Background: Brain-derived neurotrophic factor (BDNF) has attracted increasing attention as a therapeutic agent because of its potentially biological activities, including osteogenesis. However, the molecular mechanisms involved in the osteogenic activity of BDNF have not been fully investigated. This study aimed to investigate the action of BDNF on the osteoblast differentiation in bone marrow stromal cells, and its influence on signaling pathways. Methods: Preosteoblast cells (MC3T3-E1), bone marrow-derived stromal cells (ST2), and a direct 2D co-culture system were treated with BDNF. The effect of BDNF on cell proliferation was determined using the CCK-8 assay. Osteoblast differentiation was assessed based on alkaline phosphatase (ALP) activity and staining and the protein expression of multiple osteoblast markers. Calcium accumulation was examined by Alizarin red S staining. Results: BDNF significantly increased ALP activity, calcium deposition, and the expression of osteoblast differentiation-related proteins, such as ALP, osteopontin, etc. in both ST-2 and the MC3T3-E1 and ST-2 co-culture system. Moreover, the effect of BDNF on osteogenic differentiation was diminished by blocking tropomyosin receptor kinase B as well as inhibiting c-Jun N-terminal kinase and p38 MAPK signals. Conclusion: Our study results showed positive effect of BDNF on osteogenesis. It provides essential evidence for clinical applications of BDNF in treating osteoporosis.

Both brain-derived neurotrophic factor (BDNF) and glucocorticoids (GCs) have multiple roles in the various aspects of neurons, including cell survival and synaptic function. BDNF and its receptor TrkB express in the central nervous system (CNS) neurons extensively, and contribution of BDNF/TrkB system in neuronal function is evident, thus, its downregulation has been considered to be involved in the pathogenesis of Alzheimer’s disease (AD). GCs, a stress-related molecule, and glucocorticoid receptor (GR) are also considered to be associated with AD, in addition to mental disorders such as depression. Importantly, a growing body of evidence suggest a close relationship between BDNF/TrkB-mediated signaling and GCs/GR system in the CNS. Here, we introduce current studies on the interaction among neurotrophic system and stress in CNS neurons, and discuss their involvement in the pathophysiology of AD.

Brain-derived neurotrophic factor (BDNF) is a key molecule in promoting neurogenesis, dendritic and synaptic health, and neuronal survival, plasticity, and excitability, all of which are disrupted in neurological and cognitive disorders such as Alzheimer’s disease (AD). Extracellular aggregates of amyloid-β (Aβ) in the form of plaques and intracellular aggregates of hyperphosphorylated tau protein have been identified as major pathological insults in AD brain, along with immune dysfunction, oxidative stress, and other toxic stressors. Although aggregated Aβ and tau lead to decreased brain BDNF expression, early losses in BDNF prior to plaque and tangle formation may be due to other insults such as oxidative stress and contribute to early synaptic dysfunction. Physical exercise, on the other hand, protects synaptic and neuronal structure and function, with increased BDNF as a major mediator of exercise-induced enhancements in cognitive function. Here, we review recent literature on mechanisms behind exercise induced BDNF upregulation and its effects on improving learning and memory and on Alzheimer’s disease pathology. Mechanisms include elevations in peripheral BDNF-inducing hormones such as osteocalcin, FNDC5/irisin, and lactate. The fundamental mechanisms of how exercise impacts BDNF and cognition are unclear but are a prerequisite to developing new biomarkers and therapies to delay or prevent cognitive decline.

Our previous studies showed that in patients with brain diseases neurotrophic factors in lacrimal fluid (LF) may change more prominently than in blood serum (BS). Since glial cell line-derived neurotrophic factor (GDNF) is involved in control of neuronal networks in epileptic brain, we aimed to assess GDNF levels in LF and BS as well as BDNF, hypothalamic-pituitary-adrenocortical and inflammation indices in BS of patients with focal epilepsy (PWFE), epilepsy and comorbid depression (PWFE+MDD) compared with major depressive disorder (PWMDD) and healthy controls (HC). GDNF levels in BS were similar in patients and HC and higher in PWFE taking valproates. GDNF levels in LF were significantly lower in all patient groups compared to controls, and independent of drugs used. LF and BS GDNF concentrations positively correlated in HC, but not patient groups. BDNF level was lower in BS of patients compared with HC and higher in PWFE+MDD taking valproates. Logistic regression models demonstrated that GDNF decrease in LF may be an important predictor of focal epilepsy. Probability of focal epilepsy can be evaluated using GDNF in LF and BDNF in BS; MDD - GDNF in LF, cortisol and TNF-α in BS; epilepsy with MDD - GDNF in LF, TNF-α and BDNF in BS.

Growing evidence suggests a possible involvement of the intestinal microbiota in generating new neurons, but a detailed breakdown of the microbiota composition is lacking. In this report, we systematically reviewed preclinical rodent reports addressing the connection between the composition of the intestinal microbiota and neurogenesis and neurogenesis-affecting neurotrophins in the hippocampus. Various changes in bacterial composition from low taxonomic resolution at the phylum level to high taxonomic resolution at the species level were identified. As for neurogenesis, studies predominantly used doublecortin (DCX) as a marker of newly formed neurons or bromodeoxyuridine (BrdU) as a marker of proliferation. Brain-derived neurotrophic factor (BDNF) was the only neurotrophin found researched in relation to the intestinal microbiota. Phylum Actinobacteria, genus Bifidobacterium and genus Lactobacillus found the strongest positive while phylum Firmicutes, phylum Bacteroidetes and family Enterobacteriaceae as well as germ-free status, showed the strongest negative correlation towards neurogenesis or BDNF mRNA expression. Age, short-chain fatty acids (SCFA), obesity and chronic stress were recurring topics in all studies identified. Overall, these findings add to the existing evidence of a connection between microbiota and processes in the brain. To better understand this interaction, further investigation based on analyses of higher taxonomic resolution and clinical studies would be a gain to the matter.

Background: This review aims to explore the regulatory mechanism of microglial exosomes, particularly focusing on the role of miR-124-3p, in modulating neuroinflammation and promoting neuronal repair following traumatic brain injury (TBI). Methods: Multiple studies investigating the impact of microglial exosomal miRNAs, specifically miR-124-3p, on injured neurons and brain microvascular endothelial cells (BMVECs) in the context of TBI were reviewed. Results: Animal models of TBI, in vitro cell culture experiments, RNA sequencing analysis, and functional assays were employed to elucidate the mechanisms underlying the effects of miR-124-3p-loaded exosomes on neuroinflammation and neuronal repair. The increased expression of miR-124-3p in microglial exosomes after TBI inhibited neuronal inflammation and promoted neurite outgrowth. This effect was achieved by promoting the anti-inflammatory M2 polarization of microglia, suppressing mTOR signaling through downregulation of PDE4B, and inducing autophagy in BMVECs. These actions collectively contributed to neuroprotection, reduced blood-brain barrier leakage, and improved neurologic outcomes in animal models of TBI. Conclusion: Microglial exosomes, particularly those carrying miR-124-3p, have emerged as promising candidates for therapeutic interventions in TBI. These exosomes exhibit neuroprotective effects, attenuate neuroinflammation, and promote neuronal repair and plasticity. Targeting miR-124-3p and utilizing microglial exosomes as therapeutic agents hold great potential for future clinical translation in TBI management. However, further research is required to fully elucidate the underlying mechanisms and optimize their delivery strategies for effective treatment in human TBI cases.

A risk of ischemic stroke increases exponentially after menopause. Even a mild-ischemic stroke can result in increased frailty. Frailty is a state of increased vulnerability to adverse outcomes, which subsequently increases risk of cerebrovascular events and severe cognitive decline, particularly after menopause. Several interventions to reduce frailty and subsequent risk of stroke and cognitive decline have been proposed in laboratory animals and patients. One of them is whole body vibration (WBV). WBV recuperates cerebral function and cognitive ability that deteriorates with increased frailty. The goal of the current study is to test the efficacy of WBV in reducing post-ischemic stroke frailty and brain damage in reproductively senescent female rats. Reproductively senescent Sprague–Dawley female rats were exposed to transient middle cerebral artery occlusion (tMCAO) and randomly assigned to either WBV or control groups. Animals placed in the WBV group underwent 30 days of WBV (40 Hz) treatment performed twice daily for 15 min each session, 5 days each week. The motor functions of animals belonging to both groups were tested intermittently and at the end of treatment period. Brains were then harvested for inflammatory markers and histopathological analysis. The results demonstrate a significant reduction in inflammatory markers and infarct volume with significant increases in brain-derived neurotrophic factor and improvement in functional activity after tMCAO in middle-aged female rats that were treated with WBV as compared to the control group. Our results may facilitate a faster translation of the WBV intervention for improved outcome after stroke, particularly among frail women.

Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer’s disease (AD). However, the relationships among AD, hypertension, and oxidative stress remain to be elucidated. In the present study, we aimed to determine whether treatment with resveratrol reduces reactive oxygen species (ROS) generation in the brain, thereby reducing cognitive impairment in rats with angiotensin II (Ang-II)-induced early AD. Male WKY rats with Ang-II-induced AD were treated with losartan or resveratrol for 2 weeks. Our results revealed that treatment with resveratrol (10 mg/kg/day) decreased blood pressure, increased levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, and decreased ROS production in the nucleus tractus solitarius (NTS) in the Ang-II groups. In addition, inhibition of Tau^T231 phosphorylation in the hippocampus using resveratrol significantly abolished Ang-II-induced expression of Ab precursors, active caspase 3, and glycogen synthase kinase 3b (GSK-3b)^Y216 while increasing Akt^S473 phosphorylation. Notably, resveratrol reversed impairments in hippocampal-dependent contextual memory induced by deleting NADPH oxidase and NOX2. Overall, our results suggest that resveratrol exerts neuroprotective effects against memory impairment and hippocampal damage in a rat model of early stage AD by reducing oxidative stress. These novel findings indicate that resveratrol may represent a pharmacological option for patients with hypertension at a risk of AD during old age.

Objective: It was aimed to investigate the cerebral vascular territories in stroke patients with NVAF as an etiologic factor. Material and Methods: A total of 104 patients who were referred to our hospital between January 2015 and September 2016, who were over 55 years of age, identified or documented as having a standard ECG or Holter ECG record on their medical history, and diagnosed with stroke were included. Our study was designed as a retrospective analysis of prospective data. Detailed history, physical examination and electrocardiography (ECG) evaluations of the patients were performed. Descriptive statistics were used in the detection of findings, and t-test, Pearson-square test and Fisher's exact test were used for differences analysis. Results: 53.8% (N = 56) of the patients were male and 46.2% (N = 48) were female. The mean age was 73.5. MCA was the most common site of vascular involvement in NVAF-dependent strokes. In MCA vascular territory, ischemic infarcts were detected most frequently in the upper and lower divisions. SCA and PCA followed MCA. Approximately 64% of the NVAF-related strokes were anterior circulation infarction (ASE) and 22% were posterior circulation infarct (PSE). There was a significant difference in age and past stroke history factors in favor of ASE (p<0.05). There was no significant difference between ASE and PSE in HT, cardiac history and DM factors (p>0.05). Conclusion: It was emphasized that the area of the vessel that underwent ischemia in the acutely displayed infarcts and the etiological factor for this vessel area could be predicted

Curcumin is a natural dietary polyphenol which that possesses potent anti-aging and neuroprotective properties through various mechanisms and signaling pathways. This study aimed to investigate the effect of curcumin on factors involved in neurogenesis and angiogenesis in the aged brain. Old female Wistar rats were divided into three equal groups (n=7): control, sham, and curcumin (received curcumin, i.p., 30 mg/kg and 5 days/week for 8 weeks) rats. Curcumin treatment caused a significant increase in the vascular endothelial growth factor (VEGF), Brain-derived neurotrophic factor (BDNF) and anti-apoptotic protein BCl-2 in the brains of aging rats but no significant effect on anti-apoptotic Bax protein. Additionally, curcumin attenuated brain lipid peroxidation and decreased transforming growth factor β1 (TGF-β1). These results suggested that curcumin possesses neuroprotective effects against brain aging, which were mediated by improvment in neurogenesis and angiogenesis. Also, curcumin could alleviate brain aging which may be due to attenuating oxidative stress, inhibiting apoptosis and down-regulating TGF-β1, which in turn enhances VEGF and BDNF. Therefore, curcumin has potential therapeutic value in the treatment of neurological apoptosis, neurogenesis and angiogenesis changes caused by brain aging.

