Background: Sugar laden foods and carbohydrate rich diets with high glycaemic index intake are associated with weight gain, increased incidence of diabetes and is linked with increased cardiovascular risk. A blend of mulberry leaf extract and apple peel extract (Glubloc™) may reduce postprandial blood glucose surge and insulin response following dietary carbohydrate intake by limiting its digestion and uptake from the gut. Methods: In this randomised, placebo-controlled, crossover study, thirty healthy male and female subjects were supplemented with either placebo or Glubloc™, 10 min before a carbohydrate and sugar rich meal intake. Changes in postprandial blood glucose (upto120 minutes) and insulin levels (at 60 minutes) were measured as the primary endpoints. Changes in blood glucose incremental area under the concentration curve (iAUC), maximum concentration (Cmax) and peak time (Tmax) were compared. Results: Thirty adults (mean age 31±7.2 years, BMI 24±3.8 kg/m2) completed the study and the Glubloc™ blend relative to placebo significantly reduced glucose iAUC at 0.5 h (− 38%, p < 0.0003), 1.0 h (− 30%, p = 0.0007), 1.5 h (− 29%, p = 0.0008), and 2.0 h (− 26%, p = 0.002). A statistically significant reduction in 1 h insulin levels (− 35%, p = 0.029) was observed. Conclusion: A single dose supplementation of Glubloc™ significantly reduced the postprandial blood glucose spike and serum insulin levels. The observation of a significant glucose reduction paralleled with a significant lower insulin response supports a reduced gastrointestinal glucose absorption. None of the subjects experienced any major gastrointestinal side effects. This study builds a body of evidence that the combination of white mulberry leaf and green apple peel extracts (Glubloc™) can be a useful supplement to manage postprandial glucose levels, further studies are necessary to evaluate its potential in type 2 diabetes and the regulation of dysglycaemia.

An automatic recognizing system of white blood cells can assist hematologists in the diagnosis of many diseases, where accuracy and efficiency are paramount for computer-based system. In this paper, we present a new image processing system to recognize the five types of white blood cells in peripheral blood with marked improvement in efficiency when juxtaposed against mainstream methods. The prevailing deep learning segmentation solutions often utilize millions of parameters to extract high-level image features and neglect the incorporation of prior domain knowledge, which consequently consume substantial computational resources and increase the risk of overfitting, especially when limited medical image samples are available for training. To address these challenges, we propose a novel memory-efficient strategy that exploits graph structures derived from the images. Specifically, we introduce a lightweight superpixel-based Graph Neural Network (GNN) and break new ground by introducing superpixel metric learning to segment nucles and cytoplasm. Remarkably, our proposed segmentation model (SMGNN) achieves state-of-the-art segmentation performance while utilizing at most 10000$\times$ less than the parameters compared to existing approaches. The subsequent segmentation-based cell type classification processes show satisfactory results that such automatic recognizing algorithms are accurate and efficient to execeute in hematological laboratories.

Knowledge on the health of banana trees is critical for farmers to profit from banana cultivation. Fusarium wilt and banana blood diseases (BDB), two significant diseases infecting banana trees, are caused by Fusarium oxysporum and Ralstonia syzygii, respectively. They have successfully caused a decline in crop yield as they destroy the trees, starting sequentially from the pseudostem to the fruits. The entire distribution of BDB and Fusarium on a plantation can be understood using advanced geospatial information obtained from multispectral aerial photographs taken using an unmanned aerial vehicle (UAV), combined with the reliable data field of infected trees. Vegetation and soil indices derived from a multispectral aerial photograph, such as normalized difference vegetation index, modified chlorophyll absorption ratio index, normalized difference water index (NDWI) and soil pH, may have to be relied on to explain the precise location of these two diseases. In this study, a random forest algorithm was used to handle a large dataset consisting of two models: the banana diseases multispectral model and the banana diseases spectral model. The results show that the soil indices, soil pH and NDWI are the most important variables for predicting the spatial distribution of these two diseases. Simultaneously, the plantation area affected by BDB is more extensive than that affected by Fusarium, if the variation of planted banana cultivars is not considered.

(1) Background: Motor neuron diseases (MNDs) are fatal neurodegenerative diseases. Biomarkers could help in defining patients’ prognosis and stratification. Beyond neurofilaments, chitinases are a promising family of possible biomarker, which correlate with neuroinflammatory status. We evaluated plasmatic levels of CHI3L1 in MNDs, MND mimics and healthy controls (HCs); (2) Methods: We used Sandwich ELISA to quantify CHI3L1 in plasma samples from 44 MNDs, 7 HSP, 9 MND mimics and 19 HCs. We collect also ALSFRSr scale, MRC scale, spirometry, mutational status, progression rate (PR), blood sampling, neuropsychological evaluation; (3) Results: Plasma levels of CHI3L1 resulted to be different among groups (p= 0.005). Particularly, MND mimics showed higher CHI3L1 levels compared to MNDs and HCs. CHI3LI levels did not differ among PMA, PLS and ALS and we do not find correlation among CHI3L1 levels and clinical scores, spirometry parameters, PR, and neuropsychological features. Of note, red blood cells count and haemoglobin correlated with CHI3L1 levels (respectively, p&lt;0.001, r=0.63; p= 0.022, r=0.52); (4) Conclusions: CHI3L1 plasma levels resulted to be increased in the MND mimics cohort when compared to MNDs. The increase of CHI3L1 in neuroinflammatory processes could explain our findings. We confirmed that CHI3L1 plasma levels did not differentiate between ALS and HCs and nor correlate with neuropsychological impairment.

The alkaloid tazopsine 1 was introduced in the late 2000's as a novel antiplasmodial hit compound active against Plasmodium falciparum hepatic stages, with potential to develop prophylactic drugs based on this novel chemical scaffold. However, the structural determinants of tazopsine 1 bioactivity, together with the exact definition of the pharmacophore, remained elusive, impeding further development. We found that the antitussive drug dextromethorphan (DXM) 3, although lacking the complex pattern of stereospecific functionalization of the natural hit, was harboring significant antiplasmodial activity in vitro despite suboptimal prophylactic activity in a murine model of malaria, which precluded its direct repurposing against malaria. The targeted N-alkylation of nor-DXM 15 delivered a small library of analogues with greatly improved activity over DXM 3 against P. falciparum asexual stages. Amongst these, N-2’-pyrrolylmethyl-nor-DXM 16i showed a 2- to 36-fold superior inhibitory potency compared to tazopsine 1 and DXM 3 against parasite liver and blood stages, with 760 ± 130 nM and 2.1 ± 0.4 µM IC50 values, respectively, as well as liver/blood phase selectivity of 2.8. Furthermore, cpd. 16i showed a 5 to 8-fold increase of activity relatively to DXM 3 against P. falciparum stages I-II and V gametocytes, with 18.5 µM and 13.2 µM IC50 values, respectively. Cpd. 16i can thus be considered a promising novel hit compound against malaria in the ent-morphinan series with putative pan-cycle activity, paving the way for further therapeutic development (e. g., investigation of its prophylactic activity in a mouse model of malaria).

There are evidences of shared biological mechanisms between obesity and hypertension during childhood in the adulthood, and loads of research literatures have proven that, it will cost the economies and health of nations profoundly if neglected. The Prevention and early diagnosis of cardiovascular risk factors such as overweight and hypertension is an essential strategy for control, effective treatment and prevention of its’ complications. The aim of the study is to assess the effect of school based Exercise and Life style Motivation Intervention (SEAL-MI) on adolescent's cardiovascular risk factors and academic performance. An experimental study was conducted among 1005 adolescents - 520 and 485 adolescents were randomly selected for control and study group, respectively. Demographic details and the data related to dietary habits, physical activity and sleep quality were collected by a structured interview questionnaire. The study group adolescents were given the SEAL-MI for six months which includes a school based rope exercise for 45 minutes per day for 5 days a week and a motivation intervention related to dietary habits, physical activity and sleep. Post-test 1 and 2 were done after 3 and 6 months of intervention. The prevalence of overweight among adolescents was 28.73% and prehypertension was 9.26%. Among overweight adolescents, the prevalence of prehypertension was found to be very high (32.25%). In post intervention, there was a significant reduction in weight, BP (p=0.000) and improvement in dietary habits, physical activity, sleep (p=0.000) and academic performance. A significant positive correlation was found between BMI and SBP (p=0.000) and BMI and academic performance (p=0.003). The linear regression analyses revealed that the gender (ß: 0.47, 95% CI: 0.39, 0.81), age (ß: 0.39, 95% CI: 0.17, 0.46), family income (ß: 0.2, 95% CI: 0.41, 0.5), residence (ß: 0.19, 95% CI: 0.01, 0.27) and type of family (ß: 0.25, 95% CI: 0.39, 0.02) had the strongest correlate with the BMI of the adolescents. Also, Mother’s education Mother’s education (ß: 0.35, 95% CI: 0.18, 0.59) had the strongest correlate with the SBP of the adolescents. In contrast, the DBP was negatively persuaded by age (ß: -0.36, 95% CI: 1.54, 0.29) and gender (ß: -0.26, 95% CI: 1.34, 0.12) of the adolescents. Regular practice of rope exercise and lifestyle modification such as diet, physical activity and sleep quality among adolescents prevent and control childhood CVD risk factors like overweight, hypertension. The SEAL-MI may lead to age appropriate development of adolescents and improves their academic performance and quality of life. Giving importance to the adolescents from urban habitat, from affluent nuclear family and catching them young will bring significant change in the disease burden.

A distinctive feature of the SARS-CoV-2 spike protein is its ability to efficiently fuse cells, thus producing syncytia found in COVID-19 patients. This commentary proposes how this ability enables spike to cause COVID-19 complications as well as side effects of COVID-19 vaccines, and suggests how these effects can be prevented..

Marine invertebrates are model organisms in several areas of biological sciences, being a source of massive biological information. Although, the scientific relevance of marine invertebrates, the research with them can be limited for their tissue characteristics and troubles for the replication of physical and chemical properties of seawater. Thence, the main goal of this laboratory workflow is to provide a useful methodological approach to reduce the experimental limitations during the study of marine invertebrates. The present study describes experimental methodologies for the collection, transport, and maintenance of sessile tunicates. Also, an approach to observe and characterize, a diverse population of blood cells in marine invertebrates, by several cytological stains and electron microscopy. Lastly, suggestions and protocols to extract quality RNA from samples with high concentrations of salts, pigments, secondary metabolites, and polysaccharides. This methodological approach can be easily adapted to other marine invertebrates, moreover uses low-cost reagents and widely available laboratory equipment. Making possible the study of different types of marine animals in diverse locations.

Probiotics make up a large and growing segment of the commercial market of dietary supplements and are touted as offering a variety of human health benefits. Some of the purported positive impacts of probiotics include, but are not limited to, stabilization of the gut microbiota, prevention of gastrointestinal disorders and modulation of the host immune system. Current research suggests that the immunomodulatory effects of probiotics are strain specific and vary in mode of action. Here, we examined the immunomodulatory properties of Bacillus subtilis strain DE111 in a healthy human population. In a randomized, double blind, placebo-controlled four-week intervention, we examined peripheral blood mononuclear cells (PBMCs) at basal levels pre- and post-treatment as well as in response to stimulation with bacterial lipopolysaccharide (LPS). We observed an anti-inflammatory effect of B. subtilis, manifested as a decrease in immune cell populations within the basal state along with an increase in anti-inflammatory immune cells in response to LPS stimulation. Overall gastrointestinal health, microbiota, and circulating and fecal markers of inflammation and gut barrier function were largely unaffected by DE111 treatment. These data suggest that the novel probiotic B. subtilis DE111 may have clinical applications in modulating immune homeostasis via anti-inflammatory mechanisms.

Background: The purpose was to develop a novel hypothetical method to increase the size of coronary arteries. Methods: In the long-term observation the coronary sizes were dilated in three unexpected scenarios. The coronary artery sizes were observed in patients with mitral stenosis (n=59) by angiogram prior to percutaneous balloon mitral valvuloplasty or valve replacement surgery for severe mitral stenosis. The coronaries of patients with patent ductus arteriosus who underwent surgical closure in the past (n=12) were examined by echocardiogram. Patients with renal failure on long-term dialysis through peripheral arterio-venous fistula without left ventricular hypertrophy (n=17) were studied by echocardiography. Normal age, weight and sex matched coronary sizes served as controls in the study. All these observations were made over a period of 11.5 years. Results: The sizes of coronaries in patients with mitral stenosis, patients who underwent closure for patent ductus arteriosus, and in patients on hemodialysis through arteriovenous fistulas were higher than normal controls (p<0.05, for all). A hypothetical model to increase the coronary sizes could be developed based on the analysis of the differential equations of Poiseuille’s. The proposed method is creating a peripheral arterio-venous fistula, which could be closed later electively by a percutaneous method/surgery. The closure time needs to be determined by experimental studies. The other methods could be a continuous exercise program or usage of beta-blockers. Conclusion: A novel hypothetical method of peripheral arteriovenous fistula formation could potentially increase the size of the coronaries, and this could be closed later.

