RepoMed (Medizinische Hochschule Hannover)
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Evaluation of the pediatric-centered integrated care AOK Junior: protocol for a mixed-method study.
Get PDFBACKGROUND:The "AOK-Junior" care program of the AOK Nordost (a German statutory health insurance) completes the primary care for children and adolescents (C&A) in the federal states of Berlin, Brandenburg and Mecklenburg-Vorpommern in Germany. The focus of this program is on prevention and early detection of illness on C&A. Furthermore, the aim is to maintain the health of C&A and to prevent, detect and treat illness on time. Elements of the program are not only the integrated care of C&A, but also, for example, weight reduction and additional medical checkups U10, U11 and J2. The evaluation of the complex intervention should provide information about the effectiveness of early disease detection and costs-effectiveness as well as of other parameters like satisfaction. METHODS:The evaluation is performed on the levels of structural-, process- and results-quality. The cost effectiveness is also assessed by means of a health economic evaluation. In addition to the collection of qualitative and quantitative primary data from participating and non-participating C&A and paediatricians, routine data from a statutory health insurance are used in the evaluation. Furthermore, a cross-sectional design is used to evaluate the structure and process quality. The effectiveness is evaluated in longitudinal section design on the basis of the secondary data. The quantitative surveys include net n = 1096 C&A and n = 340 pediatricians. For the focus groups, a sample of 72 to 96 parents as well as pediatricians will be sought by using the method of theoretical sampling. DISCUSSION:Around 560 pediatricians and 63,000 C&A currently participate in the AOK Nordost care program. The project provides information to what extent secondary preventive measures can lead to the early detection of diseases and on the associated cost-effectiveness. Furthermore, potentials and barriers of the program implementation are identified. The results of the evaluation study are expected not only to contribute to the further development of the care program, but also to derive recommendations for action. TRIAL REGISTRATION:German Clinical Trials Register (DRKS), DRKS-ID: DRKS00015280. Prospectively registered on 18 March 2019
Risiko von akutem Nierenversagen und renalen Nebenwirkungen unter Behandlung mit SGLT2-Inhibitoren
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Differential expression patterns of glycosphingolipids and C-type lectin receptors on immune cells in absence of functional regulatory T cells.
Get PDFBackground Glycosylation is a common and complex type of protein posttranslational modification. Altered glycosylation of immunoglobulins in autoimmune diseases has led to the "altered glycan hypothesis" postulating existence of a unique glycan signature on immune cells and extracellular proteins characterized by site-specific relative abundances of individual glycan structures and glycosylation patterns. However, it is not clear how glycosylation on leukocyte subpopulations differ between states of health or inflammation. Hypothesis Glycosphingolipid patterns on immune cells of forkhead-box-P3-deficient scurfy mice differs from those on wild-type immune cells. Methods T cells and dendritic cells were isolated from spleens of either wild-type or age-matched scurfy mice. Glycosphingolipids of CD4+ T cells and splenic dendritic cells from wild-type and scurfy mice were then analyzed by multiplexed capillary gel electrophoresis coupled to laser-induced fluorescence detection (xCGE-LIF). In addition, flow cytometry and ChipCytometry were used to access expression patterns of various C-type lectin receptors on antigen-presenting cells from various organs of both wild-type and scurfy mice. Results We, hereby report differential expression of glycosphingolipids in health and under inflammatory conditions as reflected in wild-type and scurfy mice. Furthermore, we observed that the absence of functional regulatory T cells correlated with elevated expression of CLEC-7A and CD205 but a reduction in levels of CLEC12A and CD206 on antigen-presenting cells. Conclusion We hereby show that the absence of functional regulatory T cells affects expression pattern and quantities of glycosphingolipids on immune cells. Thus, glycosphingolipids could serve as biomarkers for mapping genetical and homeostatic perturbances such as those resulting from a diseased condition
The Loss of HLA-F/KIR3DS1 Ligation Is Mediated by Hemoglobin Peptides.
Get PDFThe human leukocyte antigen (HLA)-Ib molecule, HLA-F, is known as a CD4+ T-cell protein and mediator of HIV progression. While HLA-Ia molecules do not have the chance to select and present viral peptides for immune recognition due to protein downregulation, HLA-F is upregulated. Post HIV infection, HLA-F loses the affinity to its activating receptor KIR3DS1 on NK cells leading to progression of the HIV infection. Several studies aimed to solve the question of the biophysical interface between HLA ligands and their cognate receptors. It became clear that even an invariant HLA molecule can be structurally modified by the variability of the bound peptide. We recently discovered the ability of HLA-F to select and present peptides and the HLA-F allele-specific peptide selection from the proteomic content using soluble HLA (sHLA) technology and a sophisticated MS method. We established recombinant K562 cells that express membrane-bound HLA-F*01:01, 01:03 or 01:04 complexes. While a recombinant soluble form of KIR3DS1 did not bind to the peptide-HLA-F complexes, acid elution of the peptides resulted in the presentation of HLA-F open conformers, and the binding of the soluble KIR3DS1 receptor increased. We used CD4+/HIV- and CD4+/HIV+ cells and performed an MS proteome analysis. We could detect hemoglobin as significantly upregulated in CD4+ T-cells post HIV infection. The expression of cellular hemoglobin in nonerythroid cells has been described, yet HLA-Ib presentation of hemoglobin-derived peptides is novel. Peptide sequence analysis from HLA-F allelic variants featured hemoglobin peptides as dominant and shared. The reciprocal experiment of binding hemoglobin peptide fractions to the HLA-F open conformers resulted in significantly diminished receptor recognition. These results underpin the molecular involvement of HLA-F and its designated peptide ligand in HIV immune escape
Structural and Computational Insights into a Blebbistatin-Bound Myosin•ADP Complex with Characteristics of an ADP-Release Conformation along the Two-Step Myosin Power Stoke.
