Non-Invasive Assessment of Micro- and Macrovascular Function after Initiation of JAK Inhibitors in Patients with Rheumatoid Arthritis

Background: Janus kinase (JAK) inhibitors constitute a novel class of oral biologic disease-modifying antirheumatic drugs for patients with rheumatoid arthritis (RA). However, their use has been associated with increased risk of major cardiovascular events. We investigated whether treatment with JAK inhibitors exerts significant alterations in the micro- and microvasculature in RA patients. Methods: Thirteen patients with RA initiating treatment with JAK inhibitors were prospectively studied. Eventually, data from 11 patients who completed the study were analyzed. Procedures were performed at baseline and 3 months after treatment. Nailfold videocapillaroscopy was applied to detect alterations of the dermal capillary network. Participants underwent 24 h ambulatory blood pressure monitoring (Mobil-O-Graph device) for the assessment of blood pressure (both brachial and aortic) and markers of large artery stiffening [pulse wave velocity (PWV), augmentation index] throughout the whole 24 h and the respective day- and nighttime periods. Carotid intima–media thickness was assessed with ultrasound. Results: Three-month treatment with JAK inhibitors was not associated with any differences in brachial and aortic blood pressure, arterial stiffness, and carotid atherosclerosis, with the only exception of nighttime PWV, which was significantly elevated at follow-up. However, three-month treatment with JAK inhibitors induced significant microvascular alterations and increased the total number of capillaroscopic abnormalities. Conclusions: Three-month treatment with JAK inhibitors may exert significant effects on microcirculation as assessed with nailfold videocapillaroscopy, whereas macrovascular structure and function appears largely unaffected. Further research toward this direction may add substantial information to the available literature regarding cardiovascular aspects of JAK inhibitors in RA

