This paper deals with the analysis of the cognitive functions of the cerebral cortex or cortex in the evolutionary context. The triune brain model is presented given its notorious popularity in fields that are not strictly neuroscientific, and its limitations and inaccuracies are also shown. Although it is an outdated theory, this one represented the passage to a new era, because it really was the model of the movement towards understanding the brain in evolutionary terms. Next, the paper illustrates the different areas of the cortex and their functions, as well as the evolution of the brain and the cortex in vertebrates. To date, the expansion of the cortex with the amniotes was placed 300 million years ago, although recent studies place it in the lampreys more than 500 million years ago. Evolutionary changes in mammalian brain and cortex size are discussed, showing the evolution from three to six cell layers and trends in different groups of mammals. Finally, the most recent contributions in the field of research are illustrated, such as the role of neurogenesis and the evolution of the connectivity of the cortex.

Background: many studies, on for example taste-visual dissonance, have shown that the influence of the visual cortex on taste sensation is enormous. The aim of the presented work is to investigate, using fNIRS, whether a taste stimulus, in this case the taste of bitter, also causes stimulation of the visual cortex in fNIR study. Methods: 51 participants (204 examinations, 9 996 records) were examined with fNIRS, which collects signals from whole left hemisphere. Differences between the maximum and minimum changes in oxyHb concentrations (ΔoxyHb) for the areas of the brain cortex considered responsible for recording visual and gustatory signals were analyzed. Protocol I, II, III and IV – activation with distillate water, coffee with lower concentration, reference (no stimulation) and coffee with higher concentration respectively, were used. Results: We recorded high signals for teste activation on channels covered gustatory cortex, which confirms the correctness of the choice of research method. What seems important, and somewhat surprising, is the fact that we also received high signals for the channels 45-49, which cover the visual cortex. The statistical analysis does not show any statistical differences between the protocols I, II and IV (different taste activation – water, coffee A and coffee B) for specific channels. As a results of the analysis of the correlation between the subjective bitterness assessment solutions, and the signal ΔoxyHb height, it was observed that statically important correlation, although weak, occurs only for 14 and gustatory channels, only for coffee with a higher concentration. Additionally we recorded the only statistically significant difference between women and men for protocol I (water), where the ΔoxyHb signal was twice as high for women. Conclusions: In conclusion, we can clearly state that the senses of sight and taste work closely together. Moreover, this cooperation is not one-sided - not only the visual activation affects the perception of taste, but interestingly, the taste stimulus can generate a hemodynamic response - activity in the visual cortex.

Stroke constitutes a significant public health concern due to its impact on mortality and morbidity. This study investigates the utility of machine learning algorithms in predicting stroke and identifying key risk factors using data from the Suita study, comprising 7,389 participants and 53 variables. Initially, unsupervised K-prototype clustering categorized participants into risk clusters, while five supervised models including Logistic Regression (LR), Random Forest (RF), Support Vector Machine (SVM), eXtreme Gradient Boosting (XGBoost), and Light Gradient Boosted Machine (Light-GBM) were employed to predict stroke outcomes. Stroke incidence disparities among identified risk clusters using the unsupervised K-prototype clustering method are substantial, according to the findings. Supervised learning, particularly RF was a preferable option because of the higher levels of performance metrics. The Shapley Additive Explanations (SHAP) method identified age, systolic blood pressure, hypertension, estimated glomerular filtration rate, metabolic syndrome, and blood glucose level as key predictors of stroke, aligning with findings from the unsupervised clustering approach in high-risk groups. Additionally, previously unidentified risk factors such as elbow joint thickness, fructosamine, hemoglobin, and calcium level demonstrate potential for stroke prediction. In conclusion, machine learning facilitated accurate stroke risk predictions and highlighted potential biomarkers, offering a data-driven framework for risk assessment and biomarker discovery.

Telomeres, located at the ends of each chromosome play a vital role in determining cellular fate and aging. Accelerated shortening of telomeres may also result in accelerated aging and occurrence of age-related degenerative diseases. Anti-aging treatments may help in increasing the telomere length along with improving quality of life, reducing dependency for daily life activities, increasing life expectancy and reducing the risks associated with aging. In this study, we evaluated the effect of anti-aging integrative therapy in 36 individuals. The treatment included a combination of HBOT, ozone therapy, colon hydrotherapy, etc. Telomere length was used as a biomarker for objectively quantifying the outcome of the treatment. The effect of treatment was also assessed on various aging symptoms. At the end of the treatment, it was found that that 97.22% individuals showed an increase in telomere length with an average increase of 0.43 Kbp and 94.44% individuals showed reduced biological age with an average decrease of 3.8 years. These improvements were statistically significant. Improvements were also recorded in the majority of the symptoms. No major adverse events were observed. These results indicate that antiaging integrative therapy has the potential to reverse aging symptoms, cellular aging and improve quality of life.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

A central hypothesis on brain functioning is that plasticity regulates the signals transfer function by modifying the efficacy of synaptic transmission. In the cerebellum, granular layer has been shown to control the gain of signals transmitted through the mossy fiber pathway. Until now, the impact of plasticity on incoming activity patterns was analyzed by combining electrophysiological recordings in acute cerebellar slices and computational modeling, unraveling a broad spectrum of different forms of synaptic plasticity in the granular layer, often along with forms of intrinsic excitability changes. Here, we attempt to provide a brief overview of the most prominent forms of plasticity at excitatory synapses formed by mossy fibers onto principal neurons (granule cells, Golgi cells and unipolar brush cells) in the granular layer. Specifically, we will highlight current understanding of the mechanisms and their functional implications of the synaptic and intrinsic plasticity, providing valuable insights into how inputs are processed and reconfigured at the cerebellar input stage.

Microglia, the resident macrophages of the central nervous system, exhibit altered gene expression in response to various neurological conditions. This study investigates the relationship between West Nile Virus infection, and microglial senescence, focusing on the role of LGALS3BP, a protein implicated in both antiviral responses and aging. Us-ing spatial transcriptomics, RNA sequencing and flow cytometry, we characterized changes in microglial gene signatures in adult and aged mice following recovery from WNV encephalitis. Additionally, we analyzed Lgals3bp expression and generated Lgals3bp-deficient mice to assess the impact on neuroinflammation and microglial phe-notypes. Our results show that WNV-activated microglia share transcriptional signa-tures with aged microglia, including upregulation of genes involved in interferon re-sponse and inflammation. Lgals3bp was broadly expressed in the CNS and robustly up-regulated during WNV infection and aging. Lgals3bp-deficient mice exhibited reduced neuroinflammation, increased homeostatic microglial numbers, and altered T cell popu-lations without differences in virologic control or survival. This data indicates that LGALS3BP has a role in regulating neuroinflammation and microglial activation and suggest that targeting LGALS3BP might provide a potential route for mitigating neu-roinflammation-related cognitive decline in aging and post-viral infections.

The knowledge of the optical properties of biological tissues in a wide spectral range is highly important for the development of noninvasive diagnostic or treatment procedures. The absorption coefficient is one of those properties, from which various information about tissue components can be retrieved. Using transmittance and reflectance spectral measurements acquired from ex vivo rabbit brain cortex samples, allowed to calculate its optical properties in the ultraviolet to the near infrared spectral range. Melanin and lipofuscin, the two pigments that are related to the ageing of tissues and cells were identified in the cortex absorption. By subtracting the absorption of these pigments from the absorption of the brain cortex, it was possible to evaluate the true ratios for the DNA/RNA and hemoglobin bands in the cortex – 12.33 fold (at 260 nm), 12.02 fold (at 411 nm) and 4.47 fold (at 555 nm). Due to the fact that the accumulation of melanin and lipofuscin increases with the ageing of the brain tissues and are related to the degeneration of neurons and their death, further studies should be performed to evaluate the evolution of pigment accumulation in the brain to prevent the development of Alzheimer, Parkinson and stroke pathologies in the brain.

Short video addiction refers to a psychological dependency on short video applications, characterized by an intense attachment and an inability to control usage, leading to typical addiction symptoms. While its definition bears similarities to substance addiction, significant differences also exist. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), published in 2013, short video addiction has not yet been officially classified as an addiction disorder. To facilitate more in-depth and standardized research on short video addiction, it is essential to synthesize and organize existing studies on its theoretical foundations and mechanisms.

The AUC-ROC is a widespread measure to assess the performance of a binary classification model across various discrimination thresholds. Yet, it is not apt for unbalanced class problems and is misleading for early retrieval. For instance, link prediction in complex networks is an unbalanced early retrieval problem, whose goal is to offer a ranking of the nonobserved network links, prioritizing a small cohort of positive links (for which we are sure the labels are reliable) on top of a list largely populated by unlabeled links (for which the labels are uncertain). Differently from binary classification, here the evaluation focuses on how the predictor prioritizes the positive class, because the negative class does not exist and is replaced by an unlabeled class. For decades, scholars have been investigating the necessity to correct and to generalize the AUC-ROC to work for both unbalanced classification and early retrieval evaluation, this is requested in many applied domains of computational science. Here we propose the area under the magnified ROC (AUC-mROC), a new measure that adjusts the standard AUC-ROC to work for unbalanced early retrieval problems such as link prediction. Finally, we introduce the area under the generalized ROC (AUC-gROC), which unifies both AUC-mROC and AUC-ROC to provide a universal and reliable evaluation measure that can work for both classification and early retrieval problems, regardless of class proportion.This discovery represents a critical achievement, culminating in success after decades of contentious research. Its solution promises to significantly impact various domains within applied computational science.

Chip pad alignment inspection is of great importance in the industrial field. However, due to the fact that chip pads are usually small, problems such as misdetection and missed detection often occur. When applying deep learning methods for chip pad detection, it is necessary to ensure accurate detection of small target chips while meeting the requirements of lightweight detection models for industrial needs. To solve the above problems, this paper proposes a lightweight model based on improved YOLOv5s. Firstly, the feature extraction part is improved to increase the network's focus on the target. Secondly, the feature fusion layer is improved to double the resolution of the prediction head, and the context-aware network is designed to enhance the context-capture ability of key features of small targets. Finally, SIoU is adopted as the loss function to improve the speed and accuracy of the regression frame. The experimental results show that the improved YOLOv5s algorithm improves the detection accuracy by 2.3% and reduces the network parameters by 81.8% compared to the original algorithm. The improved algorithm is combined with image processing techniques to design correction methods for alignment anomalies and realize real-time alignment anomaly correction in industry.

Brain vascular health appears to be of critical importance for protection against the development of amyotrophic lateral sclerosis (ALS) as well as the slowing of disease progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in the small cerebral vessels. Impaired vascular brain health has detrimental effects on motor neurons as lowered vascular endothelial growth factor levels compromise endothelial cell formation, promoting blood-brain barrier leakage and inflammation. Increased turnover of neurovascular unit cells precedes their senescence, which, together with pericyte alterations, further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview of the pathogenesis of impaired brain vascular health in ALS and how novel magnetic resonance imaging techniques can aid its detection. In particular, we discuss vascular patterns of blood supply to the motor cortex with the number of branches from the anterior and middle cerebral arteries acting as a novel marker of resistance and resilience against downstream effects of vascular risk and events in ALS. We outline how certain interventions adapted to patient needs and capabilities have the potential to mechanistically target the brain microvasculature towards favorable motor cortex blood supply patterns. Through this strategy, we aim to guide novel approaches to ALS management and a better understanding of ALS pathophysiology.

Sparse training (ST) aims to ameliorate deep learning by replacing fully connected artificial neural networks (ANNs) with sparse or ultra-sparse ones, such as brain networks are, therefore it might benefit to borrow brain-inspired learning paradigms from complex network intelligence theory. Here, we launch the ultra-sparse advantage challenge, whose goal is to offer evidence on the extent to which ultra-sparse (around 1% connection retained) topologies can achieve any leaning advantage against fully connected. Epitopological learning is a field of network science and complex network intelligence that studies how to implement learning on complex networks by changing the shape of their connectivity structure (epitopological plasticity). One way to implement Epitopological (epi- means new) Learning is via link prediction: predicting the likelihood of non-observed links to appear in the network. Cannistraci-Hebb learning theory inspired the CH3-L3 network automata rule for link prediction which is effective for general-purpose link prediction. Here, starting from CH3-L3 we propose Epitopological Sparse Meta-deep Learning (ESML) to apply Epitopological Learning to sparse training. In empirical experiments, we find that ESML learns ANNs with ultra-sparse hyperbolic (epi-)topology in which emerges a community layer organization that is meta-deep (meaning that each layer also has an internal depth due to power-law node hierarchy). Furthermore, we discover that ESML can in many cases automatically sparse the neurons during training (arriving even to 30% neurons left in hidden layers), this process of node dynamic removal is called percolation. Starting from this network science evidence, we design Cannistraci-Hebb training (CHT), a 4-step training methodology that puts ESML at its heart. We conduct experiments on 7 datasets and 5 network structures comparing CHT to dynamic sparse training SOTA algorithms and the fully connected counterparts. The results indicate that, with a mere 1% of links retained during training, CHT surpasses fully connected networks on VGG16, GoogLeNet, ResNet50, and ResNet152. This key finding is an evidence for ultra-sparse advantage and signs a milestone in deep learning. CHT acts akin to a gradient-free oracle that adopts CH3-L3-based epitopological learning to guide the placement of new links in the ultra-sparse network topology to facilitate sparse-weight gradient learning, and this in turn reduces the convergence time of ultra-sparse training. Finally, CHT offers the first examples of parsimony dynamic sparse training because, in many datasets, it can retain network performance by percolating and significantly reducing the node network size. Our code is available at: https://github.com/biomedical-cybernetics/Cannistraci-Hebb-training.