Brain plasticity is induced by learning during wakefulness and is consolidated during sleep. But the molecular mechanisms involved are poorly understood and their relation to experience-dependent changes in brain activity remains to be clarified. Localized mRNA translation is im-portant for the structural changes at synapses supporting brain plasticity consolidation. Sleep has been shown activate the translation mTOR pathway, via phosphorylation of 4E-BPs, during brain plasticity, but whether this activation is specific to synapses is not known. We investigated this question using acute exposure of rats to an enriched environment (EE). We measured brain activity with EEGs and 4E-BPs phosphorylation at cortical and cerebellar synapses with Western Blot. Sleep significantly increased the conversion of 4E-BPs to its hyperphosphorylated form at synapses, especially after EE exposure. EE exposure increased oscillations in the alpha band dur-ing active exploration and in the theta to beta (4-30Hz) range, as well as spindle density, during NREM sleep. Theta activity during exploration and NREM spindle frequency predicted changes in 4E-BPs hyperphosphorylation at synapses. Our results provide a link between EEG and mo-lecular markers of plasticity across wake and sleep.

The introduction of anti-amyloid monoclonal antibodies against Alzheimer’s disease (AD) is of high importance. However, even though treated patients show very little amyloid pathology, there is only a modest effect on the rate of cognitive decline. Although this effect possibly can increase over time, there is still a need for alternative treatments that will improve the cognitive function in patients with AD. Therefore, the purpose of this study was to characterize the triazinetrione ACD856, a novel pan-Trk positive allosteric modulator, in multiple models to address its neuroprotective and potential disease modifying effects. The pharmacological effect of ACD856 was tested in recombinant cell lines, primary cortical neurons or animals. We demonstrate that ACD856 enhanced NGF-induced neurite outgrowth, increased the levels of the pre-synaptic protein SNAP25 in PC12 cells and increased the degree of phosphorylated TrkB in SH-SY5Y cells. In primary cortical neurons, ACD856 led to increased levels of phospho-ERK1/2, showed neuroprotective effect against amyloid-beta or energy-deprivation induced neurotoxicity, and increased the levels of brain derived neurotrophic factor (BDNF). Consequently, administration of ACD856 resulted in a significant increase of BDNF in the brains of 21-months old mice. Furthermore, repeated administration of ACD856 resulted in a sustained anti-depressant effect which lasted up to seven days, suggesting effects that go beyond merely symptomatic effects. In conclusion, the results confirm ACD856 as a cognitive enhancer, but more importantly, they provide substantial in vitro and in vivo evidence of neuroprotective and long-term effects that contribute to neurotrophic support and increased neuroplasticity. Presumably, the described effects of ACD856 may improve cognition, increase resilience, and promote neurorestorative processes, thereby leading to a healthier brain in patients with AD.

Depression is the commonest mental disorder worldwide. Both antidepressants and psychotherapy are effective in treating depression, but response to these treatments is often incomplete. Yoga-based interventions (YBIs) have emerged as a promising adjunctive treatment for depression. Recent research has attempted to identify the biological mechanisms associated with the antidepressant actions of YBIs. In this scoping review, conducted according to the PRISMA-ScR guidelines, the PubMed and Scopus databases were searched to retrieve research on biomarkers of response to YBIs in patients with depression. Eleven studies were included in the review. Based on these studies, YBIs may improve depression through beneficial effects on systemic inflammation, stress axis regulation, cardiac autonomic functioning, and possibly reductions in oxidative stress-related cellular damage. Increases in brain-derived neurotrophic factor (BDNF) may represent a final common pathway upon which these processes converge. Though these results are theoretically plausible, they should be interpreted with caution due to certain methodological limitations in the existing research. Replication of these results and improvements in study methodology, and the evaluation of other biomarkers relevant to the pathophysiology of depression, could further elucidate the mechanism of action of YBIs in this disorder, and identify which patients would benefit most from this treatment approach.

Healthcare faces a major problem with the increased emergence of antimicrobial resistance due to the over-prescription of antibiotics. This causes dysbiosis and major disruption of the gut microbiome, leading to the development of intestinal diseases, abnormalities in the regulation of immune responses, malfunctioning of entero-endocrine signaling, and an imbalance in communication with the central nervous system (CNS). Bacteriophages may provide a solution to the treatment of bacterial infections given their specificity. This approach increased rapidly over the last ten years, because of the rapid rise of multi-drug-resistant bacteria worldwide coupled with a decline in the development and production of novel antibacterial agents. Eradication of multidrug-resistant bacteria is often only possible with bacteriophage treatment. Phage proteins are used to stimulate immune responses against specific pathogens, improve antibiotic susceptibility, prevent biofilm formation, and characterize bacterial pathogens. This review discusses the therapeutic potential of bacteriophage-derived proteins.

Composites with HDPE and PLA matrix have been tested to analyse the effect of natural fillers (wood flour, recycled waste paper and a mix of both fillers) and temperature on polymer degradation. Composting tests have been performed in both mesophilic (35°C) and thermophilic (58°C) conditions. Degradation development has been evaluated through mass variation, TGA and DSC. HDPE, as expected, did not display any relevant variation, confirming its stability under our composting conditions. PLA is sensibly influenced by temperature and humidity, with higher reduction of Mw when composting is performed at 58°C. Natural fillers seem to influence degradation process of composites, already at 35°C. In fact, degradation of fillers at 35°C allows a mass reduction during composting of composites, while neat PLA do not display any variation.

The neuroglial extracellular matrix (ECM) provides critical support and physiological cues for the proper growth, differentiation, and function of neuronal cells in the brain. However, in most in vitro settings that study neural physiology, cells are grown as monolayers on stiff surfaces that maximize adhesion and proliferation, and therefore lack the physiological cues that ECM in native neuronal tissues provides. Macromolecular crowding (MMC) is a biophysical phenomenon based on the principle of excluded volume that can be harnessed to induce native ECM deposition by cells in culture. Here, we show that MMC using two species of Ficoll with vitamin C supplementation significantly boosts deposition of relevant brain ECM by cultured human astrocytes. Dopaminergic neurons co-cultured on this astrocyte-ECM bed prepared under MMC treatment showed longer and denser neuronal extensions, a higher number of pre ad post synaptic contacts, and increased physiological activity as evidenced by higher frequency calcium oscillation, compared to standard co-culture conditions. When the pharmacological activity of various compounds was tested on MMC-treated co-cultures, their responses were enhanced, and for apomorphine, a D2-receptor agonist, it was inverted in comparison to control cell culture conditions, thus emulating responses observed in in vivo settings. These results indicate that macromolecular crowding can harness the ECM-building potential of human astrocytes in vitro forming an ultra-flat 3D microenvironment that makes neural cultures more physiological and pharmacological relevant.

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.

Blood-derived products (BP) like citrate-platelet-rich plasma (CPRP) or hyperacute serum (HAS) are known to contain many growth factors. Combined mitogenic and DNA damaging stimuli might lead to increased senescent cell burden and altered senescence-associated secretory pheno-type (SASP). Therefore, the senescent state was extensively tested by γH2AX staining, p21 Q-PCR and western blot, growth curves and senescence associated ß-galactosidase staining. Two main treatments with BP were performed early (immediately after etoposide) and late (after addition-al 11days). Effects of the BP treatment was evaluated by IL-6 and IL-8 measurement as well as collagen (COL1) and p21 mRNA expression. Additionally, XTT assays, cell size measurements, viability assays, and cell number calculations were performed. HAS treated cells in early treat-ment had the lowest observed IL-6 and IL-8. In contrast, there was a clear inflammatory response for IL-8 on HAS and CPRP treated cells in late treatment. For COL1 expression an upregulation in early treatment could be shown, meanwhile cells in the late treatment group remained unaf-fected. In CPRP treated cells, the COL1 expression decreased. All in all, BP treatment seems to have slightly positive effects regarding skin rejuvenation.

If an algebra of type $A$ contains a subalgebra which is also an algebra of type $B$, then it is a Smarandache $B$-type $A$-algebra provided the subalgebra of type $B$ contains at least two elements. This generalizes the notion of Smarandache group, where the group of order $\geq 2$ is a subsemigroup of a semigroup. In this paper we investigate a number of such pairings and we deduce a number of conclusions as a consequence.

Based on recent contributions regarding the treatment of unsteady hydraulic conditions into the state-of-the-art of scour literature, the theoretically derived probability distribution of bridge scour is introduced. The model is derived assuming a rectangular hydrograph shape with a given duration, and random flood peak following a Gumbel distribution. A model extension for a more complex flood event is also presented, assuming a synthetic exponential hydrograph shape. The mathematical formulation can be extended to any flood-peak probability distribution. The aim of the manuscript is to move forward the current approaches adopted for the bridge design coupling hydrological, hydraulic, and erosional models in a mathematical closed form.

Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation to gene expression control and cellular stress response. Recent evidence indicates that tsRNAs are also modified, however, the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. The tRNA methyltransferase TRMT2A catalyzes this modification, but its biological role remains mostly unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification, resulting in angiogenin (ANG) dependent tsRNA formation. More specifically, m5U54 hypomodification is followed by ANG overexpression and tRNA cleavage near the anticodon, resulting in accumulation of 5’tRNA-derived stress-induced RNAs (5’tiRNAs), in particular 5’tiRNA-GlyGCC and 5’tiRNA-GluCTC. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tsRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tsRNA formation in mammalian cells. These results establish a link between tRNA demethylation and ANG-dependent tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.

Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality among all ages; despite the advances, understanding pathophysiological responses after TBI is still complex, involving multiple mechanisms. Previous reviews have focused on potential targets; however, the research on potential targets has continuously grown in the last five years, bringing even more alternatives and elucidating previous mechanisms. Knowing the key and updated pathophysiology concepts is vital for adequate management and better outcomes. This article reviews the underlying molecular mechanisms, the latest updates, and future directions for pathophysiology-based TBI management.

Intracortical microelectrodes that can be implanted have the ability to capture fast-changing neuron action potentials in the living brain. Despite this potential, many obstacles must still be overcome for reliable, long-term, high-quality recordings and accurate analysis of brain activity. These challenges include improving recording quality, enhancing recording stability, increasing recording capacity, and adding multi-functional features. One potential approach to enhance implantable microelectrodes involves the advancement of materials, refinement of implantation methodologies, and augmentation of the number of sites for recording. However, these challenges are still being actively researched, and advancements in microelectrode technology are underway. The difficulties with implantable microelectrodes are evaluated, and solutions are presented from different perspectives. The latest advancements in microelectrode technology are reviewed and condensed, and future possibilities are explored.

Along just over a century of research we moved from learning how to cultivate tissues in a dish to grasping the concepts for creating an entire brain in a vat. As we approach the divisive moment in which we can first detect signs of awareness in such artificially developed organoids, we need to lay foundation for what lays ahead. It is crucial that ethical, legal and moral implications of organoid research are clear and that boundaries are set to separate scientific progress from human life preservation. The largest obstacle may be the definition of consciousness itself, which has arguably been historically neglected by philosophy, psychology and neurosciences at large. One reason may be the difficulties posed by the underlying qualities of awareness, such as its subjective and heterogeneous nature. Another reason may lie on the possibly that consciousness is an overarching emergent property of our brain. For the time being, one can see brain organoids as philosophical zombies, physical analogues of the human brain which mimic sentient human reactions but lack experiential properties of sensation (a.k.a. qualia).

