The Two-Way Route between Delirium Disorder and Dementia: Insights from COVID-19.

Delirium disorder is a frequent neurological complication of SARS-CoV-2 infection and associated with increased disease severity and mortality. Cognitive impairment is a major risk factor for developing delirium disorder during COVID-19, which, in turn, increases the risk of subsequent neurological complications and cognitive decline. The bidirectional connection between delirium disorder and dementia likely resides at multiple levels, and its pathophysiological mechanisms during COVID-19 include endothelial damage, blood-brain barrier dysfunction, and local inflammation, with activation of microglia and astrocytes. Here, we describe the putative pathogenic pathways underlying delirium disorder during COVID-19 and highlight how they cross with the ones leading to neurodegenerative dementia. The analysis of the two-sided link can offer useful insights for confronting with long-term neurological consequences of COVID-19 and framing future prevention and early treatment strategies

Myostatin mediates abdominal aortic atherosclerosis progression by inducing vascular smooth muscle cell dysfunction and monocyte recruitment

Myostatin (Mstn) is a skeletal muscle growth inhibitor involved in metabolic disorders and heart fibrosis. In this study we sought to verify whether Mstn is also operative in atherosclerosis of abdominal aorta. In human specimens, Mstn expression was almost absent in normal vessels, became detectable in the media of non-progressive lesions and increased with the severity of the damage. In progressive atherosclerotic lesions, Mstn was present in the media, neointima, plaque shoulder and in infiltrating macrophages. Mstn co-localized with \uce\ub1-smooth muscle actin (\uce\ub1-SMA) staining and with some CD45+ cells, indicating Mstn expression in VSMCs and bloodstream-derived leukocytes. In vitro, Mstn was tested in VSMCs and monocytes. In A7r5 VSMCs, Mstn downregulated proliferation and Smoothelin mRNA, induced cytoskeletal rearrangement, increased migratory rate and MCP-1/CCR2 expression. In monocytes (THP-1 cells and human monocytes), Mstn acted as a chemoattractant and increased the MCP-1-dependent chemotaxis, F-actin, \uce\ub1-SMA, MCP-1 and CCR2 expression; in turn, MCP-1 increased Mstn mRNA. Mstn induced JNK phosphorylation both in VSMCs and monocytes. Our results indicate that Mstn is overexpressed in abdominal aortic wall deterioration, affects VSMCs and monocyte biology and sustains a chronic inflammatory milieu. These findings propose to consider Mstn as a new playmaker in atherosclerosis progression

Sentient Spaces: Intelligent Totem Use Case in the ECSEL FRACTAL Project

The objective of the FRACTAL project is to create a novel approach to reliable edge computing. The FRACTAL computing node will be the building block of scalable Internet of Things (from Low Computing to High Computing Edge Nodes). The node will also have the capability of learning how to improve its performance against the uncertainty of the environment. In such a context, this paper presents in detail one of the key use cases: an Internet-of-Things solution, represented by intelligent totems for advertisement and wayfinding services, within advanced ICT-based shopping malls conceived as a sentient space. The paper outlines the reference scenario and provides an overview of the architecture and the functionality of the demonstrator, as well as a roadmap for its development and evaluation

The antimicrobial activity of annona emarginata (Schltdl.) H. Rainer and most active isolated compounds against clinically important bacteria

This research was partially supported by grants from Universidad Nacional de San Luis and PIP 444-CONICET. J.D. thanks a fellowship from CONICET. E.S. and R.M. appreciate National Science Centre grant No 2013/09/B/NZ7/00423. J.K. and J.J. were supported by the grant of the Faculty of Pharmacy of Comenius University in Bratislava No. FaF UK/37/2018 and by SANOFI-AVENTIS Pharma Slovakia, s.r.o. The authors thank Luis A. Del Vitto (UNSL) for his help in the botanical classification and Marcos Maiocchi (UNNE) for the help in the collection of the plant material. B.L., G.E.F. and A.T. thank CICITCA-UNSJ.Annona emarginata (Schltdl.) H. Rainer, commonly known as “arachichú”, “araticú”, “aratigú”, and “yerba mora”, is a plant that grows in Argentina. Infusions and decoctions are used in folk medicine as a gargle against throat pain and for calming toothache; another way to use the plant for these purposes is chewing its leaves. Extracts from bark, flowers, leaves, and fruits from A. emarginata were subjected to antibacterial assays against a panel of Gram (+) and Gram (−) pathogenic bacteria according to Clinical and Laboratory Standards Institute protocols. Extracts from the stem bark and leaves showed moderate activity against the bacteria tested with values between 250–1000 µg/mL. Regarding flower extracts, less polar extracts (hexane, dichloromethane) showed very strong antibacterial activity against methicillin-sensitive Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus ATCC 43300 with values between 16–125 µg/mL. Additionally, hexane extract showed activity against Klebsiella pneumoniae (MIC = 250 µg/mL). The global methanolic extract of the fruits (MeOHGEF) was also active against the three strains mentioned above, with MICs values 250–500 µg/mL. Bioassay-guided fractionation of MeOHGEF led to the isolation of a new main compound—(R)-2-(4-methylcyclohex-3-en-1-yl)propan-2-yl (E)-3-(4-hydroxyphenyl)acrylate (1). The structure and relative configurations have been determined by means of 1D and 2D NMR techniques, including COSY, HMQC, HMBC, and NOESY correlations. Compound 1 showed strong antimicrobial activity against all Gram (+) species tested (MICs = 3.12–6.25 µg/mL). In addition, the synthesis and antibacterial activity of some compounds structurally related to compound 1 (including four new compounds) are reported. A SAR study for these compounds was performed based on the results obtained by using molecular calculations.NC

