Injuries from exposure to blasts are of significant concern in military operational settings, including tactical training, and is associated with self-reported concussion-like symptomology and physiological changes as increased intestinal permeability (IP) investigated herein. Timeseries gene expression and IP biomarker data were generated from “breachers” exposed to controlled, low-level explosive blast during training. Samples from 30 male participants at pre, post, follow-up blast exposure the next day were assayed via RNA-seq and ELISA. A battery of symptom data was also collected at each of these time points that acutely showed elevated symptom reporting related to headache, concentration, dizziness, and slowed thinking, dissipating ~16hrs following blast exposure. Evidence for bacterial translocation into circulation following blast exposure was detected by significant stepwise increase in microbial diversity (measured via alpha-diversity p=0.049). Alterations in levels of IP protein biomarkers (i.e., Zonulin, LBP, Claudin-3, I-FABP) assessed in a subset of these participants (n=23) further evidenced blast exposure associates with IP. The observed symptom profile was consistent with mTBI and was further associated with changes in bacterial translocation and intestinal permeability, suggesting that IP may be linked to a decrease in cognitive performance. These preliminary findings show for the first

Emerging research has revealed a complex bidirectional interaction between the gut microbiome and cannabis. Preclinical studies have demonstrated that the gut microbiota can significantly influence the pharmacological effects of cannabinoids. One notable finding is the ability of the gut microbiota to metabolise cannabinoids, including Δ^9-tetrahydrocannabinol (THC). This metabolic transformation can alter the potency and duration of cannabinoid effects, potentially impacting their efficacy in cancer treatment. Additionally, the capacity of gut microbiota to activate cannabinoid receptors through the production of secondary bile acids underscores its role in directly influencing the pharmacological activity of cannabinoids. While the literature reveals promising avenues for leveraging the gut microbiome-cannabis axis in cancer therapy, several critical considerations must be accounted for. Firstly, the variability in gut microbiota composition among individuals presents a challenge in developing universal treatment strategies. The diversity in gut microbiota may lead to variations in cannabinoid metabolism and treatment responses, emphasising the need for personalised medicine approaches. The growing interest in understanding how the gut microbiome and cannabis may impact cancer has created a demand for up-to-date, comprehensive reviews to inform researchers and healthcare practitioners. This review provides a timely and invaluable resource by synthesizing the most recent research findings and spotlighting emerging trends. A thorough examination of the literature on the interplay between the gut microbiome and cannabis, specifically focusing on their potential implications for cancer, is presented in this review to devise innovative and effective therapeutic strategies for managing cancer.

About 10% of angiosperms, an estimated 20,000 species, produce latex from ubiquitous isoprene precursors. Latex, an aqueous suspension of rubber particles and other compounds, functions as an antifeedant and herbivory deterrent. Here, I propose that the solubility of latex in neutral to alkaline pH supports the hypothesis that foregut-fermenting herbivores such as ruminants, kangaroos, sloths, insect larvae and tadpoles have evolved to adapt to the ingestion of latex with the evolution of alkaline anterior digestive chamber(s). However, they consequently become susceptible to the action of Bacillus thuringiensis (Bt) -endotoxin and related bioinsecticides which are activated in alkaline environments. By contrast, hindgut-fermenting herbivores such as horses and rabbits have acidic anterior digestive chambers in which latex coagulates and may cause gut blockage, but in which Bt is not activated. The latex-adapted foregut herbivore vs. latex-maladapted hindgut herbivore hypothesis developed in this paper has implications for foregut-fermenting husbanded livestock and zoo animals which may be provided with latex-containing forage that is detrimental to their gut health. Further, ruminants and herbivorous tadpoles with alkaline anterior chambers are at risk for damage by the supposedly “environmentally-friendly” Bt bioinsecticide which is widely disseminated, or engineered into crops which may enter animal feed streams.

The aim of the study was to investigate the association between maternal dietary iron intake during pregnancy and the gut microbiota characteristics of both the mother and neonate in a well-characterized cohort. A total of 95 mother-neonate dyads were included in our study, with basic information collected through questionnaires. A semi-quantitative Food Frequency Questionnaire (FFQ) was used to assess maternal dietary intake during pregnancy, and maternal dietary iron intake was categorized into <20 mg/d and ≥20 mg/d groups. Fecal samples were collected from the mother in the third trimester and the neonate, allowing for assessment of the community profile and diversity of gut microbiota via 16S rRNA amplicon sequencing. Then, a comparison between different maternal dietary iron intake groups was conducted, adjusting for delivery mode (VD, vaginal delivery; CS, cesarean section) and other potential confounding factors. No significant differences in community profile and diversity were observed for the maternal gut microbiota in different dietary iron intake groups. In neonate fecal samples, the Shannon (P = 0.044) and Simpson (P = 0.010) diversity indices of the gut microbiota were higher in the maternal dietary iron intake ≥20 mg/d group, while Simpson diversity presented the same tendency in vaginal delivery (P = 0.041) after stratification. The relative abundance of the core genus Bifidobacterium showed a significant difference between groups (4.69 [1.19–12.77] vs. 13.98 [3.44–27.28]; P = 0.044). The abundance of Lactobacillus was different in the ≥20 mg/d group under both delivery modes (VD: beta = 2.9, w = 4.13; CS: beta = 2.77, w = 3.8). Our findings suggest that adequate dietary iron intake during pregnancy may promote beneficial bacterial colonization and increase the biodiversity of the neonate gut microbiota.

Purpose The objective of this study was to eliminate any ambiguity by examining the correlation between gut microbiota and both AMD and glaucoma. Methods Mendelian randomization studies were conducted utilizing the data sourced from the GWAS database for the gut microbiome, AMD, and glaucoma. SNP estimates were summarized through five MR methods. We utilized Cochran's Q statistic to evaluate the heterogeneity of the instrumental variables. Additionally, we employed a "leave-one-out" approach to verify the stability of our findings. Results IVW suggests that Eubacterium (oxidoreducens group) and Parabacteroides had a protective effect on AMD. Both weighted median and IVW suggests that Lachnospiraceae (NK4A136 group) and Ruminococcaceae (UCG009) had a protective effect on AMD. However, both weighted median and IVW suggests that Dorea had a risk effect on AMD. Similarly, The IVW of Eubacterium (ventriosum group) showed a risk effect on AMD. The weighted median of Eubacterium (nodatum group), Lachnospiraceae (NC2004 group), and Roseburia had a risk effect on glaucoma. IVW suggested that Ruminococcaceae (UCG004) had a risk effect on glaucoma. Reverse MR analysis found a causal link between Eubacterium (nodatum group) and glaucoma. No causal relationships were found between AMD or glaucoma and the other mentioned bacterial groups. No significant heterogeneity or evidence of horizontal pleiotropy was detected. Conclusions This study found that certain gut bacteria had protective effects on AMD, while others may be risk factors for AMD or glaucoma. Besides, reverse MR found that glaucoma led to increased abundance of certain gut bacteria. Further trials are needed to clarify the specific mechanisms involved.

Some biologically active compounds isolated from sea cucumbers stimulate the body’s immune response through activating immune cells. Immune function is closed related to the integrity intestinal barrier and balanced gut microbiota. However, it is unknown whether daily administration of holothurian wall hydrolysates (HWH) ameliorated intestinal dysbiosis and barrier injury induced by immunodeficiency. This study aimed to investigate the immunomodulatory effect and the underlying mechanism of HWH in cyclophosphamide (CTX)-induced immunocompromised mice. BALB/c mice received CTX (80 mg/kg, intraperitoneally) once a day for 3 days to induce immunodeficiency, and then oral administration of HWH (80 or 240 mg/kg), levamisole hydrochloride (LH, 40 mg/kg, positive control) respectively once a day for 7 days. We utilized 16S rRNA sequencing for microbial composition alterations, histopathological analysis for splenic and colonic morphology, Western blotting for expressions of tight junction proteins (TJs), and quantitative real-time (qRT-PCR) for measurements of pro-inflammatory cytokines. HWH attenuated the immune organ damage induced by CTX, increased the secretions of interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α, and promoted the recovery of goblet cells and the productions of TJs (claudin-1, occludin, and ZO-1) in the colon of the immunocompromised mice. Moreover, HWH promoted the growth of beneficial microorganisms such as Lactobacillus, Lachnospiraceae, Christensenellaceae, and Bifidobacterium, while suppressed the populations of Ruminococcus, Staphylococcus, and Streptococcus. These results demonstrate that HWH elicits intestinal mucosal immunity, repairs the damage to intestinal mucosal integrity, and normalizes the imbalanced intestinal microbial profiles in immunocompromised mice. It may be helpful to identify the biological activities of HWH, and supports the potential as new prebiotics, immunomodulatory agents, and medical additive for intestinal repair.

The aquaculture sector has become increasingly reliant on soybean meal (SBM) and soy-derived proteins, because of their large abundance, low price and favorable amino acid profile. However, for Atlantic salmon, a major aquaculture species, the inclusion of soybean meal, and soy protein concentrate (SPC) in certain combinations has adverse impacts on its gut health and welfare. This study evaluated two enhanced SBM targeting improved gut health for inclusion in freshwater phase salmon diets, enzyme pre-treatment (ETS) and addition of fructose oligosaccharide (USP), respectively in comparison to untreated soybean meal (US) and fish meal (FM). The impact on growth performance, gut microbiome, and behaviors relevant to welfare was investigated. Both enhancements of SBM were found to support comparable growth performance to FM. Both targeted treatments altered the gut microbiome community. Fish fed SBM showed a tendency for more reactive behavior compared to those fed the FM-based control. All fish had a similarly low response to elicited stress, although ETS fed fish responded more actively than those fed the US diet. SBM fed fish also had lower repeatability of behavior, which may have implications for welfare. Both enhancements provide a promising basis to optimize the application of this widely used protein source.

Enteric protozoan pathogenic infections significantly contribute to the global burden of gastrointestinal illnesses. Their occurrence is considerable within remote and indigenous communities and regions due to reduced access to clean water and adequate sanitation. The robustness of these pathogens means requirement of harsh treatment methods such as medicinal drugs or antibiotics. However, such treatments impact the gut microbiome, and create dysbiosis, often leading to opportunistic pathogens, anti-microbial resistance, or functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS). Recent studies have shown that these impacts do not remain confined to gut, and are reflected across the gut-brain, gut-liver, and gut-lung axes, among others. Therefore, apart from the medicinal treatment, nutritional supplementation is also a key aspect of providing the recovery from this dysbiosis. Future proteins, prebiotics, probiotics, synbiotics, and food formulations offer a good solution to remedy this dysbiosis. Furthermore, the nutritional supplementation also helps to build a resilience against the opportunistic pathogens and potential future infections and disorders that may arise due to the dysbiosis. Systems biology techniques have shown to be highly effective tools to understand the biochemistry of these processes. Systems biology techniques characterises the fundamental host-pathogen interaction biochemical pathways, at various infection and recovery stages. This same mechanism also allows to track the impact of abovementioned treatment methods of gut microbiome remediation. This manuscript is organised in sections delving into system biology approaches and upcoming developments to understand (1) Infection mechanism and current global status; (2) Cross-organ impacts of dysbiosis, particularly within gut-liver and gut-lung axes; (3) Nutritional interventions. It highlights the impact of antimicrobial resistance (AMR) and Multi-drug resistance (MDR) from a perspective of protozoal infections. It also highlights the role of nutritional interventions to add resilience against the chronic problems caused by these phenomena.

Natural herbs and functional foods contain bioactive molecules capable of augmenting the immune system and mediating anti-viral functions. Functional foods, such as prebiotics, probiotics, and dietary fibers, have been shown to have positive effects on gut microbiota diversity and immune function. The use of functional foods has been linked with en-hanced immunity, regeneration, improved cognitive function, maintenance of gut mi-crobiota, and significant improvement in overall health. The gut microbiota plays a critical role in maintaining overall health and immune function, and disruptions to its balance have been linked to various health problems. SARS-CoV-2 infection has been shown to affect gut microbiota diversity, and the emergence of variants poses new challenges to combat the virus. SARS-CoV-2 recognizes and infects human cells through ACE2 receptors prevalent in lung and gut epithelial cells. Humans are prone to SARS-CoV-2 infection because the respiratory and gastrointestinal tracts are rich in microbial diversity and contain high ACE2 and TMPRSS2. This review article explores the potential use of functional foods in mitigating the impact of SARS-CoV-2 variants on gut microbiota diversity and the potential use of functional foods as a strategy to combat these effects.

Numerous studies have demonstrated that multiple intrinsic and extrinsic factors shape the structure and composition of gut microbiota in a host. The disorder of gut microbiota may trigger various host diseases. Here, we collected fecal samples from wild-caught Japanese geckos (Gekko japonicus) and captive conspecifics fed with mealworms (mealworm-fed geckos) and fruit flies (fly-fed geckos), aiming to examine dietary and sexual correlates of gut microbiota. We used the 16S rRNA gene sequencing technology to determine the composition of gut microbiota. The dominant phyla with a mean relative abundance higher than 10% were Verrucomicrobiota, Bacteroidota and Firmicutes. Gut microbial community richness was higher in mealworm-fed geckos than in fly-fed and wild geckos, and community diversity was higher in mealworm-fed geckos than in wild geckos. Neither alpha nor beta diversity of gut microbiota differed among wild, mealworm-fed and fly-fed geckos. The beta rather than alpha diversity of gut microbiota was sex-dependent. Based on the relative abundance of gut bacteria and its gene functions, we concluded that gut microbiota contributed more significantly to the host’s metabolic and immune functions. Higher diversity of gut microbiota in mealworm-fed geckos could result from higher chitin contents of insects of the order Coleoptera. This study not only provides basic information about the gut microbiota of G. japonicus, but also shows that gut microbiota correlates with dietary habit and sex in the species.

