The Integrative Nature of Interculturalism in Galicia at The Beginning of the 20th Century

The article outlines the main aspects of interculturalism in Galicia at the beginning of the 20th century. The interculturalism has been defined as the initial basis of communication, formed by a combination of social and educational environment. In modern society with many political and intercultural problems, the communicative competence and formation of tolerant attitudes towards people play a significant role. Linguistic education is one of the main tasks of educational pedagogy, linguistics, methodology, language rules, principles, and methods of teaching, ways of investigating education. The level of language culture of the personality in the mother tongue and foreign languages is evidence of the development of linguistic competence. The changes in the cultural sphere of society determine the need to investigate linguistic problems, focusing on improving language culture to achieve efficiency. The language problems have gone beyond the framework of philology and have become the general problems of society to regulate language culture in the process of social communication, social processes, the development of society as a whole system. In the political sphere, the culture of language promotes the emergence of mutual interest and respect between people of different nationalities and the stabilization of interethnic and international relations. The described innovative approach in the organization of social communication and interculturalism in Galicia space can be creatively and practically adapted in the conditions of any modern multicultural society

Spontaneous In Vivo Chondrogenesis of Bone Marrow-Derived Mesenchymal Progenitor Cells by Blocking Vascular Endothelial Growth Factor Signaling

Chondrogenic differentiation of bone marrow-derived mesenchymal stromal/stem cells (MSCs) can be induced by presenting morphogenetic factors or soluble signals but typically suffers from limited efficiency, reproducibility across primary batches, and maintenance of phenotypic stability. Considering the avascular and hypoxic milieu of articular cartilage, we hypothesized that sole inhibition of angiogenesis can provide physiological cues to direct in vivo differentiation of uncommitted MSCs to stable cartilage formation. Human MSCs were retrovirally transduced to express a decoy soluble vascular endothelial growth factor (VEGF) receptor-2 (sFlk1), which efficiently sequesters endogenous VEGF in vivo, seeded on collagen sponges and immediately implanted ectopically in nude mice. Although naïve cells formed vascularized fibrous tissue, sFlk1-MSCs abolished vascular ingrowth into engineered constructs, which efficiently and reproducibly developed into hyaline cartilage. The generated cartilage was phenotypically stable and showed no sign of hypertrophic evolution up to 12 weeks. In vitro analyses indicated that spontaneous chondrogenic differentiation by blockade of angiogenesis was related to the generation of a hypoxic environment, in turn activating the transforming growth factor-β pathway. These findings suggest that VEGF blockade is a robust strategy to enhance cartilage repair by endogenous or grafted mesenchymal progenitors. This article outlines the general paradigm of controlling the fate of implanted stem/progenitor cells by engineering their ability to establish specific microenvironmental conditions rather than directly providing individual morphogenic cues.; Chondrogenic differentiation of mesenchymal stromal/stem cells (MSCs) is typically targeted by morphogen delivery, which is often associated with limited efficiency, stability, and robustness. This article proposes a strategy to engineer MSCs with the capacity to establish specific microenvironmental conditions, supporting their own targeted differentiation program. Sole blockade of angiogenesis mediated by transduction for sFlk-1, without delivery of additional morphogens, is sufficient for inducing MSC chondrogenic differentiation. The findings represent a relevant step forward in the field because the method allowed reducing interdonor variability in MSC differentiation efficiency and, importantly, onset of a stable, nonhypertrophic chondrocyte phenotype

CRUSE®-An innovative mobile application for patient monitoring and management in chronic spontaneous urticaria

