07-09), p. 4573-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 14 ( 2023-07-09), p. 4573-
    Abstract: Percutaneous left atrial appendage closure (LAAC) has emerged as a non-pharmacological alternative for stroke prevention in patients with atrial fibrillation (AF) not suitable for anticoagulation therapy. Real-world data on peri-procedural outcomes are limited. The aim of this study was to analyze outcomes of peri-procedural safety and healthcare resource utilization in 11,240 adult patients undergoing LAAC in the United States between 2016 and 2019. Primary outcomes (safety) were in-hospital ischemic stroke or systemic embolism (SE), pericardial effusion (PE), major bleeding, device embolization and mortality. Secondary outcomes (resource utilization) were adverse discharge disposition, hospital length of stay (LOS) and costs. Logistic and Poisson regression models were used to analyze outcomes by adjusting for 10 confounders. SE decreased by 97% between 2016 and 2019 [95% Confidence Interval (CI) 0–0.24] (p = 0.003), while a trend to lower numbers of other peri-procedural complications was determined. In-hospital mortality (0.14%) remained stable. Hospital LOS decreased by 17% (0.78–0.87, p 〈 0.001) and adverse discharge rate by 41% (95% CI 0.41–0.86, p = 0.005) between 2016 and 2019, while hospital costs did not significantly change (p = 0.2). Female patients had a higher risk of PE (OR 2.86 [95% CI 2.41–6.39]) and SE (OR 5.0 [95% CI 1.28–43.6] ) while multi-morbid patients had higher risks of major bleeding (p 〈 0.001) and mortality (p = 0.031), longer hospital LOS (p 〈 0.001) and increased treatment costs (p = 0.073). Significant differences in all outcomes were observed between male and female patients across US regions. In conclusion, LAAC has become a safer and more efficient procedure. Significant sex differences existed across US regions. Careful considerations should be taken when performing LAAC in female and comorbid patients.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12144573
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 4
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    Clinical Relevance of Immersive Virtual Reality in the Assessment and Treatment of Addictive Disorders: A Systematic Review and Future Perspective
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 16 ( 2021-08-18), p. 3658-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 16 ( 2021-08-18), p. 3658-
    Abstract: (1) Background: Virtual reality (VR) has been investigated in a variety of psychiatric disorders, including addictive disorders (ADs); (2) Objective: This systematic review evaluates the current evidence of immersive VR (using head-mounted displays) in the clinical assessment and treatment of ADs; (3) Method: PubMed and PsycINFO were queried for publications up to November 2020; (4) Results: We screened 4519 titles, 114 abstracts and 85 full-texts, and analyzed 36 articles regarding the clinical assessment (i.e., diagnostic and prognostic value; n = 19) and treatment (i.e., interventions; n = 17) of ADs. Though most VR assessment studies (n = 15/19) showed associations between VR-induced cue-reactivity and clinical parameters, only two studies specified diagnostic value. VR treatment studies based on exposure therapy showed no or negative effects. However, other VR interventions like embodied and aversive learning paradigms demonstrated positive findings. The overall study quality was rather poor; (5) Conclusion: Though VR in ADs provides ecologically valid environments to induce cue-reactivity and provide new treatment paradigms, the added clinical value in assessment and therapy remains to be elucidated before VR can be applied in clinical care. Therefore, future work should investigate VR efficacy in randomized clinical trials using well-defined clinical endpoints.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10163658
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 5
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    Online Resource
    Characterisation of Lipoma-Preferred Partner as a Novel Mechanotransducer in Vascular Smooth Muscle Cells
    MDPI AG ; 2023
    In:  Cells Vol. 12, No. 18 ( 2023-09-19), p. 2315-
    Details
    In: Cells, MDPI AG, Vol. 12, No. 18 ( 2023-09-19), p. 2315-
    Abstract: In arteries and arterioles, a chronic increase in blood pressure raises wall tension. This continuous biomechanical strain causes a change in gene expression in vascular smooth muscle cells (VSMCs) that may lead to pathological changes. Here we have characterised the functional properties of lipoma-preferred partner (LPP), a Lin11–Isl1–Mec3 (LIM)-domain protein, which is most closely related to the mechanotransducer zyxin but selectively expressed by smooth muscle cells, including VSMCs in adult mice. VSMCs isolated from the aorta of LPP knockout (LPP-KO) mice displayed a higher rate of proliferation than their wildtype (WT) counterparts, and when cultured as three-dimensional spheroids, they revealed a higher expression of the proliferation marker Ki 67 and showed greater invasion into a collagen gel. Accordingly, the gelatinase activity was increased in LPP-KO but not WT spheroids. The LPP-KO spheroids adhering to the collagen gel responded with decreased contraction to potassium chloride. The relaxation response to caffeine and norepinephrine was also smaller in the LPP-KO spheroids than in their WT counterparts. The overexpression of zyxin in LPP-KO VSMCs resulted in a reversal to a more quiescent differentiated phenotype. In native VSMCs, i.e., in isolated perfused segments of the mesenteric artery (MA), the contractile responses of LPP-KO segments to potassium chloride, phenylephrine or endothelin-1 did not vary from those in isolated perfused WT segments. In contrast, the myogenic response of LPP-KO MA segments was significantly attenuated while zyxin-deficient MA segments displayed a normal myogenic response. We propose that LPP, which we found to be expressed solely in the medial layer of different arteries from adult mice, may play an important role in controlling the quiescent contractile phenotype of VSMCs.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells12182315
