RepoMed (Medizinische Hochschule Hannover)
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Eosinophilic cationic protein as marker for response to antibody therapy in severe asthma
No full textContribution of human stem cell-derived cardiomyocyte subtypes to bioartificial cardiac tissue formation and function
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Real-Time Characterization of Clonal Fate Decisions in Complex Leukemia Samples by Fluorescent Genetic Barcoding
Get PDFClonal heterogeneity in acute myeloid leukemia (AML) forms the basis for treatment failure and relapse. Attempts to decipher clonal evolution and clonal competition primarily depend on deep sequencing approaches. However, this prevents the experimental confirmation of the identified disease-relevant traits on the same cell material. Here, we describe the development and application of a complex fluorescent genetic barcoding (cFGB) lentiviral vector system for the labeling and subsequent multiplex tracking of up to 48 viable AML clones by flow cytometry. This approach allowed the visualization of longitudinal changes in the in vitro growth behavior of multiplexed color-coded AML clones for up to 137 days. Functional studies of flow cytometry-enriched clones documented their stably inherited increase in competitiveness, despite the absence of growth-promoting mutations in exome sequencing data. Transplantation of aliquots of a color-coded AML cell mix into mice revealed the initial engraftment of similar clones and their subsequent differential distribution in the animals over time. Targeted RNA-sequencing of paired pre-malignant and de novo expanded clones linked gene sets associated with Myc-targets, embryonic stem cells, and RAS signaling to the foundation of clonal expansion. These results demonstrate the potency of cFGB-mediated clonal tracking for the deconvolution of verifiable driver-mechanisms underlying clonal selection in leukemia
White Blood Cell and Platelet Counts Are Not Suitable as Biomarkers in the Differential Diagnostics of Dementia
Get PDFApart from Alzheimer's disease (AD), no biomarkers for the differential diagnosis of dementia have been established to date. Inflammatory processes contribute to the pathogenesis of dementia subtypes, e.g., AD or frontotemporal dementia (FTD). In the context of cancer or cardiovascular diseases, white blood cell (WBC) populations and platelet counts, as well as C-reactive protein (CRP), have emerged as biomarkers. Their clinical relevance in dementia, however, is currently only insufficiently investigated. In the present study, hematological and inflammatory parameters were measured in the peripheral blood of 97 patients admitted to the gerontopsychiatric ward of Hannover Medical School, a university hospital in Germany, for dementia assessment. The study population comprised 20 non-demented, depressed patients (control group) and 77 demented patients who were assigned to five different groups based on their underlying dementia etiology: AD, n = 33; vascular dementia, n = 12; mixed dementia, n = 21; FTD, n = 5; and Korsakoff syndrome, n = 6. We observed neither statistically significant differences regarding total WBC populations, platelet counts, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, nor CRP levels between the control group and the five dementia groups. CRP levels tended to be higher in patients with Korsakoff syndrome than in the control group and in AD patients. Thus, CRP could possibly play a role in the differential diagnosis of dementia. This should be investigated further in future prospective studies with larger sample sizes. WBC and platelet counts, by contrast, do not appear to be suitable biomarkers in the differential diagnosis of dementia
Psychometric properties, factor structure, and German population norms of the multidimensional fatigue inventory (MFI-20)
Get PDFObjective The Multidimensional Fatigue Inventory (MFI-20) is commonly used, but its factor structure remains unclear. The MFI-20 consists of five subscales (general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue). This study investigates the psychometric properties, including the factor structure, of a general German population sample and tests group hypotheses on gender and age. Another objective is to provide normative data by gender and age groups. Methods Using data from a representative German sample (n=2,509), reliability and convergent validity measures, group hypothesis testing, and confirmatory/exploratory factor analyses were conducted. Results The MFI-20 demonstrated satisfactory internal consistency and showed adequate convergent validity with the SF-36. All subscales of the MFI-20 were significantly correlated (0.71-0.85). Physical fatigue exhibited the highest (0.42) and mental fatigue had the lowest (0.19) correlation with age. Fatigue scores were significantly higher for women and significantly increased with age. A five-factor structure showed poor model fit; using an exploratory factor analysis, a two-factor structure emerged (a general factor and a mental/motivational factor). Conclusion The MFI-20 is a reliable and valid instrument for measuring fatigue in the general population, but the five-factor structure is not supported. The subscale general fatigue or the MFI-20 total score might measure fatigue sufficiently. The provided norms can be used for further research and individual assessment