Background: Chronic spontaneous urticaria (CSU) is unpredictable and can severely impair patients' quality of life. Patients with CSU need a convenient, user-friendly platform to complete patient-reported outcome measures (PROMs) on their mobile devices. CRUSE ®, the Chronic Urticaria Self Evaluation app, aims to address this unmet need. Methods: CRUSE ® was developed by an international steering committee of urticaria specialists. Priorities for the app based on recent findings in CSU were defined to allow patients to track and record their symptoms and medication use over time and send photographs. The CRUSE ® app collects patient data such as age, sex, disease onset, triggers, medication, and CSU characteristics that can be sent securely to physicians, providing real-time insights. Additionally, CRUSE ® contains PROMs to assess disease activity and control, which are individualised to patient profiles and clinical manifestations. Results: CRUSE ® was launched in Germany in March 2022 and is now available for free in 17 countries. It is adapted to the local language and displays a country-specific list of available urticaria medications. English and Ukrainian versions are available worldwide. From July 2022 to June 2023, 25,710 observations were documented by 2540 users; 72.7% were females, with a mean age of 39.6 years. At baseline, 93.7% and 51.3% of users had wheals and angioedema, respectively. Second-generation antihistamines were used in 74.0% of days. Conclusions: The initial data from CRUSE ® show the wide use and utility of effectively tracking patients' disease activity and control, paving the way for personalised CSU management.</p

UCRAID (Ukrainian Citizen and refugee electronic support in Respiratory diseases, Allergy, Immunology and Dermatology) action plan.

Eight million Ukrainians have taken refuge in the European Union. Many have asthma and/or allergic rhinitis and/or urticaria, and around 100,000 may have a severe disease. Cultural and language barriers are a major obstacle to appropriate management. Two widely available mHealth apps, MASK-air® (Mobile Airways Sentinel NetworK) for the management of rhinitis and asthma and CRUSE® (Chronic Urticaria Self Evaluation) for patients with chronic spontaneous urticaria, were updated to include Ukrainian versions that make the documented information available to treating physicians in their own language. The Ukrainian patients fill in the questionnaires and daily symptom-medication scores for asthma, rhinitis (MASK-air) or urticaria (CRUSE) in Ukrainian. Then, following the GDPR, patients grant their physician access to the app by scanning a QR code displayed on the physician's computer enabling the physician to read the app contents in his/her own language. This service is available freely. It takes less than a minute to show patient data to the physician in the physician's web browser. UCRAID-developed by ARIA (Allergic Rhinitis and its Impact on Asthma) and UCARE (Urticaria Centers of Reference and Excellence)-is under the auspices of the Ukraine Ministry of Health as well as European (European Academy of Allergy and Clinical immunology, EAACI, European Respiratory Society, ERS, European Society of Dermatologic Research, ESDR) and national societies