Dynamic sparse training is an effective strategy to alleviate the training and inference demands of artificial neural networks. However, current sparse training methods face a challenge in achieving high levels of sparsity while maintaining performance comparable to that of their fully connected counterparts. The Cannistraci-Hebb training (CHT) method produces an ultra-sparse advantage compared to fully connected training in various tasks by using a gradient-free link regrowth method, which relies solely on the network topology. However, its rigid selection based on link prediction scores may lead to epitopological local minima, especially at the beginning of the training process when the network topology might be noisy and unreliable. In this article, we introduce the Cannistraci-Hebb training soft rule (CHTs), which applies a flexible approach to both the removal and regrowth of links during training, fostering a balance between exploring and exploiting network topology. Additionally, we investigate the network topology initialization using several approaches, including the bipartite scale-free and bipartite small-world network models. Empirical results show that CHTs can surpass the performance of fully connected networks with MLP architecture by using only 1% of the connections (99% sparsity) on the MNIST, EMNIST, and Fashion MNIST datasets and can provide remarkable results with only 0.1% of the links (99.9% sparsity). In some MLPs for image classification tasks, CHTs can reduce the active neuron network size to 20% of the original nodes (neurons), demonstrating a remarkable ability to generalize better than fully connected architectures, reducing the entire model size. This represents a relevant result for dynamic sparse training. Finally, we present evidence from larger network models such as Transformers, with 10% of the connections (90% sparsity), where CHTs outperform other prevalent dynamic sparse training methods in machine translation tasks.

Major depressive disorder (MDD) is a prevalent mental health condition with substantial social and economic consequences. This study focuses on the interplay between genetic and environmen-tal factors in MDD, with particular emphasis on epigenetic mechanisms such as stochastic epige-netic mutations (SEMs), epigenetic age acceleration, and epigenetic drift. We conducted a meta-analysis of DNA methylation patterns across six datasets (n=1125 MDD cases, 398 controls in whole blood; n=95 MDD cases, 96 controls in brain tissues) from the Gene Expression Omnibus. The analysis did not reveal significant global methylation differences between MDD cases and controls. However, a brain-specific probe (cg25801113) near the SHF gene consistently exhibited hypomethylation, suggesting its potential relevance to MDD. SEMs were assessed, revealing a dis-tinct burden at the gene level in MDD cases, though no significant findings emerged for epigenetic age acceleration, indicating it may not play a central role in MDD. The study also identified rare epivariations in specific genes unique to MDD cases. In blood tissue, 51 genes were associated with these unique epivariations, while 1 gene was highlighted in the brain tissue. These results un-derscore the importance of exploring rare epivariations in understanding the molecular mecha-nisms underlying MDD and offer potential targets for further investigation.

The origin of neurodegenerative diseases is linked to the abnormal folding of disease-associated proteins. The traditional amyloid hypothesis has been a focal point of research, but recent findings suggest a more complex picture. This review explores the role of physiological conformation of aggregation-prone domain (also known as prion-like low complexity domain) and multiple co-misfolded proteins in neurodegenerative diseases. We highlight the importance of targeting multi-heterotypic misfolded proteins for effective treatments and emphasize the irreversible neurodegeneration stemming from the loss of physiological folding in prion-like disease-causing proteins underscores the criticality of refolding. Additionally, we introduce the concept of ReproFold Therapeutics, a novel approach aimed at restoring the cellular prion-like folding of disease-causing proteins to rebuild normal cross-β interactomes and mitigate neurodegeneration. Baicalein, a potential drug candidate for this approach, shows promise in vitro and in animal models. Moreover, prion-like low complexity domains implicated in neurodegeneration are also associated with other disorders such as diabetes, cancers, and mental illnesses. Understanding the core pathology of neurodegenerative diseases and the broader implications of prion-like LC domains could revolutionize healthcare approaches and policies worldwide.

Molecular analysis of growing teratoma syndrome has not been extensively studied. Here, we report a 14-year-old boy with a growing mass during treatment for a mixed germ cell tumor of the pineal region. Tumor markers were negative; thus, growing teratoma syndrome was suspected. A radical resection via the occipital transtentorial approach was performed, and histopathological examination revealed a teratoma with malignant features. Methylation classifier analysis confirmed the diagnosis of teratoma, and DMRT1 loss and 12p gain were identified by copy number variation analysis, potentially elucidating the cause of growth and malignant transformation of the teratoma. The patient remains in remission after intense chemoradiation treatment as a high-risk germ cell tumor.

Regardless of the SARS-CoV-2 pandemic containment, it remains paramount to comprehensively understand its underlying mechanisms to mitigate potential future health and economic impacts, comparable to those experienced throughout the course of the pandemic. The angiotensin-converting enzyme 2 (ACE2) provide anchorage for SARS-CoV-2 binding, thus implicating that ACE and ACE2 might contribute to the variability in infection severity. This study aimed to elucidate predisposing factors influencing the disease course among people infected by SARS-CoV-2, focusing on angiotensin-converting enzyme (ACE) and ACE2 polymorphisms. Notably, despite similar demographics and comorbidities, COVID-19 patients exhibit substantial differences in prognosis. Genetic polymorphisms in ACE and ACE2 have been implicated in disease progression, prompting our investigation into their role in COVID-19 evolution. Using next-generation sequencing (NGS), we analyzed ACE and ACE2 genes in a sample group comprising six subjects infected by SARS-CoV-2. Our findings revealed a correlation between specific polymorphisms and COVID-19 outcomes. Specifically, ACE and ACE2 intronic deletions were observed in all deceased patients, suggesting a potential association with mortality. These results highlight the significance of genetic factors in shaping the clinical course of COVID-19, emphasizing the importance of further research into the impact of genetic variations on COVID-19 severity.

This study explores innovative strategies to enhance hands-on learning experiences in a Database Management Systems (DBMS) course while addressing challenges related to software installation complexities and financial barriers. The investigation focuses on an online course format catering to students majoring in information systems, healthcare administration, business administration, and marketing. Traditional software installation hurdles, especially for complex systems like Microsoft Access and MySQL, can impede students' engagement and access. To overcome these challenges, the study proposes leveraging cloud-based solutions and clientless remote desktop gateways like Apache Guacamole. Results indicate that these approaches effectively eliminate software installation obstacles, ensuring seamless access to essential tools for all students. The study underscores the importance of innovative technological solutions in promoting inclusive and impactful learning environments in higher education.

The representation of intelligence is achieved by patterns of connections among neurons in brains and machines. Brains grow continuously, such that their patterns of connections develop through activity-dependent specification with the continuing ontogenesis of individual experience. The theory of active inference proposes that the developmental organization of sentient systems reflects general processes of informatic self-evidencing, through the minimization of free energy, that may be described in information terms that are not dependent on a specific physical substrate. At a certain level of complexity, self-evidencing of living (self-organizing) information systems becomes hierarchic and reentrant, such that effective consciousness emerges as the consequence of a good regulator. These principles imply that an adequate reconstruction of the computational dynamics of an individual human brain is possible with a sufficient neuromorphic emulation.

The neurovascular niche is crucial for constant blood supply and blood-brain barrier (BBB) function and is altered in a number of different neurological conditions, making this an intensely active field of research. Brain vasculature is unique for its tight association of endothelial cells with astrocytic endfeet processes. Separation of the vascular compartment by centrifugation-based methods confirmed enrichment of astrocytic endfeet processes, making it possible to study the entire vascular niche with such methods. Several centrifugation-based separation protocols are found in the literature; however, with some constraints which limit their applicability and the scope of the studies. Here, we describe and validate a protocol for physically separating the neurovascular niche from the parenchyma, which is optimized for smaller tissue quantities. Using endothelial, neuronal and astrocyte markers, we show that quantitative Western blot-based target detection can be performed of both the vascular and parenchymal fractions using as little as a single mouse brain hemisphere. Validation of our protocol in rodent stroke models by detecting changes in serum albumin signals and astrocyte activation, i.e. increased glial fibrillary acidic protein expression, between the ipsilateral and the lesion-free contralateral hemisphere demonstrates this protocol as a new way of detecting BBB breakdown and astrogliosis, respectively.

The landscape of business intelligence (BI) is marked by rapid growth, extensive research, and practical implementations, reflecting its sustained relevance in modern business strategies. This paper delves into the dynamics of BI, particularly focusing on the interplay between maturity and agility. While BI maturity emphasizes optimization and predefined goals, BI agility prioritizes adaptability and response to change. The paper highlights the contradictions between these concepts, emphasizing the need for a balanced approach in BI strategy formulation.The role of organizational culture in fostering BI agility is explored through literature review and interviews with BI professionals. Key insights include the necessity of an open culture for effective BI utilization, clear strategic vision, decision delegation, information sharing, business-IT cooperation, and a learning-oriented mindset. These cultural factors contribute significantly to BI effectiveness and the ability to navigate dynamic business landscapes. The paper proposes pillars of agile maturity supported by an open organizational culture, including efficient communication, information integration, creative problem-solving, and close collaboration between business and IT. These pillars underscore the importance of a flexible and open mindset in navigating BI challenges and ensuring sustained value. Empirical validation and further research are suggested to deepen our understanding of the impact of organizational culture on BI agility and effectiveness.

Clinical and pre-clinical studies of neuropsychiatric (NP) disorders show altered astrocyte properties and synaptic networks. These are refined during early postnatal developmental (PND) stages. Thus, investigating early brain maturational trajectories is essential to understand NP disorders. However, animal experiments are highly time-/resource-consuming, thereby calling for alternative methodological approaches. The function of MEGF10 in astrocyte-mediated synapse elimination (pruning) is crucial to refine neuronal networks during development and adulthood. To investigate the impact of MEGF10 during PND in the rat prefrontal cortex (PFC) and its putative role in brain disorders, we established and validated an Organotypic Brain Slice Culture (OBSC) system.Using Western blot, we characterized the expression of MEGF10 and the synaptic markers synaptophysin and PSD95 in the cortex of developing pups. We then combined immunofluorescent-immunohistochemistry with Imaris-supported 3D-analysis to compare age- and sex-dependent astrocyte-mediated pruning within the PFC in pups and OBSCs. We thereby validated this system to investigate age-dependent astrocyte-mediated changes in pruning during PND. However, further optimizations are required to use OBSCs for revealing sex-dependent differences. In conclusion, OBSCs offer a valid alternative to study physiological astrocyte-mediated synaptic remodelling during PND and might be exploited to investigate pathomechanisms of brain disorders with aberrant synaptic development.

The Neurovascular Unit (NVU), comprised of glia (astrocytes, oligodendrocytes, microglia), neurons, pericytes and endothelial cells, is a dynamic interface ensuring physiological functioning of the central nervous system (CNS), that gets affected and contributes to the pathology of several neurodegenerative diseases. Neuroinflammation is a common feature of neurodegenerative diseases and is primarily related to the activation state of perivascular microglia and astrocytes, which constitute two of its major cellular components. Our studies focus on monitoring in real time the morphological changes of perivascular astrocytes and microglia, as well as their dynamic interactions with the brain vasculature, under physiological conditions and following systemic neuroinflammation triggering both microgliosis and astrogliosis. To this end, we performed 2-photon laser scanning microscopy (2P-LSM) for intravital imaging of the cortex of transgenic mice visualizing the dynamics of microglia and astroglia following neuroinflammation induced by systemic administration of the endotoxin lipopolysaccharide (LPS). Our results indicate that following neuroinflammation the end-feet of activated perivascular astrocytes lose their close proximity and physiological crosstalk with vasculature, an event that most possibly contributes to a loss of blood-brain-barrier (BBB) integrity. At the same time, microglial cells get activated with more frequent contacts of the blood vessels. These dynamic responses of perivascular astrocytes and microglial are peaking at 4 days following LPS administration, however they still persist at a lower level 8 days after LPS, revealing incomplete reversal of inflammation affecting the glial properties and interactions with the NVU.

Survivors of severe brain injury may require care in a neurointensive care unit (neuro-ICU), where the brain is vulnerable to secondary brain injury. Thus, there is a need for noninvasive, bedside, continuous cerebral blood flow monitoring approaches in the neuro-ICU. Our goal is to address this need through combined measurements of EEG and functional optical spectroscopy (EEG-Optical) instrumentation and analysis to provide a complementary fusion of data about brain activity and function. The present case demonstrates in a patient with traumatic brain injury, noninvasive cerebral blood flow transients can be recorded that correlate with gold-standard invasive measurements and with the frequency content changes in the EEG data during clinical care.

Cortex Periplocae, as a traditional Chinese herbal medicine, has been widely used for autoimmune diseases, especially rheumatoid arthritis. Due to its potential pharmaceutical values, more studies about the biological activities of Cortex Periplocae have been conducted recently. Meanwhile, the adverse reaction of Cortex Periplocae is not a negligible problem in clinic. In this article, we reviewed a series of articles and summarized the recent studies of Cortex Periplocae in the areas of phytochemistry and pharmacology. More than 100 constituents have been isolated and identified from Cortex Periplocae, including steroids, cardiac glycosides, terpenoids, and fatty acid compounds. The crude extracts of Cortex Periplocae and its active compounds exhibit various biological activities, such as cardiotonic effect, anticancer action, and anti-inflammatory effect. This paper aims to provide an overall review on the bioactive ingredients, pharmacological effect, and toxicity of this plant. Furthermore, this review suggests investigating and developing new clinical usages according to the above pharmacological effects.