Antibiotics have been used in various fields such as livestock farm and fish farm as well as hospital in order to treat diseases caused by bacteria. However, the antibiotics that are not completely decomposed, but remains as residue and discharge to aquatic environment, can cause an imbalance in the gut flora of host, as well as regulate abnormal host gene regulatory system. We investigated the effects of chronic exposure with the low concentrations of erythromycin and ampicillin on gut microbiome and immune and stress-related gene expression using Korea native ricefish (Oryzias latipes). As a result of microbiome analysis, the proportion of Proteobacteria was increased in the ricefish when exposed to erythromycin and ampicillin chronically, whereas the proportion of other bacterial phyla decreased. In addition, the immune and stress-related genes were significantly influenced in the ricefish under the chronic antibiotics exposure. These results show that the internal microbial flora and the host gene expression are susceptible even in the low concentration of chronic antibiotic existing environments. This study provides the importance of the appropriate use of antibiotics dose to maintain the sustainable and healthy aquaculture industry and water ecosystem.

Recent research has identified the gut-brain axis as a key mechanistic pathway and potential therapeutic target in depression. In this paper, the potential role of gut hormones as potential treatments or predictors of response in depression is examined, with specific reference to the peptide hormone motilin. This possibility is explored through two methods: (a) a conceptual review of the possible links between motilin and depression, including evidence from animal and human research as well as clinical trials, and (b) an analysis of the relationship between a functional polymorphism (rs2281820) of the motilin (MLN) gene and cross-national variations in the prevalence of depression. It was observed that (a) there are several plausible mechanisms, including interactions with diet, monoamine, and neuroendocrine pathways, to suggest that motilin may be relevant to the pathophysiology and treatment of depression, and (b) there was a significant correlation between rs2281820 allele frequencies and the prevalence of depression after correcting for multiple confounding factors. These results suggest that further evaluation of the utility of motilin and related gut peptides as markers of antidepressant response is required, and that these molecular pathways represent potential future mechanisms for antidepressant drug development.

The Human Gut Microbiome is an important host’s component defining its health. These microorganisms are mutualistic symbionts dependent on factors such as host’s age, subsistence models and sociocultural practices, among others. The conjunction of these factors define the microbial ecosystem dynamics. Using a fecal microbiome approach in children, a comparison of two Mexican communities with contrasting lifestyles: “westernized” (Mexico City) and “non-westernized” (Me’phaa indigenous group) was evaluated. The main differences between these two communities are in bacteria associated with different types of diets (high animal protein and refined sugars vs high fiber food, respectively). In addition, the gut microbiome of Me’phaa children showed higher total diversity and the presence of exclusive phyla, such as Deinococcus-Thermus, Chloroflexi, Elusimicrobia, Acidobacteria and Fibrobacteres. In contrast, Mexico City children had less diversity and the exclusive presence of Saccharibacteria phylum which is associated with the degradation of sugar compounds. This comparison allows further exploration of the selective pressures affecting microbial ecosystemic composition over the course of human evolution and the potential consequences of pathophysiological states correlated with westernization lifestyles.

Although it is known that the gut microbiota (GM) can be modulated by diet, the efficacy of specific dietary interventions in determining its composition and diversity in obese patients remains to be ascertained. The present work aims to evaluate the impact of a moderately hypocaloric Mediterranean diet on the GM of obese and overweight patients (OB). The GM of 23 OB patients (F/M= 20/3) was compared before (T0) and after 3 months (T3) of the nutritional intervention (NI). Fecal samples were analyzed by Illumina MiSeq sequencing of the 16S rRNA gene. At baseline, the GM characterization confirmed the typical obesity-associated dysbiosis. After 3 months of NI, patients presented a statistically significant reduction of the body weight and fat mass, along with changes in the relative abundance of many microbial patterns. In fact, we observed an increased abundance in several Bacteroidetes taxa (i.e. Sphingobacteriaceae, Sphingobacterium, Bacteroides spp., Prevotella stercorea) and depletion of many Firmicutes taxa (i.e. Lachnospiraceae members, Ruminococcaceae and Ruminococcus, Veillonellaceae, Catenibacterium, Megamonas). In addition, the phylum Proteobacteria showed an increased abundance, while the genus Sutterella, within the same phylum, decreased after the intervention. Metabolic pathways, predicted by bioinformatic analyses, showed a decrease in membrane transport and cell motility after NI. The present study extends our knowledge of the GM profiles in OB, highlighting the potential benefit of a moderate caloric restriction in counteracting the gut dysbiosis.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Given the growing evidence of gut microbiota being involved in psychiatric (including neurodevelopmental) disorders, we aimed to identify differences in gut microbiota composition between participants with ADHD and controls and to investigate the role of the microbiota in inattention and hyperactivity/impulsivity. Fecal samples were collected from 107 participants (NADHD=42; Ncontrols=50; NsubthreholdADHD=15; range age: 13-29 years). The relative quantification of bacterial taxa was done using 16S ribosomal RNA gene amplicon sequencing. Beta-diversity revealed significant differences in bacterial composition between participants with ADHD and healthy controls, which was also significant for inattention, but showing a trend in case of hyperactivity/impulsivity only. Ten genera showed nominal differences (P < 0.05) between both groups, of which seven genera were tested for their association with ADHD symptom scores (adjusting for age, sex, body mass index, time delay between feces collection and symptoms assessment, medication use and family relatedness). Our results show that variation of a genus from the Ruminococcaceae family (Ruminococcaceae_UCG_004) is associated (after multiple testing correction) with inattention symptoms, and suggest a role of gut microbiota in ADHD pathophysiology.

The composition of bacteria in the gastrointestinal tract of piglets is easily affected by environmental changes, particularly during the weaning period. Compound strains of Lactobacillus reuteri and Lactobacillus salivarius were supplemented to piglets during pre- and post-weaning to determine their effects in improving the growth performance and ameliorating the diarrhea rate and stress caused by antioxidation in piglets. A larger number of L. reuteri and L. salivarius colonized the distal segment of the ileum and the total numbers of Lactobacillus spp. and Bifidobacterium were higher in the ileal mucous membrane and cecal lumen with probiotics supplementation. The numbers of antioxidative and immune molecules were increased in the plasma following compound bacteria (CL) supplementation, whereas cortisol and endotoxin levels were lower and growth hormone and insulin-like growth factor 1 were higher. Spearman’s and KEGG analysis of the bacterial operational taxonomic unit and antioxidative and immune indices and metabolic genes indicated that the body growth modulation by CL supplementation could be attributed to optimization of the intestinal bacterial composition. Collectively, these results suggest that supplementation with CL could reduce stress and improve the growth performance of piglets during weaning by optimizing the intestinal bacterial composition.

Biological nitrogen (N) provisioning is a seminal function of the gut microbes in several terrestrial insects, given the unbalanced carbon (C) and N ratios of their diets. Although freshwater insects face comparable dietary N limitations like terrestrial insects, little is known about this function by their gut microbiomes. In this study, we investigated microbial nitrate reduction to ammonium pathways as possible routes of biological N provisioning in two freshwater insects; filter-feeding Hydropsychidae and grazers/collectors Baetidae. After incubation in filtered (microbe-free) artificial stream water (ASW) containing dissolved ¹⁵N-labeled nitrate (treatment) or standard nitrate (control), bulk δ¹⁵N values of treatment samples (Baetidae = 100.62 ± 10.23, mean ± S.E.; Hydropsychidae = 76.82 ± 7.20) were significantly higher than controls (Baetidae = 10.14 ± 0.12 ; Hydropsychidae = 9.03 ± 0.20) in both functional feeding groups (F _{(3, 13)} = 296, P < 0.0001). The treatment δ¹⁵N values are cautiously interpreted as reflecting uptake and incorporation of microbe-derived ¹⁵N-metabolites (¹⁵NH₄ or ¹⁵N-amino acids) into host tissues following nitrate reduction to ammonium pathways in the gut lumen. Microbial nitrate reduction to ammonium activities was assessed via the quantification of dissimilatory (nrfA) and assimilatory (nasA) nitrate reduction to ammonium gene transcripts. There were no significant differences between control and treatment groups within each insect groups. Overall, this study provides a demonstration of the feasibility of applying ¹⁵N-stable isotope analysis for investigating, potential symbiotic functions of freshwater insect gut microbiomes, despite the preliminary nature of the results.

Agavins consumption has lead to accelerate body weight loss in mice. We investigated the changes on cecal microbiota and short chain fatty acids (SCFA) associated to body weight loss in overweight mice. Firstly, mice were fed with standard (ST5) or high fat (HF5) diet for 5 weeks. Secondly, overweight mice were shifted to standard diet alone (HF-ST10) or supplemented with agavins (HF-ST+A10) or oligofructose (HF-ST+O10), five more weeks. Cecal contents were collected before and after supplementation to determine microbiota and SCFA concentrations. At the end of first phase, HF5 mice showed a significant increase of body weight, which was associated with reduction of cecal microbiota diversity (PD whole tree; non-parametric t-test, P < 0.05), increased Firmicutes/Bacteroidetes ratio and reduced SCFA concentrations (t-test, P < 0.05). After diet shifted, HF-ST10 normalized its microbiota, increase its diversity and SCFA levels, whereas agavins (HF-ST+A10) or oligofructose (HF-ST+O10) led to partial microbiota restoration, with normalization of the Firmicutes/Bacteroides ratio as well as higher SCFA levels (P < 0.1). Moreover, agavins noticeably enriched Klebsiella and Citrobacter (LDA > 3.0); this enrichment has not been reported previously under a prebiotic treatment. In conclusion, agavins or oligofructose modulated cecal microbiota composition, reduced extent of diversity and increased SCFA. Furthermore, identification of bacteria enriched by agavins, opens opportunities to explore new probiotics.

In Brain-Computer Interface Motor Imagery (BCI-MI) systems, Convolutional Neural Networks (CNNs) have traditionally dominated as the deep learning method of choice, demonstrating significant advancements in state-of-the-art studies. Recently, Transformer models with attention mechanisms have emerged as a sophisticated technique, enhancing the capture of long-term dependencies and intricate feature relationships in BCI-MI. This research investigates the performance of EEG-TCNet and EEG-Conformer models, which are trained and validated using various hyperparameters and bandpass filters during preprocessing to assess improvements in model accuracy. Additionally, this study introduces the EEG-TCNTransformer, a novel model that integrates the convolutional architecture of EEG-TCNet with a series of self-attention blocks employing a multi-head structure. The EEG-TCNTransformer achieves an accuracy of 82.97% without the application of bandpass filtering. The source code of EEG-TCNTransformer is available on GitHub.

Brain-Computer Interface (BCI) systems can assist physically challenged people to interact with their surroundings and improve the quality of their lives. Decoding human thoughts is a powerful technique that can assist paralyzed people who have lost their speech production ability. Speaking is a combined process involving synchronizing the brain and the oral articulators. This paper proposed a high-accuracy brain wave pattern recognition based on inner speech using a novel feature extraction method. Only eight EEG electrodes were used in this study, and they were set on selected spots on the scalp. Support Vector Machine (SVM) was employed to decode the recorded EEG dataset into four internally spoken words which are: Up, Down, Left, and Right. The proposed approach achieved overall classification accuracy that ranges between 96.20% to 97.5%. In addition, more performance evaluation metrics were estimated to test the reliability of classifying the EEG-based inner speech data, and we obtained 97.61%, 97.50%, and 97.73% for F1-score, recall, and precision respectively. Furthermore, the Area Under Curve of the Receiver Operating Characteristic (AUC-ROC) proved the strength of the proposed approach for classifying the specified inner speech commands by achieving a macro-average amount of 99.32%. The inner speech classification method using electroencephalography proposed in this work can clinically help improve communication for patients with problems including speech disorder, mutism, cognitive development, executive function, and psychopathology.

The Brain-Computer Interface (BCI) technology has emerged as a groundbreaking innovation with profound implications across diverse domains, particularly in healthcare. By establishing a direct communication pathway between the human brain and external devices, BCI systems offer unprecedented opportunities for diagnosis, treatment, and rehabilitation, thereby reshaping the landscape of medical practice. However, despite its immense potential, the widespread adoption of BCI technology in clinical settings faces several challenges. These include the need for robust signal acquisition and processing techniques, ensuring user safety and privacy, addressing ethical considerations, and optimizing user training and adaptation. Overcoming these challenges is crucial to unleashing the complete potential of BCI technology in healthcare and realizing its promise of personalized, patient-centric care. This review work underscores the transformative potential of BCI technology in revolutionizing medical practice. This paper offers a comprehensive analysis of medical-oriented BCI applications by exploring the various uses of BCI technology and its potential to transform patient care.

Human language and social cognition are two key disciplines that have traditionally been studied as separate domains. However, emerging research from detailed studies of comparative animal behavior, human social behavior, language acquisition in children, social cognitive neuroscience, and the cognitive neuroscience of language suggest that language and social cognition are two deeply interrelated capacities of the human species. For instance, recent developmental studies on the acquisition of language in infants and young children, draw attention to the important crucial benefits associated with several different aspects of social stimulation for youngsters, including the quantity and quality of linguistic input, dyadic infant/child-to-parent verbal and non-verbal social interactions, and other important social cues integral for facilitating language learning and social bonding. Studies of the adult human brain further suggest a high degree of specialization for sociolinguistic information processing, memory retrieval, and comprehension, suggesting the function of these regions may link language with social cognition and social bonding. In effect, the social brain and social complexity hypotheses may jointly help to explain how neurotypical children and adults learn language, why autistic adults and children exhibit simultaneous deficits in language and social cognition, and why nonhuman primates and other animals with significant computational abilities do not acquire the capacity for language. But perhaps most critically, the following article argues that this and related research will allow scientists to generate a holistic profile and deeper understanding of the healthy adult social brain, while developing more innovative and effective diagnoses, prognoses, and treatments for maladies and deficits also associated with the social brain.

