Institutional Philanthropy: A Focus On Disability

In the context of the 10th anniversary of the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD), the European Foundation Centre undertook a survey of its members and other institutional philanthropy actors who are funding, supporting, advocating, and partnering to advance the situation of people with disabilities in Europe and beyond, including those with disabilities related to ageing.This publication summarises the survey results which provide an up-to-date picture of EFC members and other funders active in the field of disability, whether it is part of their core mission or just one of their fields of action, and an insight to better understand their practices. The survey results are based on input from 34 philanthropic organisations. Data supplied refers to the year 2015 unless otherwise specified.The report comprises two parts:Part 1: A profile of this sample of disability funders, addressing in particular who they are, their main area(s) of focus, who they support, how they work, and if they cooperate and why.Part 2: A snapshot of 24 initiatives and projects supported by these organisations to illustrate some of their disability-related work, outlining their approach and achievements, as well as some challenges and learnings.This publication was produced with the support of the EFC's Disability Thematic Network (DTN). Network members include: King Baudouin Foundation, Essl Foundation, Fundacion Once, Fondazione Bianca del Monte di Lucca, Genio, Karuna Foundation, Light for the world, and Sabanci Vakfi

STEM-24. THERAPEUTIC APPROACH OF STEM CELL CARRYING RETROVIRAL REPLICATING VECTORS IN HUMAN GLIOMA MODEL

Abstract Toca 511, an improved retroviral replicating vectors (RRVs) expressing a codon-optimized cytosine deaminase, has shown highly promising evidence of therapeutic benefit in preclinical and clinical studies for gene therapy of glioma. In the present study, we engineered human mesenchymal stem cells (MSC) as tumor-homing cellular carriers that produce and release RRV, and evaluated the effect of this mode of virus delivery on the time course of intratumoral RRV dissemination. Human MSC isolates were engineered to produce RRV (MSC-RRV). Cytotoxicity assays confirmed efficient prodrug activator function in U-87 glioma cells transduced with vectors produced from MSC-RRV. To evaluate intratumoral migration activity and tumor-homing migration activity in vivo, individual MSC isolates were injected either directly into human glioma xenografts, or into the contralateral brain hemisphere. MSC-RRV isolates showing the highest levels of intratumoral migration activity were selected, and the efficiency of intratumoral dissemination and tumoricidal activity achieved by these isolates was compared against injection of RRV virus preparations in subcutaneous glioma models. Compared to virus injection, MSC-RRV achieved 1.6x-higher levels of tumor transduction (p< 0.05), and 2x-reduced tumor growth (p=0.018) at earlier time points. In short-term survival studies using lower doses of MSC-RRV cells vs. RRV virus injected 14 days post-establishment of intracranial U-87 gliomas, a small but statistically significant prolongation of median survival was seen with intracranial tumors treated with MSC-RRV as compared to RRV (26 vs. 20 days, p< 0.05) after only a single cycle of 5-FC prodrug. Thus, MSC can be employed as mobile tumor-homing RRV-producer cells, which release RRV as they migrate to tumor foci in vivo and actively penetrate into individual tumor masses, resulting in more rapid tumor transduction and earlier therapeutic efficacy, which may be advantageous particularly for multi-focal and metastatic disease. This study was funded by the California Institute for Regenerative Medicine (TR2-01791)

Effectiveness of pure argon for renal transplant preservation in a preclinical pig model of heterotopic autotransplantation

International audienceBackground: In kidney transplantation, the conditions of organ preservation following removal influence function recovery. Current static preservation procedures are generally based on immersion in a cold‑storage solution used under atmospheric air (approximately 78 kPa N2, 21 kPa O2, 1 kPa Ar). Research on static cold‑preservation solutions has stalled, and modifying the gas composition of the storage medium for improving preservation was considered. Organoprotective strategies successfully used noble gases and we addressed here the effects of argon and xenon on graft preservation in an established preclinical pig model of autotransplantation. Methods: The preservation solution Celsior saturated with pure argon (Argon‑Celsior) or xenon (Xenon‑Celsior) at atmospheric pressure was tested versus Celsior saturated with atmospheric air (Air‑Celsior). The left kidney was removed, and Air‑Celsior (n = 8 pigs), Argon‑Celsior (n = 8) or Xenon‑Celsior (n = 6) was used at 4 °C to flush and store the transplant for 30 h, a duration that induced ischemic injury in our model when Air‑Celsior was used. Hetero‑ topic autotransplantation and contralateral nephrectomy were performed. Animals were followed for 21 days. Results: The use of Argon‑Celsior vs. Air‑Celsior: (1) improved function recovery as monitored via creatinine clear‑ ance, the fraction of excreted sodium and tubulopathy duration; (2) enabled diuresis recovery 2–3 days earlier; (3) improved survival (7/8 vs. 3/8 pigs survived at postoperative day‑21); (4) decreased tubular necrosis, interstitial fibrosis, apoptosis and inflammation, and preserved tissue structures as observed after the natural death/euthanasia; (5) stimulated plasma antioxidant defences during the days following transplantation as shown by monitoring the " reduced ascorbic acid/thiobarbituric acid reactive substances " ratio and Hsp27 expression; (6) limited the inflamma‑ tory response as shown by expression of TNF‑alpha, IL1‑beta and IL6 as observed after the natural death/euthanasia. Conversely, Xenon‑Celsior was detrimental, no animal surviving by day‑8 in a context where functional recovery, renal tissue properties and the antioxidant and inflammation responses were significantly altered. Thus, the positive effects of argon were not attributable to the noble gases as a group. Conclusions: The saturation of Celsior with argon improved early functional recovery, graft quality and survival. Manipulating the gas composition of a preservation medium constitutes therefore a promising approach to improve preservation

