Imbalanced pattern completion vs. separation in cognitive disease: network simulations of synaptic pathologies predict a personalized therapeutics strategy

<p>Abstract</p> <p>Background</p> <p>Diverse Mouse genetic models of neurodevelopmental, neuropsychiatric, and neurodegenerative causes of impaired cognition exhibit at least four convergent points of synaptic malfunction: 1) Strength of long-term potentiation (LTP), 2) Strength of long-term depression (LTD), 3) Relative inhibition levels (Inhibition), and 4) Excitatory connectivity levels (Connectivity).</p> <p>Results</p> <p>To test the hypothesis that pathological increases or decreases in these synaptic properties could underlie imbalances at the level of basic neural network function, we explored each type of malfunction in a simulation of autoassociative memory. These network simulations revealed that one impact of impairments or excesses in each of these synaptic properties is to shift the trade-off between pattern separation and pattern completion performance during memory storage and recall. Each type of synaptic pathology either pushed the network balance towards intolerable error in pattern separation or intolerable error in pattern completion. Imbalances caused by pathological impairments or excesses in LTP, LTD, inhibition, or connectivity, could all be exacerbated, or rescued, by the simultaneous modulation of any of the other three synaptic properties.</p> <p>Conclusions</p> <p>Because appropriate modulation of any of the synaptic properties could help re-balance network function, regardless of the origins of the imbalance, we propose a new strategy of personalized cognitive therapeutics guided by assay of pattern completion vs. pattern separation function. Simulated examples and testable predictions of this theorized approach to cognitive therapeutics are presented.</p

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Health-related quality of life in young adult patients with rheumatoid arthritis in Iran: reliability and validity of the Persian translation of the PedsQL™ 4.0 Generic Core Scales Young Adult Version

The objective of the present study was to determine the reliability and validity of the Persian translation of the Pediatric Quality of Life Inventory (PedsQL™) 4.0 Generic Core Scales Young Adult Version in an Iranian sample of young adult patients with rheumatoid arthritis (RA). One hundred ninety-seven young adult patients with RA completed the 23-item PedsQL™ and the 36-item Short-Form Health Survey (SF-36). Disease activity based on Disease Activity Score 28 was also measured. Internal consistency and test-retest reliability, as well as construct, discriminant, and convergent validity, were tested. Confirmatory factor analysis (CFA) was used to verify the original factor structure of the PedsQL™. Also, responsiveness to change in PedsQL™ scores over time was assessed. Cronbach's alpha coefficients ranged from α = 0.82 to α = 0.91. Test-retest reproducibility was satisfactory for all scales and the total scale score. The PedsQL proved good convergent validity with the SF-36. The PedsQL distinguished well between young adult patients and healthy young adults and also RA groups with different comorbidities. The CFA did not confirm the original four-factor model, instead, analyses revealed a best-fitting five-factor model for the PedsQL™ Young Adult Version. Repeated measures analysis of variance indicated that the PedsQL scale scores for young adults increased significantly over time. The Persian translation of the PedsQL™ 4.0 Generic Core Scales Young Adult Version demonstrated good psychometric properties in young adult patients with RA and can be recommended for the use in RA research in Iran

Ecological succession reveals potential signatures of marine-terrestrial transition in salt marsh fungal communities

Marine-to-terrestrial transition represents one of the most fundamental shifts in microbial life. Understanding the distribution and drivers of soil microbial communities across coastal ecosystems is critical given the roles of microbes in soil biogeochemistry and their multifaceted influence on landscape succession. Here, we studied the fungal community dynamics in a well-established salt marsh chronosequence that spans over a century of ecosystem development. We focussed on providing high-resolution assessments of community composition, diversity and ecophysiological shifts that yielded patterns of ecological succession through soil formation. Notably, despite containing 10- to 100-fold lower fungal internal transcribed spacer abundances, early-successional sites revealed fungal richnesses comparable to those of more mature soils. These newly formed sites also exhibited significant temporal variations in beta-diversity that may be attributed to the highly dynamic nature of the system imposed by the tidal regime. The fungal community compositions and ecophysiological assignments changed substantially along the successional gradient, revealing a clear signature of ecological replacement and gradually transforming the environment from a marine into a terrestrial system. Moreover, distance-based linear modelling revealed soil physical structure and organic matter to be the best predictors of the shifts in fungal beta-diversity along the chronosequence. Taken together, our study lays the basis for a better understanding of the spatiotemporally determined fungal community dynamics in salt marshes and highlights their ecophysiological traits and adaptation in an evolving ecosystem