The dysfunctional brain dynamic of Lewy body dementia and its behavioural and clinical correlates : an fMRI and EEG analysis

PhD ThesisBackground: Lewy body dementia (LBD), which comprises dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), is characterised by transient clinical symptoms such as cognitive fluctuations which may be caused by alterations of intrinsic brain dynamics. The aim of this thesis is to investigate how dysfunctional brain connectivity and dynamics relate to the cognitive LBD phenotype, especially to attentional impairment and cognitive fluctuations. Methods: In order to investigate behavioural aspects of cognitive fluctuations in LBD, reaction time (RT) data from an attention task were analysed to study how attentional impairment in LBD differs from Alzheimer’s disease (AD) and healthy controls. Additionally, brain structural correlates of attentional dysfunction were assessed using voxel-based morphometry. Subsequently, resting-state fMRI data were analysed using static and dynamic functional connectivity and dynamic network analyses. Faster brain dynamics were assessed by EEG microstate analysis. Results: AD and LBD patients exhibited slower and more variable RTs than controls, with greater impairment in LBD than AD. Extremely slow responses occurred with comparable frequency in both dementia groups. There were widespread correlations between RT abnormalities and structural changes in AD patients, but not LBD. Functional connectivity was decreased in DLB patients compared to controls, mainly in motor, temporal, and frontal networks with sparing of the DMN. Differences between AD and DLB were subtle. Considering time-varying connectivity, AD and DLB patients spent more time in sparse connectivity configurations than controls and switched less often into more highly connected states. Compared to controls, variability of global network efficiency was reduced in patients with DLB. Microstate analysis revealed a marked and generalised increase in microstate duration in LBD patients compared to controls, which was not seen in AD and was related to a loss of dynamic connectivity between basal ganglia/thalamic and large-scale cortical networks. Microstate slowing was correlated with fluctuation severity in the DLB group and with RT slowing and variability across all participants. Conclusions: Different aspects of RT performance are differentially affected by AD and LBD, with a ii difference in structural neural correlates. The dynamic connectivity and microstate results indicate a loss of brain dynamics in LBD which might lead to a breakdown of the intricate dynamic properties of the brain, thereby causing loss of flexibility that is crucial for healthy brain function. This might lead to a network configuration which gives rise to the cognitive LBD phenotype characterised by attentional impairment and cognitive fluctuations.the Alzheimer’s Societ

Genetic Engineering of the Rock Inhabitant Knufia petricola Provides Insight Into the Biology of Extremotolerant Black Fungi

Black microcolonial fungi (Ascomycetes from Arthonio-, Dothideo-, and Eurotiomycetes) are stress-tolerant and persistent dwellers of natural and anthropogenic extreme habitats. They exhibit slow yeast-like or meristematic growth, do not form specialized reproduction structures and accumulate the black pigment 1,8-dihydroxynaphthalene (DHN) melanin in the multilayered cell walls. To understand how black fungi live, survive, colonize mineral substrates, and interact with phototrophs genetic methods are needed to test these functions and interactions. We chose the rock inhabitant Knufia petricola of the Chaetothyriales as a model for developing methods for genetic manipulation. Here, we report on the expansion of the genetic toolkit by more efficient multiplex CRISPR/Cas9 using a plasmid-based system for expression of Cas9 and multiple sgRNAs and the implementation of the three resistance selection markers genR (geneticin/nptII), baR (glufosinate/bar), and suR (chlorimuron ethyl/sur). The targeted integration of expression constructs by replacement of essential genes for pigment synthesis allows for an additional color screening of the transformants. The black-pink screening due to the elimination of pks1 (melanin) was applied for promoter studies using GFP fluorescence as reporter. The black-white screening due to the concurrent elimination of pks1 and phs1 (carotenoids) allows to identify transformants that contain the two expression constructs for co-localization or bimolecular fluorescence complementation (BiFC) studies. The co-localization and interaction of the two K. petricola White Collar orthologs were demonstrated. Two intergenic regions (igr1, igr2) were identified in which expression constructs can be inserted without causing obvious phenotypes. Plasmids of the pNXR-XXX series and new compatible entry plasmids were used for fast and easy generation of expression constructs and are suitable for a broad implementation in other fungi. This variety of genetic tools is opening a completely new perspective for mechanistic and very detailed study of expression, functioning and regulation of the genes/proteins encoded by the genomes of black fungi