Η εικόνα της γυναίκας στα Εγχειρίδια του Γυμνασίου και του Λυκείου

Στη σύγχρονη κοινωνία η θέση της γυναίκας δεν έχει την αναβάθμιση και την εξέλιξη που θα περιμέναμε να έχει. Η γυναίκα παλεύει καθημερινά να αποδείξει την αξία της και να ανταμειφθεί επάξια στον επαγγελματικό στιβο και στην κοινωνική της ζωή. Σε μια σύγχρονη κοινωνία είναι αναγκαίο λοιπόν οι πολίτες της να εκπαιδεύονται με τις αξίες της ισότητας και της ισοτιμίας, έτσι ώστε να εξαφανιστούν τα στερεότυπα που αφορούν την ισότητα των δύο φύλων. Στο πλαίσιο της σύγχρονης παιδαγωγικής εξατάζεται το θέμα της προσέγγισης της ισότητας των δύο φύλων και των καθορισμένων ρόλων τους στο σχολικό περιβάλλον. Τα σχολικά εγχειρίσια όπως θα αναδειχθεί και από την παρούσα εργασία, είναι φορείς μετάδοσης γνώσεων, αντιλήψεων, στάσεων και συμπεριφοράς. Μέσα από τα κείμενα τους και τις εικονογραφίσεις περνάνε μηνύματα στους/ στις μαθητές/ μαθήτριες για το ρόλο και το πρότυπο της γυναίκας, όπου επηρεάζουν την αντίληψή τους γύρω από αυτό. Η παρούσα εργασία χωρίζεται σε δύο μέρη, το θεωρητικό και το ερευνητικό. Στο θεωρητικό γίνεται μια προσπάθεια παρουσίασης του γυναικείου ρόλου όπως παρουσιάζεται στα σχολικά εγχειρίδια του γυμνασίου και του λυκείου. Αρχικά, αναλύονται τα διάφορα φεμινιστικά κινήματα, τα οποία έδωσαν την έναρξη για την ανάδειξη του ρόλου της γυναίκας στην κοινωνία και αποτέλεσαν την εναρκτήριο δύναμη να ξεκινήσουν οι έρευνες και οι μελέτες που αφορούσα την ύπαρξη στερεοτύπων στα σχολικά εγχειρίδια όλων των βαθμίδων και στις διαστάσεις που αυτό περιελάμβανε. Στη συνέχεια αναλύεται ο ρόλος των βιβλίων και των σχολικών εγχειριδίων κυρίως ως φορέας κοινωνικοπόιησης και διαμόρφωσης προσωπικοτήτων. Το σχολικό εγχειρίδιο με τα ποικίλα μηνύματα που μεταδίδει, δημιουργεί θέσεις υποκειμένων εκφράζοντας αποδεκτές κοινωνικές παραδοχές. Οι απόψεις που προωθεί για τα δύο φύλα, επηρεάζουν τους/ τις μαθητές, μαθήτριες και καθορίζει τις πεποιθήσεις των παιδιών για την συνείδηση και την έμφυλη ταυτότητά τους. Στην παρούσα εργασία εξετάζεται ο ρόλος όχι μόνο των ελληνικών σχολικών εγχειριδίων αλλά και των ξένων με σκοπό να αναδειχθεί η δύναμή του βιβλίου ως βασικό εργαλείο της εκπαίδευσης. Στο θεωρητικό μέρος επίσης, παρουσιάζονται και αναλύονται έρευνες σχετικά με τον ρόλο της γυναίκας όπως παρουσιάζεται σε διάφορα σχολικά εγχειρίδια της δευτεροβάθμιας εκπαίδευσης. Μέσα από τη μελέτη αυτή με αναφορά αρκετών παραδειγμάτων θα αναδειχθεί η διαιώνιση των στερεοτύπων που αφορούν το γυναικείο φύλο και πως αυτά τελικά επιδρούν στους/ στις μαθητές/ τριες διαμορφώνοντας την αντίληψή τους γύρω από τους ρόλους των δύο φύλων. Στο δεύτερο μέρος, το ερευνητικό, θα μελετηθεί η περίπτωση των βιβλίων της Πληροφορικής που διδάσκεται στη δευτεροβάθμια Εκπαίδευση. Ο λόγος που επιλέχθηκαν τα βιβλία αυτού του επιστημονικού πεδίου είναι για να αναδειχθεί καλύτερα το πόσο αποκομμένη, ακόμα και στη σύγχρονη κοινωνία, είναι η γυναίκα από την τεχνολογία. Η μελέτη περιλαμβάνει τον γλωσσικό σεξισμό, την υποβάθμιση της γυναίκας μέσω της εικονογράφισης και την ανάδειξη των στερεοτυπικών χαρακτηριστικών και των ρόλων των δύο φύλων.In modern society, the position of women does not have the upgrade and development that we expected. The woman struggles every day to prove her worth and to be deservedly rewarded in the professional arena and in her social life. In a modern society it is therefore necessary for its citizens to be educated with the values of equality and equity, so that the stereotypes concerning the equality of the two sexes disappear. In the context of modern pedagogy, the issue of approaching the equality of both sexes and their defined roles in the school environment is examined. The school manuals, as this work will show, are carriers of knowledge, perceptions, attitudes and behavior. Through their texts and illustrations, they send messages to the students about the role and role model of women, where they influence their perception of it. This work is divided into two parts, the theoretical and the research. In theory, an attempt is made to present the female role as it is presented in high school textbooks. Initially, the different feminist movements are analyzed, which gave the start to the promotion of the role of women in society and were the starting force to start the researches and studies concerning the existence of stereotypes in school textbooks of all grades and the dimensions that this included. Then the role of books and school textbooks is analyzed mainly as an agent of socialization and shaping of personalities. The school textbook, with the various messages it conveys, creates subject positions by expressing accepted social assumptions. The views it promotes about the two sexes affect the male and female students and determines the children's beliefs about their consciousness and gender identity. In this paper, is examined not only the role of Greek school textbooks but also foreign textbooks in order to highlight the power of the book as a basic tool of education. In the theoretical part as well, research is presented and analyzed regarding the role of women as presented in various secondary school textbooks. Through this study, citing several examples, the perpetuation of stereotypes concerning the female gender will be highlighted and how these ultimately affect the students, shaping their perception of the roles of the two sexes. In the second part, the research part, the case of Informatics books taught in secondary education will be studied. The reason that the books of this scientific field were chosen is to better highlight how cut off, even in modern society, women are from technology. The study includes linguistic sexism, the degradation of women through iconography and the highlighting of stereotypical characteristics and gender roles

Microbiome in Chronic Kidney Disease

The gut microbiome is a complex collection of microorganisms with discrete characteristics and activities. Its important role is not restricted to food digestion and metabolism, but extends to the evolution, activation and function of the immune system. Several factors, such as mode of birth, diet, medication, ageing and chronic inflammation, can modify the intestinal microbiota. Chronic kidney disease (CKD) seems to have a direct and unique effect, as increased urea levels result in alteration of the gut microbiome, leading to overproduction of its metabolites. Therefore, potentially noxious microbial uremic toxins, which have predominantly renal clearance, including p-cresyl sulfate, indoxyl sulfate and N-oxide of trimethylamine [Trimethylamine-N-Oxide (TMAO)], accumulate in human’s body, and are responsible not only for the clinical implications of CKD, but also for the progression of renal failure itself. Certain changes in gut microbiome are observed in patients with end stage renal disease (ESRD), either when undergoing hemodialysis or after kidney transplantation. The purpose of this review is to summarize the changes of gut microbiome and the protein bound uremic toxins which are observed in CKD and in different kidney replacement strategies. In addition, we attempt to review the connection between microbiome, clinical implications and immune response in CKD