Estimating trends in working life expectancy based on health insurance data from Germany: challenges and advantages
Get PDFAgainst the backdrop of population aging and growing strain on pension systems, monitoring the development of Working Life Expectancy (WLE) is vital to assess whether the policies taken are effective. This is the first study investigating time trends and educational inequalities in WLE based on German health insurance data. The analyses are based on the data of the AOK Lower Saxony (N = 3,347,912) covering three time periods (2006-08, 2011-13, and 2016-18). WLE is defined as years spent in the labor force (i.e. in employment and unemployment) and was calculated for each age between 18 and 69 years for the three periods to depict changes over time using multistate life table analysis. Educational inequalities in 2011-13 are reported for two educational levels (8-11 years and 12-13 years of schooling). WLE increased in both sexes with increases being stronger among women. This holds irrespective of whether WLE at age 18 (35.8-38.3 years in men, 27.5-34.0 years in women) or the older working-age (e.g. at age 50 10.2-11.7 years in men, 7.8-10.5 years in men) is considered. Among women at all ages and men from their mid-20s onwards, WLE was higher among higher-educated individuals. Inequalities were most pronounced among women (e.g. Δ3.1 years in women, Δ1.3 years in men at age 50). The study supports previous research indicating that measures to extend working life are effective, but that noticeable inequalities in WLE exist. Health insurance data represent a valuable source for such research that has so far remained untapped. The data provide a suitable basis to investigate trends and inequalities in WLE. Future research should build on the strengths of the data by broadening the research towards a more comprehensive analysis of the development of WLE from a health perspective
Brain-derived neurotrophic factor and immune cells in osteoarthritis, chronic low back pain, and chronic widespread pain patients: association with anxiety and depression
Get PDFSelective attention decoding in bimodal cochlear implant users
Get PDFThe growing group of cochlear implant (CI) users includes subjects with preserved acoustic hearing on the opposite side to the CI. The use of both listening sides results in improved speech perception in comparison to listening with one side alone. However, large variability in the measured benefit is observed. It is possible that this variability is associated with the integration of speech across electric and acoustic stimulation modalities. However, there is a lack of established methods to assess speech integration between electric and acoustic stimulation and consequently to adequately program the devices. Moreover, existing methods do not provide information about the underlying physiological mechanisms of this integration or are based on simple stimuli that are difficult to relate to speech integration. Electroencephalography (EEG) to continuous speech is promising as an objective measure of speech perception, however, its application in CIs is challenging because it is influenced by the electrical artifact introduced by these devices. For this reason, the main goal of this work is to investigate a possible electrophysiological measure of speech integration between electric and acoustic stimulation in bimodal CI users. For this purpose, a selective attention decoding paradigm has been designed and validated in bimodal CI users. The current study included behavioral and electrophysiological measures. The behavioral measure consisted of a speech understanding test, where subjects repeated words to a target speaker in the presence of a competing voice listening with the CI side (CIS) only, with the acoustic side (AS) only or with both listening sides (CIS+AS). Electrophysiological measures included cortical auditory evoked potentials (CAEPs) and selective attention decoding through EEG. CAEPs were recorded to broadband stimuli to confirm the feasibility to record cortical responses with CIS only, AS only, and CIS+AS listening modes. In the selective attention decoding paradigm a co-located target and a competing speech stream were presented to the subjects using the three listening modes (CIS only, AS only, and CIS+AS). The main hypothesis of the current study is that selective attention can be decoded in CI users despite the presence of CI electrical artifact. If selective attention decoding improves combining electric and acoustic stimulation with respect to electric stimulation alone, the hypothesis can be confirmed. No significant difference in behavioral speech understanding performance when listening with CIS+AS and AS only was found, mainly due to the ceiling effect observed with these two listening modes. The main finding of the current study is the possibility to decode selective attention in CI users even if continuous artifact is present. Moreover, an amplitude reduction of the forward transfer response function (TRF) of selective attention decoding was observed when listening with CIS+AS compared to AS only. Further studies to validate selective attention decoding as an electrophysiological measure of electric acoustic speech integration are required