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661518-6
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  • 6
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    Lipoic Acid Synergizes with Antineoplastic Drugs in Colorectal Cancer by Targeting p53 for Proteasomal Degradation
    MDPI AG ; 2019
    In:  Cells Vol. 8, No. 8 ( 2019-07-30), p. 794-
    Details
    In: Cells, MDPI AG, Vol. 8, No. 8 ( 2019-07-30), p. 794-
    Abstract: Lipoic acid (LA) is a redox-active disulphide compound, which functions as a pivotal co-factor for mitochondrial oxidative decarboxylation. LA and chemical derivatives were shown to target mitochondria in cancer cells with altered energy metabolism, thereby inducing cell death. In this study, the impact of LA on the tumor suppressor protein p53 was analyzed in various colorectal cancer (CRC) cell lines, with a focus on the mechanisms driving p53 degradation. First, LA was demonstrated to trigger the depletion of both wildtype and mutant p53 protein in all CRC cells tested without influencing its gene expression and preceded LA-triggered cytotoxicity. Depletion of p53 coincided with a moderate, LA-dependent ROS production, but was not rescued by antioxidant treatment. LA induced the autophagy receptor p62 and differentially modulated autophagosome formation in CRC cells. However, p53 degradation was not mediated via autophagy as shown by chemical inhibition and genetic abrogation of autophagy. LA treatment also stabilized and activated the transcription factor Nrf2 in CRC cells, which was however dispensable for p53 degradation. Mechanistically, p53 was found to be readily ubiquitinylated and degraded by the proteasomal machinery following LA treatment, which did not involve the E3 ubiquitin ligase MDM2. Intriguingly, the combination of LA and anticancer drugs (doxorubicin, 5-fluorouracil) attenuated p53-mediated stabilization of p21 and resulted in synergistic killing in CRC cells in a p53-dependant manner.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells8080794
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2661518-6
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  • 7
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    Symptom Severity and Health-Related Quality of Life in Patients with Atrial Fibrillation: Findings from the Observational ARENA Study
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 4 ( 2022-02-21), p. 1140-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 4 ( 2022-02-21), p. 1140-
    Abstract: Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with impaired health-related quality of life (HRQoL), high symptom severity, and poor cardiovascular outcomes. Both clinical and psychological factors may contribute to symptom severity and HRQoL in AF. Methods: Using data from the observational Atrial Fibrillation Rhine-Neckar Region (ARENA) trial, we identified medical and psychosocial factors associated with AF-related symptom severity using European Heart Rhythm Association symptom classification and HRQoL using 5-level EuroQoL- 5D. Results: In 1218 AF patients (mean age 71.1 ± 10.5 years, 34.5% female), female sex (OR 3.7, p 〈 0.001), preexisting coronary artery disease (CAD) (OR 1.7, p = 0.020), a history of cardioversion (OR 1.4, p = 0.041), cardiac anxiety (OR 1.2; p 〈 0.001), stress from noise (OR 1.4, p = 0.005), work-related stress (OR 1.3, p = 0.026), and sleep disturbance (OR 1.2, p = 0.016) were associated with higher AF-related symptom severity. CAD (β = −0.23, p = 0.001), diabetes mellitus (β = −0.25, p 〈 0.001), generalized anxiety (β = −0.30, p 〈 0.001), cardiac anxiety (β = −0.16, p 〈 0.001), financial stress (β = −0.11, p 〈 0.001), and sleep disturbance (β = 0.11, p 〈 0.001) were associated with impaired HRQoL. Conclusions: Psychological characteristics, preexisting CAD, and diabetes may play an important role in the identification of individuals at highest risk for impaired HRQoL and high symptom severity in patients with AF.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11041140
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 8
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    Global Sensitivity Analysis and Uncertainty Quantification for Simulated Atrial Electrocardiograms
    MDPI AG ; 2022
    In:  Metrology Vol. 3, No. 1 ( 2022-12-26), p. 1-28
    Details
    In: Metrology, MDPI AG, Vol. 3, No. 1 ( 2022-12-26), p. 1-28
    Abstract: The numerical modeling of cardiac electrophysiology has reached a mature and advanced state that allows for quantitative modeling of many clinically relevant processes. As a result, complex computational tasks such as the creation of a variety of electrocardiograms (ECGs) from virtual cohorts of models representing biological variation are within reach. This requires a correct representation of the variability of a population by suitable distributions of a number of input parameters. Hence, the assessment of the dependence and variation of model outputs by sensitivity analysis and uncertainty quantification become crucial. Since the standard metrological approach of using Monte–Carlo simulations is computationally prohibitive, we use a nonintrusive polynomial chaos-based approximation of the forward model used for obtaining the atrial contribution to a realistic electrocardiogram. The surrogate increases the speed of computations for varying parameters by orders of magnitude and thereby greatly enhances the versatility of uncertainty quantification. It further allows for the quantification of parameter influences via Sobol indices for the time series of 12 lead ECGs and provides bounds for the accuracy of the obtained sensitivities derived from an estimation of the surrogate approximation error. Thus, it is capable of supporting and improving the creation of synthetic databases of ECGs from a virtual cohort mapping a representative sample of the human population based on physiologically and anatomically realistic three-dimensional models.