Background: There is an increasing interest in the role of EEG in neurorehabilitation. We primarily aimed to identify the knowledge base through highly influential studies. Our secondary aims were to imprint the relevant thematic hotspots, research trends, and social networks within the scientific community. Methods: We performed an electronic search in Scopus looking for studies reporting on rehabilitation in patients with neurological disabilities. The most influential papers outlined the knowledge base, while a word co-occurrence analysis imprinted the research hotspots. Likewise, co-citation analyses highlighted collaboration networks between Universities, authors, and countries. The results were presented in summary tables, burst detection plots, and geospatial maps. Finally, a content review based on the top-20 most cited articles completed our study. Results: Our current bibliometric study was based on 874 records from 420 sources. There was a vivid research interest in EEG use for neurorehabilitation, with an annual growth rate as high as 14.3%. The most influential paper was the study titled "Brain-computer interfaces, a review" by Nicolas-Alfonso LF and Gomez-Gill J, with 997 citations, followed by "Brain-computer interfaces in neurological rehabilitation" by Daly J. and Wolpaw JR (708 citations). The USA, Italy, and Germany were among the most productive countries. The research hotspots shifted with time from the use of “functional magnetic imaging” to EEG-based “brain-machine interface”, “motor imagery”, and “deep learning”. Conclusions: EEG constitutes the most significant input in brain-computer interfaces (BCI) and can be successfully used in the neurorehabilitation of patients with stroke, amyotrophic lateral sclerosis, and traumatic brain and spinal injury. EEG-based BCI facilitates training, communication, and control of wheelchair and exoskeletons. However, research is limited to specific scientific groups from developed countries. Evidence is expected to change with the broader availability of BCI and improvement in EEG filtering algorithms.

Recent progress in microfabrication technique allowed the rapid development of neural implants. They are getting categorized as effective tools for clinical practice, especially to treat traumatic and neurodegenerative disorders. Microelectrode arrays already have been used in numerous neural interface devices. Basically, almost all neural implants have been developed based on BCI (Brain Computer Interface) system. When BCI system falls under invasive technique, it is referred as BMI or Brain Machine Interface. BMIs hold promises for neurorehabilitation of motor and sensory function, cognitive state evaluation and treatment of neurological chaos. A directed overview of the field of neural implants is discussed in this article. The aim of this review is to give a brief introduction of neural prosthetics as well as their exciting applications in treating neurological disorders and a deep discussion on their functionality are mentioned. BCI system and their different types, their functionality, their pros and cons, how other neural implants developed, and their present status have been covered. Different possibilities and possible future of deep brain stimulation (DBS), Neuralink, motor and sensory neural prosthetics are further discussed.

Tissues of the brain, especially white matter, are extremely heterogeneous - with constitutive response varying spatially. In this paper, we implement a high-resolution Finite Element (FE) head model where heterogeneities of white matter structures are introduced through Magnetic Resonance Elastography (MRE) experiments. Displacement of white matter under shear wave excitation is captured and the material properties determined though an inversion algorithm are directly used in the FE model. This approach is found to improve model predictions when compared to experimental results. In the first place, responses in the cerebrum near stiff structures such as the corpus callosum and corona radiata are markedly different compared with a homogenized material model. Additionally, the heterogeneities introduce additional attenuation of the shear wave due to wave scattering within the cerebrum.

One of the biggest queries in cognitive sciences is the emergence of consciousness from matter. Modern neurobiological theories of consciousness propose that conscious experience is the result of interactions between large-scale neuronal networks in the brain, traditionally described within the realm of classical physics. Here, we propose a generalized connectionist framework in which the emergence of “conscious networks” is not exclusive of large brain areas, but can be identified in sub-cellular networks exhibiting non-trivial quantum phenomena. The essential feature of such networks is the existence of strong correlations in the system (classical or quantum coherence) and the presence of an optimal point at which the system’s complexity is maximized, expressed either by maximization of the information content in large scale functional networks or by achieving optimal efficiency through the quantum Goldilock effect.

Background: Monocyte-derived dendritic cells (mo-DCs) play a vital role in the innate immune response by activating Th17 cells, which in turn release the pro-inflammatory cytokine IL-17. We hypothesised that following repetitive mechanical strain, tenocytes activate monocyte-derived dendritic cells, which in turn, drive the pathogenesis of tendinopathy. Aim: The aim of the study was to determine if monocyte-derived dendritic cells are upregulated in a human tendinopathy model. Method: Torn supraspinatus tendon and matched intact subscapularis tendon samples were collected from 7 patients undergoing arthroscopic shoulder surgery. Healthy control samples of subscapularis tendon were collected from 5 patients undergoing arthroscopic stabilization surgery. Tendon biopsy samples were evaluated immunohistochemically by quantifying the presence of monocyte-derived dendritic cells (CD11C and CD206). Results: Tendinopathic tendon samples exhibited significantly greater (2-3-fold) monocyte-derived dendritic cell expression when compared with healthy control tissue (P &lt; .05). Conclusion: This study provides evidence for a monocyte-derived dendritic cell upregulation in early-stage human tendinopathy.

Krill oil (KO) shows promise as a natural marine-derived ingredient for improving skin health. This study investigated its antioxidant, anti-inflammatory, anti-wrinkle, and moisturizing effects on skin cells and UVB-induced skin photoaging in hairless mice. In vitro assays on HDF, HaCaT, and B16/F10 cells, and in vivo experiments on 66 hairless mice, were conducted. Mice received oral KO administration (100, 200, or 400 mg/kg) once a day for 15 weeks and UVB radiation three times a week. In vitro, KO significantly countered UVB-induced oxidative stress, reduced wrinkles, and prevented skin water loss by enhancing collagen and hyaluronic synthesis. In vivo, all KO dosages showed dose-dependent inhibition of oxidative stress-induced inflammatory photoaging-related skin changes. Skin mRNA expressions for hyaluronan synthesis and collagen synthesis genes also increased dose-dependently after KO treatment. Histopathological analysis confirmed that Krill Oil (KO) ameliorated the damage caused by UVB-irradiated skin tissues. These findings suggest that KO may be a valuable intervention to mitigate UVB-induced skin photoaging and address various skin concerns.

Background: Chronic Back Pain due to Facet Joint Syndrome is a common and debilitating con-dition. Advances in regenerative medicine have shown that Autologous Unmodified Adipose Tissue-Derived Regenerative Cells (ADRC) provide several beneficial effects [1,2]. These regen-erative cells can differentiate into various tissues [3] and exhibit a strong anti-inflammatory po-tential. ADRCs can be obtained from a small amount of fatty tissue derived from the patient´s abdominal fat. Methods: We report long-term results of 37 patients (age 31-78 years, mean 62.5) suffering from “Facet Joint Syndrome” The pathology was confirmed by clinical, radiological examinations and fluoroscopically guided test injections. Then liposuction was performed. 50-100 cc of fat were harvested. To recover stem cells from adipose tissue, we use the CE-certified Transpose RT™ system from InGeneron GmbH. The cells were then injected under fluoroscopic control in the periarticular fat. Follow-up examinations were performed at one week 1 and 5 years. Results: Every patient reported improved VAS pain at any follow-up (1 week, 1, and 5 years) with ADRCs compared to the baseline. Conclusion: Our observational data indicate that facet joint syndrome patients treated with unmodified adipose tissue-derived regenerative cells experience improved quality of life in the long term.

Currently, there are no pharmacological treatments able to reverse nigral degeneration in Parkinson’s disease (PD), hence the unmet need for the provision of neuroprotective agents. Cannabis-derived phytocannabinoids (CDCs) and resveratrol (RSV) may be useful neuroprotective agents for PD due to their anti-oxidative and anti-inflammatory properties. To evaluate this, we undertook a systematic review of the scientific literature to assess the neuroprotective effects of CDCs and RSV treatments in pre-clinical in vivo animal models of PD. The literature databases MEDLINE, EMBASE, PsychINFO, PubMed and Web of Science core collection were systematically searched to cover relevant studies. A total of 1034 publications were analyzed, of which 18 met the eligibility criteria for this review. Collectively, the majority of neurotoxin-induced PD rodent studies demonstrated that treatment with CDCs or RSV produced a significant improvement in motor function and mitigated the loss of dopaminergic neurons. Biochemical analysis of rodent brain tissue suggested that neuroprotection was mediated by anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms. This review highlights the neuroprotective potential of CDCs and RSV for in vivo models of PD, and therefore suggests their potential translation to human clinical trials to either ameliorate PD progression and/or be implemented as a prophylactic means to reduce the risk of development of PD.

This paper aims to review the challenges, toxicity, and routes of synthesis and usage of silver nanoparticles in different applications but also highlighting their sustainability from both medical and environmental issues. Regarding their toxicity, it is known that silver nanoparticles can destroy over 650 microorganisms comparing with antibiotics. Supplementary, will be presented in a comparative manner some conventional synthesis routes (physical and chemical methods) and green synthesis routes using plant extracts. The approach using plant extracts have various advantages comparing with physical, chemical and microbial synthesis methods because there is no need to use chemicals, wasteful purifications and high energy requirements. The paper presents an overview on “green nanotechnology” focused on using either biological micro-organisms or plant extracts as an alternative to the classical chemical and physical methods. An important issue discussed in the paper is an overview of the synthesis routes of silver nanoparticles, some expected applications of silver based active agents and their toxicity and challenges that must be overcome. Also, it needs to focus our attention on the dismissal of silver nanoparticles into the environment and especially in water systems, fact which suggests that this issue must be fully understood and applied the law.

Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. Almost all cell types release EVs, thus they are naturally present in all body fluids. Among the several potential applications, EVs could be used as drug delivery vehicles in disease treatment, in immune therapy because of their immunomodulatory properties and in regenerative medicine. In addition to general markers, EVs are characterized by the presence of specific biomarkers (proteins, miRNAs) that allow the identification of their cell- or tissue-origin. For these features, they represent a potential powerful diagnostic tool to monitor state and progression of specific diseases. As regards, a large body of studies supports the idea that endothelial derived (EMPs) together with platelet-derived microparticles (PMPs) are deeply involved in the pathogenesis of diseases characterized by micro- and macrovascular damages, including diabetes. Existing literature suggests that the detection of circulating EMPs and PMPs and their specific miRNA profile may represent a very useful non-invasive signature to achieve informations about the onset of peculiar disease manifestations. In this Review, we discuss the possible utility of EVs in the early diagnosis of diabetes-associated microvascular complications, specifically related to kidney.

A brain tumor is an abnormal mass of tissue found inside the brain that consists of cells that grow and multiply without any control and unchecked by the mechanisms that regulate normal cell growth. It is one of the leading causes of death in many different regions worldwide, affecting various ages, sex, race, or ethnicities. Besides being a life-threatening condition, it can also disrupt normal brain function leading to severe cognitive morbidity. Additionally, the cost associated with active treatment and palliative care of the brain tumor most often proves to be out of reach for many people. Over the past decades, even though we have several published literature showing the epidemiology and characteristics of brain tumors, up-to-date epidemiological data is yet to be published. This review will provide comparable recent statistics regarding the incidence of brain tumors in 3 different regions; - the USA, the UK, and Australia. Also, a focus will be given to brain tumor’s key characteristics, classifications, and treatment protocol.

The blood-brain barrier (BBB) acts as a specialized structure separating the brain from peripheral blood circulation and plays an important role in brain function. Following an ischaemic stroke or cerebral ischaemia, the BBB is damaged leading to degraded proteins being released into blood circulation. However, little is known about cerebral ischaemia and reperfusion (I/R) induced BBB damage and changes in circulatory biomarkers. This study aims to use both immunohistochemistry and western blotting (WB) to examine neuronal death, glial cell alterations and changes in BBB tight junction (TJ) proteins such as zonula occludens-1 (ZO-1), Occludin and Claudin-5 in the hippocampus in a murine model of cerebral I/R. The changes in these proteins in the blood serum of this model were assessed by enzyme-linked immunosorbent assay. The results showed neuronal death and a significant increase in glial fibrillary acidic protein (GFAP), a protein primarily expressed in astrocytes and a significant decrease in TJ proteins, ZO-1, Occludin and Claudin-5 in the hippocampus of occluded mice as compared to sham-operated mice. These changes are associated with an increased level of these proteins in blood serum in ischaemic mice, suggesting that these proteins can be used as potential biomarkers for determining ischaemic stroke.

