Fibroblasts in atherosclerosis:heterogeneous and plastic participants

Purpose of review Fibroblasts are very heterogeneous and plastic cells in the vasculature. A growing interest in fibroblasts in healthy and atherosclerotic vasculature is observed, next to macrophages, endothelial cells, and smooth muscle cells (SMCs). In this review, we discuss fibroblast presence, heterogeneity, origin, and plasticity in health and atherosclerosis based on latest literature. Recent findings With help of single cell sequencing (SCS) techniques, we have gained more insight into presence and functions of fibroblasts in atherosclerosis. Next to SMCs, fibroblasts are extracellular matrix-producing cells abundant in the vasculature and involved in atherogenesis. Fibroblasts encompass a heterogeneous population and SCS data reveal several fibroblast clusters in healthy and atherosclerotic tissue with varying gene expression and function. Moreover, recent findings indicate interesting similarities between adventitial stem and/or progenitor cells and fibroblasts. Also, communication with inflammatory cells opens up a new therapeutic avenue. Because of their highly plastic and heterogeneous nature, modulating fibroblast cell function and communication in the atherosclerotic vessel might be useful in battling atherosclerosis from within the plaque

The proof of the pudding is in the eating? Implementation of cooperative learning:Differences in teachers’ attitudes and beliefs

In the current study differences between primary school teachers classified as high-performing in their implementation of cooperative learning (CL) in their classrooms and teachers who were less successful in implementing cooperative learning were investigated. The levels of implementation of cooperative learning differed significantly between teachers, especially in teaching students the needed cooperative behaviours. Based on semi-structured interviews, it was found that low-performing CL teachers struggle more with student behaviour during cooperative learning, while high-performing CL teachers feel more able to regulate student behaviour. We concluded that teachers who differed in their teacher performance of implementation of cooperative learning also differed in their attitudes and beliefs about this approach. An integrated model on professional development and teacher change is proposed to interpret the results of differences between teachers. This model shows that positive attitudes and beliefs before implementation, but also experiencing positive student outcomes (incl. positive student behaviour) during implementation are important factors in making cooperative learning successful in practice. We suggest that teachers should be prevented from entering a negative spiral in which they experience student behaviour during cooperative learning only as difficult and, therefore, do not succeed in improving students’ cognitive and behavioural outcomes

A framework for realistic 3D tele-immersion

Meeting, socializing and conversing online with a group of people using teleconferencing systems is still quite differ- ent from the experience of meeting face to face. We are abruptly aware that we are online and that the people we are engaging with are not in close proximity. Analogous to how talking on the telephone does not replicate the experi- ence of talking in person. Several causes for these differences have been identified and we propose inspiring and innova- tive solutions to these hurdles in attempt to provide a more realistic, believable and engaging online conversational expe- rience. We present the distributed and scalable framework REVERIE that provides a balanced mix of these solutions. Applications build on top of the REVERIE framework will be able to provide interactive, immersive, photo-realistic ex- periences to a multitude of users that for them will feel much more similar to having face to face meetings than the expe- rience offered by conventional teleconferencing systems

TWEAK and its receptor Fn14 in the synovium of patients with rheumatoid arthritis compared to psoriatic arthritis and its response to tumour necrosis factor blockade

Objective: To investigate the expression of tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor inducible 14 (Fn14) in the inflamed synovium of patients with arthritis, as TWEAK blockade has been observed to have a beneficial effect in an animal model of rheumatoid arthritis (RA). Methods: Synovial tissue (ST) biopsies were obtained from 6 early, methotrexate-naive patients with RA as well as 13 patients with RA and 16 patients with psoriatic arthritis (PsA) who were matched for treatment and disease duration. Serial ST samples were obtained from a separate cohort of 13 patients with RA before and after infliximab treatment. TWEAK and Fn14 expression was evaluated by immunohistochemistry and digital image analysis. Results: TWEAK and Fn14 were clearly expressed in ST of patients with RA and PsA. TWEAK expression was significantly higher in RA (sub) lining samples compared to PsA (p = 0.005 and p = 0.014, respectively), but Fn14 expression was comparable. Double immunofluorescence showed TWEAK and Fn14 expression on fibroblast-like synoviocytes and macrophages, but not T cells. Of interest, persistent TWEAK and Fn14 expression was found after anti-TNF therapy. Conclusions: TWEAK and Fn14 are abundantly expressed in the inflamed synovium of patients with RA and PsA. This raises the possibility that blocking TWEAK/Fn14 signalling could be of therapeutic benefit in inflammatory arthriti

Анализ влияния глобальных угроз на устойчивое развитие стран и регионов мира с помощью байесовских сетей доверия

Застосовано байєсівські мережі довіри для встановлення на якісному рівні причинно-наслідкових залежностей між глобальними загрозами і індексами сталого розвитку. Використання запропонованих в роботі методів синтезу мережі довіри та узагальнення результатів моделвання дозволило отримати цілісну інтерпетацію процесів впливу глобальних загроз на сталий розвиток країн і регіонів світу.Belief Bayesian Networks are used to establish the qualitative cause-effect relationships between global threats and indices of sustainable development. The method of belief network synthesis and the method of final results generalization were proposed. This made it possible to obtain a holistic understanding of effects of global threats to the sustainable development of countries and regions of the world

Prognostic Significance of Carbonic Anhydrase IX Expression in Cancer Patients: A Meta-Analysis

Hypoxia is a characteristic of many solid tumors and an adverse prognostic factor for treatment outcome. Hypoxia increases the expression of carbonic anhydrase IX, an enzyme that is predominantly found on tumor cells and is involved in maintaining the cellular pH balance. Many clinical studies investigated the prognostic value of carbonic anhydrase IX expression, but most have been inconclusive, partly due to small numbers of patients included. The present meta-analysis was therefore performed utilizing the results of all clinical studies to determine the prognostic value of carbonic anhydrase IX expression in solid tumors. Renal cell carcinoma was excluded from this meta-analysis due to an alternative mechanism of upregulation. 958 papers were identified from a literature search performed in Pubmed and Embase. These papers were independently evaluated by two reviewers and 147 studies were included in the analysis. The meta-analysis revealed strong significant associations between CAIX expression and all endpoints: overall survival (HR=1.76, 95%CI 1.58 – 1.98), disease-free survival (HR=1.87, 95%CI 1.62 – 2.16), locoregional control (HR=1.54, 95%CI 1.22 – 1.93), disease-specific survival (HR=1.78, 95%CI 1.41 – 2.25), metastasis-free survival (HR=1.82, 95%CI 1.33 – 2.50), and progression-free survival (HR=1.58, 95%CI 1.27 – 1.96). Subgroup analyses revealed similar associations in the majority of tumor sites and types. In conclusion, these results show that patients having tumors with high carbonic anhydrase IX expression have higher risk of locoregional failure, disease progression, and higher risk to develop metastases, independent of tumor type or site. The results of this meta-analysis further support the development of a clinical test to determine patient prognosis based on CAIX expression and may have important implications for the development of new treatment strategies