CXCR4 is a chemokine receptor crucial in tumor progression, although the angiogenic role of CXCR4 in oral squamous cell carcinoma (OSCC) has not been investigated. Here we show that CXCR4 is crucial for tumor angiogenesis thereby supports tumor survival in OSCC. Immunohistochemistry on human clinical specimens revealed that CXCR4 and a tumor vasculature marker CD34 were co-distributed in tumor vessels in human OSCC specimens. To ask the effects of CXCR4 inhibition, we treated the OSCC-xenografted mice with AMD3100, so-called plerixafor, an antagonist of CXCR4. Notably, we found a unique pathophysiological structure defined as Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) induced by the CXCR4 antagonism. Treatment with AMD3100 increased necrotic area with the induction of hypoxia-inducible factor-1α in the xenografted tumors, suggesting that AMD3100-induced TAITN was involved in hypoxia and ischemia. Taken together, we demonstrated that CXCR4 plays a crucial role in tumor angiogenesis required for OSCC progression, whereas TAITN induced by CXCR4 antagonism could be an effective anti-angiogenic therapeutic strategy in OSCC treatment.

The authors determined mass concentrations of 12 elements (As, Cd, Cr, Cu, Mn, Ni, Pb, Se, Sr, Tl, V, Zn) in blood and urine taken from 100 rural children living in unremarkable condition in the West Ural region of the Russian Federation. We applied inductively coupled plasma mass spectrometry in conformity with Methodical Guidelines 4.1. 3230-14 (FR.1.31.2014.17064) designed by us and detailed in the paper. The article contains setting parameters for Agilent 7500cx quadrupole inductively coupled plasma mass spectrometer . The authors present grounds for an optimal scheme of samples preparation which helps to eliminate "matrix" effect and explain why it is advisable to use reaction/collision functioning mode as it enables interference overlaps suppression.To prepare whole blood samples for analysis, we used acid dissolution in concentrated nitric acid followed by centrifugation. The arithmetic mean (AM) of element content in blood amounted to 0.34 µg/l (As); 0.39 µg/l (Cd); 6.41 µg/l (Cr); 866.11 µg/l (Сu); 13.73 µg/l (Mn); 5.86 µg/l (Ni); 23.65 µg/l (Pb); 87.43 µg/l (Se); 33.54 µg/l (Sr); 0.04 µg/l (Tl); 0.16 µg/l (V); 4713.48 µg/l (Zn). The validity of the results was confirmed by means of SERONORM ^TM Whole Blood L2 standard samples (Norway). Urine samples were directly analyzed after 1/10 (V/V) dilution with 1% nitric acid solution. The arithmetic mean of element content of urine corresponded to 18.99 µg/l (As); 0.12 µg/l (Cd); 1.91 µg/l (Cr); 13.28 µg/l (Сu); 0.96 µg/l (Mn); 1.84 µg/l (Ni); 0.83 µg/l (Pb); 22.55 µg/l (Se); 239.09 µg/l (Sr); 0.16 µg/l (Tl); 0.68 µg/l (V); 270.56 µg/l (Zn). The validity of the results was confirmed by analyzing the SERONORM ^TM standard urine samples (Norway). Regional differences from levels found in other countries included higher concentrations of Cr, Mn and Ni in blood and lower levels of Se and Zn levels in West Ural children. Urine concentrations of West Ural children showed higher levels of As and Sr.

Background: Globally, hot cooked refined rice is consumed in large quantities and is a major contributor to dietary glycaemic load. This study aimed to compare the glycaemic potency of hot and cold stored parboiled rice to widely available medium grain white rice. Method: Twenty-eight healthy volunteers participated in a three treatment experiment where postprandial blood glucose was measured over 120 minutes after consumption of 140g of rice. Three rice samples were freshly cooked medium-grain white rice, freshly cooked parboiled rice, and parboiled rice stored overnight at 4 ºC. All rice was served warm at 65 ºC. Chewing time was recorded. Results: The 24-hours cold-stored and reheated parboiled rice resulted in a 42% and 12% lower blood glucose concentration trajectory than freshly cooked medium-grain white rice and freshly cooked parboiled rice. Chewing time for 10g cold stored parboiled rice was 6 seconds (25%) longer and was considered more palatable, visually appealing and better tasting than freshly cooked medium grain (all P<0.05). Conclusions:. For regular consumers of rice reheating cooked rice after cold storage would lower the dietary glycaemic load and long term may reduce risk for type 2 and gestational diabetes. More trials are needed to identify the significance.

This study investigates the effects of chanting Nam-Myoho-Renge-Kyo on sound frequencies, brain activity, and microbial metabolism. Spectral analysis of chanting revealed peaks at 8 Hz and 116 Hz, corresponding to the first Schumann resonance and a frequency linked to chloride ion movements, respectively. Additionally, five peaks corresponding to solfeggio frequencies were identified. These frequencies are known to exert a positive impact on the human endocrine and autonomous nervous systems; improve survival of human brain cells; decrease anxiety in rats; reverse cognitive and endocrine deficits in zebra fish; reduce total concentration of reactive oxidative species in brain tissue. Brain activity changes were measured using functional near-infrared spectroscopy. Prefrontal cortex activity increased modestly during chanting compared to a pre-chanting baseline, but significantly increased afterwards. This suggests a shift towards focused attention during chanting and enhanced activity afterward. The study also examines the effects of chanting on microbial metabolism. Cultures exposed to chanting, either directly or indirectly, showed increased metabolic activity. This suggests local and non-local effects, similar to previously reported phenomena. Importantly, the study clarifies that the spiritual practice of Nichiren Shoshu Buddhism can't be reduced to mere neurophysiological mechanisms in the brain or any other part of the body. The religious and spiritual experience of practicing Buddhism and chanting Nam-Myoho-Renge-Kyo goes well beyond brain activity, neurotransmitters or quantum phenomena of consciousness. It encompasses a mystic dimension that, although not in contradiction with science, can’t be explained solely by science.

Brain pathological changes impair cognition early in disease etiology. There is an urgent need for understanding aging-linked mechanisms of early memory loss to develop therapeutic strategies and prevent the development of cognitive impairment. Tusc2, also named Fus1, is a mitochondrial-resident protein regulating Ca2+ fluxes to and from mitochondria impacting overall health. We reported that Tusc2-/- female mice develop chronic inflammation and age prematurely, causing age- and gender-dependent spatial memory deficits at 5 m.o. Therefore, we investigated Tusc2-dependent mechanisms of memory impairment in mice, comparing changes in resident and brain-infiltrating immune cells. Interestingly, Tusc2-/- female mice demonstrated proinflammatory increase in astrocytes, IFN-γ expression in CD4+T cells and Granzyme-B in CD8+T cells. We also found fewer FOXP3+ T-regulatory cells and Ly49G+ NK and Ly49G+ NKT cells in female Tusc2-/- brain, suggesting a weakened anti-inflammatory response. Moreover, Tusc2-/- hippocampi exhibited Tusc2- and sex-specific protein changes associated with brain plasticity, including mTOR activation, and Calbindin and CamKII dysregulation affecting intracellular Ca2+ dynamics. Overall, data suggest that dysregulation of Ca2+-dependent processes and proinflammatory brain microenvironment heighten in Tusc2-/- mice could underlie cognitive impairment. Thus, strategies to modulate the brain’s Tusc2-, Ca2+, and mitochondria-dependent pathways should be explored to improve cognitive health.

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

Motor intention is a high-level brain function related to planning for movement. Although studies have shown that motor intentions can be decoded from brain signals before movement execution, it was unclear whether intentions relating to mental imagery of movement could be decoded. Here, we investigated whether differences in spatial and temporal patterns of brain activation were elicited by intentions to perform different types of motor imagery and whether the patterns could be used by a multivariate pattern classifier to detect such differential intentions. The results showed that it is possible to decode intentions before the onset of different types of motor imagery from functional MR signals obtained from fronto-parietal brain regions, such as the premotor cortex and posterior parietal cortex, while controlling for eye movements and for muscular activity of the hands. These results highlight the critical role played by the aforementioned brain regions in covert motor intentions. Moreover, they have substantial implications for rehabilitating patients with motor disabilities.

Few studies have examined the dietary protein intake and sources in combination with the longitudinal changes in brain structure markers. Our study aimed to examine the association between dietary protein intake and different sources of dietary protein with the longitudinal rate of change in brain structural markers. A total of 2723 and 2679 participants from the UK Biobank were included in the analysis. The relative and absolute amounts of dietary protein intake were calculated through a 24-hour dietary recall questionnaire. The longitudinal change rates of brain structural biomarkers were computed using two waves of brain imaging data. We utilized multiple linear regression to examine the association between dietary protein and different sources and the longitudinal changes in brain structural biomarkers. Restrictive cubic splines were used to explore nonlinear relationships, and stratified and sensitivity analyses were conducted. Increasing the proportion of animal protein in dietary protein intake is associated with a slower reduction in the total hippocampus volume (THV, β: -0.02524, P&lt;0.05), left hippocampus volume (LHV, β: -0.02435, P&lt;0.01) and right hippocampus volume (RHV, β: -0.02544, P&lt;0.05).Higher intake of animal protein relative to plant protein is linked to a lower atrophy rate in THV (β: -0.01249, P&lt;0.05) and LHV (β: -0.01173, P&lt;0.05) and RHV (β: -0.01193, P&lt;0.05). Individuals with higher intake of seafood exhibit lower longitudinal rate of change in HV compared to those with no consume (THV, β: -0.004514; P&lt;0.05; RHV, β: -0.005527, P&lt;0.05). In subgroup and sensitivity analyses, there was not a significantly alteration. A moderate increase in the intake and proportion of animal protein in the diet, especially from seafood, is associated with a lower longitudinal change rate in hippocampus volume.

A great deal of studies have assessed the expression of noncoding RNAs (ncRNAs) as well as their relevant molecular functions and biological mechanisms in the individuals of alcohol dependence. Alcohol dependence is one of the most prevalent neuropsychological disorders worldwide, and its pathogenesis is intricate and inadequately understood. There is considerable evidence demonstrating substantial links between multiple genetic factors and the development of alcohol dependence. Critical roles of ncRNAs have been emphasized in the pathophysiology of mental diseases including alcohol dependence. In the comprehension of ncRNAs action and their mechanisms of modification, they have emerged as therapeutic targets for a variety of psychiatric illness including alcohol dependence. Worth mentioning, dysregulated expression of ncRNAs has been regularly detected in individuals of alcohol dependence. An in-depth knowledge of roles of ncRNAs and m6A modification may be valuable for the development of a novel treatment against alcohol dependence. In general, a deeper comprehension of functional roles ncRNAs may make significant contributions to the precise diagnosis and/or actual treatment of alcohol dependence. Here in this review, we mostly focused on the up-to-date knowledge regarding alterations and/or modifications in the expression of ncRNAs in alcohol dependence, and then, presented their prospects for future research and therapeutic application with a novel concept of engram-system.

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

The advent of deep learning (DL) has revolutionized medical imaging, offering unprecedented avenues for accurate disease classification and diagnosis. DL models have shown remarkable promise for classifying brain tumor from Magnetic Resonance Imaging (MRI) scans. However, despite their impressive performance, the opaque nature of DL models poses challenges in understanding their decision-making processes, particularly crucial in medical contexts where interpretability is essential. This paper explores the intersection of medical image analysis and DL interpretability, aiming to elucidate the decision-making rationale of DL models in brain tumor classification. Leveraging state-of-the-art DL frameworks with transfer learning, we conduct a comprehensive evaluation encompassing both classification accuracy and interpretability. Using state-of-the-art DL frameworks with transfer learning, we conduct a thorough evaluation covering both classification accuracy and interpretability. We employ adaptive path-based techniques to understand the underlying decision-making mechanisms of these models. Grad-CAM and Grad-CAM++ highlight critical image regions where the tumors are located.