Diabetes mellitus (DM) is the most common metabolic disease in humans, and its prevalence is increasing worldwide in parallel with the obesity pandemic. A lack of insulin or insulin resistance, and consequently hyperglycemia, leads to many systemic disorders, among which diabetic encephalopathy (DE) is a long-term complication of the central nervous system (CNS), characterized by cognitive impairment and motor dysfunctions. The role of oxidative stress and neuroinflammation in the pathomechanism of DE has been proven. Fractalkine (CX3CL1) has unique properties as an adhesion molecule and chemoattractant, and by acting on its only receptor, CX3CR1, it regulates the activity of microglia in physiological states and neuroinflammation. Depending on the clinical context, CX3CL1-CX3CR1 signaling may have neuroprotective effects by inhibiting the inflammatory process in microglia or, conversely, maintaining/intensifying inflammation and neurotoxicity. This review discusses the evidence supporting that the CX3CL1-CX3CR1 pair is neuroprotective and other evidence that it is neurotoxic. Interrupting the vicious cycle within neuron-microglia interactions may be a therapeutic goal in DE by limiting the inflammatory response.

The pathogenesis of Cerebral Small Vessel Disease (CSVD) is largely unknown. Endothelial disfunction has been suggested as the turning point in CSVD development. In this study we tested the effect of plasma from CSVD patients on human cerebral microvascular endothelial cells with the aim of describing the pattern of endothelial activation. Plasma samples from 3 groups of young subjects have been tested: PTs (subjects affected by early stage CSVD); CTRLs (control subjects without abnormalities at MRI scanning); BDs (blood donors). Human Brain Endothelial Cells 5i (HBEC5i) were treated with plasma and total RNA was extracted. RNAs were pooled to reduce gene expression-based variability and NGS analysis was performed. Differentially expressed genes were highlighted comparing PTs, CTRLs and BDs with HBEC5i untreated cells. No significantly altered pathway was evaluated in BD related treatment. Regulation of p38 MAPK cascade (GO:1900744) was the solely pathway altered in CTRLs related treatment. Indeed, 36 different biological processes turned out to be deregulated after PTs treatment of HBEC5i, i.e., the cytokine-mediated signaling pathway (GO:0019221). Endothelial cells activate inflammatory pathways in response to stimuli from CSVD patients’ plasma, suggesting the pathogenetic role of neuroinflammation from the early asymptomatic phases of cerebrovascular disease.

With the rapid growth of large language models (LLMs), there is increasing demand for memory and computation in LLMs. Recent efforts on post-training pruning of LLMs aim to reduce the model size and computation requirements, yet the performance is still sub-optimal. In this paper, we present a plug-and-play solution for post-training pruning of LLMs. The proposed solution has two innovative components: 1) Relative Importance and Activations (RIA), a new pruning metric that jointly considers the weight and activations efficiently on LLMs; and 2) Channel Permutation, a new approach to maximally preserve important weights under N:M sparsity. The two proposed components can be readily combined to further enhance the N:M semi-structured pruning of LLMs. Our empirical experiments show that RIA alone can already surpass all existing post-training pruning methods on prevalent LLMs, e.g., LLaMA ranging from 7B to 65B. Furthermore, N:M semi-structured pruning with channel permutation can even outperform the original LLaMA2-70B on zero-shot tasks, together with practical speed-up on specific hardware. Our code is available at: https://github.com/biomedical-cybernetics/Relative-importance-and-activation-pruning

This study examines the contribution of early executive functions (EFs) in the association between fluency in reading and arithmetic. Kindergarten children (N = 1,185) were assessed on Executive Functions skills and on reading and arithmetic fluency in Grade 1 and Grade 3. The analysis revealed that beyond the connection within each domain there is a unidirectional effect between fluency measures, with Grade 1 reading fluency significantly influencing the development of arithmetic fluency in Grade 3. Furthermore, the findings indicate that kindergarten EFs significantly contribute to arithmetic fluency at both time points and to reading fluency in the first grade. Early EF skills also emerged as a mediator of associations between fluency performance in reading and arithmetic, suggesting that the influence of EFs extends beyond individual academic domains. These findings have implications for understanding the cognitive mechanisms that underlie the relations between these academic skills.

Abstract Cerebral microbleed(s) (CMBs) are increasingly being viewed not only as a marker for cerebral small vessel disease (SVD) but also as having an increased risk for the development of stroke (hemorrhagic/ischemic) and aging-related dementia. Recently, brain endothelial cell activation and dysfunction and blood-brain barrier dysfunction and/or disruption have been shown to be associated with SVD, enlarged perivascular spaces, and the development and evolution of CMBs. CMBs are a known disorder of cerebral microvessels that are visualized as 3-5mm, smooth, round or oval, and hypointense (black) lesions seen only on T2*-weighted gradient recall echo or susceptibility-weighted sequences on MRI images. CMBs (a global problem) are known to occur with high prevalence in community-dwelling older individuals. Since our current global population is the oldest recorded in history and only expected to continue to grow, we can only expect the health care burdens associated with CMBs to also grow. CMBs should raise a red flag regarding the increased risk of large symptomatic neurologic intracerebral hemorrhages. Importantly, CMBs are also currently regarded as markers of diffuse vascular and neurodegenerative brain damage. Thus, it is essential that we try to learn as much as we can about their development, evolution, and their relation to impaired cognition, dementia, and neurodegeneration.

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of DR. It mainly includes hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, which plays a key role in the pathological changes of DR.High-sucrose diets(HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of AGEs and VEGF, causes plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. Early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes, and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss, and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies we give, patients can change their poor eating habits timely, avoid the retinopathy that can be avoided theoretically, and obtain a excellent outcome.

Background: This study was designed to adapt the Delis-Kaplan Executive System (D-KEFS) version of the Color-Word Interference (CWIT) and Trail making Tests (TMT) in Greek adult population from 20 to 49 years old, since it is of research as well as clinical importance to detect executive functions’ impairment in young adults with neurological or/and psychiatric conditions. Aims: Norms for the Greek adult population have been calculated to be available for neuropsychologists and health professionals who work in relevant settings. Methods: The study sample consisted of 101 healthy adults (41% male and 60% female), aged 20 to 49 years (M=32.16, SD=11.57) with education from 12 to 19 years of schooling (M=14.51, SD= .89). Pearson correlation test as well as chi square test were conducted to examine potential associations between gender, age, education, and participants’ performance. Afterwards, we calculated normative data using raw scores and transformed them to percentile scores. Finally, Greek norms were compared to the original raw scores, which were transformed in scaled scores by Delis et al. (2001). Results: The findings showed that age was the only variable which affected CWIT, whereas level of education as well as age were predictive factors for most TMT conditions, except for the visual scanning test (Condition 1). Gender did not affect both tests. Finally, D-KEFS norms for CWIT and TMT are available for Greek adult population to help clinicians detect executive functions’ deficits and therefore adjust tailored therapeutic strategies. Additionally, it is of great importance to use these tests for research purposes. Conclusion: Given that executive functions are assumed as high- level skills, which are highly related to everyday functionality, adapted tests contribute not only to assess the progression of any existing neurological as well as psychiatric disorders, but they can also be used to evaluate patients’ ability to live independently, as well as their access to work.

As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”

Complexity science studies physical phenomena that cannot be explained by the mere analysis of the single units of a system but requires to account for their interactions. A feature of complexity in connected systems is the emergence of mesoscale patterns in a geometric space, such as groupings in bird flocks. These patterns are formed by groups of points that tend to separate from each other, creating mesoscale structures. When multidimensional data or complex networks are embedded in a geometric space, some mesoscale patterns can appear respectively as clusters or communities, and their geometric separability is a feature according to which the performance of an algorithm for network embedding can be evaluated. Here, we introduce a framework for the definition and measure of the geometric separability (linear and nonlinear) of mesoscale patterns by solving the travelling salesman problem (TSP), and we offer experimental evidence on embedding and visualization of multidimensional data or complex networks, which are generated artificially or are derived from real complex systems. For the first time in literature the TSP’s solution is used to define a criterion of nonlinear separability of points in a geometric space, hence redefining the separability problem in terms of the travelling salesman problem is an innovation which impacts both computer science and complexity theory.

Traumatic brain injury represents one of the main health problems in developed countries. Growth Hormone (GH) and rehabilitation have been claimed to significantly contribute to the recovery of lost motor function after acquired brain injury, but the mechanisms by which this occurs are not well understood. In this work, we have investigated cell proliferation in the piriform cortex (PC) of adult rats with ablation of the frontal motor cortex treated with GH and rehabilitation, in order to evaluate if this region of the brain, related to the sense of smell, could be involved in benefits of GH treatment. Male rats were either ablated the frontal motor cortex in the dominant hemisphere or sham-operated and treated with GH or vehicle at 35 days post-injury (dpi) for five days. At 36 dpi, all rats received daily injections of bromodeoxyuridine (BrdU) for 4 days. We assessed motor function through the paw-reaching-for-food task. GH treatment and rehabilitation at 35 dpi significantly improved the motor deficit caused by the injury and promoted an increase of cell proliferation in the PC ipsilateral to the injury, which could be involved in the improvement observed. Cortical ablation promoted greater number of BrdU+ cells in the piriform cortex that was maintained long-term, which could be involved in the compensatory mechanisms of the brain after injury.

: Background: Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. Methods: Twenty-five healthy adults (25.8±3.3 years, 15 female) were analyzed in a randomized, controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO₂] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO₂ were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. Results: NH decreased SpO₂ (p<.001, η_p²=.747) and increased heart rate (p=.006, η_p²=.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p <.001, η_p²=.581) and plasma (p <.001, η_p²=.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p=.018) in serum and after 30 min (p=.040) and 90 min (p=.005) in plasma. There was no significant BDNF decline under NH. 24 h Follow-up examination showed a significant decline of serum BDNF, both after NH and NOR. Conclusion: Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

Cerebral palsy (CP) presents challenges in movement and posture due to central nervous system damage, necessitating lifelong management. The COVID-19 pandemic has limited access to traditional treatments, increasing demand for home-based therapies and digital resources. This study analyzed the qualitative and quantitative aspects of YouTube videos focusing on CP therapy for children. In total, 95 videos were evaluated for content quality, therapeutic program efficacy, and popularity. Most videos were uploaded by health professionals. Neuromotor therapy types varied, with Bobath therapy being prominent. The quality assessments revealed moderate to high reliability in video content; nonetheless, shortcomings in addressing uncertainties were observed. Therapeutic programs often lack crucial details such as intensity and outcome assessment methods. No significant differences were found between professional and non-professional uploads. Classifiable videos based on exercise type, in contrast to the types of neuromotor therapy, exhibited better therapeutic quality than unclassified ones. Notably, video popularity did not correlate with quality. This study underscores the need for improved educational content on YouTube, particularly in providing comprehensive therapeutic information for CP management. Further refinement of evaluation tools is essential for assessing the rationale behind neuromotor therapeutic modalities for children with CP.

To elucidate mesenchymal stromal cells (MSC)-tumor intricate and ambiguous interactions, the reliable cell labeling and tracking techniques are imperative. Traditional methods of cell labelling have limitations mostly relevant to need for genetic modification what demands the exploration for alternative strategies. Here, we propose using fluorescent photoconvertible microcapsules containing Rhodamine B (RhB) to study mMSC migration in brain tumors. These 3 μm sized microcapsules are readily internalised by cells and undergo photoconversion under 561 nm laser exposure with fluorescence blue shift on demand. Optimal photoconversion was achieved with a laser irradiation duration of 0.4 ms, which provide a maximal brightness of photoconverted label without an excessive laser exposure on cells. Capsules modified with polyallylamine hydrochloride demonstrated the best potential for intracellular uptake without significantly affecting cell viability, motility, or proliferation. The optimal ratio of 20 capsules per mMSC was determined for labeling. Moreover, migration of individual mMSCs within 2D and 3D glioblastoma cell (EPNT-5) colonies over 2 days and in vivo tumor settings over 7 days was tracked. Our study unveils a robust platform for investigating MSC-tumor dynamics, offering insights into therapeutic strategies. Photoconvertible microcapsules could also become an indispensable tool for studying complex fundamental processes of cell-cell interactions for a wide range of problems in biology and medicine.

Arguably the most important parameter in treating cognitive decline associated with Alzheimer’s disease is the length of time in which improvement, if achieved at all, is sustained. However, monotherapies such as donepezil and memantine are associated with a more rapid decline than no treatment in patients over multi-year follow-ups {Kennedy, 2018 #535}. Furthermore, anti-amyloid antibody treatment, which at best simply slows decline, is associated with accelerated cerebral atrophy [2], resulting in earlier dementia-associated brain volumes for those treated at the MCI stage than untreated patients. In contrast, a precision medicine approach, in which the multiple potential drivers of cognitive decline are identified for each patient and then targeted with a personalized protocol (such as ReCODE), has led to documented improvement in patients with cognitive decline [3]; [4]; [5], but long-term follow-up (>5 years) has not been reported previously. Therefore, we report here sustained cognitive improvement, in some cases for over a decade, in patients treated with a precision medicine protocol—something that has not been reported in patients treated with anti-cholinesterase, glutamate receptor inhibitory, anti-amyloid, or other therapeutic methods. These case studies warrant long-term cohort studies to determine how frequently such sustained cognitive improvements occur in patients treated with precision medicine protocols.

