The triterpene echinocystic acid and its 3-O-glucoside derivative are revealed as potent and selective glucocorticoid receptor agonists

Glucocorticoids are steroid hormones widely used to control many inflammatory conditions. These effects are primarily attributed to glucocorticoid receptor transrepressional activities but with concomitant receptor transactivation associated with considerable side effects. Accordingly, there is an immediate need for selective glucocorticoid receptor agonists able to dissociate transactivation from transrepression. Triterpenoids have structural similarities with glucocorticoids and exhibit anti-inflammatory and apoptotic activities via mechanisms that are not well-defined. In this study, we examined whether echinocystic acid and its 3-O-glucoside derivative act, at least in part, through the regulation of glucocorticoid receptor and whether they can constitute selective receptor activators. We showed that echinocystic acid and its glucoside induced glucocorticoid receptor nuclear translocation by 75% and 55%. They suppressed the nuclear factor-kappa beta transcriptional activity by 20% and 70%, respectively, whereas they have no glucocorticoid receptor transactivation capability and stimulatory effect on the expression of the phosphoenolopyruvate carboxykinase target gene in HeLa cells. Interestingly, their suppressive effect is diminished in glucocorticoid receptor low level COS-7 cells, verifying the receptor involvement in this process. Induced fit docking calculations predicted favorable binding in the ligand binding domain and structural characteristics which can be considered consistent with the experimental observations. Further, glucocorticoids exert apoptotic activities; we have demonstrated here that the echinocystic acids in combination with the synthetic glucocorticoid, dexamethasone, induce apoptosis. Taken together, our results indicate that echinocystic acids are potent glucocorticoid receptor regulators with selective transrepressional activities (dissociated from transactivation), highlighting the potential of echinocystic acid derivatives as more promising treatments for inflammatory conditions

Health effects of desert dust storm events in the south-eastern Mediterranean: perceptions and practices of local stakeholders

Background: The south-eastern Mediterranean experiences frequent desert dust storm events (DDS) that have been shown to be associated with adverse health effects. Aims: This study assessed the perceptions and practices towards DDS of local authorities and stakeholders from 3 countries in the region, Cyprus, Greece and Israel. Methods: Between October 2017 and April 2018, we administered a semi-structured questionnaire to regulatory authorities involved in public protection from DDS as well as social stakeholders in the 3 countries. The questionnaire addressed their knowledge regarding DDS, perceptions on the relationship between DDS and health effects and relevant actions taken towards public protection. Results: Out of 58 stakeholders contacted, 49 participated in the study (84.5% response rate). Fourteen (28.6%) were regulatory authorities and 35 (71.4%) were social stakeholders. All responders were familiar with DDS but several underestimated the frequency of events while the majority (73%) instinctively reported that elders, children and respiratory patients are susceptible subpopulations. Nevertheless, 71% were unaware of a national policy on DDS, or considered that this was lacking in their country. Although several stakeholders reportedly receive questions from the public regarding DDS effects, only few reply according to a pre-determined action plan. Conclusions: Regulatory authorities and social stakeholders in Cyprus, Greece and Israel are characterized by good knowledge of DDS and associated health effects, although implementation of pre-determined action plans for public protection is limited. Future efforts should concentrate on increasing awareness among stakeholders and the public and developing national policies, including effective measures to minimize DDS exposure

Polychaetes (Annelida) of Cyprus (Eastern Mediterranean Sea): An Updated and Annotated Checklist including New Distribution Records

The diversity and distribution of polychaetes in the coastal area and the EEZ of the Republic of Cyprus is presented based on both the literature records and new data acquired in a wide range of environmental monitoring programmes and research projects. A total of 585 polychaete species belonging to 49 families were reported in Cyprus waters; among them, 205 species (34%) were recorded based on the literature only, 149 (26%) were new records based on our own data, and a total of 231 spp. (40%) were recorded from both the literature and new data. A total of 51 polychaete species were identified as non-indigenous; among them, 32 were confirmed as alien species, 4 were considered cryptogenic, and 15 were considered questionable as there were doubts about their identity. The Indo-Pacific Schistomeringos loveni was reported for the first time in the Mediterranean Sea, while four species already reported in the literature, namely, Bispira melanostigma, Fimbriosthenelais longipinnis Leonnates aylaoberi, and Rhodopsis pusilla, were added to the list of non-indigenous polychaetes in the Mediterranean Sea. The current work highlights the importance of implementing environmental monitoring programmes and carrying out research surveys targeting benthic macrofauna assemblages

EULAR/eumusc.net standards of care for rheumatoid arthritis : cross-sectional analyses of importance, level of implementation and care gaps experienced by patients and rheumatologists across 35 European countries

Objective As part of European League against Rheumatism (EULAR)/European Musculoskeletal Conditions Surveillance and Information Network, 20 user-focused standards of care (SoCs) for rheumatoid arthritis (RA) addressing 16 domains of care were developed. This study aimed to explore gaps in implementation of these SoCs across Europe. Methods Two cross-sectional surveys on the importance, level of and barriers (patients only) to implementation of each SoC (0-10, 10 highest) were designed to be conducted among patients and rheumatologists in 50 European countries. Care gaps were calculated as the difference between the actual and maximum possible score for implementation (ie, 10) multiplied by the care importance score, resulting in care gaps (0-100, maximal gap). Factors associated with the problematic care gaps (ie, gap≥30 and importance≥6 and implementation<6) and strong barriers (≥6) were further analysed in multilevel logistic regression models. Results Overall, 26 and 31 countries provided data from 1873 patients and 1131 rheumatologists, respectively. 19 out of 20 SoCs were problematic from the perspectives of more than 20% of patients, while this was true for only 10 SoCs for rheumatologists. Rheumatologists in countries with lower gross domestic product and non-European Union countries were more likely to report problematic gaps in 15 of 20 SoCs, while virtually no differences were observed among patients. Lack of relevance of some SoCs (71%) and limited time of professionals (66%) were the most frequent implementation barriers identified by patients. Conclusions Many problematic gaps were reported across several essential aspects of RA care. More efforts need to be devoted to implementation of EULAR SoCs

Patients with rheumatoid arthritis facing sick leave or work disability meet varying regulations: a study among rheumatologists and patients from 44 European countries

To describe and explore differences in formal regulations around sick leave and work disability (WD) for patients with rheumatoid arthritis (RA), as well as perceptions by rheumatologists and patients on the system's performance, across European countries