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WNT1-inducible signaling protein-1 induced by TGF-β1 contributes to fibrosis in Crohn’s disease
Get PDFBackground: Intestinal fibrosis is a common and serious complication of Crohn’s disease (CD), oftentimes leading to intestinal obstruction and necessitating surgical intervention. The exact pathomechanisms are still incompletely understood, and no specific anti-fibrotic therapy for CD is currently available. Wnt-signaling components have been shown to play a significant role in fibrosis formation in other organs, however, their role in intestinal fibrosis formation is not fully known.
Methods: Wnt signaling-specific qPCR arrays were used to analyze 84 Wnt-mediated signal transduction genes in fibrotic and non-fibrotic surgical specimen of patients with stricturing CD. Primary fibroblasts from a fibrotic section and non-fibrotic section were isolated. Cell proliferation and migration were measured by Ki-67 staining and wound healing assays. Cells were treated with TGF-β1 and WISP-1 for qPCR and functional analysis.
Results: Several Wnt related genes were differentially expressed in fibrotic regions. A histopathological score showed a strong correlation between WISP-1 expression and fibrosis in fibrotic intestinal segments. Primary fibroblasts isolated from intestinal tissue of CD showed a significant difference in cell proliferation, migration, and ECM production between the fibrotic and control group. Stimulation of the cells with proinflammatory TGF-β1 induced the activation of Wnt signaling components and induced WISP-1 expression. The presence of WISP-1 induced migration but not proliferation of fibroblasts.
Conclusions: Our results show that WISP-1 expression was associated with fibrosis formation in CD. According to this, WISP-1 might be a potential therapeutic target for attenuation of intestinal fibrosis in CD
Probing neuronal (dys)function in motor cortex of ALS transgenic mice by in vivo two-photon calcium imaging
Get PDFEinfluss der Digitalisierung in der Medizin auf die mentale Arbeitsbelastung von Ärzten und Pflegepersonal
Get PDFEin Ziel der Digitalisierung im Gesundheitswesen ist einen sektoren- und institutionsübergreifenden Datenaustausch zu ermöglichen. Vor dem Hintergrund von steigenden Kosten durch den demographischen Wandel und unter anderem der Weiterentwicklung der Möglichkeiten der medizinischen Behandlung, wird der Einsatz digitaler Technologien zur Verbesserung der Wirtschaftlichkeit und steigender Versorgungsqualität gesehen. Beachtet werden müssen dabei die Schwierigkeiten und Hürden der Umsetzung im klinischen Alltag. Bislang gibt es wenig Evidenz darüber ob und welche Herausforderungen die Digitalisierung für das Personal im klinischen Alltag mit sich bringt.
Eines der großen Handlungsfelder der Digitalisierung in der Medizin ist die elektronische Patientenakte (ePA). In vielen Ländern ist sie bereits großflächig implementiert. In den letzten Jahren ist die elektronische Patientenakte zu-nehmend auch an deutschen Kliniken eingeführt worden. Die Optimierung der Patientenversorgung ist einer der Vorteile der ePA und sollte als Unterstützung für die ärztlichen und pflegerischen Tätigkeiten in den medizinischen Workflow integriert werden.
Die vorliegende Dissertation zum „Einfluss der Digitalisierung in der Medizin auf die mentale Arbeitsbelastung von Ärzten und Pflegepersonal“ beschäftigt sich mit den Auswirkungen auf die mentale Arbeitsbelastung des medizinischen Personals durch die Umstellung auf eine elektronische Patientenakte.
In dieser Dissertation wurden die Auswirkung von Technostress durch die Umstellung von der papierbasierten Patientenakte zu einer elektronischen Patientenakte untersucht. In zwei Kliniken erfolgte vor und nach der Einführung der elektronischen Patientenakte eine Befragung der Ärzte und des Pflegepersonals hinsichtlich unterschiedlicher Einflussfaktoren wie z.B. allgemeine Zufriedenheit, Burnout, Verfügbarkeit von Hardware und Software. Im Zeit-raum von September 2021 bis Juni 2022 nahmen 161 Probanden an der Studie teil, davon 78 Ärzte und 83 Pflegekräfte.
Die Ergebnisse der Studie zeigen, dass die Umstellung auf eine elektronische Patientenakte mit einer Zunahme der mentalen Arbeitsbelastung verbunden sein kann. Die Auswahl der Software und die zur Verfügung stehende Hardware spielen ebenso eine Rolle, wie die demographischen Merkmale der Anwender. Jüngere und IT-affine Anwender achten besonders auf die Intuitivität der Software und verbinden mentale Arbeitsbelastung mit einer schlechten Usability der ePA.
Mehrfach Eingaben und fehlende Schnittstellen zu anderen Systemen wer-den als Auslöser für mentale Arbeitsbelastung angeführt.