Magnetic Nanoparticles (MNPs) is a promising technique to cure brain diseases. On the one hand, by serving as drug carriers, they can bypass the blood-brain barrier and deliver drug molecules to the brain parenchyma; on the other hand, their transport trajectory can be manipulated by applying an external magnetic field. However, due to the complex microstructure of brain tissues, e.g. the anisotropy of white matter (WM), how to achieve desired drug distribution patterns, e.g. uniform distribution, by tuning the drug delivery system is largely unknown. Here, in this study, by adopting a mathematical model capable of capturing the diffusion trajectories of MNPs in the microstructures, we systematically investigated the effects of key parameters in the MNPs delivery system on the equivalent diffusion coefficient of MNPs in the microenvironment of brain WM. The results show that uniform distribution of MNPs in anisotropic tissues can be achieved by adjusting the particle size and magnetic field. We have not only obtained a deeper understanding on how to optimise the MNPs delivery system, it can also be anticipated that an improved mathematical model could even help to achieve complex drug distribution patterns in the complicated brain environment by designing an appropriate combination of the key parameters.

Proper nutrition is crucial for normal brain and neurocognitive development. Failure to optimize neurodevelopment early in life can have profound long-term implications for both mental health and quality of life. Although the first 1000 days of life represent the most critical period of neurodevelopment, the central and peripheral nervous systems continue to develop and change throughout life. All this time, development and functioning depend on many factors, including adequate nutrition. In this review, we outline the role of nutrients in cognitive, emotional, and neural development in infants and young children with special attention to the emerging roles of polar lipids and high quality (available) protein. Furthermore, we discuss the dynamic nature of the gut-brain axis and the importance of microbial diversity in relation to a variety of outcomes, including brain maturation/function and behavior are discussed. Finally, the promising therapeutic potential of psychobiotics to modify gut microbial ecology in order to improve mental well-being is presented. Here we show that the individual contribution of nutrients, their interaction with other micro-and macronutrients, and the way in which they are organized in the food matrix are of crucial importance for normal neurocognitive development.

Lathyrane-type diterpenes have a wide range of biological activities. Among them, euphoboetirane A (1) exerts neurogenesis-promoting activity. In order to increase the structural diversity of this type of lathyranes to explore their potential use in neurodegenerative disorders, the biotransformation of 1 by Streptomyces puniceus BC-5GB.11 has been investigated. The strain BC-5GB.11, isolated from surface sediments collected from the intertidal zone of the inner Bay of Cadiz, was identified as Streptomyces puniceus, as determined by phylogenetic analysis using 16S rRNA gene sequence. Biotransformation of 1 by BC-5GB.11 afforded five products (3-7), all of them reported here for the first time. The main biotransformation pathways involved regioselective oxidation at non-activated carbons (3-5) and isomerization of the D^12,13 double bond (6). In addition, a cyclopropane-rearranged compound was found (7). The structures of all compounds were elucidated on the basis of extensive NMR and HRESIMS spectroscopic studies.

Current methodologies for developing patient-derived xenografts (PDX) in humanized mice in preclinical trials to test response to immune-based therapies are limited by graft versus host disease. Here we compared two approaches for establishing PDX tumors in humanized mice: 1) PDX are first established in immune-deficient mice; 2) PDX are initially established in humanized mice, before transplanting established PDX’s to a larger cohort of humanized mice for preclinical trials. With the first approach, there was rapid wasting of PDX-bearing humanized mice with high levels of activated T cells in the circulation and organs, indicating immune-mediated toxicity. In contrast, with the second approach, toxicity was less of an issue and long-term human melanoma tumor growth and maintenance of human chimerism was achieved. Pre-clinical trials from the second approach revealed that rigosertib, but not anti-PD-1, increased CD8/CD4 T cell ratios in spleen and blood and inhibited PDX tumor growth. Resistance to anti-PD-1 was associated with limited infiltration of CD8+ T cell into the tumor. Our findings suggest that it is essential to carefully manage immune editing by first establishing PDX tumors in the presence of human immune cells before expanding PDX tumors into a larger cohort of humanized mice to evaluate therapy response.

3D bioprinting is the process of manipulating cell-laden bioinks to fabricate living structures. 3D bioprinting techniques have brought considerable innovation in biomedicine, especially in the field of tissue engineering, allowing the production of 3D organ and tissue models for in vivo transplantation purposes or for in-depth and precise in vitro analyses. Natural-derived hydrogels, especially those obtained from the decellularization of biological tissues, are promising bioinks for 3D printing purposes, as they present the best biocompatibility characteristics. Despite this, many natural hydrogels do not possess the necessary mechanical properties to allow a simple and immediate application in the 3D printing process. In this review, we focus on the bioactive and mechanical characteristics that natural hydrogels may possess to allow efficient production of organs and tissues for biomedical applications, emphasizing the reinforcement techniques to improve their biomechanical properties.

High density polyethylene (HDPE) and poly(lactic) acid (PLA) blends with different ratios of both polymers, namely 30:70, 50:50 and 70:30, were produced. Polyethylene grafted maleic anhydride and a random copolymer of ethylene and glycidyl methacrylate, were also proposed as compatibilizers to modify HDPE-PLA optimal blends and were added in the amounts of 1, 3 and 5 wt.%. Blends properties have been evaluated through different aspects by performing tensile tests, scanning electron microscopy to analyze blend morphology and interfaces, and thermomechanical analysis through differential scanning calorimetry, thermo-gravimetric analyses and infrared spectroscopy. The second blend, the one with equal amounts of HDPE and PLA seems to represent a good balance between high amount of bio-derived charge and acceptable mechanical properties. This suggests a good potential of these blends, which would be a good starting point for the production of composites with lingo-cellulosic fillers.

Sporotrichosis is a subcutaneous mycosis affecting humans and other animals that can be transmitted a zoonosis with cats as the main vector. The conventional anti-fungal therapy is especially inefficient in immunocompromised patients, who tend to develop the most severe forms of the disease, thus prompting the search for alternative therapies. Given their antigen-presenting properties, dendritic cells (DCs) have been used in both prophylactic and therapeutic vaccination strategies. Hence, this study aims to assess the use of DCs as a prophylactic tool in sporotrichosis by evaluating the immune profile induced by Sporothrix schenckii cell wall proteins (SsCWP)-stimulated bone-marrow-derived DCs (BMDCs). Mouse BMDCs were stimulated with SsCWP for 24 hours and analyzed for the surface expression of co-stimulatory molecules and TLR-4, as well as the secretion of proinflammatory cytokines and IL-10. Following that, activated BMDCs were cocultured with splenocytes for 72 hours and had the same cytokines measured in the supernatant. SsCWP-stimulated BMDCs showed higher expression of CD80, CD86, and CD40, but not TLR-4, and higher secretion of IL-6, IL-17A, and TNF. On the other hand, higher levels of IFN-γ, IL-10, and IL-2 were found in the supernatants of the coculture as compared with the BMDCs alone; TNF secretion was almost completely abrogated, whereas IL-6 was only partially inhibited and IL-17A was unaffected. Our results thus suggest SsCWP-stimulated BMDCs are able to induce a Th1-prone cytokine profile, known to be protective against other fungal diseases. This result could lead to evaluate the development of prophylactic and/or therapeutic DC-based tools against sporotrichosis.

Our knowledge on the plastic functions of the serotonin (5-HT) receptor subtype 7 (5-HT7R) in the brain physiology and pathology considerably advanced in the last few years. A wealth of data show that the 5-HT7R is a key player in the establishment and remodeling of neuronal cytoarchitecture during development and in the mature brain, and its dysfunction is linked to neuropsychiatric and neurodevelopmental diseases. The involvement of this receptor in synaptic plasticity is further demonstrated by data showing that its activation allows to rescue long term potentiation (LTP) and long term depression (LTD) deficits in various animal models of neurodevelopmental diseases. In addition, it is becoming clear that the 5-HT7R is involved in inflammatory intestinal diseases, possibly playing a role in the gut-brain axis, and modulates the function of immune cells. In this review, we will mainly focus on recent findings on this receptor’s role in the structural and synaptic plasticity of the mammalian brain, although we will also illustrate novel aspects highlighted in gut and immune system.

Non-suicidal self-injurious behavior (NSSI), prevalent in patients with non-psychotic mental disorders (NPMD), is associated with numerous adverse outcomes. Despite active research into the clinical and psychological aspects of NSSI, the underlying biological mechanisms remain obscure. Early adverse experiences are believed to induce long-lasting changes in neuroendocrine mechanisms of stress control playing a key role in NSSI development. The aim of the study was to evaluate parameters potentially predicting development of NSSI in female patients with NPMD. Eighty female patients over 18 years with NPMD and suicidal ideation (40 with and 40 without NSSI) and 48 age matching women without evidence of mental illness (healthy controls) were enrolled. Diagnostic interviews and self-report measures were used to assess childhood maltreatment, presence, frequency, and characteristics of suicidal and self-injurious thoughts and behaviors, the Beck Depression Inventory scale to assess severity of depression. Hypothalamic-pituitary-adrenal axis markers, hormones, and neurotrophic factors were measured in blood serum. The likelihood of developing NSSI in patients with NPMD was associated with early adverse family history and elevated adrenocorticotropic hormone levels. Dysregulation of hypothalamic-pituitary-adrenal axis as a result of early chronic stress experiences may represent critical biological mechanism promoting the development of NSSI behaviors in patients with NPMD.

Epilepsy is a neurological disorder that affects approximately 1% of the world's population. To diagnose and estimate the occurrence of epilepsy, the analysis of recorded brain activity is performed by a neurologist, which is not only time-consuming and tedious but also occasionally accompanied by human error. Therefore, in recent decades, researchers have aimed to unravel an approach for designing and building an automated method for diagnosing and estimating the occurrence of epilepsy. Accordingly, the present study proposed two new-fangled ways based on brain signals and a convolutional neural network (CNN). Moreover, this research implements a CNN with a sequential three-layer structure. Numerous experiments were performed, and the accuracy of estimating epilepsy using the developed methods was achieved at 95% without feedback and 97% with feedback. The proposed methods were proven to be more accurate than the previous techniques and can be employed as a physician's assistant once entering the field of operation.

Here, we review findings and trends in sleep research in 2020-2021 demonstrating how COVID-19 and sleep disorders can induce the BBB leakage via neuroinflammation, which might contribute to the 'coronasomnia' phenomenon. The new studies suggest that the controlling of sleep hygiene and quality should be incorporated into the rehabilitation of COVID-19 patients. We also discuss perspective strategies for prevention of COVID-19-related BBB disorders. We demonstrate that sleep might be a novel biomarker of the BBB leakage and the analysis of sleep EEG patterns can be a breakthrough non-invasive technology for diagnosis of the COVID-19-caused BBB disruption.

New research points to a possible link between Autism Spectrum Disorder and the gut microbiota as many autistic children have co-occurring gastrointestinal problems. This review focuses on specific alterations of gut microbiota mostly observed in autistic patients. Particularly, the mechanisms through which such alterations may trigger the production of the bacterial metabolites or leaky gut in autistic people are described. Various altered metabolite levels were observed in autistic children, many of those were of bacterial origin such as short chain fatty acids (SCFAs), indoles and lipopolysaccharides. A less integrative gut-blood-barrier is abundant in autistic individuals. This explains the leakage of bacterial metabolites into the patients triggering new body responses or altered metabolism. Some other co-occurring symptoms such as mitochondrial dysfunction, oxidative stress in the cells, altered tight junctions in the blood brain barrier and structural changes in cortex, hippocampus, amygdala and cerebellum were detected. Moreover, this paper suggests that autism is associated with an unbalanced gut microbiota (dysbiosis). Although the cause-effect relationship between autism and gut microbiota is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health. Diagnostic and therapeutic value of new biomarkers leading to the perturbation in the phenylalanine metabolism will be discussed.

