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In couples dealing with health problems, we-disease appraisals can influence dyadic coping strategies to alleviate distress. This study describes the development and validation of a self-report scale to assess we-disease appraisals of health problems. The newly developed We-Disease Questionnaire (WDQ) was administered in three samples: parents of children with type 1 diabetes (n = 240) or cancer (n = 125) and individuals with visual impairment and their partners (n = 216). Reliability was measured by coefficient omega. To assess construct validity, correlations with other measures of individual and dyadic adjustment were examined. Descriptive statistics across all samples were compared. A 4-item version of the WDQ demonstrated good reliability and validity and showed meaningful associations with established scales. We-disease appraisals were highest among parents of children with cancer and lowest among couples with visual impairment. The WDQ is a reliable and valid measure that can be used across different health problems. [ABSTRACT FROM AUTHOR]

Background: Vascular anomalies comprise a diverse group of rare diseases with altered blood flow and are often associated with coagulation disorders. The most common example is a localized intravascular coagulopathy in venous malformations leading to elevated D-dimers. In severe cases, this may progress to a disseminated intravascular coagulopathy with subsequent consumption of fibrinogen and thrombocytes predisposing to serious bleeding. A separate coagulopathy is the Kasabach–Merritt phenomenon in kaposiform hemangioendothelioma characterized by platelet trapping leading to thrombocytopenia and eventually consumptive coagulopathy. Our previous work showed impaired von Willebrand factor and platelet aggregometry due to abnormal blood flow, i.e., in ventricular assist devices or extracorporeal membrane oxygenation. With altered blood flow also present in vascular anomalies, we hypothesized that, in particular, the von Willebrand factor parameters and the platelet function may be similarly impacted. Methods: We prospectively recruited 73 patients with different vascular anomaly entities and analyzed their coagulation parameters. Results: Acquired von Willebrand syndrome was observed in both of our patients with Kasabach–Merritt phenomenon. In six out of nine patients with complex lymphatic anomalies, both the vWF antigen and activity were upregulated. Platelet aggregometry was impaired in both patients with Kasabach–Merritt phenomenon and in seven out of eight patients with an arteriovenous malformation. Conclusions: The analysis of coagulation parameters in our patients with vascular anomalies advanced our understanding of the underlying pathophysiologies of the observed coagulopathies. This may lead to new treatment options for the, in part, life-threatening bleeding risks in these patients in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Rhabdomyosarcoma accounts for more than 50% of all soft tissue sarcomas in childhood and adolescence. Despite intensified multimodality treatment, prognosis is extremely poor, with an overall survival rate of approximately 20% in the advanced stage. Therefore, there is an urgent need for targeted treatment options to improve overall survival rates, and to limit long-term side effects. Tumor-targeting peptides offer the possibility to deliver drugs selectively to the tumor site. Here, we select F3 as the best rhabdomyosarcoma-targeting peptide among a panel of 20 different tumor-targeting peptides. F3 peptide showed strong and specific binding to rhabdomyosarcoma, but not to normal cells, and efficient internalization with effective cytoplasmic delivery of the toxin Saporin. We show that nucleolin, the target of F3 peptide, is expressed on the surface of rhabdomyosarcoma cells. F3 peptide is a promising candidate for targeted drug delivery to rhabdomyosarcoma, e.g., by targeting drug-loaded nanoparticles. Active drug delivery by tumor-targeting peptides is a promising approach to improve existing therapies for rhabdomyosarcoma (RMS), by increasing the therapeutic effect and decreasing the systemic toxicity, e.g., by drug-loaded peptide-targeted nanoparticles. Here, we tested 20 different tumor-targeting peptides for their ability to bind to two RMS cell lines, Rh30 and RD, using quantum dots Streptavidin and biotin-peptides conjugates as a model for nanoparticles. Four peptides revealed a very strong binding to RMS cells: NCAM-1-targeting NTP peptide, nucleolin-targeting F3 peptide, and two Furin-targeting peptides, TmR and shTmR. F3 peptide showed the strongest binding to all RMS cell lines tested, low binding to normal control myoblasts and fibroblasts, and efficient internalization into RMS cells demonstrated by the cytoplasmic delivery of the Saporin toxin. The expression of the nucleophosphoprotein nucleolin, the target of F3, on the surface of RMS cell lines was validated by competition with the natural ligand lactoferrin, by colocalization with the nucleolin-binding aptamer AS1411, and by the marked sensitivity of RMS cell lines to the growth inhibitory nucleolin-binding N6L pseudopeptide. Taken together, our results indicate that nucleolin-targeting by F3 peptide represents a potential therapeutic approach for RMS. [ABSTRACT FROM AUTHOR]

Simple Summary: Rhabdomyosarcoma (RMS) accounts for more than 50% of all soft tissue sarcomas in childhood and adolescence. Despite progress and intensified multimodality treatment, prognoses are extremely poor with an overall survival rate of approximately 20% in the advanced stage. Therefore, there is an urgent need for targeted treatment options to improve overall survival rates, and to limit long-term side effects. The fibroblast growth factor receptor 4 (FGFR4) is overexpressed in RMS and other tumors as well. The goal of this work was to select FGFR4 specific single-domain antibodies (sdAb) and to develop FGFR4-targeted therapies. We could show that FGFR4-targeted liposomes have the potential to deliver drugs specifically to FGFR4-positive tumor cells and that chimeric antigen receptor T cells built with the selected antibodies can kill specifically FGFR4-expressing RMS cells. The fibroblast growth factor receptor 4 (FGFR4) is overexpressed in rhabdomyosarcoma (RMS) and represents a promising target for treatments based on specific and efficient antibodies. Despite progress, there is an urgent need for targeted treatment options to improve survival rates, and to limit long-term side effects. From phage display libraries we selected FGFR4-specific single-domain antibodies (sdAb) binding to recombinant FGFR4 and validated them by flow cytometry, surface plasmon resonance, and fluorescence microscopy. The specificity of the selected sdAb was verified on FGFR4-wild type and FGFR4-knock out cells. FGFR4-sdAb were used to decorate vincristine-loaded liposomes and to generate chimeric antigen receptor (CAR) T cells. First, incubation of RMS cells with FGFR4-sdAb revealed that FGFR4-sdAb can block FGF19-FGFR4 signaling via the MAPK pathway and could therefore serve as therapeutics for FGFR4-dependent cancers. Second, FGFR4-targeted vincristine-loaded liposomes bound specifically to RMS cells and were internalized by the receptor, demonstrating the potential for active drug delivery to the tumor. Third, FGFR4-CAR T cells, generated with one sdAb candidate, demonstrated strong and specific cytotoxicity against FGFR4 expressing RMS cells. We selected novel FGFR4-sdAb with high specificity and nano- to picomolar affinities for FGFR4 which have the potential to enable multiple FGFR4-targeted cancer therapy approaches. [ABSTRACT FROM AUTHOR]