Molecular Mechanisms of Peripheral T cell Tolerance : Identification of Dickkopf 3 as a novel immune modulator

Protection of tissues from the devastating effects of immune responses is essential for the integrity of the organism. Tolerance mechanisms, such as T cell depletion or anergy induction by natural and adaptive regulatory T cells, tolerogenic dendritic cells and parenchymal cells control potentially auto-reactive lymphocytes. In addition, organs that are particularly sensitive to damage by inflammation, so called immune privileged sites, are protected by tissue barriers and contain an immunosuppressive microenvironment. There is increasing evidence that processes establishing immune privilege overlap with those associated with tolerance induction. However, there is much yet to learn about the molecules with a role in immune regulation. This knowledge could help in the understanding of systemic diseases, such as autoimmunity and cancer, and introduce novel principles concerning transplantation tolerance. Aim of this study was the identification of novel molecules that are potential mediators of peripheral tolerance. Starting from a transgenic mouse model for peripheral CD8 T cell tolerance, identification of such candidate genes was attempted by wide range gene expression analysis. Dickkopf 3 (Dkk3) was 10-fold upregulated in regulatory CD8 T cells. Interestingly, Dkk3 mRNA was previously shown to be present in peripheral tissues, such as the brain, the eye, the spinal cord, the ovary and the uterus, pointing to a possible role in immune privilege. Moreover, Dkk3 was reported to inhibit the ERK MAPK pathway in tumor cells, which is also crucial for T cell receptor signal transduction. Taking all the above into consideration, it was hypothesized that Dkk3 might be involved in immune regulation. Here, Dkk3 was identified as a novel modulator of immune responses. Dkk3 protein was shown to be expressed by the transgenic regulatory CD8 T cells and was indispensable for the suppression of naïve T cells. In detail, Dkk3 deficient transgenic mice displayed no CD8 T cell tolerance and regulatory CD8 T cells could not exert their suppressive function in the presence of anti-Dkk3 blocking antibody. The immune regulatory function of Dkk3 was not limited to the transgenic mouse model of CD8 T cell tolerance. Polyclonal T cells from Dkk3 deficient mice showed hyperproliferation and increased IL-2 production. This effect could be explained by the fact that the ERK MAPK is overactivated in the absence of Dkk3. Among the tissues that express Dkk3 in high amounts are the immune privileged organs(central nervous system (CNS), ovaries, placenta), the liver, which is a crucial site for the establishment of T cell tolerance to oral antigens, the heart and the lung. On the other hand, Dkk3 expression could not be detected in the lymphoid organs and the serum. Given the observed suppressive activity of Dkk3. it might control potentially harmful T cell responses in the above mentioned immune privileged organs. Indeed, the immune regulatory role of Dkk3 in the CNS could be demonstrated in the context of experimental autoimmune encephalitis (EAE). Absence of neuron-derived Dkk3 led to severe and persistent EAE, due to lack of suppression of activated CD8 T cells. In addition, blocking of the secreted Dkk3 with the respective anti-Dkk3 antibody resulted in increased disease chronicity. In conclusion, Dkk3 is a universal immune regulator, employed by transgenic tolerant CD8 T cells and immune privileged organs in order to control excessive T cell responses

Bilingualism in a Case of the Non-fluent/agrammatic Variant of Primary Progressive Aphasia

There is a growing body of research on language impairment in bilingual speakers with neurodegenerative diseases. Evidence as to which language is better preserved is rather inconclusive. Various factors seem to influence language performance, most notably age of acquisition, level of proficiency, immersion and degree of exposure to each language. The present study examined fluency, lexical, discourse and grammatical abilities of a Greek-French late bilingual man with the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA). Speech samples derived from three different narrative tasks in both languages were analyzed using quantitative production analysis (QPA) and fluency measures. The first aim of the study was to compare the participant's connected speech production to that of Greek-speaking normal controls. The second aim was to determine whether Greek (L1) and French (L2) were differentially impaired. To our knowledge, this is the first report of connected speech deficits in a Greek-speaking patient with PPA and the first study which uses QPA to compare L1 and L2 narratives in a bilingual speaker with PPA. Compared to neurologically healthy controls, our participant was impaired in lexical, discourse and grammatical productivity measures, but did not differ in measures of grammatical accuracy. The presence of dysfluencies, reduced speech rate and simplified syntax is consistent with the pattern of impairment reported for the nfvPPA. Results showed that narrative production measures did not differ significantly between languages. However, they suggest a slightly worse performance in his second, non-dominant, language despite a similar pattern of impairment in both languages. Lengthy exposure to L2 and regular activation of L2 through daily use may explain the preservation of discourse abilities in his non-dominant language. This study calls attention to factors such as language dominance, proficiency, patterns of use, and exposure to a language. These factors play a key role in assessing bilingual individuals with PPA and making clinical decisions

Safeguarding cancer research funding by European charities amidst the COVID‐19 pandemic

The COVID‐19 outbreak has affected cancer research and cancer care. European cancer charities need to reconsider strategies for safeguarding income and supporting cancer researchers, in times when sustaining cancer research funding is more crucial than ever