MiR130b from Schlafen4+ MDSCs stimulates epithelial proliferation and correlates with preneoplastic changes prior to gastric cancer

The myeloid differentiation factor Schlafen4 (Slfn4) marks a subset of myeloid-derived suppressor cells (MDSCs) in the stomach during Helicobacter-induced spasmolytic polypeptide-expressing metaplasia (SPEM). OBJECTIVE: To identify the gene products expressed by Slfn4+-MDSCs and to determine how they promote SPEM. DESIGN: We performed transcriptome analyses for both coding genes (mRNA by RNA-Seq) and non-coding genes (microRNAs using NanoString nCounter) using flow-sorted SLFN4+ and SLFN4- cells from Helicobacter-infected mice exhibiting metaplasia at 6 months postinfection. Thioglycollate-elicited myeloid cells from the peritoneum were cultured and treated with IFNα to induce the T cell suppressor phenotype, expression of MIR130b and SLFN4. MIR130b expression in human gastric tissue including gastric cancer and patient sera was determined by qPCR and in situ hybridisation. Knockdown of MiR130b in vivo in Helicobacter-infected mice was performed using Invivofectamine. Organoids from primary gastric cancers were used to generate xenografts. ChIP assay and Western blots were performed to demonstrate NFκb p65 activation by MIR130b. RESULTS: MicroRNA analysis identified an increase in MiR130b in gastric SLFN4+ cells. Moreover, MIR130b colocalised with SLFN12L, a human homologue of SLFN4, in gastric cancers. MiR130b was required for the T-cell suppressor phenotype exhibited by the SLFN4+ cells and promoted Helicobacter-induced metaplasia. Treating gastric organoids with the MIR130b mimic induced epithelial cell proliferation and promoted xenograft tumour growth. CONCLUSION: Taken together, MiR130b plays an essential role in MDSC function and supports metaplastic transformation.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Int J Environ Res Public Health

This scoping study aims to explore the relationships between urban green spaces (UGSs) and the onset, remission and recovery of cancer. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews (protocol published in 2018). Eligibility criteria for papers were: (1) to be concerned with UGSs, (2) reporting effects of UGSs on cancer-related outcomes including direct or indirect measures, (3) reporting randomized controlled trials, prospective cohort studies, case studies, observational studies, non-comparative studies, (4) in English or French. The search covered primary studies in the published and unpublished (grey) literatures searching by hand and electronic databases (MEDLINE, Green File, Cumulative Index to Nursing and Allied Health Literature and ScienceDirect). Among 1703 records screened by two reviewers independently, 29 were included for qualitative synthesis. We classify the cancers concerned and the effects reported i.e., protective effect, risk or without association. The most investigated cancers are bladder, breast and lung cancer. Our study also identified contributing factors and their mediating effects between UGSs and cancer. Even though the strength of the evidence of the associations between UGSs and cancer is still weak due to the low number of studies and their design, results highlight the wide variety of possible mediating factors between the use of green spaces and cancer occurrence, remission and/or prevention. Knowledge gaps and future research perspectives should be oriented to qualitative research on protective factors with an attention to equity in UGS access and use

Laser monitoring system for the CMS lead tungstate crystal calorimeter

We report on the multiple wavelength laser monitoring system designed for the CMS lead tungstate crystal calorimeter read-out with avalanche photodiodes (Barrel calorimeters) and vacuum phototriodes (End Cap calorimeters). Results are presented for the test beam performance of the system designed to achieve 0.5% relative inter-calibration of the optical transmittance for lead tungstate scintillation emission over nearly 80 000 channels. The system operates in continuous measurement cycles to follow each crystal?s evolution under irradiation and recovery periods foreseen during operation at the LHC