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Increased VLCFA-lipids along with ELOVL4 underlie neurodegeneration in frontotemporal dementia.
Copyright (c) 2020 by ASME.Importance Risk factors for in-hospital mortality of patients with head and neck cancer (HNC) are multilevel. Studies have examined the effect of patient-level characteristics on in-hospital mortality; however, there is a paucity of data on multilevel correlates of in-hospital mortality. CHQ inhibitor supplier Objective To examine the multilevel associations of patient- and hospital-level factors with in-hospital mortality and develop a nomogram to predict the risk of in-hospital mortality among patients diagnosed with HNC. Design, Setting, and Participants This cross-sectional study used the 2008-2013 National Inpatient Sample database. Hospitalized patients 18 years and older diagnosed (both primary and secondary diagnosis) as having HNC using the International Classification of Diseases, Ninth Revision, Clinical Modification codes were included. Analysis began December 2018. Main Outcomes and Measures The primary outcome of interest was in-hospital mortality. A weighted multivariable hierarchical logistic regression model estimain-hospital mortality discrimination (area under the curve of 72%). Conclusions and Relevance This cross-sectional study found that both patient- and hospital-level factors were associated with in-hospital mortality, and the nomogram estimated with fair accuracy the probability of in-hospital death among patients with HNC. These multilevel factors are critical indicators of survivorship and should thus be considered when planning programs or interventions aimed to improve survival among this unique population.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. link2 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. The aim of this systematic review was to summarize the evidence on dietary potassium intake and CKD progression. link3 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] This study investigated endothelial function in HIV-positive patients with acute coronary syndrome (ACS). Flow-mediated dilatation, pulse-wave velocity, carotid intima-media thickness and endothelial biomarkers were used to non-invasively investigate endothelial dysfunction. METHODS Twenty HIV-positive patients with ACS (HIV+/ACS) were compared to 20 HIV-negative patients with ACS (HIV-/ACS) and 20 HIV-positive patients without ACS (HIV+/no ACS). RESULTS Endothelial function measured by flow-mediated dilatation (FMD) was similar in both the HIV+/ACS (5.2; IQR 1.4-13.4%) and HIV-/ACS groups (3.7; IQR 2.3-4.4%) (p = 0.78). Arterial stiffness, measured by pulse-wave velocity (PWV) was low in all three cohorts. Carotid intima-media thickness (CIMT) was also low in all three cohorts. The vascular cellular adhesion molecule-1 (VCAM-1) levels in HIV-positive patients with and without ACS were significantly higher than in the HIV-/ACS cohort (p = 0.033 and 0.024, respectively). CONCLUSIONS Non-invasive investigations such as FMD, CIMT and PWV did not identify patients with HIV who were at high risk of ACS. Endothelial biomarkers may be more useful markers to identify HIV-positive patients who have endothelial dysfunction and increased risk of ACS.Toxicometabolomic studies involving zebrafish embryos have become increasingly popular for linking apical endpoints to biochemical perturbations as part of adverse outcome pathway determination. These experiments involve pooling embryos to generate sufficient biomass for metabolomic measurement, which adds both time and cost. To address this limitation, we developed a high-throughput toxicometabolomic assay involving single zebrafish embryos. Incubation, microscopy, embryo extraction, and instrumental metabolomic analysis were all performed in the same 96-well plate, following acquisition of conventional toxicological endpoints. The total time for the assay (including testing of 6 doses/n = 12 embryos per dose plus positive and negative controls, assessing conventional endpoints, instrumental analysis, data processing and multivariate statistics) is less then 14 days. Metabolomic perturbations at low dose were linked statistically to those observed at high dose and in the presence of an adverse effect, thereby contextualizing omic data amongst apical endpoints. Overall, this assay enables collection of high resolution metabolomic data in a high throughput manner, suitable for mode of action hypothesis generation in the context of pharmaceutical or toxicological screening.Liquid suspensions of carbon nanotubes, graphene and transition metal dichalcogenides have exhibited excellent performance in optical limiting. However, the underlying mechanism has remained elusive and is generally ascribed to their superior nonlinear optical properties such as nonlinear absorption or nonlinear scattering. Using graphene as an example, we show that photo-thermal microbubbles are responsible for optical limiting as strong light scattering centers graphene sheets absorb incident light and become heated up above the boiling point of water, resulting in vapor and microbubble generation. This conclusion is based on the direct observation of bubbles above the laser beam as well as a strong correlation between laser-induced ultrasound and optical limiting. In situ Raman scattering of graphene further confirms that the temperature of graphene under laser pulses rises above the boiling point of water but still remains too low to vaporize graphene and create graphene plasma bubbles. Photo-thermal bubble scattering is not a nonlinear optical process and requires very low laser intensity.
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