Proteoglycan-4 Regulates Fibroblast to Myofibroblast Transition and Expression of Fibrotic Genes in the Synovium

Background: Synovial tissue fibrosis is common in advanced OA with features including the presence of stress fiber-positive myofibroblasts and deposition of cross-linked collagen type-I. Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and is a major component of synovial fluid. PRG4 is a ligand of the CD44 receptor. Our objective was to examine the role of PRG4-CD44 interaction in regulating synovial tissue fibrosis in vitro and in vivo. Methods: OA synoviocytes were treated with TGF-β ± PRG4 for 24h and α-SMA content was determined using immunofluorescence. Rhodamine-labeled rhPRG4 was incubated with OA synoviocytes ± anti-CD44 or isotype control antibodies and cellular uptake of rhPRG4 was determined following a 30-min incubation and α-SMA expression following a 24-h incubation. HEK-TGF-β cells were treated with TGF-β ± rhPRG4 and Smad3 phosphorylation was determined using immunofluorescence and TGF-β/Smad pathway activation was determined colorimetrically. We probed for stress fibers and focal adhesions (FAs) in TGF-β-treated murine fibroblasts and fibroblast migration was quantified ± rhPRG4. Synovial expression of fibrotic markers: α-SMA, collagen type-I, and PLOD2 in Prg4 gene-trap (Prg4GT) and recombined Prg4GTR animals were studied at 2 and 9 months of age. Synovial expression of α-SMA and PLOD2 was determined in 2-month-old Prg4GT/GT&Cd44−/− and Prg4GTR/GTR&Cd44−/− animals. Results: PRG4 reduced α-SMA content in OA synoviocytes (p \u3c 0.001). rhPRG4 was internalized by OA synoviocytes via CD44 and CD44 neutralization attenuated rhPRG4’s antifibrotic effect (p \u3c 0.05). rhPRG4 reduced pSmad3 signal in HEKTGF- β cells (p \u3c 0.001) and TGF-β/Smad pathway activation (p \u3c 0.001). rhPRG4 reduced the number of stress fiberpositive myofibroblasts, FAs mean size, and cell migration in TGF-β-treated NIH3T3 fibroblasts (p \u3c 0.05). rhPRG4 inhibited fibroblast migration in a macrophage and fibroblast co-culture model without altering active or total TGF-β levels. Synovial tissues of 9-month-old Prg4GT/GT animals had higher α-SMA, collagen type-I, and PLOD2 (p \u3c 0.001) content and Prg4 re-expression reduced these markers (p \u3c 0.01). Prg4 re-expression also reduced α-SMA and PLOD2 staining in CD44-deficient mice. Conclusion: PRG4 is an endogenous antifibrotic modulator in the joint and its effect on myofibroblast formation is partially mediated by CD44, but CD44 is not required to demonstrate an antifibrotic effect in vivo

Soft tissue pseudotumours: A pictorial review with emphasis on MRI

Background: Several tumour-like conditions of the soft tissues may be encountered in clinical practice, or when patients undergo radiologic examinations. Al-though advances in cross sectional imaging (ultra-sound, MDCT and MRI) play a pivotal role in the correct evaluation of tumour-like lesions, a systematic approach is needed to achieve a definitive diagnosis or limit the differential diagnosis. Clinical history, physical examination and anatomic location are of paramount importance. Methods: In this pictorial essay we review some of the most frequent benign soft tissue conditions which may be mistaken for malignancy and thus lead to need-less referrals, unnecessary biopsies and great anxi-ety to the patients and their carers. Level of evidence: IV. © 2017, CIC Edizioni Internazionali s.r.l. All rights reserved

Overview of challenges of residential nearly Zero Energy Buildings (nZEB) in Southern Europe

In times of great transition of the European construction sector to energy efficient and nearly zero energy buildings (nZEBs), a market observation containing qualitative and quantitative indications should help to fill out the enormous information gaps concerning the EU 2020 carbon targets. Next to the economic challenges, there are equally important factors that hinder renovating the existing residential building stock and adding newly constructed high performance buildings. Under these circumstances this paper summarizes the findings of a cross-comparative study of the societal and technical barriers of nZEBs implementation in 7 Southern European countries. The aim of the study was to enhance the understanding and provide and overview on future challenges of residential nZEBs in Southern Europe. The result presents an overview of challenges and provides recommendations based on available empirical evidence to further lower those barriers in the European construction sector. The paper finds that the most Southern European countries are poorly prepared for nZEBs implementation and especially for existing buildings. It is essential creating a common approach to further develop nZEBs concepts and definitions in adaptation with the climatic, societal and technical state of progress in Southern Europe. The paper provides suggestions for minimum energy efficiency and renewable energy thresholds to shift the identified gaps into opportunities for future development in deep renovation of buildings.2n

The technology and production of glazed ceramics from Middle Islamic Jerash, Jordan

Jerash in northern Jordan was, despite a focus on its classical heritage, also active in the Middle Islamic period, but little is known about actual developments during this period. This study represents the first study on the Middle Islamic glazed pottery from the site using scanning electron microscopy energy‐dispersive spectrometry (SEM‐EDS) and thin‐section petrography. The results show that two production traditions existed, each with different provenances. The local production is characterized by a non‐calcareous ceramic body and the use of a high‐lead glaze coloured with iron and copper oxides, whereas the turquoise‐glazed samples, likely imported from Mesopotamia, have a calcareous ceramic body and alkali or alkali‐lead glaze.</jats:p

Ten-years experience of a global and freely accessible e-Learning website for paediatric endocrinology and diabetes

The European Society for Paediatric Endocrinology (ESPE) interactive website https://www.espe-elearning.org was first published online in 2012. We describe the various applications of the content of the e-Learning website that has been greatly expanded over the last 10 years. A large module on paediatric diabetes was added with the support of the International Society for Paediatric and Adolescent Diabetes (ISPAD). A separate multilingual module was created that focuses on front-line health care providers in limited resource settings. This module has been well received particularly in targeted parts of the world. E-learning may also be an opportunity to expand or tailor educational activities for learners according to their differing learning needs. The e-Learning website provides guidelines for those interested in general pediatrics, neonatology, clinical genetics and pediatric gynecology. We also describe various new applications such as masterclasses in the format of interactive video lectures and joined and complementary e-Learning/e-Consultation webinars. Finally, international certification was recently realized as e-Learning courses were recognized by the European Accreditation Council for Continuing Medical Education (EACCME). As a result of the social distancing measures introduced to control the COVID-19 pandemic digital education, whether individual or in a virtual classroom setting, has become even more important since e-Learning can connect and engage individuals across geographic boundaries as well as those who live in remote areas. The future of education delivery may include hybrid learning strategies, which include in-person and e-Learning platforms. Combined e-Learning and e-Consultation webinars illustrate how international academic institutions, learned medical specialty societies and networks are uniquely placed to deliver balanced, disease oriented and patient-centred e-Learning education and at the same time as providing expert consultation