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Importance Comprehensive understanding of the genomic and gene-expression differences between retinoblastoma tumors from patients with bilateral disease may help to characterize risk and optimize treatment according to individual tumor characteristics. Objective To compare the genomic features between each eye and a specimen from an orbital relapse in patients with bilateral retinoblastoma. Design, Setting, and Participants In this case, 2 patients with retinoblastoma underwent upfront bilateral enucleation. Tumor samples were subjected to genomic and gene-expression analysis. Primary cell cultures were established from both of the tumors of 1 patient and were used for gene-expression studies. Main Outcomes and Measures Whole-exome sequencing was performed on an Illumina platform for fresh tumor samples and DNA arrays (CytoScan or OncoScan) were used for paraffin-embedded samples and cell lines. Gene-expression analysis was performed using Agilent microarrays. Germinal and somatic alterations, copy number alt) gene pathways between the left and right tumors. Conclusions and Relevance Differential genomic and gene expression features were observed between tumors in 2 patients with bilateral disease, confirming intereye heterogeneity that might be considered if targeted therapies are used in such patients. Chromosomal alteration profile supported the origin of the orbital recurrence from the homolateral eye in 1 patient. Loss in chromosome 11q may have been associated with extraocular relapse in this patient.Importance Retinal hypopigmentation and hyperpigmentation are precursors of geographic atrophy (GA). Incidence and progression to GA in eyes treated with anti-vascular endothelial growth factor for neovascular age-related macular degeneration (nAMD) have not been investigated. Objective To determine the incidence and progression of non-GA (NGA) and associated risk factors. Design, Setting, and Participants This study is a post hoc analysis of a cohort study within the Comparison of Age-Related Treatments Trials (CATT) clinical trial. Participants were recruited February 20, 2008, through December 9, 2009; released from protocol follow-up and treatment after 2 years; and recalled from March 14, 2014, through March 31, 2015. Data analyses were conducted from January 11, 2019, through November 27, 2019. Interventions Participants were randomized to ranibizumab or bevacizumab for (1) 2 years of monthly or as-needed injections or (2) monthly injections for 1 year and as-needed injections the following year. Partictional years of regular care, half of them progressed to GA. Trial Registration ClinicalTrials.gov Identifier NCT00593450.The prevalence of chronic kidney disease (CKD) is increasing and dietary interventions may be a strategy to reduce this burden. In the general population, higher potassium intake is considered protective for cardiovascular health. Due to the risk of hyperkalemia in CKD, limiting potassium intake is often recommended. However, given that poor cardiovascular function can cause kidney damage, following a low-potassium diet may be deleterious for patients with CKD. selleck products The aim of this systematic review was to summarize the evidence on dietary potassium intake and CKD progression. Multiple databases were searched on 7 June 2019 and data were managed with Covidence. No intervention trials met the inclusion criteria. Eleven observational studies met the inclusion criteria (10 post hoc analyses, 1 retrospective cohort), representing 49,573 stage 1-5 predialysis patients with CKD from 41 different countries. Of the 11 studies, 6 studies reported exclusively on early CKD (stage 1-2), 4 studies separately reported analyses e Author(s) 2020.The dynamics of the human middle ear (ME) has been studied in the past using several computational and experimental approaches in order to observe the effect on hearing of different conditions, such as conductive disease, corrective surgery or implantation of a middle ear prosthesis. Multi-body (MB) models combine the analysis of flexible structures with rigid body dynamics, involving fewer degrees of freedom than finite element (FE) models, but a more detailed description than traditional 1-D lumped parameter (LP) models. This study describes the reduction of a reference FE model of the human middle ear to a MB model and compares the results obtained considering different levels of model simplification. All models are compared by means of the frequency response of the stapes velocity vs. sound pressure at the tympanic membrane, as well as the system natural frequencies and mode shapes. It can be seen that the flexibility of the ossicles has a limited impact on the system FRF and modes, and the stiffness of the tendons and ligaments only plays a role when above certain levels. On the other hand, the restriction of the stapes footplate movement to a piston-like behavior can considerably affect the vibrational modes, while constrains to the incudomalleolar and incudostapedial joints can have a strong impact on the system FRF. Copyright (c) 2020 by ASME.The molecular processes underlying the aging-related decline in cognitive performance and memory observed in humans are poorly understood. Studies in rodents have shown a decrease in N-methyl-D-aspartate receptors (NMDARs) that contain the GluN2B subunit in aging synapses, and this decrease is correlated with impaired memory functions. However, the age-dependent contribution of GluN2B-containing receptors to synaptic transmission in human cortical synapses has not been previously studied. We investigated the synaptic contribution of GluN2A and GluN2B-containing NMDARs in adult human neurons using fresh nonpathological temporal cortical tissue resected during neurosurgical procedures. The tissue we obtained fulfilled quality criteria by the absence of inflammation markers and proteomic degradation. We show an age-dependent decline in the NMDA/AMPA receptor ratio in adult human temporal cortical synapses. We demonstrate that GluN2B-containing NMDA receptors contribute to synaptic responses in the adult human brain with a reduced contribution in older individuals. With previous evidence demonstrating the critical role of synaptic GluN2B in regulating synaptic strength and memory storage in mice, this progressive reduction of GluN2B in the human brain during aging may underlie a molecular mechanism in the age-related decline in cognitive abilities and memory observed in humans. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail [email protected].
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