Kommunikation zwischen medizinischem Fachpersonal und Personen mit idiopathischer Lungenfibrose : eine Onlinebefragung zur Ableitung von Massnahmen in der Schweiz

Darstellung des Themas: Die Kommunikation mit Patienten/-innen, die an idiopathischer Lungenfibrose (IPF) erkrankt sind, stellt für Ärzte/-innen eine grosse Herausforderung dar, weil es sich um eine seltene und unheilbare Krankheit handelt, die generell eine schlechte Prognose aufweist und sehr individuell verlaufen kann. Patienten/-innen und Angehörige haben zugleich hohe Ansprüche an die Thematisierung belastender Themen. Ziel: Bislang gibt es kaum Daten zur Ärzte/-innen-Patienten/-innen-Kommunikation (APK) bei IPF in der Schweiz. Das Ziel dieser Arbeit ist es daher, eine Grundlage für eine bedürfnisgerechte und optimale APK aus Sicht der Patienten/-innen abzuleiten. Methodik: Mittels einer elektronischen Erhebung in der Patienten/-innen Kohorte wurde der IST- und SOLL-Zustand in der APK bei IPF erhoben. Dafür wurden insgesamt 66 IPF-Patienten/-innen und Angehörige zu ihren Erfahrungen und Bedürfnissen in der APK befragt. Resultate: Zusammengefasst über alle Bereiche zeigt sich, dass fast die Hälfte (45%) keine zufriedenstellenden Erfahrungen mit der APK gemacht hat. Für eine gelungene Kommunikation auf Patienten/-innenseite ist laut Befragung die Berücksichtigung der individuellen Bedürfnisse im Gespräch sowie die präzise Aufklärung über die Behandlungsoptionen massgeblich. Schlussfolgerung: Für Ärzte/-innen ist es wichtig, angemessen auf Ängste, Wünsche und Sorgen zu reagieren und Behandlungsmöglichkeiten transparent zu vermitteln. Diesbezüglich wird empfohlen, das Kommunikationsverhalten in der Praxis zu reflektieren und eine bedürfnisorientierte Kommunikation anzustreben

