Oxidative stress and dysregulated long noncoding RNAs in the pathogenesis of Parkinson's disease.

Parkinson's disease (PD) is a progressive age-related neurodegenerative disease whose annual incidence is increasing as populations continue to age. Although its pathogenesis has not been fully elucidated, oxidative stress has been shown to play an important role in promoting the occurrence and development of the disease. Long noncoding RNAs (lncRNAs), which are more than 200 nucleotides in length, are also involved in the pathogenesis of PD at the transcriptional level via epigenetic regulation, or at the post-transcriptional level by participating in physiological processes, including aggregation of the α-synuclein, mitochondrial dysfunction, oxidative stress, calcium stabilization, and neuroinflammation.

Increased interferon I signaling, DNA damage response and evidence of T-cell exhaustion in a patient with combined interferonopathy (Aicardi-Goutières Syndrome, AGS) and cohesinopathy (Cornelia de Lange Syndrome, CdLS).

Background: Type I interferonopathies including Aicardi-Goutiéres Syndrome (AGS) represent a heterogeneous group of clinical phenotypes. Herein, we present a Case with combined AGS and Cornelia de Lange Syndrome (CdLS)-a cohesinopathy-with comprehensive analysis of the immune and genomic abnormalities.

Case And Methods: A 20-year old man presented with chilblain lesions and resorption of distal phalanges of fingers and toes, somatic and psychomotor retardation, microcephaly, synophrys, hearing losing and other aberrancies consistent with the phenotype of CdLS.

Multiple Sclerosis Nursing to Improve Care and Education (MSNICE): an observational study.

Objective: To explore differences in patient reported outcomes, health care resources and expenditures in persons with multiple sclerosis (pwMS) with or without access to an MS-nurse.

Methodology: An observational, multicenter and cross-sectional study was conducted. Seven centers with, and twelve centers without an MS-nurse participated.

Studying Alzheimer's disease through an integrative serum metabolomic and lipoproteomic approach.

Background: Alzheimer's disease (AD) is the most frequent neurodegenerative disorder worldwide. The great variability in disease evolution and the incomplete understanding of the molecular mechanisms underlying AD make it difficult to predict when a patient will convert from prodromal stage to dementia. We hypothesize that metabolic alterations present at the level of the brain could be reflected at a systemic level in blood serum of patients, and that these alterations could be used as prognostic biomarkers.

ROS-regulated SUR1-TRPM4 drives persistent activation of NLRP3 inflammasome in microglia after whole-brain radiation.

Delayed radiation-induced brain injury (RIBI) characterized by progressive cognitive decline significantly impacts patient outcomes after radiotherapy. The activation of NLRP3 inflammasome within microglia after brain radiation is involved in the progression of RIBI by mediating inflammatory responses. We have previously shown that sulfonylurea receptor 1-transient receptor potential M4 (SUR1-TRPM4) mediates microglial NLRP3-related inflammation following global brain ischemia.

Does diabetes modify the triglyceride-glucose index associated with cardiovascular events and mortality? A meta-analysis of 50 cohorts involving 7,239,790 participants.

Introduction: Previous studies highlighted the association between the triglyceride-glucose (TyG) index and cardiovascular events in patients with diabetes. However, whether diabetes affects TyG-cardiovascular diseases (CVD) is still unclear. This study aimed to evaluate the association between the TyG index and CVD risk, stratified by diabetes status, as well as the potential modifying effect of diabetic status.

Relationship between social support, functional outcomes and health-related quality of life in working-aged adults at three months after ischemic stroke: results from the FRAILTY study.

Background: The relationship between social support and functional outcomes and health-related quality of life (HRQoL) after ischemic stroke (IS) remains unclear, especially in working-aged patients.

Aim: To assess the relationship between perceived social support, functional outcomes, post-stroke psychosocial symptoms, and HRQoL in working-aged adults three months after IS.

Methods: A prospective and correlational design was used.

Number of children and dementia risk: a causal mediation analysis using data from the HUNT study linked with national registries in Norway.

Background: Childlessness, as well as having a high number of children, has been reported to be associated with an elevated risk of dementia compared to having 2-3 children. The mechanisms underlying these relationships are not well understood and may be mediated by different midlife risk factors. We examined the mediating role of various factors on the relationship between the number of children and dementia risk.

The effect of transcranial direct current stimulation and inhibitory control training on depression and anxiety among post-stroke individuals.

Background: Recent research has highlighted the role of fronto-parietal brain networks and cognitive control in mood disorders. Transcranial direct current stimulation (tDCS) and computer-based cognitive training are used in post-stroke rehabilitation. This study examined the combined effects ofof computer-based inhibitory control training (ICCT) and anodal tDCS on post-stroke depression and anxiety.

Mechanisms underlying CSD initiation implicated by genetic mouse models of migraine.

