Institutes
Refine
Year of publication
- 2021 (672) (remove)
Document Type
- Article (623)
- Preprint (32)
- Conference Proceeding (11)
- Doctoral Thesis (6)
Language
- English (672) (remove)
Has Fulltext
- yes (672)
Is part of the Bibliography
- no (672)
Keywords
- SARS-CoV-2 (24)
- COVID-19 (20)
- inflammation (12)
- prostate cancer (9)
- autophagy (8)
- Epilepsy (7)
- survival (7)
- ADHD (6)
- breast cancer (6)
- radical prostatectomy (6)
Institute
- Medizin (672)
- Biochemie, Chemie und Pharmazie (8)
- Biowissenschaften (7)
- Psychologie und Sportwissenschaften (6)
- Buchmann Institut für Molekulare Lebenswissenschaften (BMLS) (5)
- Georg-Speyer-Haus (4)
- Physik (3)
- Biodiversität und Klima Forschungszentrum (BiK-F) (2)
- Ernst Strüngmann Institut (2)
- Erziehungswissenschaften (2)
Iron deficiency (ID) is a common manifestation of inflammatory bowel disease (IBD), arising primarily due to chronic inflammation and/or blood loss. There is no gold standard for ID diagnosis, which is often complicated by concomitant inflammation. Zinc protoporphyrin (ZnPP) correlates with parameters of iron homeostasis and has been identified as a promising marker for ID, irrespective of inflammation. We investigated the diagnostic performance of ZnPP in ID, iron deficiency anemia, anemia of chronic disease and mixed anemia in a cross-sectional study in 130 patients with IBD. Different parameters were compared by receiver operator characteristic (ROC) analysis as detectors of iron-restricted erythropoiesis (IRE). IRE was detected in 91 patients (70.0%); fifty-nine (64.8%) had absolute ID and 23 (25.4%) functional ID. When inflammation was present, ZnPP was a more reliable sole biomarker of IRE than MCV, transferrin saturation (TSAT) or ferritin (AUC; 0.855 vs. 0.763, 0.834% and 0.772, respectively). The specificity of TSAT was significantly lower than ZnPP when inflammation was present (38% vs. 71%, respectively). We conclude that ZnPP is a reliable biomarker of functional ID in patients with IBD and more dependable than ferritin or TSAT, which are influenced by chronic inflammation. We propose that ZnPP may also have utility in patients with other chronic diseases.
Background: Peanuts are a member of the legume family (botanical family Leguminosae) and peanut allergies are the most common cause of food anaphylaxis in many countries. The prevalence of peanut allergy is increasing.
Methods: Experts from Germany and Austria performed a standardized literature search and published their consensus recommendations in a White Paper on Peanut Allergy, which this care pathway is based upon, thus, providing a comprehensive diagnosis and treatment algorithm.
Results: The most important diagnostic key elements include a detailed clinical medical history, evidence of peanut-specific sensitization by means of skin prick testing and/or in vitro determination of the peanut (extract)-specific IgE and/or the molecular component diagnostics (most important Ara h 2-specific IgE, sometimes also Ara h1-, 3-, 6-, 8- and 9-specific IgE) as well as the gold standard, the double-blind, placebo-controlled food challenge. The diagnostic algorithms were created for the following constellations: Suspected primary peanut allergy with a clear history of systemic immediate-type reaction, suspected primary peanut allergy with questionable symptoms, suspected secondary (possibly pollen-associated) peanut allergy with a history of solely oropharyngeal symptoms and incidental finding of sensitization and no peanut ingestion so far.
Conclusions: After established diagnosis the standard of care is counseling to avoid peanut contact and prescription of emergency medications (oral antihistamines, oral steroids, inhaled β2-agonists, injectable intramuscular epinephrine) as needed. Instruction on the use of these emergency medications should be provided. A preparation for oral immunotherapy (OIT) for 4 to 17 years old peanut allergic children/ adolescents has been recently approved by the regulatory authorities. OIT for peanut allergy shows high efficacy and an acceptable safety profile, improves quality of life, and health economic aspects. Thus it offers a therapeutic option for peanut allergic children and adolescents.
