A European Survey to Identify Challenges in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe subtype, metabolic dysfunction-associated steatohepatitis (MASH), are highly prevalent and strongly associated with obesity and type 2 diabetes (T2D). This study sought to identify challenges to the diagnosis, treatment and management of people living with MASLD and MASH and understand the key barriers to adopting relevant clinical guidelines.

Methods: A real-world, cross-sectional study (BARRIERS-MASLD) consisting of a quantitative survey and qualitative interviews of physicians in France, Germany, Italy, Spain and the United Kingdom was conducted from March to September 2023.

User Experiences of and Preferences for Self-Guided Digital Interventions for the Treatment of Mild to Moderate Eating Disorders: Systematic Review and Metasynthesis.

Background: Digital interventions typically involve using smartphones or PCs to access online or downloadable self-help and may offer a more accessible and convenient option than face-to-face interventions for some people with mild to moderate eating disorders. They have been shown to substantially reduce eating disorder symptoms, but treatment dropout rates are higher than for face-to-face interventions. We need to understand user experiences and preferences for digital interventions to support the design and development of user-centered digital interventions that are engaging and meet users' needs.

Anticipatory smooth pursuit eye movements scale with the probability of visual motion: The role of target speed and acceleration.

Sensory-motor systems can extract statistical regularities in dynamic uncertain environments, enabling quicker responses and anticipatory behavior for expected events. Anticipatory smooth pursuit eye movements (aSP) have been observed in primates when the temporal and kinematic properties of a forthcoming visual moving target are fully or partially predictable. To investigate the nature of the internal model of target kinematics underlying aSP, we tested the effect of varying the target kinematics and its predictability.

Mortality Risk Prediction Models for People With Kidney Failure: A Systematic Review.

Importance: People with kidney failure have a high risk of death and poor quality of life. Mortality risk prediction models may help them decide which form of treatment they prefer.

Objective: To systematically review the quality of existing mortality prediction models for people with kidney failure and assess whether they can be applied in clinical practice.

Mental Disorders Among Offspring Prenatally Exposed to Systemic Glucocorticoids.

Importance: Current evidence of the association between prenatal exposure to glucocorticoids and long-term mental disorders is scarce and has limitations.

Objective: To investigate the association between prenatal exposure to systemic glucocorticoids and mental disorders in offspring at the age of 15 years, comparing exposed vs unexposed offspring born to mothers with the same underlying disease (risk of preterm delivery and autoimmune or inflammatory disorders).

Design, Setting, And Participants: This nationwide population-based cohort study used data from registries in Denmark with follow-up until December 31, 2018.

Steps towards a New Humanism in the Mental Health Disciplines - An Interview with Tim Ingold.

This interview article explores how British anthropologist Tim Ingold's work can inspire innovation in mental health and the psy disciplines. Ingold critiques dominant biomedical and individualistic approaches, arguing for the importance of caring attentiveness and abolishing dichotomies like those between surface and depth, when engaging with people to understand and assist them. Instead, he suggests viewing human existence as correspondences with environmental, social, and relational others.

Basic Science and Pathogenesis.

Background: Psychosis occurs in 30-40% of individuals with AD. New insights into disease mechanisms may lead to novel pharmacological targets and treatments. Previous studies have focused on bulk tissue analysis with limited results.

Basic Science and Pathogenesis.

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder involving pathological deposition of tau that includes glial inclusions and specific regional vulnerability patterns. Therapeutic developments are hampered by incomplete understanding of disease mechanisms. Few studies have examined its cell type-specific effects.

Basic Science and Pathogenesis.

Background: Huntington's disease (HD) is an autosomal dominant condition causing severe neurodegeneration in the striatum and the entorhinal cortex (EC). An epigenome wide association study of DNA methylation in HD by our group, identified potential hypomethylation at the PTGDS gene in the striatum. We aimed to validate this result through pyrosequencing, examining the locus in fine detail, and to assess the signal specificity by profiling multiple neurodegenerative diseases.

Basic Science and Pathogenesis.

Background: Traumatic brain injury (TBI) is recognized as one major, potentially modifiable risk factor for neurodegenerative disease (NDD). Autopsy studies describe a range of neuropathologies in a proportion of individuals surviving late after TBI, most frequently the tau associated pathology, chronic traumatic encephalopathy neuropathologic change (CTE-NC). In addition to tau, other NDD pathologies are described.

Microfragmented Adipose Tissue Has No Advantage Over Platelet-Rich Plasma and Bone Marrow Aspirate Injections for Symptomatic Knee Osteoarthritis: A Systematic Review and Meta-analysis.

Background: Microfragmented adipose tissue has been proposed for intra-articular treatment of knee osteoarthritis. There are little data comparing the outcomes of treatment between microfragmented adipose tissue and other biological treatments.

Purpose: To perform a systematic review and meta-analysis comparing microfragmented aspirated fat injections to other orthobiologics, hyaluronic acid, and corticosteroid injections for symptomatic knee osteoarthritis.

Co-evolution of atypical BRAF and KRAS mutations in colorectal tumorigenesis.

BRAF mutations in colorectal cancer (CRC) comprise three functional classes: Class 1 (V600E) with strong constitutive activation, Class 2 with pathogenic kinase activity lower than Class 1, and Class 3 which paradoxically lacks kinase activity. Non-Class 1 mutations associate with better prognosis, microsatellite stability, distal tumour location and better anti-EGFR response. Analysis of 13 CRC cohorts (n=6,605 tumours) compared Class 1 (n=709, 10.

Basic Science and Pathogenesis.

