T Regulatory Cells in Systemic Lupus Erythematosus: Current Knowledge and Future Prospects

Systemic lupus erythematosus (SLE) is one of the most diverse autoimmune diseases, regarding clinical manifestations and therapeutic management. Visceral involvement is often and is generally associated with increased mortality and/or permanent disability. Thus, a reliable assessment of disease activity is required in order to follow‐up disease activity and apply appropriate therapy. Several serological indexes have been studied due to their competence in assessing disease activity in SLE. Apart from conventional and currently assessed serological indexes, regulatory T cells (Tregs), a CD4+ cellular population of the acquired immune compartment with homeostatic phenotype, are currently under intense investigation in SLE. In this chapter, Tregs ontogenesis and subpopulations are discussed focusing on their implications in immunopathophysiology of SLE. The authors present data indicating that this CD4+ population is highly associated with disease activity and response to treatment, concluding that Tregs are a promising biomarker in SLE. Future prospective includes Tregs implication in SLE therapeutic interventions

Chronic Brucellosis Patients Retain Low Frequency of CD4+ T-Lymphocytes Expressing CD25 and CD28 after Escherichia coli LPS Stimulation of PHA-Cultured PBMCs

Chronic brucellosis patients display a defective Th1 response to PHA. We have previously shown that heat-killed B. abortus (HKBA) can downregulate the PHA-induced increase of CD4+/CD25+ and CD14+/CD80+ cells of brucellosis patients. In the present study, we investigate the effect of E. coli LPS, as a potent stimulant of monocytes and autologous T-lymphocytes, on the PHA-cultured PBMCs of the same groups of patients. Thirteen acute brucellosis (AB) patients, 22 chronic brucellosis (CB) patients, 11 “cured” subjects, and 15 healthy volunteers were studied. The percentage of CD4+/CD25+ and CD4+/CD28+ T-lymphocytes as well as CD14+/CD80+ monocytes were analyzed by flow cytometry after PBMCs culture with PHA plus E. coli LPS. A significant decrease in the percentage of CD4+/CD25+ and CD4+/CD28+ T-lymphocytes was observed in CB compared to AB. In HKBA cultures, compared to E. coli LPS-cultures, there was a significant reduction of CD4+/CD25+ T-lymphocytes in all groups and CD14+/CD80+ in patients groups. We suggest that Brucella can modulate host immune response, leading to T-cell anergy and chronic infection

CD14/TLR4 in sepsis pathogenesis and therapy

Sepsis still remains one of the leading causes of death in critical care units all over the world. It seems that one of the major pathophysiological events in sepsis is the extreme activation of the immune system, which leads to massive production of several cytokines and other mediators of inflammation. Pattern Recognition Receptors (PRRs) are responsible for the recognition of the pathogens by the innate immunity cells and for the consequent cytokine production. This fact shows that PRRs could possibly play an important role in sepsis pathogenesis. Among all PRRs, TLR4 (Toll Like Receptor 4) and CD14 are primarily responsible for the recognition of Gram(-) bacteria, which are responsible for the majority of sepsis cases. It seems that the expression of TLR4 and CD14 present alterations during sepsis. Some of these alterations could be used as prognostic factors in septic patients, as they have been correlated with better or worse outcome. Finally, TLR4 and CD14 represent possible targets in sepsis treatment. Many attempts have been done to block these two receptors at many levels, using monoclonal antibodies, soluble analogues and especially antagonists. Results, in some cases encouraging in others disappointing, are still being tested

Expression of phosphorylated ribosomal protein S6 in mesothelioma patients - correlation with clinico-pathological characteristics and outcome: results from the European Thoracic Oncology Platform (ETOP) Mesoscape project

Pleural mesothelioma (PM) is an aggressive malignancy with poor prognosis. Although histology and pathologic stage are important prognostic factors, better prognostic biomarkers are needed. The ribosomal protein S6 is a downstream target of the phosphatidylinositol 3-kinase (PI3K) pathway involved in protein synthesis and cell proliferation. In previous studies, low phosphorylated S6 (pS6) immunoreactivity was significantly correlated with longer progression-free survival (PFS) and overall survival (OS) in PM patients. We aimed to correlate pS6 expression to clinical data in a large multi-centre PM cohort as part of the European Thoracic Oncology Platform (ETOP) Mesoscape project. Tissue Micro Arrays (TMAs) of PM were constructed and expression of pS6 was evaluated by a semiquantitatively aggregate H-score. Expression results were correlated to patient characteristics as well as OS/PFS. pS6 IHC results of 364 patients from 9 centres, diagnosed between 1999 and 2017 were available. The primary histology of included tumours was epithelioid (70.3%), followed by biphasic (24.2%) and sarcomatoid (5.5%). TMAs included both treatment-naive and tumour tissue taken after induction chemotherapy. High pS6 expression (181 patients with H-score>1.41) was significantly associated with less complete resection. In the overall cohort, OS/PFS were not significantly different between pS6-low and pS6-high patients. In a subgroup analysis nonepithelioid (biphasic and sarcomatoid) patients with high pS6 expression showed a significantly shorter OS (p< 0.001, 10.7 versus 16.9 months) and PFS (p < 0.001, 6.2 versus 10.8 months). In subgroup analysis, in non-epithelioid PM patients high pS6 expression was associated with significantly shorter OS and PFS. These exploratory findings suggest a clinically relevant PI3K pathway activation in non-epithelioid PM which might lay the foundation for future targeted treatment strategies