Effects of metal-induced oxidative stress on endothelial cells in vitro

Aseptic loosening of metal implants is mainly attributed to the formation of metal degradation products. These include particulate debris and corrosion products, such as metal ions (anodic half-reaction) and ROS (cathodic half-reaction). While numerous clinical studies describe various adverse effects of metal degradation products, detailed knowledge of metal-induced cellular reactions, which might be important for possible therapeutic intervention, is not comprehensive. Since endothelial cells are involved in inflammation and angiogenesis, two processes which are critical for wound healing and integration of metal implants, the effects of different metal alloys and their degradation products on these cells were investigated. Endothelial cells on Ti6Al4V alloy showed signs of oxidative stress, which was similar to the response of endothelial cells to cathodic partial reaction of corrosion induced directly on Ti6Al4V surfaces. Furthermore, oxidative stress on Ti6Al4V alloy reduced the pro-inflammatory stimulation of endothelial cells by TNF-α and LPS. Oxidative stress and other stress-related responses were observed in endothelial cells in contact with Co28Cr6Mo alloy. Importantly, these features could be reduced by coating Co28Cr6Mo with a TiO2 layer, thus favouring the use of such surface modification in the development of medical devices for orthopaedic surgery. The reaction of endothelial cells to Co28Cr6Mo alloy was partially similar to the effects exerted by Co2+, which is known to be released from metal implants. Co2+ also induced ROS formation and DNA damage in endothelial cells. This correlated with p53 and p21 up-regulation, indicating the possibility of cell cycle arrest. Since CoCl2 is used as an hypoxia-mimicking agent, HIF-1α-dependence of cellular responses to Co2+ was studied in comparison to anoxia-induced effects. Although important HIF-1α-dependent genes were identified, a more detailed analysis of microarray data will be required to provide additional information about the mechanisms of Co2+ action. All these reactions of endothelial cells to metal degradation products might play their role in the complex processes taking place in the body following metal device implantation. In the worst case this can lead to aseptic loosening of the implant and requirement for revision surgery. Knowledge of molecular mechanisms of metal-induced responses will hopefully provide the possibility to interfere with undesirable processes at the implant/tissue interface, thus extending the life-time of the implant and the overall success of metal implant applications.Eine aseptische Lockerung eines Metallimplantats wird zumeist auf die Bildung von Abbauprodukten des Metalls zurückgeführt, die aus Partikel-förmigen Bruchstücken und Korrosionsprodukten, wie Metallionen (anodische Halbreaktion) und ROS (kathodische Halbreaktion) bestehen. Zahlreiche klinische Studien beschreiben verschiedene nachteilige Effekte dieser Metallabbauprodukte. Detaillierte Kenntnisse über die durch die Metalle verursachten zellulären Reaktionen, die möglicherweise für therapeutische Interventionen wichtig wären, liegen noch nicht vor. rnDa Endothelzellen am Entzündungsprozess und der Angiogenese beteiligt sind, zwei Prozesse, die für die Wundheilung und die Integration des Metallimplantats entscheidend sind, werden die Effekte der verschiedenen Metalllegierungen und ihre Abbauprodukte auf die Zellen untersucht. Endothelzellen auf Ti6Al4V-Legierung zeigen Zeichen von oxidativem Stress, die Ähnlichkeiten zu der Reaktion von Endothelzellen zeigen, die durch kathodische korrosive Teilreaktion direkt auf der Ti6Al4V-Oberfläche verursacht wurde. Darüber hinaus reduziert der oxidative Stress auf Ti6Al4V-Legierung die pro-inflammatorische Stimulation der Endothelzellen durch TNF- α und LPS. Oxidativer Stress und andere stress-verwandte Reaktionen wurden in Endothelzellen beobachtet, die Kontakt mit Co28Cr6Mo-Legierung hatten. Hervorzuheben ist, dass diese Reaktionen reduziert werden konnten, indem man das Co28Cr6Mo mit einer TiO2-Schicht überzieht. Es erscheint demnach günstig zu sein, solche Oberflächenmodifikationen bei der Entwicklung von Medizinprodukten für die orthopädische Behandlung einzusetzen. Die Reaktion der Endothelzellen auf die Co28Cr6Mo-Legierung zeigte teilweise Ähnlichkeiten zu der Reaktion auf Co2+, von dem bekannt ist, dass es von Metallimplantaten frei gesetzt wird. Co2+ induziert ROS-Bildung und schädigt DNS in Endothelzellen. Dies korreliert mit einer erhöhten Expression von p53 und p21, was wiederum darauf hindeutet, dass der Zellzyklus gestoppt wird. Da CoCl2 die gleichen Effekte hervorruft wie Hypoxie, wurde die HIF-1α –Abhängigkeit der zellulären Antwort auf Co2+ im Vergleich zu den durch die Anoxie-verursachenden Effekte untersucht. All diese Reaktionen der Endothelzellen auf Metall-Abbauprodukte spielen möglicherweise eine Rolle in den komplexen Prozessen, die im Körper als Folge einer Implantation von Metallprodukten ablaufen. Im schlimmsten Fall kann dies zu einer aseptischen Lockerung des Implantats und einer erneuten OP führen. Die Kenntnisse der molekularen Mechanismen der durch Metall induzierten Reaktionen werden hoffentlich die Möglichkeiten bieten, die unerwünschten Wirkungen an der Grenzschicht von Implantat und Gewebe zu beeinflussen. Dies sollte dann die Lebenszeit von Implantaten erhöhen und die Erfolgsrate bei der Anwendung von Metallimplantaten steigern. r

The Integrative Nature of Interculturalism in Galicia at The Beginning of the 20th Century