Private Narratives and Infant Views: Iconizing 1970s Militancy in Contemporary Argentine Cinema

This is the author's accepted manuscript, made available with the permission of the publisher.This article analyses the connections between the subjective turn in the representation of militancy, iconicity, and historical examination in Infancia clandestina, a recent Argentine film that portrays the 1970s armed struggle through a child’s lens. Breaking with the leading interpretation that praises the movie because of its original exposition of left-leaning violence, I contend that this coming-of-age story fits within a version of militancy that originated in the mid-1990s and that has become quite common since the advent of the Kirchner administration in 2003. This particular version relies on a privatized and archaic image of activism that is at the core of the global iconization of 1970s militancy. An analysis of the filmic use of an infant perspective and of anime-style cartoons illuminates how contemporary Argentine cinema both registers and participates in this iconizing process

Quantification of amyloid PET for future clinical use: a state-of-the-art review

Amyloid-β (Aβ) pathology is one of the earliest detectable brain changes in Alzheimer's disease (AD) pathogenesis. The overall load and spatial distribution of brain Aβ can be determined in vivo using positron emission tomography (PET), for which three fluorine-18 labelled radiotracers have been approved for clinical use. In clinical practice, trained readers will categorise scans as either Aβ positive or negative, based on visual inspection. Diagnostic decisions are often based on these reads and patient selection for clinical trials is increasingly guided by amyloid status. However, tracer deposition in the grey matter as a function of amyloid load is an inherently continuous process, which is not sufficiently appreciated through binary cut-offs alone. State-of-the-art methods for amyloid PET quantification can generate tracer-independent measures of Aβ burden. Recent research has shown the ability of these quantitative measures to highlight pathological changes at the earliest stages of the AD continuum and generate more sensitive thresholds, as well as improving diagnostic confidence around established binary cut-offs. With the recent FDA approval of aducanumab and more candidate drugs on the horizon, early identification of amyloid burden using quantitative measures is critical for enrolling appropriate subjects to help establish the optimal window for therapeutic intervention and secondary prevention. In addition, quantitative amyloid measurements are used for treatment response monitoring in clinical trials. In clinical settings, large multi-centre studies have shown that amyloid PET results change both diagnosis and patient management and that quantification can accurately predict rates of cognitive decline. Whether these changes in management reflect an improvement in clinical outcomes is yet to be determined and further validation work is required to establish the utility of quantification for supporting treatment endpoint decisions. In this state-of-the-art review, several tools and measures available for amyloid PET quantification are summarised and discussed. Use of these methods is growing both clinically and in the research domain. Concurrently, there is a duty of care to the wider dementia community to increase visibility and understanding of these methods

Quantification of amyloid PET for future clinical use: a state-of-the-art review

Amyloid-β (Aβ) pathology is one of the earliest detectable brain changes in Alzheimer's disease (AD) pathogenesis. The overall load and spatial distribution of brain Aβ can be determined in vivo using positron emission tomography (PET), for which three fluorine-18 labelled radiotracers have been approved for clinical use. In clinical practice, trained readers will categorise scans as either Aβ positive or negative, based on visual inspection. Diagnostic decisions are often based on these reads and patient selection for clinical trials is increasingly guided by amyloid status. However, tracer deposition in the grey matter as a function of amyloid load is an inherently continuous process, which is not sufficiently appreciated through binary cut-offs alone. State-of-the-art methods for amyloid PET quantification can generate tracer-independent measures of Aβ burden. Recent research has shown the ability of these quantitative measures to highlight pathological changes at the earliest stages of the AD continuum and generate more sensitive thresholds, as well as improving diagnostic confidence around established binary cut-offs. With the recent FDA approval of aducanumab and more candidate drugs on the horizon, early identification of amyloid burden using quantitative measures is critical for enrolling appropriate subjects to help establish the optimal window for therapeutic intervention and secondary prevention. In addition, quantitative amyloid measurements are used for treatment response monitoring in clinical trials. In clinical settings, large multi-centre studies have shown that amyloid PET results change both diagnosis and patient management and that quantification can accurately predict rates of cognitive decline. Whether these changes in management reflect an improvement in clinical outcomes is yet to be determined and further validation work is required to establish the utility of quantification for supporting treatment endpoint decisions. In this state-of-the-art review, several tools and measures available for amyloid PET quantification are summarised and discussed. Use of these methods is growing both clinically and in the research domain. Concurrently, there is a duty of care to the wider dementia community to increase visibility and understanding of these methods