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Author Ramke, J.; Petkovic, J.; Welch, V.; Blignault, I.; Gilbert, C.; Blanchet, K.; Christensen, R.; Zwi, A.B.; Tugwell, P.
Title Interventions to improve access to cataract surgical services and their impact on equity in low- and middle-income countries Type Journal Article
Year 2017 Publication (down) The Cochrane Database of Systematic Reviews Abbreviated Journal Cochrane Database Syst Rev
Volume 11 Issue Pages Cd011307
Keywords
Abstract BACKGROUND: Cataract is the leading cause of blindness in low- and middle-income countries (LMICs), and the prevalence is inequitably distributed between and within countries. Interventions have been undertaken to improve cataract surgical services, however, the effectiveness of these interventions on promoting equity is not known. OBJECTIVES: To assess the effects on equity of interventions to improve access to cataract services for populations with cataract blindness (and visual impairment) in LMICs. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 3), MEDLINE Ovid (1946 to 12 April 2017), Embase Ovid (1980 to 12 April 2017), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 12 April 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 12 April 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 12 April 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 12 April 2017. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We included studies that reported on strategies to improve access to cataract services in LMICs using the following study designs: randomised and quasi-randomised controlled trials (RCTs), controlled before-and-after studies, and interrupted time series studies. Included studies were conducted in LMICs, and were targeted at disadvantaged populations, or disaggregated outcome data by 'PROGRESS-Plus' factors (Place of residence; Race/ethnicity/ culture/ language; Occupation; Gender/sex; Religion; Education; Socio-economic status; Social capital/networks. The 'Plus' component includes disability, sexual orientation and age). DATA COLLECTION AND ANALYSIS: Two authors (JR and JP) independently selected studies, extracted data and assessed them for risk of bias. Meta-analysis was not possible, so included studies were synthesised in table and text. MAIN RESULTS: From a total of 2865 studies identified in the search, two met our eligibility criteria, both of which were cluster-RCTs conducted in rural China. The way in which the trials were conducted means that the risk of bias is unclear. In both studies, villages were randomised to be either an intervention or control group. Adults identified with vision-impairing cataract, following village-based vision and eye health assessment, either received an intervention to increase uptake of cataract surgery (if their village was an intervention group), or to receive 'standard care' (if their village was a control group).One study (n = 434), randomly allocated 26 villages or townships to the intervention, which involved watching an informational video and receiving counselling about cataract and cataract surgery, while the control group were advised that they had decreased vision due to cataract and it could be treated, without being shown the video or receiving counselling. There was low-certainty evidence that providing information and counselling had no effect on uptake of referral to the hospital (OR 1.03, 95% CI 0.63 to 1.67, 1 RCT, 434 participants) and little or no effect on the uptake of surgery (OR 1.11, 95% CI 0.67 to 1.84, 1 RCT, 434 participants). We assessed the level of evidence to be of low-certainty for both outcomes, due to indirectness of evidence and imprecision of results.The other study (n = 355, 24 towns randomised) included three intervention arms: free surgery; free surgery plus reimbursement of transport costs; and free surgery plus free transport to and from the hospital. These were compared to the control group, which was reminded to use the “low-cost” ( USD 38) surgical service. There was low-certainty evidence that surgical fee waiver with/without transport provision or reimbursement increased uptake of surgery (RR 1.94, 95% CI 1.14 to 3.31, 1 RCT, 355 participants). We assessed the level of evidence to be of low-certainty due to indirectness of evidence and imprecision of results.Neither of the studies reported our primary outcome of change in prevalence of cataract blindness, or other outcomes such as cataract surgical coverage, surgical outcome, or adverse effects. Neither study disaggregated outcomes by social subgroups to enable further assessment of equity effects. We sought data from both studies and obtained data from one; the information video and counselling intervention did not have a differential effect across the PROGRESS-Plus categories with available data (place of residence, gender, education level, socioeconomic status and social capital). AUTHORS' CONCLUSIONS: Current evidence on the effect on equity of interventions to improve access to cataract services in LMICs is limited. We identified only two studies, both conducted in rural China. Assessment of equity effects will be improved if future studies disaggregate outcomes by relevant social subgroups. To assist with assessing generalisability of findings to other settings, robust data on contextual factors are also needed.
