50 Years of the Glasgow Coma Scale: A historical perspective.

The Glasgow Coma Scale (GCS) was first published in The Lancet by Sir Graham Teasdale and Bryan Jennett 50 years ago based on their pioneering work on developing a numerical scale to describe coma in clear and reproducible terms and to avoid the confusion associated with the wide variety of descriptive terms for consciousness that were in use at the time. It's difficult to know if Teasdale and Jennett could have predicted how influential, widespread and long-lasting the GCS would become, but in retrospect it seems clear that the GCS was introduced at a perfect stage in the development of modern clinical neurosurgery and neuroscience research. The simplicity of the scale, its recognition by senior academics and the emerging radiology technologies in the 1970s heralded a new era of neuroscience and an approach to the management of not only traumatic brain injury (TBI) but other types of central nervous system disease in which consciousness was affected, such as aneurysmal subarachnoid haemorrhage and stroke.

Protocol for generating splice isoform-specific mouse mutants using CRISPR-Cas9 and a minigene splicing reporter.

Here, we present a protocol to alter the production of alternatively spliced mRNA variants, without affecting the overall gene expression, through CRISPR-Cas9-engineered genomic mutations in mice. We describe steps for designing guide RNA to direct Cas9 endonuclease to consensus splice sites, producing transgenic mice through pronuclear injection, and screening for desired mutations in cultured mammalian cells using a minigene splicing reporter. Splice isoform-specific mouse mutants provide valuable tools for genetic analyses beyond loss-of-function and transgenic alleles.

Ref-1 is overexpressed in neovascular eye disease and targetable with a novel inhibitor.

Reduction-oxidation factor-1 or apurinic/apyrimidinic endonuclease 1 (Ref-1/APE1) is a crucial redox-sensitive activator of transcription factors such as NF-κB, HIF-1α, STAT-3 and others. It could contribute to key features of ocular neovascularization including inflammation and angiogenesis; these underlie diseases like neovascular age-related macular degeneration (nAMD). We previously revealed a role for Ref-1 in the growth of ocular endothelial cells and in choroidal neovascularization (CNV).

Imagine, Discover, Inspire: Proceedings of the 4th International Conference of the Trisomy 21 Research Society.

Down syndrome (DS) or trisomy 21 (T21) is present in a significant number of children and adults around the world and is associated with cognitive and medical challenges. Through research, the T21 Research Society (T21RS), established in 2014, unites a worldwide community dedicated to understanding the impact of T21 on biological systems and improving the quality of life of people with DS across the lifespan. T21RS hosts an international conference every two years to support collaboration, dissemination, and information sharing for this goal.

A Novel RAGE Modulator Induces Soluble RAGE to Reduce BACE1 Expression in Alzheimer's Disease.

β-secretase (BACE1) is instrumental in amyloid-β (Aβ) production, with overexpression noted in Alzheimer's disease (AD) neuropathology. The interaction of Aβ with the receptor for advanced glycation endproducts (RAGE) facilitates cerebral uptake of Aβ and exacerbates its neurotoxicity and neuroinflammation, further augmenting BACE1 expression. Given the limitations of previous BACE1 inhibition efforts, the study explores reducing BACE1 expression to mitigate AD pathology.

C19orf12 gene variants causing mitochondrial membrane protein-associated neurodegeneration (MPAN).

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a rare neurodegenerative disorder characterized by spastic paraplegia, parkinsonism and psychiatric and/or behavioral symptoms caused by variants in gene encoding chromosome-19 open reading frame-12 (C19orf12). We present here seven patients from six unrelated families with detailed clinical, radiological, and genetic investigations. Childhood-onset patients predominantly had a spastic ataxic phenotype with optic atrophy, while adult-onset patients were presented with cognitive, behavioral, and parkinsonian symptoms.

Humans rationally balance detailed and temporally abstract world models.

How do people model the world's dynamics to guide mental simulation and evaluate choices? One prominent approach, the Successor Representation (SR), takes advantage of temporal abstraction of future states: by aggregating trajectory predictions over multiple timesteps, the brain can avoid the costs of iterative, multi-step mental simulation. Human behavior broadly shows signatures of such temporal abstraction, but finer-grained characterization of individuals' strategies and their dynamic adjustment remains an open question. We developed a task to measure SR usage during dynamic, trial-by-trial learning.