(1) Background The SKT is a short cognitive performance test designed to assess impairments in memory and cognitive abilities such as attention and speed of information processing. In 2019, new regression-based norms for the English version of the SKT were calculated applying data from older cognitively healthy adults living in the US, Ireland and Australia (the norming sample) The study has two aims: to establish valid cut-offs for distinguishing between no cognitive impairment, mild cognitive impairment (MCI) and dementia (1), and to cross-validate the new norms for detecting MCI and dementia (2) in a community sample of older adults with clinical diagnoses; (2)Methods: The validation sample included 142 older adults (mean age=87.7, SD=3.55) from the Sydney Memory and Aging Study (MAS Study). Participants were classified as having normal cognition, MCI, or dementia through a consensus diagnosis as well as by the SKT; (3)Results: The sensitivity of the SKT for the differentiation of cognitive impairment (MCI or dementia) from normal cognition was 80.6%. The convergence between the SKT and the consensus diagnoses was 60.1% for all three diagnostic groups. The correlation between the SKT and the Addenbrooke’s Cognitive Examination III (ACE-III), a well validated measure of cognitive ability in older adults, was r = 0.3;. (4) Conclusions: In sum, it can be stated that the SKT is a valid tool for detecting early stages of cognitive impairment, performing very well in discriminating between no cognitive impairment and cognitive impairment (MCI or dementia).

Early detection of neurological conditions is critical for timely diagnosis and treatment. Identifying cellular-level changes is essential for implementing therapeutic interventions prior to symptomatic disease onset. However, monitoring brain tissue directly through biopsies is invasive and high-risk. Bodily fluids such as blood or cerebrospinal fluid contain information in many forms, including proteins and nucleic acids. Particularly, cell-free DNA (cfDNA) has potential as a versatile neurological biomarker. Yet, our knowledge of cfDNA released by brain tissue and how cfDNA changes in response to deleterious events within the brain is incomplete. Mapping changes in cfDNA to specific cellular events is difficult in vivo, where many tissues contribute to circulating cfDNA. Organoids are tractable systems for examining specific changes consistently in a human background. However, few studies have investigated cfDNA released from organoids. Here, we examined cfDNA isolated from cerebral organoids. We found that cerebral organoids release quantities of cfDNA sufficient for downstream analysis with droplet-digital PCR and whole-genome sequencing. Further, gene ontology analysis of genes aligning with sequenced cfDNA fragments revealed association with terms related to neurodevelopment and autism spectrum disorder. We conclude that cerebral organoids hold promise as tools for the discovery of cfDNA biomarkers related to neurodevelopmental and neurological disorders.

Iron (Fe) is co-factor for enzymes of the developing brain necessitating sufficient supply. We investigated the effects of administering ferric derisomaltose/Fe isomaltoside (FDI) subcutaneously to Fe deficient (ID) pregnant rats on cerebral and hepatic concentrations of essential metals and gene expression of ferroportin and hepcidin. Pregnant rats subjected to ID were injected with FDI on the day of mating (E0), 14 days into pregnancy (E14), or the day of birth (Postnatal (P0)). The efficacy was evaluated by determination of cerebral and hepatic Fe in pups on P0 and as adults on P70, and the concentration of copper (Cu) and zinc (Zn). Females fed an ID diet (5.2 mg/kg Fe) had offspring with significantly lower cerebral and hepatic Fe compared to female controls fed a standard diet (158 mg/kg Fe). Cerebral Cu increased irrespective of supplying a standard diet or administering FDI combined with the standard diet. Hepatic hepcidin was significantly lower following ID, whereas cerebral hepcidin was virtually undetectable in all experimental groups. In conclusion, administering FDI subcutaneously to ID pregnant rats on EO normalizes cerebral Fe in the fetus, but when applied at later gestational ages, additional Fe to the offspring is needed to normalize cerebral and hepatic Fe.

(1) Background: Alzheimer’s disease (AD) presents a significant challenge in terms of discovering novel diagnostic methods and therapies. Previous research has shed light on the neuroprotective properties of Apelin-13 in neurodegenerative disorders. However, elucidating the mechanism underlying its efficacy in combating AD-related nerve injury is imperative. In this study, we aimed to investigate the mechanism of action of Apelin-13 in an in vivo model of AD induced by streptozocin (STZ); (2) Methods: We utilized an STZ-induced nerve injury model of AD in mice to investigate the effects of Apelin-13 administration. The Apelin-13 was administered intranasally, and cognitive impairment was assessed using standardized behavioral tests. The main methods included behavioral assessment, histological analysis, and biochemical assays to evaluate synaptic plasticity and oxidative stress signaling pathways; (3) Results: Our findings indicate that intranasal administration of Apelin-13 ameliorated cognitive impairment in the STZ-induced AD model. Furthermore, we observed that this effect was potentially mediated through the enhancement of synaptic plasticity and attenuation of oxidative stress signaling pathways; (4) Conclusions: The results of this study suggest that intranasal administration of Apelin-13 holds promise as a therapeutic strategy for preventing neurodegenerative diseases such as AD. By improving synaptic plasticity and mitigating oxidative stress, Apelin-13 may offer a novel approach to neuroprotection in AD and related conditions.

Hypnotizability is a cognitive trait associated with differences in the brachial artery flow-mediated dilatation of individuals with high hypnotizability (highs) and low hypnotizability scores (lows). The study investigated possible hypnotizability-related cerebrovascular differences. Among 24 healthy volunteers the Stanford Hypnotic Susceptibility Scale Form A, identified 13 medium-to-lows (med-lows), 11 medium-to-highs (med-highs), 1 medium hypnotizable. Hypnotizability did not influence the significant changes produced by the trail making task (TMT), mental arithmetic task (MAT), hyperventilation (HVT) and rebreathing (RBT) on Heart rate (HR), arterial blood pressure (ABP) and partial pressure of end-tidal CO2 (PETCO2) and oxygenation (TOI); but moderated the correlations between the changes occurring during tasks with respect to basal conditions (Δ) in ABP and PETCO2 with MCAv. In HVT, med-lows exhibited a significant correlation between ΔMCAv and ΔPETCO2, med-highs showed a significant correlation between ΔABP and ΔMCAv; a significant correlation between ΔTHI and ΔTOI was observed in medium lows. Cerebrovascular reactivity (CVR) and conductance (ΔCVCi) were significantly correlated with ΔMCAv in med-lows during HVT and RBT. Findings represent the first assessment of hypnotizability-related differences in the mechanisms controlling the middle cerebral artery flow velocity, cerebrovascular reactivity and conductance in response to hyperventilation and rebreathing.

This study aimed to investigate the relationship between sleep duration, dementia severity, age, and ANS regulation. This cross-sectional pilot study included 27 older patients with probable Alzheimer’s disease, hospitalized at a psychiatric center. We measured heart rate variability to assess ANS regulation at night, evaluated dementia severity using the Clinical Dementia Rating scale, and obtained sleep duration data from sleep diaries maintained by psychiatric nurses. The data were analyzed using repeated-measures generalized linear models with age, sex, dementia severity, and medication (antipsychotics) as covariates. A sleep duration of 7–8 h per night was associated with better ANS regulation than other sleep durations, as indicated by sympathovagal balance (p = 0.005). ANS dysregulation was characterized by a 20.7% increase in sympathetic nervous system activity and a 14.8% decrease in parasympathetic nervous system (PSNS) activity. We found a significant correlation between dementia severity and PSNS activity (p = 0.04) and observed an inverted U-shaped association between sleep duration and ANS regulation. This pilot study demonstrated that a sleep duration of 7–8 h per night may be critical in maintaining optimal ANS regulation. Bidirectional associations between sleep duration, inadequate sleep duration, aging, and ANS regulation warrant further investigation.

Introduction: Migraine is a highly disabling neurological condition with substantial variability in its clinical presentation. This study aimed to explore the influence of familial transmission of comorbid medical conditions on the phenotype of chronic and episodic migraine. Methods: A total of 500 patients who presented to a private tertiary headache clinic were categorized into episodic and chronic migraine groups based on the International Classification of Headache Disorders-3 criteria. Data on demographics, clinical symptoms, and familial medical history were collected. Statistical analysis included chi-square and independent sample t-tests to evaluate the impact of familial comorbidities on migraine phenotypes. Results: Of the participants, 63% were diagnosed with episodic migraine and 37% with chronic migraine. Significant findings included higher rates of medication overuse (63.31%) and allodynia (58.82%) in patients with chronic migraine. Notably, patients with a maternal history of hypercholesterolemia showed a higher prevalence of chronic migraine (78.6%), whereas those with both parents affected tended to have episodic migraine. Educational levels are inversely correlated with the prevalence of chronic migraine, suggesting a socioeconomic influence on migraine chronification. Discussion: This study highlights significant associations between familial health conditions and migraine phenotypes. The findings suggest that the maternal transmission of comorbidities, particularly hypercholesterolemia, may influence the development of chronic migraine. These results underscore the importance of considering familial medical history in the management and understanding of migraine.

This review explores the nuanced decision-making surrounding postoperative radiotherapy for diffuse low-grade glioma (DLGG) patients, emphasizing the need for personalized treatment to balance the benefits of tumor control with the risks of long-term side effects. Radiotherapy is a cornerstone of DLGG treatment, offering significant improvements in progression-free survival, but its potential for cognitive decline and vascular lesions necessitates careful consideration of individual patient factors. The review delves into the complexities of radiotherapy timing, revealing that while early radiotherapy enhances progression-free survival, it does not significantly impact overall survival and may lead to earlier onset of cognitive decline. Conversely, delayed radiotherapy may mitigate cognitive decline but may result in shorter progression-free survival and the onset of neurological symptoms. The review advocates for a patient-centered approach, emphasizing the importance of weighing individual risks and benefits, and highlights the potential of artificial intelligence in predicting cognitive decline and the need to revisit previous research findings in light of the 2021 WHO (World Health Organization) classification update, underscoring the evolving nature of DLGG treatment and the ongoing quest for optimal therapeutic strategies.

Intraprocedural rupture (IPR) is a severe complication of coil embolization (CE) for intracranial aneurysms, yet the clinical and hemodynamic features of rupture risk areas remain unclear. From January 2013 to December 2023, 435 saccular cerebral aneurysms (316 unruptured, 119 ruptured) underwent CE at our institution. Included were cases where extravasation or coil protrusion occurred during CE. The rupture point was determined from postoperative data, and computational fluid dynamics (CFD) analysis was conducted to assess hemodynamic features. IPR occurred in six aneurysms (1.3%; three ruptured, three unruptured; dome size: 4.7±1.8 mm, D/N: 1.5±0.5, locations: four internal carotid artery [ICA], one anterior cerebral artery, one middle cerebral artery). ICA aneurysms were treated using adjunctive techniques (three balloon-assisted, one stent-assisted). Two aneurysms (M1M2 and A1) were treated simply, yet had relatively small and misaligned domes. CFD analysis identified the rupture point as a flow impingement zone with maximum pressure (Pmax) in five aneurysms (83.3%). Time-averaged wall shear stress (WSS) was locally reduced around this area (1.3±0.7 [Pa]). Hemodynamically unstable areas indicated fragile, thin walls with rupture risk. Microcatheter insertion along the inflow zone, directed towards the caution area, was practiced. The presence of a flow impingement zone with Pmax and low WSS suggests potential aneurysm rupture in CE, particularly with adjunctive techniques. Small aneurysms, especially those with axial misalignment, warrant careful consideration due to the risk of excessive flow impact stress on the aneurysm wall.

The blood-brain barrier (BBB) acts as a structural and functional barrier for brain homeostasis. This review highlights the pathological contribution of BBB dysfunction to neuroimmunological diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), autoimmune encephalitis (AE) and paraneoplastic neurological syndrome (PNS). The transmigration of massive lymphocytes across the BBB caused by the activation of cell adhesion molecules is involved in the early phase of MS, and dysfunction of the cortical BBB is associated with the atrophy of gray matter in the late phase of MS. In the onset of NMOSD, increased permeability of the BBB causes the entry of circulating AQP4 autoantibodies into the central nervous system (CNS). Recent reports have shown the importance of glucose-regulated protein (GRP) autoantibodies as BBB-reactive autoantibodies in NMOSD, inducing antibody-mediated BBB dysfunction. BBB breakdown has also been observed in MOGAD, NPSLE, and AE with anti-NMDAR antibodies. Our recent report demonstrated the presence of GRP78 autoantibodies in patients with MOGAD and the molecular mechanism responsible for GRP78 autoantibody-mediated BBB impairment. Disruption of the BBB may explain the symptoms in the brain and cerebellum in the development of PNS, as it induces the entry of pathogenic autoantibodies or lymphocytes into the CNS by autoimmunity against tumors in the periphery. GRP78 autoantibodies were detected in paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome and were associated with cerebellar ataxia with anti-P/Q type voltage-gated calcium channel antibodies. This review reports that therapies affecting the BBB that are currently available for disease-modifying therapies for neuroimmunological diseases have the potential to prevent BBB damage.

(1) Background: Central nervous system (CNS) development is characterized by dynamic changes in cell proliferation and differentiation. Key regulators of these transitions are the transcription factors such as SOX2 and SOX9. SOX2 is involved in the maintenance of progenitor cell state and neural stem cell multipotency, while SOX9, expressed in neurogenic niches, plays an important role in neuron/glia switch with predominant expression in astrocytes in the adult brain. (2) Methods: To validate SOX2 and SOX9 expression pattern in dissociated primary neuronal cultures derived from opossum (Monodelphis domestica), we used immunohistochemistry (IHC) and the isotropic fractionator method on fixed cortical tissue from comparable postnatal ages; (3) Results: Neurons positive for both neuronal (NeuN or TUJ1) and stem cell (SOX2) markers were identified and their presence was confirmed with all methods and postnatal age groups (P4-6, P6-18 and P30) analyzed. SOX9 showed exclusive staining in non-neuronal cells, and it was coexpressed with SOX2. (4) Conclusions: The persistence of SOX2 expression in developing cortical neurons of M. domestica during first post-natal month implies the functional role of SOX2 during neuronal differentiation and maturation, which was not previously reported in opossums.