Traumatic brain injury (TBI) stands as a prominent global cause of disability, with motor deficits being a common consequence. Despite its widespread impact, the precise pathological mechanisms underlying motor deficits after TBI remain elusive. In this study, hindlimb postural asymmetry (HL-PA) development in rats subjected to focal TBI was investigated to explore the potential roles of laminin and collagen IV within the ECM of selected hindlimb muscles in the emergence of motor deficits following TBI. A focal TBI was induced by ablating the left sensorimotor cortex in rats and motor deficits were assessed by measuring HL-PA. The expression of laminin and collagen IV in eight selected muscles on each side of the hindlimbs from both TBI and sham-operated rats were studied using immunohistochemistry and semi-quantitatively analyzed. Results indicated that the TBI rats exhibited HL-PA, characterized by flexion of the contralateral (right) hindlimb. In the sham-operated rats the immunoreactive components of laminin and collagen IV were evenly and smoothly distributed along the border of the muscle fibers in all the investigated muscles. In contrast, in the TBI rats the pattern was broken into aggregated granule-like immunoreactive components. Such a labeling pattern was detected in all the investigated muscles both from the contra-and ipsilateral side of the TBI rats. However, in TBI rats most of the muscles from the contralateral hindlimb showed a significant increased expression of these two proteins in comparison with those from the ipsilateral hindlimb. In comparison to sham-operated rats, there was a significant increase in laminin and collagen IV expression in various contralateral hindlimb muscles in the TBI rats. These findings suggest potential implications of laminin and collagen IV in the development of motor deficits following a focal TBI.

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

Cancers of the brain and nervous system account for 1 in every 100 cancer diagnoses in the United States and about 0.3 million diagnoses globally, every year. Surgery, radiotherapy, and chemo-therapy constitute the standard of care. Despite advancements in diagnosis and treatment delivery, mortality rate for these cancers have remained steady for over three decades. Immunotherapy is an emerging fourth treatment modality which has been effective against several cancers but not brain cancers, such as glioblastoma, GBM. Here, we develop in vitro assays to quantify molecular readouts of cell death, cell migration and clonogenicity, and synopsize these as biophysical markers for the rapid evaluation of immune checkpoint inhibitors (ICI), durvalumab and pembrolizumab, alone and in combination with radiotherapy (radioimmunotherapy). We find different trends in their direct action on two GBM cell lines (T98G and U87), even in the absence of immune cells. Radiation alone, and pembrolizumab with radiation, both reduced (p < 0.05) cell-cell adhesion. This reduction suggests increased potential for local invasion. Our assays offer additional insights regarding ICIs, may enable evaluation of their potential efficacy, and could set the stage for pa-tient-specific radioimmunotherapy against brain cancers, engendering improved treatment out-comes.

(1) Background: Environmental and public health research has given considerable attention to the impact of air quality on brain health, with systematic reviews widespread. No literature review has been done for cognitive frailty – a multidimensional syndrome combining physical frailty and cognitive impairment and their apparent co-dependence, linked to increased vulnerability and adverse health outcomes, including dementia. Instead, cognitive decline and frailty is implicitly explored through research on air quality and comorbid cognitive and physical decline in elderly populations. (2) Methods: A scoping review was conducted to explore the need for a systematic review. Combining Arksey and O’Malley [1] and PRISMA-ScR checklist [2], a scoping review of SCOPUS using ‘cogniti*’ + ‘resilience’ + ‘air quality’ or ‘cogniti*’ + ‘ageing’ + ‘air quality’ resulted in N=2503 articles, screened and reduced using inclusion and exclusion criteria, to N=16 articles. (3) Results: Air quality appears to be a critical risk factor for cognitive decline, even at air quality levels below WHO targets. Moderate long-term ambient air pollution appears linked to increased risk of cognitive frailty, suggesting earlier and more active interventions to protect older people. There are varied effects on cognition across the life course, with both emotional and functional impacts. Effects may be more detrimental to elderly people with existing conditions, including economic and health inequalities. Generalisation of results is limited due to the absence of a dose-response, variations in methods, controlling for comorbid effects, and variance across studies. (4) Conclusions: The findings support the need for more research and a more extensive summary of the literature.

Research conducted on individuals with depression reveals that major depressive disorders (MDDs) coincide with diminished levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain, as well as modifications in the subunit composition of the primary receptors (GABAA receptors) responsible for mediating GABAergic inhibition. Furthermore, there is substantial evidence supporting the significant role of GABA in regulating stress within the brain, which is a pivotal vulnerability factor in mood disorders. Although there is substantial evidence indicating that GABA may be affecting GABA receptors in peripheral tissues, there is comparatively less evidence supporting its direct action within the brain. Emerging evidence highlights that GABA may exert beneficial effects on the brain and psyche through the gut-brain axis. GABA is readily available and approved as a food supplement in many countries. While GABA enjoys wide consumer acceptance in Eastern Asian markets, with many consumers reporting favorable effects on stress regulation, mood, and sleep, rigorous independent research is still largely lacking. Basic research, coupled with initial clinical findings, makes GABA an intriguing neuro-nutritional compound deserving of clinical studies in individuals with depression and other psychological problems.

Emotion recognition and social inference impairments are well-documented post-traumatic brain injury (TBI) yet the mechanisms underpinning these are not fully understood. We examined dynamic emotion recognition, social inference abilities, and eye fixation patterns between adults with and without TBI. Eighteen individuals with TBI and 18 matched non-TBI participants were recruited and underwent all three components of The Assessment of Social Inference Test (TASIT). The TBI group were less accurate in identifying emotions compared to the non-TBI group. Individuals with TBI also scored lower when distinguishing sincere and sarcastic conversations but scored similarly to those without TBI during lie vignettes. Finally, those with TBI also had difficulty understanding the actor’s intentions, feelings, and beliefs compared to participants without TBI. No group differences were found for eye fixation patterns and there were no associations between fixations and behavioural accuracy scores. This conflicts with previous studies and might be related to an important distinction between static and dynamic stimuli. Visual strategies appeared goal- and stimulus-driven, with attention being distributed to the most diagnostic area of the face for each emotion. These findings suggest that low-level visual deficits may not be modulating emotion recognition and social inference disturbances post-TBI.

Intracortical microelectrode arrays (MEAs) can be used in a range of applications, from basic neuroscience research to providing an intimate interface with the brain as part of a Brain-Computer Interface (BCI) system aimed to restore function for people living with neurological disorders or injuries. Unfortunately, MEAs tend to fail prematurely, leading to a loss in functionality for many applications. An important contributing factor in MEA failure is oxidative stress resulting from chronically inflammatory-activated microglia and macrophages releasing reactive oxygen species (ROS) around the implant site. Antioxidants offer a means for mitigating oxidative stress and improving tissue health and MEA performance. Here, we investigate using the clinically available antioxidant dimethyl fumarate (DMF) to reduce the neuroinflammatory response and improve MEA performance in a rat MEA model. Daily treatment of DMF for 16 weeks resulted in a significant improvement in the recording capabilities of MEA devices during the sub-chronic (Weeks 5-11) phase (42% active electrode yield vs. 35% for control). However, these sub-chronic improvements were lost in the chronic implantation phase, as a more exacerbated neuroinflammatory response occurs in DMF-treated animals by 16 weeks post-implantation. Yet, neuroinflammation was indiscriminate between treatment and control groups during the sub-chronic phase. Although worse for chronic use, a temporary improvement (&lt;12 weeks) in MEA performance is meaningful. Providing short-term improvement to MEA devices using DMF can allow for improved use for limited-duration studies. Further efforts should be taken to explore the mechanism behind a worsened neuroinflammatory response at the 16-week time point for DMF-treated animals to assess its usefulness to specific applications.

When “hijacked” by compulsive behaviors that affect the reward and stress centers of the brain, functional changes in dopamine circuitry occur as the consequence of pathological brain adaptation. As a brain explanans for mental health, with a central functional role in behavioral regulation from healthy reward seeking to pathological adaptation to stress in response to adversity, we may use dopamine regulation in interaction with other brain mechanisms, as discussed herein, to gather a deeper insight into environmentally triggered mental health changes to understand, for example, specific behavioral changes observed during and after the COVID-19 pandemic. Pandemic-related adversities, the stresses they engendered, and the long lockdown periods where people had to rely on digital tools to get feed-back rewards via the internet can be seen as the major triggers of changes in motivation and reward seeking behavior worldwide. The pathological adaptation of dopamine-mediated reward circuitry in the brain offers a highly plausible explanation why, when pushed by fate and circumstance into a physiological brain state of anti-reward, human behavior and mental health changes almost inevitably depending on individual vulnerability to stress. A unified conceptual account that places dopamine function at the centre of the current global mental health context is proposed.

Brain-computer interfaces (BCI) from electroencephalography (EEG) provide a practical approach to support human-technology interaction. In particular, motor imagery (MI) is a widely-used BCI paradigm that guides the mental trial of motor tasks without physical movement. Here, we present a deep learning methodology, named Kernel-based Regularized EEGNet (KREEGNet), leveled on Centered Kernel Alignment and Gaussian Functional Connectivity, explicitly designed for EEG-based MI classification. The approach proactively tackles the challenge of intra-subject variability brought on by noisy EEG records and the lack of spatial interpretability within end-to-end frameworks applied for MI classification. KREEGNet is a refinement of the widely accepted EEGNet architecture, featuring an additional kernel-based layer for regularized Gaussian functional connectivity estimation based on CKA. The superiority of KREEGNet is evidenced by our experimental results from binary and multi-class MI classification databases, outperforming the baseline EEGNet and other state-of-the-art methods. Further exploration of our model’s interpretability is conducted at individual and group levels, utilizing classification performance measures and pruned functional connectivities. Our approach is a suitable alternative for interpretable end-to-end EEG-BCI based on deep learning.

Mild TBI (mTBI) accounts for most TBI cases, the leading cause of morbidity and mortality worldwide. Despite their high incidence, mTBI pathophysiology remains largely unknown. Recent studies have shown that the inflammatory response is activated early after mTBI and can persist for several weeks or months. However, limited evidence on the utility of inflammatory biomarkers as predictors of clinical outcomes in mTBI was previously provided. Thus, this study aims to provide an overview of the current knowledge on the role of inflammation in the pathogenesis of mTBI and the potential of some inflammatory biomolecules as biomarkers of mTBI. Thus, it was shown that the increase of IL-6, TNF-α, and IL-1β plasma levels could be implicated in the development of the early post-concussion symptoms. On the other hand, the persistence of the increased plasmatic concentrations of IL-10 and IL-8 for as long as six months following the brain injury event could suggest chronic inflammation leading to neuroinflammation and late or persistent symptoms. In this context, our findings showed that the inflammatory biomarkers could be relevant in diagnosing or predicting recovery or long-term outcomes of mTBI.

This review examines the evidence supporting the role of dysbiosis in the development of obses-sive-compulsive disorders (OCD). We review the molecular mechanisms and role of the microbiota in the microbiota-gut-brain axis, focusing on the endocrine, nervous, and immune pathways. We then propose a model that positions dysbiosis as the central unifying element in the neurochemi-cal, immunological, genetic, and environmental factors leading to OCD. Based on this, we review the animal and human clinical evidence for the use of microbial reprogramming strategies such as probiotic or fecal microbiota transplants to treat OCD. Finally, we discuss the unique challenges that must be addressed in future clinical interventions.

Deep-Brain Stimulation (DBS) is a a highly effective and safe medical treatment that improves the lives of patients with a wide range of neurological and psychiatric deceases, and has been consolidated as a first-line tool in the treatment of these conditionsin the last two decades. Closed Loop Deep-Brain Stimulation (CLDBS) pushes this tool further by automatically adjusting the stimulation parameters to the brain response in real time. In this context, this paper presents a Low-Noise Amplifier (LNA) and a Neurostimulator circuits fabricated in the low-power/low-voltage 65 nm CMOS process from the TSMC, which were designed targeting implantable applications. To achieve the best trade-off between input-referred noise and power consuption, metaheuristic algorithms were employed to determine and optimizes the dimentions of the LNA devices during the design phase. The measurement results showed that the LNA had a gain of 40.6 dB, a 3 dB bandwidth spanning over three decades from 10 Hz to 8.6 kHz, and a power consumption of 6.19 uW. Simulations results indicated an input-referred noise of 4.86 uVrms for the LNA. The circuit of the Neurostimulator is a programmable Howland Current-Pump, whose measurements showed its ability to generate currents with arbitrary shapes ranging from between 325 uA to +318 uA. The simulations showed a quiescent power consumption of 0.13 W with a zero neurostimulation current. The LNA and the Neurostimulator circuits are supplied with 1.2 V voltage and occupy a microdevice area of 145 um x 311 um and 88 um x 89 um, respectively, making them suitable for implantation in applications involving Closed Loop Deep-Brain Stimulation.

