Systems Development of Organizational Memory: A Literature Survey

Currently, there is no commonly accepted methodology for developing organizational memory systems (OM) that is comprehensive in the sense that it guides the development process from beginning to end and is in sufficient detail to be implemented successfully. Using the ideas of memory metaphor and the user\u27s perspective, we review recent work on OM through two dimensions: the stages of developing OM and the architecture of OM. We then examine the implications of this review on for the OM systems development life cycle and the components of its architecture. This work should therefore prove useful to anyone considering the development of OM

Dexamethasone Intravitreal Implant as Adjunctive Therapy to Ranibizumab in Neovascular Age-Related Macular Degeneration: A Multicenter Randomized Controlled Trial

Purpose: To evaluate the efficacy and safety of dexamethasone intravitreal implant 0.7 mg (DEX) as adjunctive therapy to ranibizumab in neovascular age-related macular degeneration (nvAMD). Procedures: This was a 6-month, single-masked, multicenter study. Patients were randomized to DEX implant (n = 123) or sham procedure (n = 120) and received 2 protocol-mandated intravitreal ranibizumab injections. The main outcome measure was injection-free interval to first as-needed ranibizumab injection. Results: DEX increased the injection-free interval versus sham (50th percentile, 34 vs. 29 days; 75th percentile, 85 vs. 56 days; p = 0.016). 8.3% of DEX versus 2.5% of sham-treated patients did not require rescue ranibizumab (p = 0.048). Visual acuity and retinal thickness outcomes were similar in DEX and sham-treated patients. Only reports of conjunctival hemorrhage (18.2 vs. 8.5%) and intraocular pressure elevation (13.2 vs. 4.2%) were significantly different in the DEX versus the sham treatment groups. Conclusion: DEX reduced the need for adjunctive ranibizumab treatment and showed acceptable tolerability in nvAMD patients

Degradation of HIF-1alpha under Hypoxia Combined with Induction of Hsp90 Polyubiquitination in Cancer Cells by Hypericin: a Unique Cancer Therapy

The perihydroxylated perylene quinone hypericin has been reported to possess potent anti-metastatic and antiangiogenic activities, generated by targeting diverse crossroads of cancer-promoting processes via unique mechanisms. Hypericin is the only known exogenous reagent that can induce forced poly-ubiquitination and accelerated degradation of heat shock protein 90 (Hsp90) in cancer cells. Hsp90 client proteins are thereby destabilized and rapidly degraded. Hsp70 client proteins may potentially be also affected via preventing formation of hsp90-hsp70 intermediate complexes. We show here that hypericin also induces enhanced degradation of hypoxia-inducible factor 1α (HIF-1α) in two human tumor cell lines, U87-MG glioblastoma and RCC-C2VHL−/− renal cell carcinoma and in the non-malignant ARPE19 retinal pigment epithelial cell line. The hypericin-accelerated turnover of HIF-1α, the regulatory precursor of the HIF-1 transcription factor which promotes hypoxic stress and angiogenic responses, overcomes the physiologic HIF-1α protein stabilization which occurs in hypoxic cells. The hypericin effect also eliminates the high HIF-1α levels expressed constitutively in the von-Hippel Lindau protein (pVHL)-deficient RCC-C2VHL−/− renal cell carcinoma cell line. Unlike the normal ubiquitin-proteasome pathway-dependent turnover of HIF-α proteins which occurs in normoxia, the hypericin-induced HIF-1α catabolism can occur independently of cellular oxygen levels or pVHL-promoted ubiquitin ligation of HIF-1α. It is mediated by lysosomal cathepsin-B enzymes with cathepsin-B activity being optimized in the cells through hypericin-mediated reduction in intracellular pH. Our findings suggest that hypericin may potentially be useful in preventing growth of tumors in which HIF-1α plays pivotal roles, and in pVHL ablated tumor cells such as renal cell carcinoma through elimination of elevated HIF-1α contents in these cells, scaling down the excessive angiogenesis which characterizes these tumors

Changes in Retinal Function and Cellular Remodeling Following Experimental Retinal Detachment in a Rabbit Model