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without changing the saturation of percutaneous oxygen. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptive area of respiration (the postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores.

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

Dextro-transposition of the great arteries (D-TGA) is a critical congenital heart defect that can impact neurodevelopment due to cerebral perfusion and oxygenation disorders. Materials and Methods: In a retrospective study conducted at a tertiary center between 2016 and 2023, we investigated the early effects of Prostaglandin E1 (PGE1) administration and balloon atrial septostomy (BAS) on cerebral blood flow and oxygenation in inborn neonates with D-TGA. Cerebral Doppler Ultrasound in the anterior cerebral artery (ACA) was performed to assess resistive index (RI), Peak Systolic Velocity (PSV), and End-Diastolic Velocity (EVD) before PGE1, before the BAS procedure and 24 hours after birth. Cerebral regional saturations of oxygen (crSO2) and cerebral fractional tissue oxygen extraction (cFTOE) were evaluated. D-TGA patients were divided into the PGE1 group and the PGE1+BAS group. Age-matched healthy controls were used for comparison. Results: All 83 D-TGA newborns received PGE1 within two hours after delivery, of whom 46 (55.42%) underwent BAS. 77 newborns composed the control group. PGE1 administration increased crSO2 from 47% to 50% in the PGE1 group but lower than in controls at 24 hours of life, while cFTOE remained elevated. The RI increased 24 hours after delivery (0.718 vs. 0.769; p=0.000002) due to decreased EDV (10.71 vs. 8.74; p&lt;0.0001) following PGE1 treatment. The BAS procedure resulted in a significant increase in crSO2 from 42% to 51% at 24 hours of life in the PGE1+BAS group. Doppler parameters exhibited a similar trend as observed in the PGE1 group. Conclusion: PGE1 treatment and BAS are lifesaving interventions that may improve cerebral perfusion and oxygenation in newborns with D-TGA during the transition period.

The nature of the interaction between Th17 cells and the blood-brain barrier (BBB) is critical for the development of autoimmune inflammation in the central nervous system (CNS). TNF-a or IL-17 stimulation is known to enhance the adherence of Th17 cells to the brain endothelium. The brain endothelial cells (bEnd.3) express VCAM-1, the receptor responsible for inflammatory cell adhesion, which binds VLA-4 on migrating effector lymphocytes at the early stage of brain inflammation. The present study examines the effect of the pro-inflammatory cytokines TNF-a and IL-17 on the adherence of Th17 cells to bEnd.3 The bEnd.3 cells were found to increase production of CCL2 and CXCL1 after stimulation by pro-inflammatory cytokines, while CCL2, CCL5, CCL20 and IL17 induced Th17 cell migration through a bEnd.3 monolayer. This interaction between Th17 cells and the brain endothelium appears to be mediated by VCAM-1 and some chemotactic cytokines. This observation may suggest potential therapeutic targets for the prevention of autoimmune neuroinflammation development in the CNS.

In recent years, advancements in brain science and neuroscience have significantly influenced the field of computer science, particularly in the domain of reinforcement learning (RL). Drawing insights from neurobiology and neuropsychology, researchers have leveraged these findings to develop novel mechanisms for understanding intelligent decision-making processes in the brain. Concurrently, the emergence of quantum computing has opened new frontiers in artificial intelligence, leading to the development of quantum machine learning (QML). This study introduces a novel model that integrates Quantum Spiking Neural Networks (QSNN) and Quantum Long Short-Term Memory (QLSTM) architectures, inspired by the complex workings of the human brain. Specifically designed for reinforcement learning tasks in energy-efficient environments, our approach progresses through two distinct stages mirroring sensory and memory systems. In the initial stage, analogous to the brain’s hypothalamus, low-level information is extracted to emulate sensory data processing patterns. Subsequently, resembling the hippocampus, this information is processed at a higher level, capturing and memorizing correlated patterns. We conduct a comparative analysis of our model against existing quantum models such as Quantum Neural Networks and their classical counterparts, elucidating its unique contributions. Through empirical results, we aim to underscore the effectiveness of our approach in optimizing energy consumption in practical scenarios.

A statistical analysis of semantic memory should reflect the complex, multifactorial structure of the relations among its items. Still, a dominant paradigm in the study of semantic memory has been the idea that the mental representation of concepts is structured along a simple branching tree spanned by superordinate and subordinate categories. We propose a generative model of item representation with correlations that overcomes the limitations of a tree structure. The items are generated through "factors" that represent semantic features or real-world attributes. The correlation between items has its source in the extent to which items share such factors and the strength of such factors: if many factors are balanced, correlations are overall low; whereas if a few factors dominate, they become strong. Our model allows for correlations that are neither trivial nor hierarchical, but may reproduce the general spectrum of correlations present in a data-set of nouns. We provide an estimate of the number of concepts that can be stored and retrieved by a large-scale cortical network, the Potts network, which is perhaps approximately 10⁷ with human cortical parameters. When this storage capacity is exceeded, however, retrieval fails completely only for balanced factors; above a critical degree of imbalance, a phase transition leads to a regime where the network still extracts considerable information about the cued item, even if not recovering its detailed representation: partial categorization seems to emerge spontaneously as a consequence of the dominance of particular factors, rather than being imposed ad hoc. We argue this to be a relevant model of semantic memory resilience in Tulving’s remember/know paradigms.

In the brain, astrocytes regulate shape and functions of the synaptic and vascular compartments through a variety of released factors and membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to the onset of severe pathologies. Clinical and pre-clinical studies show alterations in astrocyte cell number, morphology, molecular makeup and astrocyte-dependent processes in different affected brain regions in neurodevelopmental (ND) and neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate and mature during the critical period of early postnatal brain development, a time window of elevated glia-dependent regulation of a proper balance between synapse formation/elimination, which is pivotal in refining synaptic connectivity. Therefore, any intrinsic and/or extrinsic factors altering these processes during the critical period may result in an aberrant synaptic remodelling and onset of mental disorders. The peculiar bridging position of astrocytes between synaptic and vascular compartments further allows them to “compute” the brain state and consequently secrete factors in the bloodstream, which may serve as diagnostic biomarkers of distinct healthy or disease conditions.Here, we collect recent advancements regarding astrogenesis and astrocyte-mediated regulation of neuronal network remodelling during early postnatal critical periods of brain development, focusing on synapse elimination. We then propose alternative hypotheses for an involvement of aberrancies in these processes in the onset of ND and NP disorders. In light of the well-known differential prevalence of certain brain disorders between males and females, we also discuss putative sex-dependent influences on these neurodevelopmental events.From a translational perspective, understanding age- and sex-dependent astrocyte-specific molecular and functional changes may help to identify biomarkers of distinct cellular (dys)functions in health and disease, favouring the development of diagnostic tools or the selection of tailored treatment options for male/female patients.

The combined use of lasmiditan and triptan is unexplored in medical literature. This study aimed to investigate whether the intake of lasmiditan following triptan improves migraine pain. Following triptan intake, if headache relief was less than 50% at 1 hour, patients took 50 mg lasmiditan within 2 hours of migraine onset. Patients recorded headache intensity and adverse events(AEs) caused by lasmiditan at 1, 2, and 4 hours after intake of additional 50 mg of lasmiditan. A significant reduction in pain scale was observed post 50 mg lasmiditan intake (p &lt; 0.001, t-test). Pain relief was reported for 32 migraine attacks (80%) at 1 hour after additional lasmiditan intake. Although AEs were observed in 63% of the patients who took an additional lasmiditan, most were mild and resolved 1 hour after lasmiditan intake. Our study revealed the significant headache reliefs provided by an additional lasmiditan for patients who did not achieve satisfactory results following initial triptan intake for treating migraine. The AEs associated with this treatment strategy were mild and lasted for a short term. This study suggested that the combination of triptan and lasmiditan is promising for the treatment of migraine and should be studied in a randomized placebo-controlled trial.

Until recently, no disease-specific health-related quality of life (HRQoL) instrument existed for pediatric traumatic brain injury (TBI). In this revalidation study, the psychometric properties and the validity of the final German version of the 35-item QOLIBRI-KID/ADO questionnaire were examined in 300 children and adolescents. It is the first self-reported TBI-specific instrument for measuring pediatric HRQoL in individuals aged 8–17 years. The six-factor model fits the data adequately. Internal consistencies were excellent for the total score and satisfactory to excellent for the scale scores. Intraclass correlations indicated good test-retest reliability. Construct validity was supported by overlaps between the QOLBRI-KID/ADO and the PedsQL, which measures generic HRQoL. Discriminant validity indicated that HRQoL was significantly lower in older children and girls, and in those with anxiety, depression, and post-concussion symptoms than in comparison groups, replicating the results of the questionnaire’s first development study. Our results suggest that the QOLIBRI-KID/ADO is a valid and reliable multidimensional instrument for assessing disease-specific HRQoL after pediatric TBI in clinical and research settings, which can additionally be used across the lifespan in combination with the adult version. This may help to improve care, treatment, daily functioning and HRQoL after TBI.

Introduction Sepsis-associated encephalopathy (SAE) is common in sepsis and is linked to high mortality and impaired neurologic outcome. Brain ultrasonography (US), including transcranial Doppler (TCD) and transcranial color-coded duplex sonography (TCCS), is a non-invasive tool for cerebral monitoring and might be useful in sepsis. The aims of this review are: 1) to explore whether brain perfusion is altered in sepsis, 2) to determine the role of brain US in guiding resuscitation, and 3) its ability to predict neurological outcomes in septic patients. Materials and methods This scoping review adhered to the PRISMA-ScR protocol and JBI methodology. A comprehensive literature search was conducted across MEDLINE, Scopus, and Web of Science. The review included studies on adults with sepsis or septic shock in the ICU. Randomised controlled trials, clinical trials, observational studies and systematic reviews were included. All the data related to the review's key questions were extracted and charted independently by two authors. Results 625 articles were screened, and 34 were ultimately included after application of exclusion criteria. 85% of the studies were observational 15% were systematic reviews with or without meta-analysis. The studies primarily focused on cerebral blood flow (CBF) alterations in sepsis, reporting variable results. Findings showed variable cerebral autoregulation (CAR) impairment, with higher incidence in the early stages of sepsis and associations with poor neurological outcomes. However, while alterations in CAR and CBF are common in septic patients, their impact on neurological outcomes and mortality is not clear. Regarding resuscitation, only a paucity of studies were found and no conclusions can be drawn. Conclusions The current body of evidence has a poor grade, but it is possible to say that brain US can identify cerebral perfusions alterations. Its usage during resuscitation is feasible and warrants further investigations. Use of brain US during resuscitation and for prediction of outcome is not currently supported by evidence. Further studies on brain perfusion, acquisition of 2D images of parenchyma (TCCS) and application of a multimodal brain monitoring might be useful in these contexts.

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammation, demyelination, and neurodegeneration within the central nervous system. Brain plasticity, the brain's ability to adapt its structure and function, plays a crucial role in mitigating MS's impact. This paper explores the potential benefits of lifestyle changes and nutraceuticals on brain plasticity in MS population. Lifestyle modifications, including physical activity and dietary adjustments, can enhance brain plasticity by upregulating neurotrophic factors, promoting synaptogenesis, and reducing oxidative stress. Nutraceuticals, such as vitamin D, omega-3 fatty acids, and antioxidants like alpha-lipoic acid, have shown promise in supporting brain health through anti-inflammatory and neuroprotective mechanisms. Regular physical activity has been linked to increased levels of brain-derived neurotrophic factor and improved cognitive function. Dietary interventions, including caloric restriction and the intake of polyphenols, can also positively influence brain plasticity. Integrating these lifestyle changes and nutraceuticals into the management of MS could provide a complementary approach to traditional therapies, potentially improving neurological outcomes and enhancing the quality of life for MS population.

Self-enhancement (SE) is often overlooked as a fundamental cognitive ability mediated via the Pre-Frontal Cortex (PFC). Here we present research that establishes the relationship between the PFC, SE, and the potential evolved beneficial mechanisms. Specifically, we believe there is now enough evidence to speculate that SE exists to provide significant benefits and should be considered a normal aspect of the self. Whatever the metabolic or social cost, the upside of SE is great enough that it is a core and fundamental psychological construct. Furthermore, though entirely theoretical, we suggest that a critical reason the PFC has evolved so significantly in Homo sapien is to, in part, sustain SE. We therefore elaborate as to its proximate and ultimate mechanisms.

Brain plasticity is the ability of the brain to change and adapt in response to experience or learning. Its hallmarks are developmental flexibility, complex interactions of genetic and environmental influences, and structure-functional changes comprising neurogenesis, axonal sprouting, and synaptic remodeling. Herein, we review brain plasticity association with non-coding RNAs (ncRNAs). Studies on brain plasticity have important practical implications. Numerous cerebral ncRNAs are linked with neurological disorders, which makes them putative targets for RNA-based diagnostics and therapeutics since molecular characteristics of brain plastic change may reveal disease course and rehabilitative potential of the patient. A new insight into the concept of brain plasticity will provide perspectives on functional recovery following brain damage. The knowledge of this phenomenon will enable physicians to exploit cerebral plastic potential and regulate eloquent networks with timely interventions. Future studies will provide pathophysiologic mechanisms of brain plasticity at macro- and microscopic levels to advance rehabilitation strategies and improve the quality of life in neurological disorders.

