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ErbB deletion effect on pulmonary intracellular surfactant distribution
Get PDFBackground: Alveolar epithelial type II cells (AEII) synthesize, store, and recycle surfactant. Lipids and primarily hydrophobic surfactant proteins (SPs) are stored in lamellar bodies (Lbs) while the hydrophilic SPs and the precursors of hydrophobic SPs are stored in multivesicular bodies (mvb). ErbB4-receptor and its ligand neuregulin (NRG) are important regulators of fetal lung development and fetal surfactant synthesis. ErbB4 deletion leads predominantly to an alveolar simplification. We hypothesized that ErbB4 deletion affects the ultrastructure of AEII, specifically Lb and the intracellular distribution of the immunomodulating hydrophilic SP-A and the hydrophobic SP-B. Material and Methods: Using a HER4 transgenic cardiac rescue mouse model, AEII were characterized stereologically in lungs of juvenile transgenic HER4heart+/- and HER4heart-/- mice. The ultrastructure of Lb and the intracellular distribution of SPs were evaluated by immune electron microscopy. A preferential nonrandom labeling of a compartment for SP is present, if the relative labeling index (RLI) > 1and the chi-quadrat test is significant. Results: HER4 deletion had no significant effects on size of AEII and volume fractions of subcellular organelles as well as on the volume weighted mean volume of Lb in HER4heart-/- when compared to HER4heart+/- mice. The cytoplasm was preferentially labeled for SP-A in the AEII of both genotypes. Lbs were preferential labeled for SP-A in the AEII of HER4heart-/-, but not in the AEII of HER4heart+/- mice. SP-B was preferentially distributed over Lbs in AEII independent of the genotype, however, the evaluated RLI was significantly higher in HER4heart-/- mice. Conclusion: HER4 deletion does not affect the ultrastructure of AEII and influence the distribution of SP-A and SP-B only moderately. Responsible for this could be compensatory mechanisms caused by the redundancy of ErbB receptors
Patient Organizations' Digital Responses to the COVID-19 Pandemic: Scoping Review
No full textBackground Patient organizations (POs) play a crucial role in supporting individuals with health conditions. Their activities range from counseling to support groups to advocacy. The COVID-19 pandemic and its related public health measures prompted rapid digital transformation efforts across multiple sectors, including health care. Objective This study aimed to explore how POs digitally responded to pandemic-related circumstances, focusing on aspects such as the technologies used, positive outcomes, and challenges encountered. Methods This scoping review followed the methodological guidance of the JBI (Joanna Briggs Institute) Scoping Review Methodology Group and adhered to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) reporting guidelines. A systematic search of PubMed, the Web of Science Core Collection, and the WHO (World Health Organization) COVID-19 database, supplemented by a citation search approach, was conducted. The initial search was performed on November 10, 2022, and updated on November 8, 2023. Publications were eligible if they were published after November 30, 2019, and addressed pandemic-related digitalization efforts of POs, defined as nonprofit organizations with a focus on health-related support. A 2-step screening process was used to identify relevant literature. Data were extracted using a standardized table to capture aspects such as digital adaptation activities (eg, types of technologies implemented, positive outcomes, challenges, and facilitating factors) and coded inductively to identify similarities across included publications, and the findings were synthesized narratively. Results The search and its subsequent update yielded 2212 records, with 13 articles included in this review. These articles revealed a range of PO services that were digitally adapted during the pandemic, with videoconferencing software emerging as the most commonly used tool (n=9 articles). The digital adaptation of group-based support activities was the most frequently reported transformation (n=9). Other adaptations included the digitalization of counseling services (n=3) and the delivery of information and education (n=3), including educational workshops, weekly webinars, and the dissemination of information through digital newsletters. While the use of digital formats, particularly for POs' group activities, often increased accessibility by breaking down preexisting barriers (n=5), they also created new barriers for certain groups, such as those lacking digital skills or resources (n=4). Some participants experienced a loss of interpersonal aspects, like a sense of community (n=3). However, further findings suggest that the digital delivery of such group activities preserved essential interpersonal aspects (n=7) and a preference among some participants to continue digital group activities (n=4), suggesting the potential for sustainability of such options post the COVID-19 pandemic. Conclusions The rapid digitalization efforts of POs demonstrate their adaptability and the potential of digital technologies to improve support services, despite some challenges. Future digitalization strategies should focus, among other things, on promoting digital literacy to ensure the accessibility and inclusiveness of digital services. Trial registration OSF Registries, https://osf.io/anvf4
