Visual Field Endpoints Based on Subgroups of Points May Be Useful in Glaucoma Clinical Trials: A Study With the Humphrey Field Analyzer and Compass Perimeter

PRECIS: Visual field endpoints based on average deviation of specific subsets of points rather than all points may offer a more homogenous dataset without necessarily worsening test-retest variability and so may be useful in clinical trials. PURPOSE: To characterize outcome measures encompassing particular subsets of visual field points and compare them as obtained with Humphrey (HVF) and Compass perimeters. METHODS: 30 patients with imaging-based glaucomatous neuropathy performed a pair of 24-2 tests with each of 2 perimeters. Non-weighted mean deviation (MD) was calculated for the whole field and separate vertical hemifields, and again after censoring of points with low sensitivity (MDc) and subsequently including only "abnormal" points with total deviation probability of <5% (MDc5%) or <2% (MDc2%). Test-retest variability was assessed using Bland-Altman 95% limits of agreement (95%LoA). RESULTS: For the whole field, using HVF, MD was -7.5±6.9▒dB, MDc -3.6±2.8▒dB, MDc5% -6.4±1.7▒dB and MDc2% -7.3±1.5▒dB. With Compass MD was -7.5±6.6, MDc -2.9±1.7▒dB, MDc5% -6.3±1.5, and MDC2% -7.9±1.6. The respective 95% LoA were 5.5, 5.3, 4.6 and 5.6 with HVF, and 4.8, 3.7, 7.1 and 7.1 with Compass. The respective number of eligible points were 52, 42±12, 20±11 and 15±9 with HVF, and 52, 41.2±12.6, 10±7 and 7±5 with Compass. With both machines, standard deviation (SD) and 95%LoA increased in hemifields compared to the total field, but this increase was mitigated after censoring. CONCLUSIONS: Restricting analysis to particular subsets of points of interest in the visual field after censoring points with low sensitivity, as compared with using the familiar total field mean deviation, can provide outcome measures with a broader range of mean deviation, a markedly reduced SD and therefore more homogenous dataset, without necessarily worsening test-retest variability

Rheological properties of magnetic biogels

We report an experimental and theoretical study of the rheological properties of magnetic biogels consisting of fibrin polymer networks with embedded magnetite nanoparticles, swollen by aqueous solutions. We studied two types of magnetic biogels, differenced by the presence or absence of an applied magnetic field during the initial steps of cross-linking. The experiments demonstrated very strong dependence of the elastic modulus of the magnetic biogels on the concentration of the magnetic particles. We finally developed some theoretical models that explain the observed strong concentration effects.This study was supported by projects FIS2013-41821-R (Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, MINECO, Spain, co-funded by ERDF, European Union) and FIS2017-85954-R (Ministerio de Economía, Industria y Competitividad, MINECO, andAgencia Estatal de Investigación, AEI, Spain, co-funded by Fondo Europeo de Desarrollo Regional, FEDER, European Union). A.Z. is grateful to the program of the Ministry of Education and Science of the Russian Federation, projects 02.A03.21.0006, 3.1438.2017/4.6, and 3.5214.2017/6.7, as well as to the Russian Fund of Basic Researches, project 18-08-00178

Antibody-conjugated, dual-modal, near-infrared fluorescent iron oxide nanoparticles for antiamyloidgenic activity and specific detection of amyloid-&beta; fibrils