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

The rhizome of Drynaria fortunei (Kunze ex Mett.) J. Sm., which is known as “Golsebo” in Korea, has been traditionally used to treat various inflammatory conditions, including bone metabolism disorders. It relieves blood extravasation, stops bleeding, repairs broken bone tissue, treats bone fractures, and kills bacteria. Recently, D. fortunei-derived polysaccharides (DFP) have been identified as bioactive compounds that act against numerous human diseases. However, the molecular mechanism underlying the bone metabolism-improving effect of DFP has not been elucidated. In this study, we evaluated the modulatory effects of DFP on the differentiation of bone marrow-derived macrophages into osteoclasts. We performed tartrate-resistant acid phosphatase assays using DFP (different concentrations and molecular weights) to evaluate the degree of bone resorption in the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis of bone marrow-derived macrophages. DFP significantly inhibited RANKL-induced osteoclastogenesis and suppressed RANKL-mediated overexpression of c-Fos and nuclear factor of activated T cells 1, thereby downregulating osteoclast-specific gene (Atp6v0d2, DC-STAMP, and cathepsin K) expression. DFP has potential as a nutraceutical candidate for treating bone loss diseases, including osteoporosis in postmenopausal women.

Introduction: Adverse events related to vaccines are reactions that can lead to serious complications, in the present that we live at the publication of this article with the need to generate high rates of vaccination have been presented in the case of vaccine agents against COVID-19 adverse events, with thrombotic events being the most important. Case Presentation: This is a 37-year-old female patient who presents 11 days after ChAdOx1-S vaccination against COVID-19 presents with intense headache associated with symptoms of intracranial hypertension, she was initially taken to simple cranial tomography showing presence of cerebral edema and indirect signs of cerebral venous thrombosis, it is proposed to carry out cerebral angiography which showed the presence of thrombosis of both transverse venous sinuses, no hypercoagulability states were found in the laboratories, the immunological tests carried out for antiphospholipid syndrome were negative, the thrombotic event was associated with the ChAdOx1-S vaccine, later the patient was taken to thrombectomy by Neuroradiology, achieving complete channeling of both transverse venous sinuses. Conclusions: Adverse events associated with vaccination have been described with multiple vaccine agents, this component against COVID-19 is also an event to consider, knowing the pathophysiology of these events is essential to be able to reduce these risks and select the least risky agent. Despite this risk, vaccination remains the only cost-effective measure to reduce the morbidity and mortality associated with COVID-19.

Brain magnetic resonance imaging (MRI) offers a unique lens to study neuroanatomic support of human neurocognition and intelligence. A core mystery is the MRI explanation of individual differences in neurocognition and intelligence. The past four decades have seen great advancement in studying this century-long mystery, but the sample size and population-level studies limit the explanation at the individual level. The recent rise of big data and artificial intelligence offers novel opportunities. Yet, data sources, harmonization, study design, and interpretation need to be carefully considered. This review aims to summarize past work, discuss rising opportunities and challenges, and facilitate further investigations on machine intelligence inferring human intelligence.

Background: Traumatic brain injury (TBI) remains a significant risk factor for post-traumatic epilepsy (PTE). The pathophysiological mechanisms underlying the injury-induced epileptogenesis are under under investigation. The dentate gyrus, a structure highly susceptible to injury, and has been implicated in the evolution of seizure development. Methods: Utilizing the murine unilateral focal control cortical impact (CCI) injury, we evaluated seizure onset using 24/7 EEG video analysis at 2-4 months post-injury. Cellular changes in the dentate gyrus and hilus of the hippocampus were quantified by non-biased stereology and Imaris image analysis to evaluate Prox1-positive cell migration, astrocyte branching and morphology, as well as neuronal loss at four months post-injury. Isolation of region-specific astrocytes and RNA-seq was performed to determine differential gene expression in PTE+ vs. PTE- that may comport with the epileptogenic process. Results: CCI injury resulted in 37% PTE+-incidence, which increased with injury severity and hippocampal damage. Histological assessments uncovered a significant loss of hilar interneurons that coincided with aberrant migration of Prox1-positive granule cells and reduced astroglial branching in PTE+ compared to PTE- mice. We uniquely identified Cst3 as a PTE+-specific gene signature in astrocytes across all brain regions. Conclusions: These findings suggest that epileptogenesis may emerge following TBI due to distinct aberrant cellular remodeling events and key molecular changes in the dentate gyrus of the hippocampus.

We introduce a mission design for an interstellar expedition to nearby earth-like exoplanets, which our analysis determined to be Tau Ceti and Gliese 667C, at the time of analysis in 2013. We review the research problems in propulsion and AGI that must be addressed to launch an AI guided interstellar probe within 100 years. We propose a new semi-autonomous agent approach for intelligent control of the spacecraft. We introduce the concept of a semi-autonomous agent as having built-in safety guarantees that constrain operation. An autonomous agent case study is presented formulating the objective, constraints, AGI implementation of the agent based on Solomono's Alpha architecture, and adding specicity. We discuss the training required to reach human-level and trans-sapient levels of intelligence which corresponds to an entire crew of AI experts specialized in elds such as astrophysics, astromechanics, astrobiology, quantum physics, computer science, molecular biology, and so forth. We project the feasibility of the human-level AI technology based on empirical ndings in neuroscience, and nd that it should be feasible by 2030. We analyze Solomono's innity point hypothesis in light of Koomey's law about energy eciency of computing and nd that the trends in 2013 indicated an early singularity by 2035, which implies that we might encounter physical bottlenecks which will decelerate computing technology improvements signicantly. We recommend thus year 2040 for launching the probe by which date other required technologies will have been developed. We discuss the scenario of a virtual crew made of brain simulations, which is a bio-information based AI approach. We detail the subsystems of command and control, communication, scientic instrumentation, power, propulsion, navigation, and shielding. We propose a variation of ICAN-II/AIMStar propulsion which uses a positron source instead of anti-protons to initiate micro-fusion reactions. We combine the positron initiated fusion pulse propulsion scheme with a miniaturized version of the Daedelus fusion thruster obtaining high performance. We derive two mission proles one for fusion pulse propulsion, and the yet hypothetical Q-Thruster. Fusion thruster requires 132.2 years for Tau Ceti, and 233.2 years for Gliese 667C, while Q-Thruster takes only 42.3 years for Tau Ceti, and 62.5 years for Gliese 667C. We also discuss extended roles for intelligent interstellar probes such as self-reproduction via nanotechnology, refueling, construction, robotic bodies, and transmission of brain simulations.

There is evidence that spaceflight poses acute and late risks on the central nervous system. To explore possible mechanisms, the proteomic changes following spaceflight in mouse brain were characterized. Space Shuttle Atlantis (STS-135) was launched at the Kennedy Space Center on a 13-day mission. Within 3–5 hours after landing, brain tissue was collected to evaluate protein expression profiles using quantitative proteomic analysis. Our results showed that there were 26 proteins that were significantly altered after spaceflight in the grey and/or white matter. While there was no overlap between the white and grey matter in terms of individual proteins, there was overlap in terms of function, synaptic plasticity, vesical activity, protein/organelle transport, and metabolism. Our data demonstrate that exposure to the spaceflight environment induces significant changes in protein expression related to neuronal structure and metabolic function. This might lead to a significant impact on brain structural and functional integrity that could affect the outcome of space missions.

Traumatic Brain Injury represents a significant public health concern due to its role in traumatic death and disability, often caused by head impacts or rapid accelerations. Despite advancements in Finite Element Head Models, existing models primarily represent adult males, neglecting anatomical and physiological differences between genders and age groups. Additionally, the mechanistic roles of specific intracranial tissues, such as the dura mater, have conventionally been overlooked. To better understand the mechanical behavior of the brain and its injured regions in the context of TBI, including the dura mater, this study proposes the development of a Female Finite Element Head Model. This model, representative of a middle-aged female subject, was developed using medical image-derived geometry and finite element modeling techniques. The validation results demonstrate a similarity between the numerical displacement curves and those obtained experimentally. In the model with dura mater, the numerical results show analogous behavior to the experimental results, despite minimal variations in the amplitude of the curves. These advancements highlight the significance of including the dura mater in biomechanical brain modeling. Incorporating the dura mater in Finite Element Head Models produces more realistic results than models without it. This emphasizes the importance of enhancing biomechanical models to better represent anatomical complexity.

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid vesicles derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted by progenitor and stem cells have been associated with the therapeutic effects observed in cell-based therapies, and they also contribute to tissue regeneration following injury, such as in orthopedic surgery cases. This review briefly explores the involvement of EVs in tissue repair and nerve regeneration, their potential as drug carriers, and their significance in stem cell research and cell-based therapies. It underscores the importance for bioengineers to comprehend and manipulate EV activity to optimize the efficacy of tissue engineering and regenerative therapies.

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.

The appearance of brain metastasis is the most serious complication of breast cancer with mostly fatal outcomes. To reach the brain, tumor cells need to pass the blood-brain barrier (BBB). The molecular mechanisms underlying penetration of the BBB are largely unknown. Previously we found that tumor-infiltrating T lymphocytes enhance the development of brain metastasis of estrogen receptor-negative (ER-) breast cancer. In the current study, we investigate the contribution of T lymphocytes and the IFN- pathway in enabling breast cancer cells to pass the in vitro BBB. CD8+ cells display the strongest stimulatory effect on breast cancer cell passage. We show that inhibition of the IFN- receptor in MDA-MB-231 breast cancer cells, or neutralization of soluble IFN-, impairs the in vitro trespassing of breast cancer cells. Importantly, we validated our findings using gene expression data of breast cancer patients. CXCL-9,-10,-11/CXCR3 axis, dependent on IFN- signaling activity, was overexpressed in primary breast cancer samples of patients who developed brain metastasis. The data support a role for T-lymphocytes and the IFN- pathway in the formation of brain metastasis of ER- breast cancer, and offer targets to design future therapies for preventing breast cancer cells to cross the BBB.

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.

Head injury is among the most devastating types of injury, specifically called Traumatic Brain Injury (TBI). There is need to diminish the morbidity related with TBI and to improve the outcome of patients suffering TBI. Among the improvements on the treatment of TBI, neuroprotection is one of the upcoming improvements. Citicoline has been used in the management of brain ischemia related disorders, such as TBI. Citicoline has biochemical, pharmacological, and pharmacokinetic characteristics that make it a potentially useful neuroprotective drug for the management of TBI. A short review of these characteristics is included in this paper. Also, a narrative review of almost all the published or communicated studies performed with this drug in the management of patients with head injury is included. Based on the results obtained in these clinical studies, it is possible to conclude that citicoline was able to accelerate recovery of consciousness and to improve the outcome of this kind of patients, with an excellent safety profile. Thus, citicoline could have a potential role in the management of TBI.

Current hypotheses implicate insulin resistance of the brain as a pathogenic factor in the development of Alzheimer’s disease and other dementias, Parkinson’s disease, type 2 diabetes, obesity, major depression, and traumatic brain injury. A variety of genetic, developmental, and metabolic abnormalities that lead to disturbances in the insulin receptor signal transduction may underlie insulin resistance. Insulin receptor substrate proteins are generally considered to be the node in the insulin signaling system that is critically involved in the development of insulin insensitivity during metabolic stress, hyperinsulinemia, and inflammation. Emerging evidence suggests that lower activation of the insulin receptor (IR) is another common, while less discussed, mechanism of insulin resistance in the brain. This review aims to discuss causes behind the diminished activation of IR in neurons, with a focus on the functional relationship between mitochondria and IR during early insulin signaling and the related roles of oxidative stress, mitochondrial hypometabolism, and glutamate excitotoxicity in the development of IR insensitivity to insulin.

Current hypotheses implicate insulin resistance of the brain as a pathogenic factor in the development of Alzheimer’s disease and other dementias, Parkinson’s disease, type 2 diabetes, obesity, major depression, and traumatic brain injury. A variety of genetic, developmental, and metabolic abnormalities that lead to disturbances in the insulin receptor signal transduction may underlie insulin resistance. Insulin receptor substrate proteins are generally considered to be the node in the insulin signaling system that is critically involved in the development of insulin insensitivity during metabolic stress, hyperinsulinemia, and inflammation. Emerging evidence suggests that lower activation of the insulin receptor (IR) is another common, while less discussed, mechanism of insulin resistance in the brain. This review aims to discuss causes behind the diminished activation of IR in neurons, with a focus on the functional relationship between mitochondria and IR during early insulin signaling and the related roles of oxidative stress, mitochondrial hypometabolism, and glutamate excitotoxicity in the development of IR insensitivity to insulin.

