Structural and Functional Neuroimaging of Visual Hallucinations in Lewy Body Disease: A Systematic Literature Review.

Patients with Lewy body disease (LBD) frequently experience visual hallucinations (VH), well-formed images perceived without the presence of real stimuli. The structural and functional brain mechanisms underlying VH in LBD are still unclear. The present review summarises the current literature on the neural correlates of VH in LBD, namely Parkinson's disease (PD), and dementia with Lewy bodies (DLB). Following a systematic literature search, 56 neuroimaging studies of VH in PD and DLB were critically reviewed and evaluated for quality assessment. The main structural neuroimaging results on VH in LBD revealed grey matter loss in frontal areas in patients with dementia, and parietal and occipito-temporal regions in PD without dementia. Parietal and temporal hypometabolism was also reported in hallucinating PD patients. Disrupted functional connectivity was detected especially in the default mode network and fronto-parietal regions. However, evidence on structural and functional connectivity is still limited and requires further investigation. The current literature is in line with integrative models of VH suggesting a role of attention and perception deficits in the development of VH. However, despite the close relationship between VH and cognitive impairment, its associations with brain structure and function have been explored only by a limited number of studies

Frontal and subcortical contribution to visual hallucinations in dementia with Lewy bodies and Parkinson’s disease

Objectives. Visual hallucinations (VH) are common in Lewy body disease (LBD), and have been associated with cognitive and structural brain alterations. Evidence so far concerns mainly Parkinson’s disease (PD), but little is known about symptom-specific pathophysiological mechanisms across the LBD spectrum, especially related to the presence of dementia. The aim of the present pilot study was to investigate the neuroanatomical, and neuropsychological characteristics related to VH in two forms of LBD, namely dementia with Lewy bodies (DLB) and PD without dementia. Methods. Whole brain voxel-based morphometry (VBM) analyses on 3D MRI acquired structural brain scans, and neuropsychological testing were performed on 28 clinically diagnosed DLB (11 with VH, 17 NVH), and 24 PD (9 with VH, and 15 NVH) patients. In order to assess differences in grey matter (GM) regional volumes, and cognitive performance, hallucinating patients for each group were compared with corresponding non-hallucinating ones. Results. DLB patients with VH presented significantly worse visual attention deficits compared to those without, which persisted even when controlling for visual perception. Whole brain VBM analysis revealed decreased GM volume in DLB with VH in the right superior and medial frontal gyri, putamen, caudate nucleus and insula. Subcortical regional volumes were also significantly associated with visual attention performance. Hallucinating PD patients, instead, presented more severe executive dysfunction, but VBM showed no volumetric differences between the two PD subgroups. Post hoc region of interest analyses revealed striatal GM loss in PD with VH. Conclusion. Frontal and striatal GM atrophy may contribute to the emergence of VH in DLB, which may be fostered by the more severe attention deficits. Striatal GM loss and executive dysfunction, instead, appeared to underlie VH in PD without dementia

Serum Squamous Cell Carcinoma Antigen-Immunoglobulin M complex levels predict survival in patients with cirrhosis

Complications of chronic liver diseases - particularly hepatocellular carcinoma (HCC) - are a major cause of mortality worldwide. Several studies have shown that high or increasing levels of serum Squamous Cell Carcinoma Antigen-Immunoglobulin M complex (SCCA-IgM) are associated with development of HCC in patients with advanced liver disease and worse survival in patients with liver cancer. The aim of the present study was to assess, in patients with advanced liver disease, differences in long-term clinical outcomes in relation to baseline levels of serum SCCA-IgM. Ninety one consecutive outpatients with liver cirrhosis of different etiologies, without hepatocellular carcinoma at presentation, were enrolled from April 2007 to October 2012 in a prospective study. For a median time of 127 months, patients were bi-annually re-evaluated. SCCA-IgM complex levels were determined with a validated enzyme-linked immunosorbent assay. The results provided evidence that serum SCCA-IgM is a predictor of overall survival. The best cut-off to discriminate both HCC-free and overall survival rates was 120\u2009AU/mL. Patients with baseline values higher than this threshold showed a substantial increase in both HCC incidence rate and all-cause mortality rate. In conclusion, a single measurement of serum SCCA-IgM helps to identify those patients with liver cirrhosis with increased risks of HCC development and mortality

Helicobacter pylori Dampens HLA-II Expression on Macrophages via the Up-Regulation of miRNAs Targeting CIITA