Serum OPG and RANKL Levels as Risk Factors for the Development of Cardiovascular Calcifications in End-Stage Renal Disease Patients in Hemodialysis

Cardiovascular calcifications (CVC) are frequently observed in chronic kidney disease (CKD) patients and contribute to their cardiovascular mortality. The aim of the present study was to investigate the impact of osteoprotegerin (OPG)/Receptor Activator of NF-κΒ (RANK)/RANK ligand (RANKL) pathway in the development and evolution of CVCs in hemodialysis patients. In total, 80 hemodialysis patients were assessed for the presence of vascular (abdominal aorta and muscular arteries) calcifications and results were correlated to serum OPG and RANKL levels and the OPG/RANKL ratio. Traditional cardiovascular risk factors and mineral bone disease parameters were also estimated. The presence of VCs was also evaluated 5 years after the initiation of the study, and results were correlated to the initial serum OPG levels. Age, diabetes mellitus, coronary artery disease and OPG levels (p p = 0.026), but they were not correlated with the progression of VCs. Serum OPG levels are positively and independently associated with VCs in HD patients, but not with their progression. RANKL levels did not show any associations, whereas further studies are needed to establish the significance of OPG/RANKL ratio

Type of ANCA May Be Indispensable in Distinguishing Subphenotypes of Different Clinical Entities in ANCA-Associated Vasculitis

The traditional nomenclature system for classifying antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) based on clinical phenotype describes granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA) as distinct clinical entities. This classification has proved its expedience in clinical trials and everyday clinical practice; yet, a substantial overlap in clinical presentation still exists and often causes difficulties in prompt definition and clinical distinction. Additionally, new insights into the AAV pathogenesis point out that PR3 and MPO-AAV may not represent expressions of the same disease spectrum but rather two distinct disorders, as they display significant differences. Thus, it is supported that a classification based on ANCA serotype (PR3-ANCA, MPO-ANCA or ANCA-negative) could be more accurate and also closer to the nature of the disease compared to the phenotype-based one. This review aims to elucidate the major differences between PR3 and MPO-AAV in terms of epidemiology, pathogenesis, histological and clinical manifestations and response to therapeutic approaches

Different Types of Chronic Inflammation Engender Distinctive Immunosenescent Profiles in Affected Patients

Immunosenescence encompasses a spectrum of lymphocyte phenotypic alterations. The aim of the study was to evaluate immunosenescent effect of two different forms of chronic inflammation, Systemic Lupus Erythematosous (SLE), a systemic autoimmune disease, and End-Stage Kidney Disease (ESKD), a chronic inflammatory disorder. Certain lymphocyte surface molecules, including CD31, CD45RA, CCR7, CD28, CD57, for T, and IgD, CD27 for B lymphocytes, were analyzed by flow cytometry in 30 SLE and 53 ESKD patients on hemodialysis (HD), and results were compared to 31 healthy controls (HC) of similar age, gender, and nationality. Significant Lymphopenia was evident in both SLE and ESKD-HD patients, compared to HC, affecting B cells 75.4 (14.4–520.8), 97 (32–341), and 214 (84–576) cells/μL, respectively, p < 0.0001, and CD4 cells 651.2 (71.1–1478.2), 713 (234–1509), and 986 (344–1591) cells/μL, respectively, p < 0.0001. The allocation of B cell subpopulations was remarkably different between SLE and ESKD-HD patients. SLE showed a clear shift to senescence (CD19IgD-CD27−) cells, compared to ESKD-HD and HC, 11.75 (10)% vs. 8 (6) vs. 8.1 (10), respectively. Regarding T lymphocytes, Central Memory CD8 cells predominated in both SLE and ESKD-HD patients compared to HC, 53 (50)%, 52 (63), and 24 (64)%, respectively, while ESKD-HD but not SLE patients also had increased expression of CD4CD28− and CD8CD28− cells. In conclusion, both diseases are followed by significant lymphopenia; however, the senescent phenomenon affects the B lymphocyte compartment in SLE patients and T lymphocytes in ESKD-HD patients

Increase in Double Negative B Lymphocytes in Patients with Systemic Lupus Erythematosus in Remission and Their Correlation with Early Differentiated T Lymphocyte Subpopulations

