New Insights for RANKL as a Proinflammatory Modulator in Modeled Inflammatory Arthritis

Receptor activator of nuclear factor-κB ligand (RANKL), a member of the Tumor Necrosis Factor (TNF) superfamily, constitutes the master regulator of osteoclast formation and bone resorption, whereas its involvement in inflammatory diseases remains unclear. Here, we used the human TNF transgenic mouse model of erosive inflammatory arthritis to determine if the progression of inflammation is affected by either genetic inactivation or overexpression of RANKL in transgenic mouse models. TNF-mediated inflammatory arthritis was significantly attenuated in the absence of functional RANKL. Notably, TNF overexpression could not compensate for RANKL-mediated osteopetrosis, but promoted osteoclastogenesis between the pannus and bone interface, suggesting RANKL-independent mechanisms of osteoclastogenesis in inflamed joints. On the other hand, simultaneous overexpression of RANKL and TNF in double transgenic mice accelerated disease onset and led to severe arthritis characterized by significantly elevated clinical and histological scores as shown by aggressive pannus formation, extended bone resorption, and massive accumulation of inflammatory cells, mainly of myeloid origin. RANKL and TNF cooperated not only in local bone loss identified in the inflamed calcaneous bone, but also systemically in distal femurs as shown by microCT analysis. Proteomic analysis in inflamed ankles from double transgenic mice overexpressing human TNF and RANKL showed an abundance of proteins involved in osteoclastogenesis, pro-inflammatory processes, gene expression regulation, and cell proliferation, while proteins participating in basic metabolic processes were downregulated compared to TNF and RANKL single transgenic mice. Collectively, these results suggest that RANKL modulates modeled inflammatory arthritis not only as a mediator of osteoclastogenesis and bone resorption but also as a disease modifier affecting inflammation and immune activation

High-Throughput Synthesis of Pillared-Layered Magnesium Tetraphosphonate Coordination Polymers: Framework Interconversions and Proton Conductivity Studies

Novel pillared-layered framework materials were synthesized by high-throughput or microwave-assisted methodology that contain Mg2+ and the zwitterionic linker HDTMP (hexamethylenediamine-N,N,N0,N0-tetrakis(methylenephosphonic acid)). Three compounds were structurally characterized by X-ray powder diffraction. In the compound {Mg[(HO3PCH2)2N(CH2)6N (CH2PO3H2)2](H2O)}n(1), obtained at 140 ºC by hydrothermal or microwave-assisted reaction, the layers are built by isolated Mg2+ octahedra coordinated by oxygen atoms from six different zwitterionic HDTMP ligands. Each amino-bis(methylenephosphonate) moiety links three Mg2+ ions, bridging two of them through one phosphonate group and connecting the third polyhedron in a monodentate fashion. In Compound 2, {Mg[(HO3PCH2)2N(CH2)6N(CH2PO3H2)2]}n, hydrothermally synthesized at 180 C, the layers are composed of bidentate amino-bis(methylenephosphonate) moieties connected to three Mg2+ ions, with one of the phosphonate groups acting as a bridging ligand. Various subtle structural changes are noted for the other two compounds. Thermodiffraction of 1 reveals that a crystalline-to-crystalline phase transformation occurs concomitantly with its dehydration, leading to a new anhydrous phase, namely, {Mg[(HO3PCH2)2N(CH2)6N(CH2PO3H2)2]}n(1deh). This process is fully reversible upon equilibrating the solid at room temperature. The reported compounds can adsorb ammonia and CO2. Compound 1 exhibits a moderate proton conductivity, ~1.5 x 10-5 S·cm-1 at 80 ºC and 95% RH, that increases a half order of magnitude after experiencing a complete dehydration/rehydration process

Drug Eluding Stents for Malignant Airway Obstruction: A Critical Review of the Literature

Lung cancer being the most prevalent malignancy in men and the 3rd most frequent in women is still associated with dismal prognosis due to advanced disease at the time of diagnosis. Novel targeted therapies are already on the market and several others are under investigation. However non-specific cytotoxic agents still remain the cornerstone of treatment for many patients. Central airways stenosis or obstruction may often complicate and decrease quality of life and survival of these patients. Interventional pulmonology modalities (mainly debulking and stent placement) can alleviate symptoms related to airways stenosis and improve the quality of life of patients. Mitomycin C and sirolimus have been observed to assist a successful stent placement by reducing granuloma tissue formation. Additionally, these drugs enhance the normal tissue ability against cancer cell infiltration. In this mini review we will concentrate on mitomycin C and sirolimus and their use in stent placement

Stem cell factor is implicated in microenvironmental interactions and cellular dynamics of chronic lymphocytic leukemia