    Type of Medium: Online Resource
    ISSN: 2673-8244
    URL: Article
    DOI: 10.3390/metrology3010001
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 3136576-0
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  • 9
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    Campylobacter concisus Impairs Sodium Absorption in Colonic Epithelium via ENaC Dysfunction and Claudin-8 Disruption
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 2 ( 2020-01-07), p. 373-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 2 ( 2020-01-07), p. 373-
    Abstract: The epithelial sodium channel (ENaC) can increase the colonic absorptive capacity for salt and water. Campylobacter concisus is a common pathogenic epsilonproteobacterium, causing enteritis and diarrhea. It can induce barrier dysfunction in the intestine, but its influence on intestinal transport function is still unknown. Therefore, our study aimed to characterize C. concisus effects on ENaC using the HT-29/B6-GR/MR (epithelial cell line HT-29/B6 transfected with glucocorticoid and mineralocorticoid receptors) cell model and mouse colon. In Ussing chambers, C. concisus infection inhibited ENaC-dependent Na+ transport as indicated by a reduction in amiloride-sensitive short circuit current (−55%, n = 15, p 〈 0.001). This occurred via down-regulation of β- and γ-ENaC mRNA expression and ENaC ubiquitination due to extracellular signal-regulated kinase (ERK)1/2 activation, predicted by Ingenuity Pathway Analysis (IPA). In parallel, C. concisus reduced the expression of the sealing tight junction (TJ) protein claudin-8 and induced claudin-8 redistribution off the TJ domain of the enterocytes, which facilitates the back leakage of Na+ ions into the intestinal lumen. In conclusion, C. concisus caused ENaC dysfunction via interleukin-32-regulated ERK1/2, as well as claudin-8-dependent barrier dysfunction—both of which contribute to Na+ malabsorption and diarrhea.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21020373
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 10
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    Cryopreservation of Duckweed Genetic Diversity as Model for Long-Term Preservation of Aquatic Flowering Plants
    MDPI AG ; 2023
    In:  Plants Vol. 12, No. 18 ( 2023-09-18), p. 3302-
    Details
    In: Plants, MDPI AG, Vol. 12, No. 18 ( 2023-09-18), p. 3302-
    Abstract: Vegetatively propagating aquatic angiosperms, the Lemnaceae family (duckweeds) represents valuable genetic resources for circular bioeconomics and other sustainable applications. Due to extremely fast growth and laborious cultivation of in vitro collections, duckweeds are an urgent subject for cryopreservation. We developed a robust and fast DMSO-free protocol for duckweed cryopreservation by vitrification. A single-use device was designed for sampling of duckweed fronds from donor culture, further spin-drying, and subsequent transferring to cryo-tubes with plant vitrification solution 3 (PVS3). Following cultivation in darkness and applying elevated temperatures during early regrowth stage, a specific pulsed illumination instead of a diurnal regime enabled successful regrowth after the cryopreservation of 21 accessions of Spirodela, Landoltia, Lemna, and Wolffia genera, including interspecific hybrids, auto- and allopolyploids. Genome size measurements revealed no quantitative genomic changes potentially caused by cryopreservation. The expression of CBF/DREB1 genes, considered as key factors in the development of freezing tolerance, was studied prior to cooling but was not linked with duckweed regrowth after rewarming. Despite preserving chlorophyll fluorescence after rewarming, the rewarmed fronds demonstrated nearly zero photosynthetic activity, which did not recover. The novel protocol provides the basis for future routine application of cryostorage to duckweed germplasm collections, saving labor for in vitro cultivation and maintaining characterized reference and mutant samples.
    Type of Medium: Online Resource
    ISSN: 2223-7747
    URL: Article
    DOI: 10.3390/plants12183302
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704341-1
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