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

Traumatic brain injury (TBI) is a major leading cause of death and disability. While previous studies regarding focal pathologies following TBI have been done, there is a lack of information concerning the role of analgesics and their influences on injury pathology. Buprenorphine (Bup), an opioid analgesic, is a commonly used analgesic in experimental TBI models. Our previous studies investigated the acute effects of Buprenorphine-sustained release-Lab (Bup-SR-Lab) on diffuse neuronal/glial pathology, neuroinflammation, cell damage, and systemic physiology. The current study investigated the longer-term chronic outcomes of Bup-SR-Lab treatment at 4 weeks following TBI utilizing a central fluid percussion injury (cFPI) model in adult male rats. Histological assessments of physiological changes, neuronal damage, cortical and thalamic cytokine expression, microglial and astrocyte morphological changes, and myelin alterations were done, as we had done in our acute study. In the current study the Whisker Nuisance Task (WNT) was also performed pre- and 4w post-injury to assess changes in somatosensory sensitivity following saline or Bup-SR-Lab treatment. Bup-SR-Lab treatment had no impact on overall physiology or neuronal damage at 4w post-injury regardless of region or injury, nor did it have any significant effects on somatosensory sensitivity. However, greater IL-4 cytokine expression with Bup-SR-Lab treatment was observed compared to saline treated animals. Microglia and astrocytes also demonstrated region-specific morphological alterations associated with Bup-SR-Lab treatment, in which cortical microglia and thalamic astrocytes were particularly vulnerable to Bup-mediated changes. There were discernable injury-specific and region-specific differences regarding myelin integrity and changes in specific myelin basic protein (MBP) isoform expression following Bup-SR-Lab treatment. This study indicates that use of Bup-SR-Lab could impact TBI-induced glial alterations in a region-specific manor 4w following diffuse brain injury.

Development of the central nervous system (CNS) depends on accurate spatiotemporal control of signalling pathways and transcription programs. Forkhead Box G1 (FOXG1) is one of the master regulators that plays fundamental roles in forebrain development, from the timing of neurogenesis to the patterning of the cerebral cortex. Mutations in the FOXG1 gene cause a rare neurodevelopmental disorder called FOXG1 syndrome, also known as congenital form of Rett syndrome. Patients presenting with FOXG1 syndrome manifest a spectrum of phenotypes ranging from severe cognitive dysfunction and microcephaly to social withdrawal and communication deficits with varying severities. To develop and improve therapeutic interventions, there has been considerable progress towards unravelling the multi-faceted functions of FOXG1 in neurodevelopment and pathogenesis of FOXG1 syndrome. Moreover, recent advances in genome editing and stem cell technologies, as well as increased yield of information from high throughput omics opened promising and important new avenues in FOXG1 research. In this review, we provide a summary of clinical features and emerging molecular mechanisms underlying FOXG1 syndrome, and explore disease-modelling approaches in animals and human-based systems to highlight prospects of research and possible clinical interventions.

Functional connectivity (FC) is a potential candidate that can increase the performance of brain-computer interfaces (BCIs) in the elderly because of its compensatory role in neural circuits. However, it is difficult to decode FC by current machine learning techniques because of a lack of its physiological understanding. To investigate the suitability of FC in BCI for the elderly, we propose the decoding of lower- and higher-order FCs using a convolutional neural network (CNN) in six cognitive-motor tasks. The layer-wise relevance propagation (LRP) method describes how age-related changes in FCs impact BCI applications for the elderly compared to younger adults. Seventeen younger (24.5±2.7 years) and twelve older (72.5±3.2 years) adults were recruited to perform tasks related to hand-force control with or without mental calculation. CNN yielded a six-class classification accuracy of 75.3% in the elderly, exceeding the 70.7% accuracy for the younger adults. In the elderly, the proposed method increases the classification accuracy by 88.3% compared to the filter-bank common spatial pattern (FBCSP). LRP results revealed that both lower- and higher-order FCs were dominantly overactivated in the prefrontal lobe depending on task type. These findings suggest a promising application of multi-order FC with deep learning on BCI systems for the elderly.

The members of the IgLON superfamily of cell adhesion molecules facilitate fundamental cellular communication during brain development, maintain functional brain circuitry, and are associated with several neuropsychiatric disorders. Usage of alternative promoter-specific 1a and 1b mRNA isoforms in Lsamp, Opcml, Ntm and the single promoter of Negr1 in the mouse and human brain has been previously described. To determine the precise spatiotemporal expression dynamics of Lsamp, Opcml, Ntm isoforms and Negr1, in the developing brain, we generated isoform-specific RNA probes and carried out in situ hybridization in the developing (embryonic, E10.5, 13.5, 17; post natal, P0) and adult mouse brains. We show that promoter-specific expression of IgLONs is established early during pallial development (at E10.5), where it remains throughout its differentiation through adulthood. In the diencephalon, midbrain and hindbrain, strong expression patterns are initiated a few days later and begin fading after birth, being only faintly expressed during adulthood. Thus, the expression of specific IgLONs in the developing brain may provide the means for regionally specific functionality as well as for specific regional vulnerabilities. The current study will therefore improve the understanding of how IgLON genes are implicated in the development of neuropsychiatric disorders.

Background: Brain oxidative lipid damage and inflammation are common in neurodegenerative diseases such as Alzheimer’s disease (AD). Paraoxonase-1 and 3 (PON1 and PON3) protein expression have been described in tissues with no PON1 and PON3 gene expression. In the present study, we aimed to examine differences in PON1 and PON3 protein expression in the brain of a mouse model of AD. Methods: We used peroxidase-based and fluorescence-based immunohistochemistry in 5 brain regions (olfactory bulb, forebrain, posterior midbrain, hindbrain and cerebellum) of transgenic (Tg2576) mice with the Swedish mutation (KM670/671NL) responsible for a familial form of AD and corresponding wild-type mice. Results: We found intense PON1 and PON3 positive staining in star-shaped cells surrounding Aβ plaques in all Tg2576 mouse brain regions studied. Although we could not co-localize PON1 and PON3 with astrocytes, brain star-shaped cells, we found some co-localization of PON3 with microglia. Conclusions: These results suggest that 1) PON1 and PON3 cross the blood-brain barrier in discoidal HDLs and are transferred to specific brain cell types, and 2) PON1 and PON3 play an important role in preventing oxidative stress and lipid peroxidation in particular cell types, likely astrocytes and microglia, in AD pathology, and potentially in other neurodegenerative diseases

Optical coherence tomography (OCT) is one of the most promising, innovative and rapidly emerging intraoperative imaging modalities for neurosurgical guidance in brain tissue imaging, "optical biopsy", brain cerebral vascular detection, nerve fibers and white matter tracts detection. In this article, we provide a short survey of cross-polarization OCT and different types of OCT probes that can be used in routine neurosurgical practice. Through different types of probes there are multiple applications where OCT can play a highly complementary role in offering the real-time microscopic assessment and imaging of normal and pathological brain tissues. The biopsy-needle based probe for CP OCT was shown to be an effective instrument for brain tissue mapping and express estimation of tissue status as well as for detecting large blood vessels to prevent causing bleeding during biopsy sampling. The folded CP OCT probe for intraoperative use for brain tissue examination was shown as a potentially efficient sensor head for CP OCT. The probe demonstrated high lateral resolution in diffractive limited probing beam quality. The length of dismountable probe tip allows using the probe under operating microscope. Due to the designed family of specialized probes CP OCT fills in the niche of devices for express brain tissue examination in situ.

We derive time evolution equations, namely the Schrodinger-like equations and the Klein-Gordon equations for coherent fi elds and the Kadanoff-Baym (KB) equations for quantum fluctuations, in Quantum Electrodynamics (QED) with electric dipoles in 2 + 1 dimensions. Next we introduce a kinetic entropy current based on the KB equations in the 1st order of the gradient expansion. We show the H-theorem for the Leading-Order self-energy in the coupling expansion (the Hartree-Fock approximation). We show a conserved energy in the spatially homogeneous systems in the time evolution. We derive aspects of the super-radiance and the equilibration in our single Lagrangian. Our analysis can be applied to Quantum Brain Dynamics, that is QED with water electric dipoles. The total energy consumption to maintain super-radiant states in microtubules seems to be within the energy consumption to maintain the ordered systems in a brain.

Ischemic neuron loss contributes to brain dysfunction in patients with cardiac arrest (CA). Histidine–tryptophan–ketoglutarate (HTK) solution is a preservative used during organ transplantation. Can HTK also protect neurons from severe hypoxia (SH) following CA? We isolated rat primary cortical neurons and induced SH with or without HTK. Changes in caspase-3, hypoxia-inducible factor 1-alpha (HIF-1α), and NADPH oxidase-4 (NOX4) expression were evaluated at different time points till 72 h. Using a rat asphyxia model, we induced CA-mediated brain damage and then completed resuscitation. HTK or sterile saline was administered into the left carotid artery. Neurological deficit scoring and mortality were evaluated for 3 days. Then the rats were sacrificed for evaluating NOX4 and H2O2 level in blood and brain. In the in vitro study, HTK attenuated SH- and H2O2-mediated cytotoxicity in a volume- and time-dependent manner, associated with persisted HIF-1α expression, reductions in procaspase-3 activation and NOX4 expression. The inhibition of HIF-1α abrogated HTK’s effect on NOX4. In the in vivo study, neurological scores were significantly improved by HTK. H2O2 level, NOX4 activity and NOX4 gene expression were all decreased in the brain specimen of HTK-treated rats. Our results suggest that HTK acts as an effective neuroprotective solution.

The expression of non-coding RNAs varies greatly depending on the cell type and physiological state. Changes in expression affect the regulatory properties of these molecules. We investigated RNA-seq data from sorted blood cells of healthy control donors and severe COVID-19 patients. Our aim was to display a distinguishable piRNA differential expression portrait for each type of cell and to study the behavior of piRNA in the blood cells of COVID-19 patients. Overall piRNA expression in sorted control cells (erythrocytes, monocytes, lymphocytes, eosinophils, basophils, neutrophils) differs depending on cell type. Four of the most abundant piRNA were expressed relatively equally in all cell types, they included piR-49145, piR-49144, piR-49143 and piR-33151. By reviewing piRNA expression in each group of sorted cells from severe COVID-19 patients we observed 3 upregulated and 10 downregulated piRNAs in erythrocytes. Monocytes were presented with a larger amount of statistically significant piRNA, 4 upregulated and 35 downregulated. In lymphocytes, all 19 piRNAs were upregulated.

This article explores the relationship between metabolic syndrome and cardiovascular disease, providing a comprehensive overview of its risk factors and prevalence. Metabolic syndrome, characterized by a cluster of interconnected risk factors, significantly increases the likelihood of developing cardiovascular disease and type II diabetes. The study, conducted over a one-year period, involved 117 patients with ages between 30 to 79 years old. Various elements such as gender, age, education level, background, smoking, alcohol consumption, dietary aspects, physical activity, and their contribution in developing the metabolic syndrome, were analysed.Central adiposity and high blood pressure emerged as prominent elements of the condition. The findings underscore the importance of a healthy lifestyle in the prevention and management of metabolic syndrome. Encouraging regular physical activity, maintaining a balanced diet, rich in fresh vegetables and fruits, and avoiding harmful behaviours, such as smoking or alcohol consumption, are essential in reducing the risk of metabolic syndrome and its associated cardiovascular complications. The study highlights the need for public health initiatives, as well as individualized preventive strategies to combat the rising prevalence of metabolic syndrome. Through promoting awareness of its risk factors and implementing effective interventions, healthcare professionals can contribute to better cardiovascular health worldwide. Further research in this area will continue to enhance our understanding of the metabolic syndrome and refine preventive and therapeutic approaches for its management.