The inflammatory cytokine Stem Cell Factor (SCF, ligand of c-kit receptor) has been implicated as a pro-oncogenic driver and an adverse prognosticator in several human cancers. Increased SCF levels have recently been reported in a small series of patients with chronic lymphocytic leukemia (CLL), however its precise role in CLL pathophysiology remains elusive. In this study, CLL cells were found to predominantly express the membrane isoform of SCF that is known to elicit a more robust activation of the c-kit receptor. SCF was significantly overexpressed in CLL cells compared to healthy tonsillar B cells whilst it correlated with adverse-prognostic biomarkers, shorter time-to-first treatment and shorter overall survival. Activation of immune receptors and long-term cell-cell interactions with the mesenchymal stroma led to an elevation of SCF primarily in adverse-prognostic CLL cases. On the contrary, suppression of oxidative stress and the BTK inhibitor Ibrutinib negated SCF levels. Interestingly, SCF significantly correlated with mitochondrial dynamics and HIF-1α which have previously been linked with clinical aggressiveness in CLL. SCF was able to elicit direct biological effects in CLL cells affecting redox homeostasis and cell proliferation. Overall, the aberrantly expressed SCF in CLL cells emerges as a key response regulator to microenvironmental stimuli whilst correlating with poor prognosis. On these grounds, specific targeting of this inflammatory molecule could serve as a novel therapeutic approach in CLL

High job demands, low support : Social work praktice realities in public social services in Crete

The overall aim of the present thesis is to gain an understanding of the working life of social workers working in public social services in Crete. It is a three-phase study, consisting of three distinct but related research parts; each research part is built upon issues and questions derived from the preceding part. In this work, both quantitative and qualitative approaches were employed. Theoretical perspectives regarding the impact of the welfare environment on social welfare workers’ behaviour and on their well being as well as gender aspects of welfare work constitute the main theoretical framework. The findings of this thesis reveal the significant impact of the organisational environment on social workers’ well being, on their effectiveness as well as on their coping behaviour with unsatisfactory organisational conditions. The main sources of social workers’ dissatisfaction were organisational and extrinsic work aspects; their main sources of satisfaction were intrinsic work aspects. Social workers found themselves facing ethically difficult situations arising from the organisations’ inability to cover clients’ needs as well as from difficulties concerning interprofessional relationships with their superiors or physicians. The most common pattern of coping that social workers used in order to deal with unsatisfactory organisational conditions was the ‘active defensive’ kind of adjustment aiming mainly at offering clients temporary relief. They adjusted their work attitudes to reflect lower expectations of their work. As their professional orientation called for altruistic behaviour towards clients, social workers tried to find solutions within the resource constraints they encountered; they did not risk trying to change the limitations imposed by the employing agencies. Certain common beliefs, such as that offering clients temporary help was the best they could do under the organisational circumstances, contributed to the forming of a dominant view: “the culture of silence”, which resulted in the perpetuation of unsatisfactory organisational conditions. There were influences on social workers’ coping behaviour which affected them in order to accept limitations in their work rather than challenge them. The inability of welfare programmes to cover social needs, organisational factors, factors related to gender and the insufficient amount of social workers’ knowledge limited their potential for intervention in order to improve unsatisfactory conditions. The most common patterns of coping resulted in the partial covering of clients’ needs. Social workers who used active strategies experienced frustration due to their limited effectiveness and the perpetuation of the organisational problems; most of them wanted to quit working in the organisation. The high job demands they experienced due to their efforts to deal with organisational constraints along with the low level of job control resulted in emotional exhaustion

Smart and Resilient Urban Futures for Sustainability in the Post COVID-19 Era: A Review of Policy Responses on Urban Mobility

The COVID-19 pandemic has put lifestyles in question, changed daily routines, and limited citizen freedoms that seemed inalienable before. A human activity that has been greatly affected since the beginning of the health crisis is mobility. Focusing on mobility, we aim to discuss the transformational impact that the pandemic brought to this specific urban domain, especially with regards to the promotion of sustainability, the smart growth agenda, and the acceleration towards the smart city paradigm. We collect 60 initial policy responses related to urban mobility from cities around the world and analyze them based on the challenge they aim to address, the exact principles of smart growth and sustainable mobility that they encapsulate, as well as the level of ICT penetration. Our findings suggest that emerging strategies, although mainly temporary, are transformational, in line with the principles of smart growth and sustainable development. Most policy responses adopted during the first months of the pandemic, however, fail to leverage advancements made in the field of smart cities, and to adopt off-the-shelf solutions such as monitoring, alerting, and operations management