In recent years, the clinical usefulness of the Wada test (WT) has been debated among researchers in the field. Therefore, we aimed to assess its contribution to the prediction of change in verbal learning and verbal memory function after epilepsy surgery. Data from 56 patients with temporal lobe epilepsy who underwent WT and subsequent surgery were analyzed retrospectively. Additionally, a standard neuropsychological assessment evaluating attentional, learning and memory, visuospatial, language, and executive function was performed both before and 12 months after surgery. Hierarchical linear regression analyses were used to determine the incremental value of WT results over socio-demographic, clinical, and neuropsychological characteristics in predicting postsurgical change in patients’ verbal learning and verbal memory function. The incorporation of WT results significantly improved the prediction models of postsurgical change in verbal learning (∆R2 = 0.233, p = .032) and verbal memory function (∆R2 = 0.386, p = .005). Presurgical performance and WT scores accounted for 41.8% of the variance in postsurgical change in verbal learning function, and 51.1% of the variance in postsurgical change in verbal memory function. Our findings confirm that WT results are of significant incremental value for the prediction of postsurgical change in verbal learning and verbal memory function. Thus, the WT contributes to determining the risks of epilepsy surgery and, therefore, remains an important part of the presurgical work-up of selected patients with clear clinical indications.
The evaluation of pharmacological data using machine learning requires high data quality. Therefore, data preprocessing, that is, cleaning analytical laboratory errors, replacing missing values or outliers, and transforming data adequately before actual data analysis, is crucial. Because current tools available for this purpose often require programming skills, preprocessing tools with graphical user interfaces that can be used interactively are needed. In collaboration between data scientists and experts in bioanalytical diagnostics, a graphical software package for data preprocessing called pguIMP is proposed, which contains a fixed sequence of preprocessing steps to enable reproducible interactive data preprocessing. As an R-based package, it also allows direct integration into this data science environment without requiring any programming knowledge. The implementation of contemporary data processing methods, including machine-learning-based imputation techniques, ensures the generation of corrected and cleaned bioanalytical data sets that preserve data structures such as clusters better than is possible with classical methods. This was evaluated on bioanalytical data sets from lipidomics and drug research using k-nearest-neighbors-based imputation followed by k-means clustering and density-based spatial clustering of applications with noise. The R package provides a Shiny-based web interface designed to be easy to use for non–data analysis experts. It is demonstrated that the spectrum of methods provided is suitable as a standard pipeline for preprocessing bioanalytical data in biomedical research domains. The R package pguIMP is freely available at the comprehensive R archive network (https://cran.r-project.org/web/packages/pguIMP/index.html).
Dual-energy CT (DECT) has emerged into clinical routine as an imaging technique with unique postprocessing utilities that improve the evaluation of different body areas. The virtual non-calcium (VNCa) reconstruction algorithm has shown beneficial effects on the depiction of bone marrow pathologies such as bone marrow edema. Its main advantage is the ability to substantially increase the image contrast of structures that are usually covered with calcium mineral, such as calcified vessels or bone marrow, and to depict a large number of traumatic, inflammatory, infiltrative, and degenerative disorders affecting either the spine or the appendicular skeleton. Therefore, VNCa imaging represents another step forward for DECT to image conditions and disorders that usually require the use of more expensive and time-consuming techniques such as magnetic resonance imaging, positron emission tomography/CT, or bone scintigraphy. The aim of this review article is to explain the technical background of VNCa imaging, showcase its applicability in the different body regions, and provide an updated outlook on the clinical impact of this technique, which goes beyond the sole improvement in image quality.
Objective: Vertigo is a common side effect of cochlear implant (CI) treatment. This prospective study examines the incidence of postoperative vertigo over time and aims to analyze influencing factors such as electrode design and insertion angle (IA).
Study Design and Setting: This is a prospective study which has been conducted at a tertiary referral center (academic hospital).
Patients: A total of 29 adults were enrolled and received a unilateral CI using one of six different electrode carriers, which were categorized into “structure-preserving” (I), “potentially structure-preserving” (II), and “not structure-preserving” (III).