Circulating extracellular microvesicles (cEVs) are characterised by presenting surface antigens of parental cells. Since their biogenesis involves the translocation of phosphatidylserine (PS) from the inner to the outer-leaflet of the plasma membrane, exposed PS has been considered as a recognition hallmark of cEVs. However, not all cEVs externalise PS. In this study we have phenotypically and quantitatively characterised cEVs by flow cytometry with special attention to the proportions of PS in chronic heart failure patients (cHF; n=119) and reference non-HF group (n=21). PS─-cEVs were predominantly found in both groups. Parental markers showed differential pattern depending on PS exposure. Endothelium-derived and connexin 43-rich cEVs were mainly PS─-cEVs and significantly increased in cHF. On the contrary, platelet-derived cEVs were mostly PS+ and were increased in non-HF. We observed similar levels of PS+- and PS─-cEVs in non-HF subjects when analysing immune cell-derived EVs, but there was a subset-specific difference in cHF patients. Indeed, those cEVs carrying CD45+, CD29+, CD11b+ and CD15+ were mainly PS+-cEVs, while those carrying CD14+, CD3+ and CD56+ were mainly PS─-cEVs. In conclusion, endothelial and red blood cells are stressed in cHF patients as detected by a high shedding of cEVs. Despite PS+-cEVs and PS─-cEVs represent two distinct cEV populations, their release and potential function as both biomarkers and shuttles for cell communication seem unrelated to PS content.

Spinal muscular atrophy 5q (SMA) is the most common neuromuscular inherited disease in neonates which is associated with homozygous deletion of exon 7 in the SMN1 gene. Recently established drugs can improve the motor functions of SMA infants when treated in the pre-symptomatic stage. With aim of providing an early diagnosis, newborn screening (NBS) for SMA using real-time PCR assay with dried blood spots (DBS) was performed in Saint-Petersburg from January 2022 through November 2022. Here, 36,140 newborns were screened by GenomeX real-time PCR-based screening test, and three genotypes were determined. Homozygous deletion carriers (4 newborns), heterozygous carriers (772 newborns) and wild-type individuals (35,364 newborns) were identified. All four newborns screened positive for homozygous SMN1 deletion were confirmed by alternate methods. Two of the newborns had two copies of SMN2, and two of the newborns had three copies. We determined Saint-Petersburg spinal muscular atrophy incidence of 1 in 9,035 and SMA carrier frequency of 1 in 47. In conclusion, it can be summarized that providing both timely SMN1 information and confirmation along with SMN2 copy number as part of SMA newborn screening algorithm can significantly improve clinical follow-up, family members testing, and SMA patients' treatment.

Background. Cardiorespiratory fitness (CRF) is a predictor of chronic disease that is impractical to routinely measure in primary care settings. We used a new estimated cardiorespiratory fitness (eCRF) algorithm that uses information routinely documented in electronic health care records to predict abnormal blood glucose incidence. Methods: Participants were adults (17.8% female) 20-81 years old at baseline from the Aerobics Center Longitudinal Study between 1979 and 2006. eCRF was based on sex, age, body mass index, resting heart rate, resting blood pressure, and smoking status. CRF was measured by maximal treadmill testing. Cox proportional hazards regression models were established using eCRF and CRF as independent variables predicting the abnormal blood glucose incidence while adjusting for covariates. Results: Of 8,602 participants at risk at baseline, 3,580 (41.6%) developed abnormal blood glucose during an average of 4.9 years follow-up. The average eCRF of 12.03 ± 1.75 METs was equivalent to the CRF of 12.15 ± 2.40 METs within the 10% equivalence limit. In fully adjusted models, the estimated risks were the same (HRs = 0.96), eCRF (95% CIs = 0.93−0.99), and CRF (95% CI of 0.94−0.98). Each 1-MET increase was associated with a 4% reduced risk. Conclusion: Higher eCRF is associated with a lower risk of abnormal glucose. eCRF can be a vital sign used for research and prevention.

Background: A malfunction of the innate immune response in COVID-19 is associated with eosinopenia particularly in more severe cases. This study tested the hypothesis that this eosinopenia is COVID-19 specific and is associated with systemic activation of eosinophils.. Methods: Blood of 15 healthy controls and 75 adult patients with suspected COVID-19 at the ER were included before PCR testing and analyzed by point-of-care automated flow cytometry (CD10, CD11b, CD16 and CD62L) in the absence or presence of a formyl peptide (fNLF). 45 SARS-CoV-2 PCR positive patients were grouped based on disease severity. PCR negative patients with proven bacterial (n=20) or other viral (n=10) infections were used as disease controls. Eosinophils were identified with the use of the FlowSom algorithm. Results: Low blood eosinophil numbers (<100 cells/microL; p<0.005) were found both in patients with COVID-19 and with other infectious diseases albeit less pronounced. Two discrete eosinophil populations were identified in healthy controls both before and after activation with fNLF based on the expression of CD11b. Before activation, the CD11bbright population consisted of 5.4% (CI95% = 3.8, 13.4) of total eosinophils. After activation, this population of CD11bbright cells comprised nearly half the population (42.21%, CI95% = 35.9, 54.1). Eosinophils in COVID-19 had a similar percentage of CD11bbright cells before activation (7.6%, CI95% = 4.5, 13.6), but were clearly refractory to activation with fNLF as a much lower percentage of cells end up in the CD11bbright fraction after activation (23.7%, CI95% = 18.5, 27.6; p<0.001). Conclusion: Low eosinophil numbers in COVID-19 are associated with refractoriness in responsiveness to fNLF, which is likely caused by migration of fully functional cells to the tissue. Such homing might be beneficial as eosinophils have been implicated in viral killing.

Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) are environmental pollutants with a great persistence, capacity of bioaccumulation, and well known important toxic effects in humans and animals. Incinerators of hazardous, municipal and medical waste, chlorine bleaching of paper pulp, cement plants, and the traffic of motor vehicles are the most frequent emission sources of these compounds. The diet, followed at a great distance by inhalation, is generally the main way of human exposure to PCDD/Fs. Human biomonitoring is of a great importance to prevent potential adverse effects derived from exposure to chemicals such as PCDD/Fs. In relation to this, blood is among the most used biological monitors. In the current review, we have summarized the recent information (2000-2009) published in the scientific literature (databases: Scopus and PubMed) on the concentrations of PCDD/Fs in blood samples of non-occupationally exposed populations, as well as in some groups of occupationally exposed individuals. We have revised a number of studies conducted in various African American, Asian and European countries, and Australia. Unfortunately, the information is quite limited. No data are available for most countries over the world. Based on the results here reviewed –where available- the current health risks for the general populations do not seem to be of concern. Moreover, taking into account the important reductions observed in the levels of PCDD/Fs in foodstuffs, new decreases in the concentrations of PCDD/Fs in blood -and other biological tissues- are very probable in the immediate years.

We report on the development of chemical vapour deposition (CVD) based graphene field effect transistor (GFET) immunosensors for the sensitive detection of Human Chorionic Gonadotropin (hCG), a glycoprotein risk biomarker of certain cancers. The GFET sensors were fabricated on Si/SiO₂ substrate using photolithography with evaporated chromium and sputtered gold contacts. GFET channels were functionalized with a linker molecule to immobile anti-hCG antibody on the surface of graphene. Binding reaction of the antibody with varying concentration levels of hCG antigen demonstrated the limit of detection of the GFET sensors to be below 1 pg/mL using four-probe electrical measurements. We also show annealing can significantly improve the carrier transport properties of GFETs and shift the Dirac point (Fermi level) with reduced p-doping in back-gated measurements. The developed GFET biosensors are generic and could find applications in a broad range of medical diagnostics in addition to cancer, such as neurodegenerative (Alzheimer’s, Parkinson’s and Lewy body) and cardiovascular disorders.

Neurotrophins, particularly brain-derived neurotrophic factor (BDNF), act as key regulators of neuronal development, survival and plasticity. In this review, we focus on the role of BDNF for corticostriatal plasticity in movement disorders, including Parkinson’s Disease (PD) and dystonia. We discuss the mechanisms how dopaminergic input modulates BDNF/TrkB signaling at corticostriatal synapses and the involvement of these mechanisms in neuronal function and synaptic plasticity. Disruption of these pathways can lead to aberrant plasticity, ultimately affecting motor function. Advancing our understanding of these mechanisms could pave the way towards innovative therapeutic strategies aiming at restoring neuroplasticity and enhancing motor function in these diseases.

: Rasmussen’s encephalitis (RE) stands as a rare neurological disorder marked by progressive cerebral hemiatrophy and epilepsy resistant to medical treatment. Despite extensive study, the primary cause of RE remains elusive, while its histopathological features encompass cortical inflammation, neuronal degeneration, and gliosis. The underlying molecular mechanisms driving disease progression remain largely unexplored. In this case study, we present a patient with RE who underwent hemispherectomy and has remained seizure-free for over six months, experiencing gradual motor improvement. Further-more, we conducted molecular analysis on the excised brain tissue, unveiling a decrease in the expres-sion of cell cycle-associated genes coupled with elevated levels of BDNF and TNF-α proteins. These findings suggest potential involvement of cell cycle regulators in the progression of RE.

Huntington’s disease (HD) is a rare but progressive and devastating neurodegenerative disease characterized by involuntary movements, cognitive decline, executive dysfunction, and neuropsychiatric conditions such as anxiety and depression. It follows an autosomal dominant inheritance pattern. Thus, a child who has a parent with the mutated huntingtin (mHTT) gene has a 50% chance of developing the disease. Since HTT protein is involved in many critical cellular processes including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, and autophagy, its aberrant aggregates lead to disruption of numerous cellular pathways and neurodegeneration. Essential heavy metals are vital at low concentrations, however, at higher concentrations, can exacerbate HD by disrupting the glial-neuronal communication, and/or causing dysbiosis (disturbance in the gut microbiota, GM), both of which can lead to neuroinflammation and further neurodegeneration. Here, we discuss in detail the interactions of iron, manganese and copper with glial-neuron communication and GM and indicate how this knowledge may pave the way for development of a new generation of disease-modifying therapies in HD.

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

The article presents an accessible route into the field of neuroscience through ardEEG device. This device allows convert Arduino UNO R4 WIFI into a brain-computer interface, making it easy to measure EEG, EMG and ECG signals with 8 channels. Over the past decade, the proliferation of artificial intelligence has significantly impacted various industries, including neurobiology. The integration of machine learning techniques has opened avenues for practical applications of EEG signals across technology sectors. This surge in interest has led to the widespread popularity of low-cost brain-computer interface devices capable of recording EEG signals using non-invasive electrodes. ardEEG device demonstrates satisfactory noise levels and accuracy for use in applied tasks. Moreover, it successfully detects alpha brain waves, showcasing its effectiveness in capturing essential neurological signals

Objective: Mechanical bowel preparation is essential for the visualisation of the colon during colonoscopy, and previous studies have identified changes in gut microbiota composition after bowel preparation and colonoscopy. Considering the gut microbiota is increasingly implicated in mood, we aimed to explore the potential impact of this intervention on mood and the microbiota-gut-brain axis. Methods: We conducted a pre-post intervention study, with timepoints of one week before and one month after bowel preparation and colonoscopy, in community-dwelling adults referred for colonoscopy. Our primary outcome was change in average Hospital Anxiety and Depression Scale depression sub-scores using generalised estimating equations. We also examined changes in average anxiety, stress, and quality of life scores, and faecal microbiota composition and potential function using 16S rRNA sequencing. We further explored associations between changes in depressive symptoms and the gut microbiota and conducted post-hoc analyses to explore potential effect modifiers. Key Results: 59 participants were included in the analyses. Depressive symptoms decreased one-month post-procedure compared to baseline (adjusted β=−0.64; 95%CI: −1.18, −0.11). Irritable bowel syndrome (IBS) appeared to moderate this relationship (1.78; 0.292, 3.26); depressive symptoms increased in those with, and decreased in those without, IBS. Changes in gut microbiome composition included reduced alpha diversity, modest effects on beta-diversity, and increases in genera associated with potential health benefits, one-month post-procedure compared to baseline. Increases in the CLR-transformed abundance of Ruminococcaceae UCG-009 were associated with improvements in depressive symptoms. Conclusions: There is preliminary evidence of a potential mental health effect of bowel preparation and colonoscopy, which may be associated with changes to the gut microbiota. There may also be a differential mental health impact of this procedure for those with and without IBS. Considering the limitations of our study, further research is required to confirm these findings and their clinical relevance.