Αριστεροχειρία και Δ.Ε.Π.Υ., μελέτη σε κορίτσια: συστηματική ανασκόπηση

Η διαταραχή ελλειμματικής προσοχής – υπερκινητικότητα (ΔΕΠΥ) πρόκειται για νευροαναπτυξιακή διαταραχή η οποία παρατηρείται ως επί το πλείστον στην παιδική ηλικία χωρίς βέβαια να μην υπάρχουν και παραδείγματα ανθρώπων με την συγκεκριμένη διαταραχή στην ενήλικη ζωή .Δείγματα της ΔΕΠΥ έχουν παρατηρηθεί από τις αρχές του 1900 ωστόσο με το πέρασμα των χρόνων οι περιπτώσεις αυξάνονται διαρκώς. Στην παρούσα εργασία θα αναλυθούν τα αίτια ,τα συμπτώματα και η σχέση των δύο φύλων με αυτή . Τα αγόρια είναι πιο επιρρεπή σε σχέση με τα κορίτσια και εμφανίζουν σχετικά διαφορετικά συμπτώματα .θα γίνει επίσης αναφορά στην διάγνωσή της από τους ειδικούς αλλά και στις προτεινόμενες θεραπείες που ακολουθούνται κάθε φορά. Ιδιαίτερα σημαντικό και κάτι το οποίο αξίζει να αναφερθεί είναι ότι η ΔΕΠΥ συνήθως συνυπάρχει και με άλλες διαταραχές ή δυσκολίες ιδιαίτερα στην ζωή των παιδιών όπως κάποιου είδους δυσλεξία . Τέλος, θα γίνει λόγος για τη σχέση της διαταραχής ελλειμματικής προσοχής - υπερκινητικότητας με την αριστεροχειρία δηλαδή την προτίμηση του αριστερού χεριού κάτι το οποίο είναι ιδιαίτερα σύνηθες σε τέτοιες περιπτώσεις και ιδιαίτερα σχετικά με το γυναικείο φύλο και τα κορίτσια κατόπιν ερευνών και παραδειγμάτων.Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is mostly observed in childhood, although there are of course no examples of people with this disorder in adulthood. Examples of ADHD have been observed since the early 1900s, however over the years the cases are constantly increasing. In this paper, the causes, symptoms and the relationship between the two sexes will be analyzed. Boys are more susceptible than girls and show relatively different symptoms. Reference will also be made to her diagnosis by the experts as well as to the proposed treatments that are followed each time. Particularly important and something worth mentioning is that ADHD usually coexists with other disorders or difficulties especially in the life of children such as some kind of dyslexia. Finally, there will be talk about the relationship between attention deficit hyperactivity disorder and left-handedness, i.e. the preference for the left hand, something which is particularly common in such cases and especially regarding the female gender and girls following research and example

The effect of taxes and other fiscal incentives on foreign direct investment, with emphasis on European integration

This doctoral dissertation is one of few studies that aims at examining the effect of tax and other fiscal incentives on fdi attraction in integrated regions, by emphasizing on an area’s degree of integration. Theoretical framework refers to OLI paradigm. Econometric analysis focuses on gravity model, as it is applied by the introduction of bilateral variables, makes possible the control of heterogeneity among home and host countries. Moreover, the problem of endogeneity is confronted with maximum likelihood method, which is solved by Heckman’s two step analysis, i.e. the investor’s decision has two stages, whether he is going to invest and if he finally invests, how much he will invest. Sample selection problem is possible to lead to biased results, especially due to insufficient or zero observations. Main result is that deep integration diminishes the effect of tax-variables, especially tax-differential, in fdi attraction. On the other hand, the effect of subsidies and grants becomes more intense in fdi attraction, under deeper integration. Other variables such as market size, technology and education play also important complementary role in fdi attractionΗ παρούσα διατριβή είναι μια από τις λίγες μελέτες που έχει ως σκοπό τη διερεύνηση της επίδρασης των φορολογικών και άλλων δημοσιονομικών κινήτρων, στην προσέλκυση ΑΞΕ σε ολοκληρωμένες οικονομικά περιφέρειες. Επιπλέον έμφαση δίδεται στη διαφοροποίηση του βαθμού ολοκλήρωσης μιας περιφέρειας. Το θεωρητικό πλαίσιο εστιάζει στο παράδειγμα του O.L.I. Dunning. Η οικονομετρική ανάλυση εστιάζει στο υπόδειγμα της βαρύτητας έτσι όπως εφαρμόζεται με την εισαγωγή δίτιμων μεταβλητών θεωρείται κατάλληλο για να ελέγξει την ετερογένεια των κινήτρων ανάμεσα σε χώρες προέλευσης και προορισμού. Περαιτέρω, το πρόβλημα της ενδογένειας αντιμετωπίζεται με τη μέθοδο της μέγιστης πιθανοφάνειας, η οποία επιλύεται με την ανάλυση δυο βημάτων του Heckman, δηλαδή η απόφαση του επενδυτή έχει δυο στάδια, εάν θα επενδύσει και πόσο. Το πρόβλημα της επιλογής δείγματος (sample selection) είναι δυνατόν να οδηγεί σε παραποιημένα αποτελέσματα, ιδιαίτερα λόγω των ανεπαρκών ή μηδενικών παρατηρήσεων. Τα βασικά συμπεράσματα είναι ότι η βαθύτερη ολοκλήρωση μειώνει την επίδραση των φορολογικών μεταβλητών, κυρίως της διαφοράς του φς, στην προσέλκυση ΑΞΕ. Τουναντίον, η επίδραση των επιδοτήσεων και επιχορηγήσεων γίνεται εντονότερη στην προσέλκυση των ΑΞΕ. Από τις λοιπές μεταβλητές ελέγχου σημαντικό ρόλο παίζουν το μέγεθος της αγοράς, η τεχνολογία και η εκπαίδευση