Untersuchungen zur Bedeutung von RNase 7 in der kutanen Abwehr

RNase 7 ist die dominante RNase der Haut und eines der AMP mit dem größten Wirkungsspektrum. Es wird konstitutiv exprimiert und ist selbst induzierbar. Diese vielfältigen Eigenschaften machen RNase 7 zu einem sehr interessanten AMP für die Forschung und ggf. auch für die zukünftige Entwicklung neuer Therapiestrategien. Verschiedene Arbeiten suggerieren, dass RNase 7 wahrscheinlich eine wichtige Rolle in der Abwehr von Keimen während einer Infektion oder eines Inflammationsprozesses in der Haut spielt. In dieser Arbeit konnte gezeigt werden, dass RNase 7 bereits in geringer Dosierung antimikrobiell gegen Pseudomonas aeruginosa wirkt. Die Expression von RNase 7 in Keratinozyten kann auch durch P. aeruginosa selbst induziert werden. Hinsichtlich der Aufklärung der beteiligten Signalwege konnte mit Antikörpern, Inhibitoren und siRNA eine Signalvermittlung sowohl über den EGFR- als auch über den TLR5-Signalweg gezeigt werden. Dabei wurde die EGFR-Beteiligung auch im ex vivo Hautmodel und im 3D-Hautäquivalent gezeigt werden. Weiterhin konnte dargestellt werden, dass es möglicherweise zur Transaktivierung des EGFR nach TLR5 Aktivierung und der Aktivierung von ADAM17 kommt. RNA wird bei Verwundung frei und induziert pro-inflammatorische Zytokine, die im weiteren Verlauf einer Verwundungsreaktion zu einer vermehrten Entzündung beitragen können. Dass RNase 7 auch eine immunmodulatorische Rolle bei der Wundheilung spielen könnte, zeigten in vitro Versuche mit dem RNA-Strukturanalogon poly I:C. RNase 7 ist, aufgrund seiner RNase Eigenschaften, in der Lage RNA zu degradieren und hemmt die RNA-vermittelte Induktion pro-inflammatorischer Zytokine. Der Ribonuklease Inhibitor (RI) könnte durch Komplexbildung mit RNase 7 eine regulatorische Rolle bei der Entzündungsreaktion spielen. Zusammenfassend untermauern die hier dargestellten Daten, dass RNase 7 eine wichtige Funktion bei der Abwehr von Pathogenen und der Modulation von Entzündungsprozessen nach Verwundung einnimmt.RNase 7 is the dominant RNase in human skin and one of the AMP with the highest range of antimicrobial efficacy. RNase 7 is expressed constitutively and additionally inducible. These versatile properties suggest that RNase 7 is a very promising AMP for research and may be a suitable AMP for the future development of new therapy strategies. Different studies suggest that RNase 7 presumably plays an important role in the defense against microorganisms during infective and inflammatory processes in human skin. These data confirmed that RNase 7 is antimicrobially active against Pseudomonas aeruginosa in low micromolar concentrations. While constitutively expressed, RNase 7 levels are further inducible by P. aeruginosa in keratinocytes. However, the involved signaling pathways are only scarcely investigated. The use of antibodies, inhibitors and siRNA revealed a participation of the EGFR- as well as the TLR5-signaling pathways in the P. aeruginosa-mediated RNase 7 expression in keratinocytes. The participation of the EGFR-mediated signaling was subsequently shown in an ex vivo skin model and in a 3D skin equivalent. Furthermore, these results point to a potential EGFR transactivation upon activation of TLR5 and ADAM17. It is known that RNA is released upon wounding and is able to induce pro-inflammatory cytokines which may trigger inflammation in injury processes. In vitro experiments with poly I:C suggest that RNase 7 may play an immunomodulatory role during wound healing. Because of its capacity to degrade RNA, RNase 7 is able to inhibit the induction of RNA-mediated pro-inflammatory cytokines. It was also demonstrated that the complex formation of the ribonuclease inhibitor (RI) with RNase 7 may play a regulatory role during inflammation. Taken together, the results of this thesis substantiate that RNase 7 engages an important role in skin defense and modulation of inflammatory processes in wounding. A better understanding of the importance of RNase 7 in cutaneous defense could lead to new concepts for therapy and prophylaxis of skin diseases and infections

The influence of the commensal skin bacterium Staphylococcus epidermidis on the epidermal barrier and inflammation: Implications for atopic dermatitis

The skin microbiota is a crucial component in maintaining cutaneous barrier function. Staphylococcus epidermidis is considered as a beneficial commensal member of the cutaneous microbiota promoting skin health. However, S. epidermidis is also frequently detectable in the skin of patients with the inflammatory skin disease atopic dermatitis (AD) and some studies reported a significantly higher presence of S. epidermidis in severe AD as compared to mild AD. Therefore, this study aimed to analyse the impact of S. epidermidis on the expression of cutaneous inflammatory mediators and skin barrier molecules. Various S. epidermidis skin-derived isolates activated the proinflammatory transcription factor NF-kappaB and induced expression of AD-associated proinflammatory cytokines in human primary keratinocytes and 3D skin equivalents. Skin barrier molecules such as filaggrin were downregulated by S. epidermidis. In general, AD-derived S. epidermidis strains elicited a higher response than strains derived from the skin of healthy individuals. Taken together, our results provide further evidence that the abundance of S. epidermidis in AD may trigger the inflammatory scenario associated with this disease

The Antimicrobial and Immunomodulatory Function of RNase 7 in Skin

The human ribonuclease RNase 7 has been originally isolated from human skin and is a member of the human RNase A superfamily. RNase 7 is constantly released by keratinocytes and accumulates on the skin surface. The expression of RNase 7 in keratinocytes can be induced by diverse stimuli such as cytokines, growth factors, and microbial factors. RNase 7 exhibits a potent broad spectrum of antimicrobial activity against various microorganisms and contributes to control bacterial growth on the skin surface. The ribonuclease and antimicrobial activity of RNase 7 can be blocked by the endogenous ribonuclease inhibitor. There is also increasing evidence that RNase 7 exerts immunomodulatory activities and may participate in antiviral defense. In this review, we discuss how these characteristics of RNase 7 contribute to innate cutaneous defense and highlight its role in skin infection and inflammation. We also speculate how a potential dysregulation of RNase 7 promotes inflammatory skin diseases and if RNase 7 may have therapeutic potential