Hydrogen sulfide (H2S) is an environmental toxicant of health concern. The brain is a major target in acute H2S poisoning. This study was to test the hypothesis that acute and subchronic ambient H2S exposures alter the brain metabolome. Male 7-8 week-old C57BL/6J mice were exposed by whole-body inhalation to 1000 ppm H2S for 45 min and euthanized at 5 min or 72 h for acute exposure. For subchronic study, mice were exposed to 5 ppm H2S 2 h/day, 5 days/week for 5 weeks. The brainstem was removed for metabolomic analysis. Enrichment analysis showed the metabolomic profiles in acute and subchronic H2S exposures matched with those of cerebral spinal fluid from patients with seizures or Alzheimer’s disease. Acute H2S exposure decreased excitatory neurotransmitters, aspartate and glutamate, while the inhibitory neurotransmitter, serotonin, was increased, which may explain H2S-induced loss of consciousness. Branched-chain amino acids and glucose were increased by acute H2S exposure. Subchronic H2S exposure within OSHA guideline surprisingly decreased serotonin altering central nervous system. In subchronic H2S exposure, glucose was decreased while polyunsaturated fatty acids, inosine, and hypoxanthine were increased. Collectively, these results provide important mechanistic clues of acute and subchronic ambient H2S poisonings and show that H2S alters brainstem metabolome.

Long Covid is a heterogeneous clinical condition in which Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and brain fog stand out among the different clinical symptoms and syndromes. The cerebral metabolic alterations and neuroendocrine disorders seem to constitute an important part of Long Covid. Given the substantial lack of drugs and effective therapeutic strategies, hypothalamic phospholipid liposomes which have been on the market for several years as adjuvant therapy of cerebral metabolic alterations resulting from neuroendocrine disorders, can be taken into consideration in an overall therapeutic strategy that aims to control the Long Covid associated symptoms and syndromes. Their pharmacological mechanisms and clinical effects strongly support their usefulness in Long Covid. Our initial clinical experience corroborates this rationale. Further research is imperative in order to obtain robust clinical evidence.

Background: Post-delivery period could be characterized by psychological distress (e.g., anxiety, sadness, and irritability), leading to post-partum depression (PPD). Objective: The present clinical study assess the effect of probiotic supplementation containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4x10⁹ CFU/day) on mother’s mood and breastfeeding quality during the first trimester after delivery. Methods: A Randomized Double Blind Controlled (RDBPC) trial has been carried out in 200 healthy new mothers divided into an active group taking a supplement containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4x10⁹ CFU/day) plus multivitamins, and a control group (multivitamin complex only) for 90 days. Symptoms related to maternal depression and breastfeeding quality were evaluated at days 45 and 90 by Edinburgh Postnatal Depression Scale (EPDS) and Breastfeeding Self-Efficacy Scale Short-Form (BSES-SF). Results: At days 45 and 90, probiotic treatment significantly ameliorated the mothers’ mood compared to the control treatment (p<0.001). Likewise, breastfeeding quality and baby’s cries significantly improved in the probiotic group (p<0.001). Conclusions: Microbiota alterations could influence post-delivery woman’s mental state. According to our results, L. reuteri PBS072 and B. breve BB077 are potential candidates able to improve stress resilience in the post-partum period.

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

In this paper, we propose an imagined speech-based brain wave pattern recognition using deep learning. Multiple features were extracted concurrently from eight-channel Electroencephalography (EEG) signals. To obtain classifiable EEG data with fewer number of sensors, we placed the EEG sensors on carefully selected spots on the scalp. To decrease the dimensions and complexity of the EEG dataset and to avoid overfitting during the deep learning algorithm, we utilized the wavelet scattering transformation. A low-cost 8-channel EEG headset was used with MATLAB 2023a to acquire the EEG data. The Long-Short Term Memory Recurrent Neural Network (LSTM-RNN) was used to decode the identified EEG signals into four audio commands: Up, Down, Left, and Right. Wavelet scattering transformation was applied to extract the most stable features by passing the EEG dataset through a series of filtration processes. Filtration has been implemented for each individual command in the EEG datasets. The proposed imagined speech-based brain wave pattern recognition approach achieved a 92.50% overall classification accuracy. This accuracy is promising for designing a trustworthy imagined speech-based Brain-Computer Interface (BCI) future real-time systems. For better evaluation of the classification performance, other metrics were considered, and we obtained 92.74%, 92.50% and 92.62% for precision, recall, and F1-score, respectively.

The enteric nervous system (ENS) is a neural network referred to as "the brain in the gut" because of its similarities to the central nervous system (CNS). The ENS consists of numerous types of neurons and glial cells distributed in two intramuscular plexuses that span the length of the intestine and control coordinated smooth muscle contractile activity and other intestinal functions. It is well-established that reciprocal communication exists between the brain and the gastrointestinal tract. Although the ENS can function independently, it is connected to the CNS through the afferent and efferent pathways of the parasympathetic and sympathetic nervous systems. In addition to regulating ENS function by the CNS, these connections are likely to be critically involved in the pathophysiology of Parkinson's disease (PD). PD is a common neurodegenerative disorder that presents with non-motor and motor symptoms. Surprisingly, ENS lesions have been shown to occur very early in the disease, even before CNS involvement. This has led to the postulation that the ENS may be central to the pathophysiology of PD. Autopsy studies have shown that α-synuclein (αS) aggregates in PD patients are found both in the substantia nigra (SN) and the ENS. Therefore, it has been hypothesized that the pathological process leading to PD may initially occur in the ENS years before the appearance of motor features. This process induces misfolding and aggregation of αS in specific subtypes of neurons in the CNS. Finally, it spreads retrogradely in the CNS through preganglionic vagal fibers to the dorsal motor nucleus of this nerve and to other central nervous structures. In addition to the presumed role in the spread of the disease process, it has also been suggested that pathological changes in the ENS might be involved in the gastrointestinal dysfunction frequently seen in Pd patients. Starting from the evidence in animal models and using a translational point of view, in this review, we aim to summarize the role of the ENS in the pathogenesis of PD and how this system could be modulated for a novel therapeutic approach. While acknowledging the presumed role of the microbiome in the gut-brain axis, we will shift the focus from this point of view to focus more on the neurons of the ENS.

Proteomic analysis revealed the preservation of many proteins in the “Heslington brain” (which is at least 2,600-year-old brain tissue uncovered within the skull excavated in 2008 from a pit in Heslington, Yorkshire, England). Five of these proteins (“main proteins”), heavy, medium, and light neurofilament proteins (NFH, NFM, and NFL), glial fibrillary acidic protein (GFAP), and myelin basic (MBP) protein are engaged in the formation non-amyloid protein aggregates, such as intermediate filaments and myelin sheath. We used a wide spectrum of bioinformatics tools to evaluate the prevalence of functional disorder in several related sets of proteins, such as “main proteins” and their 44 interactors, as well as all other protein identified in the Heslington brain. These analyses revealed that all five “main proteins”, half of their interactors and almost one third of the Heslington brain proteins are expected to be mostly disordered. Furthermore, most of the remaining proteins are expected to contain sizable disordered regions. This is in contrary the expected substantial (if not complete) elimination of the disordered proteins from the Heslington brain. Therefore, it seems that the intrinsic disorder of NFH, NFM, NFL, GFAP, and MBP, their interactors and many other proteins might play a crucial role in preserving the Heslington brain by forming tightly folded brain protein aggregates, in which different parts are glued together via the disorder-to-order transitions.

Surgical methods for treating spasmodic torticollis include denervation and myotomy (DAM) of the affected muscles, and deep brain stimulation (DBS). This study reports on the long-term efficacy, prognostic factors, safety, and hospitalization costs following these two procedures. We collected data from 94 patients with spasmodic torticollis, of whom 41 and 53 were treated with DAM and DBS, respectively, from June 2008 to December 2020 at the Chinese People’s Liberation Army General Hospital. We used the Tsui scale and the global outcome score of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) to evaluate the preoperative and postoperative clinical condition in all patients. We also determined the cost of hospitalization, prognostic factors, and serious adverse events following the two surgical procedures. The mean follow-up time was 68.83 months (range = 13–116). Both resection surgery and DBS showed good results in terms of Tsui (Z = -5.103, P = 0.000; Z = -6.210, P = 0.000) and TWSTRS scores (t = 8.762, P = 0.000; Z = -6.308, P = 0.000). Compared with the DAM group, the preoperative (47.71, range 24–67.25) and postoperative (18.57, range 0–53) TWSTRS scores in the DBS group were significantly higher (Z = -3.161, P = 0.002). We found no correlation between prognostic factors and the patient age, gender, or disease duration for either surgical procedure. However, prognostic factors were related to the length of the postoperative follow-up period in the DBS surgery group (Z = -2.068, P = 0.039; Z = -3.287, P = 0.001). The mean hospitalization cost in the DBS group was 6.85 times that found in the resection group (Z = -8.284, P = 0.000). The total complication rate was 4.26%. We found, both resection surgery and DBS, showed good results in the patients with spasmodic torticollis. Although DBS had a greater impact on the quality of life and the degree of pain relief, it was more expensive. Prognostic factors were related to the length of the postoperative follow-up period in patients who underwent DBS surgery.

Our brain continuously interacts with the body as we engage with the world. Although we are mostly unaware of internal bodily processes, such as our heartbeats, they may be influenced by and in turn influence our perception and emotional feelings. While there is a recent focus on understanding cardiac interoceptive activity and interaction with brain activity during emotion processing, the investigation of cardiac-brain interactions with more ecologically valid naturalistic emotional stimuli is still very limited. We also do not understand how an essential aspect of emotions like context familiarity influences affective feelings and is linked to cardiac-brain interactions. Hence to answer these questions, we designed an exploratory study by recording ECG and EEG signals for the emotional events while participants were watching emotional movie clips. Participants also rated their familiarity with the stimulus on the familiarity scale. Linear mixed effect modelling was performed in which the ECG power and familiarity were considered as predictors of EEG power. We focused on three brain regions, including prefrontal (PF), frontocentral (FC) and parietooccipital (PO). The analyses showed that cardiac-brain interaction is dependent on familiarity such that the interaction is stronger with high familiarity. In addition, the results indicate that arousal is predicted by cardiac-brain interaction, which also depends on familiarity. The results support emotional theories that emphasize context dependency and interoception. Multimodal studies with more realistic stimuli would further enable us to understand and predict different aspects of emotional experience.

Image segmentation is a new challenge prob- lem in medical application. The use of medical imaging has become an integral part of research, as it allows us to see inside the human body without surgical intervention. Many researcher have studied brain segmentation. One stage method is used to segment the brain tissues. In this paper, we proposed the multi-stage generative ad- versarial network to solve the problem of information loss in the one-stage. We utilize the coarse-to-fine to improve brain segmentation using multi-stage generative adversar- ial networks (GAN). In the first stage, our model generated a coarse outline for (i) background and (ii) brain tissues. Then, in the second stage, the model generated outline for (i) white matter (WM), (ii) gray matter (GM) and (iii) cerebrospinal fluid (CSF). A good result can be achieved by fusing the coarse outline and refine outline. We conclude that our model is more efficient and accu- rate in practice for both infant and adult brain segmenta- tion. Moreover, we observe that multi-stage model is faster than prior models. To be more specific, the main goal of multi-stage model is to see the performance of the model in a few shot learning case where a few labeled data are available. For medical image, this proposed model can work in a wide range of image segmentation where the convolution neural networks and one-stage methods have failed.

Psychotic disorders occur as a result of pathobiochemical processes in the brain, which disrupt the central neurotransmission of molecules such as dopamine and glutamate. The dopamine hypothesis, adopted more than 2 decades ago, has repeatedly asserted its position as an etiopathogenetic substrate through the action of psychostimulants and neuroleptics on the mesolimbic and mesocortical systems, giving insight into the origin of positive and negative schizophrenic symptoms. On the other hand, cognitive impairments in schizophrenia remain not fully understood but are thought to be present during all stages of the disease, as well as in the prodromal the interictal and residual phases. Over the last decade, functional magnetic resonance imaging has focused on research of brain networks like the Default mode network, the Salience network and Central executive network, enabling a deeper understanding of cognitive deficits, as well as other phenomena such as disorganization of thought and behavior. The study of the nodes of these networks, such as the precuneus and insula, informs about their complex significant roles as structures responsible for important cognitive domains such as concentration, attention, ability to understand and reproduce information, as well as memory functions. It is suggested that the neurotransmission of dopamine and glutamate play a key role in these processes and their successful modulation in the correct brain regions through psychopharmacological and biomedical instrumental methods may lead to a significant reversal of conventional paradigms. Pharmaco-magnetic resonance imaging is a neuroimaging method that can provide the translation of scientific knowledge about the neural networks and the disruptions in and between different brain regions, into clinically applicable and effective therapeutic results in the management of severe psychotic disorders.