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.

Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying non-invasive biomarkers in body fluids such as blood and urine. A source of biomarkers in these biofluids are extracellular vesicles (EVs), nanosized vesicles that contain a wide array of molecular cargo, including small non-coding RNA such as microRNA and transfer RNA-derived fragments (tRF). Here we performed small-RNA next-generation sequencing for urine EVs, serum EVs and serum supernatant from 41 patients with non-muscle invasive BC (27 stage Ta, 14 stage T1) and 15 non-cancer patients (NCP) with benign cystoscopy findings. Serum and urine samples were collected before transurethral resection of bladder tumors (TUR-b) and at routine postsurgery check-ups. Expression levels of tRFs in presurgery samples were compared to those at postsurgery check-ups and to NCPs. To strengthen the reliability of our results, samples from 10 patients with stage T1 disease were resequenced. When comparing tRF expression in urine EVs between BC patients with stage T1 disease and NCPs, 14 differentially expressed tRFs (DEtRFs) were identified. In serum supernatant, six DEtRFs were identified among stage T1 patients when comparing presurgery to postsurgery samples, and four DEtRFs were found when comparing presurgery samples to NCPs. By performing a blast search, we found that sequences of DEtRFs aligned with genomic sequences pertaining to processes relevant to cancer development, such as enhancers, regulatory elements and CpG islands. Our findings display a number of tRFs that may hold potential as biomarkers for the diagnosis and recurrence-free survival of BC.

Cell junction that is usually associated with dynamic cytoskeletons is essential for a wide range of cellular activities such as cell migration, cell communication, barrier function and signal transduction. Real-time observation of cell junction facilitates understanding of the mechanisms by which cell junction regulate relevant cellular activities. In this study, we examined the binding capacity of a modified tridecapeptide from Cx43 to cell junction protein ZO-1 and sought to create a fluorescent peptide that could be used to label cell junction. To introduce the fluorescent peptide into the cells, a cell-penetrating peptide was linked to the modified tridecapeptide and synthesized. The binding of the modified tridecapeptide was tested using pull down and immunoprecipitation assay. The ability of the peptide to label cell junction was assessed by adding it to fixed or cultured Caco-2 cells. Testing assay revealed that the Cx43-derived peptide can bind to ZO-1. Besides, the peptide was able to label cell junction of fixed cell, although no obvious cell junction labeling was observed clearly in living cells, probably due to the inadequate affinity. These results indicate that a peptide-based strategy for labeling cell junction may be feasible, and efforts to improve its affinity are warranted in the future.

Although the COVID-19 pandemic appears to be diminishing, the emergence of SARS-CoV-2 variants represents a threat to humans due to its inherent transmissibility, immunological evasion, virulence, and invulnerability to existing therapies. The previous COVID-19 pandemic affected more than 500 million people and caused over 6 million deaths. Vaccines are essential, but in circumstances when vaccination is not accessible or in individuals with compromised immune systems, drugs can give additional protection. Targeting host signaling pathways is recommended due to their genomic stability and resistance barriers. Plant-derived products, which have been used in traditional medicine for treating pathological conditions, offer structurally novel therapeutic compounds including anti-viral. In addition, plant-derived bioactive substances might serve as the ideal basis for developing sustainable/efficient/cost-effective anti-viral alternatives. Epigenetic modifications in the genome can affect gene expression without altering DNA sequence. Host cells can use epigenetic gene regulation as a mechanism to silence incoming viral DNA molecules, while viruses have recruited cellular epi transcriptomic (covalent modifications of RNAs) modifiers to increase the translational efficiency and transcript stability of viral transcripts to enhance viral gene expression and replication. Moreover, viruses manipulate host cells' epigenetic machinery to ensure productive viral infections. Environmental factors, such as natural products, may influence epigenetic modifications. In this review, we are exploring the potential of plant-derived substances as epigenetic modifiers for broad-spectrum anti-viral activity, reviewing modulation processes and anti-viral effects on DNA and RNA viruses, and addressing future research objectives in this rapidly emerging field.

The concept of targeted drug delivery can be described in terms of the drug’s ability to mimic the other biological objects’ property to localize to target cells or tissues. For example, drug delivery systems based on red blood cells or mimicking some of their useful features, such as long circulation in stealth mode, have been known for decades. On the contrary, therapeutic strategies based on macrophages have gained very limited attention until recently. Here we review two biomimetic strategies associated with macrophages, that can be used to develop new therapeutic modalities: First, the mimicry of certain types of macrophages (i.e., the use of macrophages, including tumor-associated, or macrophage-like particles as a carrier for targeted delivery of therapeutic agents); and Second, the mimicry of ligands, naturally absorbed by macrophages (i.e., the use of therapeutic agents specifically targeted at macrophages). We discuss potential applications of biomimetic systems involving macrophages for the new advancements in treatment of infections, inflammatory diseases, and cancer.

Chronic wounds are associated with considerable patient morbidity and present a significant economic burden to the healthcare system. Often, chronic wounds are in a state of persistent in-flammation and unable to progress to the next phase of wound healing. Placental-derived bio-materials are recognized for their biocompatibility, biodegradability, angiogenic, an-ti-inflammatory, anti-microbial, anti-fibrotic, immunomodulatory, and immune privileged prop-erties. As such, placental-derived biomaterials have been used in wound management for more than a century. Placental-derived scaffolds are composed of an extracellular matrix (ECM) that can mimic the native tissue, creating a reparative environment to promote ECM remodeling, cell migration, proliferation, and differentiation. Reliable evidence exists throughout the literature to support the safety and effectiveness of placental-derived biomaterials in wound healing. How-ever, differences in source (i.e., anatomical regions of the placenta), preservation techniques, decellularization status, design, and clinical application have not been fully evaluated. This re-view provides an overview of wound healing and placental-derived biomaterials, summarizes the clinical results of placental-derived scaffolds in wound healing, and suggests directions for future work.

The SiBOC precursor ceramics were fabricated by polymer-derived method SiBOC precursors with different B/Si molar ratios were synthesized by controlling monomer content. The effects of different process conditions on SiBOC ceramics and the oxidation resistance of SiBOC ceramics at a high temperature (1400 ℃) were studied. The SiBOC precursor’s bonds of Si-O-C, Si-O-Si, and Si-O-B were detected by FTIR. The precursor is converted to a rigid ceramic material that has an 85.3 wt % ceramic yield of SiBOC ceramics with B/Si=0.4 by TG-DSC. The results of SEM analysis show that the SiBOC ceramics surface bulges and folds increase with the increase of boric acid content. With the increase of pyrolysis temperature and pyrolysis time, the size and number of pores on the surface of SiBOC ceramics also increase. Static oxidation tests show that SiBOC ceramics with B/Si=0.4 have better oxidation resistance under other conditions being the same.

In the present day and age, cancer is still a life-limiting factor whose one of the therapeutic strategies is immunotherapy with vaccines. This research aims to prepare and characterize nanoliposomal vaccine formulation attached to HER2/neu-derived peptide (AE36) with or without CpG-ODN, and to evaluate its immunological responses to the therapy using BALB/c mice with HER2 overexpressing breast cancer. Methods: AE36 was conjugated to the liposomes containing DOTAP, DOPE and Cholesterol. Such formulations are able to produce CD8+ and CD4+ responses and induce synthesis of cytokines detectable via Enzyme-linked immunosorbent assay kits, cytotoxicity testing and intracellular cytokine staining combined with flow cytometry. Therapeutic and prophylactic effectiveness were evaluated through the formulation in samples. The highest effectiveness was found in DDC-peptide + CpG-ODN in both prophylactic and therapeutic studies, which decreased the size of tumors significantly and increased time of survival. These nanoliposomes linked to AE36 could be regarded as an appropriate candidate for the treatment and also for prophylaxis of HER2+ breast cancer; however further studies are needed.

Adipose-derived stem cells (ADSCs) were suggested for treating degenerative osteoarthritis, suppressing inflammatory responses, and repairing damaged soft tissues. Moreover, the ADSCs have the potential to undergo self-renewal and differentiate into bone, tendon, cartilage, and ligament. Recently, investigation of the self-renewal and differentiation of the ADSCs becomes an attractive area. In this work, a pneumatic microdevice has been developed to study the gene expression of the ADSCs after the stimulation of multi-axial tensile strain. The ADSCs were cultured on the microdevice and experienced multi-axial tensile strain during a 3-day culture course. Self-renewal and differentiation abilities were investigated by mRNA expressions of NANOG, SOX2, OCT4, SOX9, PPAR-γ, and RUNX2. The result showed that the genes related self-renewal were significantly up-regulated after the tensile stimulation. Higher proliferation ratio of the ADSCs was also shown by cell viability assay. The microdevice provides a promising platform for cell-based study under mechanical tensile stimulation.

Mesenchymal stem cells (MSCs) have emerged as a promising treatment for inflammatory diseases. It is described that the immunomodulatory effect of MSCs takes place both by direct cell-to-cell contact and by means of soluble factors that leads to an increased accumulation of regulatory immune cells at the sites of inflammation. Similar efficacy of MSCs has been described regardless the route of administration used, the inflammation conditions and the MHC context. These observations arise the question as to whether the migration of the MSCs to the inflamed tissues is a pre-requisite to achieve their beneficial effect. To address this, we examined the biodistribution and the efficacy of intraperitoneal luciferase-expressing human expanded adipose derived stem cells (Luci-eASCs) in a mouse model of colitis. Luci-eASC-infused mice were stratified according to their response to the Luci-eASC treatment. According to the stratification criteria, there was a tendency to increase the bioluminescence signal in the intestine at the expense of a decrease in the bioluminescence signal in the liver in the `responder´ mice. These data thus suggest that the accumulation of the eASCs to the inflamed tissues is beneficial to achieve an optimal modulation of inflammation.

The question of what generates conscious experience has mesmerized thinkers since the dawn of humanity, yet its origins remain a mystery. The topic of consciousness has gained traction in recent years, thanks to the development of large language models that now arguably pass the Turing test, an operational test for intelligence. However, intelligence and consciousness are not related in obvious ways, as anyone who suffers from a bad toothache can attest - pain generates intense feelings and absorbs all our conscious awareness yet nothing particularly intelligent is going on. Still, in the hard sciences, this topic is frequently met with skepticism because to date no protocol to measure the content or intensity of conscious experiences in an observer-independent manner has been agreed upon. Here we present a novel proposal: Conscious experience arises whenever a quantum mechanical superposition forms. Our proposal has several implications: First, it suggests that the structure of the superposition determines the qualia of the experience. Second, quantum entanglement naturally solves the binding problem, ensuring the unity of phenomenal experience. Finally, a moment of agency may coincide with the formation of a superposition state. We outline a research program to experimentally test our conjecture via a sequence of quantum biology experiments. Applying these ideas opens up the possibility of expanding human experience through brain-quantum computer interfaces.

Brain models present a viewpoint on the fundamental structural components of the brain and their mutual organization, generally relative to a particular concept of the brain axis. A model may be based on adult brain structure or on developmental morphogenetic aspects. Brain models usually have functional implications, depending on which functional properties derive from the postulated organization. This essay examines the present scenario about brain models, emphasizing the contrast between columnar or other longitudinal models and transverse subdivisional neuromeric models. In each case, the main functional implications and apparent problems are explored and commented. Particular attention is given to the modern molecularly based ‘prosomeric model’, which postulates a set of 20 transverse prosomeres as the developmental units that serve to construct all the cerebral parts and the particular typology of many different neuronal populations within the forebrain and the hindbrain, plus a number of additional spinal cord units. These metameric developmental units (serially repeated, but with unique molecular profiles) confer to this model remarkable functional properties based mainly on its multiplicity and modularity. Many important brain functions can be decomposed into subfunctions attended to by combined sets of neuronal elements derived from different neuromeres. Each neuromere may participate in multiple functions. Most aspects related to creation of precise order in neural connections (axonal navigation and synaptogenesis) and function is due to the influence of neuromeric anteroposterior and dorsoventral positional information. Research on neuromeric functionality aspects is increasing significantly in recent times.