Reversal of neuronal tau pathology via adiponectin receptor activation.

Changes in brain mitochondrial metabolism are coincident with functional decline; however, direct links between the two have not been established. Here, we show that mitochondrial targeting via the adiponectin receptor activator AdipoRon (AR) clears neurofibrillary tangles (NFTs) and rescues neuronal tauopathy-associated defects. AR reduced levels of phospho-tau and lowered NFT burden by a mechanism involving the energy-sensing kinase AMPK and the growth-sensing kinase GSK3b.

Prevalence of anhedonia in women with deep endometriosis.

Anhedonia, characterized by diminished motivation and pleasure sensitivity, is increasingly recognized as prevalent among patients with chronic pain. Deep Endometriosis (DE), the most severe endophenotype of the disease, is commonly presented with chronic pelvic pain. This cross-sectional study reports, for the first time, the prevalence of anhedonia in a sample comprised by 212 premenopausal women with suspected DE referred to a tertiary hospital.

Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity.

Identifying cell types and brain regions critical for psychiatric disorders and brain traits is essential for targeted neurobiological research. By integrating genomic insights from genome-wide association studies with a comprehensive single-cell transcriptomic atlas of the adult human brain, we prioritized specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals the whole-brain impact of schizophrenia genetic risk, with subregions in the hippocampus and amygdala exhibiting the most significant enrichment of SNP-heritability.

Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson's disease.

Metabotropic glutamate (mGlu) receptors are candidate drug targets for therapeutic intervention in Parkinson's disease (PD). Here we focused on mGlu3, a receptor subtype involved in synaptic regulation and neuroinflammation. mGlu3 mice showed an enhanced nigro-striatal damage and microglial activation in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Profiling of pathogenic variants in Japanese patients with sarcoglycanopathy.

Background: Sarcoglycanopathies (SGPs) are limb-girdle muscular dystrophies (LGMDs) that can be classified into four types, LGMDR3, LGMDR4, LGMDR5, and LGMDR6, caused by mutations in the genes, SGCA, SGCB, SGCG, and SGCD, respectively. SGPs are relatively rare in Japan. This study aims to profile the genetic variants that cause SGPs in Japanese patients.

Antithrombin III deficiency and idiopathic intracranial hypertension: a case report.

Background: Idiopathic intracranial hypertension (IIH) is a condition where the pressure of the cerebrospinal fluid in the brain increases without a known cause. It typically affects adults but can also occur in adolescents and children, although it is less common. Numerous elements, including coagulopathy, have been documented in previous cases as potential etiological factors of IIH.

Therapeutic reduction of neurocan in murine intracerebral hemorrhage lesions promotes oligodendrogenesis and functional recovery.

Background: Intracerebral hemorrhage (ICH) causes prominent deposition of extracellular matrix molecules, particularly the chondroitin sulphate proteoglycan (CSPG) member neurocan. In tissue culture, neurocan impedes the properties of oligodendrocytes. Whether therapeutic reduction of neurocan promotes oligodendrogenesis and functional recovery in ICH is unknown.

A lack of sexual autonomy is associated with increased loneliness in young mothers.

Background: Loneliness is a significant risk factor for both mental and physical health issues, including depression and increased mortality. Loneliness is reported at higher levels during life transitions, such as the transition to motherhood. Loneliness in mothers has far-reaching detrimental impacts on both mother and child, such as an increased risk of maternal depression and child abuse.

Investigating a caregiver-assisted social skills group programme for primary and early high school-aged children with acquired brain injury or cerebral palsy: protocol for a pilot mixed-methods, two-group randomised trial of PEERS Plus.

Introduction: Reaching social milestones is an important goal of childhood. Children with acquired brain injury (ABI) and cerebral palsy (CP) frequently experience challenges with social functioning and participation. The Programme for the Education and Enrichment of Relational Skills (PEERS) is a group-based social skills programme for adolescents.

Changing the trajectories of mental health difficulties in Norfolk and Suffolk: a research-priority-setting project with patients, the public, clinicians, policymakers and other stakeholders-study protocol.

Introduction: Mental health problems are the most significant cause of disability and have high annual economic costs; hence, they are a priority for the government, service providers and policymakers. Consisting of largely coastal and rural communities, the populations of Norfolk and Suffolk, UK, have elevated burdens of mental health problems, areas with high levels of deprivation and an increasing migrant population. However, these communities are underserved by research and areas with the greatest mental health needs are not represented or engaged in research.