Kosten und gesundheitsbezogene Lebensqualität von Patient:innen mit Neuromyelitis optica-Spektrum-Erkrankungen und Myelin-Oligodendrozyten-Glykoprotein- Antikörper assoziierten Erkrankungen (CHANCENMO-Studie)
No full textIdentifizierung und Charakterisierung ätiopathologischer sowie klinischer Faktoren der Persistent Genital Arousal Disorder (PGAD)
No full textTargeting BCL11B in chimeric antigen receptor-engineered lymphoid progenitors propagates adaptive NK-like cell responses against leukemia
No full textGut microbiota-derived butyrate selectively interferes with growth of carbapenem-resistant Escherichia coli based on their resistance mechanism
No full textWe investigated consequences of resistance acquisition in Escherichia coli clinical isolates during anaerobic (continuous culture) growth and examined their sensitivity to butyrate, a hallmark metabolite of healthy gut microbiota. Strains were stratified based on carrying either a carbapenemase (CARB) or displaying porin malfunctioning (POR). POR displayed markedly altered growth efficiencies, lower membrane stability and increased sensitivity to butyrate compared with CARB. Major differences in global gene expression between the two groups during anaerobic growth were revealed involving increased expression of alternative substrate influx routes, the stringent response and iron acquisition together with lower expression of various stress response systems in POR. Longitudinal analyses during butyrate wash-in showed common responses for all strains as well as specific features of POR that displayed strong initial "overshoot" reactions affecting various stress responses that balanced out over time. Results were partly reproduced in a mutant strain verifying porin deficiencies as the major underlying mechanism for results observed in clinical isolates. Furthermore, direct competition experiments confirmed butyrate as key for amplifying fitness disadvantages based on porin malfunctioning. Results provide new (molecular) insights into ecological consequences of resistance acquisition and can assist in developing measures to prevent colonization and infection based on the underlying resistance mechanism
miRNAs as potential biomarkers for subclinical atherosclerosis in Sjögren's disease.
No full textBackground MicroRNAs (miRNAs) can regulate gene expression, controlling numerous cellular processes. Dysregulation of miRNA function is linked to various diseases, making them attractive diagnostic and therapeutic targets. Examples include hsa-miR-92a-3p, hsa-miR-126-3p, hsa-miR-143-3p, hsa-miR-145-5p and hsa-miR-204-5p, which are associated with endothelial function. Their prevalence in Sjögren's disease (SjD) is unknown. We assessed the prevalence of these miRNAs in serum of patients with SjD, correlating levels with cardiovascular risk factors and carotid intima-media thickness (cIMT) to evaluate their utility in risk stratification. Methods 199 patients with SjD and 100 age and sex-matched healthy controls (HC) were included in the study. Five different miRNAs (hsa-miR-92a-3p; hsa-miR-126-3p; hsa-miR143-3p; hsa-miR-145-5p; hsa-miR-204-5p) were analysed by quantitative real-time PCR. The miRNA results were compared with known clinical and disease-related parameters. Results Four miRNAs showed significantly different expressions compared with HC. MiR-92a-3p was upregulated (p=0.025) and miR-126-3p (p=0.044), miR-143-3p (p=0.006) and miR-204-5p (p=0.009) downregulated in SjD compared with HC. The comparison between HC and SjD with/without organ involvement revealed descriptively increased miR-92a-3p levels in patients with SjD with organ involvement (p=0.087). Furthermore, miR-92a-3p levels correlated positively with cIMT as an expression of subclinical atherosclerosis (r=0.148, p=0.04). Conclusion In conclusion, patients with SjD demonstrated differences in their expression of miRNAs linked to regulation of endothelial function. Reduction of specific miRNAs was associated with increased cardiovascular risk, suggesting a potentially protective role for these miRNAs. Furthermore, miR-92a-3p could be helpful for molecular detection of early-stage atherosclerosis and increased cardiovascular risk in SjD