Macrophages have a major role in infectious and inflammatory diseases, and the available data suggest that Helicobacter pylori persistence can be explained in part by the failure of the bacterium to be killed by professional phagocytes. Macrophages are cells ready to kill the engulfed pathogen, through oxygen-dependent and -independent mechanisms; however, their killing potential can be further augmented by the intervention of T helper (Th) cells upon the specific recognition of human leukocyte antigen (HLA)-II\u2013peptide complexes on the surface of the phagocytic cells. As it pertains to H. pylori, the bacterium is engulfed by macrophages, but it interferes with the phagosome maturation process leading to phagosomes with an altered degradative capacity, and to megasomes, wherein H. pylori resists killing. We recently showed that macrophages infected with H. pylori strongly reduce the expression of HLA-II molecules on the plasma membrane and this compromises the bacterial antigen presentation to Th lymphocytes. In this work, we demonstrate that H. pylori hampers HLA-II expression in macrophages, activated or non-activated by IFN-\u3b3, by down-regulating the expression of the class II major histocompatibility complex transactivator (CIITA), the \u201cmaster control factor\u201d for the expression of HLA class II genes. We provided evidence that this effect relies on the up-regulation of let-7f-5p, let-7i-5p, miR-146b-5p, and -185-5p targeting CIITA. MiRNA expression analysis performed on biopsies from H. pylori-infected patients confirmed the up-regulation of let-7i-5p, miR-146b-5p, and -185-5p in gastritis, in pre-invasive lesions, and in gastric cancer. Taken together, our results suggest that specific miRNAs may be directly involved in the H. pylori infection persistence and may contribute to confer the risk of developing gastric neoplasia in infected patients

The geometrical nature of optical resonances : from a sphere to fused dimer nanoparticles

We study the electromagnetic response of smooth gold nanoparticles with shapes varying from a single sphere to two ellipsoids joined smoothly at their vertices. We show that the plasmonic resonance visible in the extinction and absorption cross sections shifts to longer wavelengths and eventually disappears as the mid-plane waist of the composite particle becomes narrower. This process corresponds to an increase of the numbers of internal and scattering modes that are mainly confined to the surface and coupled to the incident field. These modes strongly affect the near field, and therefore are of great importance in surface spectroscopy, but are almost undetectable in the far field

Metabolomic Alterations Do Not Induce Metabolic Burden in the Industrial Yeast M2n[pBKD2-Pccbgl1]-C1 Engineered by Multiple \u3b4-Integration of a Fungal \u3b2-Glucosidase Gene

In the lignocellulosic yeast development, metabolic burden relates to redirection of resources from regular cellular activities toward the needs created by recombinant protein production. As a result, growth parameters may be greatly affected. Noteworthy, Saccharomyces cerevisiae M2n[pBKD2-Pccbgl1]-C1, previously developed by multiple d-integration of the b-glucosidase BGL3, did not show any detectable metabolic burden. This work aims to test the hypothesis that the metabolic burden and the metabolomic perturbation induced by the d-integration of a yeast strain, could differ significantly. The engineered strain was evaluated in terms of metabolic performances and metabolomic alterations in different conditions typical of the bioethanol industry. Results indicate that the multiple d-integration did not affect the ability of the engineered strain to grow on different carbon sources and to tolerate increasing concentrations of ethanol and inhibitory compounds. Conversely, metabolomic profiles were significantly altered both under growing and stressing conditions, indicating a large extent of metabolic reshuffling involved in the maintenance of the metabolic homeostasis. Considering that four copies of BGL3 gene have been integrated without affecting any parental genes or promoter sequences, deeper studies are needed to unveil the mechanisms implied in these metabolomic changes, thus supporting the optimization of protein production in engineered strains

Indoor particulate matter measurement as a tool in the process of the implementation of Smoke-free Hospitals

Aim of the study: There are International and National standards that requires hospitals and health premises to be smoke-free. According to recent data from Italy and other European Countries, smoking is a widespread habit in hospitals. To get smoke-free hospitals in an Italian region, we have adopted the European Code for smoke-free hospitals, which sets standards and provides instruments for its implementation. According to the Code, whenever possible, each step towards a smoke-free hospital, should be shared by all staff. As a mean for achieving this goal, in our region the certification of single units as smoke-free units has been chosen. For getting the certification, besides implementing the Code, we planned to use ETS (Environmental Tobacco Smoke) monitoring, as ETS should not be present in hospitals. As a marker of ETS we have chosen Particulate Matter (PM), as it can easily be measured in real-time with a portable instrument and, when other - even outdoor - sources of combustion can be ruled out, it is an accurate detector of cigarette smoke. Here the first experience of measuring PM in hospitals for monitoring ETS and certificating smoke-free health premises, is described. Materials and methods: PM measurements were carried out without any previous notification in different areas of two Network hospitals of the Veneto Region, during a single working day. A real time laser-operated aerosol mass analyser was used. Several classes of PM (PM1, PM2.5, PM7, PM10, TSP Total Suspended Particles) were measured. Results: Outdoor PM levels were found to be repeatedly lower than the annual official limits of 65 mcg/m3 and around the 24 hour official limits of 15 mcg/m3 [15 to 20 mcg/m3, with an overall mean (±SD) of 17.8 (1.9)] throughout the whole day. Very good indoor air quality was found in the operating theaters and isolation department, where PM2.5 concentrations were much lower than outdoor levels [1.6 (0.9) and 5.9 (0.6) mcg/m3, respectively]. No increase in PM pollution was found in the surveyed medical offices, halls and waiting rooms where smoking was positively forbidden [PM2.5 concentrations of 14.8 (2.2) and 12.9 (1.1) mcg/m3] except in a medical office and in two coffee rooms for staff only where high PM levels were recorded [PM2.5 58.7 (29.1), 27.0 (10.6) and 107.1 (47.8) mcg/m3] and an offence of smoking restrictions could be proved. Conclusions: The measurement of PM in hospital for monitoring ETS proved to be both feasible and sensible. PM measurements with a portable instrument can be used both for controlling the compliance with rules or chosen standards and for educating staff about smoking related hazards, thus gaining consensus for the implementation of the tobacco control policy. In our experience, PM measurement can be used as an aid inside all actions designed by the European Code for smoke-free hospitals

Functional Brain Connectivity Patterns Associated with Visual Hallucinations in Dementia with Lewy Bodies

The supplementary material is available in the electronic version of this article: https://doi.org/ 10.3233/ADR-200288.Copyright © 2021 – The authors. Background: The presence of recurrent, complex visual hallucinations (VH) is among the core clinical features of dementia with Lewy bodies (DLB). It has been proposed that VH arise from a disrupted organization of functional brain networks. However, studies are still limited, especially investigating the resting-state functional brain features underpinning VH in patients with dementia. Objective: The aim of the present pilot study was to investigate whether there were any alterations in functional connectivity associated with VH in DLB. Methods: Seed-based analyses and independent component analysis (ICA) of resting-state fMRI scans were carried out to explore differences in functional connectivity between DLB patients with and without VH. Results: Seed-based analyses reported decreased connectivity of the lateral geniculate nucleus, the superior parietal lobule and the putamen with the medial frontal gyrus in DLB patients with VH. Visual areas showed a pattern of both decreased and increased functional connectivity. ICA revealed between-group differences in the default mode network (DMN). Conclusion: Functional connectivity analyses suggest dysfunctional top-down and bottom-up processes and DMN-related alterations in DLB patients with VH. This impairment might foster the generation of false visual images that are misinterpreted, ultimately resulting in VH.Faculty of Medicine, Dentistry and Health, University of Sheffield, UK matched funding studentship

[11C]-DPA-713 and [18F]-DPA-714 as New PET Tracers for TSPO: A Comparison with [11C]-(R)-PK11195 in a Rat Model of Herpes Encephalitis

Background: Activation of microglia cells plays an important role in neurological diseases. Positron emission tomography (PET) with [C-11]-(R)-PK11195 has already been used to visualize activated microglia cells in neurological diseases. However, [C-11]-(R)-PK11195 may not possess the required sensitivity to visualize mild neuroinflammation. In this study, we evaluated the PET tracers [C-11]-DPA-713 and [F-18]-DPA-714 as agents for imaging of activated microglia in a rat model of herpes encephalitis. Materials and Methods: Rats were intranasally inoculated with HSV-1. On day 6 or 7 after inoculation, small animal PET studies were performed to compare [C-11]-(R)-PK11195, [C-11]-DPA-713, and [F-18]-DPA-714. Results: Uptake of [C-11]-DPA-713 in infected brain areas was comparable to that of [C-11]-(R)-PK11195, but [C-11]-DPA-713 showed lower non-specific binding. Non-specific uptake of [F-18]-DPA-714 was lower than that of [C-11]-(R)-PK11195. In the infected brain, total [F-18]-DPA-714 uptake was lower than that of [C-11]-(R)-PK11195, with comparable specific uptake. Conclusions: [C-11]-DPA-713 may be more suitable for visualizing mild inflammation than [C-11]-(R)-PK11195. In addition, the fact that [F-18]-DPA-714 is an agonist PET tracer opens new possibilities to evaluate different aspects of neuroinflammation. Therefore, both tracers warrant further investigation in animal models and in a clinical setting