Οι Τεχνολογίες Πληροφορίας & Επικοινωνίας στην κοινωνική ένταξη του προσφυγικού πληθυσμού: Δημιουργία ψηφιακού εργαλείου για την πρόσβαση στις e-Services της Υπηρεσίας Ασύλου

Αντικείμενο: Οι κοινωνικοπολιτικές και υγειονομικές μεταβολές σε ολόκληρο τον κόσμο, συνδυαστικά με την ταχεία τεχνολογική πρόοδο, έχουν οδηγήσει τα τελευταία χρόνια σε ραγδαία ψηφιοποίηση υπηρεσιών και διαδικασιών. Συγχρόνως, η Ελλάδα, αποτελεί μία χώρα, η οποία αποτελεί σημείο εισόδου στην ευρωπαϊκή ήπειρο και παραδοσιακά υποδέχεται μεγάλα ρεύματα προσφυγικών ροών από τρίτες χώρες που αιτούνται άσυλο σε αυτήν. Οι υπηρεσίες που συνδέονται με το νομικό καθεστώς αυτής της πληθυσμιακής μερίδας υπάγονται στην κατηγορία των υπηρεσιών που έχουν ψηφιοποιηθεί, χωρίς ωστόσο να λαμβάνουν υπόψη τα ιδιαίτερα χαρακτηριστικά και τις ανάγκες των ανθρώπων στους οποίους απευθύνονται. Σκοπός: 1) Η αιτιολογημένη επιλογή της ομάδας στόχου, μέσα από την ανάλυση των διαδικασιών ασύλου και των ιδιαίτερων χαρακτηριστικών και αναγκών τους σε συνάφεια με την ψηφιοποίηση της κοινωνίας υποδοχής 2) Η θεωρητική παρουσίαση των Τεχνολογιών Πληροφορίας και Επικοινωνίας (ΤΠΕ) και της σύνδεσης αυτών με την ψηφιοποίηση υπηρεσιών και διαδικασιών σε εθνικό και ευρωπαϊκό επίπεδο 3) Η δημιουργία ενός ψηφιακού μαθησιακού εργαλείου καθοδήγησης και ανάπτυξης ψηφιακών δεξιοτήτων για την αποτελεσματική και αυτόνομη πρόσβαση της ομάδας στόχου στις ψηφιοποιημένες υπηρεσίες ασύλου. Μεθοδολογία: Αρχικά, πραγματοποιήθηκε έρευνα στην υπάρχουσα ελληνόφωνη και ξενόγλωσση βιβλιογραφία σχετικά με την προσφυγική ιδιότητα και τις συναφείς διαδικασίες στο ελληνικό πλαίσιο. Η ίδια μέθοδος ακολουθήθηκε τόσο για την παρουσίαση των ΤΠΕ στο ελληνικό και ευρωπαϊκό πλαίσιο ψηφιοποίησης διαδικασιών όσο και για τη διαμόρφωση του γνωστικού περιεχομένου του εργαλείου που δημιουργήθηκε. Στο τελευταίο, πραγματοποιήθηκε επίσης συνεργασία με διεπιστημονική ομάδα επαγγελματιών για την αξιοποίηση της εμπειρίας της στον προσφυγικό τομέα. Τέλος, δημιουργήθηκε το ψηφιακό εργαλείο με αξιοποίηση πολλαπλών τεχνολογικών μέσων. Συμπεράσματα: Η επιτακτική ανάγκη για μαζική ψηφιοποίηση υπηρεσιών και διαδικασιών έχει οδηγήσει στη διαμόρφωση ψηφιακών περιβαλλόντων, τα οποία καλύπτουν μεν τις ανάγκες της σύγχρονης εποχής, αλλά δεν ανταποκρίνονται στις ανάγκες και τα χαρακτηριστικά των πληθυσμιακών ομάδων στις οποίες απευθύνονται, οπότε ανακύπτουν προβλήματα δυσχρηστίας και αδυναμίας αυτόνομης πρόσβασης σε αυτά. Λαμβάνοντας υπόψη την ενσωμάτωση των Τεχνολογιών Πληροφορίας και Επικοινωνίας στην καθημερινότητα και το γεγονός ότι μπορούν να αξιοποιηθούν για τη διαμόρφωση μαθησιακών εργαλείων, τα οποία προσφέρουν υποστήριξη, καθοδήγηση, και συμβάλλουν στην ανάπτυξη αναγκαίων ψηφιακών δεξιοτήτων, στο πλαίσιο της παρούσας εργασίας δημιουργήθηκε ψηφιακό μαθησιακό εργαλείο, το οποίο υπηρετεί τους ανωτέρω σκοπούς και εστιάζει, με πολυμεσικό αλλά απλό τρόπο, στην πρόσβαση του προσφυγικού πληθυσμού στις ηλεκτρονικές υπηρεσίες ασύλου της Υπηρεσίας Ασύλου, συνιστώντας μία πρωτοποριακή προσπάθεια με εξαιρετικές προοπτικές, η οποία έχει λάβει την αποδοχή του Οργανισμού με τον οποίο υπήρξε άμεση συνεργασία κατά τη διαμόρφωσή του και πρόκειται να δοκιμαστεί μέσα από τη διάθεσή του στους ανθρώπους που ωφελεί στις υπηρεσίες που λειτουργεί.Object: Socio-political and health alterations throughout the world combined with massive technological progress, have led in recent years to a rapid digitalization of services and processes. At the same time, Greece is a country that consists an entry point to the European continent and traditionally receives large streams of refugee flows from third countries that seek asylum. The services related to the legal status of this population fall under the category of services that have been digitalized, without, however, taking into account the particular characteristics and needs of the people to whom they are addressed. Purpose: 1) The justified selection of the target group, through the analysis of the asylum procedures and their particular characteristics and needs in relation to the digitalization of the host society 2) The theoretical presentation of Information and Communication Technologies (ICT) and their connection with the digitalization of services and processes at national and European level 3) The creation of a digital learning tool for guiding and developing digital skills for the effective and autonomous access of the target group to the digitalized asylum services. Methodology: Initially, a search was carried out in the existing Greek-language and foreign-language bibliography on refugee status and the relevant procedures in the Greek framework. The same method was followed both for the presentation of ICT in the Greek and European context of processes’ digitalization and for the formation of the cognitive content of the tool created. In the latter, there was also collaboration with a multidisciplinary team of professionals to make good use of their experience in the refugee field. Finally, the digital tool was created using multiple technological means. Conclusions: The sudden need for mass digitalization of services and processes has led to the formation of electronic systems, which -although meeting the needs of the modern era- do not meet the needs and characteristics of the population groups to which they are addressed, so problems of usability and inability to autonomously access them arise. Taking into account the integration of Information and Communication Technologies in everyday life and the fact that they can be used for the formation of learning tools, which offer support, guidance, and the development of necessary digital skills, in the context of this work a digital learning tool was created, which serves the above purposes and focuses, in a multimedia but simple way, on the access of the refugee population to the electronic asylum services of the Asylum Service, recommending a pioneering effort with excellent prospects, which has received the acceptance of the Organization with which there was direct collaboration during its development and is about to be tested through its disposition to the people it benefits through its services