Im Rahmen der Studie konnte gezeigt werden, dass das Thema Changemanagement und Peoplemanagement bei der Einführung digitaler Anwendungen im klinischen Umfeld Beachtung finden sollte. Die Schulung der Mitarbeiter und die für die Erlernung der Software zur Verfügung gestellte Zeit spielt eine entscheidende Rolle bei der Akzeptanz der ePA und damit verbundener mentaler Arbeitsbelastung.One goal of digitization in the healthcare sector is to enable data exchange across sectors and institutions. Against the backdrop of rising costs due to demographic change and, among other things, the further development of the possibilities of medical treatment, the use of digital technologies is seen as improving efficiency and increasing the quality of care. However, the difficulties and hurdles of implementation in everyday clinical practice must be taken into account. To date, there is little evidence as to whether and what challenges digitalization poses for staff in everyday clinical practice.
One of the major fields of action for digitization in medicine is the electronic patient record (EHR). It has already been implemented on a large scale in many countries. In recent years, the electronic patient file has also been increasingly introduced at German hospitals. Optimizing patient care is one of the benefits of the ePA and should be integrated into the medical workflow as a support for the medical and nursing activities.
This dissertation on the "Influence of digitalization in medicine on the mental workload of physicians and nursing staff" deals with the effects on the mental workload of medical staff of the switch to an electronic patient record.
In this dissertation, the impact of technostress due to the changeover from pa-perbased patient records to electronic patient records was investigated. In two hospitals, physicians and nursing staff were surveyed before and after the in-troduction of the electronic patient record with regard to different influencing factors such as general satisfaction, burnout, availability of hardware and software. In the period from September 2021 to June 2022, 161 subjects took part in the study, 78 of them physicians and 83 nurses.
The results of the study show that the switch to an electronic patient record can be associated with an increase in mental workload. The choice of software and the available hardware play a role, as do the demographic characteristics of the users. Younger and IT-savvy users pay particular attention to the intuitiveness of the software and associate mental workload with poor usability of the ePA.
Multiple inputs and lack of interfaces to other systems are cited as reasons for mental workload.
The topic of change management should be considered when introducing digital applications in the clinical environment. Staff training and the time allocated for learning the software plays a decisive role in acceptance and the associated mental workload
Micro-RNA-125a erhöht die endotheliale Permeabilität über direkte Interaktion mit VE-Cadherin und indirekte Interaktion mit dem TGF-β-Rezeptor-2
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Serum Biomarker als Prädiktor für das Therapieansprechen bei Erwachsenen mit einer Depression
Get PDFIdentifikation inflammatorischer und nutritiver Marker als Prädiktoren für Prognose und Therapieansprechen bei Patienten mit Lungenkarzinom
Get PDFCharacterizing the epigenetic response to stress using next generation sequencing
Get PDFStress-related disorders have complex etiologies and high incidences, with mood disorders expected to become the leading cause of disability in the coming years. The mechanisms leading to resilience or susceptibility are not well understood and involve both genetic and environmental aspects, especially exposure to stress and adversity, integrated in the form of epigenetic changes such as DNA methylation or histone modification. In recent years, next generation sequencing (NGS) has become a powerful tool for epigenetic profiling. This thesis aims to improve on existing, as well as designing new NGS methods with increased sensitivity and accuracy for improved detection of small epigenetic changes even in composite tissues such as blood. We apply these methods to study DNA methylation changes in the context of stress by genotype interaction within the FKBP5 gene locus.
In the scope of minimizing the bias and maximizing the sensitivity of NGS technology, the first part of this work represents an in-depth characterization and reduction of GC bias on the SOLiD sequencers relative to the currently dominant Illumina sequencing technology.
Subsequently, we present a new method, termed HAM-TBS, which enables highly sensitive assessment of methylation levels of a target set of CpG sites in studies with cohort-level sample sizes. Using HAM-TBS, we can tailor the set of CpGs to fit the biological question at hand. To our knowledge, this is the most sensitive method to detect methylation levels in NGS data to date allowing us to resolve small changes. With it, we supply a fully tested panel of amplicons targeting selected CpGs in functionally relevant regions within the FKBP5 locus including glucocorticoid receptor elements, CTCF binding sites, topologically associating domain boundaries and the transcription start site.
Finally, we apply HAM-TBS using the established amplicon panel to assess dynamic methylation changes in the FKBP5 gene locus following a stress challenge. We expose a cohort of healthy individuals to dexamethasone (DEX), a synthetic glucocorticoid activating the stress reactive hypothalamic-pituitary- adrenal axis. We found dynamic and lasting methylation changes in blood as well as a genotype-dependent response following DEX exposure.
This work demonstrates the potential of NGS technologies to aid in improving our understanding of epigenetics in the context of the stress response system