Gene Therapy for Leber's Congenital Amaurosis is Safe and Effective Through 1.5 Years After Vector Administration

The safety and efficacy of gene therapy for inherited retinal diseases is being tested in humans affected with Leber's congenital amaurosis (LCA), an autosomal recessive blinding disease. Three independent studies have provided evidence that the subretinal administration of adeno-associated viral (AAV) vectors encoding RPE65 in patients affected with LCA2 due to mutations in the RPE65 gene, is safe and, in some cases, results in efficacy. We evaluated the long-term safety and efficacy (global effects on retinal/visual function) resulting from subretinal administration of AAV2-hRPE65v2. Both the safety and the efficacy noted at early timepoints persist through at least 1.5 years after injection in the three LCA2 patients enrolled in the low dose cohort of our trial. A transient rise in neutralizing antibodies to AAV capsid was observed but there was no humoral response to RPE65 protein. The persistence of functional amelioration suggests that AAV-mediated gene transfer to the human retina does not elicit immunological responses which cause significant loss of transduced cells. The persistence of physiologic effect supports the possibility that gene therapy may influence LCA2 disease progression. The safety of the intervention and the stability of the improvement in visual and retinal function in these subjects support the use of AAV-mediated gene augmentation therapy for treatment of inherited retinal diseases

A method to determine silver partitioning and lability in soils

There is increasing potential for pollution of soils by silver because of an increased use of this metal in consumer and industrial products. Silver may undergo reactions with soil components that mitigate its availability and potential toxicity, so that the total concentration of this metal in soil is not a useful indicator of potential risk. We developed an isotopic dilution method to simultaneously measure the partitioning (Kd-value) and lability (E-value) of Ag in soils, using the 110mAg isotope. An equilibration solution containing 10 mM Ca(NO3)2 was used along with a cation exchange resin to correct for possible interferences from non-isotopically exchangeable Ag associated with soil colloids in suspension (Er-value). The quantification limits for Kd and Er will depend on the amounts of radioisotope spiked and daily detection limits of inductively coupled plasma-mass spectrometry instrumentation but are typically >4000 L kg–1 and <0.92 mg kg–1. Measurement of Kd values for Ag in a range of soils indicated strong partitioning to the solid phase is positively associated with soil cation-exchange capacity or total organic carbon and pH. The concentrations of labile Ag in soils geogenically enriched in Ag were not detectable indicating occlusion of the Ag within poorly soluble solid phases. Measurement of labile Ag in soils spiked with a soluble Ag salt and aged for 2 weeks indicated rapid conversion of soluble Ag into non-isotopically exchangeable forms, either irreversibly adsorbed or precipitated in the soil. These results indicate that measurement of labile Ag will be important to estimate toxicity risks to soil organisms or to predict bioaccumulation through the food chain.Lara Settimio, Mike J. McLaughlin, Jason K. Kirby and Kate A. Langdo

Complexation of silver and dissolved organic matter in soil water extracts

Abstract not available.Lara Settimio, Mike J. McLaughlin, Jason K. Kirby, Kate A. Langdon, Les Janik, Scott Smit

The endothelial dysfunction in chronic venous disease. a systematic review.

Normal endothelial function maintains vascular homeosta- sis. Evidences have shown that inflammation, Matrix met- alloproteinases (MMPs) and glycocalix disfunction may be pivotal factors that lead to endothelial dysfunction, both on arterial and venous disease including chronic venous disease (CVD). PubMed and ScienceDirect databases were searched for relevant articles on these issues. This study performed a systematic analysis of the most recent scientific literature on the structure of the vascular venous endothelium and the pathophysiological processes which determine the alteration of endothelial function in CVD. An updated insight into the world of venous endothelial dysfunction might help physi- cians in better evaluating pathophysiological mechanisms of endothelial damage and in programming appropriate inter- ventions to modify it

Time resolved X-ray diffraction experiments during annealing of Co15Cu85 granula alloy

Granular alloys composed of nanoclusters of a magnetic element (e.g. Co, Fe, Ni) embedded in a non-magnetic metallic matrix (e.g. Cu, Au, Ag) present giant magnetoresistance (GMR). The GMR is caused by spin-scattering phenomena at the interfaces between magnetic granules and the matrix, and thus is closely correlated to microstructure of the samples. In melt-spun CoxCu100−x samples the GMR exhibits a maximum after annealing at the temperature of 450°C largely independent of the sample composition. The dynamics of the Co–Cu segregation process has directly been probed observing in situ annealing process of the samples in time resolved X-ray diffraction experiments. The results of accurate Rietveld analysis definitively demonstrated that the activation of Co–Cu remixing, when heating the samples around 500°C, is largely independent of the annealing kinetics

Can we utilize photorefractive keratectomy to improve visual acuity in adult amblyopic eyes?

Purpose: To report the results of photorefractive keratectomy (PRK) in adult amblyopic patients. Design: Noncomparative case series. Participants: Thirty-eight amblyopic eyes of 36 adult patients who had undergone PRK ranging from *14.63 diopters (D) to *3.75 D (mean, *6.38*4.10) were analyzed. Methods: Preoperative and postoperative (1, 3, and 6 months) refractions and measurements of the best spectacle-corrected visual acuity (BSCVA) were reviewed. Statistical evaluation was performed using a paired Student’s t test. Main Outcome Measures: Best-corrected visual acuity before and after PRK. Results: Before PRK, BSCVA ranged between 0.2 and 0.7 lines (mean, 0.60*0.13). One month after PRK, BSCVA ranged between 0.2 and 1.2 lines (mean, 0.77*0.24), with a significant difference (P * 3*10*5). Three months after PRK, BSCVA ranged between 0.15 and 1.15 lines (mean, 0.84*0.23), with a significant difference (P * 5*10*7). Six months after PRK, BSCVA ranged between 0.25 and 1.3 lines (mean, 0.88*0.25), with a significant difference (P * 8*10*8). Conclusions: Our study does not imply that refractive surgery should or may be performed in young children but, rather, that adults wishing to undergo refractive surgery may undertake such procedures despite an amblyopic eye thought to be refractory to visual rehabilitation by conventional methods, such as spectacles and contact lenses