AbstractPurposeTo analyse the current vision screening programme for children attending school with respect to identifying children with significant refractive errors.MethodsA total of 950 children from the municipality of Roskilde, Denmark, were invited to participate in a cross‐sectional study of vision screening. 447 children aged 4.5–7 years participated in the study. The children completed a vision screening and a full eye examination. The vision screening consisted of visual acuity at distance (VA), visual acuity at distance with +2.0 glasses (VA+2), visual acuity at near (VAnear) and Lang II stereotest. A LogMAR‐based picture chart was used for the vision testing. Significant refractive errors were defined as hyperopia ≥+3.5 D, myopia >1.0 D, astigmatism ≥1.25 D and anisometropia >1.0 D.ResultsUsing receiver operating characteristic (ROC) curves, we could compare the efficiency of VA, VA+2, VAnear, VA in combination with VA+2 and VA in combination with VAnear. Area under the curve (AUC) for VA, VA combined with VA+2 and VA combined with VAnear was 0.841, 0.857 and 0.857, respectively, that is all classified as ‘very good’ screening tools, whereas VA+2 and VAnear as single screening tools were classified as ‘good’ with AUC of 0.704 and 0.775, respectively. Using the optimal cut‐off limit from the ROC curves, VA above 0.05 LogMAR as cut‐off limit showed a sensitivity of 85.2% with a specificity of 74.9%. A slightly higher sensitivity could be found when combining screening tests, but with declining specificities.ConclusionVisual acuity at distance with the use of LogMAR‐based charts is the optimal screening tool of choice; only minor improvements can be obtained combining with other tests.

01 May 2015·Bioorganic & Medicinal ChemistryQ3 · MEDICINE

Design, synthesis and in vitro cell-based evaluation of the anti-cancer activities of hispolon analogs

Q3 · MEDICINE

Article

Author: Subbaraju, Gottumukkala V ; Gana, Theophilus J ; White, Jason ; Lee, Crystal ; Tiwari, Amit K ; Balaji, Neduri V ; Sanglard, Leticia P ; Viana, Arabela G ; Egiebor, Nosa O ; Ramani, Modukuri V ; Mulabagal, Vanisree

Phytochemicals play an important role in cancer therapy. Hispolon and 26 of its analogs (9 known and 17 new) were synthesized and evaluated for their antiproliferative activities in a panel of six independent human cancer cell lines using the in vitro cell-based MTT assay. Among the hispolon analogs tested, compound VA-2, the most potent overall, produced its most significant effect in the colon cancer cell lines HCT-116 (IC₅₀ 1.4 ± 1.3 μM) and S1 (IC₅₀ 1.8 ± 0.9 μM) compared to its activity in the normal HEK293/pcDNA3.1 cell line (IC₅₀ 15.8±3.7 μM; p<0.01 for each comparison). Based on our results, VA-2 was about 9- to 11-times more potent in colon cancer cells and 2- to 3-times more potent in prostate cancer cells compared to HEK293/pcDNA3.1 cells. Morphological analysis of VA-2 showed significant reduction of cell number, while the cells' sizes were also markedly increased and were obvious at 68 h of treatment with 1 μM in HCT-116 (colon) and PC-3 (prostate) cancer cells. A known analog, compound VA-4, prepared by simple modifications on the aromatic functional groups of hispolon, inhibited prostate and colon cancer cell lines with IC₅₀ values <10 μM. In addition, hispolon isoxazole and pyrazole analogs, VA-7 and VA-15 (known), respectively, have shown significant activity with the mean ICv values in the range 3.3-10.7 μM in all the cancer cell lines tested. Activity varied among the analogs in which aromatic functional groups and β-diketone functional groups are modified. But the activity of analogs VA-16 to VA-27 was completely lost when the side chain double-bond was hydrogenated indicating the crucial role of this functionality for anticancer activity. Furthermore, many of the compounds synthesized were not substrates for the ABCB1-transporter, the most common cause of multidrug resistance in anti-cancer drugs, suggesting they may be more effective anticancer agents.

01 Jan 1983·The Journal of AntibioticsQ4 · MEDICINE

Studies on a new antibiotic M-92 produced by Micromonospora V. Mechanism of action of the component VA-2.

Q4 · MEDICINE

Article

Author: Tani, Kato ; Yamaguchi, Toutaro

Effects of VA-2, a component of quinoid antibiotic M-92, on the incorporation of radioisotope-labeled compounds into the cells of Staphylococcus aureus were studied. Deoxyribonucleic acid (DNA) synthesis was immediately inhibited by the addition of VA-2. Significant inhibitions of ribonucleic acid and protein syntheses and minor reduction of peptidoglycan synthesis were observed after a short delay. VA-2 immediately induced the degradation of DNA prelabelled with [14C]thymidine in the cells of S. aureus. In the examinations using E. coli enzyme and calf thymus DNA as a template, VA-2 prevented DNA-dependent DNA polymerase reaction. The inhibition of DNA polymerase I reaction was fairly reversed by increasing the concentration of template DNA, but slightly by that of the enzyme. Agarose gel electrophoresis showed that VA-2 elicited an extensive cleavage of PM2 cccDNA. VA-2 caused a primary conversion of the cccDNA to ocDNA at a low concentration (0.2 micrograms/ml), while at high concentrations (2.0 and 20 micrograms/ml) it cleaved the cccDNA to ocDNA and linear DNA progressively. These cleavages were observed even at 0 degrees C as well as at 37 degrees C, and were enhanced with the addition of a reducing agent such as 2-mercaptoethanol or sodium borohydride.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Phase 3	-	Valorum Biologics, Inc.	-

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