The circadian clock is a 24-hour cycle within the body that regulates various factors, including sleep, body temperature, and hormone secretion. It allows the body to adjust to the light and dark cycle. Disruptions to the circadian rhythm are important risk factors for many diseases, including neurodegenerative illnesses. The central clock is controlled by the clock genes in the suprachiasmatic nucleus (SCN) of the brain, and one of the main functions of the circadian clock is to regulate lipid metabolism. There has been a lack of investigation on the circadian regulation of lipid metabolism-related apolipoprotein genes in the brain; thus, this study sought to summarize the rhythmic expression of clock genes and lipid metabolism-related apolipoprotein genes within the SCN of Mus musculus. Out of the 20 apolipoprotein genes that were studied by the published database, all 9 genes were highly expressed in the SCN. Most of the 6 genes showed rhythmic expression in the brain of mice, suggesting that the master clock might regulate them. The results, therefore, reveal a potential target for preventing and treating circadian disorders. We summarized most studies of lipid-related apolipoprotein genes within limited locations of the SCN and brain to further understand how disordered cerebral lipid metabolism causes multiple brain diseases and disorders. We reviewed recent studies, determined the unexplored questions, and identified a potential direction for further research.

Following ischemic stroke, the degradation of myelin and other cellular membranes surpasses the lipid-processing capabilities of resident microglia and infiltrating macrophages. This imbalance leads to foam cell formation in the infarct and areas of secondary neurodegeneration, instigating sustained inflammation and furthering neurological damage. Given that mitochondria are the primary sites of fatty acid metabolism, augmenting mitochondrial biogenesis (MB) may enhance lipid processing, curtailing foam cell formation and post-stroke chronic inflammation. Previous studies have shown that the pharmacological activation of the β2-adrenergic receptor (β2-AR) stimulates MB. Consequently, our study sought to discern the effects of intensified β2-AR signal-ing on MB, the processing of brain lipid debris, and neurological outcome using a mouse stroke model. To achieve this goal, aged mice were treated with formoterol, a long-acting β2-AR ago-nist, daily for two and eight weeks following stroke. Formoterol increased MB in the infarct re-gion, modified fatty acid metabolism, and reduced foam cell formation. However, it did not re-duce markers of post-stroke neurodegeneration or improve recovery. Our findings suggest that boosting MB in myeloid cells is one component of a therapeutic avenue for improving brain lipid debris processing after stroke.

Device-mediated, non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive techniques and devices have been proposed or investigated to enhance drug delivery across the BBB. This paper presents the current state of the art and case studies that address the pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.

Approximately 6 million youth aged 12 to 20 consume alcohol monthly in the United States. The effect of alcohol consumption in adolescence on behavior and cognition is heavily researched, however, little is known about how alcohol consumption in adolescence may alter brain function, leading to long-term developmental detriments. In order to investigate differences in brain connectivity associated with alcohol use in adolescents, brain networks were constructed using resting state functional magnetic resonance imaging data collected by the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) from 698 youth (12-21 years, 117 hazardous drinkers and 581 no/low drinkers). Analyses assessed differences in brain network topology based on alcohol consumption in eight pre-defined brain networks, as well as in whole-brain connectivity. Within the central executive network (CEN), basal ganglia network (BGN), and sensorimotor network (SMN), no/low drinkers demonstrated stronger and more frequent connections between highly globally efficient nodes, with fewer and weaker connections between highly clustered nodes. Inverse results were observed within the dorsal attention network (DAN), visual network (VN), and frontotemporal network (FTN), with no/low drinkers demonstrating weaker connections between nodes with high efficiency and increased frequency of clustered nodes compared to hazardous drinkers. Results from this study show clear organizational differences between adolescents with no/low or hazardous alcohol use, suggesting that aberrant connectivity in these brain networks is associated with risky drinking behaviors.

Clinical management in neuro-oncology has changed to an integrative approach that incorporates molecular profile alongside histopathology and imaging findings. While the WHO guideline recommends genotyping of informative alterations as a routine clinical practice for central nervous system (CNS) tumors, acquisition of tumor tissue in the CNS is invasive and not always possible. Liquid biopsy is a non-invasive approach that provides the opportunity to capture the complex molecular heterogeneity of the whole tumor through detection of circulating tumor biomarkers in body fluids, such as blood or cerebrospinal fluid. Despite all the advantages, the low abundance of tumor-derived biomarkers, particularly in CNS tumors, as well as their short half-life has limited the application of liquid biopsy in clinical practice. Thus, it is crucial to identify factors that are associated with the presence of these biomarkers and explore possible strategies that can increase the shedding of these tumoral components into biological fluids. In this review, we first describe the clinical applications of liquid biopsy in CNS tumors including its roles in early detection of recurrence and monitoring of treatment response. We then discuss the utilization of imaging in identifying factors that affect the detection of circulating biomarkers as well as how image-guided interventions such as focused ultrasound can help enhance the presence of tumor biomarkers through blood-brain barrier disruption.

This article presents a study on brain tumor detection using the VGG-16 model, a convolutional neural network known for its performance in computer vision tasks. The aim of the study is to classify magnetic resonance imaging (MRI) images and accurately identify the presence of brain tumors. The dataset used consists of brain tumor MRI images, categorized into two classes: "NO" (no tumor) and "YES" (tumor). The methodology involves setting up the environment, importing and preprocessing the data, building the VGG-16 model, and evaluating its performance using metrics such as accuracy, precision, and recall. The results demonstrate an accuracy of approximately 88% on the validation set and 80% on the test set, indicating the potential of the VGG-16 model in supporting healthcare professionals in diagnosing brain tumors. The study contributes to the field of medical image analysis and offers insights into the application of deep learning for brain tumor detection.

Humans learn from a lot of information sources to make decisions. Once this information is learned in the brain, spatio-temporal associations are made, connecting all these sources (variables) in space and time represented as brain connectivity. In reality, to make a decision, we usually have only part of the infor-mation, either as a limited number of variables, or limited time to make the decision, or both. The brain functions as spatio-temporal associative memory. Inspired by the ability of the human brain, a brain-inspired spatio-temporal associative memory was proposed earlier, that utilizes the NeuCube brain-inspired spiking neural network framework. Here we apply the STAM framework to develop STAM for neuroimaging data, on the cases of EEG and fMRI, resulting in STAM-EEG and STAM-fMRI. The paper shows that once a NeuCube STAM classification model is trained on a complete spatio-temporal EEG or fMRI data, it can be recalled using only part of the time series, or/and only part of the used variables. We evaluate accordingly the temporal association accuracy and spatial association accuracy. This is a pilot study that opens the field for the development of multimodal classification systems on other multimodal neuroimaging data, such as the also shown longitudinal MRI data, trained on complete data, but recalled on partial data collected across different settings, in different labs and clinics, that may vary in terms of variables, time of data collection, and other parameters. The proposed methods will allow also for brain diagnostic/prognostic marker discovery using spatio-temporal neuroimaging data.

Deep brain stimulation (DBS) is an effective and safe medical treatment that improves the lives of patients with a wide range of neurological and psychiatric diseases, and has been consolidated as a first-line tool in the last two decades. Closed loop deep brain stimulation (CLDBS) pushes this tool further by automatically adjusting the stimulation parameters to the brain response in real-time. This paper presents a CLDBS with 2 stimulation channels and 2 acquisition channels. Each channel has a low-noise amplifier (LNA) buffer in differential configuration to eliminate the DC signal component of the input. Energy management is efficiently done by the control and communication unit. The battery supports almost 9 hours with both the acquisition and stimulation circuits active. If only the stimulation circuit is used as an Open Loop DBS (OLDBS), the battery can hold sufficient voltage for 24 hours of operation. The whole system is low-cost and portable and therefore it could be used as a wearable.

We aimed to evaluate the effect of hypoxia caused by different levels of chronic carbon monoxide (CO) exposure via total AgNOR area/total nuclear area (TAA/TNA) ratio and mean AgNOR number on rat brain tissue. Eighteen Albino Wistar adult male rats were randomly divided into three groups (control as group A, 1000ppm and 3000ppm concentration of CO gas exposed as group B and C, respectively). CO gas was chronically given as 30 min a day during seven days. Statistically significant differences were found among the groups for both mean AgNOR number (χ2=12.051, p=0.002) and TAA/TNA (χ2=12.316, p=0.002), respectively. When the two groups are compared in terms of TAA/TNA ratio, statistically significant differences were detected between control and 1000ppm (Z=-2.882, p=0.004), between control and 3000 ppm (Z=-2.882, p=0.004) for TAA/TNA ratio. Statistically significant differences were found between control and 1000 ppm (Z=-2.882, p=0.004), between control and 3000 ppm (Z=-2.887, p=0.004) for mean AgNOR number. It is important to determine new markers with high sensitivity and easy to apply in order to determine the effect of toxication in different organs and tissues (especially brain tissues) that are chronically exposed to carbon monoxide intoxication. It seems that AgNOR may be used for this purpose.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite extensive research efforts, the majority of trialed monotherapies to date have failed to demonstrate significant benefit. It has been suggested that this is due to the complex pathophysiology of TBI, which may possibly be addressed by a combination of therapeutic interventions. In this article, we have reviewed combinations of different pharmacologic treatments, combinations of non-pharmacologic interventions, and combined pharmacologic and non-pharmacologic interventions for TBI. Both preclinical and clinical studies have been included. While promising results have been found in animal models, clinical trials of combination therapies have not yet shown clear benefit. This may possibly be due to their application without consideration of the evolving pathophysiology of TBI. Improvements of this paradigm may come from novel interventions guided by multimodal neuromonitoring and multimodal imaging techniques, as well as the application of multi-targeted non-pharmacologic and endogenous therapies. There also needs to be a greater representation of female subjects in preclinical and clinical studies.

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.

Background: Due to the importance of brain death (BD) diagnostic do not mistake, reliable confirmatory exams should be performed to enhance its security. This study aims to evaluate the intracranial pressure (ICP) pulse morphology behavior in brain-dead patients through a noninvasive monitoring system. Methods: A pilot case-control study was conducted in adults that met the BD national protocol criteria. Quantitative data from the ICP waveforms were extracted and analyzed comparing BD patients and health subjects. Results: Fifteen patients were included. ICP waveforms presented substantial differences amidst BD patients when compared to the control group. Moreover, pulse amplitude and time to peak variables values in the case group were also statistically significant. Conclusions: In this exploratory study, noninvasive ICP waveforms have shown potential as a screening method in patients with suspected brain death. Future studies should be carried out in a larger population.

Malignant gliomas are the most common primary brain tumors in adults up to an extent of 78% of all primary malignant brain tumors. However, total surgical resection is almost unachievable due to considerable infiltrative ability of glial cells. The efficacy of current multimodal therapeutic strategies is, furthermore, limited by the lack of specific therapies against malignant cells, and, therefore, the prognosis these in patients is still very unfavorable. The limitation of conventional therapies, which may result from inefficient delivery of the therapeutic or contrast agent to brain tumors are major reasons for this unsolved clinical problem. The major problem in brain drug delivery is the presence of the blood brain barrier which limits the delivery of many chemotherapeutic agents. Nanoparticles, thanks to their chemical configuration, are able to go through the blood-brain barrier carrying drugs or genes targeted against gliomas. Carbon nanomaterials show distinct properties including electronic properties, penetrating capability on the cell membrane, high drug-loading and pH-dependent therapeutic unloading capacities, thermal properties, large surface area and easy modification with molecules, which render them as a suitable candidate to deliver drugs. In this review we will focus on the potential effectiveness of the use of carbon nanomaterials in the treatment of malignant gliomas discussing the current progress of in vitro and in vivo researches of carbon nanomaterials-based drug delivery to brain.

Decision making is a complex process involving various parts of the brain which are active during different times. It is challenging to measure externally the exact instance when any given region becomes active during the decision-making process. Here we try to extract and visualize the dynamic functional brain activation information from the observed fMRI data. We propose the use of a regularized deconvolution model to simultaneously map various activation regions within the brain and track how different activation regions changes with time. Thus, providing both spatial and temporal brain activation information. The activation information can then be further analyzed as per need and requirements. The proposed technique was validated using simulated data and then applied to a simple decision-making task for identification of various brain regions involved in different stages of decision making. The visualization aspect of the algorithm allows us to actually see the flow of activation (and deactivation) in form of a motion picture. The dynamic estimate may aid in understanding the causality of activation between various brain regions in a better way.

If the development of machine learning and artificial intelligence plays a role in many fields of research and technology today, it has a special relationship with neurosciences. Indeed, historically inspired by our knowledge of the brain, deep learning shares some vocabularies with neurosciences and can sometimes be considered a brain’s model. Taking the particular example of epileptic seizure, which can develop in any biological neural tissue, we raise the question if and how the models used for deep learning can capture or model these pathological events. This particular example is a starting point to discuss the nature, limits, and functions of these models, and what we expect from a model of the brain. Finally, we argue that a pluralistic approach leading to the integrated coexistence of different models is necessary to study the brain in all its complexity.