Η πανδημία του κορωνοϊού και η διαχείριση της από την ελληνική κυβέρνηση

Η παρούσα διπλωματική εργασία πραγματεύεται το επίκαιρο ζήτημα της πανδημίας του κορωνοϊού και την διαχείριση της από την ελληνική κυβέρνηση. Στόχος της έρευνας είναι να αναδειχτεί η κυβερνητική στρατηγική αναφορικά με τη διαχείριση της πανδημίας, οι πολιτικές που εφάρμοσε και ο αντίκτυπος τους στο κοινωνικό και πολιτικό επίπεδο. Τα ερευνητικά ερωτήματα που καλείται να απαντήσει είναι ποιος ήταν ο βασικός λόγος εφαρμογής ενός αυστηρού και καθολικού lockdown (καραντίνας) και στα τρία κύματα της πανδημίας, εάν εμπλέκεται η επιστήμη στη διαμόρφωση και χάραξη της κρατικής πολιτικής, εάν οι ιδεολογικοί λόγοι διαμορφώνουν ένα νέο εσωτερικό εχθρό και ένα νέο υποκείμενο και τέλος εάν υφίσταται κοινωνική αντίσταση απέναντι στα περιοριστικά μέτρα και στο νομοθετικό έργο της κυβέρνησης. Υπόθεση εργασίας της παρούσας διπλωματικής είναι ότι η ελληνική κυβέρνηση αξιοποιώντας την πανδημία και τα μέτρα περιορισμού και εργαλειοποιώντας την επιστήμη προωθεί νεοφιλελεύθερες πολιτικές.This master's thesis deals with the current issue of the coronavirus pandemic and its management by the Greek government. The aim of the research is to highlight the government strategy regarding the management of the pandemic, the policies it has implemented and their impact on the social and political level. The research questions to be answered are what was the main reason for the implementation of a strict and universal lockdown in all three waves of the pandemic, if science is involved in shaping and formulating state policy, if ideological discources form a new internal enemy and a new subject and finally if there is social resistance to the restrictive measures and the legislative work of the government. The working hypothesis of the present thesis is that the Greek government, utilizing the pandemic and the restrictive measures and instrumentalizing the science, promotes neoliberal policies

The Perioperative Use of Levosimendan as a Means of Optimizing the Surgical Outcome in Patients with Severe Heart Insufficiency Undergoing Cardiac Surgery.

BACKGROUND Postoperative myocardial dysfunction following cardiac surgery is a relatively common occurrence. Levosimendan, a calcium sensitizer and inotropic drug, has shown potential in improving outcomes for patients with low preoperative ejection fraction (EF) and myocardial dysfunction after cardiac surgery. This study aims to evaluate the efficacy of levosimendan in optimizing the surgical outcome for such patients. METHODS A retrospective analysis was conducted on 314 patients with preoperative severe heart failure who underwent cardiac surgery. Among them, 184 patients received perioperative adjunctive therapy with levosimendan, while a comparable group of 130 patients received conventional treatment. RESULTS The use of levosimendan demonstrated several advantages in postoperative outcomes. It significantly improved short- and long-term survival rates after cardiac surgery, enhanced hemodynamic stability, reduced the requirement for inotropic support, and facilitated faster weaning from ventilator support. Patients who received levosimendan reported reduced angina and dyspnea symptoms, as well as fewer postoperative arrhythmias. Furthermore, levosimendan helped minimize myocardial injury inevitable after cardiac surgery. The levosimendan group also exhibited a notable reduction in hospital readmissions. CONCLUSIONS This study provides evidence of several benefits associated with the perioperative use of levosimendan. However, further prospective randomized studies are warranted to standardize and comprehensively document the other perioperative therapies, in order to validate these findings and establish stronger conclusions

The History of Public Relations in Greece from 1950 to 1980: Professionalization of the “art”

The early development of public relations in Greece is explored through a focus on the period between 1950 and 1980. Specifically, the article considers the origins and early developments, important actors, international influences, professional bodies and the field of practice. It found that Greek business public relations was greatly influenced by American practices and through influential practitioners’ contact with the International Public Relations Association (IPRA)

Perioperative Application of Levosimendan Optimizes Postoperative Renal Function and Organ Perfusion in Patients with Severe Heart Failure.

Background: Renal dysfunction and impaired organ perfusion are common concerns following cardiac surgery. Levosimendan, a calcium sensitizer inotropic drug, is investigated in this study for its potential to improve postoperative renal function and organ perfusion in patients with low preoperative ejection fraction and severe myocardial dysfunction after cardiac surgery. Methods: A retrospective analysis was conducted on 314 patients with preoperative heart failure who underwent cardiac surgery. Among them, 184 patients received perioperative adjunctive therapy with levosimendan, while 130 patients with similar characteristics received conventional treatment. Results: The perioperative administration of levosimendan resulted in a significantly lower need for renal replacement therapy (p < 0.001) and improvements in the serum creatinine levels, glomerular filtration rate, and creatinine clearance. Similarly, the C-reactive protein levels, blood pH, and lactic acid levels showed comparable improvements. Conclusions: The use of levosimendan was associated with a significant enhancement in postoperative renal function and a reduction in the need for renal replacement therapy. Furthermore, it resulted in a decrease in the extent of organ malperfusion. Postoperative inflammatory reactions and metabolic balance also exhibited improvements