Serum levels of soluble interleukin - 6 receptor (SIL - 6R) in patient s with myelomatosis and monoclonal eammopathy of undetermined scienifi cance

We measured with an ELISA immunoassay the levels of soluble interleukin-6 receptor (SIL-6R) in the serum of 40 patients with multiple myeloma and also the serum of 10 patients with other plasma-cell dyscrasias. We found that SIL-6R levels were increased by 40% in patients with multiple myeloma. No significant correlation between SIL-6R levels and serum IL-6, TNFa or albumin levels could be demonstrated but we found a highly significant positive correlation between SIL-6R levels and other previously recognized prognastic factors such as B2m, CRP, creatinine, fernitin and LDH. We also found that SIL-6R levels in multiple myeloma patients reflect the activity of the disease, but they cannot be used as a prognostic factor regarding survivalΠροσδιορίστηκαν με ανοσολογική τεχνική ELISA τα επίπεδα του διαλυτού υποδοχέα της IL-6(SIL-6R) στον ορό 40 ασθενών με πολλαπλούν μυέλωμα και 10 ασθενών με άλλες πλασματοκυτταρικές δυσχέριες. Βρήκαμε ότι τα επίπεδα του SIL-6R είναι αυξημένα σε ποσοστό 40% των αρρώστων με πολλαπλούν μυέλωμα. δεν βρέθηκε συσχέτιση μεταξύ των επιπέδων του SIL-6R και των επιπέδων της IL-6, TNFa ή αλβουμήνης, αλλά βρέθηκε θετική συσχέτιση μεταξύ των επιπέδων του SIL-6R και άλλων προγνωστικών παραγόντων όπως Β2m, CRP, κρεατίνης, φερριτίνης και LDH. Βρήκαμε επίσης ότι τα επίπεδα του SIL-6R στους ασθενείς με πολλαπλούν μυέλωμα αντανακλούν τη δραστηριότητα της νόσου, ωστόσο δεν μπορούν να χρησιμοποιηθούν ως προγνωστιός παράγοντας με κριτήριο την επιβίωση