Scientific theories on the functioning and dysfunction of the human brain require a good understanding of both its development — before and after birth, and through maturation to adulthood — and its evolution from the ancestral primate brain. Adopting a complex-systems approach, here we propose that the apparent uniqueness of humans’ cognitive capacities might best be understood as emerging from multiple nested “virtuous cycles.” In particular, we propose that the intimate link that exists between oxygen metabolic loops, cortical expansion, and ultimately cognitive and social demands is a key driver of genetic developmental programs for the human brain. Overall, our proposed evolutionary model makes explicit mechanistic links between metabolism, molecular and cellular brain heterogeneity, and behaviour that may in time provide a clearer understanding of brain developmental trajectories and their disorders.

The neural-crest derived enteric nervous system (ENS) is the intrinsic nervous system of the gastrointestinal (GI) tract and controls all gut functions, including motility. Lack of ENS neurons causes various ENS disorders such as Hirschsprung Disease. One treatment option for ENS dis-orders includes the activation of resident stem cells to regenerate ENS neurons. Regeneration in the ENS has mainly been studied in mammalian species using surgical or chemically-induced injury methods. These mammalian studies showed a variety of regenerative responses with generally limited regeneration of ENS neurons, but (partial) regrowth and functional recovery of nerve fibers. Several aspects might contribute to the variety in regenerative responses, including observation time after injury, species, and gut region targeted. Zebrafish have recently emerged as a promising model system to study ENS regeneration as larvae possess the ability to generate new neurons after ablation. As the next steps in ENS regeneration research, we need a detailed under-standing of how regeneration is regulated on a cellular and molecular level both in animal models with high and low regenerative capacity. Understanding the regulatory programs necessary for robust ENS regeneration will pave the way for using neural regeneration as a therapeutic approach to treating ENS disorders.

During the 90 days following hospitalization for acute heart failure, ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart failure. Two mechanisms of sudden unexpected death have been suggested to possibly result from 4 significant influences on pathophysiology in the brain. The two causes of death are severe cardiac arrhythmia, and neurogenic pulmonary edema. They are both mediated through the brainstem autonomic nuclei generally, and executed specifically through the dorsal motor nucleus of the vagus nerve. The four significant influences on pathophysiology in the brainstem autonomic nuclei are: 1) Hyper-stimulation of neurons in the solitary tract nucleus, increasing their metabolic requirements; 2) Inadequate blood flow at a vascular watershed terminus; 3) Additionally decreased blood flow following vasoconstriction related to relative hyperventilation and decreased pCO2 levels; 4) Gravitational ischemia in the brain—caused by the weight of the brain mass sitting above the brainstem. Changes in head tilt release gravitational ischemia in the brain. There is no specific head position (relative to gravity) that is considered favorable or unfavorable for an extended period of time (i.e. more than 24 hours). Even a small degree of head elevation, used in managing pulmonary congestion, may increase gravitational ischemia in the posterior fossa and brainstem. In this paper we suggest a new and important research avenue for intervening in cardiac arrhythmias, and preventing their occurrence, through the non-invasive use of head-tilting, and other head repositioning maneuvers. This could potentially help many geriatric patients with heart failure, who have decreased mobility in bed, and who tend to stay in one position longer, thereby increasing gravitational ischemia in the brain.

Epigenetic mechanisms, including post-translational modifications of DNA and histones that influence chromatin structure, regulate gene expression during normal development, and are also involved in carcinogenesis and cancer progression. The histone methyltransferase G9a (euchromatic histone lysine methyltransferase 2, EHMT2), which mostly mediates mono- and dimethylation by histone H3 lysine 9 (H3K9), influences gene expression involved in embryonic development and tissue differentiation. Overexpression of G9a has been observed in several cancer types, and different classes of G9a inhibitors have been developed as potential anticancer agents. Here, we review the emerging evidence suggesting the involvement of changes in G9a activity in brain tumors, namely glioblastoma (GBM), the main type of primary malignant brain cancer in adults, and medulloblastoma (MB), the most common type of malignant brain cancer in children. We also discuss the role of G9a in neuroblastoma (NB) and the drug development of G9a inhibitors.

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.

Blood-brain-barrier is a major obstacle in treating brain-related disorders as it does not allow to deliver drugs in the brain. In order to facilitate delivery of drugs in brain, we developed a method for predicting blood-brain-barrier penetrating peptides. These blood-brain barriers penetrating peptides (B3PPs) can act as therapeutic as well as drug delivery agents. We trained, tested, and evaluated our models on blood-brain-barrier peptides obtained from the B3Pdb database. First, we compute a wide range of peptide features then we select relevant peptide features. Finally, we developed numerous machine learning-based models for predicting blood-brain-barrier peptides using selected features. Our model based on random forest performed best on the top 80 selected features and achieved a maximum 85.08% accuracy with 0.93 AUROC. We also developed a web server, B3pred that implements our best models. It has three major modules that allow users to; i) predict B3PPs, ii) scanning B3PPs in a protein sequence, and iii) designing B3PPs using analogs. Our web server and standalone software is freely available at https://webs.iiitd.edu.in/raghava/b3pred/.

Brain, the most complex object known in the universe, uses few watts of power. To mimic it a nuclear power plant will be required and this power house controls the human body, single handedly. Surprisingly, “On the left side, nothing is right and on the right side there is nothing left”. Typically, there are two lateral halves of the brain: Left hemisphere and right hemisphere working distinctly. Left hemisphere is inclined towards logic; Right hemisphere is the root cause of imagination added with critical thinking. In situations like the current pandemic, COVID-19, it is the right half which tends to dominate the processing. This gives birth to mental stress, anxiety thus, aggravating the existing medical condition. Considering this pattern, a survey was conducted in Durg district of Chhattisgarh, which is one of the most hard hit epicentre of the COVID-19 second wave in India. According to this survey, it was revealed that largely women of all age groups (10-25, 26-40, 40 above) were right brained i.e. dominance of right over left hemisphere. Being more imaginative and creative thinkers they are more likely to suffer from mental issues than males. The aim of this research is to improve the mental wellbeing of the citizens in such threatening conditions. To prevent this situation awareness is a must and some stress relieving games have also been created.

Brain development during the prenatal period is rapid and unparalleled by any other time during development. Biological systems undergoing rapid development are at higher risk for disorganizing influences. Therefore, certain prenatal exposures impact brain development, increasing risk for negative neurodevelopmental outcome. While prenatal exposures have been associated with cognitive and behavioral outcomes later in life, the underlying macroscopic brain pathways remain unclear. Here, we review studies investigating the association between prenatal exposures and infant brain development focusing on prenatal exposures via maternal physical health factors, maternal mental health factors, and maternal drug and medication use. Further, we discuss the need for studies to consider multiple prenatal exposures in parallel and suggest future directions for this body of research.

The heterogeneity of tumor infiltrating lymphocytes is not well characterized in brain metastasis. To address this, we performed a targeted analysis of immune cell subsets in brain metastasis tissues to test which immunosuppressive routes are involved in brain metastasis. We performed multiplex immunofluorescence (mIF), using commercially available validated antibodies on twenty formalin-fixed paraffin embedded whole sections. We quantitated the subsets of immune cells utilizing a targeted panel of proteins including PanCK, CD8, CD4, VISTA and Iba1, and analyzed an average of 15000 cells per sample. We classified tumours as either high (>30%) or low (<30%) tumour infiltrating lymphocytes (TILs) and found that increased TILs density correlated with survival. We next sought out to phenotype these TILs using mIF. The tumours with low TILs (n=9) had significantly higher expression of the immune-checkpoint molecule VISTA in tumor cells (p<0.01) as well as in their microenvironment (p<0.001). Contrastingly, the brain metastatic tumours with high TILs (n=8) displayed higher levels of activated microglia, as measured by Iba1 expression. Low TILs-tumours displayed CD8+ T-cells that co-express VISTA (p<0.01) significantly more compared to high TILs group, where CD8+ T-cells significantly co-express Iba1 (p<0.05). Interestingly, no definite phenotypes of CD4+ subsets were observed. These results were supported by RNA analysis of a publicly available, independent cohort. In conclusion, our work contributes to a growing understanding of the immune surveillance escape routes active in brain metastasis.

The effect of Alzheimer's disease (AD) medications on CD4+ T cells homing has not been thoroughly investigated. Alzheimer's disturbs the life of at least five million persons in the USA. CD4+ T cells could both exacerbate and reduce AD symptoms. Regulating CD4+ T cells homing to the leaky blood-brain barrier (BBB) constitutes a new hope for enhancing AD prognosis. Alzheimer's drugs such as Donepezil (Aricept), Rivastigmine (Exelon), Galantamine (Razadyne) and memantine are known to play an important part in regulating the neurotransmitters mechanisms. However, little is known about the effect of these drugs on CD4+ T cells homing. In this review, we focus on current and new drugs that could modulate CD4+ T cells interactions with the BBB in AD.

Machine Learning (ML) approaches have been fruitfully applied to several classification problems of neurophysiological activity. Considering the relevance of emotion in human cognition and behaviour, ML found an important application field in emotion identification based on neurophysiological activity. Nonetheless, the literature results present a high variability depending on the neuronal activity measurement, the signal features and the classifier type. The present work aims to provide new methodological insight on ML applied to emotion identification based on electrophysiological brain activity. For this reason, we recorded EEG activity while emotional stimuli, high and low arousal (auditory and visual) were provided to a group of healthy participants. Our target signal to classify was the pre-stimulus onset brain activity. Classification performance of three different classifiers (LDA, SVM and kNN) was compared using both spectral and temporal features. Furthermore, we also contrasted the classifiers performance with static and dynamic (time evolving) features. The results show a clear increased in classification accuracy with temporal dynamic features. In particular, the SVM classifiers with temporal features showed the best accuracy (63.8 %) in classifying high vs. low arousal auditory stimuli.

Mammalian genomes encode tens of thousands of long-noncoding RNAs (lncRNAs), which are capable of interactions with DNA, RNA and protein molecules, thereby enabling a variety of transcriptional and post-transcriptional regulatory activities. Strikingly, about 40% of lncRNAs are expressed specifically in the brain in precisely regulated temporal and spatial expression patterns. In stark contrast to the highly conserved repertoire of protein-coding genes, thousands of new lncRNAs have appeared during primate nervous system evolution with hundreds of human-specific lncRNAs. Their evolvable nature and the myriad of potential functions make lncRNAs ideal candidates for drivers of human brain evolution. The human brain displays the largest relative volume of any animal species and the most remarkable cognitive abilities. In addition to brain size, structural reorganization and adaptive changes represent crucial hallmarks of human brain evolution. LncRNAs are increasingly reported to be involved in neurodevelopmental processes including proliferation, neurite outgrowth and synaptogenesis, as well as in neuroplasticity, suggested to underlie human brain evolution. Hence, evolutionary human brain adaptations are proposed to be essentially driven by lncRNAs, which will be discussed in this review.

Cognitive deterioration caused by illness or aging often occurs before symptoms arise, and their timely diagnosis is crucial to reducing its medical, personal, and societal impacts. Brain-Computer Interfaces (BCIs) stimulate and analyze key cerebral rhythms, enabling reliable cognitive assessment that can accelerate diagnosis. The BCI system presented analyzes Steady-State Visually Evoked Potentials (SSVEPs) elicited in subjects of varying age to detect cognitive aging, predict its magnitude, and identify its relationship with SSVEP features (band power and frequency detection accuracy), which were hypothesized to indicate cognitive decline due to aging. The BCI system was tested with subjects of varying age to assess its ability to detect aging-induced cognitive deterioration. Rectangular stimuli flickering at theta, alpha, and beta frequencies were presented to subjects, and frontal and occipital EEG responses were recorded. These were processed to calculate detection accuracy for each subject and calculate SSVEP band power. A neural network was trained using the features to predict cognitive age. The results showed potential cognitive deterioration through age-related variations in SSVEP features. Frequency detection accuracy declined after age group 20–40 and band power, throughout all age groups. SSVEPs generated at theta and alpha frequencies, especially 7.5 Hz, were the best indicators of cognitive deterioration. Here, frequency detection accuracy consistently declined after age group 20-40 from an average of 96.64% to 69.23%. The presented system can be used as an effective diagnosis tool for age related cognitive decline.

Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults, remains one of the least treatable cancers. Current standard of care—combining surgical resection, radiation, and alkylating chemotherapy—results in a median survival of only 15 months. Despite decades of investment and research into the development of new therapies, most candidate anti-glioma compounds fail to translate into effective treatments in clinical trials. One key issue underlying this failure of therapies that work in pre-clinical models to generate meaningful improvement in human patients is the profound mismatch between drug discovery systems—cell cultures and mouse models—and the actual tumors they are supposed to imitate. Indeed, current strategies that evaluate the effects of novel treatments on GBM cells in vitro fail to account for a wide range of factors known to influence tumor growth. These include secreted factors, the brain’s unique extracellular matrix, circulatory structures, the presence of non-tumor brain cells, and nutrient sources available for tumor metabolism. While mouse models provide a more realistic testing ground for potential therapies, they still fail to account for the full complexity of tumor-microenvironment interactions, as well as the role of the immune system. Based on the limitations of current models, researchers have begun to develop and implement novel culture systems that better recapitulate the complex reality of brain tumors growing in situ. A rise in the use of patient derived cells, creative combinations of added growth factors and supplements, may provide a more effective proving ground for the development of novel therapies. This review will summarize and analyze these exciting developments in 3D culturing systems. Special attention will be paid to how they enhance the design and identification of compounds that increase the efficacy of radiotherapy, a bedrock of GBM treatment.