Get PDFThe motor protein myosin drives a wide range of cellular and muscular functions by generating directed movement and force, fueled through adenosine triphosphate (ATP) hydrolysis. Release of the hydrolysis product adenosine diphosphate (ADP) is a fundamental and regulatory process during force production. However, details about the molecular mechanism accompanying ADP release are scarce due to the lack of representative structures. Here we solved a novel blebbistatin-bound myosin conformation with critical structural elements in positions between the myosin pre-power stroke and rigor states. ADP in this structure is repositioned towards the surface by the phosphate-sensing P-loop, and stabilized in a partially unbound conformation via a salt-bridge between Arg131 and Glu187. A 5 Å rotation separates the mechanical converter in this conformation from the rigor position. The crystallized myosin structure thus resembles a conformation towards the end of the two-step power stroke, associated with ADP release. Computationally reconstructing ADP release from myosin by means of molecular dynamics simulations further supported the existence of an equivalent conformation along the power stroke that shows the same major characteristics in the myosin motor domain as the resolved blebbistatin-bound myosin-II·ADP crystal structure, and identified a communication hub centered on Arg232 that mediates chemomechanical energy transduction
The perception of the stereo effect in bilateral and bimodal cochlear implant users and its contribution to music enjoyment.
Get PDFOBJECTIVES:In this clinical study, stereo perception of music samples and its contribution to music enjoyment in CI users is investigated. It is studied in free field as well as direct audio presentation. METHODS:20 bilateral and 9 bimodal CI users performed stereo detection tests and music enjoyment ratings. Music was presented either in mono or in stereo in free field or with direct audio presentation. Stereo detection was assessed with a 3-AFC paradigm. Music enjoyment was studied with scale ratings. RESULTS:For bilateral CI users, stereo detection increased from 52% correct in free field to 86% with direct audio presentation. Increased music enjoyment with improved stereo detection was obtained. Bimodal CI users could not identify stereo sounds. Music enjoyment did not increase for stereo presentations in bimodal subjects. DISCUSSION:For bilateral CI users, improved stereo detection might increase music enjoyment with direct audio presentation, which is likely due to bypassing the room acoustics. In bimodal CI users, no clear improvement was found, which is likely attributed due to the different hearing losses and therefore individually different interaural frequency overlaps between the hearing aid and the cochlear implant. CONCLUSION:Direct audio presentation is an efficient method to improve music enjoyment in bilateral CI users
Auswirkungen qualitativer Aspekte von Körperbewegung auf die Hauttemperatur: eine randomisierte Studie zur Eurythmie Therapie
No full textIncome inequalities in stroke incidence and mortality: Trends in stroke-free and stroke-affected life years based on German health insurance data.
No full textBACKGROUND:Due to substantial improvements in prevention and therapy, stroke incidence and mortality rates have decreased during the last decades, but evidence is still lacking on whether all socioeconomic groups benefited equally and how the length of life affected by stroke developed over time. Our study investigates time trends in stroke-free life years and life years affected by stroke. Special emphasis is given to the question whether trends differ between income groups, leading to decreasing or increasing social inequalities. METHODS:The analyses are based on claims data of a German statutory health insurance company of the two time periods 2006-2008 and 2014-2016. Income inequalities and time trends in incidence and mortality risks were estimated using multistate survival models. Trends in stroke-free life years and life years affected by stroke are analysed separately for income groups by applying multistate life table analyses. RESULTS:Stroke incidence and mortality risks decreased in men and women in all income groups. While stroke-free lifetime could be gained in men having higher incomes, improvements in mortality counterbalanced decreasing incidences, leading to increases in life years affected by stroke among men of the lower and higher income group. Among women, no significant changes in life years could be observed. CONCLUSIONS:Changes in stroke-affected life years occur among men in all income groups, but are more pronounced in the higher income group. However, irrespective of the income group the proportion of stroke-affected life years remains quite stable over time, pointing towards constant inequalities. Further research is needed on whether impairments due to stroke reduced over time and whether all socioeconomic groups are affected equally