Serotonin (5-hydroxytryptamine: 5-HT), a neurotransmitter that regulates mood in the brain and signaling in the gut, has receptors throughout the body that serve various functions. Selective serotonin reuptake inhibitors (SSRIs) are used to treat depression, but their efficacy is uncertain. Depression is often associated with early gastrointestinal symptoms. Gut disorders such as functional dyspepsia (FD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are linked to elevated serotonin levels. In this review, we would like to discuss the approach of using serotonin as a biomarker for gut-brain and body-wide organ communication may lead to the development of preventive and innovative treatments for gut-brain disorders, offering improved visibility and therapeutic monitoring. It could also be used to gauge stress intensity for self-care and mental health improvement.

Advanced glycation end products (AGEs) play a significant role in the aging processes, further regarding as a hallmark of aging. Despite the importance, a lack of monitoring tools has hampered the study of relationship between AGEs and aging. Here, we firstly report a novel AGEs-selective probe, AGO. AGO presented its ability to detect AGEs more sensitively than a conventional approach of measuring autofluorescence from AGEs. In addition, we confirmed that AGO can detect AGEs depending on kinetics, reflecting by a preference to ribose-derived AGEs. Finally, AGO revealed its competence to visualize glycation products in glycation mimicking model, made by collagen framework. We believe that this study will enrich molecular toolboxes to understand physiological processes of AGEs during aging processes.

Health-Related Quality of Life (HRQoL) encompasses the comprehensive evaluation of an indi-vidual's health and well-being across multiple dimensions. Mindfulness, recognized as a scientifi-cally supported strategy for anxiety management, plays a role in enhancing both physical and mental health. The Gut-Brain Axis (GBA) serves as the bidirectional communication link between the gastrointestinal system and the central nervous system. This study aims to explore the associa-tion between Mindfulness and factors influencing the GBA in both healthy individuals and those with Inflammatory Bowel Diseases (IBD). A cross-sectional investigation involved 338 adults, in-cluding 50 IBD patients, utilizing validated Greek scales for Mindfulness (MAAS-15), Mediterra-nean Diet (14-MEDAS), and HRQoL (EQ-5D-5L). The questionnaire gathered demographic, an-thropometric, and lifestyle data. Among healthy participants, EQ-5D-5L showed a moderate cor-relation with the MAAS-15 scale (r=0.389, p

Rabies remains a significant global threat, yet accurate estimations of its impact are hindered by the lack of confirmatory diagnoses. Postmortem confirmation of rabies traditionally involves invasive brain tissue testing, a process met with resistance from deceased patients' families, impeding consent. This paper presents and evaluates an innovative yet unpublished transnasal approach for postmortem brain tissue collection, offering a minimally invasive, easier, faster, and safer method. This method preserves the cadaver's integrity, potentially easing family reluctance towards autopsies. The limited testing of both human and animal rabies in Ghana highlights the challenges in diagnosing this fatal disease. Scarce diagnostic resources and the complexity of obtaining brain tissue samples exacerbate the issue. Cultural and religious beliefs surrounding autopsies contribute to familial hesitation, viewing these procedures as disruptive and disfiguring, further complicating consent. The transnasal technique involves approaching the brain tissue through the nostrils and cribriform plate without any superficial manipulation of the patient's head and face, thereby preserving aesthetics and natural features of the person. Technological advancements and seamless One Health collaboration among governmental, non-governmental, and research entities locally and globally culminated in Ghana's first confirmed rabies diagnosis using this method of brain tissue collection. This success emphasizes the efficiency and feasibility of transnasal brain collection approach and the invaluable role of the One Health approach and collaborative efforts in overcoming diagnostic challenges in rabies control.

Fever control is essential in patients with severe traumatic brain injury (TBI). The efficacy of therapeutic hypothermia (TH) in severe TBI has been investigated over the last few decades; however, in contrast to experimental studies showing benefits, no evidence of efficacy has been demonstrated in clinical practice. In this review, the mechanisms and history of hypothermia were briefly outlined, while the results of major randomized controlled trials (RCTs) and meta-analyses investigating TH for adult TBI are introduced and discussed. The retrieved meta-analyses showed conflicting results, with a limited number of studies indicating benefits of TH. Some studies have shown benefits of long-term TH compared with short-term TH. Although TH is effective at lowering elevated intracranial pressure (ICP), reduced ICP does not lead to favorable outcomes. Low-quality RCTs overestimated the benefits of TH, while high-quality RCTs showed no difference or worse outcomes with TH. RCTs assessing standardized TH quality demonstrated the benefits of TH. As TBI has heterogeneous and complicated pathologies, applying a uniform treatment may not be ideal. A meta-analysis of young patients who underwent early cooling and hematoma removal showed better TH results. TH should not be abandoned, and its optimal should be advocated on an individual basis.

The reasons for the circular sense of human color perception generated by two sorts of color opponent neurons and three cone types are not well understood. Here we use geometrical analysis to examine the hypothesis that opponency, the recursive nature of color perception, and trichromacy arise as the most efficient ways of distinguishing spectrally different points on a plane using a minimum of color classes and receptor types.

Abstract Aim of the study: Presentation of ophthalmic symptoms of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infracts and Leucoencephalopathy (CADASIL). Material and methods: Clinical presentation of female patient with diagnosed CADASIL, manifested by transient loss of vision, migraine, convergence insufficiency, diplopia, increased deep tendon reflexes of upper left limb, subcortical infarcts, mood disturbances and dementia. Results: Confirmed NOTCH3 gene mutation (p.Cys212Gly), and presence of granular osmiophilic material (GOM) in cutaneous small vessel wall in immunohistochemistry laboratory test (IHC). Magnetic resonance imaging (MRI) revealed bilateral focal vasogenic lesions in white matter of cerebral hemisphere with single micro-focal infarct in the left external capsule. Furthermore, a left eye exophoria, a bilateral peripheral visual field loss of 20 degrees and a loss of nasolabial fold was confirmed during ophthalmic tests. An eye fundus examination as well as a fluorescein angiography (FA) revealed vessel constriction of retinal arteries and a peripheral retinal pigment epithelium (RPE) atrophy with focal drusen in the left eye. The doppler ultrasonography (USG) confirmed a decreased blood flow and an increased vascular resistance of the extraocular vessels. The pattern electroretinogram (PERG) revealed a reduced P50 wave amplitude in the patient’s left eye. Conclusions: intermittent blindness, migraine, convergence failure, diplopia with specific MRI signs, NOTCH3 mutation, and the presence of GOM in the skin of small blood vessels in a young or middle-aged patient suggests CADASIL. New observations include: atrophic changes in the RPE, hemodynamic disturbances in blood flow in the short posterior ciliary arteries and in the central retinal artery, single drusen in the retina, and a reduced amplitude of the P50 wave in PERG.

Cerebral cavernous malformation (CCM) is a collection of irregular small blood vessels that may be present in the brain or spinal cord. These vessels contain slow – moving blood that commonly clot. These malformations are frequently caused by mutations in one of the CCM genes. The CCM1 (also known as KRIT1) gene is essential for vascular morphogenesis however, its interactions with transcriptional regulators are unknown. Inhibitor of DNA-Binding/Differentiation-3 (ID3) has been recognized to be involved in different vascular/blood vessel diseases such as peripheral arterial disease, stroke, arteriovenous malformations, and atherosclerosis. We show interactions between ID3 and additional key differential expressed genes (DEGs) in microarray data of overexpressed CCM1 in endothelial cells through bioinformatic and data analytic tools. Improved understanding of how ID3, CCM1, and DEGs interact will play an important role in adding to the increasing knowledge for creating therapeutic targets for cerebral cavernous malformations.

Introduction: Cerebral palsy is the most common childhood disability Aims: Analyze and determine the main risk factors for the development of cerebral palsy in the population of Kazakhstan Materials and methods: Retrospective, analytical "case" - "control". Core group "case" - medical records of 100 pregnant women whose children at different ages has been diagnosed with cere-bral palsy Results: Thus, a retrospective analysis revealed the following features and complications in the perinatal period, which could promote the formation of cerebral palsy in children. Analytical results of the study are set significant results in cerebral palsy development Conclusion: Premature birth and urinary tract infections turned out to be the largest contribu-tors to the development of cerebral palsy, however, according to statistics, the rate of preterm birth, as well as the detection of infections, stably remains at the same level, while the number of cerebral palsy has been steadily growing since the early 1990s in Kazakhstan.

Despite existing strong evidence on oxidative markers overproduction following ischemia/reperfusion (I/R), the mechanism by which oxidative enzyme Cytochrome P450-2E1 (CYP2E1) contributes to I/R outcomes is not clear. In this study, we sought to evaluate the functional significance of CYP2E1 in I/R. CYP2E1 KO mice and controls were subjected to middle cerebral artery occlusion (MCAo-90min) followed by 24hr of reperfusion to induce focal I/R injury models. Then, histological and chemical analyses were conducted to investigate the role of CYP2E1 in lesion volume, oxidative stress, and inflammation exacerbation. Also, the role of CYP2E1 on the BBB integrity was investigated by measuring 20-Hydroxyecosatetraenoic acid (20-HETE) activity, as well as, in vivo BBB transfer rate. Following I/R, the CYP2E1 KO mice exhibited a significantly lower lesion volume, and neurological deficits compared to controls (p<0.005). Also, ROS production, apoptosis, and the neurodegeneration were significantly lower in the CYP2E1(-/-) I/R group (p<0.001). The BBB damage was significantly lower in CYP2E1(-/-) mice compared to WT (p<0.001), while 20-HETE production was increased by 41%. Besides, inflammatory cytokines expression and the number of activated microglia were significantly lower in CYP2E1(-/-) mice following I/R. CYP2E1 suppression ameliorates I/R injury and protects BBB integrity by reducing both oxidative stress and inflammation.

Serotonergic neurons constitute one of the main systems of neuromodulators, whose diffuse projections regulate the functions of the cerebral cortex. Serotonin (5-HT) is known to play a crucial role in the differential modulation of cortical activity related to behavioral contexts. Certain aspects of the 5-HT signaling framework hint at its potential role as a modulator of activity-dependent synaptic changes within the critical period of the primary visual cortex (V1). Cells of the serotonergic system are among the first neurons to differentiate and operate. During postnatal development, ramifications from raphe nuclei become massively distributed in the visual cortical area, remarkably increasing the availability of 5-HT for the regulation of excitatory and inhibitory synaptic activity. A substantial amount of evidence has demonstrated that synaptic plasticity at pyramidal neurons of the superficial layers of V1 critically depends on a fine regulation of the balance between excitation and inhibition (E/I). Therefore, 5-HT could play an important role in controlling this balance, providing the appropriate excitability conditions that favor synaptic modifications. In order to explore this possibility, the present work used in vitro intracellular electrophysiological recording techniques to study the effects of 5-HT on the E/I balance of V1 layer 2/3 neurons, during the critical period. Serotonergic modulation of the E/I balance has been analyzed on spontaneous activity, evoked synaptic responses, and long-term depression (LTD). Our results pointed out that the predominant action of 5-HT implies a reduction of the E/I balance. 5-HT promoted LTD at excitatory synapses while blocking LTD at inhibitory synaptic sites, thus shifting the Hebbian alterations of synaptic strength towards lower levels of E/I balance.

Neural microprobes represent an important component of neural prosthetic systems where implanted microprobes record the electro-potentials generated by specific thoughts in the brain and convey the signals to algorithms trained to interpret these thoughts. Here, we present novel elongated multi-site neural probe that can reach depths greater than 10mm. We hypothesize that reaching such depth allows the recording of cognitive signals required to drive cognitive prosthetics. The impedance of the recording sites on the probes was on the order of 500 kΩ at 1 kHz, which is consistent with probes used for neurophysiological recordings. The probes were made porous using Xenon Difluoride (XeF₂) dry etching to improve the biocompatibility and their adherence to the surrounding neural tissue. Numerical studies were performed to determine the reliability of the porous probes. We implanted the elongated probe in rats and show that the elongated probes are capable of simultaneously recording both spikes and local field potentials (LFPs) from various recording sites.