Defensive behavior is a function of specific survival circuits, the “aversive brain system”, that are thought to be conserved across vertebrates, and involve threat detection and the organization of defensive responses to reduce or eliminate threat. In mammals, these circuits involve amygdalar and hypothalamic subnuclei and midbrain circuits. The increased interest in teleost fishes as model organisms in neuroscience created a demand to understand which brain circuits are involved in defensive behavior. Telencephalic and habenular circuits represent a “forebrain circuit” for threat processing and organization of responses, being important to mounting appropriate coping responses. Specific hypothalamic circuits organize neuroendocrine and neurovegetative outputs, but are the less well-studied in fish. A “midbrain circuit” is represented by projections to interneurons in the optic tectum which mediate fast escape responses via projections to the central gray and/or the brainstem escape network. Threatening stimuli (especially visual stimuli) can bypass the “high road” and directly activate this system, initiating escape responses. Increased attention to these circuits in an evolutionary framework is still needed.

Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in ischemic condition is also presented.

We take what we see, hear, smell and feel for the reality. However, as neuroscientists, we know that this reality, that is, our perceptual world, is in fact made up by the brain from the processing of the nerve impulses coming from receptors. Ancient Greeks used to think that this perceptual world, sometimes called our 3D movie (Chalmers), is emitted and has its own physical nature. Given how real the 3D movie looks to us, it is still difficult today to consider that all we would be dealing with would be patterns of brain activity The present study thus aimed at testing whether the perceptual world could have some physical existence in addition to that of the neural patterns responsible for it. To achieve that goal, we tried to see whether brains could be sensitive to the 3D movie of others. This, admittedly unusual, operational hypothesis was based on two assumptions. First, brains are sensitive to the 3D movie, as our experience includes reactions to our perceptual world. Second, the physicality at stake does not differ across individuals. We recorded the event-related brain potentials (ERPs) evoked by stimuli of the international affective picture system in pairs of closely-related participants. Most importantly, they could neither see the stimuli simultaneously presented to their partners nor their reactions to them. As in Bouten et al. (2015), around 400 ms after the onset of the stimuli, ERPs started being more positive in inconsistent conditions. Namely, when the two subjects of each pair were presented with the same stimulus whereas they were told it would be a different one and vice-versa (i.e., different-stimuli expected to be same). ERPs were less positive when the two subjects of a pair were presented with the same stimuli and were told they were the same and conversely (i.e., different-stimuli expected to be different). The same experiment was then run in pairs of strangers. No significant effect of consistency on ERPs was observed even though participants could, this time, see, in the very periphery of their visual field, the reactions of their partner to the stimuli. We thus use the results of both studies to support a new version of the emission theory of consciousness and to suggest that the sensitivity to the perceptual world of others may depend on their prior familiarity with it.

In the field of nasal delivery, one of the most fascinating applications is the delivery of drugs directly to the central nervous system bypassing the blood brain barrier. This approach would provide a series of benefits, such as dose lowering and direct targeting of potent drugs, ultimately reducing their systemic side effects. Recently, clinical trials have explored the nasal administration of insulin for the treatment of Alzheimer’s disease, with promising results. The use of nanomedicines could provide further options for making nose-to-brain delivery reality. In particular, apart from the selection of devices able to deposit the formulation in the upper part of the nose, surface modification of these nanomedicines appears the key strategy to optimize the delivery of drugs from the nasal cavity to the brain. In this review, nanomedicines delivery approaches based on surface electrostatic charges, mucoadhesive polymers, as well as chemical moieties targeting nasal epithelium, will be discussed and critically evaluated for nose-to-brain delivery.

Traumatic brain injury (TBI) can result in persistent sensorimotor and cognitive deficits, which occur through a cascade of deleterious pathophysiological events over time. In this study, we investigated the hypothesis that neurodegeneration caused by TBI leads to impairments in sensorimotor function. TBI induces the activation of the caspase-3 enzyme, which triggers cell apoptosis in an in vivo model of fluid percussion injury (FPI). We analyzed caspase-3 mediated apoptosis by TUNEL staining and PARP and annexin V western blotting. We correlated the neurodegeneration with sensorimotor deficits by conducting the animal behavioral tests including grid walk, balance beam, inverted screen test, and climb test. Our study demonstrated that the excess cell death or neurodegeneration correlated with the neuronal dysfunction and sensorimotor impairments associated with TBI.

Urea cycle disorders (UCDs) are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD). OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA) induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological changes include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of plasma ammonia level at presentation and duration of hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days post natal with plasma ammonia and glutamine of 677 and 4024 micromol/L and had a missense mutation in Exon 4 (p.R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. He suffered recurrent acute hyperammonemic episodes despite compliance, triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI based disease biomarkers.

Here we performed a comparative experimental analysis by EPR spectroscopy of the intensity of nitric oxide (NO) production and copper content in the injured and uninjured areas of the frontal lobes and the hippocampus of the brain of male Wistar rats, after modeling of combined brain and spinal cord injury. Brain and spinal cord injury were modelled by local destruction of the left precentral region of the brain using a stylet followed by hemorrhage injury at the level of the first lumbar vertebra of the spinal cord. We found a significant decrease in NO production 7 days after injury modeling in the injured and uninjured (contralateral) brain regions, but the copper content remained unchanged one week after injury modeling. Thus, combined brain and spinal cord injury is not accompanied by a radical change in the activity of the antioxidant system in the brain, which is also confirmed by the absence of changes in NO production and copper content in the hippocampus.

The hematopoietic system plays a crucial role in immune defense response and normal development, and is regulated by various factors from other tissues. The dysregulation of hematopoiesis is associated with melanotic mass formation; however, the molecular mechanisms underlying this process are poorly understood. Here, we observed that the overexpression of miR-274 in the fat body resulted in the formation of melanotic masses. Moreover, abnormal activation of the JNK and JAK/STAT signaling pathways was linked to these consequences. In addition to this defect, miR-274 overexpression in the larval fat body decreased the total tissue mass, leading to a reduction in body weight. miR-274-5p was found to directly suppress the expression of found-in-neurons (fne), which encodes an RNA-binding protein. Similar to the effects of miR-274 overexpression, fne depletion led to melanotic mass formation and growth reduction. Collectively, miR-274 plays a regulatory role in the fne-JNK signaling axis in melanotic mass formation and growth control.

Considering the relevance of the pathogenesis research of different liver diseases, in our study we investigated the possible activity of IL-23/IL-17 axis on the im-munohepatotoxicity of two etiologically different CLD. A total of patients with CHC infection, 19 with NASH and 20 healthy controls (CG) were recruited. After histological verification from liver tissue obtain by liver biopsy, patients with CHC were divided into two groups: CHC-NSF (F0/F1/F2)-non-significant fibrosis, 20 patients, and CHC-SF (F3/F4)-significant fibrosis/cirrhosis, 16 patients. All anthropometric, biochemical, immunological cytokines (IL-6, IL-10, IL-17 and IL-23) tests were performed accordance to standard procedure. The plasma levels of IL-6, Il-17A and IL-23 were significantly higher in CHC-SF and NASH in compared with CG. Also, plasma levels of IL-23/IL-17A were significantly higher in NASH in compared to CHC-SF. In CHC-SF we had significantly lowest IL-10 level in compared with all three groups. Liver tissue levels of IL-17A and IL-23 in CHC-NSF were significantly lower in compared with NASH. IN CHC-SF and NASH, IL17-A and IL-23 in liver tissue were significantly higher in compare to plasma levels. In conclusan, proinflammatory response of IL-23/17A axis is dominant in plasma and liver tissue in CHC with higher levels of liver fibrosis and in NASH patients.

In this paper, dual-rotor counter-rotating (CR) configurations of vertical axis wind turbines (VAWT) are briefly inspected and divided into three types. This investigation was focused on one of these types – the CR-VAWT with co-axial rotors, in which two equal rotors are placed on the same shaft, displaced from each other along it and rotate in opposite directions. For this CR-VAWT with three-blade H-Darrieus rotors, the properties of the design in terms of aerodynamics, mechanical transmission and electric generator, as well as control system are analyzed. A new direct-driven dual-rotor (DR) permanent magnet synchronous generator (PMSG) was proposed, in which two built-in low-power PM electric machines have been added. They perform two functions – start-up and overclocking of the rotors to the angular velocity at which the lifting force of the blades is generated and stabilizing the CR-VAWT work as wind gusts act on the two rotors. Detailed in this paper is the evaluation of aerodynamic performance of the CR-VAWT via 3D computational fluid dynamics (CFD) simulations. The evaluation was conducted using the CONVERGE CFD software with the inclusion of the actuator line model for the rotor aerodynamics, which significantly reduces the computational effort. Obtained results show that both rotors, while they rotate in opposite directions, had a positive impact on each other: the power coefficients of the upper and lower rotors in the CR-VAWT increased by 5.5% and 13.3% respectively compared to the single-rotor VAWT at the optimal distance between the rotors of 0.3 from a rotor height.

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.

Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/CFS) and Long COVID are characterized by debilitating post-exertional malaise and other core symptoms related to immune dysregulation resultant from post-viral infection, including mitochondrial dysfunction, chronic neuroinflammation and gut dysbiosis. The reported associations between altered microbiota composition and cardinal symptoms of ME/CFS and Long COVID, suggesting that use of microbial preparations, such as probiotics, by restoring the homeostasis of the brain-immune-gut axis may help in the management of symptoms in both conditions. Therefore, this review aims to investigate the implications of alerted gut microbiome and assess the evidence supporting use of microbial-based preparations, including probiotics, synbiotics, postbiotics alone and/or in combination with other nutraceuticals in the management of fatigue, inflammation, as well as neuropsychiatric and gastrointestinal symptoms among patients with ME/CFS and Long COVID.

Polyphenols and fermentable fibers have shown favorable effects on gut microbiota composition and metabolic function. However, few studies have investigated whether combining multiple fermentable fibers or polyphenols may have additive beneficial effects on gut microbial states. Here, an in vitro fer-mentation model, seeded with human stool combined from 30 healthy volunteers, was supplemented with blends of polyphenols (PP), dietary fibers (FB) or their combination (PPFB) to determine influence on gut bacteria growth dynamics and select metabolite changes. PP and FB blends independently lead to significant increases in the absolute abundance of select beneficial taxa, namely Ruminococcus bromii, Bifidobacterium spp., Lactobacillus spp. and Dorea spp. Total short chain fatty acid concentrations, relative to non-supplemented control (F), increased significantly with PPFB and FB supplementation, but not PP. Indole and ammonia concentrations decreased with FB and PPFB supplementation, but not PP alone while increased antioxidant capacity was only evident with both PP and PPFB. These findings demonstrated that, while the independent blends displayed selective positive impacts on gut states, combination of both blends provided an additive effect. The work outlines the potential of mixed substrate blends to elicit a broader positive influence on gut microbial composition and function to build resiliency toward dysbiosis.

Intestinal epithelial cell activities during homeostasis and regeneration are well described, but their potential interactions with stromal cells remain unresolved. Exploring the functions of these heterogeneous intestinal mesenchymal stromal cells (iMSCs) remains challenging due to the lack of specific markers for most functionally homogenous subpopulations. In recent years, however, novel clustering techniques such as single-cell RNA sequencing (scRNA-seq), fluorescence-activated cell sorting (FACS), confocal microscope, and computational remodeling of intestinal anatomy have helped identify and characterize some specific iMSC subsets. These methods help researchers learn more about the localization and functions of iMSC populations during intestinal morphogenic and homeostatic conditions. Furthermore, it is imperative to understand their cellular pathways for activation and how they interact with surrounding cellular components, particularly during intestinal epithelial regeneration that follows mucosal injury. This review provides insights into the spatial distribution and functions of some identified iMSC subtypes in intestinal morphogenesis, homeostasis, and regeneration. We reviewed related signaling mechanisms implicated during epithelial and subepithelial stromal cell crosstalk. Future research should focus on elucidating the molecular intermediates of these regulatory pathways to open a new frontier for potential therapeutic targets that can alleviate intestinal mucosa-related injuries.

This study evaluated the influence of methotrexate (MTX) and non-surgical periodontal treatment (NSPT) on the composition of the oral-gut microbiota in patients with rheumatoid arthritis (RA). Assessments were performed at baseline (T0), 6 months after MTX treatment (T1), and 45 days after NSPT (T2). The composition of the oral and gut microbiota was assessed by amplifying the V4 region of the 16S gene from subgingival plaques and stools. The results of the analysis of continuous variables were presented descriptively and non-parametric tests were adopted. Thirty-seven patients (27 with periodontitis) were evaluated at T0; 32 patients (24 with periodontitis) at T1; and 28 patients (17 with periodontitis) at T2. Nine individuals were lost to follow-up. MTX tended to reduce the alpha diversity of the oral-gut microbiota, while NSPT appeared to increase the number of different species of oral microbiota. MTX and NSPT influenced beta diversity in the oral microbiota. The relative abundance of oral microbiota was directly influenced by periodontal status. MTX did not affect the periodontal condition but modified the interactions between clinical parameters and the oral-gut microbiota. MTX and NSPT directly affected the composition and richness of the oral-gut microbiota. However, MTX did not influence periodontal clinical parameters.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to significant global health implications. Although the respiratory manifestations of COVID-19 are widely recognized, emerging evidence suggests that the disease may also significantly affect the gut microbiota, the intricate community of bacteria that lives within the gastrointestinal system. This extensive article intends to investigate the impact of COVID-19 on the gut microbiota, examining the underlying mechanisms, clinical implications, and potential therapeutic interventions. Understanding the complex interactions between COVID-19 and the gut microbiota will help us to gain valuable insights into the broader consequences of this viral infection on human health.