Purpose. To explore functional electroretinographic (ERG) changes and associated cellular remodeling following experimental retinal detachment in a rabbit model. Methods. Retinal detachment was created in ten rabbits by injecting 0.1 ml balanced salt solution under the retina. Fundus imaging was performed 0, 3, 7, 14, and 21 days postoperatively. ERGs were recorded pre- and 7 and 21 days postoperatively. Eyes were harvested on day 21 and evaluated immunohistochemically (IHC) for remodeling of second- and third-order neurons. Results. Retinal reattachment occurred within two weeks following surgery. No attenuation was observed in the photopic or scotopic a- and b-waves. A secondary wavefront on the descending slope of the scotopic b-wave was the only ERG result that was attenuated in detached retinas. IHC demonstrated anatomical changes in both ON and OFF bipolar cells. Bassoon staining was observed in the remodeled dendrites. Amacrine and horizontal cells did not alter, but Muller cells were clearly reactive with marked extension. Conclusion. Retinal detachment and reattachment were associated with functional and anatomical changes. Exploring the significance of the secondary scotopic wavefront and its association with the remodeling of 2nd- and 3rd-order neurons will shade more light on functional changes and recovery of the retina

Laser capsulotomy following cataract surgery: Comparing time to capsulotomy with implantation of two broadly used intraocular lenses

Purpose: The aim of this study is to compare the length of time from uneventful cataract surgery using one of two common posterior chamber intraocular lenses (IOLs) (hydrophilic versus hydrophobic acrylic) to laser capsulotomy. Materials and Methods: Retrospective analysis of all patients who underwent neodymium: yttrium-aluminum-garnet laser capsulotomy between 2011 and 2014 following uneventful phacoemulsification surgery at a tertiary university-affiliated medical center. Medical records were reviewed for demographics, ocular comorbidities, operative details, postoperative follow-up, and findings of the precapsulotomy ophthalmologic examination. Parameters, including age, sex, laterality, visual acuity, surgeon's experience, and time from cataract surgery to capsulotomy, were compared between patients who received hydrophilic (SeeLens AF, Kibbutz Hanita, Israel) or hydrophobic (AcrySof SA60AT, Alcon Laboratories, Fort Worth, TX, USA) IOLs. Results: The cohort included 222 patients (255 eyes), of which, 107 were male and 115 female, of mean age 73 ± 8 years. Mean interval from cataract surgery to laser capsulotomy was 24 months (range 2–70) and was significantly shorter in patients with SeeLens (23 ± 13 months) than AcrySof IOL implantation (28 ± 13 months, P = 0.04). Lens type remained significant in multivariate analysis after including surgeon's experience and age as potential confounders (P = 0.04). Conclusion: The hydrophilic SeeLens IOL is associated with a significantly shorter time interval from cataract surgery to laser capsulotomy than the hydrophobic AcrySof IOL

Transcleral approach for closing retinal tears using DuraSeal™ hydrogel sealant

Purpose: The aim of this study was to evaluate an innovative approach for closing retinal tears using DuraSeal™ (DS) hydrogel sealant in a rabbit model. Methods: Retinal detachment with a small tear was performed on 20 New Zealand rabbits. Thereafter, rabbits were divided into two groups; the experimental group received a transscleral injection of 0.1 ml DS into the subretinal space whereas the control group received sham injection of saline. Eyes were clinically evaluated using indirect ophthalmoscopy, retinal function was recorded in ten rabbits by electroretinography and the sealant's toxicity was evaluated histopathologically. Results: We found that the DS hydrogel was easily injected transsclerally into the subretinal space of the detached retinas with no major complications. Retinal reattachment was seen in both groups within 2 weeks with no toxicity to the sensory retina. There were no significant differences in retinal function between groups. Conclusion: Subretinal injection of hydrogel through a transscleral route is easy to perform and may open a new avenue in the treatment of retinal detachment. However, the efficacy of the DS as a tamponade for sealing retinal tear is yet to be definite. Long-term clinical, functional, and toxicological studies are needed to evaluate its full potential for clinical applications