Address School of Population Health, Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1361-6137 ISBN Medium
Area Expedition Conference
Notes PMID:29119547 Approved no
Call Number ref @ user @ Serial 97624
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Author Basso, C.; Garcia da Rosa, E.; Lairihoy, R.; Caffera, R.M.; Roche, I.; Gonzalez, C.; da Rosa, R.; Gularte, A.; Alfonso-Sierra, E.; Petzold, M.; Kroeger, A.; Sommerfeld, J.
Title Scaling Up of an Innovative Intervention to Reduce Risk of Dengue, Chikungunya, and Zika Transmission in Uruguay in the Framework of an Intersectoral Approach with and without Community Participation Type Journal Article
Year 2017 Publication (down) The American Journal of Tropical Medicine and Hygiene Abbreviated Journal Am J Trop Med Hyg
Volume Issue Pages
Keywords
Abstract To contribute to the prevention of dengue, chikungunya, and Zika, a process of scaling up an innovative intervention to reduce Aedes aegypti habitats, was carried out in the city of Salto (Uruguay) based on a transdisciplinary analysis of the eco-bio-social determinants. The intervention in one-third of the city included the distributions of plastic bags for all households to collect all discarded water containers that were recollected by the Ministry of Health and the Municipality vector control services. The results were evaluated in 20 randomly assigned clusters of 100 households each, in the intervention and control arm. The intervention resulted in a significantly larger decrease in the number of pupae per person index (as a proxy for adult vector abundance) than the corresponding decrease in the control areas (both areas decreased by winter effects). The reduction of intervention costs (“incremental costs”) in relation to routine vector control activities was 46%. Community participation increased the collaboration with the intervention program considerably (from 48% of bags handed back out of the total of bags delivered to 59% of bags handed back). Although the costs increased by 26% compared with intervention without community participation, the acceptability of actions by residents increased from 66% to 78%.
Address Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization (WHO), Geneva, Switzerland
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0002-9637 ISBN Medium
Area Expedition Conference
Notes PMID:28820690 Approved no
Call Number ref @ user @ Serial 97631
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Author Li, M.; Zhao, H.; Ananiev, G.E.; Musser, M.T.; Ness, K.H.; Maglaque, D.L.; Saha, K.; Bhattacharyya, A.; Zhao, X.
Title Establishment of Reporter Lines for Detecting Fragile X Mental Retardation (FMR1) Gene Reactivation in Human Neural Cells Type Journal Article
Year 2017 Publication (down) Stem Cells (Dayton, Ohio) Abbreviated Journal Stem Cells
Volume 35 Issue 1 Pages 158-169
Keywords Drug discovery; Fmr1; Fmrp; Fragile X syndrome; High throughput; Induced pluripotent stem cells; Luciferase
Abstract Human patient-derived induced pluripotent stem cells (hiPSCs) provide unique opportunities for disease modeling and drug development. However, adapting hiPSCs or their differentiated progenies to high throughput assays for phenotyping or drug screening has been challenging. Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and a major genetic cause of autism. FXS is caused by mutational trinucleotide expansion in the FMR1 gene leading to hypermethylation and gene silencing. One potential therapeutic strategy is to reactivate the silenced FMR1 gene, which has been attempted using both candidate chemicals and cell-based screening. However, molecules that effectively reactivate the silenced FMR1 gene are yet to be identified; therefore, a high throughput unbiased screen is needed. Here we demonstrate the creation of a robust FMR1-Nluc reporter hiPSC line by knocking in a Nano luciferase (Nluc) gene into the endogenous human FMR1 gene using the CRISPR/Cas9 genome editing method. We confirmed that luciferase activities faithfully report FMR1 gene expression levels and showed that neural progenitor cells derived from this line could be optimized for high throughput screening. The FMR1-Nluc reporter line is a good resource for drug screening as well as for testing potential genetic reactivation strategies. In addition, our data provide valuable information for the generation of knockin human iPSC reporter lines for disease modeling, drug screening, and mechanistic studies. Stem Cells 2017;35:158-169.
Address Department of Neuroscience, University of Wisconsin-Madison, Madison, Wisconsin, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1066-5099 ISBN Medium
Area Expedition Conference
Notes PMID:27422057 Approved no
Call Number ref @ user @ Serial 95937
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Author Voss, D.M.; Spina, R.; Carter, D.L.; Lim, K.S.; Jeffery, C.J.; Bar, E.E.