Phage, which is often used therapeutically, has begun to receive interest as an alternative to antibiotic growth promoters (AGPs) to enhance chicken growth. Another option that has been extensively studied as a growth promoter in chicken is probiotics. However, there are no studies using phages and probiotics as prospective feed additives for broiler chickens. Therefore, this study demonstrated the effects of phage cocktail, probiotics and their combinations on growth performance and gut microbiota of broiler chickens. A total of 288 one-day-old male Cobb 500 broilers were randomly allotted to 1 of 6 treatments in a completely randomised design. The treatments were: (i) C (basal diet (BD) only), (ii) 1ɸ (BD + 0.1% phage cocktail), (iii) 2ɸ (BD + 0.2% phage cocktail), (iv) P (BD + 0.1% probiotic), (v) 1ɸP (BD + 0.1% phage cocktail + 0.1% probiotic), (vi) 2ɸP (BD + 0.2% phage cocktail + 0.1% probiotic). The 1ɸP treatment had significantly (P < 0.05) better BW (35 d), BWG (22 – 35 d, 1 – 35d), and FCR (1-21 d. 22-35 d, 1-35 d) compared to C. Unique gut microbiota diversity was also found between the ɸP (1ɸP and 2ɸP) and non-ɸP groups (C, 1ɸ, 2ɸ and P) in ilea, particularly in the 35 d chickens. Microorganisms associated with short-chain fatty acid (SCFA) producers were significantly (P <0.05) present in the ɸP group than in the non- ɸP group. The carbohydrate and amino acid metabolism predicted genes were significantly upregulated in ɸP groups compared to non- ɸP groups. These genes were involved in the digestion and absorption of nutrients as well as the production of energy. Our findings showed that 1ɸP treatment could be a potential alternative to AGPs for poultry where growth performance was enhanced, and gut microbiota was positively modulated.

Celiac disease (CD) is a permanent intolerance to dietary protein, gluten, from wheat rye and barley. It occurs in about 1% worldwide population, in genetically predisposed individuals bearing human leukocyte antigen (HLA) DQ2/DQ8. Gut epithelial cell stress and innate immune activation are responsible for breaking oral tolerance to gliadin, the gluten component. To date, the only treatment available for CD is a long-term gluten-free diet. Several evidences show that an altered composition of the intestinal microbiota (dysbiosis) could play a key role in the pathogenesis of CD, through the modulation of intestinal permeability and the regulation of the immune system. Here we show that gliadin induces a chronic ER stress condition in the small intestine of a CD mouse model and that the co-administration of probiotics efficiently attenuates both UPR and gut inflammation. Moreover, the composition of probiotics formulations might differ in their activity at molecular level, especially toward the three axes of the UPR. Therefore, rebalancing the gut microbiota composition by probiotics administration might rep-resent a new strategy to treat CD affected patients.

Emerging data have demonstrated a strong association between the gut microbiota and the development of cardiovascular disease (CVD) risk factors such as atherosclerosis, inflammation, obesity, insulin resistance, platelet hyperactivity, and plasma lipid abnormalities. Several studies in humans and animal models have demonstrated an association between gut microbial metabolites, such as trimethylamine-N-oxide (TMAO), short-chain fatty acids, and bile acid metabolites, amino acid breakdown products, with CVD. Human blood platelets are a critical contributor to the hemostatic process. Besides, these blood cells play a crucial role in developing atherosclerosis and, finally, contribute to cardiac events. Since the TMAO, and other metabolites of the gut microbiota, are associated with platelet hyperactivity, lipid disorders, and oxidative stress, the diet-gut microbiota interactions have become an important research area in the cardiovascular field. Platelets became hyperactive in people with diabetes mellitus, sedentary lifestyle, obesity, and insulin resistance and exhibited increased sensitivity at a baseline level and in response to agonists, ultimately contributing to increased aggregation plaque development. In addition to these factors, TMAO also contributes to platelet hyperactivity. Several approaches are now suggested to reduce plasma TMAO levels, such as microbiota modulation using probiotics, prebiotics, and oral broad-spectrum antibiotics. This review describes the association between microbiota-derived metabolites and CVD development.

Probiotics are increasingly used by consumers and practitioners to reduce gastrointestinal (GI) distress and improve gut function. Here, we sought to determine whether addition of supplemental bacteriophages (PreforPro) could enhance the effects of a common probiotic, Bifidobacterium animalis subsp. lactis (B. lactis) on GI health. We conducted a 4-week, randomized, parallel-arm, double-blind, placebo-controlled trial where primary outcomes included self-assessments of GI health, a daily stool log, and 16s rRNA analysis of gut microbial populations. We observed within group improvements in GI inflammation (p=0.01) and a trending improvement in colon pain (p=0.08) in individuals consuming B. lactis with PreforPro, but not in the group consuming only the probiotic. There was also a larger increase in Lactobacillus and short chain fatty acid-producing microbial taxa detected in stool of participants taking PreforPro with B. lactis compared to the probiotic alone. Overall, these results suggest the addition of PreforPro as a combination therapy may alter gut ecology to extend the GI benefits of consuming B. lactis or other probiotics.

Opioids are highly addictive substances with a relapse rate of over 90%. While preclinical models of chronic opioid exposure exist for studying opioid dependence, none recapitulate the relapses observed in human opioid addiction. The mechanisms associated with opioid dependence, the accompanying withdrawal symptoms and the relapses that are often observed months or years after opioid dependence are poorly understood. Therefore, we developed a novel model of chronic opioid exposure whereby the level of administration is self-directed with periods of behavior acquisition, maintenance and then extinction alternating with reinstatement. This profile arguably mirrors that seen in humans, with initial opioid use followed by alternating periods of abstinence and relapse. Recent evidence suggests that dietary interventions that reduce inflammation, including omega-3 fatty acids such as docosahexaenoic acid (DHA), may reduce substance misuse liability. Using the self-directed intake model, we characterize the observed profile of opioid use and demonstrate that a diet enriched in polyunsaturated fat acids (PUFAs) ameliorates oxycodone-seeking behaviors in the absence of drug availability and reduces anxiety. Guided by the major role gut microbiota have on brain function, neuropathology, and anxiety, we profile the microbiome composition and the effects of chronic opioid exposure and DHA supplementation. We demonstrate that withdrawal of opioids led to a significant depletion in specific microbiota genera whereas DHA supplementation increased microbial richness, phylogenetic diversity, and evenness. Lastly, we examined the activation state of microglia in the striatum and found that DHA supplementation reduced the basal activation state of microglia. These preclinical data suggest that a diet enriched in PUFAs could be used as a treatment to alleviate anxiety induced opioid-seeking behavior and relapse in human opioid addiction.

Mass insect rearing can have a range of applications, for example in biological control of insects. Since the performance of released biological control agents determines efficacy, the competitive fitness of insects post release is a key variable. Here, we tested whether inoculation with a gut symbiont, Enterobacter cloacae, and gnotobiotic rearing of larvae could improve insect growth and male competitive fitness of a transgenic diamondback moth, which has shown variation in fitness when reared in different insectaries. All larvae were readily infected with the focal symbiont. Under gnotobiotic rearing pupal weights were reduced and there was a marginal reduction in larval survival. However, gnotobiotic rearing substantially improved the fitness of transgenic males. In addition, in gnotobiotic conditions, inoculation with the gut symbiont increased pupal weights and male fitness, increasing the proportion of transgenic progeny from 20 to 30% relative to symbiont-free insects. Gnotobiotic conditions may improve the fitness of transgenic males by excluding microbial contaminants, while symbiont inoculation could further improve fitness by providing additional protection against infections, or by normalizing insect physiology. The simple innovation of incorporating antibiotic into diet, and inoculating insects with symbiotic bacteria that are resistant to that antibiotic, could provide a readily transferable tool for other insect rearing systems.

Using a randomized, double-blinded, placebo-controlled, parallel group design, this investigation determined if the combination of 2-weeks flavonoid supplementation (329 mg/day, quercetin, anthocyanins, flavan-3-ols mixture) and a 45-minute walking bout (62.2±0.9% VO_2max) enhanced the translocation of gut-derived phenolics into circulation in a group of walkers (N = 77). The walkers (flavonoid, placebo groups) were randomized to either sit or walk briskly on treadmills for 45 minutes (thus four groups: placebo-sit, placebo-walk, flavonoid-sit, flavonoid-walk). A comparator group of runners (N = 19) ingested a double flavonoid dose for 2 weeks (658 mg/day) and ran for 2.5 h (69.2±1.2% VO_2max). Four blood samples were collected (pre- and post-supplementation, immediately-post- and 24-h post-exercise/rest). Of the 76 metabolites detected in this targeted analysis, 15 increased after the 2.5-h run, and when grouped were also elevated post-exercise (versus placebo-sit) for the placebo- and flavonoid-walking groups (P < 0.05). A secondary analysis showed that pre-study plasma concentrations of gut-derived phenolics in the runners were 40% higher compared to walkers (P = 0.031). These data indicate that acute exercise bouts (brisk walking, intensive running) are linked to an increased translocation of gut-derived phenolics into circulation, an effect that is amplified when combined with a 2-week period of increased flavonoid intake or chronic training as a runner.

Prebiotic dietary fiber supplements are commonly consumed to help meet fiber recommendations and improve gastrointestinal health by stimulating beneficial bacteria and the production of short-chain fatty acids (SCFAs), molecules beneficial to host health. The objective of this research project was to compare potential prebiotic effects and fermentability of five commonly consumed fibers using an in vitro fermentation system measuring changes in fecal microbiota, total gas production and formation of common SCFAs. Fecal donations were collected from three healthy volunteers. Materials analyzed included: pure beta-glucan, Oatwell (commercially available oat-bran containing 22% oat β-glucan), xylooligosaccharides (XOS), WholeFiber (dried chicory root containing inulin, pectin, and hemi/celluloses), and pure inulin. Oatwell had the highest production of propionate at 12 h (4.76 μmol/mL) compared to inulin, WholeFiber and XOS samples (p<0.03). Oatwell’s effect was similar to those of the pure beta-glucan samples, both samples promoted the highest mean propionate production at 24 h. XOS resulted in a significant increase in the genus Bifidobacterium after 24 h of fermentation (0 h: 0.67 OTUs; 24 h: 5.22 OTUs; p = 0.038). Inulin and WholeFiber increased the beneficial genus Collinsella, consistent with findings in clinical studies. All analyzed compounds were fermentable and promoted the formation of beneficial SCFAs.

Inflammatory bowel diseases (IBD) represent a growing public health concern due to increasing incidence worldwide. The current notion on the pathogenesis of IBD is that genetically susceptible individuals develop intolerance to dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental triggers. Among the environmental factors associated to IBD, diet plays an important role in modulating the gut microbiome, influencing epigenetic changes and, therefore, could be applied as a therapeutic tool to improve the disease course. Nevertheless, the current dietary recommendations for disease prevention and management are scarce and of weak evidence. This review summarizes the current knowledge on the complex interactions among diet, microbiome and epigenetics in IBD. Whereas over-abundance of calories and some macronutrients increases gut inflammation, several micronutrients have the potential to modulate it. Immunonutrition has emerged as a new concept putting forward the importance of vitamins such as vitamins A, C, E, D, folic acid and beta-carotene and trace elements such as zinc, selenium, manganese and iron. However, when assessed in clinical trials, specific micronutrients exerted a limited benefit. Beyond nutrients, anti-inflammatory dietary patterns as a complex intervention approach have become popular over the recent years. Hence, exclusive enteral nutrition in pediatric Crohn’s disease is the only nutritional intervention currently recommended as a first-line therapy. Other nutritional interventions or specific diets including the Specific Carbohydrate Diet, the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol diet and most recently the Mediterranean diet have shown strong anti-inflammatory properties and provide a promise for improving disease symptoms. Definitely, more work is required to evaluate the role of individual food compounds and complex nutritional interventions with potential to decrease inflammation as means for prevention and management of IBD.

Background: Inflammatory demyelination and impaired recovery processes result in permanent neurodegeneration and neurological disability in patients with multiple sclerosis (MS). In terms of smoldering MS, chronic neuroinflammation develops in the early period of the disease and leads to confirmed disability accumulation. There is a great need to identify biomarkers of neuro-degeneration and disease progression. Methods: We evaluated the concentrations of the param-eters of brain injury (NF-H, GPAF, S100B, UCHL1) in the cerebrospinal fluid (CSF) and the se-lected interleukins (ILs) in serum of 123 relapsing-remitting MS (RRMS) and 88 progressive MS (PMS) patients. Results: The levels of GFAP, S100B and UCHL were higher in the PMS group compared to RRMS as opposed to the levels of NF-H. We observed a positive correlation be-tween the selected pro-inflammatory cytokines and the parameters of brain injury. The Ex-panded Disability Status Scale score (EDSS) increased with GFA and NF-H levels and correlated with the selected ILs. The concentrations of S100B, UCHL1 and NF-H reflected the duration of MS symptoms. Conclusions: The levels of brain injury parameters in the CSF and the selected serum ILs in MS patients seem to be promising biomarkers to determine neurodegeneration and neuroinflammation in smoldering MS. Further studies are warranted in this respect.

Genetic factors influence medication response (pharmacogenetics), affecting the pharmacody-namics and pharmacokinetics of many medicaments used in clinical care. The ability of medica-tions to cross the blood-brain barrier (BBB) represents a critical putative factor in the effectiveness and tolerability of various central nervous system (CNS) medications at a pharmacokinetic (dosing) level. Pharmacogenetics has the potential to personalise medicine to a greater extent than has been possible, with the potential to help reduce heuristic delays to effective tolerable pharmacotherapy. Here, we critically examine and summarise the evidence, particularly for ABCB1 polymorphisms associated with various CNS medications. These transporters appear to have a role in BBB pharmacogenetics. We identify some of the most promising variants for clinical translation while spotlighting the complexities of the involved systems and limitations of the current empirical literature.