Platelet-Released Growth Factors Induce Genes Involved in Extracellular Matrix Formation in Human Fibroblasts

Platelet concentrate products are increasingly used in many medical disciplines due to their regenerative properties. As they contain a variety of chemokines, cytokines, and growth factors, they are used to support the healing of chronic or complicated wounds. To date, underlying cellular mechanisms have been insufficiently investigated. Therefore, we analyzed the influence of Platelet-Released Growth Factors (PRGF) on human dermal fibroblasts. Whole transcriptome sequencing and gene ontology (GO) enrichment analysis of PRGF-treated fibroblasts revealed an induction of several genes involved in the formation of the extracellular matrix (ECM). Real-time PCR analyses of PRGF-treated fibroblasts and skin explants confirmed the induction of ECM-related genes, in particular transforming growth factor beta-induced protein (TGFBI), fibronectin 1 (FN1), matrix metalloproteinase-9 (MMP-9), transglutaminase 2 (TGM2), fermitin family member 1 (FERMT1), collagen type I alpha 1 (COL1A1), a disintegrin and metalloproteinase 19 (ADAM19), serpin family E member 1 (SERPINE1) and lysyl oxidase-like 3 (LOXL3). The induction of these genes was time-dependent and in part influenced by the epidermal growth factor receptor (EGFR). Moreover, PRGF induced migration and proliferation of the fibroblasts. Taken together, the observed effects of PRGF on human fibroblasts may contribute to the underlying mechanisms that support the beneficial wound-healing effects of thrombocyte concentrate products

Antimicrobial skin peptides in premature infants: Comparison with term infants and impact of perinatal factors

IntroductionPreterm infants have an immature epidermis barrier function that may lead to an increased permeability to pathogens. On the surface of the human skin, antimicrobial peptides (AMPs) are important molecules of the innate immune system, have broad antimicrobial properties, and provide an essential role in integrity of the microbiome. Given the marked susceptibility of preterm infants to infection, we hypothesize a decreased expression of AMPs on the skin of preterm infants.Materials and methodsIn a prospective single-center study with 35 preterm and 20 term infants, we analyzed skin rinsing probes for the presence of the AMPs psoriasin (S100A7) and ribonuclease 7 (RNase 7) via enzyme-linked immunosorbent assay. Samples were taken from preterm infants < 34 0/7 weeks gestational age (mean ± SD gestational age, 28.8 ± 2.4 weeks) on days 0, 7, 14, and 28 after birth. Term infants (> 36 6/7 weeks) (controls) were washed on days 0 and 28.ResultsPsoriasin and RNase 7 were both expressed on skin of preterm and term infants and increased in concentration significantly over time. RNase 7 was more expressed in term infants on day 0 [preterm = 1.1 (0.7–2.9) vs. term = 2.0 (1.1–3.4) ng/ml, p = 0.017]. On day 28, premature infants showed higher values of psoriasin [preterm = 10.9 (5.6–14.2) vs. term = 6.3 (3.4–9.0) ng/ml, p < 0.001]. Notably, preterm infants with infectious or inflammatory context driven by histological proof of chorioamnionitis and early-onset or late-onset sepsis had higher concentrations of psoriasin as compared with non-affected preterm infants. After exclusion of infants with inflammatory hit, median concentrations of RNase 7 and psoriasin did not differ between preterm and full-term infants on days 0 and 28.DiscussionPsoriasin and RNase 7 concentrations increase over time on the skin of newborn infants and seem to play a role in the first defense against infection. This is of particularly interest as the role of AMPs on a maturing skin microbiome and its possible new prevention strategies is unclear and needs to be determined

RNase 7 in Cutaneous Defense

RNase 7 belongs to the RNase A superfamily and exhibits a broad spectrum of antimicrobial activity against various microorganisms. RNase 7 is expressed in human skin, and expression in keratinocytes can be induced by cytokines and microbes. These properties suggest that RNase 7 participates in innate cutaneous defense. In this review, we provide an overview about the role of RNase 7 in cutaneous defense with focus on the molecular mechanism of the antimicrobial activity of RNase 7, the regulation of RNase 7 expression, and the role of RNase 7 in skin diseases