Cerebral venous sinus thrombosis after intrathecal administration of nusinersen.

Cerebral venous sinus thrombosis is an uncommon sequela of low intracranial pressure, which may result from a lumbar puncture (LP). We describe a case of a patient in their 40s presenting with 48 hours of persistent headache following intrathecal administration of nusinersen for spinal muscular atrophy (SMA) type 3. There were no focal neurological signs or symptoms apart from baseline symmetrical proximal limb weakness attributed to SMA.

Protein quality control machinery: regulators of condensate architecture and functionality.

Protein quality control (PQC) mechanisms including the ubiquitin (Ub)-proteasome system (UPS), autophagy, and chaperone-mediated refolding are essential to maintain protein homeostasis in cells. Recent studies show that these PQC mechanisms are further modulated by biomolecular condensates that sequester PQC components and compartmentalize reactions. Accumulating evidence points towards the PQC machinery playing a pivotal role in regulating the assembly, disassembly, and viscoelastic properties of several condensates.

Identification of potential therapeutic targets for Alzheimer's disease from the proteomes of plasma and cerebrospinal fluid in a multicenter Mendelian randomization study.

Background: Certain peripheral proteins are believed to be involved in the development of Alzheimer's disease (AD), but the roles of other new protein biomarkers are still unclear. Current treatments aim to manage symptoms, but they are not effective in stopping the progression of the disease. New drug targets are needed to prevent Alzheimer's disease.

Habituation of the biological response to repeated psychosocial stress: a systematic review and meta-analysis.

Recurrent psychosocial stress poses a significant health challenge, prompting research into mechanisms of successful adaptation. Physiological habituation, defined as decreased reactivity to repeated stressors, is pivotal in protecting the organism from allostatic load. Here, we systematically review and meta-analyze data from studies investigating the capacity of central stress systems to habituate when repeatedly exposed to a standardized psychosocial stressor, the Trier Social Stress Test (k=47).

Temporal Dynamics of Affective Scene Processing in the Healthy Adult Human Brain.

Understanding how the brain distinguishes emotional from neutral scenes is crucial for advancing brain-computer interfaces, enabling real-time emotion detection for faster, more effective responses, and improving treatments for emotional disorders like depression and anxiety. However, inconsistent research findings have arisen from differences in study settings, such as variations in the time windows, brain regions, and emotion categories examined across studies. This review sought to compile the existing literature on the timing at which the adult brain differentiates basic affective from neutral scenes in less than one second, as previous studies have consistently shown that the brain can begin recognizing emotions within just a few milliseconds.

Low-dose aspirin use in low-risk nulliparous pregnancies: a systematic review and meta-analysis of randomized controlled trials.

Objective: To assess the efficacy of low-dose aspirin in the prevention of adverse outcomes in low-risk, nulliparous singleton pregnancies.

Data Sources: PubMed, Ovid MEDLINE, Scopus, Cochrane Library, clinicaltrials.gov, and ScienceDirect were searched from their inception to August 5, 2023.

Number of subfields of the rat dorsal subiculum defined by the NOS and PCP4 immunoreactivities changes according to the different levels of observation.

The subiculum is a main output part of the hippocampal formation and important for learning and memory. According to connection studies, the distal and proximal regions of the subiculum project to the brain regions related to the spatial and emotional memories, respectively. Our previous morphological studies indicated that the ventral subiculum (vSub) consists of two regions, the distal subiculum (Sub1) and the proximal subiculum (Sub2), while the dorsal subiculum (dSub) seemed to comprise only one region (Sub1).

High-order network degree revealed shared and distinct features among schizophrenia, bipolar disorder and ADHD.

Schizophrenia (SCHZ), bipolar disorder (BD), and attention-deficit/hyperactivity disorder (ADHD) share clinical symptoms and risk genes, but the shared and distinct neural dynamic mechanisms remain inadequately understood. Degree is a fundamental and important graph measure in network neuroscience, and we here extended the degree to hierarchical levels based on eigenmodes and compared the resting-state brain networks of three disorders and healthy controls (HC). First, compared to HC, SCHZ and BD patients exhibited substantially overlapped abnormalities in brain networks, wherein BD patients displayed more significant alterations.