Background and aims: Brain metastases are prevalent in the late stages of malignant melanoma. Multimodal therapy remains challenging. Patient-derived organoids (PDOs) represent a valuable pre-clinical model, faithfully recapitulating key aspects of the original tumor, including the heterogeneity and the mutational status. This study aimed to establish PDOs from melanoma brain metastases (MBM-PDOs) and to test the feasibility of using them as a model for in vitro targeted-therapy drug testing.Methods: Surgical resection samples from eight patients with melanoma brain metastases were used to establish MBM-PDOs. Samples were enzymatically dissociated followed by seeding into low-attachment plates to generate floating organoids. The MBM-PDOs were characterized genetically, histologically, immunohistologically and compared with the parental tissue. The MBM-PDO cultures were exposed to dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) followed by cell viability assessment.Results: Seven out of eight cases were successfully cultivated, maintaining the histological, immunhistological phenotype, and the mutational status of the parental tumors. Five out of seven cases harbored BRAF V600E mutations and were responsive to BRAF and MEK inhibitors in vitro. Two out of seven cases were BRAF wild type, one case harboring an NRAS mutation and the other harboring a KIT mutation, and both were resistant to BRAF and MEK inhibitor therapy. Conclusion:We successfully established PDOs from melanoma brain metastases surgical specimens, which exhibited a consistent histological and mutational profile with the parental tissue. Using FDA-approved BRAF and MEK inhibitors, our data demonstrates the feasibility of employing MBM-PDOs for targeted-therapy in vitro testing.

Based on non-invasive neuroimaging techniques and graph theory-based network analyses, many researchers have tried to use small-world network model to elucidate sex differences in the brain. This manuscript aims to compile the related research findings from the past few years and summarize the sex differences in human brain networks from the perspective of small-world properties. We reviewed published reports examining altered small-world properties in both the functional and structural brain networks between males and females. Based on four patterns of altered small-world properties proposed--randomization, regularization, stronger small-worldization and weaker small-worldization, we found that current results point to a significant trend toward more regularization in females and more randomization in males in the functional brain networks. As for particular topological properties, the most consistent findings include a significant shift toward higher global efficiency in males and higher local efficiency in females in the functional network studies. On the other hand, there seems to be no consensus to date on the sex differences in small-world properties of the structural brain networks. Nevertheless, we noticed that the sample sizes in many published studies are limited, and future studies with larger samples are warranted to obtain more reliable results. We anticipate that the conclusions in this manuscript will contribute to a deeper understanding of neurobiological mechanisms underlying the sex differences in the brain.

The endeavor to decode the brain's intricate architecture and its multifaceted functions has propelled scientists into the domain of complex differential equations, aiming to construct a computational framework capable of representing its uncountable intricacies. This article delves into the sophisticated and daunting task of modeling the brain, a system of seemingly uncountable coupled differential equations, each symbolizing the vast array of interconnected neural pathways and processes. We discuss the current limitations of computational resources and the significant challenges faced in accurately capturing the non-linear, high-dimensional, and plastic nature of neural dynamics. Despite these challenges, we explore the progressive strides in computational neuroscience that lay the groundwork for partial models, offering insights into the brain's localized circuits and broader network interactions. These models serve as pivotal stepping stones towards a more comprehensive understanding, which is incrementally built upon by interdisciplinary approaches, leveraging advancements in neuroimaging, data analysis, and theoretical biology. Looking ahead, the article speculates on the potential paradigm shifts that could arise from breakthroughs in computational technology, such as quantum computing, that may one day enable the simulation of the brain in its entirety. The article ultimately paints a picture of cautious optimism, where each incremental discovery is a valuable piece of the grand puzzle, bringing us closer to the epochal goal of comprehensively modeling the human brain.

The management of brain tumors presents numerous challenges, despite the employment of multimodal therapies including surgical intervention, radiotherapy, chemotherapy, and immunotherapy. Owing to the distinct location of brain tumors and the presence of the blood-brain barrier (BBB), these tumors exhibit considerable heterogeneity and invasiveness at a histological level. Recent advancements in hydrogel research for the local treatment of brain tumors have sought to overcome the primary challenge of delivering therapeutics past the BBB, thereby ensuring efficient accumulation within brain tumor tissues. This article elaborates on various hydrogel-based delivery vectors, examining their efficacy in the local treatment of brain tumors. Additionally, it reviews the fundamental principles involved in designing intelligent hydrogels that can circumvent the BBB and penetrate larger tumor areas, thereby facilitating precise, controlled drug release. Hydrogel-based drug delivery systems (DDSs) are posited to offer a groundbreaking approach in addressing the challenges and limitations inherent in traditional oncological therapies, which are significantly impeded by the unique structural and pathological characteristics of brain tumors.

This study assesses the predictive performance of six machine learning models in forecasting tumor dynamics within three months following Gamma Knife Radiosurgery (GKRS) in 77 brain metastasis (BM) patients. The analysis meticulously evaluates each model before and after hyperparameter tuning, utilizing accuracy, AUC and other metrics derived from confusion matrices. Initial findings highlighted that XGBoost significantly outperformed other models with an accuracy of 0.95 and an AUC of 0.95 before tuning. Post-tuning, the Support Vector Machine (SVM) demonstrated the most substantial improvement, achieving an accuracy of 0.98 and an AUC of 0.98. Conversely, XGBoost showed a decline in performance after tuning, indicating potential overfitting. The study also explores feature importance across models, noting that features like “control at one year”, “age of the patient”, and “beam on time for volume V1 treated”, were consistently influential across various models, albeit their impacts were interpreted differently depending on the model’s underlying mechanics. This comprehensive evaluation not only underscores the importance of model selection and hyperparameter tuning but also highlights the practical implications in medical diagnostic scenarios, where the accuracy of positive predictions can be crucial.

The main purpose of this article is to identify brain diseases such as Alzheimer's and Parkinson's in an intelligent way using Python software and processing the function of neurons in the neural network areas of the brain, which are classified into different components, and the data is based on the information obtained from FMRI images using algorithms artificial intelligence can intelligently diagnose the type of disease. Therefore, by using spatial clustering based on the deep learning method with noise algorithm (DBSCAN), fMRI brain image and fMRI brain surface complexity are classified, and then image preprocessing will be applied to fMRI images by using artificial intelligence neural networks (ANN) algorithm. became. Then, by using the ANN algorithm and Deep CNN topology of the brain neural network, the type of disease in the brain can be diagnosed by simulating the performance of an artificial neural network (ANN) in Python software. Deep machine learning-based methods, especially algorithms based on neural networks, have shown great success in medical image analysis for various tasks including brain tumor detection, segmentation, and classification, and Alzheimer's and epilepsy. In this research, we propose an integrated model based on a convolutional neural network for simultaneous recognition and classification of brain diseases for intelligent diagnosis of tumors and epilepsy. The average accuracy obtained from our proposed model is 97.89 percent accuracy and 91.66 percent specificity.

: Medial temporal lobe atrophy (MTA) remains an important imaging biomarker in brain magnetic resonance imaging (MRI) for diagnosing and evaluating Alzheimer's disease (AD). We compared the detection performance for determining significant MTA and the correlation with Scheltens' scale between two automatic volumetry software, NeuroQuant® and Aqua®, in non-AD and AD groups. Overall, 127 (non-AD, 54; AD, 73) individuals who underwent three-dimensional T1-weighted volumetric MRI in our hospital between January and August 2011 were enrolled and retrospectively analyzed using NeuroQuant® and Aqua®. The accuracy, sensitivity, and specificity for detecting significant MTA and the correlation for Scheltens' scale with the mean hippocampal volume of each software were evaluated. The study sample’s mean age was 78 (range, 59–97) years. Regarding accuracy and specificity, Aqua® was non-inferior to NeuroQuant®. Aqua® had significantly higher overall specificity than NeuroQuant® for detecting significant MTA. Additionally, the calculated mean hippocampal volume of Aqua® was more correlated with Scheltens' scale (Kendall's τ, - 0.48) than that of NeuroQuant® (Kendall's τ, - 0.20). The accuracy and specificity of Aqua® in detecting MTA are not inferior to those of NeuroQuant®. Additionally, Aqua® has a stronger correlation of mean hippocampal volume with Scheltens' scale than NeuroQuant®.

Bifenthrin is a synthetic pyrethroid insecticide. It is used worldwide against different agricultural pests. Nervous system (NS) is the primary target organ for the pyrethroid group of insecticide which causes hyper excitation. The aim of this study to determine the effects of bifenthrin on the brain of rabbits. The animals were treated for 14 days with three different doses (1/5th, 1/10th and 1/15th of LD50) of bifenthrin. Neurotransmitters and Histopathological alterations were observed at the end of the experiments. Neurochemical parameters were checked 24 hours after the last dose. Significant changes in the level of biogenic amines were observed. The levels of epinephrine (EPN), dopamine (DA), 3, 4 dihydroxyphenylacetic acid (DOPAC) were decreased as compared to controls group with the increase in insecticide. However, norepinephrine (NE) and homovanillic acid (HVA) levels were found to be significantly higher than those of the controls. A significant reduction in the activity of the acetyl cholinesterase enzyme was found in the frontal cortex’s erythrocyte, plasma and brain of rabbit with the increase in administered bifenthrin. The oxidative stress showed significantly decrease in the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and glutathione S- transferase (GST) with the increase in dose of bifenthrin. Histopathological study of brain tissues showed normal GC (glial cells) and NC (neuronal cells) in the frontal cortex of brain tissue of control groups while the treated groups showed evacuation (odema), elongation of pyramidal nucleus, glial cell damage and brain haemorrhage.

Previous studies on the mechanisms underlying willed actions reported that the premotor cortex may be involved in the construction of motor awareness. However, its exact role is still under investigation. Here we investigated the role of the dorsal premotor cortex (PMd) in motor awareness by modulating its activity applying inhibitory rTMS to PMd, before a specific motor awareness task (under three conditions: without stimulation, after rTMS and after sham stimulation). During the task, subjects had to trace straight lines to a given target, receiving a visual feedback of the line trajectories on a computer screen. Crucially, in most trials the trajectories on the screen were deviated and to produce straight lines, subjects had to correct their movements towards the opposite direction. After each trial, participants were asked to judge whether the line seen on the computer screen corresponded to the line actually drawn. Results show that participants in the no stimulation condition did not recognize the perturbation until 14 degrees of deviation. Importantly, active, but not sham, rTMS significantly modulated motor awareness, decreasing the amplitude of the angle at which participants became aware of the trajectory correction. These results suggest that PMd plays a crucial role in action self- monitoring.

Whole-brain radiation therapy and stereotactic radiosurgery are two treatment modalities commonly utilized to treat brain metastases (BMs). The aim of this study is to retrospectively analyze the main radio-oncologic and clinical-demographic aspects of a cohort of BM patients treated with Volumetric Modulated Arc Therapy for radiosurgery (VMAT-RS). This is a cross-sectional observational design study with retrospective review of medical records of patients with brain metastases treated with VMAT- RS between 2012 and 2018. Clinical and demographic data, with special attention to sex, age, primary tumor, brain tumor-related epilepsy (BTRE), number and brain location of BMs, Karnofsky Performance Status (KPS), the updated DS-GPA prognostic index and the survival estimated according to the Kaplan-Meier model from the date of radiosurgery were analyzed. One hundred and twenty-one patients with 229 BMs were treated with VMAT-RS. Patients presented 1-4 BMs, which were treated with 5 non-coplanar VMAT arcs. Sixty-eight percent of the patients had lung cancer and 35% of the BMs were in the frontal lobe. Proportion of local control was 88.5%. BTRE prevalence was 30.6%. The median survival time (MST) was 7.7 months. In the multivariate analysis of the Cox Regression model KPS70 (HRKPS&lt;70=2.59; p=0.001) and higher DS-GPA (HRDS-GPAII =0.55, p=0.022; HRDS-GPAIII-IV =0.38, p=0.006) were associated with improved survival. In the univariate analysis, primary tumor, age and the presence of metastases in the posterior fossa (PFBMs) were also significative. In conclusion, the VMAT-RS is a technique with an overall survival comparable to other radiosurgery techniques. The median survival is significantly longer in those with higher KPS and DS-GPA. Other variables such as the type of primary tumor, age and PFBMs could also influence survival, although further studies are needed.

The abnormal accumulation of cells in the human brain, if left untreated, may cause brain damage. Management and treatment of these tumours require an early and accurate diagnosis, while their prognostic characterisation can also be beneficial in the choice of care planning for the patient. CDSSs are being continuously developed and integrated into routine clinical practice as they assist clinicians and radiologists to deal with an enormous amount of medical data, reduce clinical errors, and improve diagnostic capabilities. They assist detection, classification, and grading of brain tumours as well as alerting physicians of requirement of change in treatment plans. The aim of this systematic review is to identify various CDSSs used in brain tumour diagnosis and prognosis, that rely on data captured by any imaging modality. Based on the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, the literature search was conducted in PubMed and Engineering Village Compendex databases. This review examines various CDSS tool types, system features, techniques used, accuracy, and outcome, to provide the latest evidence available in the field of neuro-oncology. An overview of different types of CDSSs used to support clinical decision-making in the management and treatment of brain tumours, along with highlighting their benefits, challenges, and future perspectives has been provided.