Intestinal Acid Sphingomyelinase Protects From Severe Pathogen-Driven Colitis

Inflammatory diseases of the gastrointestinal tract are emerging as a global problem with increased evidence and prevalence in numerous countries. A dysregulated sphingolipid metabolism occurs in patients with ulcerative colitis and is discussed to contribute to its pathogenesis. In the present study, we determined the impact of acid sphingomyelinase (Asm), which catalyzes the hydrolysis of sphingomyelin to ceramide, on the course of Citrobacter (C.) rodentium-driven colitis. C. rodentium is an enteric pathogen and induces colonic inflammation very similar to the pathology in patients with ulcerative colitis. We found that mice with Asm deficiency or Asm inhibition were strongly susceptible to C. rodentium infection. These mice showed increased levels of C. rodentium in the feces and were prone to bacterial spreading to the systemic organs. In addition, mice lacking Asm activity showed an uncontrolled inflammatory Th1 and Th17 response, which was accompanied by a stronger colonic pathology compared to infected wild type mice. These findings identified Asm as an essential regulator of mucosal immunity to the enteric pathogen C. rodentium

Towards Explanatory Feedback for User Training in Brain–Computer Interfaces

International audienceDespite their potential for many applications, Brain-Computer Interfaces (BCI) are still rarely used due to their low reliability and long training. These limitations are partly due to inappropriate training protocols, which includes the feedback provided to the user. While feedback should theoretically be explanatory, motivating and meaningful, current BCI feedback is usually boring, corrective only and difficult to understand. In this study, different features of the electroencephalogram signals were explored to be used as a richer, explanatory BCI feedback. First, based on offline mental imagery BCI data, muscular relaxation was notably found to be negatively correlated to BCI performance. Second, this study reports on an online BCI evaluation using muscular relaxation as additional feedback. While this additional feedback did not lead to significant change in BCI performance, this study showed that multiple feedbacks can be used without deteriorating performance and provided interesting insights for explanatory BCI feedback design

Multimodal prediction of conversion to Alzheimer's disease based on incomplete biomarkers.

BACKGROUND: This study investigates the prediction of mild cognitive impairment-to-Alzheimer's disease (MCI-to-AD) conversion based on extensive multimodal data with varying degrees of missing values. METHODS: Based on Alzheimer's Disease Neuroimaging Initiative data from MCI-patients including all available modalities, we predicted the conversion to AD within 3 years. Different ways of replacing missing data in combination with different classification algorithms are compared. The performance was evaluated on features prioritized by experts and automatically selected features. RESULTS: The conversion to AD could be predicted with a maximal accuracy of 73% using support vector machines and features chosen by experts. Among data modalities, neuropsychological, magnetic resonance imaging, and positron emission tomography data were most informative. The best single feature was the functional activities questionnaire. CONCLUSION: Extensive multimodal and incomplete data can be adequately handled by a combination of missing data substitution, feature selection, and classification

An Intervention to Increase Condom Use Among Users of Sexually Transmitted Infection Self-sampling Websites (Wrapped) : Protocol for a Randomized Controlled Feasibility Trial