Hadas Skaat,1 Enav Corem-Slakmon,1 Igor Grinberg,1 David Last,2 David Goez,2 Yael Mardor,2,3 Shlomo Margel1 1Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Ramat-Gan, Israel; 2Advanced Technology Center, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel; 3Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Abstract: Amyloid-&beta; (A&beta;) peptide is the main fibrillar component of plaque deposits found in brains affected by Alzheimer&#39;s disease (AD) and is related to the pathogenesis of AD. Passive anti-A&beta; immunotherapy has emerged as a promising approach for the therapy of AD, based on the administration of specific anti-A&beta; monoclonal antibodies (aA&beta;mAbs) to delay A&beta; aggregation in the brain. However, the main disadvantage of this approach is the required readministration of the aA&beta;mAbs at frequent intervals. There are only a few reports describing in vitro study for the immobilization of aA&beta;mAbs to nanoparticles as potential targeting agents of A&beta; aggregates. In this article, we report the immobilization of the aA&beta;mAb clone BAM10 to near-infrared fluorescent maghemite nanoparticles for the inhibition of A&beta;40 fibrillation kinetics and the specific detection of A&beta;40 fibrils. The BAM10-conjugated iron oxide nanoparticles were well-characterized, including their immunogold labeling and cytotoxic effect on PC-12 (pheochromocytoma cell line). Indeed, these antibody-conjugated nanoparticles significantly inhibit the A&beta;40 fibrillation kinetics compared with the same concentration, or even five times higher, of the free BAM10. This inhibitory effect was confirmed by different assays such as the photo-induced crosslinking of unmodified proteins combined with sodium dodecyl sulfate&ndash;polyacrylamide gel electrophoresis. A cell viability assay also confirmed that these antibody-conjugated nanoparticles significantly reduced the A&beta;40-induced cytotoxicity to PC-12 cells. Furthermore, the selective labeling of the A&beta;40 fibrils with the BAM10-conjugated near-infrared fluorescent iron oxide nanoparticles enabled specific detection of A&beta;40 fibrils ex vivo by both magnetic resonance imaging and fluorescence imaging. This study highlights the immobilization of the aA&beta;mAb to dual-modal nanoparticles as a potential approach for aA&beta;mAb delivery, eliminating the issue of readministration, and contributes to the development of multifunctional agents for diagnosis and therapy of AD. Keywords: near-infrared fluorescent &gamma;-Fe2O3 nanoparticles, protein folding, amyloid-&beta; peptide, passive immunotherapy, neurodegenerative disease

Visual field endpoints based on subgroups of points may be useful in glaucoma clinical trials: A study with the humphrey field analyzer and compass perimeter

Precis: Visual field (VF) endpoints based on average deviation of specific subsets of points rather than all points may offer a more homogeneous data set without necessarily worsening test-retest variability and so may be useful in clinical trials. Purpose: The purpose of this study was to characterize the outcome measures encompassing particular subsets of VF points and compare them as obtained with Humphrey [Humphrey visual field analyser (HVF)] and Compass perimeters. Methods: Thirty patients with imaging-based glaucomatous neuropathy performed a pair of 24-2 tests with each of 2 perimeters. Nonweighted mean deviation (MD) was calculated for the whole field and separate vertical hemifields, and again after censoring of points with low sensitivity (MDc) and subsequently including only “abnormal” points with a total deviation probability of < 5% (MDc5%) or <2% (MDc2%). Test-retest variability was assessed using Bland-Altman 95% limits of agreement (95%LoA). Results: For the whole field, using HVF, MD was −7.5 ± 6.9 dB, MDc −3.6 ± 2.8 dB, MDc5% −6.4 ± 1.7 dB, and MDc2% −7.3 ± 1.5 dB. With Compass the MD was −7.5 ± 6.6, MDc −2.9 ± 1.7 dB, MDc5% −6.3 ± 1.5, and MDC2% −7.9 ± 1.6. The respective 95%LoA were 5.5, 5.3, 4.6, and 5.6 with HVF, and 4.8, 3.7, 7.1, and 7.1 with Compass. The respective number of eligible points were 52, 42 ± 12, 20 ± 11, and 15 ± 9 with HVF, and 52, 41.2 ± 12.6, 10 ± 7, and 7 ± 5 with Compass. With both machines, SD and 95%LoA increased in hemifields compared with the total field, but this increase was mitigated after censoring. Conclusion: Restricting analysis to particular subsets of points of interest in the VF after censoring points with low sensitivity, as compared with using the familiar total field MD, can provide outcome measures with a broader range of MD, a markedly reduced SD and therefore more homogeneous data set, without necessarily worsening test-retest variability

Influence of the Physiochemical Properties of Superparamagnetic Iron Oxide Nanoparticles on Amyloid β Protein Fibrillation in Solution

[Image: see text] Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized as promising nanodiagnostic materials due to their biocompatibility, unique magnetic properties, and their application as multimodal contrast agents. As coated SPIONs have potential use in the diagnosis and treatment of various brain diseases such as Alzheimer’s, a comprehensive understanding of their interactions with Aβ and other amyloidogenic proteins is essential prior to their clinical application. Here we demonstrate the effect of thickness and surface charge of the coating layer of SPIONs on the kinetics of fibrillation of Aβ in aqueous solution. A size and surface area dependent “dual” effect on Aβ fibrillation was observed. While lower concentrations of SPIONs inhibited fibrillation, higher concentrations increased the rate of Aβ fibrillation. With respect to coating charge, it is evident that the positively charged SPIONs are capable of promoting fibrillation at significantly lower particle concentrations compared with negatively charged or uncharged SPIONs. This suggests that in addition to the presence of particles, which affect the concentration of monomeric protein in solution (and thereby the nucleation time), there are also effects of binding on the protein conformation