Intervention: Subjective vertigo was assessed by questionnaires at five different time-points before up to 6 months after surgery. The participants were divided into four groups depending on the time of the presence of vertigo before and after surgery. Preoperatively and at 6 months postoperatively, a comprehensive vertigo diagnosis consisting of Romberg test, Unterberger test, subjective visual vertical, optokinetic test, video head impulse test, and caloric irrigation test was performed. In addition, the IA was determined, and the patients were divided in two groups (<430°; ≥430°).
Main Outcome Measures: The incidence of vertigo after CI surgery (group 1) was reported, as well as the correlation of subjective vertigo with electrode array categories (I–III) and IA.
Results: Among the participants, 45.8% experienced new vertigo after implantation. Based on the questionnaire data, a vestibular origin was suspected in 72.7%. The results did not show a significant correlation with subjective vertigo for any of the performed tests. In group 1 with postoperative vertigo, 18% of patients showed conspicuous results in a quantitative analysis of caloric irrigation test despite the fact that the category I or II electrodes were implanted, which are suitable for structure preservation. Average IA was 404° for the overall group and 409° for group 1. There was no statistically significant correlation between IA and perceived vertigo.
Conclusions: Though vertigo after CI surgery seems to be a common complication, the test battery used here could not objectify the symptoms. Further studies should clarify whether this is due to the multifactorial cause of vertigo or to the lack of sensitivity of the tests currently in use. The proof of reduced probability for vertigo when using atraumatic electrode carrier was not successful, nor was the proof of a negative influence of the insertion depth.
Adolescence has been linked to an enhanced tolerance of uncertainty and risky behavior and is possibly connected to an increased response toward rewards. However, previous research has produced inconsistent findings. To investigate whether these findings are due to different reward probabilities used in the experimental design, we extended a monetary incentive delay (MID) task by including three different reward probabilities. Using functional magnetic resonance imaging, 25 healthy adolescents and 22 adults were studied during anticipation of rewards in the VS. Differently colored cue stimuli indicated either a monetary or verbal trial and symbolized different reward probabilities, to which the participants were blinded. Results demonstrated faster reaction times for lower reward probabilities (33%) in both age groups. Adolescents were slower through all conditions and had less activation on a neural level. Imaging results showed a three-way interaction between age group x condition x reward probability with differences in percent signal change between adolescents and adults for the high reward probabilities (66%, 88%) while adolescents demonstrated differences for the lowest (33%). Therefore, previous inconsistent findings could be due to different reward probabilities, which makes examining these crucial for a better understanding of adolescent and adult behavior.
Vascular biotransformation of organic nitrates is independent of cytochrome P450 monooxygenases
(2021)
Background and Purpose: Organic nitrates such as nitroglycerin (NTG) or pentaerythritol tetranitrate (PETN) have been used for over a century in the treatment of angina or ischaemic heart disease. These compounds are prodrugs which release their nitrovasodilators upon enzymic bioactivation by aldehyde dehydrogenase (ALDH2) or cytochromes P450 (CYP). Whereas ALDH2 is known to directly activate organic nitrates in vessels, the contribution of vascular CYPs is unknown and was studied here.
Experimental Approach: As all CYPs depend on cytochrome P450 reductase (POR) as electron donor, we generated a smooth muscle cell-specific, inducible knockout mouse of POR (smcPOR−/−) to investigate the contribution of POR/CYP to vascular biotransformation of organic nitrates.
Key Results: Microsomes containing recombinant CYPs expressed in human vascular tissues released nitrite from NTG and PETN with CYP2C9 and CYP2C8 being most efficient. SFK525, a CYP suicide inhibitor, blocked this effect. smcPOR−/− mice exhibited no obvious cardiovascular phenotype (normal cardiac weight and endothelium-dependent relaxation) and plasma and vascular nitrite production was similar to control (CTL) animals. NTG- and PETN-induced relaxation of isolated endothelium-intact or endothelium-denuded vessels were identical between CTL and smcPOR−/−. Likewise, nitrite release from organic nitrates in aortic rings was not affected by deletion of POR in smooth muscle cells (SMCs). In contrast, inhibition of ALDH2 by benomyl (10 μM) inhibited NTG-induced nitrite production and relaxation. Deletion of POR did not modulate this response.
Conclusions and Implications: Our data suggest that metabolism by vascular CYPs does not contribute to the pharmacological function of organic nitrates.
Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.