Background: Recent research reported that cancer patients had lower risk of Alzheimer's disease (AD). Common signaling pathways, hormonal systems, and genetic predispositions have been hypothesized as important factors contributing to this inverse association. However, the exact mechanisms are still unknown.

Basic Science and Pathogenesis.

Background: Microglia are key players in Alzheimer's disease (AD): Genetic risk for AD is enriched in microglial enhancers, and microglial gene regulatory networks have been shown to be disrupted in AD. Here, we studied polygenic and variant-specific (APOE) risk burden for AD in a xenotransplantation model of AD and human post-mortem brain tissue.

Method: We profiled gene regulation by RNA-seq and ATAC-seq in human iPS-derived microglia, xenotransplanted into the APPNL-G-F mouse model of AD.

Basic Science and Pathogenesis.

Background: Possession of the APOE4 allele is the strongest genetic risk factor for developing the sporadic form of Alzheimer's disease (AD). Studies investigating APOE4's associated AD risk have largely centered on APOE4's propensity to regulate the deposition of extracellular amyloid beta plaques. More recent attempts to characterize APOE4's role in AD have brought into question the role APOE4 may possess in modulating the pathogenesis of intracellular tau tangles.

Basic Science and Pathogenesis.

Background: We aim to investigate efficacies of Ras homolog (Rho)-associated kinases (ROCK) inhibitors on Alzheimer's disease (AD) pathological proteins in human induced pluripotent stem cell (iPSC)-differentiated human neurons and the P301S tau transgenic mouse model (PS19).

Method: Quantitative liquid chromatography-mass spectrometry (LC-MS/MS) and targeted ELISA were implemented to investigate the effect of treatment with fasudil or its derivatives on the human neurons and brains from PS19 mice. We explored the efficacy of these ROCK inhibitors in reducing tau phosphorylation, and the brain proteomic profiles after their administration in mice.

Basic Science and Pathogenesis.

Background: Astrocytes are a numerous and diverse glial subtype specialised to carry out distinct roles involving maintaining homeostasis and effective functioning of the nervous system. To do so effectively, they respond to and secrete various proteins. In addition, astrocytes have been linked to Alzheimer's disease (AD), where they are believed to become reactive and contribute to neuroinflammation.

Basic Science and Pathogenesis.

Background: Psychosis (broadly delusions and hallucinations) has a cumulative disease prevalence of around 40% in Alzheimer's disease (AD). The epigenomic, genomic, and neuropathological data provide powerful evidence that AD+P has a distinct neurobiological profile. Here, we used the weighted gene co-expression network analysis (WGCNA) method to investigate DNA methylation associated with AD+P in the dorsolateral prefrontal cortex of 153 post-mortem brain samples.

Basic Science and Pathogenesis.

Background: Lewy body pathology (LBP) is common in autosomal dominant (ADAD) or sporadic Alzheimer disease (sAD). LBP seems to be the most frequent co-pathology in sAD and even in the relatively young ADAD population, where other co-pathologies are rare. Knowledge of neuropathological distribution patterns of LBP and associated survival and genetic characteristics in both AD variants is incomplete.

Basic Science and Pathogenesis.

Background: The onset and progression of Alzheimer's disease (AD) has been widely linked with inflammation both in the periphery and within the brain. Indeed, infections during life can increase the risk of developing dementia and the rate of cognitive decline in AD patients, with many AD sufferers ultimately dying with a systemic infection. One of the aims of this study is to investigate the molecular mechanisms involved in the brain's response to systemic infections in AD through the analysis of gene expression changes.

Basic Science and Pathogenesis.

Background: A significant proportion of individuals preserve cognitive function despite meeting neuropathological criteria for Alzheimer's disease (AD) at autopsy, known as cognitive resilience. We aimed to define the molecular and cellular signatures of cognitive resilience against AD.

Method: We integrated multi-modal data from the Religious Order Study and Memory and Aging Project (ROSMAP), including bulk (n = 631) and multi-regional single nucleus (n = 48) RNA sequencing.

Basic Science and Pathogenesis.

Background: Published data have highlighted associations between Alzheimer's disease (AD) susceptibility loci and AD-related brain changes. The amyloid imaging to prevent AD (AMYPAD) consortium is a European collaboration consisting of several parent cohorts, four of which had raw genotype array data available. We sought to integrate and harmonise the genetic data, calculate AD polygenic risk scores (PRS), and investigate their association with global amyloid deposition.

Basic Science and Pathogenesis.

Background: Tau abnormalities are a central feature of Alzheimer's disease (AD) and the defining feature of non-AD tauopathies, which include frontotemporal lobar degeneration (FTLD) due to Pick's disease (PiD) or Mapt mutations (FTLD-tau), as well as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and others. Mapt transcripts undergo alternative splicing to produce 6 distinct isoforms. Exon 2 splicing produces 0, 1 or 2 inserts; exclusion or inclusion of exon 10 results in 3-repeat (3R) or 4-repeat (4R) forms, respectively.

Basic Science and Pathogenesis.

Background: While social and medical debate about the efficacy and safety of anti-Aβ immunotherapy is ongoing, one thing that emerged is that we have little understanding of the working mechanisms of these antibodies and this lack of knowledge complicates the interpretation of the clinical results. Here, we aimed to establish if microglia are required for the efficacy of Lecanemab, one of the most promising FDA-approved disease-modifying therapy for AD (Van Dyck et al. N Engl J Med 2023).

Basic Science and Pathogenesis.

Background: Small vessel disease (SVD) is a disorder of the brain's microvessels and a common cause of dementia and stroke. Evidence links normal ageing features to SVD progression, involving endothelial activation, pericyte dysfunction, BBB failure, and microglia response. Here, we aim to examine this relationship through a series of translational investigations.