Alphavirus species are globally distributed zoonoses, primarily transmitted by arthropods. In Costa Rica, Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV) are endemic. The objective of this study is to detect these viruses in brain samples from equines displaying nervous signs. For this purpose, four published universal RT-PCR methods were compared. The most sensitive and specific RT-PCR method was used to test a total of 70 brain samples, including 40 from bovines and 30 from equines, all exhibiting nervous signs. In the positive cases, eight different brain regions were extracted and tested using this RT-PCR. Positive cases were confirmed through sequencing. Among the four universal RT-PCR assays, Torii RT-PCR demonstrated the highest sensitivity and specificity for diagnosing VEEV and EEEV. Not all assessed brain regions showed DNA amplification. None of the bovine brains was positive and out of the 30 equine brain samples, only four tested positive, and sequencing confirmed two of these samples as VEEV subtype IE. Torii RT-PCR successfully detected VEEV in pools of the hip-pocampus, spinal cord, and basal nuclei, making these brain regions suitable for diagnosing this virus. None of the samples were positive for EEEV.

The restriction of normal blood flow is the cause of many diseases including stroke and coronary artery diseases. To study the consequences of vessel blockade, previous models mainly focused on major arteries and have been well studied. However, the sequela from interruption of capillary vessels by microemboli was less well characterized. In this study, we exploited polystyrene microspheres as a mimicry of microemboli and found that microspheres of this size can be trapped in capillary vessels of all organs without causing apparent acute morbidities of the host. Interestingly, we accidentally found significantly increased recruitment of monocyte to the brain vasculature expressing low levels of Ly6C expression, but not to other organs. Further study revealed the spleen is the major origin of the recruited monocyte. Most importantly, VCAM-1 which is constitutively expressed on mouse brain vasculature orchestrates the recruitment of monocyte. Blockade of VCAM-1 in mice can substantially reduce monocyte recruitment. Interestingly, monocytes get activated through TNF- signaling which likely happens in the spleen instead of the brain. Collectively, we found a unique monocyte recruitment strategy in the brain comparing to other orangs, in response to capillary blockade induced by polystyrene microspheres.

Astroviruses (AstVs) have been detected in a wide range of animal species, including mammals and birds. Recently, a novel AstVs associated with neurological symptoms has been detected in the brain of some mammals. Raccoon dog AstV has been reported recently in China. However, there have been no reports in South Korea. Therefore, the present study aimed to detect and genetically characterize AstVs in intestine and brain tissues of 133 wild raccoon dogs collected in Korea between 2017 and 2019. Seven wild raccoon dogs were positive for AstV, four of which were also detected in brain tissue. Analysis of the capsid protein amino acid sequences of raccoon dog AstVs detected in Korea revealed a high similarity to canine AstVs, suggesting possible interspecies transmission between raccoon dogs and dogs. Phylogenetic and capsid protein amino acid sequence analysis of raccoon dog AstVs detected in brain 17-148B strain belonged to the HMO clade and exhibited conserved sequences found in neurotropic AstVs (NT-AstVs), indicating their potential as NT-AstVs. However, the pathogenicity and transmission routes of the raccoon dog AstV detected in Korea have not yet been elucidated, so further research and continued surveillance for AstV in wild raccoon dogs are needed.

Objective: Design and validate a wireless, low-cost, easy-to-use, mobile, dry-electrode headset for scalp electroencephalography (EEG) recordings for closed-loop brain-computer (BCI) interface and internet-of-things (IoT) applications. Approach: The EEG-based BCI headset was designed from commercial off-the-shelf (COTS) components using a multi-pronged approach that balanced interoperability, cost, portability, usability, form factor, reliability, and closed-loop operation. Main Results: The adjustable headset was designed to accommodate 90\% of the population. A patent-pending self-positioning dry electrode bracket allowed for vertical self-positioning while parting the user's hair to ensure contact of the electrode with the scalp. In the current prototype, five EEG electrodes were incorporated in the electrode bracket spanning the sensorimotor cortices bilaterally, and three skin sensors were included to measure eye movement and blinks. An accelerometer provides monitoring of head movements. The EEG amplifier operates with 24 bits resolution up to 500 Hz sampling frequency, and can communicate with other devices using 802.11 {b/g/n/WiFi}. It has high SNR and CMRR (121 dB and 110 dB, respectively), and low input noise. In closed-loop BCI mode, the system can operate at 40 Hz, including real-time adaptive noise cancellation and 512 MB of processor memory. It supports LabVIEW as backend coding language and JS, CSS, HTML as front-end coding languages, and includes training and optimization of Support Vector Machine (SVM) neural classifiers. Extensive bench testing supports the technical specifications and human subject pilot testing of a closed-loop BCI application to support upper-limb rehabilitation provides proof-of-concept validation for device use at both the clinic and at home. Significance: The low-cost, accessibility, usability, interoperability, and programmability of the proposed closed-loop BCI system provides a low-cost solution for BCI and neurorehabilitation research and IoT applications.

Schizophrenia (SCZ) is a severe mental disorder that may result in hallucinations, delusions, and extremely disordered thinking. How each cell type in the brain contributes to SCZ occurrence is still unclear. Here, we leveraged the human dorsolateral prefrontal cortex bulk RNA-seq data, then used the RNA-seq deconvolution algorithm CIBERSORTx to generate SCZ brain single-cell RNA-seq data for a comprehensive analysis to understand SCZ-associated brain cell types and gene expression changes. Firstly, we observed that the proportions of brain cell types in SCZ differed from normal samples. Among these cell types, astrocyte, pericyte, and PAX6 cells were found to have a higher proportion in SCZ patients (astrocyte: SCZ = 0.163, Control = 0.145, P.adj = 4.9×10-4; pericyte: SCZ = 0.057, Control = 0.066, P.adj = 1.1×10-4; PAX6 : SCZ = 0.014, Control = 0.011, P.adj = 0.014), while the L5/6_IT_CAR3 cells and LAMP5 cells are the exact opposite (L5/6_IT_Car3 : SCZ = 0.102, Control = 0.108, P.adj = 0.016; LAMP5 : SCZ = 0.057, Control = 0.066, P.adj = 2.2×10-6). Next, we investigated gene expression in cell types and functional pathways in SCZ. We observed chemical synaptic transmission dysregulation in two types of GABAergic neurons (PVALB and LAMP5), and immune reaction involvement in GABAergic neurons (SST) and non-neuronal cell types (endothelial and oligodendrocyte). Furthermore, we observed that some differential expression genes from bulk RNA-seq displayed cell-type-specific abnormal in the expression of molecules in SCZ. Finally, the cell types with the SCZ-related transcriptomic changes could be considered to belong to the same module since we observed two major similar coordinated transcriptomic changes across these cell types. Together, our results offer novel insights into cellular heterogeneity and the molecular mechanisms underlying SCZ.

Methylmercury is a neurotoxin present in fish tissues that permeates the blood-brain barrier after consumption. Previous research has shown that methylmercury is harmful to neurons, causing pH alterations, oxidative stress, excitotoxicity, and parenchymal damage. Methylmercury is a known factor of neurological disorders including Alzheimer's and Parkinson's. The method by which methylmercury passes through the blood-brain barrier is largely unknown. According to preliminary studies, one way methylmercury crosses the blood-brain barrier is by creating a complex with L-Cysteine, which facilitates its passage by the LATs system through mimicking another amino acid existing in the body. The human blood-brain barrier was studied using C. elegans as a model organism. It was hypothesized that if methylmercury passes through the blood-brain barrier of C. elegans faster with L-Cysteine present than without L-Cysteine present, the methylmercury's adverse effects (death and locomotive difficulty) will occur sooner. Each of the four experimental groups contained one C. elegans: the control, the L-Cysteine group, the methylmercury group, and the methylmercury and L-Cysteine combination group. The effects of L-Cysteine and methylmercury on C. elegans were studied using three metrics: viability, locomotive disability, and time for locomotive effects to occur. The group that received both methylmercury and L-Cysteine had reduced viability rates and a decreased time for locomotive difficulty to develop, supporting the hypothesis. These findings suggest that L-Cysteine aids methylmercury permeation through the blood-brain barrier. Because the experiment indicates how methylmercury penetrates the blood-brain barrier, these results aid in finding a therapeutic solution to reverse methylmercury neurotoxicity in the brain. Additionally, this study further opens channels into potential therapeutic and preventative measures for dementia, improving morbidity and mortality in neurodegenerative diseases.

Objective A trained T1 class Convolutional Neural Network (CNN) model will be used to examine its ability to successfully identify motor imagery when fed pre-processed electroencephalography (EEG) data. In theory, and if the model has been trained accurately, it should be able to identify a class and label it accordingly. The CNN model will then be restored and used to try and identify the same class of motor imagery data using much smaller sampled data in an attempt to simulate live data. Approach PyCharm, a Python platform, will be used to house and process the CNN. The raw data used for the training of the CNN will be sourced from the PhysioBank website. The EEG signal data will then be pre-processed using Brainstorm software that is a toolbox used in conjunction with MATLAB. The sample data used to validate and test the trained CNN, will be also be extracted from Brainstorm but in a much smaller size compared to the training data which is comprised of thousands of images. The sample size would be comparable to a person wearing a Brain Computer Interface (BCI), offering approximately 20 seconds of motor imagery signal data. Results The raw EEG data was successfully extracted and pre-processed. The deep learning model was trained using the extracted image data along with their corresponding labels. After training, it was able to accurately identify the T1 class label at 100 percent. The python coding was then modified to restore the trained model and feed it test sample data in which it was found to recognise 6 out of 10 lines of T1 signal image data. The result suggested that the initial training of the model required a different, more varying approach, so that it would be able to detect varying sample signal image data. The outcome of which could mean that the model could be used in applications for multiple patients wearing the same BCI hardware to control a device or interface.

The development of a fast and accurate intraoperative method that enables the differentiation and stratification of cancerous lesions is still a challenging problem in laboratory medicine. Therefore, it is important to find and optimize a simple and effective analytical method that enables the selection of distinctive metabolites. This study aims to assess the usefulness of solid-phase microextraction (SPME) probes as a sampling method for the lipidomic analysis of brain tumors. To this end, SPME was applied to sample brain tumors immediately after excision, followed by lipidomic analysis via liquid chromatography-high resolution mass spectrometry (LC-HRMS). The results showed that long fibers were a good option for extracting analytes from an entire lesion to obtain an average lipidomic profile. Moreover, significant differences between tumors of different histological origin were observed. In-depth investigation of the glioma samples revealed that malignancy grade and isocitrate dehydrogenase (IDH) mutation status impact the lipidomic composition of the tumor, whereas 1p/19q co-deletion did not appear to alter the lipid profile. This first on-site lipidomic analysis of intact tumors proved that chemical biopsy with SPME is a promising tool for the simple and fast extraction of lipid markers in neurooncology.

It is proposed to incorporate the concepts of brain microbiota and microbial consciousness in the Orchestrated Objective Reduction (Orch OR) theory of human consciousness with the goal of increasing its explanatory and predictive powers. If consciousness arises from quantum computations in cytoskeletal structures inside human neurons, there is no theoretical impediment at hypothesizing that it might also occur in the cytoskeletal structures of the microbes resident in the human brains. If the concept of the brain microbiota is integrated in a general Orch OR theory, its explanatory and predictive powers would be vastly increased.

Physical symptoms are defined as symptoms for which adequate examination does not reveal a sufficient underlying root cause, e.g., pain and fatigue. The extant literature of the neurobiological underpinnings of physical symptoms has been largely inconsistent and primarily consists of (clinical) case-control studies with relatively small samples sizes. Therefore, we studied the association of brain morphology with physical symptoms in pre-adolescents from two independent and population-based cohorts. This study included 2,683 individuals from the Generation R Study (51% girls, 10.1 ± 0.6 years old) and 10,567 pre-adolescents from the ABCD Study (48% girls, 9.9 ± 0.6 years old). High- resolution structural magnetic resonance imaging (MRI) was collected using 3-Tesla MRI systems. Physical symptoms were evaluated using the somatic complaints syndrome scale from the parent-reported school-age version of the Child Behavior Checklist. Linear regression models were fitted for global brain metrics (i.e., cortical and subcortical grey matter volume and total white matter volume) as well as surface-based vertex-wise measures (surface area and cortical thickness). Analyses were initially conducted separately in each cohort and later meta-analysed. No associations were observed in either cohort separately. In the combined vertex-wise meta-analysis of both cohorts; the right hemisphere surface area, most notably the rostral middle frontal gyrus, superior frontal gyrus and anterior cingulate cortex, were related to physical symptoms after correcting for multiple comparisons (cluster area = 1,882 mm2). The present study, which is the most representative and well-powered to date, suggests that surface area, but not other measures of brain morphology, are modestly related to physical symptoms in pre- adolescents. While these effects are subtle, future longitudinal research is warranted to elucidate whether such associations indicate a cause or a consequence of the physical symptoms.

Adult neurogenesis is an evolutionary conserved process occurring in all vertebrates. However, striking differences are observed between the taxa, considering the number of neurogenic niches, the neural stem cell (NSC) identity and brain plasticity under constitutive and injury-induced conditions. Zebrafish has become a popular model for the investigation of the molecular and cellular mechanisms involved in adult neurogenesis. Compared to mammals, the adult zebrafish displays a high number of neurogenic niches distributed throughout the brain. Furthermore, it exhibits a strong regenerative capacity without scar formation or any obvious disabilities. In this review, we will first discuss the similarities and differences regarding (i) the distribution of neurogenic niches in the brain of adult zebrafish and mammals (mainly mouse) and (ii) the nature of the neural stem cells within the main telencephalic niches. In the second part, we will describe the cascade of cellular events occurring after telencephalic injury in zebrafish and mouse. Our study clearly shows that most early events happening right after the brain injury are shared between zebrafish and mouse including cell death, microglia and oligodendrocyte recruitment, as well as injury-induced neurogenesis. In mammals one of the consequences following an injury is the formation of a glial scar that is persistent. This is not the case in zebrafish, which may be one of the main reasons that zebrafish display a higher regenerative capacity.