Sedation is a ubiquitous practice in ICUs and NCCUs. It has the benefit of reducing cerebral energy demands, but also precludes an accurate neurologic assessment. Because of this, sedation is intermittently stopped for the purposes of a neurologic assessment, which is termed a neurologic wake-up test (NWT). NWTs are considered to be the gold-standard in continued assessment of brain-injured patients under sedation. NWTs also produce an acute stress response that is accompanied by elevations in blood pressure, respiratory rate, heart rate, and ICP. Utilization of cerebral microdialysis and brain tissue oxygen monitoring indicates that this is not mirrored by alterations in overall cerebral metabolism, and seldom affects oxygenation. The hard contraindications for the NWT are preexisting intracranial hypertension, barbiturate treatment, status epilepticus, and hyperthermia. However, hemodynamic instability, sedative use for primary ICP control, and sedative use for severe agitation or respiratory distress are considered significant safety concerns. Despite ubiquitous recommendation, it is not clear if additional clinically relevant information is gleaned through its use, especially with the contemporaneous utilization of multimodality monitoring. Various monitoring modalities provide unique and pertinent information about neurologic function, however, their role in improving patient outcomes and guiding treatment plans has not been fully elucidated. There is a paucity of information pertaining to the optimal frequency of NWTs, and if it differs based on type of injury. Only one concrete recommendation was found in the literature, exemplifying the uncertainty surrounding its utility. The most common sedative used and recommended is propofol because of its rapid onset, short duration, and reduction of cerebral energy requirements. Dexmedetomidine may be employed to facilitate serial NWTs, and should always be used in the non-intubated patient or if propofol infusion syndrome (PRIS) develops. Midazolam is not recommended due to tissue accumulation and residual sedation confounding a reliable NWT. Thus, NWTs are well tolerated in most patients and remain recommended as the gold-standard for continued neuromonitoring. Predicated upon one expert panel, they should be performed at least one time per day. Propofol or dexmedetomidine are the main sedative choices, both enabling a rapid awakening and consistent NWT.

Purpose: Dysarthria, a neurological injury of the motor component of the speech circuitry, is of common consequences of traumatic brain injury (TBI). Palilalia is a speech disorder characterized by involuntary repetition of words, phrases, or sentences. Based on the evidence supporting the effectiveness of transcranial direct current stimulation (tDCS) in some speech and language disorders, we hypothesized that using tDCS would enhances the effectiveness of speech therapy in a client with chronic dysarthria following TBI. Method: We applied the constructs of the “Be Clear” protocol, a relatively new approach in speech therapy in dysarthria, together with tDCS on a chronic subject who affected by dysarthria and palilalia after TBI. Since there was no research on the use of tDCS in such cases, regions of interest (ROIs) were identified based on deviant brain electrophysiological patterns in speech tasks and resting state compared with normal expected patterns using the Quantitative Electroencephalography (QEEG) analysis. Results: Measures of perceptual assessments of intelligibility, an important index in the assessment of dysarthria, ​​were superior to the primary protocol results immediately and 4 months after intervention. We did not find any factor other than the use of tDCS to justify this superiority. The percentage of repeated words, an index in palilalia assessment, had a remarkable improvement immediately after intervention but fell somewhat after 4 months. We justified this case with subcortical origins of palilalia. Conclusion: Our present case-based findings suggested that applying tDCS together with speech therapy may improve intelligibility in similar case profiles as compared to traditional speech therapy. To reconfirm the effectiveness of the above approach in cases with dysarthria following TBI, more investigation need to be pursued.

Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its copy number alteration (CNA) and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2 and 12p13.31 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.

In quantum approaches to consciousness, the authors try to propose a model and mechanism for the mind-brain interaction using modern physics and some quantum concepts which do not exist in the classical physics. The independent effect of mind on the brain has been one of the challenging issues in the history of science and philosophy. In some recent mind-brain interaction models, the direct influence of mind on matter is either not accepted (as in Stapp’s model) or not clear, and there have not been any clear mechanism for it (as in Penrose-Hameroff’s model or in Eccles’s model). In this manuscript we propose a model and mechanism for mind’s effect on the matter using an extended Bohmian quantum mechanics and Avicenna’s ideas. We show that mind and mental states can affect brain’s activity without any violation of physical laws. This is a mathematical and descriptive model which shows the possibility of providing a causal model for mind’s effect on matter. It is shown that this model guarantees the realistic philosophical constraints and respects the laws of nature. In addition, it is shown that it is in agreement with the Libet style experimental results and parapsychological data. To propose this model, we obtained a modified (non-unitary) Schrödinger equation via second quantization method which affects the particle through a modified quantum potential and a new term in the continuity equation. At the second quantized level, which is equivalent to quantum field theory level (QFT), we can use the path integral formalism of Feynman. We show that there are three methods to extend Bohmian QM via path integral formalism, which has different interpretations. By numerical simulation of trajectories in the two-slits experiment, we show their differences and choose one of these methods for our mind-brain model which can be the basis for explaining some phenomena which are not possible to explain in the standard Bohmian QM.

Non-invasive, electroencephalography (EEG)-based brain-computer interfaces (BCIs) on motor imagery movements translate the subject’s motor intention into control signals through classifying the EEG patterns caused by different imagination tasks, e.g. hand movements. This type of BCI has been widely studied and used as an alternative mode of communication and environmental control for disabled patients, such as those suffering from a brainstem stroke or a spinal cord injury (SCI). Notwithstanding the success of traditional machine learning methods in classifying EEG signals, these methods still rely on hand-crafted features. The extraction of such features is a difficult task due to the high non-stationarity of EEG signals, which is a major cause for the stagnating progress in classification performance. Remarkable advances in deep learning methods allow end-to-end learning without any feature engineering, which could benefit BCI motor imagery applications. We developed three deep learning models: 1) a long short-term memory (LSTM); 2) a proposed spectrogram-based convolutional neural network model (pCNN); and 3) a recurrent convolutional neural network (RCNN), for decoding motor imagery movements directly from raw EEG signals without (manual) feature engineering. Results were evaluated on our own, publicly available, EEG data collected from 20 subjects and on an existing dataset known as 2b EEG dataset from "BCI Competition IV". Overall, better classification performance was achieved with deep learning models compared to state-of-the art machine learning techniques, which could chart a route ahead for developing new robust techniques for EEG signal decoding. We underpin this point by demonstrating the successful real-time control of a robotic arm using our CNN based BCI.

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

High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham=-7.499, LogIC50 Stroke=-7.350, P=0.0132, n= 19, 31 respectively). Vasodilatory responses to SNP were identical in isolated aortas in sham and stroke groups. Phenylephrine induced vasoconstriction was impaired in aortas isolated from stroke animals in comparison to sham counterparts (Sham LogEC50= -6.652 vs Stroke LogEC50=-6.475, P< 0.001). Our study demonstrates that 24 hours post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. Aortas from stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while endothelium-independent vasodilatory responses were preserved. Since both vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke.

Prediabetes, a pivotal phase in glucose metabolism between normalcy and diabetes, exerts a profound influence on the aging process and the risk of age-related diseases. This comprehensive review delves into the intricate web of blood-based biomarkers that collectively expedite senescence, marking the transition from a state of health to age-related complications. Key findings underscore the significance of diverse biomarkers, such as telomere length, p16INK4a, senescence-associated secretory phenotype (SASP) factors, DNA methylation clocks, advanced glycation end products (AGEs), inflammatory and oxidative stress markers, circulating hormones, and additional factors like folate, B12, osteocalcin, and more. Not only do these biomarkers serve as indicators of senescence, but they actively fuel chronic inflammation, oxidative stress, and metabolic dysregulation, all of which contribute to accelerated aging. The implications of this understanding are profound, as prediabetes emerges as a critical period in an individual's life, influencing various physiological systems, including the vascular and neural systems, metabolic functions, hormonal regulation, and bone health. Recognizing the profound influence of prediabetes on senescence provides a foundation for personalized intervention strategies to mitigate age-related complications and promote healthy aging. Future research directions call for a more diverse array of biomarkers, in-depth exploration of their roles, and the development of tailored precision medicine strategies to ensure a holistic understanding and effective management of prediabetes-induced senescence and its implications for aging. This knowledge has far-reaching implications for public health and clinical practice, emphasizing the need for early detection and intervention in prediabetic individuals to enhance the quality of life in an aging population with diverse needs.

Superficial discolored spots on Atlantic salmon (Salmo salar) fillets are a serious quality problem for commercial seafood farming. Previous reports proposed that the black spots (called melanized focal changes (MFC)) may be melanin, but no convincing evidence has been reported. In this study, we performed chemical characterization of MFC, and also of red pigment (called red focal changes (RFC)), of salmon fillets using alkaline hydrogen peroxide oxidation and hydroiodic acid hydrolysis. This revealed that the MFC contain 3,4-dihydroxyphenylalanine (DOPA)-derived eumelanin whereas the RFC only contain trace amounts of eumelanin. Therefore, probably, the black color of MFC can be explained by the presence of eumelanin from accumulated melanomacrophages. For the red pigment, we could not find a significant signature of either eumelanin or pheomelanin, and the red color is probably predominantly hemorrhagic in nature. However, we found that in RFC the level of pigmentation did increase together with some melanogenic metabolites. Comparison with a “mimicking experiment,” in which a mixture of a salmon homogenate + DOPA was oxidized with tyrosinase, suggested that the RFC include conjugations of DOPAquinone and/or DOPAchrome with salmon muscle tissue proteins. In short, the results suggest that melanogenic metabolites in MFC and RFC derive from different chemical pathways, which would agree with the two different colorations deriving from distinct cellular origins, namely melanomacrophages and red blood cells, respectively.

Severe COVID-19 alters the biochemical and morphological characteristics of blood cells in a wide variety of ways. To date, however, the vast majority of research has been devoted to the study of leukocytes, while erythrocyte morphological changes have received significantly less attention. The purpose of this research was to identify erythrocyte types that were unique to COVID-19, compare the number of different poikilocyte types, and measure erythrocyte sizes to provide data on size dispersion. Red blood cells obtained from 6 control donors (800-2200 cells for each donor) and 5 COVID-19 patients (800-1900 cells for each patient) were examined using low voltage scanning electron microscopy. We did not discover any forms of poikilocytes that would be unique to COVID-19. Among COVID-19 patients, we observed an increase in the number of acanthocytes (p=0.01) and a decrease in the number of spherocytes (p=0.03). In addition, our research demonstrates that COVID-19 causes an increase in the median (p=0.004) and interquartile range (p=0.009) when assessing erythrocyte size.

Background: The fulminant course of COVID-19, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents with a high mortality rate and still lacks a causative treatment. C-reactive protein (CRP) has been shown to increase dramatically during the disease progression and correlates with deleterious outcomes. Selective CRP apheresis can reduce circulating CRP levels fast and effective. Methods: Seven hospitalized patients with documented severe COVID-19 progression, elevated CRP plasma levels (> 100 mg/L) and signs of respiratory failure were treated with CRP apheresis. 2-12 CRP apheresis sessions were performed generally in 24 h time intervals and depending on CRP plasma levels. Results: CRP apheresis reduced CRP plasma levels by up to 84% within a few hours, without exhibiting side effects in any patient. Despite signs of severe lung infiltration in all patients, only one patient died. The other patients showed improvements within the chest x-ray after CRP apheresis and were able to recover regardless of intubation and/or ECMO (4 patients). All remaining six patients were discharged from the hospital in good clinical condition. All patients had comorbidities. Conclusions: This case series presents a mortality rate of only 14%, which is dramatically lower than expected from the presented CRP levels as well as comorbidities and ventilation require-ments. Our clinical observations regarding the here presented seven patients support the hypoth-esis that CRP is a candidate to be therapeutically targeted in the early stage of severe COVID-19.

Medically underserved communities have limited access to effective disease management resources in the U.S. Mobile health applications (mHealth apps) offer patients a cost-effective way to monitor and self-manage their condition and to communicate with providers; however, current diabetes self-management apps have rarely included end-users from underserved communities in the design process. This research documents key stakeholder-driven design requirements for a diabetes self-management app for medically underserved patients. Semi-structured survey-interviews were carried out with 97 patients with diabetes and 11 healthcare providers from medically underserved counties in South Texas to elicit perspectives and preferences regarding a diabetes self-management app, and their beliefs regarding such an app’s usage and utility. Patients emphasized the need for accessible educational content and for quick access to guidance on regulating blood sugar, diet, and exercise and physical activity using multimedia rather than textual form. Healthcare providers indicated that glucose monitoring, educational content, and graphical visualization of diabetes data were among the top-rated app features. These findings suggest that specific design requirements for the underserved may improve the adoption, usability, and sustainability of such interventions. Designers should consider health literacy and numeracy, linguistic barriers, data visualization, data entry complexity, and information exchange capabilities.

