Refine
Document Type
- Article (3)
Language
- English (3) (remove)
Has Fulltext
- yes (3)
Is part of the Bibliography
- no (3)
Keywords
- screening (3) (remove)
Institute
Publisher
- MDPI (2)
- Frontiers Media S.A. (1)
Chronic kidney disease (CKD) is a major public health burden affecting more than 500 million people worldwide. Podocytopathies are the main cause for the majority of CKD cases due to pathogenic morphological as well as molecular biological alterations of postmitotic podocytes. Podocyte de-differentiation is associated with foot process effacement subsequently leading to proteinuria. Since currently no curative drugs are available, high throughput screening methods using a small number of animals are a promising and essential tool to identify potential drugs against CKD in the near future. Our study presents the implementation of the already established mouse GlomAssay as a semi-automated high-throughput screening method—shGlomAssay—allowing the analysis of several hundreds of FDA-verified compounds in combination with downstream pathway analysis like transcriptomic and proteomic analyses from the same samples, using a small number of animals. In an initial prescreening we have identified vitamin D3 and its analog calcipotriol to be protective on podocytes. Furthermore, by using RT-qPCR, Western blot, and RNA sequencing, we found that mRNA and protein expression of nephrin, the vitamin D receptor and specific podocyte markers were significantly up-regulated due to vitamin D3- and calcipotriol-treatment. In contrast, kidney injury markers were significantly down-regulated. Additionally, we found that vitamin D3 and calcipotriol have had neither influence on the expression of the miR-21 and miR-30a nor on miR-125a/b, a miRNA described to regulate the vitamin D receptor. In summary, we advanced the established mouse GlomAssay to a semi-automated high-throughput assay and combined it with downstream analysis techniques by using only a minimum number of animals. Hereby, we identified the vitamin D signaling pathway as podocyte protective and to be counteracting their de-differentiation.
Introduction: Germany has established a national mammography screening program (MSP). Despite extensive awareness campaigns, the participation rate is only 54%, which is considerably below the European guidelines’ recommendation of at least 70%. Several reasons why women do not participate are already known. Telephone consultations along with invitation letters have improved the participation rate. Here, we analyzed the reasons for non-participation and offered barrier-specific counseling to examine which impediments can be overcome to improve participation. Study Design: In a randomized controlled trial, women who had not attended their proposed screening appointment in the MSP after a written invitation were contacted by telephone and asked why they did not attend. Barrier-specific counseling via telephone was then offered. Participation in the MSP was rechecked 3 months after counseling. Setting: 1772 women, aged 50–69 years, who had not scheduled a mammography screening after a written invitation were contacted by telephone and asked for their reasons for non-participation. Intervention: The reasons were recorded by the calling consultant and categorized either during the call or later based on their recorded statements. Afterward, the women received counseling specific to their statements and were given general information about the MSP. Main outcome measures: We categorized the reasons given, calculated their frequency, and analyzed the probabilities to which they could be successfully addressed in individual counseling. Participation rates were determined post-consultation according to the reason(s) indicated. Results: The data were analyzed in 2022. After exclusions, 1494 records were analyzed. Allowing for multiple reasons to be stated by every individual 3280 reasons for not attending were abstracted. The most frequent reason was participation in “gray screening” (51.5%), which included various breast cancer prevention measures outside the national MSP. Time problems (26.6%) and health reasons (17.3%) were also important. Counseling was most effective when women had not participated for scheduling reasons. Conclusion: Several reasons prevented women from participating in the MSP. Some reasons, such as time-related issues, could be overcome by telephone counseling, but others, like barriers resulting from fear of the examination procedure or its result, could not.