Light is an electromagnetic radiation that has visible and invisible wavelength spectrum. The visible light can only be detected by the eyes through the optic pathways. With the presence of scalp, cranium and meninges, the brain is seen as being protected from direct exposure to light. For that reason, the brain can be viewed as a black body lying inside a black box. In physics, a black body tends to be in thermal equilibrium with its environment and can tightly regulate its temperature via thermodynamics principles. Therefore, a healthy brain inside a black box should not get exposed to light. On the contrary, photobiomodulation, a form of light therapy to the brain has been shown to have beneficial effects for some neurological conditions. The proposed underlying mechanisms are multiple. Herein we present our intraoperative findings of rapid electrocorticographic brainwave changes when the brain was shone directly with different wavelengths of light during awake brain surgery. Our findings provide literature proof on light’s ability to influence human brain energy and function. Our proposed mechanism for these rapid changes is the presence of plasma-like energy inside the brain which causes fast brain activities that are akin to lightning strikes.

Stereotactic radiosurgery (SRS) has become increasingly important in the management of brain metastases due to improving systemic disease control and rising incidence. Initial trials demonstrated SRS with whole brain radiotherapy (WBRT) improved local control rates versus WBRT alone. Concerns with WBRT associated neurocognitive toxicity have contributed to greater use of SRS alone, including for patients with multiple metastases and following surgical resection. Molecular information, targeted agents and immunotherapy have also altered the landscape for the management of brain metastases. This review summarises current and emerging data on the role of SRS in the management of brain metastases.

Despite impressive progress in quantum biology, many questions about perception, cognition, memory, and their relation to processing of information remain unanswered. Here is an attempt to draw a unified picture starting with the basic quantum-mechanical phenomenon of nano-superconductivity in the microtubules and extending it to quantum processing of information, and generation of coherent Josephson radiation. A model for the generation in the axons of neurons is suggested. Like in a symphony, but on frequencies ten orders of magnitude higher, the radiation forms resonant standing electromagnetic waves, which are defined by the anatomy, synchronize all the functions in organism, and are behind the memory, perception, and cognition of a living being. It is true that we are made of atoms, but we are coherent electromagnetic waves.

Oligodendroglioma (OG) is a brain tumor that contributes to < 1% of brain tumor diagnoses in the pediatric population. Unfortunately, pediatric OG remains without definitive molecular characteristics to aid in diagnosis, and little is known about the tumor microenvironment. Tumor cells' metabolism and proliferation rate are generally higher than healthy cells, so their iron demand is also significantly increased. This consideration underlines the great importance of iron for tumor development and progression. In this context, this study aims to evaluate the effect of iron in a cellular in vitro model of human oligodendroglioma brain tumor. Cell morphology, the effect of siderotic medium on cell growth, iron uptake, and the expression of iron metabolism-related genes were evaluated by optic microscopy, ICP-MS, confocal microscopy, and RealTime PCR, respectively. This study underlines the great importance of iron for tumor development and progression, but also the possibility of reducing the available iron concentration to determine an antiproliferative effect on OGs. Therefore, every attempt can be promising to defeat the OGs for which there are currently no long-term curative therapies.

Brain capillary endothelial cell(s) (BECs) have numerous functions including their semipermeable interface-barrier (transfer and diffusion of solutes), trophic (metabolic homeostasis), tonic (vascular hemodynamics), and trafficking (vascular permeability, coagulation, and leukocyte extravasation) functions to provide brain homeostasis. BECs also serve as the brain’s sentinel cell of the innate immune system and are capable of antigen presentation. In metabolic syndrome (MetS) there are two regions resulting in proinflammatory signaling of BECs. Namely, visceral adipose tissue depots supplying excessive peripheral cytokines/chemokines (pCC) and gut microbiota dysbiotic regions supplying excessive soluble lipopolysaccharide (sLPS), small LPS-enriched extracellular vesicle exosomes (lpsEVexos), and pCC. This dual signaling of BECs at their receptor sites results in BEC activation and dysfunction (BECact/dys) and neuroinflammation. sLPS and lpsEVexos signal BECs toll-like receptor four, which then signals translocated nuclear factor kappa B (NFkB). Translocated NFkB promotes the synthesis and secretion of BEC proinflammatory cytokines and chemokines. Specifically, the chemokine CCL5 (RANTES) is capable of attracting microglia cells to BECs. BEC neuroinflammation activates perivascular space(s) (PVS) resident macrophages. Excessive phagocytosis by reactive resident PVS macrophages results in a stagnation-like obstruction, which along with increased capillary permeability due to BECact/dys could expand the fluid volume within the PVS to result in enlarged PVS (EPVS). Importantly, this remodeling may result in pre- and post-capillary EPVS that would contribute to their identification on T2-weighted MRI, which are considered to be biomarkers for cerebral small vessel disease.

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.

Glioblastoma (GBM) is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. GBM shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including GBM. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of the inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss the potential metformin’s antitumoral effects on GBM, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of GBM patients.

In recent years, pathoconnectomics emerged as an interesting framework for the investigation and better comprehension of disorders affecting the brain. Research in this field has used so far structural, functional, metabolic and genetic data, but limited attention was addressed to the possible role of vascularization. In the present work the following aspects making it a valuable candidate to pathoconnectomics investigation are discussed: i) The vascular system is by its nature a network, endowed with directionality information on the basis of circulation; ii) The current imaging techniques allow in vivo detection of the vascular system to a good level of detail; iii) The information extracted from this kind of data could interact in a meaningful way with the functional profile of the brain, being the BOLD effect in turn based on blood flow; iv) Further evidence could be found in support of the trophic failure hypothesis; v) Data about vascularization could allow to bring in the pathoconnectomics framework cardiovascular and metabolic disorders. We suggest, therefore, that the evaluation of vascular connectivity (which we propose to name “vesselomics”) could enhance the pathoconnectomics paradigm, and provide new elements towards the understanding of brain pathology.

Since matter, energy and information are the three major components of the world, is there an interaction between information and matter? In the present work, the coevolution of human language and brain is taken as a case of interaction between information and brain. Some evidence that may show interactions between human language and brain revealed by previous researches is summarized in this paper, such as the language areas in the cerebral cortex of the modern human brain, the evolution of human language and brain in human history, and the genetic basis for the evolution of language. Based on the evidence, a dynamic model is developed to investigate the possible mechanism of coevolution of human language and brain. In the model, human language development and brain development reinforce each other: the developmental level of language can be promoted by advances in brain function due to language-related gene mutations, in turn, whether such mutations are selected positively can be influenced by the current developmental level of language. The coevolution of human language and brain can be taken as a case of interaction between information and matter.

Background and objectives: Primary brain tumors include any tumors arising in the brain whose prognosis is poor due to their histologic characteristics. The aim of this research was to evaluate the frequency of HER2 tumor marker in primary malignant brain tumors. Materials and Methods: This descriptive study was conducted on the samples admitted to the pathology laboratory with diagnosis of primary brain tumor during 2008–2015. Results: From among 107 patients (61.7% males and the rest females) with mean age of 40.4 years, the highest frequency of tumor location was in supratentorial region of the brain (including lobes and ventricles) (63.85% cases). High-grade astrocytoma had the highest prevalence at diagnosis (43.9%), followed by low-grade astrocytoma (37.4%). As for HER2 score, 42.1% of patients were HER2-positive (scores 2 & 3). On the other hand, 5.6% of patients were HER2-negative (-), 40.2% were positive (+), and 54.2% were positive (++). The patients with high-grade astrocytoma had older age (P < 0.001), higher HER2 positivity (P = 0.024) and percentage (P < 0.001) compared to the patients with low-grade astrocytoma. Conclusions: HER2 expression is dependent on the type of brain tumors. High expression of HER2 in high-grade astrocytoma may be useful for therapeutic purposes. The future research is needed to confirm these results with a large number of patients in different areas.

This study aimed to investigate the potential of Cord Blood Stem Cell-derived exosome vesicles (CBSC-EVs) in regulating cancer growth and preventing cellular damage. The study aimed to examine the effects of CBSC-EVs on CHL1 cancer cells and healthy fibroblasts. The study results reveal that CBSC-EVs have an anti-cancer/antioxidant effect on CHL1 cancer cells without inducing any toxic effects on healthy lymphocytes. Further analysis of CBSC-EVs revealed the presence of seven miRNAs (noncoding RNA molecules), including three from the Let 7 family, two from the Let 5 family, and two novel miRNAs. The function of the novel miRNAs was the main focus of the study. To assess the efficacy of CBSC-EVs, CHL1 cells (a type of malignant melanoma cell line) and human fibroblasts were grouped into different treatments. One group of those cell lines were treated with CBSC-EVs, and in the second group, the cells were transfected with either miRNA inhibitor Novel 1 (miRNA IN1) plus CBSC-EVs or miRNA inhibitor Novel 2 (miRNA IN2) and CBSC-EVs to knock down those novel miRNAs in the CBSC-EVs. Therefore, by comparing these groups, the function of novel miRNAs is more understandable. In this study, the Comet assay was employed to evaluate cancer cells' DNA damage and CCK8 to measure cell viability. The findings revealed that CBSC-EVs caused an increase in DNA damage in CHL1 cells compared to cells without treatment (p

Pesticides are chemical products are used to protect crops to prevent or eliminate undesirable organisms. Pesticides can contaminate continental waters, air, soil and food products. The presence of pesticide residues must therefore be monitored in water and food using sensitive, reliable and broad-spectrum analytical methods, as there is a huge variety of pesticides. Biosensors are one of the screening methods with great potential for detecting residues below the maximum residue limits. The different sensing principles of enzymatic biosensors for pesticide analysis will be described. This review highlights the great potential of colorimetric, enzymatic biosensors for detecting pesticide residues in water and food. Moreover the development of dual colorimetric and fluorimetric sensors during the past years is presented. These methods are most often based on the enzyme acetylcholinesterase, whose activity is inhibited by pesticides. The different approaches used in the development of these biosensors will be detailed, based on different chemical substrates, fluorophores and nanomaterials. The advantages and disadvantages of each approach will be discussed. Finally, the development prospects for improving these biosensors will be presented.

Human pluripotent stem cells (hPSCs) have become a powerful tool to generate various kinds of cell types comprising the human body. Recently, organoid technology emerged as a platform to build a physiologically relevant tissue-like structure from the PSCs, which provides a more relevant three-dimensional microenvironment to the actual human body than the conventional monolayer culture system for transplantation, disease modeling, and drug development. Although it holds so many advantages, the organoid culture system still has various problems related to culture methods, which became a challenge to get similar physiological properties to their original tissue counterparts. Here, we discuss the current development of organoid culture methods, including the problem that may arise from the currently available culture systems as well as the possible approach to overcoming the current limitation and improving their optimum utilization for translational application purposes.

Development of supervised AI algorithms requires a large amount of labeled images. Image labelling is both time-consuming and expensive. Therefore, we explored the value of e-learning derived annotations for AI algorithm development in medical imaging. Methods We have developed an e-learning platform that involves image-based single click labelling as part of the educational learning process. Ten radiology residents, as part of their residency training, trained the recognition of pneumothorax on 1161 chest X-rays in posterior-anterior projection. Using this data, multiple AI algorithms for detecting pneumothorax were developed. Classification and localization performance of the models was tested on an independent internal testing dataset and on the public NIH ChestX-ray14 dataset. Results The AI models F1 scores on the internal and the NIH dataset were 0.87 and 0.44, respectively. Sensitivity was 0.85 and 0.80 for classification and specificity 0.96 and 0.48 for classification. F1 scores were 0.72 and 0.66, sensitivity 0.72 and 0.72. False positive rate was 0.36 and 0.32 for localisation. Conclusion Our results demonstrated that e-learning derived annotations are a valuable data source for algorithm development. Further work is needed to include additional parameters such as user performance, consensus of diagnosis, and quality control in the development pipeline.

