Towards a European health research and innovation cloud (HRIC).

The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the community in terms of technologies, governance, management, regulation, and ethics requirements. Here, we describe the vision and expected benefits of digital data sharing in health research activities and present a roadmap that fosters the opportunities while answering the challenges of implementing a HRIC. For this, we put forward five specific recommendations and action points to ensure that a European HRIC: i) is built on established standards and guidelines, providing cloud technologies through an open and decentralized infrastructure; ii) is developed and certified to the highest standards of interoperability and data security that can be trusted by all stakeholders; iii) is supported by a robust ethical and legal framework that is compliant with the EU General Data Protection Regulation (GDPR); iv) establishes a proper environment for the training of new generations of data and medical scientists; and v) stimulates research and innovation in transnational collaborations through public and private initiatives and partnerships funded by the EU through Horizon 2020 and Horizon Europe.

Sister chromatid exchanges and cell proliferative abilities in cultured peripheral blood lymphocytes of patients with rheumatoid and reactive arthritis.

OBJECTIVE: Analysis of cytogenetic alterations in peripheral blood lymphocytes (PBL) of patients with acute and chronic reactive arthritis (AcReA and ChrReA) and rheumatoid arthritis (RA). METHODS: The frequencies of sister chromatid exchanges (SCE) and cell proliferative abilities were analysed in PBL from 69 patients with arthritis and 30 healthy controls. The analyses were done on metaphase chromosomes from PBL grown in cell culture for 72 hours. Cytogenetic parameters were compared among study groups and correlations with different clinical, immune and demographic characteristics were analysed. RESULTS: No significant increases in the frequencies of SCE were detected in PBL from patients with AcReA, ChrReA and RA as compared to controls. However, marked impairment of cell proliferative abilities was detected in cultured lymphocytes from patients with arthritis as compared to healthy controls. Significant associations between measures of disease activity and proliferative abilities of PBL were established. Parameters of lymphocyte proliferation were also influenced by concentration of anti-inflammatory cytokine interleukin-10 in the blood of patients. CONCLUSION: No increased risk of genetic alterations as measured by the rate of SCE was found in patients with RA and ReA. It is most likely that impaired proliferative abilities of peripheral blood lymphocytes are related to disease activity and could reflect systemic changes in cytokines production and intracellular signal transduction.

In vitro interaction between two antineoplastic drugs--phopurinum and interferon alpha 2.

Induction of sister chromatid exchanges (SCEs) and chromosome aberrations (CAs) by two antineoplastic drugs--phopurinum (2-dimethylamino-6-diethyleneiminophosphamido-7-methylpurine) and recombinant human interferon alpha 2 (rHuIFN-alpha 2) was studied in human lymphocytes in vitro. Phopurinum was found to cause a significant increase of both SCEs and CAs in lymphocytes, while rHuIFN-alpha 2 induced only SCEs. Combined treatment with these two drugs reduced SCE and CA levels as compared with those induced by phopurinum alone. The maximal extent of reduction, however, was observed at intermediate doses of phopurinum.

Modifying effects of interferon and puromycin on cytogenetic damage induced by alkylating drug phopurine in human lymphocytes.

The induction of sister chromatid exchanges (SCEs) by the bifunctional alkylating antineoplastic drug phopurine (2-dimethyl-amino-6-diethyleneiminophosphamido-7-methylpurine) and its modification by human recombinant interferons alpha 2, beta and gamma (HuIFN alpha 2, HuIFN beta and HuIFN gamma) and puromycin (PM) were studied in human lymphocytes. Results demonstrated a striking similarity in the modifying action of HuIFN alpha 2 and PM: 1) both modifiers reduced SCE values induced by phopurine, 2) at high and low doses of phopurine the effect of both modifiers was minimal, and 3) both agents were able to convert DNA lesions from short-term to long-term.

Different cytokine profiles in patients with chronic and acute reactive arthritis.

OBJECTIVE: Analysis of cytokine production in patients with acute and chronic reactive arthritis (AcReA/ChrReA) in order to search for new treatment possibilities. METHODS: Cytokine production by peripheral blood and synovial fluid mononuclear cells (PBMCs/SFMCs) of 28 patients with AcReA, 27 patients with ChrReA, 26 patients with rheumatoid arthritis (RA) and 31 healthy controls was analysed by enzyme-linked immunosorbent assay (ELISA) and flow-cytometry. Production of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin (IL)-10 was measured by ELISA, while the percentages of TNF-alpha-, IFN-gamma- and IL-4-positive CD3+ cells were determined in the same groups of patients and healthy subjects using flow cytometry. RESULTS: Spontaneous TNF-alpha production observed in PBMCs of ChrReA, but not of AcReA, patients was significantly higher (P<0.001) than in healthy controls. The percentages of TNF-alpha-positive CD3+ blood cells in ChrReA exceeded that of RA patients and healthy controls (P<0.05 and P<0.001, respectively). Also, the percentages of IFN-gamma-positive CD3+ cells were significantly higher in peripheral blood and synovial fluid of ChrReA patients (P<0.05 and P<0.05, respectively) as compared with AcReA. In ChrReA spontaneous IL-10 production in PBMCs was similar to that observed in healthy controls, while in RA and AcReA the production of IL-10 was significantly increased (P<0.05 and P<0.05, respectively). IL-4 production was low in all study groups with no significant differences detected. CONCLUSIONS: High production of TNF-alpha and IFN-gamma detected in ChrReA supports the possible use of anti-TNF-alpha treatment in ChrReA.