Objective. To test the hypothesis that a session of unilateral tSMS over the dominant primary motor cortex (M1) in healthy subjects produces a transient decrease in manual dexterity. Methods. A triple-blinded randomized control trial was conducted in 40 healthy participants who were allocated to real- or sham-tSMS group. Each participant underwent one session of tSMS and were assessed before, immediately after, 15 minutes, and 40 minutes after stimulation. Outcome measures were Finger Tapping Test (FTT), 5-seconds FTT, nine Hole Peg Test, and the hand grip assessment. Results: Significant differences were found between groups 15 minutes after stimulation in favor of the tSMS group in the FTT (2.2 ± 0.99; CI= .18-4.22; d= .84p=.034), and 5-second FTT (4.2 ± 1.98; CI= .199-8.2, d= .68; p=.04). In the intragroup analysis, a significantly lower number of taps 15 minutes after stimulation was observed in sham group (3.3 ± 1.01; CI= .47-6.13; d= .42; p=.015), but not in the real stimulation group. Conclusion: A unilateral session of tSMS in the M1 of the dominant hemisphere of healthy individuals does not reduce manual dexterity or grip strength. This technique could have benefits on the motor performance of the arm contralateral to the stimulated motor cortex

Parkinson's disease (PD) is a prevalent neurodegenerative disorder marked by progressive motor and non-motor symptoms. Traditional treatments primarily manage symptoms rather than address the disease's root causes, highlighting the need for novel therapeutic approaches. Natural phytochemicals, particularly phenolic compounds, have shown potential due to their neuroprotective effects. Antiaris africana is commonly used in traditional African medicines to treat several illnesses including neurodegenerative disorders. However, its neuroprotective mechanism remains elusive. This study aimed to employ network pharmacology-based prediction to identify key targets and pathways through which A. africana exerts its effects on PD. Targets associated with Parkinsonism were identified and analyzed for interaction with compounds from A. africana. Protein-protein interaction (PPI) networks were constructed, and key hub genes were identified using Cytoscape. Functional enrichment analysis highlighted significant pathways involved in PD. Molecular docking was performed to evaluate the binding affinities of the compounds to PD-related targets. Our results reveal that compounds such as caffeic acid, chlorogenic acid, catechin, ellagic acid, epigallocatechin, gallic acid, isoquercitrin, kaempferol, quercetin, quercitrin, and rutin interact with key proteins implicated in PD, including APP, EGFR, CASP3, ESR1, AKT1, and MAPK8. Notably, rutin exhibited strong binding affinity for EGFR, and chlorogenic acid showed potential in modulating the APP pathway. These findings suggest that phenolic compounds in A. africana may exert neuroprotective effects through multiple molecular mechanisms, offering potential therapeutic strategies for PD. This study underscores the importance of integrating molecular docking and network pharmacology to elucidate the therapeutic potential of natural compounds in complex diseases like Parkinson's disease

Background: Delis-Kaplan Executive Function System (D-KEFS) is a neuropsychological tool used in clinical practice to measure executive function in clinical and non-clinical populations, in individuals aged 8-89 years, and consists of nine subtests that can be administered either as a single system or separately. Aims: In the present study, were established norms for the Verbal Fluency Test as well as the Design Fluency Test of the D-KEFS in a Greek population aged 20 to 49 years, since there is no previous study conducted in Greece for these age clusters. Methods: The study sample consisted of 100 healthy adults (44.4% male and 55.6% female), aged 20 to 49 years (M=32.81 SD=11.04) with education from 12 to 18 years (M=14.73, SD= .91). First, Spearman and Pearson tests explored the associations of gender, age and education with D-KEFS subtests’ performance. Afterwards, we calculated normative data using raw scores and transformed to percentile scores. Results: The present study is the first attempt to calculate norms for the two fluency subtests of the D-KEFS in Greek adult population stratified by age and educational level. Conclusion: Future research will promote the use of D-KEFS, in order to introduce a widely used tool which measures all basic executive functions subtypes for Greek adult population. Given that the majority of neuropsychological tools are adapted for older adult population, the current study aims at filling the gap in neuropsychological assessment of young adults as well as those who have co existing neurological or psychiatric disorders.

Loss of function of the hippocampus or frontal cortex is associated with reduced performance on memory tasks in which subjects are incidentally exposed to cues at specific places in the environment and are subsequently asked to recollect the location at which the cue was experienced. Here, we examined the roles of the rodent hippocampus and frontal cortex in cue-directed attention during encoding of memory for the location of a single incidentally experienced cue. During a spatial sensory preconditioning task, rats explored an elevated platform while an auditory cue was incidentally presented at one corner. The opposite corner acted as an unpaired control location. The rats demonstrated recollection of location by avoiding the paired corner after the auditory cue was in turn paired with shock. Damage to either the dorsal hippocampus or the frontal cortex impaired this memory ability. However, we also found that hippocampal lesions enhanced attention directed towards the cue during the encoding phase while frontal cortical lesions reduced cue-directed attention. These results suggest that the deficit in spatial sensory preconditioning caused by frontal cortical damage may be mediated by inattention to the location of cues during the latent encoding phase, while deficits following hippocampal damage must be related to other mechanisms such as generation of neural plasticity.

The contribution of genetic and environmental factors to the pathophysiology of cerebral aneurysms in monozygotic twins is under-reported and presents ambiguous arguments. The morphology and hemodynamics of neurovascular arteries in a pair of monozygotic twins (MTs) were investigated to reveal the underlying mechanisms. Four arterial models were reconstructed for the twin A-right brain and left brain, twin B-left brain, and B-left brain without anterior cerebral arteries based on preclinical scanned information. Subsequently, the dimensions, configurations and outlined curves of the three-perspective geometries were compared between the MTs. Adopting an in-vitro validated numerical cerebral aneurysm model, hemodynamic patterns were investigated and compared in the MT models, respectively. Morphological comparisons of the MTs show the size and shape of cerebral arteries exist significant differences, despite of the expected genetic similarities. These differences can be attributed to variations during embryological development and external environmental influences. Qualitatively and generally, numerical results indicate the MTs have some hemodynamic similarities (e.g., time-averaged pressure (TAP) distributions (~13400 Pa), and oscillatory shear index (0~0.49), but present significant differences in specific local arteries due to morphological variances. Specifically, the difference in the volumetric blood flow rate in corresponding arteries between the MTs is from 16% (smallest) in anterior choroidal artery (AChA) to 221% (largest) in the ophthalmic artery (OphA), varying with specific compared arteries. Also, the registered hemodynamic indicators, such as the maximum time-averaged wall shear stress (TWSS) (53.6 Pa vs. 37.8 Pa), and different local OSI distributions were observed between the MTs. The findings revealed that morphological variations in MTs could be generated by embryological and environmental factors, thus assuming they share the identical morphology in cardiovascular and neurovascular systems may lead to significant misevaluations in hemodynamics quantifications and further lesions.

Background: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low levels of a constant current via scalp electrodes to specifically targeted areas of the brain. The effects of tDCS on whole-body exercise performance has been of interest in recent literature. The purpose of the current investigation was to investigate if tDCS, administered via Halo Sport, influences time trial performance in trained cyclists, and if changes in exercise performance are associated with prefrontal cortex (PFC) activation and/or muscle oxygenation (SmO2). Methods: Twelve recreationally trained cyclists volunteered to participate in two 10-kilometer time trials following 20 minutes of tDCS or a sham condition. Results: T-tests showed there was no significant difference in performance (time to completion) or physiological measures (BLa-, HR, SmO2, PFC oxygenation) between the Halo and sham conditions. Conclusions: These results indicate that the application of tDCS via Halo Sport does not induce changes in exercise performance or related physiological parameters during a 10-kilometer cycling time trial.

The brain's unique characteristics make it exceptionally susceptible to oxidative stress, which arises from an imbalance between reactive oxygen species (ROS) production, reactive nitrogen species (RNS) production, and antioxidant defense mechanisms. This review explores the factors contributing to the brain vascular tone vulnerability in the presence of oxidative damage, which can be of clinical interest in critically ill patients or presenting acute brain injuries. The brain's high metabolic rate and inefficient electron transport chain in mitochondria lead to significant ROS generation. Moreover, non-replicating neuronal cells and low repair capacity increase susceptibility to oxidative insult. ROS can influence cerebral vascular tone and permeability, with a potential impact on cerebral autoregulation. Different ROS species, including superoxide and hydrogen peroxide, exhibit vasodilatory or vasoconstrictive effects on cerebral blood vessels. Reactive nitrogen species (RNS), particularly NO and peroxynitrite, also exert vasoactive effects. This review further investigates the neuroprotective effects of antioxidants, including superoxide dismutase (SOD), vitamin C, vitamin E, and the glutathione redox system. Various studies suggest that these antioxidants could be used as adjunct therapies to protect the cerebral vascular tone during high oxidative stress conditions. Nevertheless, more extensive research is required to comprehensively grasp the relationship between oxidative stress and cerebrovascular tone, as well as to explore the potential benefits of antioxidants as adjunctive therapies in critical illnesses and acute brain injuries.

Background: Road safety improvement is a governmental priority due to driver-caused accidents. Driving styles variation affects safety, with emotional regulation being pivotal. However, functional Near-Infrared spectroscopy (fNIRS) studies show inconsistent prefrontal cortex activity during emotion processing. This study examines prefrontal cortex response to negative emotional stimuli, particularly traffic accident images, across diverse drivers in age and gender. Method: The study involved 118 healthy males (44.38 ± 12.98 years) and 84 females (38.89 ± 10.60 years). The Multidimensional Driving Styles Inventory (MDSI) was used to assess driving behaviour alongside fNIRS recordings. Participants viewed traffic accident and neutral images while prefrontal oxygenation was monitored. Results: Women rated traffic accidents (t-test = 2.43; p < .016) and neutral images (t-test = 2.19; p < .030) lower in valence than men. Arousal differences were significant for traffic accident images (t-test = -3.06; p < .002). Correlational analysis found an inverse relationship between Dissociative scale scores and oxygenation (all p-values ≤ .013). Greater prefrontal oxygenation occurred with neutral images compared to traffic accidents. Left hemisphere differences (t-test = 3.23; p < .001) exceeded right hemisphere differences (t-test = 2.46; p < .015). Subgroup analysis showed male participants to be driving these disparities. Among adaptive drivers, significant oxygenation differences between neutral and accident images were evident in both hemispheres (left : t-test = 2.72, p < .009; right: t-test = 2.22, p < .030). Conclusion: Male drivers with maladaptive driving styles, particularly dissociative ones, exhibit reduced prefrontal oxygenation when exposed to neutral and traffic accident images. This response was absent in female drivers, with no notable age-related differences.

The question of whether the early visual cortex (EVC) is involved in visual mental imagery remains a topic of debate. In this paper, I propose that the inconsistency in findings can be explained by the unique challenges associated with investigating EVC activity during imagery. During perception, the EVC processes low-level features which means that activity is highly sensitive to variation in visual details. If the EVC has the same role during visual mental imagery, any change in the visual details of the mental image would lead to corresponding changes in EVC activity. Within this context, the question should not be whether EVC is ‘active’ during imagery but how its activity relates to specific imagery properties. Studies using methods that are sensitive to variation in low-level features reveal that imagery can recruit the EVC in similar ways as perception. However, not all mental images contain a high level of visual details. Therefore, I end by considering a more nuanced view which states that imagery can recruit the EVC, but that does not mean that it always does so.

Brain is the most complex organ in the human body and it is divided into two hemispheres - left and right hemispheres. Left hemisphere is responsible for control of right side of our body whereas right hemisphere is responsible for control of left side of our body. Brain image segmentation from different neuroimaging modalities is one of the important parts in clinical diagnostic tools. Neuroimaging based digital imagery generally contain noise, inhomogeneity, aliasing artifacts, and orientational deviations. Therefore, accurate segmentation of brain images is a very difficult task. However, the development of accurate segmentation of brain images is very important and crucial for a correct diagnosis of any brain related diseases. One of the fundamental segmentation tasks is to identify and segment inter-hemispheric fissure/mid-sagittal plane, which separate the two hemispheres of the brain. Moreover, the symmetric/asymmetric analyses of left and right hemispheres of brain structures are important for radiologists to analyze diseases such as Alzheimer's, Autism, Schizophrenia, Lesions and Epilepsy. Therefore, in this paper we have analyzed the existing computational techniques used to find brain symmetric/asymmetric analysis in various neuroimaging techniques (MRI/CT/PET/SPECT), which are utilized for detecting various brain related disorders.

Introduction: This population-based retrospective cohort study assesses rates of adverse events (AEs) involving cerebral thromboembolism (CTE) after COVID-19 vaccines. Methods: Data were collected from the U.S. Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) Vaccine Adverse Event Reporting System (VAERS) database from January 1, 1990 to December 31, 2023. CTE AEs after COVID-19 vaccines were compared to those after influenza vaccines and after all other vaccines using proportional reporting ratio (PRR) analysis by time. Results: There are 5137 cerebral thromboembolism AEs reported in the 3 years (36 months) after COVID-19 vaccines compared to 52 AEs for the influenza vaccines over the past 34 years (408 months) and 282 AEs for all other vaccines (excluding COVID-19) over the past 34 years (408 months). The PRR’s are significant when comparing AEs by time from COVID-19 vaccines to that of the influenza vaccines (p < 0.0001) or to that of all other vaccines (p < 0.0001). The CTE AEs PRR by time (95% confidence intervals) for the COVID-19 vaccine AEs vs influenza AEs is 1120 (95% confidence interval (723-1730), p < 0.0001) and for COVID-19 vaccines vs all others is 207 (95% confidence interval (144-296), p < 0.0001). Cerebral venous thromboembolism AEs are female predominant with a female/male odds ratio of 1.63 (95% confidence interval (1.52-1.74), p < 0.0001). Conversely, cerebral arterial thromboembolism has a nonsignificant male preponderance. Cerebral venous thromboembolism is far more common than cerebral arterial thromboembolism over 36 months with an odds ratio (OR) of 14.8 (95% confidence interval 14.0-15.5, p < 0.0001). Atrial fibrillation, the most common identifiable cause of cerebral arterial thromboembolism, occurs far more commonly after the COVID-19 as compared to all other vaccines with a PRR of 123 (95% CI 88.3-172, p < 0.0001) Conclusions: There is an alarming breach in the safety signal threshold concerning cerebral thrombosis AEs after COVID-19 vaccines compared to that of the influenza vaccines and even when compared to that of all other vaccines. An immediate global moratorium on the use of COVID-19 vaccines is necessary with an absolute contraindication in women of reproductive age.

The importance of detecting and diagnosing the imminence of aneurysm rupture before it occurs cannot be overstated. However, this process is often time-consuming and challenging, with variability in conclusions not uncommon among experts. Furthermore, current state-of-the-art models in medical image segmentation suffer from limited availability of large annotated datasets for training, exacerbated by an immense data imbalance. In most segmentation tasks, 3D segmentation is preferred due to its capacity to leverage more contextual information. However, these models require more data, which is constrained by the aforementioned issues. In the realm of current diagnosis models, those lacking geographic context are notably ineffective. To address these issues, the aim is to develop a model pipeline to accurately detect cerebral intracranial aneurysms and diagnose rupture imminence through 3D magnetic resonance angiography (MRA) and tabular input, augmented with the implementation of neuro-symbolic ai. The utilization of data fusion to tackle the lack of context in tabular models is proposed, leveraging extracted geographical features from a segmentation model. To enhance segmentation results and tackle the data imbalance in aneurysm segmentation, a two-stage model pipeline that extracts contextual geographic features before aneurysm segmentation is suggested. Segmentation results are additionally improved through ensemble techniques and novel preprocessing techniques. Finally, a neuro-symbolic aspect is introduced to enhance model diagnosis, interpretability and performance. The multi-step Integrated Neuro-Symbolic Analysis Pipeline for Cerebral Aneurysm Rupture Diagnosis is introduced.