B and T lymphocytes demonstrate important alterations in patients with systemic lupus erythematous (SLE), with a significant upregulation of double negative (DN) B cells. The aim of this study was to evaluate the correlation of T cell immunity changes with the distinct B-cell-pattern SLE. In the present study, flow cytometry was performed in 30 patients in remission of SLE and 31 healthy controls to detect DN B cells (CD19+IgD-CD27-) and a wide range of T lymphocyte subpopulations based on the presence of CD45RA, CCR7, CD31, CD28, and CD57, defined as naive, memory, and advanced differentiated/senescent T cells. Both B and T lymphocytes were significantly reduced in SLE patients. However, the percentage of DN B cells were increased compared to HC (12.9 (2.3–74.2) vs. 8 (1.7–35), p = 0.04). The distribution of CD4 and CD8 lymphocytes demonstrated a shift to advanced differentiated subsets. The population of DN B cells had a significant positive correlation with most of the early differentiated T lymphocytes, CD4CD31+, CD4CD45RA+CD28+, CD4CD45RA+CD57-, CD4CD45RA-CD57-, CD4CD28+CD57-, CD4CD28+CD57+, CD4 CM, CD8 CD31+, CD8 NAÏVE, CD8CD45RA-CD57-, CD8CD28+CD57-, and CD8CD28+CD57+. Multiple regression analysis revealed CD4CD31+, CD8CD45RA-CD57-, and CD8CD28+CD57- cells as independent parameters contributing to DN B cells, with adjusted R2 = 0.534 and p < 0.0001. The predominance of DN B cells in patients with SLE is closely associated with early differentiated T lymphocyte subsets, indicating a potential causality role of DN B cells in T lymphocyte activation

Immunosenescence and Immune Exhaustion Are Associated with Levels of Protein-Bound Uremic Toxins in Patients on Hemodialysis

Background: The accumulation of protein-bound uremic toxins (PBUTs) in chronic kidney disease may affect patients’ immune status. The aim of the study was to evaluate their potential impacts on lymphocyte alterations in patients on hemodialysis (HD). Methods: The plasma levels of PBUTs were assessed in 54 patients on HD and 31 healthy individuals, using ultra-performance liquid chromatography. The results correlated with the senescent and exhausted status of lymphocytes, based on certain surface molecules, analyzed by flow cytometry. Results: The plasma levels of PBUTs were significantly increased in the patients on HD compared with the healthy controls. The patients with residual kidney function had reduced hippuric acid (HA) levels, total (p = 0.03) and free (p = 0.04), and free IxS levels (p = 0.02). The total and free HA levels correlated negatively with less differentiated subpopulations, CD4+CD45RA+CD31+ (p = 0.037 and p = 0.027), CD8+CD28+CD57− (p = 0.01, p = 0.01), and naïve B cells (CD19+IgD+CD27−) (p = 0.04, p = 0.03). Both the total and the free pCS levels correlated positively with exhausted CD4 cells, p = 0.02 and p = 0.01, respectively. A multivariate analysis showed that IxS and age were the main independent parameters implicated in the reduction intotal CD4 and B lymphocytes and their naïve and early differentiated subsets. Conclusions: Increased PBUTs levels are associated with immune disturbances of patients on HD, HA, and IxS in the immunosenescent and pCS in the immunoexhaustion alterations

Prospective Analysis of B Lymphocyte Subtypes, before and after Initiation of Dialysis, in Patients with End-Stage Renal Disease

End-stage renal disease (ESRD) is followed by alterations in adaptive immunity. The aim of this study was to evaluate B lymphocyte subtypes in ESRD patients before and after hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Patients and Methods. CD5, CD27, BAFF, IgM and annexin were evaluated by flow cytometry on CD19+ cells in ESRD patients (n = 40), at time of initiating HD or CAPD (T0) and 6 months later (T6). Results. A significant reduction in ESRD-T0 compared to controls was noticed for CD19+, 70.8 (46.5) vs. 171 (249), p p p p = 0.002, CD19+BAFF+, 59.7 (37.8) vs. 127.9 (123.7), p p p = 0.03). CD19+CD5+ cells were the only cell type with an increased proportion in ESRD-T0 patients (2.7 (3.7) vs. 0.6 (1.1), p p = 0.02. Conclusions. B cells and most of their subtypes were significantly reduced in ESRD-T0 patients compared to controls, the only exception being CD19+CD5+ cells. Apoptotic changes were prominent in ESRD-T0 patients and were exacerbated by HD