Title Disruption of the monocarboxylate transporter-4-basigin interaction inhibits the hypoxic response, proliferation, and tumor progression Type Journal Article
Year 2017 Publication (down) Scientific Reports Abbreviated Journal Sci Rep
Volume 7 Issue 1 Pages 4292
Keywords
Abstract We have previously shown that glioblastoma stem cells (GSCs) are enriched in the hypoxic tumor microenvironment, and that monocarboxylate transporter-4 (MCT4) is critical for mediating GSC signaling in hypoxia. Basigin is involved in many physiological functions during early stages of development and in cancer and is required for functional plasma membrane expression of MCT4. We sought to determine if disruption of the MCT-Basigin interaction may be achieved with a small molecule. Using a cell-based drug-screening assay, we identified Acriflavine (ACF), a small molecule that inhibits the binding between Basigin and MCT4. Surface plasmon resonance and cellular thermal-shift-assays confirmed ACF binding to basigin in vitro and in live glioblastoma cells, respectively. ACF significantly inhibited growth and self-renewal potential of several glioblastoma neurosphere lines in vitro, and this activity was further augmented by hypoxia. Finally, treatment of mice bearing GSC-derived xenografts resulted in significant inhibition of tumor progression in early and late-stage disease. ACF treatment inhibited intratumoral expression of VEGF and tumor vascularization. Our work serves as a proof-of-concept as it shows, for the first time, that disruption of MCT binding to their chaperon, Basigin, may be an effective approach to target GSC and to inhibit angiogenesis and tumor progression.
Address Department of Neurological Surgery, Case Western Reserve University School of Medicine and The Case Comprehensive Cancer Center, Cleveland, OH, USA. eli.bar@case.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2045-2322 ISBN Medium
Area Expedition Conference
Notes PMID:28655889 Approved no
Call Number ref @ user @ Serial 96580
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Author Momeny, M.; Moghaddaskho, F.; Gortany, N.K.; Yousefi, H.; Sabourinejad, Z.; Zarrinrad, G.; Mirshahvaladi, S.; Eyvani, H.; Barghi, F.; Ahmadinia, L.; Ghazi-Khansari, M.; Dehpour, A.R.; Amanpour, S.; Tavangar, S.M.; Dardaei, L.; Emami, A.H.; Alimoghaddam, K.; Ghavamzadeh, A.; Ghaffari, S.H.
Title Blockade of vascular endothelial growth factor receptors by tivozanib has potential anti-tumour effects on human glioblastoma cells Type Journal Article
Year 2017 Publication (down) Scientific Reports Abbreviated Journal Sci Rep
Volume 7 Issue Pages 44075
Keywords
Abstract Glioblastoma (GBM) remains one of the most fatal human malignancies due to its high angiogenic and infiltrative capacities. Even with optimal therapy including surgery, radiotherapy and temozolomide, it is essentially incurable. GBM is among the most neovascularised neoplasms and its malignant progression associates with striking neovascularisation, evidenced by vasoproliferation and endothelial cell hyperplasia. Targeting the pro-angiogenic pathways is therefore a promising anti-glioma strategy. Here we show that tivozanib, a pan-inhibitor of vascular endothelial growth factor (VEGF) receptors, inhibited proliferation of GBM cells through a G2/M cell cycle arrest via inhibition of polo-like kinase 1 (PLK1) signalling pathway and down-modulation of Aurora kinases A and B, cyclin B1 and CDC25C. Moreover, tivozanib decreased adhesive potential of these cells through reduction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Tivozanib diminished GBM cell invasion through impairing the proteolytic cascade of cathepsin B/urokinase-type plasminogen activator (uPA)/matrix metalloproteinase-2 (MMP-2). Combination of tivozanib with EGFR small molecule inhibitor gefitinib synergistically increased sensitivity to gefitinib. Altogether, these findings suggest that VEGFR blockade by tivozanib has potential anti-glioma effects in vitro. Further in vivo studies are warranted to explore the anti-tumour activity of tivozanib in combinatorial approaches in GBM.
Address Haematology/Oncology and Stem Cell Transplantation Research Centre, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2045-2322 ISBN Medium
Area Expedition Conference
Notes PMID:28287096 Approved no
Call Number ref @ user @ Serial 96601
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