The gut microbiota (GM) communicates with the brain via biochemical signaling constituting the gut-brain axis, which significantly regulates the body's physiological processes. The GM dysbiosis can impact the digestive system and the functioning of the central nervous system (CNS) linked to the onset of neurodegenerative diseases. In this review, the scientific data compiled from diverse sources primarily emphasizes the neuropathological characteristics linked to the accumulation of modified insoluble proteins (such as β-Amyloid peptides and hyperphosphorylated tau proteins) in Alzheimer’s Disease (AD) and the potential impact of gut microbiota (GM) on AD susceptibility or resilience. The specific GM profile of human beings may serve as an essential tool for preventing or progressing neurodegenerative diseases like AD. This review focuses mainly on the effect of gut microfauna on the gut-brain axis in the onset and progression of AD. The GM produces various bioactive molecules that may serve as proinflammatory or anti-inflammatory signaling, contributing directly or indirectly to the repression or progression of neurodegenerative disorders by modulating the response of the brain axis. Human studies must focus on further understanding the gut-brain axis and venture to clarify microbiota-based therapeutic strategies for AD.

Astrocytes, the most abundant glial cells in the brain, are an integral part of the synaptic compartment and contribute to synaptic pruning, a key process for refining neural circuits during early postnatal development (PND). Dysregulations in this process are implicated in various neuropsychiatric disorders, including major depressive disorder (MDD). To investigate astrocyte functions in a physiologically relevant context, organotypic brain slice cultures (OBSCs) offer a powerful model, reproducing more closely in vivo conditions than traditional cell cultures and preserving complex brain architecture and interactions. Here, we present OBSCs as an ex vivo culturing method to provide a platform to explore astrocyte-mediated synaptic pruning dynamics in the rat prefrontal cortex (PFC) during PND. Our approach is based on assessing the role of MEGF10, a key protein involved in synaptic pruning, alongside the synaptic markers synaptophysin and PSD95, using Western blotting to analyse the expression levels of these markers in the cortex of developing rat pups. Additionally, we combine immunofluorescence staining with confocal imaging and IMARIS 9.8 software-assisted analysis to investigate the co-localization of the lysosomal marker LAMP1 with synaptic and astrocytic markers to evaluate the precise rate of synaptic engulfment. The methods presented here allow a deeper examination of an astrocyte-mediated synaptic remodelling in healthy and pathophysiological conditions.

Background: Clinical trails have revealed that patients with depression generally accompanied with learning and memory impairment, which critically impact on individual’s health and development. Danggui-Shaoyao-San (DSS), a famous Chinese complex prescription, significantly overcame depression and relieved cognitive disorder based on previous research and publication. However, its effectsand potential mechanism against chronic restraint stress (CRS) remained unknown. Methods: CRS animal model was established and mice were divided to six groups while they were oral administrated with Danggui-Shaoyao-San at doses of 1.25, 2.5 and 5 g/kg for 14 days. Emotional and cognitive performances were detected by behavior tests, meanwhile neural plasticity and its molecular mechanism were examined by Dil staining, western blot and immunofluorescence. Results: DSS treatment dose-dependently improved locomotion ability in open filed test, overcame depression behavior in forced swimming test and elevated plus maze test, enhanced learning and memory ability in Morris water maze test. CRS decreased number of total spines and mushroom spines, while DSS treatment dose-dependently restored these by Dil staining. Expression of BDNF and GluR1 were significantly down-regulated in CRS group, which were significantly normalized by DSS. Conclusions: DSS treatment dose-dependently reversed CRS-induced cognitive impairments by inducing structural remodeling of neurons.

Under physiological conditions the blood-brain barrier (BBB) is required for regulating the passage of substances between the bloodstream and the brain. To date, disruption of the BBB has been associated with nearly all neurological diseases. Dye and tracer experiments have been used to assess BBB integrity for decades, yet quantitative assessment of these experiments has only recently been implemented. Further, interpretation of these results requires the consideration of tracer-specific properties. Here, we describe a protocol for evaluating BBB leakage using the small molecule cadaverine in quantitative way. We also cover advantages/disadvantages of using some reagents and highlight limitations in data interpretations based on assays used to assess BBB permeability.

Modularity is arguably one of the most influential theses guiding research on brain and cognitive function since phrenology. This paper considers the following question: is modularity entailed by recent Bayesian models of brain and cognitive function, especially the predictive processing framework? It starts by considering three of the most well-articulated arguments for the view that modularity and predictive processing work well together. It argues that all three kinds of arguments for modularity come up short, albeit for different reasons. The analysis in this paper, although formulated in the context of predictive processing, speaks to broader issues with how to understand the relationship between functional segregation and integration and the reciprocal architecture of the predictive brain. These conclusions have implications for how to study brain and cognitive function. Specifically, when cognitive neuroscience works within an acyclic Markov decision scheme, adopted by most Bayesian models of brain and cognitive function, it may very well be methodologically misguided. This speaks to an increasing tendency within the cognitive neurosciences to emphasise recurrent and reciprocal neuronal processing captured within newly emerging dynamical causal modelling frameworks. The conclusions also suggest that functional integration is an organising principle of brain and cognitive function.

A recent study demonstrated that noninvasive measurements of cortical hemodynamics and metabolism in the resting human prefrontal cortex can facilitate quantitative metrics of unilateral mitochondrial-hemodynamic coupling and bilateral connectivity in infraslow oscillation (ISO) frequencies in young adults (YA). The ISO includes three distinct vasomotions with endogenic (E), neurogenic (N), and myogenic (M) frequency bands. The goal of this study was to prove the hypothesis that there are significant differences between young and older adults (OA) in the unilateral coupling (uCOP) and bilateral connectivity (bCON) in the prefrontal cortex. Accordingly, we performed measurements from 24 OA (67.2 ± 5.9 years of age) using the same 2-channel broadband near-infrared spectroscopy (bbNIRS) setup and resting-state experimental protocol as those in the recent study (Shahdadian et al, Cerebral Cortex Communications, 2022). After quantification of uCOP and bCON in three E/N/M frequencies and statistical analysis, we demonstrated that OA had significantly weaker bilateral hemodynamic connectivity but significantly stronger bilateral metabolic connectivity than YA in the M band. Furthermore, OA exhibited significantly stronger unilateral coupling on both prefrontal sides in all E/N/M bands, particularly with a very large effect size in the M band (&gt; 1.9). These age-related results clearly support our hypothesis and were well interpreted following neurophysiological principles. The key finding of this paper is that the neurophysiological metrics of uCOP and bCON are highly associated with age and may have the potential to become meaningful features for human brain health and be translatable for future clinical applications, such as early detection of Alzheimer’s disease.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive neurological disorder and shares many radiological and clinical features with other more prevalent myelopathies. Here, we quantified spinal cord and brain volumes in adults with HAM/TSP in comparison with healthy volunteers (HVs) and participants diagnosed with multiple sclerosis (MS). Clinical disability and MRI were assessed in 24 HVs, 43 HAM/TSP, and 46 MS participants. Spinal cord cross-sectional area (SCCSA) and brain tissue volumes were measured and compared. HAM/TSP participants had significantly lower SCCSA at C2-3 (54.0±8 mm2), C4-5 (57.8±8 mm2), and T4-9 (22.7±4 mm2) and significantly elevated brain white matter hyperintensity (WMH) fraction (0.004±0.008) was compared to HVs (C2-3: 69.4±8 mm2, C4-5: 75.1±9 mm2, T4-9: 34.1±4 mm2; all p &lt; 0.0001; and WMH: 0.0004±0.0007; p &lt; 0.001). In HAM/TSP, SCCSA at all levels but not WMH showed the significant correlation with clinical disability scores. Brain white matter hyperintensities in HAM/TSP, therefore, may not be related to clinical disability. SCCSA and WMH in our limited MS cohort were higher than the HAM/TSP cohort (67.6±8 mm2, 72.7±9 mm2, 33.4±5 mm2; p &lt; 0.0001). Principal component analysis suggested that SCCSA and WMH may be used to differentiated HAM/TSP from MS. Understanding these differences may help establish early diagnostic criteria for HAM/TSP patients.

The blood-brain barrier (BBB) strictly regulates the penetration of substances into the brain, which, although important for maintaining brain homeostasis, may delay drug development because of the difficulties in predicting pharmacokinetics/pharmacodynamics (PKPD), toxicokinetics/toxicodynamics (TKTD), toxicity, safety, and efficacy in the central nervous system (CNS). Moreover, BBB functional proteins show species differences; therefore, humanized in vitro BBB models are urgently needed to improve the predictability of preclinical studies. Recently, international trends in the 3Rs in animal experiments and the approval of the FDA Modernization Act 2.0 have accelerated the application of microphysiological systems (MPSs) in preclinical studies, and in vitro BBB models have become synonymous with BBB-MPSs. Recently, we developed an industrialized humanized BBB-MPS, BBB-NET. In our previous report, we reproduced transferrin receptor (TfR)-mediated transcytosis with high efficiency and robustness with hydrogels that include fibrin and collagen I microfibers (CMFs). Herein, we investigated how adding CMFs to the fibrin gel benefits BBB-NETs, showed that CMFs accelerated capillary network formation and maturation by promoting astrocyte (AC) survival, and clarified that integrin 1 is involved in the mechanism of CMFs. Our data suggest that quality control (QC) of CMFs is important for ensuring the stable production of BBB-NETs.

It has been widely established that the characterization of extracellular vesicles (EVs), particularly small EVs (sEVs), shed by different cell types into biofluids, helps identify biomarkers and therapeutic targets in neurological and neurodegenerative diseases. Recent studies are also exploring the efficacy of mesenchymal stem cell-derived extracellular vesicles naturally enriched with therapeutic microRNAs and proteins for treating various diseases. Besides, EVs released by various neural cells play a crucial function in the modulation of signal transmission in the brain in physiological conditions. However, in pathological conditions, such EVs can facilitate the spread of pathological proteins from one brain region to the other. On the other hand, analysis of EVs in biofluids can identify sensitive biomarkers for diagnosis, prognosis, and disease progression. This review discusses the potential therapeutic use of stem cell-derived EVs in several central nervous system diseases. It lists their differences and similarities and confers various studies exploring EVs as biomarkers. Further advances in EV research in the coming years will likely lead to the routine use of EVs in therapeutic settings.

Electrolyte disturbances are common in patients with traumatic brain injury (TBI), particularly affecting sodium, potassium, chloride and calcium levels. This study aims to provide insights into these disturbances within the first 24 hours post-injury. We conducted a cross-sectional analysis of 50 TBI patients, excluding those with conditions affecting electrolyte balance. Electrolyte levels were measured, and correlations with demographic data, trauma mechanisms, imaging findings, and Glasgow Coma Scale (GCS) scores were analyzed. Results indicated that chloride levels inversely correlated with GCS scores (ρ = -0.515; p = 0.002), suggesting that elevated chloride may indicate severe neurological impairment. Potassium levels were significantly associated with subdural hematoma (p = 0.032) and subarachnoid hemorrhage (p = 0.043), highlighting their potential as markers for severe brain injuries. No significant associations were found between sodium or calcium levels and the studied variables. These findings underscore the importance of early monitoring of chloride and potassium levels in TBI patients to improve management and outcomes. Future research should focus on larger, multi-center studies to validate these findings and develop comprehensive guidelines for managing electrolyte imbalances in TBI patients.

Stress mechanisms have long been associated with neuronal loss and neurodegenerative diseases. The origin of cell stress and neuronal loss likely stems from multiple pathways. These include (but are not limited to) bioenergetic failure, neuroinflammation, and loss of proteostasis. Cells have adapted compensatory mechanisms to overcome stress and circumvent death. One mechanism is mitophagy. Recent studies have implicated mitophagy in several neurodegenerative diseases and clinical trials are underway which target mitophagy pathways. Here, we review mitophagy pathways, the role of mitophagy in neurodegeneration, potential therapeutics, and the need for further study.

It’s been reported that Mori Folium (MF) and Eucommiae Cortex (EC) exhibit pharmacological effects on the treatment of immunosuppression. However, the mechanism of MF and EC against immunosuppression remains unclear. This study aims to explore the mechanism of action of MF and EC for the treatment of immunosuppression through network pharmacology, molecular docking, molecular dynamics simulations and animal experiments. As a result, 11 critical components, 9 hub targets, and related-signaling pathways of treatment of immunosuppression were obtained based on network pharmacology. The molecular docking suggested that 11 critical components exhibited great binding affinity to 9 hub targets of immunosuppression. The molecular dynamics simulations results showed that (-)-Tabernemontanine-AR, beta-sitosterol-AR and Dehydrodieugenol-HSP90AA1 complexes are stably bound. Additionally, in the animal experiments, the treated group results compared to the control group suggest that MF and EC have a significant effect on the treatment of immunosuppression. Therefore, the MF and EC treatment for immunosuppression may take effects in a multi-component, multi-target, and multi-pathway manner. The results would provide novel insights into the treatment of immunosuppression in humans.