A key unanswered question in migraine neurobiology concerns the mechanisms that make the brain of migraineurs susceptible to cortical spreading depression (CSD, a spreading depolarization that underlies migraine aura and may trigger the migraine pain mechanisms). Important insights into this question can be obtained by studying the mechanisms of facilitation of CSD initiation in genetic mouse models of the disease. These models, all generated from families with hereditary migraine, allow the investigation of the functional consequences of disease-causing mutations at the molecular, cellular, synaptic and neural circuit levels.

Validating the Accuracy of Parkinson's Disease Clinical Diagnosis: A UK Brain Bank Case-Control Study.

Objective: Despite diagnostic criteria refinements, Parkinson's disease (PD) clinical diagnosis still suffers from a not satisfying accuracy, with the post-mortem examination as the gold standard for diagnosis. Seminal clinicopathological series highlighted that a relevant number of patients alive-diagnosed with idiopathic PD have an alternative post-mortem diagnosis. We evaluated the diagnostic accuracy of PD comparing the in-vivo clinical diagnosis with the post-mortem diagnosis performed through the pathological examination in 2 groups.

Preserved brain youthfulness: longitudinal evidence of slower brain aging in superagers.

Background: Superagers, older adults with exceptional cognitive abilities, show preserved brain structure compared to typical older adults. We investigated whether superagers have biologically younger brains based on their structural integrity.

Methods: A cohort of 153 older adults (aged 61-93) was recruited, with 63 classified as superagers based on superior episodic memory and 90 as typical older adults, of whom 64 were followed up after two years.

Rethinking the residual approach: leveraging statistical learning to operationalize cognitive resilience in Alzheimer's disease.

Cognitive resilience (CR) describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer's disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be directly observed. The residual approach has been widely applied to estimate CR, where the degree of resilience is estimated through a linear model's residuals.

Machine learning meta-analysis identifies individual characteristics moderating cognitive intervention efficacy for anxiety and depression symptoms.

Cognitive training is a promising intervention for psychological distress; however, its effectiveness has yielded inconsistent outcomes across studies. This research is a pre-registered individual-level meta-analysis to identify factors contributing to cognitive training efficacy for anxiety and depression symptoms. Machine learning methods, alongside traditional statistical approaches, were employed to analyze 22 datasets with 1544 participants who underwent working memory training, attention bias modification, interpretation bias modification, or inhibitory control training.

The interplay of uncertainty, relevance and learning influences auditory categorization.

Auditory perception requires categorizing sound sequences, such as speech or music, into classes, such as syllables or notes. Auditory categorization depends not only on the acoustic waveform, but also on variability and uncertainty in how the listener perceives the sound - including sensory and stimulus uncertainty, the listener's estimated relevance of the particular sound to the task, and their ability to learn the past statistics of the acoustic environment. Whereas these factors have been studied in isolation, whether and how these factors interact to shape categorization remains unknown.

Patients with neurological or psychiatric complications of COVID-19 have worse long-term functional outcomes: COVID-CNS-A multicentre case-control study.

It is established that patients hospitalised with COVID-19 often have ongoing morbidity affecting activity of daily living (ADL), employment, and mental health. However, little is known about the relative outcomes in patients with COVID-19 neurological or psychiatric complications. We conducted a UK multicentre case-control study of patients hospitalised with COVID-19 (controls) and those who developed COVID-19 associated acute neurological or psychiatric complications (cases).

Genetic coupling of enhancer activity and connectivity in gene expression control.

Gene enhancers often form long-range contacts with promoters, but it remains unclear if the activity of enhancers and their chromosomal contacts are mediated by the same DNA sequences and recruited factors. Here, we study the effects of expression quantitative trait loci (eQTLs) on enhancer activity and promoter contacts in primary monocytes isolated from 34 male individuals. Using eQTL-Capture Hi-C and a Bayesian approach considering both intra- and inter-individual variation, we initially detect 19 eQTLs associated with enhancer-eGene promoter contacts, most of which also associate with enhancer accessibility and activity.

Splicing accuracy varies across human introns, tissues, age and disease.

Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we investigate splicing accuracy using RNA-sequencing data from >14k control samples and 40 human body sites, focusing on split reads partially mapping to known transcripts in annotation.

Characterizing olfactory brain responses in young infants.

Odor perception plays a critical role in early human development, but the underlying neural mechanisms are not fully understood. To investigate these, we presented appetitive and aversive odors to infants of both sexes at one month of age while recording functional magnetic resonance imaging (fMRI) and nasal airflow data. Infants slept during odor presentation to allow MRI scanning.

Workflow improvements from automated large vessel occlusion detection algorithms are dependent on care team engagement.

Background: Automated machine learning (ML)-based large vessel occlusion (LVO) detection algorithms have been shown to improve in-hospital workflow metrics including door-to-groin time (DTG). The degree to which care team engagement and interaction are required for these benefits remains incompletely characterized.

Methods: This analysis was conducted as a pre-planned post-hoc analysis of a randomized prospective clinical trial.