The microtubule-associated protein TAU is sorted into the axon in healthy brain neurons. Somatodendritic missorting of TAU is a pathological hallmark of many neurodegenerative diseases called tauopathies, including Alzheimer’s Disease (AD). Cause, consequence, and (patho)physiological mechanisms of TAU sorting and missorting are understudied, in part also due to the lack of readily available human neuronal model systems. The human neuroblastoma cell line SH-SY5Y is widely used for studying TAU physiology and TAU-related pathology in AD and related tauopathies. SH-SY5Y cells can be differentiated into neuron-like cells (SH-SY5Y-derived neurons) using various substances. This review evaluates whether SH-SY5Y-derived neurons are a suitable model for i) investigating intracellular TAU sorting in general, and ii) with respect to neuron subtype-specific TAU vulnerability. I) SH-SY5Y-derived neurons show pronounced axodendritic polarity, high levels of axonally localized TAU protein, expression of all six major human brain isoforms, and TAU phosphorylation similar to the human brain. As proliferative cells, SH-SY5Y cells are readily accessible for genetic engineering, stable transgene integration and leading-edge genome editing are valuable and promising tools for TAU-related studies. II) Depending on the used differentiation procedure, SH-SY5Y-derived neurons resemble cells of distinct subcortical nuclei, i.e. the Locus coeruleus (LC), Nucleus basalis (NB) and Substantia nigra (SN), all of which early affected in many tauopathies. This allows to analyse neuron-specific TAU isoform expression and intracellular localization, also in the context of vulnerability to TAU pathology. Limitations are e.g. the lack of mimicking age-related tauopathy risk factors and the difficulty to define the exact neuronal subtype of SH-SY5Y-derived neurons. In brief, this review discusses the suitability of SH-SY5Y-derived neurons for investigating TAU (mis)sorting mechanisms and neuron-specific TAU vulnerability in disease paradigms.

Patient derived model systems are important tools for studying novel anti-cancer therapies. Patient derived xenografts (PDXs) have gained favor over the last 10 years as newer mouse strains have improved the success rate of establishing PDXs from patient biopsies. PDXs can be engrafted from head and neck cancer (HNC) samples across a wide range of cancer stages, retain the genetic features of their human source, and can be treated with both chemotherapy and radiation, allowing for clinically relevant studies. Not only do PDXs allow for study of patient tissues in an in vivo model, they can also provide a renewable source of cancer cells for organoid cultures. Herein, we review the uses of HNC patient derived models for radiation research including approaches to establishing both orthotopic and heterotopic PDXs, approaches and potential pitfalls to delivering chemotherapy and radiation to these animal models, biological advantages and limitations, and alternatives to animal studies that still use patient-derived tissues.

Cachexia is a syndrome characterized by an ongoing loss of skeletal muscle mass associated with poor patient prognosis in non-small cell lung cancer (NSCLC). However, prognostic cachexia biomarkers in NSCLC are unknown. Here, we analyzed computed tomography (CT) images and tumor transcriptome data to identify potentially secreted cachexia biomarkers (PSCB) in NSCLC patients with low-muscularity. We integrated radiomics features (pectoralis muscle, sternum, and T10 vertebra) from CT of 89 NSCLC patients, which allowed us to identify an index for screening muscularity. Next, a tumor transcriptomic-based secretome analysis from these patients (discovery set) was evaluated to identify potential cachexia biomarkers in patients with low-muscularity. The prognostic value of these biomarkers for predicting recurrence and survival outcome was confirmed using expression data from eight lung cancer datasets (validation set). Finally, C2C12 myoblasts differentiated into myotubes were used to evaluate the ability of the selected biomarker, IL-8, in inducing muscle cell atrophy. We identified 75 over-expressed transcripts in patients with low-muscularity, which included IL6, CSF3, and IL8. Also, we identified NCAM1, CNTN1, SCG2, CADM1, IL8, NPTX1, and APOD as PSCB in the tumor secretome. These PSCB were capable of distinguishing worse and better prognosis (recurrence and survival) in NSCLC patients. IL8 was confirmed as a predictor of worse prognosis in all validation sets. In vitro assays revealed that IL-8 promoted C2C12 myotube atrophy. Tumors from low-muscularity patients presented a set of upregulated genes encoding for secreted proteins, including pro-inflammatory cytokines that predict worse overall survival in NSCLC. Among these up-regulated genes, IL8 expression in NSCLC tissues was associated with worse prognosis and the recombinant IL-8 was capable of triggering atrophy in C2C12 myotubes.

Near-infrared spectroscopy (NIRS) has become a key modality in medical imaging, finding application in both brain and breast imaging. This paper discusses the current trends in NIRS for brain and breast imaging, exploring advances in multi-modal integration with modalities such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Challenges related to spatial resolution, depth sensitivity, and the impact of extracerebral tissues on signal specificity are examined. In addition, ongoing efforts to enhance hemodynamic measurements’ quantitative accuracy. Challenges, including limited spatial resolution and tissue heterogeneity, are discussed. The discussion extends to diffuse optical tomography and ongoing instrumentation development, clinical trials and studies validating NIRS diagnostic efficacy in breast imaging. The paper emphasizes the need for standardization, integration into routine clinical practice, and motivates for future work.

There is a growing interest in glial cells in the central nervous system due to their important role in maintaining brain homeostasis both under physiological conditions and after injury. A significant amount of evidence has been accumulated regarding their capacity to exert either pro-inflammatory or anti-inflammatory effects under different pathological conditions. In combination with their known proliferative potential, they contribute not only to the limitation of brain damage and tissue remodeling but also to neuronal repair and synaptic recovery. Moreover, reactive glial cells can modulate the processes of neurogenesis, proliferation, and migration of neurons in the existing neural circuits in the adult brain. By discovering precise signals within specific niches, the regulation of sequential processes in adult neurogenesis holds the potential to unlock strategies that can stimulate the generation of functional neurons, whether in response to injury or as a means of addressing degenerative neurological conditions. Cerebral ischemic stroke, a condition falling within the realm of acute vascular disorders affecting the circulation of the brain, stands as a prominent global cause of disability and mortality. Extensive investigations into glial plasticity and their intricate interactions with other cells in the central nervous system have predominantly relied on studies conducted on experimental animals, including rodents and primates. However, valuable insights have also been gleaned from in vivo studies involving post-stroke patients, utilizing highly specialized imaging techniques. Following the attempts to map brain cells, the role of various transcription factors in modulating gene expression in response to cerebral ischemia is gaining increasing popularity. Although the results obtained thus far remain incomplete and occasionally ambiguous, they serve as a solid foundation for the development of strategies aimed at influencing the recovery process after ischemic brain injury.

The study of the human psyche has elucidated a bipartite structure of logic reflecting the quantum--classical nature of the world. Accordingly, we posited an approach toward studying the brain by means of the quantum--classical dynamics of a mixed Weyl symbol. The mixed Weyl symbol can be used to describe brain processes at the microscopic level and, when averaged over an appropriate ensemble, can provide a link to the results of measurements made at the meso and macro scale. Within this approach, quantum variables (such as, for example, nuclear and electron spins, dipole momenta of particles or molecules, tunneling degrees of freedom, and so on) can be represented by spinors, whereas the electromagnetic fields and phonon modes can be treated either classically or semi-classically in phase space by also considering quantum zero-point fluctuations. Quantum zero-point effects can be incorporated into numerical simulations by controlling the temperature of each field mode via coupling to a dedicated Nos\'e-Hoover chain thermostat. The temperature of each thermostat was chosen in order to reproduce quantum statistics in the canonical ensemble. In this first paper, we introduce a general quantum--classical Hamiltonian model that can be tailored to study physical processes at the interface between the quantum and the classical world in the brain. While the approach is discussed in detail, numerical calculations are not reported in the present paper, but they are planned for future work. Our theory of brain dynamics subsumes some compatible aspects of three well-known quantum approaches to brain dynamics, namely the electromagnetic field theory approach, the orchestrated objective reduction theory, and the dissipative quantum model of the brain. All three models are reviewed.

The advancement of the pediatric traumatic brain injury (TBI) knowledge base requires biospecimens and data from large samples. This study seeks to describe a novel clinical research modality to establish best practices for enrolling a diverse pediatric TBI population and quantifying key information on enrollment into biobanks. Screening form responses were standardized and cleaned through Google Sheets. Data was used to analyze total individuals at each enrollment stage. R was utilized for final analysis, including chi-square goodness of fit and proportion statistical tests, to determine further significance and relationships. Issues throughout data cleaning shed light on limitations of the consent modality. Results suggest that through a diverse research team, the recruited sample exceeds traditional measures of representation (e.g. sex, race, ethnicity). Sex demographics of the study are representative of the local population. Screening for candidates is critical to the success of the consent modality. The consent modality may be modified to increase diversity of study population and accept bilingual candidates. Researchers must implement best practices, including increasing inclusivity of bilingual populations, utilizing technology, and improving participant follow-up, to improve health disparities for understudied clinical populations.

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.

The basal ganglia (BG) are a central component of the brain, crucial to the initiation, execution and learning of adaptive actions. The BG are the major site of the action of dopamine. An important aspect of the BG architecture is the existence of two paths, direct and indirect, having different projection targets and dopamine receptor expression. To understand the BG, dopamine, and related disorders, it is imperative to understand the two paths. The standard account used in neuroscience research for decades posits that the role of the direct path is to support movements, while that of the indirect path is to suppress unselected or completed movements. This account is contradicted by converging evidence. Here, we explain why the arguments supporting the standard account are flawed, and present a new account, in which the role of the indirect path is completely opposite: to support automated execution. During acute events, the direct path allows coarse responses. These are refined by competition, and the resulting focused response is executed and learned by the indirect path, assisted by cholinergic interneurons and the subthalamic nucleus (STN). The new account allows a novel understanding of the symptoms of Parkinson's disease, in particular tremor and rigidity, and of its treatment by STN deep brain stimulation.

The paper presents a study of two novel visual motion onset stimulus-based brain–computer interfaces (vmoBCI). Two settings are compared with afferent and efferent to a computer screen center motion patterns. Online vmoBCI experiments are conducted in an oddball event–related potential (ERP) paradigm allowing for “aha–responses” decoding in EEG brainwaves. A subsequent stepwise linear discriminant analysis classification (swLDA) classification accuracy comparison is discussed based on two inter–stimulus–interval (ISI) settings of 700 and 150 ms in two online vmoBCI applications with six and eight command settings. A research hypothesis of classification accuracy non–significant differences with various ISIs is confirmed based on the two settings of 700 ms and 150 ms, as well as with various numbers of ERP response averaging scenarios.The efferent in respect to display center visual motion patterns allowed for a faster interfacing and thus they are recommended as more suitable for the no–eye–movements requiring visual BCIs.

A chronic activated pro-inflammatory cytokine network (“inflamm-aging”) may amplify the neurodegenerative effects of a fall induced brain trauma in geriatric subjects. Our research aimed to evaluate how a trained machine learning algorithm may predict recent antecedent falls based only on specific serologic cytokines network analysis and how the consequences of these falls can be substantiated on standard head MRIs. All 279 subjects included in our study were selected from the ADNI1 dataset and all had a mild cognitive impairment diagnostic at the ADNI1 study baseline. A “train group” was built and included 14 subjects with a history of a recent, simple, standing-level fall. These were carefully matched with 14 similar subjects without any antecedent trauma. The “test group” included 251 subjects, all without any history of recent fall. The machine learning algorithm (classic C4.5 decision tree) was trained to detect a pattern of variation in 23 clinically relevant cytokines in relation with an antecedent fall. Changes in five cytokines (matrix metalloproteinase-7, eotaxin-1, interleukin-3, interleukin-8 and matrix metalloproteinase-9) were used for fall prediction in the “test” group. Once trained, the algorithm predicted a recent fall in 119 cases from the test group. The mean brain ventricular volume that was significantly different between fall/non-fall subgroups (41645.5±10337.2 vs 27127.3±6749.4 mm3, p=0.005) remained significant in the test group, after prediction between (41544.24±17343.4 vs 34553.5±10543.2 mm3, p=0.042). The hippocampus mean volume was also significantly different between in the test group (6297.3±1080.1 vs 6745.9±1123.7, p=0.0015). A significant brain ventricular difference was observed in the “65<y.o.” subgroup (p=0.04). If confirmed by larger prospective studies, our findings may increase the precision of the neuro-cognitive assessments in geriatric subjects.