The article outlines the main aspects of interculturalism in Galicia at the beginning of the 20th century. The interculturalism has been defined as the initial basis of communication, formed by a combination of social and educational environment. In modern society with many political and intercultural problems, the communicative competence and formation of tolerant attitudes towards people play a significant role. Linguistic education is one of the main tasks of educational pedagogy, linguistics, methodology, language rules, principles, and methods of teaching, ways of investigating education. The level of language culture of the personality in the mother tongue and foreign languages is evidence of the development of linguistic competence. The changes in the cultural sphere of society determine the need to investigate linguistic problems, focusing on improving language culture to achieve efficiency. The language problems have gone beyond the framework of philology and have become the general problems of society to regulate language culture in the process of social communication, social processes, the development of society as a whole system. In the political sphere, the culture of language promotes the emergence of mutual interest and respect between people of different nationalities and the stabilization of interethnic and international relations. The described innovative approach in the organization of social communication and interculturalism in Galicia space can be creatively and practically adapted in the conditions of any modern multicultural society.El artículo describe los principales aspectos de la interculturalidad en Galicia a principios del siglo XX. La interculturalidad se ha definido como la base inicial de la comunicación, formada por una combinación de entorno social y educativo. En una sociedad moderna con muchos problemas políticos e interculturales, la competencia comunicativa y la formación de actitudes tolerantes hacia las personas juegan un papel importante. La educación lingüística es una de las principales tareas de la pedagogía educativa, lingüística, metodología, reglas del lenguaje, principios y métodos de enseñanza, formas de investigar la educación. El nivel de cultura lingüística de la personalidad en la lengua materna y las lenguas extranjeras es evidencia del desarrollo de la competencia lingüística. Los cambios en el ámbito cultural de la sociedad determinan la necesidad de investigar los problemas lingüísticos, centrándose en la mejora de la cultura lingüística para lograr la eficiencia. Los problemas del lenguaje han ido más allá del marco de la filología y se han convertido en los problemas generales de la sociedad para regular la cultura del lenguaje en el proceso de comunicación social, los procesos sociales, el desarrollo de la sociedad en su conjunto. En el ámbito político, la cultura del lenguaje promueve el surgimiento del interés mutuo y el respeto entre personas de diferentes nacionalidades y la estabilización de las relaciones interétnicas e internacionales. El enfoque innovador descrito en la organización de la comunicación social y la interculturalidad en el espacio de Galicia puede adaptarse creativa y prácticamente a las condiciones de cualquier sociedad multicultural moderna

Function and mutual interaction of BiP-, PERK-, and IRE1 alpha-dependent signalling pathways in vascular tumours

Spontaneously regressing infantile haemangiomas and aggressive angiosarcomas are vascular tumours with excessive angiogenesis. When analysing haemangiomas and angiosarcomas immunohistochemically with respect to their chaperone profiles we found that angiosarcomas have significantly elevated protein levels of binding immunoglobulin protein (BIP) and PERK with concomitant attenuated IRE1 alpha levels, whereas haemangioma tissue exhibits the same pattern as embryonal skin tissue. We show that BiP is essential for the maintenance of VEGFR2 protein, which is expressed in the endothelium of both tumour types. When studying the effects of BiP, the IRE1 alpha/Xbp1 -, and PERK/ATF4-signalling pathways on the migration and tube-forming potential of endothelial cells, we show that downregulation of BiP, as well as inhibition of the kinase activity of IRE1 alpha, inhibit in vitro angiogenesis. Downregulation of PERK (PKR-like kinase; PKR = protein kinase R) levels promotes Xbp1 splicing in endoplasmic reticulum (ER)-stressed cells, indicating that in angiosarcoma the elevated PERK levels might result in high levels of unspliced Xbp1, which have been reported to promote cell proliferation and increase tumour malignancy. The data presented in this study revealed that in addition to BiP or PERK, the kinase domains of IRE1 alpha and Xbp1 could be potential targets for the development of novel therapeutic approaches for treating angiosarcomas and to control tumour angiogenesis. (c) 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland