Amphetamine is a psychostimulant drug with a high risk of toxicity and death when misused. Abuse of amphetamines is associated with an altered organic profile, which includes omega fatty acids. Low omega fatty acid levels are linked to mental disorders. Using the Comparative Toxicogenomic Database (CTD), we investigated the chemical profile of the brain in amphetamine-related fatalities and the possibility of neurotoxicity. We classified amphetamine cases as low (0-0.5 g/ml), medium (>0.5 to 1.5 g/ml), and high (>1.5 g/ml) based on amphetamine levels in brain samples. All three groups shared 1-octadecene, 1-tridecene, 2,4-di-tert-butylphenol, arachidonic acid, docosahexaenoic acid (DHA), eicosane, and oleylamide. We identified chemical-disease associations using the CTD tools and predict an association between docosahexaenoic and arachidonic acids and curated conditions like autistic disorder, disorders related to cocaine, Alzheimer's disease, and cognitive dysfunction. An amphetamine challenge may cause neurotoxicity in the human brain due to a decrease in omega-3 fatty acids and an increase in oxidative products. Therefore, in cases of amphetamine toxicity, supplement therapy may necessitate preventing omega-3 fatty acid deficiency.

Background: Anemia is one of the most frequent diseases worldwide, affecting a third of the general population. Anemia in general and in particular, iron-deficient anemia (IDA), has been associated to a higher risk of thrombotic manifestations, including ischemic stroke and cerebral venous thrombosis (CVT), as well as systemic extra cerebral arterial and venous thrombosis. Despite these data, anemia is seldom considered as an etiological factor of stroke. Methods: An individual case encompassing all known neurovascular and systemic arterial and venous thrombotic manifestations related to IDA is presented with the focus on clinical reasoning issues in the diagnostic pathways, starting from the neuroradiological signs. The main questions have been identified and addressed in a narrative review of the most relevant data in the literature from a pragmatic and clinical viewpoint. Results and Discussion: The presented case concerns a 46 years old man admitted to the Stroke Unit because of acute is-chemic stroke with multiple thrombi in large intracranial and extracranial vessels, multifocal ischemic lesions in several arterial territories and the concurrent finding of asymptomatic CVT, pulmonary embolism with lung infarction and aortic thrombosis. An extended diagnostic work-up excluded the main etiologies (arterial dissection, cardiac embolism, genetic and acquired prothrombotic disorders, as cancer and antiphospholipid syndrome), except for a severe IDA, such as to require blood transfusions followed by anticoagulant therapy for the several thrombotic manifestations. Neuroimaging and systemic vascular findings have been analyzed and the main issues proposed by the case in the diagnostic pathway have been identified and discussed in a pragmatic clinical road map reviewing the data provided by the literature. Conclusions: IDA is a common but treatable condition that, independently or synergically, may increase the risk of thrombotic events. The diagnostic and therapeutic approach has not yet defined and each case should be individually addressed in a pragmatic clinical road map.

‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked to pathological alteration of brain func-tion and behavior. Moreover, gut microbiota composition constantly controls microglia matura-tion as revealed by morphological observations and gene expression analysis. However, it is un-clear whether gut microbiota influences microglia functional properties and crosstalk with neu-rons, known to shape and modulate synaptic development and function. Here, we investigated how antibiotic mediated alteration of the gut microbiota influences microglial and neuronal functions in adult mice hippocampus. Hippocampal microglia from adult mice treated with oral antibiotics exhibited increased microglia density, altered basal patrolling activity, and impaired process rearrangement in response to damage. Patch clamp recordings at CA3-CA1 synapses revealed that antibiotics treatment alters neuronal functions, reducing spontaneous postsynaptic glutamatergic currents and decreasing synaptic connectivity, without reducing dendritic spines density. The effect of dysbiosis on neuronal functions are mediated by microglia-neuron cross-talk through the CX3CL1-CX3CR1 axis, as antibiotics treatment of CX3CR1 deficient mice, mod-ulates microglia density and processes rearrangement leaving unaltered synaptic function. To-gether, our findings show that the antibiotics alteration of gut microbiota impairs synaptic effi-cacy, probably through CX3CL1-CX3CR1 signaling supporting microglia as a major player in in the gut-brain axis, and in particular in the gut microbiota-to-neuron communication pathway.

Levodopa remains the primary drug for controlling motor symptoms in Parkinson's disease through the whole course, but over time complications develop in the form of dyskinesias, which gradually become more frequent and severe. These abnormal, involuntary, hyperkinetic movements are mostly characteristic of the ON phase and reflect an excess of exogenous levodopa. They may also occur during OFF phase, or in both phases. Over the past 10 years, the issue of levodopa-induced dyskinesia has been the subject of research into both the substrate of this pathology and potential remedial strategies. The purpose of the present study was to review the results of recent research on the background and treatment of dyskinesia. To this end, databases were reviewed using a search strategy that included both relevant keywords related to the topic and appropriate filters to limit results to English-language literature published since 2010. Based on the selected papers, the current state of knowledge on morphological, functional, genetic, and clinical features of levodopa-induced dyskinesia, as well as pharmacological, genetic treatment and other therapies such as deep brain stimulation are described.

Pervasive and wide-ranging cognitive deficits are a core feature of schizophrenia and an important determinant of long-term functional outcome. The lack of sufficiently effective treatments for cognitive impairment associated with schizophrenia (CIAS) represents a major unmet need and a central roadblock towards recovery. This is partly due to the current therapeutic focus on clinical symptoms, and the relative neglect of cognitive impairments despite their functionally disabling effects. Furthermore, effective treatment is impeded by our limited knowledge of the complex pathophysiology, which gives rise to perturbed information processing. Here, we review mechanisms and effectiveness of available pharmacological and non-pharmacological treatments for CIAS. Current evidence indicates, that while techniques which broadly enhance neural plasticity show the greatest therapeutic potential, effect sizes are at best moderate. Among other reasons, this is due to a considerable heterogeneity of responses to individual interventions. Furthermore, we discuss how recent conceptual advances in operationalizing cognitive impairments based on cognitive neuroscience have the potential to address these issues and facilitate the development of novel treatment strategies for CIAS. This includes more clearly elucidating pathophysiological mechanisms in both humans and animal models, identifying new treatment targets as well as establishing biomarkers for a better prediction of treatment responses.

A case report of the diagnosis of Long Term Sequelae of West Nile Neuroinvasive Disease in a patient with 9 years history. Empirical data of symptoms and test reports has been presented and based on the available data likely pathogenesis of the disease has been discussed. The empirical data has been compared to the published literature to reach a highly confident diagnosis.

Studies in animal models have suggested that the ketogenic diet may be effective in the treatment of cancer. However, human cohort studies on the ketogenic diet have, thus far, failed to show benefits in cancer survival or in any other hard clinical endpoints of the disease. This paper presents a case report of a patient with glioblastoma multiforme. The patient had initially been treated with standard oncotherapy including surgery, radiotherapy and chemotherapy. Despite standard treatment, the patient experienced a recurrence of the glioblastoma seven months later. Subsequently, the patient refused radiotherapy and chemotherapy and opted to use the paleolithic ketogenic diet (PKD) as a stand-alone therapy. Following the adoption of the PKD, progression of the disease has been completely halted. At the time of writing, the patient has remained in remission for 48 months, is without side-effects and experiences an excellent quality of life without the use of any drugs.

Noninvasive and portable diagnoses via angle-resolved coherent spectral data are presented. ACTIRS (Angle- resolved coherent tomographic IR spectroscopy) through angle-coherent return spectra from photonic quantum ring laser of whispering gallery modes, which is not photocurrent-converted after the cortical, vascular or muscular diffuse paths, can be a new method for brain/heart studies. Also it will be eligible for frequent do-it-yourself diagnoses of breast cancer before hospital visits. The unique angle-coherent multi-spectra will eventually lead to study ionic or protein contents of cranial, arterial or lactiferous ducts that have been obtained only from uncomfortable biopsy, NMR, CT or mammography. The spectral data can be spatially or temporally improved and correlated for extracting more meaningful diagnostic conclusions

The New Zealand brushtail possum (Trichosurus vulpecula), introduced from Australia in the 1850s, is an invasive species that is widespread throughout New Zealand and forms the largest self-sustained reservoir of bovine tuberculosis (Mycobacterium bovis) in the wild. Conservation and agricultural authorities regularly apply a series of population control measures to suppress brushtail possum populations. The evolutionary consequence of more than half a century of intensive population control operations on the species genomic diversity and population structure is hindered by a paucity of available genomic resources for the species. This study is the first to characterise the functional content and diversity of brushtail possum liver and brain cerebral cortex transcriptomes. Raw sequences from hepatic cells and cerebral cortex were assembled into 58,001 and 64,735 transcripts in hepatic cells and cerebral cortex, respectively. Functional annotation and polymorphism assignment of the assembled transcripts demonstrated a considerable level of variation in the core metabolic pathways that represent potential targets for selection pressure exerted by chemical toxicants. This study suggests that the brushtail possum population in New Zealand harbours considerable levels of variation in metabolic pathways that could potentially promote the development of tolerance against chemical toxicants.

Glioblastoma (GBM) is the most lethal form of brain tumor, characterized by rapid growth and surrounding tissue invasion. The current standard treatment is surgery followed by radiotherapy, and concurrent chemotherapy, typically with temozolomide. Although extensive research has been performed over the past years to develop an effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in the overall survival of patients with GBM. Thus, new therapeutic approaches are urgently needed. A major challenge in the development of therapies for central nervous system (CNS) disorders is overcoming the blood–brain barrier (BBB). In this context, the intranasal (IN) route of drug administration has been proposed as a non-invasive alternative route to directly targeting the CNS. In fact, this route of drug administration may bypass the blood-brain barrier and reduce systemic side effects. Recently, formulations have been developed to further enhance nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review will be on the strategies developed to deliver a number of anticancer compounds for the treatment of GBM using the nasal administration. In particular, the specific properties of nanomedicines proposed for the nose-to-brain delivery will be critically evaluated. The number of preclinical and clinical data reviewed support the idea that nasal delivery of anticancer drugs might represent a breakthrough advancement in the fight against GBM.

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

Perception and motor interaction with physical surroundings can be analyzed by the changes in probability laws governing two possible outcomes of neuronal activity, namely the presence or absence of spikes (binary states). Perception and motor interaction with physical environment are accounted partly by the reduction in entropy within the probability distributions of binary states of neurons in distributed neural circuits, given the knowledge about the characteristics of stimuli in physical surroundings. This reduction in the total entropy of multiple pairs of circuits in networks, by an amount equal to the increase of mutual information among them, occurs as sensory information is processed successively from lower to higher cortical areas or between different areas at the same hierarchical level but belonging to different networks. The increase in mutual information is partly accounted by temporal coupling as well as synaptic connections as proposed by Bahmer and Gupta [1]. We propose that robust increases in mutual information, measuring the association between the characteristics of sensory inputs and neural circuits connectivity patterns, are partly responsible for perception and successful motor interactions with physical surroundings. It is also argued that perception from a sensory input is the result of networking of many circuits to a common circuit that primarily processes the given sensory input.

This cross-sectional study evaluated the validity of three alternative methods compared to the gold standard 24-h urine collection for estimating dietary sodium intake, a modifiable risk factor for hypertension, among middle-aged and older adults with elevated blood pressure. These included spot urine collection (using Kawasaki, Tanaka, and INTERSALT equations), 24-h dietary recall, and food frequency questionnaire responses, compared against 24-h urine collection in a subset of 65 participants (aged 50–75 years, 58.5 % women, 61.6 % hypertensive) from the DePEC-Nutrition trial. The validity of the methods was assessed using bias, Spearman correlation coefficient (SCC), intraclass correlation coefficient (ICC), and Bland-Altman analysis. Among the alternative methods, spot urine collection using the Kawasaki equation showed the strongest correlation (SCC 0.238; ICC 0.119, 95 % CI -0.079 to 0.323) but it exhibited a significant bias (1414 mg/day, p-value < 0.001) relative to 24-h urine collection. Conversely, dietary surveys had a smaller bias but wider limits of agreement. These findings underscore the complexities of accurately estimating dietary sodium intake using spot urine collection or dietary surveys in this specific population, suggesting that a combination or refinement of existing methodologies might improve accuracy. Further research with larger samples is necessary to develop more reliable methods for assessing sodium intake in this high-risk group.

Diabetes mellitus is a widespread chronic metabolic disorder demanding regular blood glucose level surveillance (BGLs). Current invasive techniques, such as finger-prick tests, often result in discomfort for patients, leading to infrequent monitoring and potential health complications. The primary objective of this study was to design a novel, portable, non-invasive system for diabetes detection using breath samples, named as DiabeticSense, an affordable digital health device for early detection, encouraging immediate intervention. The device employed MOSFET-based electrochemical sensors to assess volatile organic compounds in breath samples, whose concentrations differ between diabetic and non-diabetic individuals. The system merged body vital signs with sensor voltages obtained by processing breath sample data to predict diabetic conditions. Our research used readings from 100 patients at a nationally recognised hospital to form the dataset. Data was then processed 10 using a Gradient Boosting Classifier model, and performance was cross-validated. The proposed system attained a promising accuracy of 86.6%, marking an improvement of 20.72% over an existing regression technique. The developed device introduces a non-invasive, cost-effective, and user-friendly solution for preliminary diabetes detection. It has the potential to increase patient adherence to regular monitoring.

Tunneled central venous catheters (CVC) are mainly considered as rescue vascular access option in dialysis but still used in about one quarter of prevalent patients worldwide as being associated with poor performances and higher risks. Study design. In this retrospective single-center study, we aimed to report on clinical performances achieved with high-flow tunneled CVC (DualCath, DCath) and compared it with arteriovenous accesses (AVAs; AV fistula, AV graft, Thomas Shunt) in a hospital-based dialysis unit. Methods. Sixty-eight stage 5 chronic kidney disease dialysis dependent patients (CKD5D) receiving high volume hemodiafiltration were followed-up for 30 months. The study consisted of two phases: baseline cross-sectional and longitudinal follow-up of key performance indicators. Clinical performances consisting of effective blood flow and blood volume, recirculation, urea and ionic Kt/V and total Kt, ultrafiltration volume and percent reduction of ß2-M were measured monthly as part of quality control in our unit. Results. At baseline, effective blood flow with DCath was close to 400 ml/min, similar to AVAs. Recirculation with DCath (7%, 6-13%) was higher than AVAs. Diffusive dialysis dose delivered with DCath (spKt and eKt/V) and convective dialysis dose achieved with DCath were slightly lower than AVAs, but still much higher than recommended by guidelines. Percent reduction of ß2-M achieved with DCath was also 4 to 10% lower than AVAs. On longitudinal follow-up, main clinical performance indicators of DCath (total Kt and total ultrafiltration volume, L/session) were maintained very stable over time and close to those achieved with AVAs. Conclusions. As shown in this study, high-flow DualCath tunneled two single lumen silicone catheters may be used to deliver high volume hemodiafiltration in a reliable and consistent manner without compromising clinical performances. These results rely from the specific design of the two silicone cannulas and the strict adherence to best catheter practices.

Background and Objectives: Ultrasound (US) is a non-invasive tool for the in-vivo detection of peripheral nerve alterations. Materials and Methods: In this study we applied nerve US to assist the discrimination between the spectrum of Amyotrophic Lateral Sclerosis (ALS, n=11), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n=5) and genetically confirmed Charcot-Marie-Tooth disease (CMT, n=5). All participants and n=15 controls without neurological diseases underwent high-resolution US of the bilateral tibial nerve. Nerve cross-sectional area (CSA) and nerve microvascular blood flow were compared between the groups and related to cerebrospinal fluid (CSF) measures, clinical symptoms and nerve conduction studies. Analyses are part of a larger multimodal study on the comparison between US and 7 Tesla (T) magnetic resonance neurography (MRN). Results: Patients and controls were matched with respect to their demographical data. CMT had the longest disease duration, followed by CIDP and ALS. CSA was related to age, weight and disease duration. CSA was larger in CMT and CIDP compared to ALS and controls. Blood flow was greatest in CIDP, and higher than in CMT, ALS and controls. In ALS, greater CSA was correlated with greater CSF total protein and higher albumin quotient. US measures did not correlate with clinical scores or nerve conduction studies in any of the subgroups. Conclusion: Our results point towards the feasibility of CSA and blood flow to discriminate between ALS, CIDP and CMT, even in small sample sized groups. In ALS, larger CSA could indicate an inflammatory disease subtype characterized by reduced blood-nerve barrier integrity. Our upcoming analysis will focus on the additive value of 7T MRN in combination with US to disentangle the spectrum between more inflammatory or more degenerative disease variants along the disease groups.

Statistical modeling of lifetime data plays an essential role in a wide range of practical fields, such as health and engineering. There have been a lot of studies done to develop statistical models that can better describe health data than traditional models. For the first time, we pioneer a novel family of continuous probability distributions called the generalized odd beta prime generalized (GOBP-G) family of distributions. The cumulative distribution and probability density functions of the new family are presented. A new generalization of the Weibull distribution called "generalized odd beta prime-Weibull" (GOBPW) is proposed using the pioneered GOBP-G family. The mixture representations of the new distribution are defined and derived. Some formal statistical properties of the GOBPW distribution, such as the moments, moment generating function, incomplete moments, information generating function, entropies, stress-strength function, quantile function, and order statistics, are derived. The estimation of the parameters of the proposed distribution is evaluated using the maximum likelihood estimation approach. Different cancer disease data sets, such as the bladder, head and neck, acute bone, and blood cancers, are used to illustrate the applicability and usefulness of the new model and were compared using several statistical accuracy measures with that of well-established extended Weibull distributions, which are the beta modified Weibull distribution, Kumaraswamy modified Weibull distribution, gamma generalized modified Weibull distribution, gamma log-logistic Weibull distribution, and beta log-logistic Weibull distribution. The results show that the proposed model gives better results than the competitive models. This study could guide the relevant stakeholders in choosing a suitable statistical model for the health data instead of relying on traditional models to enhance decision-making.

Human adipose stem cell-derived extracellular vesicles (hASC-EVs) are key mediators of paracrine signaling with promising therapeutic applications. Although hASC-EVs are derived from human cells and are less immunogenic, their immunogenicity cannot be completely excluded. Here, we evaluate the immune responses of ICR and C57BL/6 mice to high doses of hASC-EVs for 10 days after injection. Lymphocyte subpopulations are analyzed using flow cytometry at 0.5, 1, 3 and 24 h post injection. In the spleen and blood of C57BL/6 mice, neutrophils sharply increased at 0.5 h and decreased at 3 h following hASC-EV treatment. We observe increased proportions of monocytes, macrophages, and natural killer cells at 3 h but returned to similar level of vehicle control at 24 h post injection in the spleen and blood of ICR mice. Although the in vivo experiments reveal different immune responses to hASC-EV treatment in C57BL/6 and ICR strains, no major changes occur in human peripheral blood mononuclear cell composition after applying hASC-EVs in vitro. In conclusion, unlike those in mice, immune responses to hASC-EVs in humans are not detectable, indicating a minimal risk of fatal side-effects from hASC-EV-based therapies.

FoxP3 is a transcription factor essential for the differentiation and function of T regulatory cells (Tregs). There are two major subsets of Tregs: natural Tregs (nTregs) generated in thymus and inducible Tregs (iTregs) produced in peripheral immune system. It has been documented that iTreg development is dependent on soluble mediators including interleukin 2 (IL2), transforming growth factor β (TGFβ) and all-trans-retinoic acid (ATRA). In our experiments we performed a gene expression array, followed by Real-time PCR experiments, to study the expression of genes regulated by 1,25-dihydroxyvitamin D (1,25D) or ATRA in cells of myeloid origin. Our experiments revealed that ATRA alone, but also a cocktail of mediators consisting of IL2, TGFβ and ATRA, upregulate the expression of FOXP3 gene in lymphoid cells, but also in normal and leukemic myeloid cells. The FoxP3 expression is followed by a phenotypic changes in cells of myeloid origin. Our results indicate that signaling pathways which are used in the late stages of T cell differentiation, are also active in the cells of myeloid lineage

Traumatic brain injury (TBI) is an important global clinical issue, requiring not only prevention but also effective treatment. Following TBI, diverse parallel and intertwined pathological mechanisms affecting biochemical, neurochemical, and inflammatory pathways can have severe impact on the patient’s quality of life. The current review summarizes evidence for utility of amantadine in TBI in connection to its mechanism of action. Amantadine combining multiple mechanisms of action may offer both neuroprotective and neuroactivating effects in TBI patients. Indeed, use of amantadine in TBI has been encouraged by several clinical practice guidelines/recommendations. Amantadine is also available as infusion which may be of particular benefit in unconscious patients with TBI, due to immediate delivery to the central nervous system and the possibility of precise dosing. In other situations, orally administered amantadine may be used. There are several questions that remain to be addressed: Can amantadine be effective in disorders of consciousness requiring long-term treatment and in combination with drugs approved for treatment of TBI? Do the observed beneficial effects of amantadine extend to disorders of consciousness due to factors other than TBI? Well controlled clinical studies are warranted to ultimately confirm its utility in the TBI and provide answers these questions.

This study presents a novel semi-supervised deep learning method utilizing 3D TOF-MRA images for the detection of brain aneurysms, employing landmark-based techniques that mimic radiologist practices to enhance detection accuracy and efficiency.

: The primary objective of this study was to investigate the association of certain genetic alterations and intraoperative fluorescent activity of 5-aminolevulinic acid (ALA) in brain metastasis (BM) of lung adenocarcinoma. A retrospective cohort study was conducted among 72 patients who underwent surgical resection of BM from lung adenocarcinoma at our institute for 5 years. Cancer cell infiltration was estimated by the intraoperative fluorescent activity of 5-ALA, and genetic alterations were analyzed by next-generation sequencing (NGS). The sensitivity and specificity for detecting cancer cell infiltration using 5-ALA were 87.5% and 96.4%, respectively. Genes associated with cell cycle regulation (p = 0.003) and cell proliferation (p = 0.044) were significantly associated with positive fluorescence activity of 5-ALA in the adjacent brain tissue. Genetic alterations in cell cycle regulation and cell proliferation were also associated with shorter recurrence-free survival (p = 0.013 and p = 0.042, respectively) and overall survival (p = 0.026 and p = 0.042, respectively) in the multivariate analysis. The results suggest that genetic alterations in cell cycle regulation and cell proliferation are associated with positive fluorescence activity of 5-ALA in the adjacent infiltrative brain tissue and influence the clinical outcome of BM of lung adenocarcinoma.

Abstract: In recent years, low frequency (LF) electroencephalogram (EEG) signals have been decoded to obtain kinematic trajectories with the aim of achieving closed loop natural control. However, decoded trajectories suffer variability and low correlation against the measured movement. This paper suggests that if EEG features of motor intents are directly associated with fixed points along a given range of motion, then the natural kinematic parameters can be quantified. A novel classification method is proposed to evaluate this hypothesis along with equations for obtaining the movement parameters (velocity, acceleration). Furthermore, this implies that the force of an end-effector and work done in moving the end-effector may be computed, leading to natural control of EEG-based robotic arms and neuroprostheses. Finally, expectations are that combining the proposed method with existing classification methods will increase the accuracy and scalability of brain-computer interface (BCI) applications.

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.

Keywords: Hypertensive emergency; diagnosis; lactate dehydrogenase; high sensitivity cardiac troponin T; brain natriuretic peptide; area under the curve.

Unwanted proteins and metabolic waste in cerebral spinal fluid are cleared from the brain by meningeal and nasal lymphatics, and perineural sheath of cranial nerves; however, the distribution and clearance of CSF along the subarachnoid space of the entire spinal cord is not fully understood. It was hypothesized that the anatomical resolution of Cryo-Fluorescence Tomography (CFT) could provide the visual evidence of clearance across the spinal cord at each level of the vertebral column. To that end, isoflurane anesthetized mice were infused into the lateral cerebroventricle with 5.0 µl of quantum dots [QdotR 605 ITKTM amino (PEG)] over two mins. Mice were allowed to recover (ca 2-3 min) and remained awake and ambulatory for 5, 15, 30, 60 and 120 minutes after which they were euthanized, and the entire intact body frozen at -800. The entire mouse was sectioned and imaged to produce an isotropic voxel resolution of 35 µm. Both white light and fluorescent images were captured after each slice to produce high resolution three-dimensional volumes for each mouse. CFT highlighted the circulation of tracer throughout the ventricular system and central canal of the spinal cord and the entire subarachnoid space of the CNS. Signal could be visualized in the nasal cavity, deep cervical lymph nodes, thoracic lymph nodes and more superficial submandibular lymph nodes as early as 15 min post infusion. Fluorescent signal could be visualized along the dorsal root ganglia and down the proximal extension of the spinal nerves of the thoracic and lumbar segments at 30 min. There was significant accumulation of tracer in the lumbar and sacral lymph nodes between 15- 60 min. The dense fluorescent signal in the thoracic vertebrae noted at 5- and 15-mins post infusion was significantly reduced by 30 min. Indeed, all signal in the spinal cord was ostensibly absent by 120 min except for trace amounts in the coccyx. The brain still had some residual signal at 120 min. These data show that Qdots with a hydrodynamic diameter of 16-20 nm rapidly clear from the brain of awake mice. These data also clearly demonstrate the rapid distribution and efflux of trace along a major length of the vertebral column and the potential contribution of the spinal cord in the clearance of brain waste.

This paper proposes several LabVIEW applications to accomplish the data acquisition, processing, features extraction and real-time classification of the electroencephalographic (EEG) signal detected by the embedded sensor of the NeuroSky Mindwave Mobile headset. The LabVIEW applications are aimed at the implementation of a Brain-Computer Interface system, which is necessary to people with neuromotor disabilities. It is analyzed a novel approach regarding the preparation and automatic generation of the EEG dataset by identifying the most relevant multiple mixtures between selected EEG rhythms (both time and frequency domains of raw signal, delta, theta, alpha, beta, gamma) and extracted statistical features (mean, median, standard deviation, route mean square, Kurtosis coefficient and others). The acquired raw EEG signal is processed and segmented into temporal sequences corresponding to the detection of the multiple voluntary eye-blinks EEG patterns. The main LabVIEW application accomplished the optimal real-time artificial neural networks techniques for the classification of the EEG temporal sequences corresponding to the four states: 0 - No Eye-Blink Detected; 1 - One Eye-Blink Detected; 2 – Two Eye-Blinks Detected and 3 – Three Eye-Blinks Detected. Nevertheless, the application can be used to classify other EEG patterns corresponding to different cognitive tasks, since the whole functionality and working principle could estimate the labels associated with various classes.

Concussion, also known as mild traumatic brain injury (mTBI), commonly causes transient neurocognitive symptoms, but in some cases, it causes cognitive impairment, including working memory (WM) deficit, which can be long-lasting and impede a patient’s return to work. The predictors of long-term cognitive outcomes following mTBI remain unclear because abnormality is often absent in structural imaging findings. The purpose of the study was to determine whether machine learning-based models using functional magnetic resonance imaging (fMRI) biomarkers and demographic or neuropsychological measures at baseline could effectively predict 1-year cognitive outcomes of concussion. We conducted a prospective, observational study of patients with mTBI who were compared with demographically-matched healthy controls enrolled between September 2015 to August 2020. Baseline assessments were collected within the first week of injury, and follow-ups were conducted at 6 weeks, 3 months, 6 months, and 1 year. Potential demographic, neuropsychological, and fMRI features were selected according to the significance of correlation with the estimated changes in WM ability. The support vector machine classifier was trained using these potential features and estimated changes in WM between the predefined time periods. Patients demonstrated significant cognitive recovery at the third month, followed by worsened performance after 6 months, which persisted until 1 year after concussion. Approximately half of the patients experienced prolonged cognitive impairment at 1-year follow up. Satisfactory predictions were achieved for patients whose WM function did not recover at 3 months (accuracy=87.5%), 6 months (accuracy=83.3%), 1 year (accuracy=83.3%), and performed worse at 1-year follow-up compared to baseline assessment (accuracy=83.3%). This study demonstrated the feasibility of personalized prediction for long-term postconcussive WM outcomes based on baseline fMRI and demographic features, opening a new avenue for early rehabilitation intervention in selected individuals with possible poor long-term cognitive outcomes.

The objective of this study was aimed to study the sensory processes of the “human-computer interaction” model when classifying visual images with an incomplete set of signs based on the analysis of early, middle, late and slow components of event-related potentials (ERPs). 26 healthy subjects (men) aged 20-22 years were investigated. ERPs in 19 monopolar sites according to the 10/20 system were recorded. Discriminant and factor analysis were applied. The component N450 is the most specialized indicator of the perception of unrecognizable (oddball) visual images. The amplitude of the ultra-late components N750 and N900 is also higher under conditions of presentation of the oddball image, regardless of the location of the registration points. The results of the study are discussed in the light of the paradigm of the P300 wave application in brain-computer interface systems, as well as with the peculiarities in brain pathology. Promising directions for the development of studies of the “Brain Computer Interface” (BCI) P300 systems are to increase the throughput of information flows. To extend the application of the P300 ERPs to multiple modalities, the underlying physiological mechanisms and responses of the brain for a particular sensory system and mental function must be carefully examined.

We constructed a novel design integrating the administration of a clinical self-assessment scale with simultaneous acquisition of functional Magnetic Resonance Imaging (fMRI), aiming at cross-validation between psychopathology evaluation and neuroimaging techniques. We hypothesized that areas demonstrating differential activation in two groups of patients (paranoid and depressive) will have distinct connectivity patterns and structural differences.

Manual interpretation of these huge amounts of image volumes are susceptible to inter-reader variability and human error. Thus, accurate automated CAD scheme is highly desirable in clinical pathological diagnosis. In this research, plethora of machine learning paradigms (e.g. feature extraction, dimensionality reduction and supervised classification methods) were explored, evaluated, compared and analyzed to identify the optimal pathway for brain MR images (normal vs neoplastic) binary classification task. External validation dataset was used to test the generalizability of the optimal predictive models implemented. Relevant and informative features were selected to construct cross-validated decision tree and eventually simple rule set was built based on the decision tree. The experimental results show that almost all pattern recognition paradigms achieve high accuracy with careful selection of number of attributes. LDA+ELM with 55 features are the optimal pipelines which achieve perfect classification when training and test data are of same source; and achieving (accuracy=97.5%, AUC=0.989, sensitivity=95% and specificity=100%) under balanced test dataset; (accuracy=99.5%, AUC=0.988, sensitivity=95% and specificity=100%). Cross-validated decision tree model also shows comparable performance: accuracy=98.8%, AUC=99.1%, sensitivity=99.6% and specificity=98.2%. Three highly relevant and robust attributes are visualized and selected for construction of decision tree models and finally a rule sets are read directly off the decision tree. This rule sets can potentially serve as fast and accurate classification algorithm.

Tspo is a receptor involved in the regulation of cellular proliferation, apoptosis and mitochondrial functions. Previous studies showed the expression of TSPO protein correlated positively with tumour malignancy and negatively with patient survival. The aim of this study was to determine the transcription of Tspo mRNA in various types of normal and cancer tissues. In situ hybridization was performed to localise the Tspo mRNA in various human normal and cancer tissues. The relative level of Tspo mRNA was quantified using fluorescent intensity and visual estimation of colorimetric staining. RT-PCR was used to confirm these mRNA levels in normal lung, lung cancer, liver cancer and cervical cancer cell lines. There was a significant increase in the level of transcription in liver, prostate, kidney and brain cancers while a significant decrease was observed in cancers of the colon and lung. Quantitative RT-PCR confirmed that the mRNA levels of Tspo are higher in a normal lung cell line than in a lung cancer cell line. An increase in the expression levels of TSPO makes it a good diagnostic biomarker and TSPO could serve as a target for anticancer drug development.

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

The transcriptional response of human blood leukocytes to SARS-CoV-2 infection was investigated focusing on the differences between mild and severe cases and between age subgroups. Weighted gene co-expression network analysis and comparative gene expression analysis were used. Three transcriptional modules positively associated with the traits of interest and their respective high hierarchy genes were identified. Enrichment analyses showed that the yellow module, associated with severe cases and older patients, had an overrepresentation of genes involved in inflammatory and innate immune responses, and neutrophil activation. The magenta and black modules, associated with disease severity and younger patients, contained genes related to innate immunity and inflammation and genes that regulate those responses. Subnetworks for these modules were constructed using genes enriched for innate immunity, inflammation, immunoregulation and differentially expressed genes (severe vs. mild). Their analysis evidenced that immunoregulatory functions are more activated in the modules associated with younger patients, what may help to explain the better disease course and faster recovery observed in younger COVID-19 patients. Comparative gene expression analysis between severe and mild groups, followed by gene enrichment and normalized gene expression analyses, revelated a set of 23 potential biomarkers for COVID-19 severity, of which 13 are newly described.

The neurologic effects of long-COVID are a therapeutic challenge. This article discusses the immunologic manifestations of long-COVID and proposes a non-androgenic, synthetic analog of dehydroepiandrosterone (DHEA), bromo-epi-androsterone (BEA), as a candidate for clinical trials for this exigent collection of neurologic conditions. Moreover, because there is an association between long-COVID and Alzheimer’s disease, the evaluation of BEA in long-COVID may serve as a proxy for its effect on neuroinflammatory biomarkers of Alzheimer’s disease that are shared with long-COVID.

Thyrotropin releasing hormone (TRH; pGlu-His-Pro-NH2) is an intercellular signal produced mainly by neurons. Among the multiple pharmacological effects of TRH, that on food-intake is not well understood. We review data that show that peripheral injection of TRH generally produces a transient anorexic effect, discuss the pathways that might initiate this effect, and explain its short half-life. In addition, central administration of TRH can produce anorexic or orexigenic effects, depending on the site of injection, that are likely due to interaction with TRH receptor 1. Anorexic effects are most notable when TRH is injected into the hypothalamus and the nucleus accumbens, while the orexigenic effect has only been detected by injection into the brain stem. Functional evidence suggests that TRH neurons that are prime candidate vectors for TRH action on food-intake include the caudal raphe nuclei projecting to the dorsal motor nucleus of the vagus, and possibly TRH neurons from the tuberal lateral hypothalamus projecting to the tuberomammillary nuclei. For other TRH neurons, the anatomical or physiological context and impact of TRH in each synaptic domain are still poorly understood. The manipulation of TRH expression in well-defined neuron types will facilitate the discovery of its role in food-intake control in each anatomical scene.

At the end of 2023 the Whole Mouse Brain Atlas was announced, revealing that there are about 5,300 molecularly defined neuronal types in the mouse brain. We ask whether brain models exist that contemplate how this is possible. The conventional columnar model, implicitly used by the authors of the Atlas, is incapable of doing so with only 20 brain columns (5 brain vesicles with 4 columns each). We argue that definition of some 1,250 distinct progenitor microzones, each producing over time minimally 4-5 neuronal types, may be sufficient. This is nearly achieved presently by the prosomeric model amplified by secondary dorsoventral and anteroposterior microzonation of progenitor areas, plus clonal variation of cell types produced on average by each of them.

The responses of inflammatory cytokines and brain-derived neurotrophic factor (BDNF) to a high-intensity interval training (HIIT) session were compared between 7 postmenopausal (57±2 y) and 8 premenopausal females (44±3 y) during the luteal phase of their menstrual cycle, when estrogen and progesterone are highest, and. HIIT consisted of 10 x 1 min running intervals (90% maximum heart rate) separated by 1 min recovery intervals. Blood samples were collected at baseline (fasted), pre-exercise (postprandial), and 0, 30 and 90 min post-HIIT and analyzed for interleukin (IL-6) and 10 (IL-10), tumour necrosis factor-alpha (TNF-α) and BDNF. IL-6 significantly increased from pre-exercise to 0 min post-HIIT in postmenopausal (+40%, p=0.01) but 30 min post-HIIT in premenopausal females (+60%, p=0.02). IL-6 remained elevated at 90 min post-HIIT in premenopausal (+104%, p=0.05) and to a higher degree in postmenopausal (+385%, p&lt;0.001). IL-10 showed no response. TNF-α increased from pre- to 0 min post-HIIT (+10%, p=0.05), then decreased to below pre-exercise at 30 min (-10%, p=0.02) and 90 min (-5%, p=0.04) in both groups. BDNF increased immediate post-HIIT in premenopausal (+60%, p&lt;0.001) but not postmenopausal females. The differences in IL-6 and BDNF response to HIIT between pre and postmenopausal females provide evidence of the role of female reproductive hormones in the regulation of these exercise-induced responses.

HIV-associated neurocognitive disorders (HAND) persist under antiretroviral therapy as a complex pathology that has been difficult to study in cellular and animal models. Therefore, we generated an ex vivo human brain slice model of HIV-1 infection from surgically resected adult brain tissue. Brain slice cultures processed for flow cytometry showed >90% viability of dissoci-ated cells within the first three weeks in vitro, with parallel detection of astrocyte, myeloid, and neuronal populations. Neurons within brain slices showed stable dendritic spine density and mature spine morphologies in the first weeks in culture, and they generated detectable activity in multi-electrode arrays. We infected cultured brain slices using patient-matched CD4+ T-cells or monocyte-derived macrophages (MDMs) that were exposed to a GFP-expressing R5-tropic HIV-1 in vitro. Infected slice cultures expressed viral RNA and developed a spreading infection up to 9-days post-infection, which were significantly decreased by antiretrovirals. We also detected infected myeloid cells and astrocytes within slices and observed minimal effect on cellular via-bility over time. Overall, this human-centered model offers a promising resource to study the cel-lular mechanisms contributing to HAND (including antiretroviral toxicity, substance use, and aging), infection of resident brain cells, and new neuroprotective therapeutics.

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

Biological neural network (BNN) is the core brain for creature to accomplish its intelligent behaviors through unique network structure and mechanisms. It also inspires controlling human-designed autonomous agents including robots to generate more advanced intelligent behaviors by mimicking the neural control mechanism of creatures at a deeper and more interactive level. Here, we constructed a whole-brain neural network model of Caenorhabditis elegans (C. elegans), which characterizes the electrochemical processes at the level of cellular synapse. The neural network simulation integrates computational programming and visualization of neurons and synapse connections of C. elegans, containing the specific controllable circuits summarization with their dynamic characteristics within the whole network. To illustrate its particular intelligent control capability in terms of robotics, we introduce the first innovative methodology for applying the BNN model to a 12-legged robot’s movement control based on the established numerical simulation platforms. We accomplished and designed two methods and corresponding encoding processes, one involving orientation control and the other involving locomotion generation, to demonstrate the intelligent control performance of BNN. Both simulation and experiment results indicate that the robot exhibits stronger autonomy and more intelligent moving performance under the control of BNN. We then summarized the contributions for digitalizing the C. elegans’ whole-brain neural network in real-time and utilizing it to control robot in a closed loop to validate its advanced intelligence control ability in terms of a scientific robot.

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

Background: Infections of Coronavirus Disease-2019 (COVID-19) can cause long-term effects known as long COVID. This pilot study aimed to evaluate the feasibility of a clinical study as well as the efficacy and safety of traditional East Asian herbal medicines in alleviating fatigue and cognitive dysfunction “brain fog” in patients with long COVID. Methods: This prospective pilot study investigated the use of three types of herbal medicines, Bojungikki-tang (BIT), Kyungok-go (KOG), and Cheonwangbosim-dan (CBD), for a 12-week period as potential treatments for fatigue and cognitive dysfunction in patients with long COVID. Forty-five patients with long COVID were recruited, and one of three drugs was given based on the patient’s symptoms and pattern identification. The effect of herbal medications on fatigue and cognitive function outcomes was assessed over a 36-week period, with patient adherence closely monitored. Results: After 12 weeks of herbal drug administration, fatigue symptoms improved significantly across all groups, with treatment success rates of 80%, 53.33%, and 46.67% in the BIT, KOG, and CBD groups, respectively. However, “brain fog” symptoms showed less improvement, with treatment success rates of 40%, 46.67%, and 13.33% in the BIT, KOG, and CBD groups, respectively. All adverse events reported were mild and unrelated to the medication. The study design was found to be feasible with high medication adherence. Conclusions: This study demonstrated the feasibility of conducting a clinical trial with three herbal medicines to treat long COVID symptoms like fatigue and “brain fog.”

This review explores the application of the conservative management model for pain to sports-related concussions (SRCs), framing concussions as a distinct form of pain syndrome with a pathophysiological foundation in central sensitization. Drawing parallels with proven pain management models, we underscore the significance of a proactive approach to concussion management. Recognizing concussions as a pain syndrome allows for the tailoring of interventions in alignment with conservative principles. This review first covers the epidemiology and controversies surrounding prolonged concussion recovery and persistent post-concussion symptoms (PPCS). Next, the pathophysiology of concussions is presented within the central sensitization framework, emphasizing the need for early intervention to mitigate the neuroplastic changes that lead to heightened pain sensitivity. Five components of the central sensitization process specific to concussion injuries are highlighted as targets for conservative interventions in the acute period: peripheral sensitization, cerebral metabolic dysfunction, neuroinflammation, glymphatic system dysfunction, and pain catastrophizing. These proactive interventions are emphasized as pivotal in accelerating concussion recovery and reducing the risk of prolonged symptoms and PPCS, in line with the philosophy of conservative management.

Non-pharmacologic options like the ketogenic diet (KD) and intermittent fasting (IF) are practical nutritional interventions with minor reported side effects like gastrointestinal symptoms, dyslipidemia, and hypomagnesemia for various medical ailments. In conjunction with IF, KD shows promise in weight loss, diabetes management, cardiovascular disorders, polycystic ovarian syndrome, cancer, and chronic neurological disorders. Based on prior research, we have examined the mechanism of action of KD and IF and their effect on neurological diseases, cancer, and obesity. We have also suggested evidence-based recommendations for the safer practice of KD and IF. Despite potential benefits, long-term adherence to KD poses challenges. Periodic KD implementation may thus benefit newly diagnosed overweight or obese patients with type 2 diabetes mellitus, aiding blood glucose and lipid management while promoting weight loss. KD is a high-fat and low-carbohydrate diet with a ratio of fat to carbohydrates and protein being 4:1 or 3:1, and thus, for peripheral tissues and the brain, fatty acids become the mandatory source of cellular energy. Ketone bodies have been used as the primary energy source during fasting. KD has been utilized as an effective treatment for refractory epilepsy since the 1920s. Evidence of the neuroprotective role of KD in diseases like epilepsy, stroke, traumatic brain injury, Alzheimer’s disease, and other neurological diseases has been noted. Since the 1960s, KD has become a popular method for obesity treatment. In addition, KD has been suggested as a potent anticancer therapy when used alone or as an adjuvant. KD may increase tumor cell sensitivity when combined with classic chemotherapy and radiotherapy. Thus, the probability that modifying the diet can help manage obesity, cancer, and chronic neurological disease without depending on pharmacological treatment and their serious side effects for a lifetime is promising and requires further investigation. KD holds promise as a potential adjunctive therapy in various neurological disorders, offering new avenues for treatment and neuroprotection. IF has shown potential in slowing the progression of neurodegenerative diseases such as Alzheimer's and Parkinson's by promoting antioxidant defense and suppressing inflammation. KD and IF show promise in cancer therapy by targeting altered cancer cell metabolism. Additionally, KD may enhance the effects of standard treatments like chemotherapy and radiotherapy. Some of the most robust reports of keto's possible benefits have come from glioblastoma, a very aggressive brain cancer. KD has also shown strong evidence for its effectiveness in weight loss, mainly attributed to its appetite-suppressing action in ketosis. However, long-term adherence to KD can be challenging, and periodic KDs may help manage blood glucose and lipid levels in overweight or obese patients with type 2 diabetes mellitus. Likewise, IF may be more effective than regular calorie restriction for achieving weight loss goals when combined with exercise programs. More prospective human studies are warranted to evaluate both KD and IF's potential therapeutic effectiveness and safety.

Chronic gastroduodenal symptoms are prevalent worldwide, and there is a need for new diagnostic and treatment approaches. Several overlapping processes may contribute to these symptoms, including gastric dysmotility, hypersensitivity, gut-brain axis disorders, gastric outflow resistance, and duodenal inflammation. Gastric Alimetry® (Alimetry, New Zealand) is a non-invasive test for evaluating gastric function that combines body surface gastric mapping (high-resolution electrophysiology) with validated symptom profiling. Together, these complementary data streams enable important new clinical insights into gastric disorders and their symptom correlations, with emerging therapeutic implications. A comprehensive database has been established, currently comprising >2,000 Gastric Alimetry tests, including both controls and patients with various gastroduodenal disorders. From studies employing this database, this pa-per presents a systematic methodology for Gastric Alimetry test interpretation, together with an extensive supporting literature review. Reporting is grouped into four sections: Test Quality, Spectral Analysis, Symptoms, and Conclusions. This review compiles, assesses, and evaluates each of these aspects of test assessment, with discussion of relevant evidence, example cases, limitations, and areas for future work. The resultant interpretation methodology is recommended for use in clinical practice and research to assist clinicians in their use of Gastric Alimetry as a diagnostic aid, and is expected to continue to evolve with further development.

There is increasing interest in identifying biological and imaging markers for the early detection of neurocognitive decline. In addition, non-pharmacological strategies including physical exercise and cognitive interventions may be beneficial for those developing cognitive impairment. The Feuerstein Instrumental Enrichment (FIE) Program is a cognitive intervention based on Structural Cognitive Modifiability and the Mediated Learning Experience (MLE) and aims to promote problem-solving strategies and metacognitive abilities. The FIE program uses a variety of instruments to enhance the cognitive capacity of the individual as a result of mediation. A specific version of the FIE program was developed for the cognitive enhancement of older adults, focusing on strengthening orientation skills, categorization skills, deductive reasoning and memory. We performed a prospective interventional pilot observational study on older subjects with MCI who participated in 30 mediated FIE sessions (two sessions weekly for 15 weeks). Of the 21 subjects who completed the study, there was a significant improvement in memory on the Neurotrax battery comparing pre- and post-intervention scores (pre: M=95.3, SD=12.2, post: M=101.2, SD=7.9, p<.05). Complete sets of anatomical MRI data for voxel-based morphometry, taken at the beginning and the end of the study, were obtained from 16 participants (mean age 83.5 years). Voxel-based morphometry showed an unexpected increase in grey matter (GM) in the anterolateral occipital border and the middle cingulate cortex. These initial findings of our pilot study support the design of randomized trials to evaluate the effect of cognitive training using the FIE Program on brain volumes and cognitive function.

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

The noradrenergic theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the upregulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the Brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD – an objective measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on Reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems.Results supported by bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g. cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are preferentially deposited within the cerebral cortex at a rapid rate. Although, the structural and functional roles of DHA in brain development are well investigated, similar roles of ARA are not well documented. The mode of action of these two fatty acids and their derivatives at different structural-functional roles and their levels in the gene expression and signaling pathways of the brain have been continuously emanating. In addition to DHA, importance of ARA has been much discussed in recent years for fetal and postnatal brain development and the maternal supply of ARA and DHA. These fatty acids are also involved in various brain developmental processes; however, their mechanistic cross talks are not clearly known yet. This review describes the importance of ARA, in addition to DHA to support the optimal brain development and growth and functional roles in the brain.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

Leukemia is a form of blood cancer that results in an increase in the number of white blood cells in the body. The correct identification of Leukemia at any stage is essential. The current traditional approaches rely mainly on field expertise' knowledge, which is time consuming. The poor understanding and a long period of examination might damage the human body. In this situation an automated Leukemia identification delivers more reliable and accurate diagnostic information. To effectively diagnose acute lymphoblastic Leukemia from blood smears pictures, a new strategy based on traditional image analysis techniques with machine learning techniques, and a composite learning approach was constructed in this experiment. To identify the type of acute Leukemia first, four well-known machine learning models were utilized. It was discovered that Support Vector Machine (SVM) Provides the highest accuracy in this scenario. To boost the performance, a deep learning model Resnet50 was hybridized with SVM model. Finally, it was revealed that this composite approach achieved 99.9% accuracy.

The liver health of Gilthead sea bream and European sea bass fed fishmeal-free diets including various proportions of plant proteins, insect and poultry by-product meals, was investigated through biochemical and histological analyses using a new Liver Index (LI) formula. Four isoproteic (45% DM) and isolipidic (20% DM) diets were compared: a control, plant-based diet (CV) and other three test ones where 40% of a plant protein-rich ingredient mixture was replaced by Hermetia illucens (H40) or poultry by-product (P40) meals alone or in combination (H10P30). The trials lasted 12 and 18 weeks for sea bream and sea bass, respectively. The results so far ob-tained highlighted species-specific differences in the physiological response to dietary changes. In sea bream, the biochemical and histological responses suggest favorable physiological status and liver health, with higher serum cholesterol (CHO) and triglyceride (TAG) levels and moderate hepatocyte lipid accumulation with the H10P30 diet compared to CV (p<0.05). In sea bass, all diets resulted in elevated serum TAG levels and liver lipid accumulation particularly in fish fed the P40 one (p<0.05) which resulted in the highest LI, coupled with higher frequency of severe lipid accumulation, hypertrophy, cord loss, peripheral nuclei displacement and pyknosis. In conclusion sea bream well adapted to the test diets, while sea bass exhibited altered hepatic lipid metabolism leading to incipient liver steatosis, likely due to the high lipid content of the diets including the insect and poultry meals. The LI developed in this study proved to be a reliable tool for assessing the effects of dietary changes on liver health of sea bream and sea bass, consistent with biochemical and histological findings.

The pressure exerted on the heart and blood vessels because of blood flow is considered as an important parameter for the cardiovascular function. It determines sufficient blood perfusion as well as transportation of nutrition, oxygen and other essential factors to every organ. Pressure in the primary arteries located near the heart and the brain, known as central blood pressure (CBP), while in peripheral arteries, known as peripheral blood pressure (PBP). Normally, CBP and PBP are correlated; however, cardiovascular disorders interfere their regulation and affect the blood flow in vital organs and accessory organs, differently. Therefore, understanding each of them in normal and disease conditions is essential for managing various cardiovascular disorders and increasing their treatment outcomes. In this review, we have described the control systems (neural, hormonal, osmotic and cellular) of the blood pressure and its regulation in hypovolemic shock using centhaquine (Lyfaquin®) as a resuscitative agent.

The early embryonic heart is a multi-layered tube consisting of (1) an outer myocardial tube; (2) an inner endocardial tube; and (3) an extracellular matrix layer interposed between myocardium and endocardium, called “cardiac jelly” (CJ). During the past decades, research on CJ has mainly focused on its molecular and cell biological aspects. This review focuses on the morphological and biomechanical aspects of CJ. Special attention is given to (1) the spatial distribution and fiber architecture of CJ; (2) the morphological dynamics of CJ during the cardiac cycle; and (3) the removal/remodeling of CJ during advanced heart looping stages, which leads to the formation of ventricular trabeculations and endocardial cushions. CJ acts as a hydraulic skeleton displaying striking structural and functional similarities with the mesoglea of jellyfish. CJ not only represents a filler substance, facilitating end-systolic occlusion of the embryonic heart lumen. Its elastic components antagonize the systolic deformations of the heart wall and thereby power the refilling phase of the ventricular tube. Non-uniform spatial distribution of CJ generates non-circular cross sections of the opened endocardial tube (initially elliptic, later deltoid), which seem to be advantageous for valveless pumping. Endocardial cushions arise from non-removed remnants of the original CJ.

There have been multiple technological advancements that promise to gradually enable devices to measure and record signals with high resolution and accuracy in the domain of Brain Computer Interfaces (BCI). This review paper provides a comprehensive overview of fNIRS, EEG, and fMRI, including their principles, advantages, limitations, and integration with other modalities for advanced BCIs. The paper highlights the advantages of integrating multiple modalities, such as increased accuracy and reliability, and discusses the challenges and limitations of multimodal integration. Applications of advanced BCIs in clinical, assistive, gaming, and entertainment domains are also discussed. Furthermore, we explain the data acquisition approaches for each of these modalities. We also demonstrate various software programs that help in extracting, cleaning, and refining the data. We conclude this paper with discussion on the available literature on data acquisition approaches and a comparison of the ease of use for each of the modalities.

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

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.

Brain-stimulation reward, also known as intracranial self-stimulation (ICSS), is a commonly used procedure for studying brain reward function and drug reward. In electrical ICSS, an electrode is surgically implanted into the medial forebrain bundle in the lateral hypothalamus or the ventral tegmental area in the midbrain. Operant lever responding leads to the delivery of electrical pulse stimulation. The alteration in the stimulation frequency-lever response curve is used to evaluate the impact of pharmacological agents on brain reward function. If a test drug induces a leftward or upward shift in the ICSS response curve, it implies a reward-enhancing or abuse-like effect. Conversely, if a drug causes a rightward or downward shift in the functional response curve, it suggests a reward-attenuating or aversive effect. A significant drawback of electrical ICSS is the lack of cellular selectivity in understanding the neural substrates underlying drug reward versus aversion. Excitingly, recent advancements in optical ICSS (oICSS) have facilitated the development of at least three cell type-specific oICSS models – dopamine-, glutamate-, and GABA-dependent oICSS. In these new models, a comparable frequency-rate response curve has been established and employed to study the substrate-specific mechanisms underlying brain reward function and a drug's rewarding versus aversive effects. In this review article, we summarize recent progress in this exciting research area. The findings in these new behavioral models have not only increased our understanding of the neural mechanisms underlying drug reward and addiction but have also introduced a novel experimental approach in preclinical medication development for treating substance use disorders.

Chronic traumatic encephalopathy (CTE) is a unique neurodegenerative disease that is associated with repetitive head impacts (RHI) in both civilian and military settings. In 2014, the research criteria for the clinical manifestation of CTE, traumatic encephalopathy syndrome (TES) were proposed to improve the clinical identification and understanding of the complex neuropathological phenomena underlying CTE. This review provides a comprehensive overview of the current understanding of the neuropathological and clinical features of CTE, proposed biomarkers of traumatic brain injury (TBI) in both research and clinical settings, and a range of treatments based on previous preclinical and clinical research studies. Due to the heterogeneity of TBI, there is no universally agreed-upon serum, CSF, or neuroimaging marker for its diagnosis. However, as our understanding of this complex disease continues to evolve, it is likely that there will be more robust, early diagnostic methods and effective clinical treatments. This is especially important given the increasing evidence of a correlation between TBI and neurodegenerative conditions, such as Alzheimer's disease and CTE¹. As public awareness of these conditions grows, it is imperative to prioritize both basic and clinical research, as well as the implementation of necessary safe and preventative measures.

Keywords: bariatric surgery, sleeve gastrectomy, Roux-en-y gastric bypass, obesity, microbiota, gut-brain axis, beck scale, depression, diet, probiotics

Background: Glioblastoma is the most common primary brain neoplasm in adults, with still a poor prognosis despite a constant effort to improve patients’ survival. Some neuroradiological volumetric parameters seem to play a predictive role on Overall Survival (OS) and Progression Free Survival (PFS). The aim of this study is to analyze the impact that the volumetric areas of contrast-enhancing tumor and perineoplastic edema have on survival of patients treated for glioblastoma; Methods: A series of 87 patients who underwent surgery was retrospectively analyzed; OS and PFS were considered as the end points of the study. For each patient a multidisciplinary revision was conducted in collaboration with the Neuroradiology and Neuro-Oncology board. A manual and semi-automatic measurement were adopted to perform the radiological evaluation: contrast Enhancement Preoperative (CE-PTV) and Postoperative Tumor Volume (CE-RTV), Edema/Infiltration Preoperative (T2/FLAIR-PV) and Postoperative Volume (T2/FLAIR-RV); necrosis volume inside the tumor (NV); total tumor volume, including necrosis (TV); Results: The median OS value was 9 months and the median PFS value was 4 m; the mean values were respectively 12,3 m and 6,9 m. Multivariate analysis showed that the OS related factors were: adjuvant chemo-radiotherapy (p &lt; 0,0001), CE-PTV &lt; 15 cm³ (p=0,03), surgical resection &gt; 95% (p=0,004) and the presence of a “pseudo-capsulated” radiological morphology (p=0,04); Conclusions: maximal safe resection is one of the most relevant predictive factors for patients’ survival. The semi-automatic pre-operative MRI evaluation could play a key role in prognostically categorizing these tumors.

The ubiquitin proteasome system (UPS) utilizes an orchestrated enzymatic cascade of E1, E2, and E3 ligases to add single or multiple ubiquitin-like molecules as post-translational modification (PTM) to proteins. Ubiquitination can alter protein functions and/ or marks ubiquitinated proteins for proteasomal degradation but deubiquitinases (DUBs) can reverse protein ubiquitination. While the importance of DUBs as regulatory factors in the UPS is undisputed, many questions remain on DUB selectivity for protein targeting, their mechanism of action, and the impact of DUBs on the regulation of diverse biological processes. Furthermore, little is known about the expression and role of DUBs in tumors of the human central nervous system (CNS). In this comprehensive review, we have used publicly available transcriptional datasets to determine the gene expression profiles of 99 deubiquitinases (DUBs) from five major DUB families in seven primary pediatric and adult CNS tumor entities. Our analysis identified selected DUBs as potential new functional players and biomarkers with prognostic value in specific subtypes of primary CNS tumors. Collectively, our analysis highlights an emerging role for DUBs in regulating CNS tumor cell biology and offers a rationale for future therapeutic targeting of DUBs in CNS tumors.

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.

Emotions play a vital role in understanding human behavior and interpersonal relationships. The ability to recognize emotions through Electroencephalogram (EEG) signals offers an alternative to traditional methods, such as questionnaires, enabling the identification of emotional states in a non-intrusive manner. Automatic emotion recognition holds great potential, eliminating the need for clinical examinations or physical visits, thereby contributing significantly to the advancement of Brain-Computer Interface (BCI) technology. However, one of the key challenges lies in effectively selecting and extracting relevant features from the EEG signal to establish meaningful distinctions between different emotional states. The process of feature selection is often time-consuming and demanding. In this research, we propose a groundbreaking approach for automatically identifying three emotional states (positive, negative, and neutral) by leveraging auditory stimulation of EEG signals. Our novel method directly applies the raw EEG signal to a Convolutional Neural Network-Long Short Term Memory (CNN-LSTM) architecture, bypassing the conventional feature extraction and selection steps. This unconventional approach offers a significant departure from existing literature. Our proposed network architecture comprises ten convolutional layers, followed by three LSTM layers and two fully connected layers. Through extensive simulations and evaluations on 12 active channels, our algorithm demonstrates exceptional performance, achieving an accuracy of 97.42\% and 95.23\% for the binary classification of negative and positive emotions, as well as a Cohen's Kappa coefficient of 0.96 and 0.93 for the three-class classification (negative, neutral, and positive), respectively. These promising results highlight the efficacy of our novel methodology and its potential implications in advancing emotion recognition using EEG signals.

Advanced MRI methods and PET using radiolabeled amino acids provide valuable information in addition to conventional MR imaging for brain tumor diagnostics. These methods are particularly helpful in challenging situations such as the differentiation of malignant processes from benign lesions, the identification of non-enhancing glioma subregions, the differentiation of tumor progression from treatment-related changes, and the early assessment of response to anticancer therapy. The debate over which of the methods is preferable in which situation is ongoing and has been addressed in numerous studies. Currently, most radiology and nuclear medicine departments perform these examinations independently of each other leading to multiple examinations for the patient. The advent of hybrid PET/MRI allowed a convergence of the methods but to date simultaneous imaging has reached little relevance in clinical neuro-oncology. This is partly due to the limited availability of hybrid PET/MRI scanners, but is also due to the fact that PET is a second-line examination in brain tumors. PET is only required in equivocal situations, and spatial co-registration of PET examinations of the brain to previous MRI is possible without disadvantage. A key factor for the benefit of PET/MRI in neuro-oncology is a multimodal approach that provides decisive improvements in the diagnostics of brain tumors compared with a single modality. This systematic review focuses on studies that were able to demonstrate the additive value of amino acid PET and ‘advanced’ MRI in the diagnosis of brain tumors. Available studies suggest that the combination of amino acid PET and advanced MRI improves grading and the histomolecular characterization of newly diagnosed tumors. However, data concerning the delineation of tumor extent and biopsy guidance are of limited value. A clear additive diagnostic value of amino acid PET and advanced MRI can be achieved regarding the differentiation of tumor recurrence from treatment-related changes. Here, PET-guided evaluation of advanced MR methods seems to be helpful. In summary, there is growing evidence that a multimodal approach can achieve decisive improvements in the diagnostics of brain tumors, for which hybrid PET/MRI offers optimal conditions.

Mental stress state recognition using electroencephalogram (EEG) signals for real-life applications needs a conventional wearable device. This requires an efficient number of EEG channels and an optimal feature set. The main objective of the study is to identify an optimal feature subset that can best discriminate mental stress states while enhancing the overall performance. Thus, multi-domain feature extraction methods were employed, namely, time domain, frequency domain, time-frequency domain, and network connectivity features, to form a large feature vector space. To avoid the computational complexity of high dimensional space, a hybrid feature selection (FS) method of minimum Redundancy Maximum Relevance with Particle Swarm Optimization and Support Vector Machine (mRMR-PSO-SVM) is proposed to remove noise, redundant, and irrelevant features and keep the optimal feature subset. The performance of the proposed method is evaluated and verified using four datasets, namely EDMSS, DEAP, SEED, and EDPMSC. To further consolidate, the effectiveness of the proposed method is compared with that of the state-of-the-art heuristic methods. The proposed model has significantly reduced the features vector space by an average of 70% in comparison to the state-of-the-art methods while significantly increasing overall detection performance.

KLHL genes and the related KBTBD genes encode components of the Cullin-E3 ubiquitin ligase complex and typically target tissue-specific proteins for degradation, thereby affecting differentiation, homeostasis, metabolism, cell signaling, and the oxidative stress response. Despite their importance in normal cell function and in disease (KLHL40, KLHL41, KBTBD13, KEAP1, and ENC1), previous studies that examined epigenetic factors affecting transcription were predominantly limited to promoter DNA methylation. Using diverse tissue and cell culture whole-genome profiles, we examined 17 KLHL or KBTBD genes preferentially expressed in skeletal muscle or brain to identify tissue-specific enhancer and promoter chromatin, open chromatin (DNaseI hypersensitivity), and DNA hypomethylation. Sixteen of the 17 genes displayed muscle- or brain-specific enhancer chromatin in their gene bodies, and most exhibited specific intergenic enhancer chromatin as well. Seven genes were embedded in a super-enhancer. The enhancer chromatin regions typically displayed foci of DNA hypomethylation at peaks of open chromatin. In addition, we found evidence that gene neighbors (HHATL and FBXO32) of KLHL40 and KLHL38 harbor enhancer chromatin that likely upregulates the adjacent KLHL gene. Many KLHL/KBTBD genes had tissue-specific promoter chromatin at their 5’ ends, but surprisingly, two (KBTBD11 and KLHL31) had constitutively unmethylated promoter chromatin in their 3’ exons that overlaps a retrotransposed KLHL gene. Our findings demonstrate the importance of expanding epigenetic analyses beyond the 5’ ends of genes in studies of normal and abnormal gene regulation.

How can neuroscience help everyone to live and care for our confined brains? Understanding and studying human behaviour allows us to measure the impact of such confinement on each of us and to identify those who need help. The challenges are to understand the psychological repercussions following confinement and to understand how neuroscience and neurotechnology can be very interesting tools for dealing with the health crisis. Neuroscience is changing our traditional philosophical and ethical views by providing information about the biological basis of our moral behaviour. The exception of the brain is at the heart of neuroethical thinking and discourse. Neuroethics is an interdisciplinary discipline placed at the intersection between the human sciences and the neurosciences, and aims to help understand how knowledge and research in neurosciences and neurotechnologies will affect the future of society, their impact on humans, relationships, daily life, the labour market ... but also how they can help and provide solutions and answers to the questions of citizens in a health crisis. But it's a double-edged sword, collecting and analyzing brain data in real time seems to be increasingly simple and within everyone's reach, without having the hindsight of the real meaning of these data, allowing one day to read people's thoughts, control them and manipulate them. It is becoming clear that the boundaries between medical and non-medical uses of neuroscience and neurotechnology are becoming very porous, inviting us to reflect on neuroethical issues in order to put safeguards on these uses.

Multidisciplinary neurotechnology holds the promise of understanding and non-invasively treating neurodegenerative diseases. In this preclinical trial on Parkinson's disease (PD), we combined neuroscience together with the nascent field of medical virtual reality and generated several important observations. First, we established the Oculus Rift virtual reality system as a potent measurement device for parkinsonian involuntary hand tremors (IHT). Interestingly, we determined changes in rotation were the most sensitive marker of PD IHT. Secondly, we determined parkinsonian tremors can be abolished in VR with algorithms that remove tremors from patients' digital hands. We also found that PD patients were interested in and were readily able to use VR hardware and software. Together these data suggest PD patients can enter VR and be asymptotic of PD IHT. Importantly, VR is an open-medium where patients can perform actions, activities, and functions that positively impact their real lives - for instance, one can sign tax return documents in VR and have them printed on real paper or directly e-sign via internet to government tax agencies. Lastly, we generated a technical framework wherein movements in the real world can be measured side-by-side with those in virtual reality. With this framework, we observed anecdotal evidence of parkinsonian tremors being reduced in real life when our algorithms abolished digital hand tremors in VR.

Victor Vasarely’s (1906-1997) important legacy to the study of human perception is brought to the forefront and discussed. A large part of his impressive work conveys the appearance of striking three-dimensional shapes and structures in a large-scale pictorial plane. Current perception science explains such effects by invoking brain mechanisms for the processing of monocular (2D) depth cues. Here in this study, we illustrate and explain the local effects of 2D color and contrast cues on the perceptual organization in terms of figure-ground assignments, i.e. which local surfaces are likely to be seen as “nearer” or “bigger” in the image plane. Paired configurations are embedded in a larger, structurally ambivalent pictorial context inspired by some of Vasarely’s creations. The figure-ground effects these configurations produce reveal a significant correlation between perceptual solutions for “nearer” and “bigger” when no other monocular depth cues are given in the image. In consistency with previous findings on similar, albeit simpler visual displays, a specific color may compete with luminance contrast in resolving the planar ambiguity of a complex pattern context. Vasarely intuitively understood, and successfully exploited, this kind of subtle context effect in his art, well before empirical investigations had set out to study and explain their genesis in terms of information processing by the visual brain.

The ability of recombinant, SARS-CoV-2 Spike (S) protein to modulate the production of two COVID-19 relevant, pro-inflammatory cytokines (IL-6 and IFN-γ) in PBMC cultures of healthy, pre-Covid-19 subjects was investigated. We observed that cytokine production was largely and diversely modulated by the S protein depending on antigen or mitogen stimulation, as well as on the protein source, insect (S-in) or human (S-hu) cells. While both proteins co-stimulated cytokine production by polyclonally CD3-activated T cells, PBMC activation by the mitogenic lectin Concanavalin A (Con A) was up modulated by S-hu protein and down-modulated by S-in protein. These modulatory effects were likely mediated by the S glycans as demonstrated by direct Con A-S binding experiments and use of yeast mannan as Con A binder. While being ineffective in modulating memory antigenic T cell responses, the S proteins and mannan were able to induce IL-6 production in unstimulated PBMC cultures and upregulate the expression of Mannose Receptor (CD206), a marker of anti-inflammatory M2 macrophage. Our data point to a relevant role of N-glycans, particularly N-mannosidic chains, decorating the S protein in the immunomodulatory effects here reported. These novel biological activities of the S glycan ectodomain may add to the comprehension of Covid-19 pathology and immunity to SARS-CoV-2.

Diabetes and mental disorders have been recognized as two significant public health concerns globally. Recent research indicates that there is a bidirectional relationship between these two conditions, with each influencing the other's course and outcomes. Nutrition plays an essential role in the prevention and treatment of both mental disorders and diabetes. A comprehensive review of existing literature was conducted to examine the impact of anxiety and depression on the development of diabetes and the influence of diabetes on the occurrence of mental health disorders such as anxiety and depression. Additionally, the effects of nutrition on the prevention and management of mental disorders, diabetes, and related complications in at risk individuals were assessed. Our findings show that mental disorders, such as depression and anxiety increase the risk of developing type 2 diabetes and are associated with poorer glycemic control, increased diabetes-related complications, and higher mortality rates. Conversely, diabetes is also linked with an increased risk of developing mental health disorders, including depression, anxiety, and cognitive decline. The biological, psychological, and social factors that contribute to the comorbidity between these two conditions are complex and multifaceted. Therefore, an integrated approach to the management of both conditions is critical for improving patient outcomes and reducing the overall burden of disease. Nutritional interventions should be utilized to reduce the risk of diabetes in patients with anxiety and depression as well as enhance mental health in patients with diabetes.

Blood gas analysis is a diagnostic tool to evaluate the partial pressures of gas in blood and acid-base content. The use of blood gas analysis enables to clear understanding the respiratory, circulatory, and metabolic disorders. The arterial blood gas (ABG) explicitly analyzes blood taken from an artery, assessing the patient's partial pressure of oxygen (PaO2), carbon dioxide (PaCO2) pH (acid/base). PaO2 indicates the oxygenation status, and PaCO2 indicates the ventilation status (chronic or acute respiratory failure). PaCO2 is affected by hyperventilation characterized by rapid or deep breathing, and hypoventilation characterized by slow or shallow breathing. The acid-base balance tested by the ABG procedure measures the pH and PaCO2 directly while the use of the Hasselbach equation gives the serum bicarbonate (HCO3) and base deficit or excess. The measured HCO3is based on strong alkali that frees all CO2 in serum, including dissolved CO2, carbamino compounds, and carbonic acid the calculation uses a standard chemistry analysis giving the amount of "total CO2", the difference will amount to around 1.2 mmol/L. Though ABG is frequently ordered in emergency medicine contests for acute conditions it may also be needed in other clinical settings. The ABG analysis shows to be an exceptional diagnostic tool including the group of those diseases known as acid-base diseases (ABDs) which include a great variety of conditions as such severe sepsis, septic shock, hypovolemic shock, diabetic ketoacidosis, renal tubular acidosis, chronic respiratory failure, chronic heart failure, and diverse metabolic diseases.

Background: Strong indicators of inflammation, such as C-reactive protein (CRP), hypersensitive CRP (hs-CRP), and a series of hematological indices, including platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), hematocrit (HCT) and red blood cell distribution width (RDW), are regarded related with the incidence of contrast induced nephropathy (CIN) closely. Whereas, it remains unclear whether they can function as predictors of CIN onset. The objective of this meta-analysis was to determine the relationship between above indicators and CIN incidence among patients receiving coronary intervention. Methods: Clinical studies were retrieved from the electronic databases of PubMed, EMBASE, Google Scholar, Clinical Trials, and science direct from their inception to June 3rd, 2020. Meta-analysis was performed on pool eligible studies. Two reviewers screened all titles and abstracts and independently assessed all articles. Results: A total of 26 studies involving 29,454 patients were included in the meta-analysis. Pooled analysis results revealed that patients with higher CRP (odds ratio [OR]=1.06, 95% confidence interval [CI]: 1.01–1.12, P=0.02), hs-CRP (OR=1.03, 95% CI: 1.01–1.06, P=0.004), NLR (OR=1.11, 95% CI: 1.01–1.20, P=0.02), RDW (OR=1.35, 95% CI: 1.19–1.53, P<0.00001), and lower HCT (OR=0.94, 95% CI: 0.92–0.97, P=0.0003) all exhibited significantly higher CIN rates, but there was no significant association between PLR and CIN risk (OR=1.12, 95% CI: 0.99–1.26, P=0.07). Conclusion: The meta-analysis reported here demonstrates that pre-angiography CRP/hs-CRP and some hematological indices are associated with CIN.

Assessment of health-related quality of life (HRQoL) after pediatric traumatic brain injury (TBI) has been limited in children and adolescents due to a lack of disease-specific instruments. To fill this gap, the Quality of Life after Traumatic Brain Injury for Children and Adolescents (QOLIBRI-KID/ADO) was developed for the German-speaking population. Reference values from a comparable general population are essential for comprehending the impact of TBI on health and well-being. This study examines the validity of the German QOLIBRI-KID/ADO in a general pediatric population in Germany and provides reference values for use in clinical practice. Overall, 1997 children and adolescents aged 8-17 years from the general population and 300 from the TBI population participated in the study. The questionnaire was tested for reliability and validity. A measurement invariance (MI) approach was used to assess the comparability of the HRQoL construct between both samples. Reference values were determined by percentile-based stratification according to factors that significantly influenced HRQoL in regression analyses. The QOLIBRI-KID/ADO demonstrated strong psychometric properties. The HRQoL construct was measured largely equivalently in both samples, and reference values could be provided. The QOLIBRI-KID/ADO was considered reliable and valid for assessing HRQoL in a general German-speaking pediatric population, allowing for clinically meaningful comparisons between general and TBI populations.

The pentose phosphate pathway (PPP) is one of three major pathways involved in glucose metabolism, regulated by glucose-6-phosphate dehydrogenase (G6PD), controlling NADPH formation. NADPH, in turn, regulates the balance of oxidative stress and reactive oxygen species (ROS) levels. G6PD dysfunction, affecting PPP, is implicated in neurological disorders, including epilepsy. However, PPP's role in epileptogenesis and ROS production during epileptic activity remains unclear. To clarify these points, we conducted electrophysiological and imaging analyses on mouse hippocampal brain slices. Using the specific G6PD inhibitor G6PDi-1, we assessed its effects on mouse hippocampal slices, examining intracellular ROS, glucose/oxygen consumption, and ROS production during synaptic stimulation and in the 4AP epilepsy model. G6PDi-1 increased basal intracellular ROS levels and reduced synaptically induced glucose consumption but had no impact on ROS production from synaptic stimulation. In the 4AP model, G6PDi-1 didn't significantly alter spontaneous seizure frequency or H2O2 release amplitude but increased the frequency and peak amplitude of interictal events. These findings suggest that short-term PPP inhibition has a minimal impact on synaptic circuit activity.

Background: Glioblastoma remains a challenging brain tumor to treat due to its infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful tumor resection. This study introduces an innovative intraoperative visualization method utilizing a surgical fluorescence microscope to precisely locate tumor cells. The focus of the study is on IR-Glint, a novel preparation comprising Cy7.5-labeled aptamers Gli-233nt and Gli-55_3L specific to human glioblastoma. Methods: The aptamers were modified using molecular modeling and quantum chemical techniques. The effectiveness of the preparation was assessed using flow cytometry and microscopy on primary cultures of human glioblastoma. In vivo studies were conducted on mouse and rabbit models, employing orthotopic xenotransplantation of human brain glioblastoma with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. Results: The experiments validated the potential of IR-Glint for intraoperative visualization of glioblastoma using infrared imaging. Surface application of the aptamer-based formulation on the brain allowed clear visualization of the tumor, aiding surgeons in tumor resection. This approach also reduces the dosage required and mitigates potential toxic effects on the patient. Conclusions: This study demonstrates the promising potential of using in-frared dye-labeled aptamers for intraoperative visualization of glioblastoma. By improving surgical treatment outcomes in neurosurgery, this novel approach may pave the way for future advancements in the field.

Neurological disorders have been reported in a large number of coronavirus disease 2019 (COVID-19) patients, suggesting that this disease may have long-term adverse neurological consequences. COVID-19 occurs from the infection by a positive-sense single-stranded RNA virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The membrane fusion protein of SARS-CoV-2, the spike protein, binds to its human host receptor, angiotensin-converting enzyme 2 (ACE2), to initiate membrane fusion between the virus and host cell. The spike protein of SARS-CoV-2 contains the furin protease recognition site and its cleavage enhances the infectivity of this virus. The binding of SARS-CoV-2 to the ACE2 receptor has been shown to downregulate ACE2, thereby increasing the levels of pathogenic angiotensin II (Ang II). The furin protease cleaves between the S1 subunit of the spike protein with the binding domain toward ACE2 and the S2 subunit with the transmembrane domain that anchors to the viral membrane, and this activity releases the S1 subunit into the blood circulation. The released S1 subunit of the spike protein also binds to and downregulates ACE2, in turn, increasing the level of Ang II. Considering that a viral particle contains many spike protein molecules, furin-dependent cleavage would release many free S1 protein molecules each of which can downregulate ACE2, while the infection with a viral particle only affects one ACE2 molecule. Therefore, the furin-dependent release of S1 protein would dramatically amplify the ability to downregulate ACE2 and produce Ang II. We hypothesize that this amplification mechanism that the virus possesses, but not the infection per se, is the major driving force behind COVID-19 associated neurological disorders.

The microbiota–gut–brain axis has garnered increasing attention in recent years for its role in various health conditions, including neuroinflammatory disorders like complex regional pain syndrome (CRPS). CRPS is a debilitating condition characterized by chronic neuropathic pain, and its etiology and pathophysiology remain elusive. Emerging research suggests that alterations in the gut microbiota composition and function could play a significant role in CRPS development and progression. Our paper explores the implications of microbiota in CRPS and the potential therapeutic role of boron (B). Studies have demonstrated that individuals with CRPS often exhibit dysbiosis, with imbalances in beneficial and pathogenic gut bacteria. Dysbiosis can lead to increased gut permeability and systemic inflammation, contributing to the chronic pain experienced in CRPS. B, an essential trace element, has shown promise in modulating the gut microbiome positively and exerting anti-inflammatory effects. Recent preclinical and clinical studies suggest that B supplementation may alleviate neuropathic pain and improve CRPS symptoms by restoring microbiota balance and reducing inflammation. Our review highlights the complex interplay between microbiota, inflammation, and neuropathic pain in CRPS and underscores the potential of B as a novel therapeutic approach to target the microbiota–gut–brain axis, offering hope for improved management of this challenging condition.

Anterior-tooth (ANT) contacts induce short latency reflex inhibition of human jaw-closing muscles. The jaw is a rigid class 1 lever for pinpoint-targeting muscle force into a single bite-point, the pivoting food particle. See-saw reflex movements around the food particle fulcrum multiply the food-crushing force. Unpredictable jolts of reaction force caused by food-crushing are subjected to the rostral ANT and caudally to the two articulate ends of the jaw triangle. Compression/distraction strains of food-crushing must be monitored and inhibited by withdrawal reflexes. The mesencephalic ganglion (Vmes), neural myelin sheath, and muscle stretch receptors evolved subsequently to the advent of jaws to improve the velocity of proprioceptive and withdrawal reflexes. In mammalians, the spindles of the taut motor units, stretched by the food-fulcrum send excitatory monosynaptic feedback for the efferent neurons of the respective ipsilateral muscle units, via Vmes. In the Vmes, the spindle-input-mediating afferent neurons are coupled with another source of afferent feedback, which is also excitatory, from the back-tooth (BAT) mechanoreceptors. The two sources of excitatory pulses are summated and targeted for the efferent neurons to boost the stretched and taut motor units. Likewise, the afferent feedback from ANT mechanoreceptors is also coupled in the Vmes with concomitant feedback from spindles. The ANT output, however, is inhibitory to negate the excitatory feedback from the stretched jaw-muscle units. The inhibitory feed from ANT temporarily blocks the excitatory potential of masticatory motor efferent neurons to protect the ANT and jaw-joints from inadvertent strains. The inhibitory inputs from ANT alternate with the excitatory inputs from BAT to determine which jaw-closing muscle units are activated or inhibited at any given instant of food-crushing. The Vmes exists in all jawed vertebrates, and its’ evolution was probably motivated by demands for the control of bite force. The monosynaptic unilateral food-crushing excitatory and inhibitory reflexes (UFCR) override the coexisting bilaterally executed feed for jaw muscles from the central nervous system. Hypothesis: The Vmes-mediated UFCR combine neural inputs from tooth contacts with concomitant feedback from muscle stretch receptors for the control of mammalian food-crushing bite force.

Astrocytes are essential for normal brain development and functioning. They respond to brain injury and disease through a process referred to as reactive astrogliosis, where the reactivity is highly heterogenous and context dependent. Reactive astrocytes are active contributors to brain pathology and can exert beneficial, detrimental, or mixed effects following brain insults. Transforming growth factor-β (TGF-β) has been identified as one of the key factors regulating astrocyte reactivity. Genetic and pharmacological manipulation of TGF-β signaling pathway in animal models of CNS injury and disease alters pathological and functional outcomes. This review aims to provide recent understanding regarding astrocyte reactivity and TGF-β signaling in brain injury, aging, and neurodegeneration. Further, it explores how TGF-β signaling modulates astrocyte reactivity and function.

Background: Continuous subcutaneous apomorphine infusion (CSAI), levodopa-carbidopa intestinal gel infusion (LCIG), and deep brain stimulation of the subthalamic nucleus (STN-DBS) have markedly changed the treatment landscape of advanced Parkinson’s disease (aPD). Despite a similar outcome of all device-aided therapies (DATs), some patients switch or combine DATs. The aim of this retrospective study was to explore the frequency and reasons for switching between or combining DATs in two movement disorders centres in Slovenia and Israel. Methods: We collected and analysed demographic and clinical data from aPD patients who switched between or combined DATs. Motor and non-motor reasons and their frequency for switching/combining were examined, as was the effect of DAT using the Global Improvement subscale of the Clinical Global Impression Scale. Non-parametric tests were used to analyse the data. Results: Of 505 aPD patients treated with DATs at both centres between January 2009 and June 2021, we identified in total 30 patients (6%), who either switched DAT (N=24: 7 LCIG-to-STN-DBS, 1 LCIG-to-CSAI, 5 CSAI-to STN-DBS, 8 CSAI-to-LCIG, 1 STN-DBS-to-LCIG, 1 LCIG-to-CSAI-to-STN-DBS, and 1 STN-DBS-to-CSAI-to-LCIG) or combined DATs (N=6: 5 STN-DBS+LCIG and 1 STN-DBS+CSAI-to-STN-DBS+LCIG). In most of these patients, inadequate control of motor symptoms was the main reason for switching or combining DATs, but non-motor reasons (related to the disease and/or DAT) were also identified. Conclusions: Switching between and combining DATs is uncommon, but in some patients brings substantial clinical improvement and should be considered in those who have either inadequate symptom control on DAT treatment or have developed DAT related complications.

This theoretical article provides a brief description of the model of living systems' functioning by defining them as resource flows patterns. It reviews the living systems growth limitation between their development cycles by the Fibonacci sequence. Besides, there are presented systems resource base criteria, necessary for accumulating the resources and their investment. The article also considers the conditions for the formation of various systems strategies. Then we reviewed the principles of elemental analysis of information by a person as a living system according to the considered model. The study also shows the possibility of forming priorities in analyzing information for 16 combinations as maximum. At that, it remains crucial to divide a human's information analysis between the two hemispheres of the brain. The described combinations of priorities in a person's information analysis are compared with the existing differential personality models, such as the big five personality traits, the Myers-Briggs type indicator, temperaments model and Honey and Mumford Learning styles.

Medical brain image analysis is a necessary step in the Computers Assisted /Aided Diagnosis (CAD) systems. Advancements in both hardware and software in the past few years have led to improved segmentation and classification of various diseases. In the present work, we review the published literature on systems and algorithms that allow for classification, identification, and detection of White Matter Hyperintensities (WMHs) of brain MRI images specifically in cases of ischemic stroke and demyelinating diseases. For the selection criteria, we used the bibliometric networks. Out of a total of 140 documents we selected 38 articles that deal with the main objectives of this study. Based on the analysis and discussion of the revised documents, there is constant growth in the research and proposal of new models of deep learning to achieve the highest accuracy and reliability of the segmentation of ischemic and demyelinating lesions. Models with indicators (Dice Score, DSC: 0.99) were found, however with little practical application due to the uses of small datasets and lack of reproducibility. Therefore, the main conclusion is to establish multidisciplinary research groups to overcome the gap between CAD developments and their complete utilization in the clinical environment.

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

In our study, we investigated the prognostic significance of hematological markers—NLR (Neutrophil-to-Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio), and RDW-CV (Red Blood Cell Distribution Width - Coefficient of Variation)—in 117 glioblastoma patients. Data collected from January 2016 to December 2018 included demographics, clinical scores, and treatment regimens. Unlike previous research, which often examined these markers solely before surgery, our unique approach analyzed them at multiple stages: preoperative, postoperative, and before adjuvant therapies. We correlated these markers with overall survival (OS) and progression-free survival (PFS) using statistical tools, including ANOVA, Cox regression, and Kaplan-Meier survival analyses, employing SPSS version 29.0. Our findings revealed notable variations in NLR, PLR, and RDW-CV across different treatment stages. NLR and PLR decreased after surgery, with some stabilization post-STUPP phase (NLR: p=0.007, η2p=0.06; PLR: p=0.001, η2p=0.23), while RDW-CV increased post-surgery and during subsequent treatments (RDW-CV: p &lt; 0.001, η2p=0.67). Importantly, we observed significant differences between the preoperative phase and other treatment phases. Additionally, higher NLR and RDW-CV at the second-line treatment and disease progression were associated with an increased risk of death (NLR at 2nd line: HR=1.03, p=0.029; RDW-CV at progression: HR=1.14, p=0.004). We proposed specific marker cutoffs that demonstrated significant associations with survival outcomes when applied to Kaplan-Meier survival curves (NLR at 2nd line &lt; 5: p&lt;0.017; RDW-CV at progression &lt; 15: p=0.007). Elevated NLR and RDW-CV at later treatment stages correlated with poorer OS and PFS. No significant preoperative differences were detected. These biomarkers may serve as non-invasive tools for glioblastoma management.

Background Although high-density lipoprotein has cardioprotective effects, the association between serum high-density lipoprotein cholesterol (HDL-C) and hypertension is poorly understood. Objective We investigated whether low and high concentrations of HDL-C are associated with hypertension using a large healthcare dataset. Methods In a community-based cross-sectional study of 1,493,152 Japanese people aged 40–74 years who underwent a health checkup, blood pressures and clinical parameters, including nine HDL-C concentrations (20–110 mg/dL or over) were investigated. Results A crude U-shaped relationship was observed between the nine HDL-C concentrations and blood pressure in males (n = 830,669), while a left-to-right inverted J-shaped relationship was observed in females(n = 662,483). An age-adjusted logistic regression analysis showed J-shaped relationships (left-to-right inversion in females) between HDL-C and odds ratios for hypertension (≥140/90 mmHg), with lower limits of 60–79 mg/dL in males and 90–99 mg/dL in females, which were unchanged after adjusting for smoking, habitual exercise, alcohol consumption, and pharmacotherapy for hypertension, dyslipidemia, and diabetes. However, further adjustment for body mass index and serum triglyceride concentration revealed latent positive linear associations between HDL-C and hypertension, although the association between extremely high HDL-C (≥100 mg/dL) and hypertension was attenuated in non-alcohol drinkers. Conclusion Both low and extremely high HDL-C concentrations are associated with hypertension. The former association may be dependent on excess fat mass, which is often concomitant with low HDL-C, whereas the latter association may be dependent on frequent alcohol consumption.

Ecklonia cava (E.cava) can alleviate vascular dysfunction in diseases associated with poor circulation. E. cava contains various polyphenols with different functions, but few studies have compared the effects of these polyphenols. Here, we comparatively investigated four major compounds present in an ethanoic extract of E. cava. These four major compounds were isolated and their effects were examined on monocyte-associated vascular inflammation and dysfunctions. Pyrogallol-phloroglucinol-6,6-bieckol (PPB) significantly inhibited monocyte migration in vitro by reducing levels of inflammatory macrophage differentiation and of its related molecular factors. In addition, PPB protected against monocyte-associated endothelial cell death by increasing the phosphorylations of PI3K-AKT and AMPK, decreasing caspase levels, and reducing monocyte-associated vascular smooth muscle cell proliferation and migration by decreasing the phosphorylations of ERK and AKT. The results of this study show that four compounds were effective for reduction of monocyte-associated vascular inflammation and dysfunctions, but PPB might be more useful for the treatment of vascular dysfunction in diseases associated with poor circulation.

It is well known that the effect of laser irradiation on the blood causes a change in the shape of red blood cells and an increase in their activity, especially in low-level laser therapy (LLLT). The aim of this study was to identify the ability of erythrocytes to deform when exposed to a blue laser.24 laboratory rats were exposed to blue laser in the gingival region of the lower jaw daily for 5 minutes over 3 days. The blue laser possessed a power of 0.5 W and was operated using a con-tactless approach, the dynamic technique in continuous wave mode, and an uninitiated fiber. A blood sample was taken from the lateral vein of the tail before the LLLT, on the first, second, third, and fifth days. The samples were stained, and cytometry was conducted. The exposure to blue laser caused a significant increase in the number of dome-shaped deformable erythrocytes in the blood of laboratory rats (p

The editorial explores the realm of emerging translational research in neurology and psychiatry, providing insights into various subjects, including neurodegenerative disorders and innovative therapeutic methods. The main objective is to study neurological and psychiatric disorders, such as Alzheimer's disease, with a particular emphasis on techniques for neural regeneration and repair. The editorial highlights the importance of taking a comprehensive approach to studying and treating complex neurological and psychiatric conditions. This involves thoroughly reviewing research papers on the causes, development, biomarkers, and treatment options for these conditions. The editorial emphasizes the necessity of using multidisciplinary and integrative methods to gain a deeper understanding and improve the treatment of these conditions. The development of an animal model for recurrent primary dysmenorrhea showcases the innovative techniques employed in the investigation of gynecological disorders, illustrating the capacity of translational research to connect fundamental scientific knowledge with practical medical applications. The cooperative endeavors of researchers and clinicians emphasized in this editorial lay the foundation for revolutionary advancements that hold the potential to enhance outcomes for individuals afflicted with neurological and psychiatric disorders globally.

Understanding the phenomena underlying the non-selective susceptibility to ischemia of py-ramidal neurons in the CA3 area of the hippocampus is important from the point of view of elu-cidating the mechanisms of memory loss and the development of post-ischemic dementia. We used an ischemic model of Alzheimer's disease to study changes in amyloid protein precursor gene expression, its cleavage enzymes and tau protein in the CA3 area of the hippocampus af-ter a 10-minute brain ischemia with 12, 18, and 24-month survival. Quantitative reverse tran-scriptase PCR assay showed that the expression of all the genes that contribute to amyloid pro-duction was dysregulated within 2 years in the CA3 area of the hippocampus after ischemia. The expression of the amyloid protein precursor gene was above the control values at all times of the study. The expression of the α-secretase gene also exceeded the control values throughout the study. In contrast, the expression of the β-secretase gene reaching its maximum increase 12 months after ischemia, was below control values after 18 months and again above control values after 24 months of survival. Presenilin 1 and 2 gene expression was significantly elevated throughout the follow-up period, with peak expression of both genes occurring 12 months after ischemia. This suggests that the genes studied are involved in the non-amyloidogenic processing of amyloid protein precursor. Also, tau protein gene expression was significantly elevated throughout the observation period, and peak gene expression was present 12 months after is-chemia. Data indicate that an episode of brain ischemia with long-term survival causes damage and death of pyramidal neurons in the CA3 area of the hippocampus in a manner dependent on modified tau protein. Thus defining a new and important mechanism of pyramidal neuronal death in the CA3 area after ischemia. In addition tau protein gene modification after brain is-chemia is useful in identifying ischemic mechanisms occurring in Alzheimer's disease.

The psychedelic renaissance has reignited interest in the therapeutic potential of psychedelics for mental health and well-being. An emerging area of interest is the potential modulation of psychedelic effects by the gut microbiome - the ecosystem of microorganisms residing in our digestive tract. This review explores the intersection of the gut microbiome and psychedelic therapy, underlining potential implications for personalized medicine and mental health. We delve into the current understanding of the gut-brain axis, its influence on mood, cognition, and behavior, and how the microbiome may affect the metabolism and bioavailability of psychedelic substances. We also discuss the role of microbiome variations in shaping individual responses to psychedelics, along with potential risks and benefits. Moreover, we consider the prospect of microbiome-targeted interventions as a fresh approach to boost or modulate psychedelic therapy's effectiveness. By synthesizing insights from the fields of psychopharmacology, microbiology, and neuroscience, our objective is to advance knowledge about the intricate relationship between the microbiome and psychedelic substances, thereby paving the way for novel strategies to optimize mental health outcomes amid the ongoing psychedelic renaissance.

Magnetic resonance elastography (MRE) has revealed sexual dimorphism in brain stiffness in healthy individuals and multiple sclerosis (MS) patients. In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), we showed previously that inflammation-induced brain softening was associated with alterations of the extracellular matrix (ECM). However, it remained unclear whether the brain ECM presents sex-specific properties that can be visualized by MRE. Therefore, we aimed here at quantifying sexual dimorphism in brain viscoelasticity in association with ECM changes in healthy and inflamed brains. Multifrequency MRE was applied to the midbrain of healthy and EAE mice of both sexes to quantitatively map regional stiffness. To define differences in brain ECM composition, gene expression of the key basement membrane components laminin (Lama4, Lama5), collagen (Col4a1, Col1a1) and fibronectin (Fn1) was investigated by RT-qPCR. We showed that the healthy male cortex expressed less Lama4, Lama5, Col4a1 but more Fn1 (all p < 0.05) than the healthy female cortex, which was associated with 9% softer properties (p = 0.044) in that region. At peak EAE, cortical softening was similar in both sexes compared to healthy tissue, with an 8% difference remaining between males and females during EAE (p < 0.001). Cortical Lama4, Lama5 and Col4a1 expression increased 2 to 3-fold in EAE in both sexes while Fn1 decreased only in males (all p < 0.05). No significant sex differences in stiffness were detected in other brain regions. In conclusion, sexual dimorphism in the ECM composition of cortical tissue in the mouse brain is reflected by in vivo stiffness measured with MRE and should be considered in future studies by sex-specific reference values.

We discuss what we believe could be an improvement in future discussions of the ever-changing brain. We do so by distinguishing different types of brain variability and outlining methods suitable to analyse them. We argue that, when studying brain and behaviour data, classical methods such as regression analysis and more advanced approaches both aim to decompose the total variance into sensible variance components. In parallel, we argue that a distinction needs to be made between innate and acquired brain variability. For varying high-dimensional brain data, we present methods useful to extract their low-dimensional representations. Finally, to trace potential causes and predict plausible consequences of brain variability, we discuss how to combine statistical principles and neurobiological insights to make associative, explanatory, predictive, and causal enquires; but cautions are needed to raise association- or prediction-based neurobiological findings to causal claims.

Transcranial direct current stimulation (tDCS) over the left Inferior Frontal Gyrus (IFG) was found to improve apraxia of speech (AOS) in post-stroke aphasia, speech fluency in adults who stutter, naming and spelling in primary progressive (PPA). This paper aims to determine whether tDCS over the left IFG coupled with AOS therapy improves speech fluency in patients with PPA more than sham. Eight patients with non-fluent PPA with AOS symptoms received either active or sham tDCS, along with speech therapy for 15 weekday sessions. Speech therapy consisted of repetition of increasing syllable-length words. Evaluations took place before, immediately after, and two months post-intervention. Words were segmented into vowels and consonants and the duration of each vowel and consonant was measured. Segmental duration was significantly shorter after tDCS than sham for both consonants and vowels. tDCS gains generalized to untrained words. The effects of tDCS sustained over two months post-treatment in trained words. Taken together, these results demonstrate that the tDCS over the left IFG facilitates speech production by reducing segmental duration. The results provide preliminary evidence that tDCS can maximize efficacy of speech therapy in non-fluent PPA with AOS.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

Autism spectrum disorder (ASD) is a neuropsychiatric condition characterized by impaired social interactions and repetitive stereotyped behaviors. Growing evidence highlights an important role of the gut-brain-microbiome axis in the pathogenesis of ASD. Research indicates an abnormal composition of the gut microbiome and the potential involvement of bacterial molecules in neuroinflammation and brain development disruptions. Concurrently, attention is directed towards the role of short-chain fatty acids (SCFAs) and impaired intestinal tightness. This comprehensive review emphasizes the potential impact of maternal gut microbiota changes on the development of autism in children, especially considering maternal immune activation (MIA). The following paper evaluates the impact of the birth route on the colonization of the child with bacteria in the first weeks of life. Furthermore, it explores the role of pro-inflammatory cytokines, such as IL-6 and IL-17a and mother’s obesity as potentially environmental factors of ASD. The purpose of the present analysis is to advance our understanding of ASD pathogenesis, while also searching for the positive implications of the latest therapies, such as probiotics, prebiotics or fecal microbiota transplantation, targeting the gut microbiota and reducing inflammation. This review aims to provide valuable insights that could instruct future studies and treatments for individuals affected by ASD.

Different nutraceuticals are often considered by parents of infants and children with abdominal pain and disorders of the gut-brain interaction. Herb extracts and natural compounds have long been used in traditional medicine, but clinical pediatric trials are very limited. This narrative review based on relevant studies identified through Pubmed-Medline literature search updated to October 2023, focused on the effect of nutraceuticals in infantile colic, functional abdominal pain and irritable bowel syndrome in children and adolescents. Significant reduction of colic episodes and crying time was reported in two studies on fennel (seeds oil or tea), in three studies on different multiple herbal extracts (all including fennel), in one study on Mentha piperita, and in at least two double-blind randomized controlled studies on Lactobacillus reuteri DSM 17938 and Bifidobacterium lactis BB-12 (108 CFU/day for at least 21 days) in breast-fed infants. Compared to placebo, in children with functional abdominal pain or irritable bowel syndrome a significant reduction of pain was reported in two studies supplementing peppermint oil capsules or psyllium fibers, in one study on corn fiber cookies or partial hydrolysed guar gum or a specific multiple herbal extract (STW-5) or vitamin D supplementation. To date, there is a moderate certainty of evidence with a weak grade of recommendation for Lactobacillus reuteri DSM 17938 (108 CFU/day) for reducing pain intensity in children with functional abdominal pain and for Lactobacillus rhamnosus GG (1-3 x109 CFU twice daily) for reducing pain frequency and intensity in children with IBS. Further large and well-designed pediatric studies are needed to prove efficacy and safety of different herbal extracts and prolonged use of studied products in infants and children with pain disorders of the gut-brain interaction.

Adult neural stem and progenitor cells (NSPCs) contribute to learning, memory, maintenance of homeostasis, energy metabolism and many other essential processes. They are highly heterogeneous populations that require input from a regionally distinct microenvironment including a mix of neurons, oligodendrocytes, astrocytes, ependymal cells, NG2+ glia, vasculature, cerebrospinal fluid (CSF), and others. The diversity of NSPCs is present in all three major parts of the CNS, i.e., the brain, spinal cord, and retina. Intrinsic and extrinsic signals, e.g., neurotrophic and growth factors, master transcription factors, and mechanical properties of the extracellular matrix (ECM), collectively regulate activities and characteristics of NSPCs: quiescence/survival, proliferation, migration, differentiation, and integration. This review discusses the heterogeneous NSPC populations in the normal physiology and highlights their potentials and roles in injured/diseased states for regenerative medicine.