© 2023 Katie Newby, Rik Crutzen, Katherine Brown, Julia Bailey, John Saunders, Ala Szczepura, Jonny Hunt, Tim Alston, S Tariq Sadiq, Satyajit Das. Originally published in JMIR Formative Research (http://formative.jmir.org). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).BACKGROUND: Reducing the rates of sexually transmitted infections (STIs) among young people is a public health priority. The best way to avoid STIs from penetrative sex is to use a condom, but young people report inconsistent use. A missed opportunity to intervene to increase condom use is when young people access self-sampling kits for STIs through the internet. The potential of this opportunity is enhanced by the increasing numbers of young people being tested through this route every year in England. Hence, in a cocreation by young people, stakeholders, and researchers, Wrapped was developed--a fully automated, multicomponent, and interactive digital behavior change intervention developed for users of STI self-sampling websites, who are aged 16-24 years. OBJECTIVE: This paper is a protocol for a feasibility randomized controlled trial (fRCT). The fRCT seeks to establish whether it is feasible to run a randomized controlled trial to test the effectiveness and cost-effectiveness of Wrapped. Wrapped aims to reduce the incidence of STIs through increasing correct and consistent use of condoms among users of STI self-sampling websites, who are aged 16-24 years. METHODS: A 2-arm parallel-group randomized fRCT of Wrapped plus usual care, compared to usual care only (basic information on STIs and condom use), with a nested qualitative study. A minimum of 230 participants (aged 16-24 years) are recruited from an existing chlamydia self-sampling website. Participants are randomized into 1 of 2 parallel groups (1:1 allocation). Primary outcomes are the percentage of users recruited to the fRCT and the percentage of randomized participants who return a chlamydia self-sampling kit at month 12. Additionally, besides chlamydia positivity based on biological samples, surveys at baseline, month 3, month 6, and month 12, are used to assess condom use attitude, behavioral capability, self-efficacy, and intention, along with details of any partnered sexual activity and condom use, and health economic data. Nested qualitative interviews with trial participants are used to gain insight into the factors affecting recruitment and attrition. RESULTS: Recruitment to the fRCT began in March 2021 and was completed in October 2021. Data collection was completed in December 2022. CONCLUSIONS: This feasibility study will provide data to inform the design of a future-definitive trial. This work is timely given a rapid rise in the use of internet testing for STIs and the sustained high levels of STIs among young people. TRIAL REGISTRATION: ISRCTN Registry ISRCTN17478654; http://www.isrctn.com/ISRCTN17478654. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43645.Peer reviewe

How do food businesses provide information on allergens in non-prepacked foods? A cross-sectional survey in Switzerland

Purpose This project aimed to investigate allergen information practices of food businesses selling nonprepacked foods after the implementation of the new Swiss food law in May 2017. Methods A cross-sectional telephone survey was conducted with food businesses selling non-prepacked foods in Switzerland. A short, standardised questionnaire was developed in German, based on previous research and literature. It was subsequently translated into French and Italian. Altogether, 882 businesses (restaurants, dairies, butcher shops and bakeries) were contacted, of which 387 were willing to participate. SPSS® (IBM, Armonk, NY, USA) was used for statistical analyses. Results The vast majority (86.0%) of food businesses provides oral allergen information. Only 14.0% currently provide written allergen information to the customer, either upfront or on request. The most frequently used labelling system in written allergen declaration was naming all ingredients (35.2%). A significant number (39.8%) do not place a notice on how to obtain allergen information, although this is a legal requirement in Switzerland when not providing written information upfront. Conclusion So far, not all food businesses have been complying with the new Swiss food law on allergen information of non-prepacked food. Therefore, awareness of the legal obligations around communicating allergen information as well as the verification of its implementation should be enhanced. To meet the needs of consumers and avoid reactions, some form of written allergen information should be promoted. Giving this information on request might encourage communication between customer and staff, thus providing an extra measure of verification

An Intervention to Increase Condom Use Among Users of STI Self-Sampling Websites (Wrapped): Protocol for a Randomized Controlled Feasibility Trial (Preprint)

Background: Reducing the rates of sexually transmitted infections (STIs) among young people is a public health priority. The best way to avoid STIs from penetrative sex is to use a condom, but young people report inconsistent use. A missed opportunity to intervene to increase condom use is when young people access self-sampling kits for STIs through the internet. The potential of this opportunity is enhanced by the increasing numbers of young people being tested through this route every year in England. Hence, in a cocreation by young people, stakeholders, and researchers, Wrapped was developed––a fully automated, multicomponent, and interactive digital behavior change intervention developed for users of STI self-sampling websites, who are aged 16-24 years. Objective: This paper is a protocol for a feasibility randomized controlled trial (fRCT). The fRCT seeks to establish whether it is feasible to run a randomized controlled trial to test the effectiveness and cost-effectiveness of Wrapped. Wrapped aims to reduce the incidence of STIs through increasing correct and consistent use of condoms among users of STI self-sampling websites, who are aged 16-24 years. Methods: A 2-arm parallel-group randomized fRCT of Wrapped plus usual care, compared to usual care only (basic information on STIs and condom use), with a nested qualitative study. A minimum of 230 participants (aged 16-24 years) are recruited from an existing chlamydia self-sampling website. Participants are randomized into 1 of 2 parallel groups (1:1 allocation). Primary outcomes are the percentage of users recruited to the fRCT and the percentage of randomized participants who return a chlamydia self-sampling kit at month 12. Additionally, besides chlamydia positivity based on biological samples, surveys at baseline, month 3, month 6, and month 12, are used to assess condom use attitude, behavioral capability, self-efficacy, and intention, along with details of any partnered sexual activity and condom use, and health economic data. Nested qualitative interviews with trial participants are used to gain insight into the factors affecting recruitment and attrition. Results: Recruitment to the fRCT began in March 2021 and was completed in October 2021. Data collection was completed in December 2022. Conclusions: This feasibility study will provide data to inform the design of a future-definitive trial. This work is timely given a rapid rise in the use of internet testing for STIs and the sustained high levels of STIs among young people. Trial Registration: ISRCTN Registry ISRCTN17478654; http://www.isrctn.com/ISRCTN17478654 International Registered Report Identifier (IRRID): DERR1-10.2196/4364

Sobre la presència de Teucrium pumilum i Teucrium libanitis (Lamiaceae) a la província de València.

12p. fotog.color.[EN] About the presence of Teucrium pumilum and Teucrium libanitis (Lamiaceae) in the Valencian province, Spain.- Teucrium pumilum and T. libanitis have been cited from Valencia province (Spain) since the middle of the XXth Century from the gypsic soils in the Valle de Ayora-Cofrentes shire. The analysis of specimens and labels is not conclusive; no specimen would certify the presence of any of these taxa. The field identification and their inclusion in a phyotosociological table (relevé) by Rivas Goday are the only basis of their presence in the territory in a particular moment of the recent Spanish botanical history. Additionally, the unique herbarium specimen from Valencia, impossible to assign a concrete geographic locality, which was traditionally assigned to T. pumilum by some authors, is actually its congeneric T. carolipaui.[ES] Sobre la presencia de Teucrium pumilum y Teucrium libanitis (Lamiaceae) en la provincia de Valencia.- Teucrium pumilum y T. libanitis son dos especies que han sido citadas como presentes en la provincia de Valencia desde mediados del siglo XX, para los yesos que afloran en la comarca del Valle de Ayora-Cofrentes. El análisis de las etiquetas de los pliegos de los herbarios no es concluyente; ningún pliego testigo certificaría la presencia de estas especies. La determinación de visu por parte de Rivas Goday, y su inclusión en una tabla de inventarios fitosociológica, son el único fundamento de su existencia en la zona en algún momento determinado de la reciente historia botánica española. Además, para T. pumilum, el pliego de herbario que tradicionalmente se ha asignado a la cita valenciana se trata de una confusión en la determinación por parte de algunos autores con su congénere T. carolipaui, siendo imposible al mismo tiempo asignar una localidad geográfica concreta a este material.[CAT] Sobre la presència de Teucrium pumilum i Teucrium libanitis (Lamiaceae) a la província de València.- Teucrium pumilum i T. libanitis són dues espècies que han estat citades com a presents a la província de València des de mitjans del segle XX, sobre els guixos que afloren a la comarca de la Vall d’Aiora-Cofrents. L’anàlisi de les etiquetes dels plecs dels herbaris no és concloent; cap plec testimoni certificaria la presència d’aquestes espècies. La determinació de visu per part de Rivas Goday, i la seva inclusió en una taula d’inventaris fitosociològica, són l’únic fonament de la seva existència a la zona en un moment determinat de la recent història botànica espanyola. A més, per a T. pumilum, el plec d’herbari que tradicionalment s’ ha assignat a la cita valenciana es tracta d’una confusió en la determinació per part d’alguns autors amb el seu congènere.Peer reviewe