Immune reconstitution inflammatory syndrome (IRIS) presents as an exaggerated immune reaction that occurs during dysregulated immune restoration in immunocompromised patients in late-stage HIV infection who commenced antiretroviral treatments. Virtually, any opportunistic pathogen can provoke this type of immune restoration disorders. In this review, we focus on recent development in the identification of risk factors for Cryptococcal IRIS and on advancements in our understanding of C-IRIS immunopathogenesis. We overview new findings in blood and cerebrospinal fluid which can potentially be useful in the diagnosis of cryptococcal meningitis IRIS. We assess the utility of these biomarkers to identify putative host-based targets, which may justify a clinical need for improvement in monitoring a patient’s laboratory results and adjusting treatment modalities in AIDS patients co-infected with Cryptococcus.

Placental growth factor (PlGF or PGF) is a member of the VEGF family, which is known to play a critical role in pathological angiogenesis, inflammation, and endothelial cell barrier function. However, the molecular mechanisms by which PlGF mediates its effects in non-proliferative diabetic retinopathy (DR) remain elusive. In this study, we performed transcriptome-wide profiling of differential gene expression for human retinal endothelial cells (HRECs) treated with PlGF antibody. The effect of antibody treatment on the samples was validated using trans-endothelial electric resistance (TEER), and western blot. A total of 3760 genes (1750 upregulated and 2010 downregulated) were found to be differentially expressed between the control and PlGF antibody treatment group. These differentially expressed genes (DEGs) were used for gene ontology and enrichment analysis to identify gene function, signal pathway, and interaction networks. The gene ontology results revealed that catalytic activity (GO:0003824) of molecular function, cell (GO:0005623) of the cellular component, and cellular process (GO:0009987) were among the most enriched biological processes. Pathways such as TGF-β, VEGF-VEGFR2, p53, apoptosis, pentose phosphate pathway, and ubiquitin-proteasome pathway, were among the most enriched, and TGF-β1 was identified as a primary upstream regulator. These data provide new insights into the underlying molecular mechanisms of PlGF in mediating biological functions, in relation to DR.

Very little is known about laboratory confirmed blood stream infections (LCBIs) in neonatal intensive care units (NICUs) in resource-limited settings. The aim of this cohort study was to determine the incidence, risk factors, and causative agents of LCBIs in a level-2 NICU in India. The diagnosis of LCBIs was established using the Centre for Disease Control, USA criteria. A predesigned questionnaire containing risk factors associated with LCBIs was filled-in. A total of 150 neonates (43% preterm) were included in the study. The overall incidence of LCBIs was 31%. The independent risk factors for LCBIs were: preterm neonates (relative risk (RR) 2.23), duration of NICU stay more than 14 days (RR 1.75), chorioamnionitis in the mother (RR 3.18), premature rupture of membrane in mothers (RR 2.32), neonate born through meconium-stained amniotic fluid (RR 2.32), malpresentation (RR 3.05), endotracheal intubation (RR 3.41), umbilical catheterization (RR 4.18), and ventilator-associated pneumonia (RR 3.17). The initiation of minimal enteral nutrition was protective from LCBIs (RR 0.22). The predominant causative organisms were gram-negative pathogens (58%). The results of the present study can be used to design antibiotic interventions to reduce LCBIs in resource-limited settings.

Neuromorphic computing, a brain inspired non-Von Neumann computing system, addresses the challenges posed by the Moore’s law memory wall phenomenon. It has the capability to increasingly enhance performance while maintaining power efficiency. Neuromorphic chip architecture requirements vary depending on the application and optimizing it for large-scale applications remains to be a challenge. Neuromorphic chips are programmed using spiking neural networks which provide them with important properties such as parallelism, asynchronism, and on-device learning. Widely used spiking neuron models include the Hodgkin-Huxley Model, Izhikevich model, integrate-and-fire model and spike response model. Hardware implementation platforms of the chip follow three approaches: analog, digital, or a combination of both. Each platform can be implemented using various memory topologies which interconnects with the learning mechanism. Current neuromorphic computing systems typically use the unsupervised learning spike timing-dependent plasticity algorithms. However, algorithms such as voltage-dependent synaptic plasticity have the potential to enhance performance. This review summarizes the potential neuromorphic chip architecture specifications and highlights which applications they are suitable for.

The detection of early biomarkers and molecular mechanisms in Parkinson’s disease (PD) remains a challenge. Recent research has pointed to potential roles for peptidylarginine deiminases (PADs), a family of calcium activated enzymes, and associated post-translational protein citrul-lination/deimination in early stages of the disease, with a focus on hippocampal and cortex re-gions of the brain. Further analysis of brain region specific changes in PAD isozymes and identi-fication of brain-region specific citrullinomes, therefore remain to be studied. This study assessed brain-region specific PAD isozyme expression (PADs 1-4; PAD6) and associated citrullinated protein targets in the 6-hydroxydopamine (6-OHDA) induced rat model of pre-motor PD. Cortex, hippocampus, striatum, midbrain, cerebellum and olfactory bulb were compared between con-trols/shams and the PD model. In cortex, a significant increase of PAD2 and PAD3 was observed in the PD model. In hippocampus, PAD3, PAD4 and PAD6 showed strongest levels, but with no significant changes observed between PD and controls. In striatum, a significant reduction in all PAD isozymes was observed in the PD model. In the olfactory bulb, PAD3 was significantly el-evated in PD. In midbrain, PAD2, PAD4 and PAD6 showed strongest signal but with no signifi-cant changes between PD and controls. In cerebellum, a significant increase was seen in PAD3, PAD4 and PAD6 in the PD model. Citrullinated protein hits were most abundant in cortex and hippocampus, while for the PD model an increase in citrullinated hits was particularly observed in cortex and cerebellum, compared to controls. For all brain regions there was a considerable difference in citrullinated protein IDs between the PD model and the controls. Citrullinome as-sociated KEGG pathways differed in the six brain regions; some were overlapping for controls and PD, some were identified for the PD model only, and some were identified in control brains only. KEGG pathways identified in PD brains onlywere: “Axon guidance”; “Spinocerebellar ataxia”; “Hippo signalling pathway”; “NOD-like receptor signalling pathway”; “Phosphatidyl-inositol signalling system”; “Rap1 signalling pathway”; “Platelet activation”; “Yersinia infection”; “Fc gamma R-mediated phagocytosis”; “Human cytomegalovirus infection”; “Inositol phosphate metabolism”; “Thyroid hormone signalling pathway”; “Progesterone-mediated oocyte matura-tion”; “Oocyte meiosis”; and “Choline metabolism in cancer”. Our findings highlight differences in PAD isozymes, citrullinated proteins and associated KEGG pathways between brain regions, in pre-motor PD.

Objective: To investigate whether the relationships between acute care occupational therapy (OT) and physical therapy (PT) utilization and community discharge are moderated by functional or physical performance at discharge among individuals hospitalized with traumatic brain injury (TBI). Setting: 14 acute care hospitals in the state of Colorado. Participants: We studied 5,599 adults hospitalized with TBI between June 2018 and April 2021. Design: In a secondary analysis of de-identified electronic health record (EHR) data, multivariable moderation logistic regression models were performed to calculate odds ratios (ORs) for the likelihood of community discharge among patients who utilized OT/PT services. Main Measures: Functional (activities of daily living [ADL]) and physical (mobility) performance at discharge, OT and PT utilization, and community discharge status. Results: Overall, 67% of patients discharged to the community. The mean age of the sample was 55 years (SD = 20 years). Most participants were male (64%) and non-Hispanic white (72%). Mean hospital length of stay was 6 days (SD = 6 days). Both OT and PT utilization (OT: OR= 1.21, 95% CI [1.11, 1.33]; PT: OR= 1.22, 95% CI [1.14, 1.30]) and discharge ADL and mobility scores (ADL: OR= 1.34, 95% CI [1.30, 1.39]; mobility: OR= 1.38, 95% CI [1.33, 1.42]) were significantly and positively associated with community discharge. The OT and PT utilization-by-discharge ADL and mobility interaction terms yielded slightly negative, but statistically significant moderation effects in both models (ORs= 0.99, 95% CIs [0.98, 1.00]); indicating the magnitude of the OT and PT utilization effect diminished as ADL and mobility scores increased. Several sociodemographic characteristics and clinical factors were also independently associated with community discharge in both models (p-values

Brain tumors are frequently classified with high accuracy using convolutional neural networks (CNNs) and better comprehend the spatial connections among pixels in complex pictures. Due to their tiny receptive fields, the majority of deep convolutional neural network (DCNN)-based techniques overfit and are unable to extract global context information from more significant regions. While dilated convolution retains data resolution at the output layer and increases the receptive field without adding computation, stacking several dilated convolutions has the drawback of producing a grid effect. To handle gridding artifacts and extract both coarse and fine features from the images, this research suggests using a dilated parallel deep convolutional neural network (PDCNN) architecture that preserves a wide receptive field. To reduce complexity, initially, input images are resized and then grayscale transformed. Data augmentation has since been used to expand the number of datasets. Dilated PDCNN makes use of the lower computational overhead and contributes to the reduction of gridding artifacts. By contrasting various dilation rates, the global path uses a low dilation rate (2,1,1), while the local path uses a high dilation rate (4,2,1) for decremental even numbers to tackle gridding artifacts and extract both coarse and fine features from the two parallel paths. Using three different types of MRI datasets, the suggested dilated PDCNN with the average ensemble method performs better. The accuracy provided by the Multiclass Kaggle dataset-III, Figshare dataset-II, and Binary tumor identification dataset-I is 98.35%, 98.13%, and 98.67%, respectively. In comparison to state-of-the-art techniques, the suggested structure improves results by extracting both fine and coarse features, making it efficient.

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

Objective: The COVID-19 pandemic inferred on neuro-oncological patients (PTS) and the caregivers regarding tumor care and emotional functioning. This study aimed to understand how COVID-19 affects their psychological state and relations between PTS and health personnel in neuro-oncology. Methods: A cross-sectional study on neuro-oncological PTS and their caregivers. Results: A total of 162 PTS and 66 caregivers completed the questionnaire. The 37.5% of PTS perceived greater risk of contracting the COVID-19 compared to the general population. On the 0-10 scale, PTS tumor-related anxiety score was 5.8 and COVID-related 4.6. The caregivers reported 7.7 and 5.5 respectively. The QoL was described at least as good in 75% of both PTS and caregivers; the caregivers’ care burden increased in 22.7% during the pandemic, with no correlation with QoL. Future perception often changed both in PTS and in the caregivers. Cancer treatment schedule was changed in 18.5%, including for PTS decision. However, the 93.5% of PTS was satisfied with the overall care. Conclusion: A considerable proportion of PTS and caregivers still perceived the tumor disease as more burdensome than the pandemic, and perceived their future as more uncertain. Such data rinforce the need to build a proficient alliance between PTS and health personnel.

Iron deficiency in the fetal and neonatal period (perinatal iron deficiency) bodes poorly to neuro-development. Given its common occurrence and the negative impact on brain development, a screening and treatment strategy that is focused on optimizing brain development in perinatal iron deficiency is necessary. Pediatric societies currently recommend a universal iron supple-mentation strategy for full-term and preterm infants that does not consider individual variation in the body iron status and could lead to under-treatment or over-treatment. Moreover, the focus is on hematological normalcy and not optimal brain development. Several serum iron indices and hematological parameters in the perinatal period are associated with risk of abnormal neurodevelopment, suggesting their potential use as biomarkers for screening and monitoring treatment in infants at risk for perinatal iron deficiency. A biomarker-based screening and treatment strategy that is focused on optimizing brain development will likely improve outcome in perinatal iron deficiency.

The microalgae Phaeodactylum tricornutum (PT) is distinguished by its rich nutrient profile, characterized by well-documented neuroprotective activities, including fucoxanthin (FX), a major carotenoid, and polyunsaturated omega-3 fatty acids (n-3 PUFA). The current study aims to evaluate the protective effects of a standardized extract of PT (Mi136) containing 2% FX on cognitive function, oxidative stress, and inflammation parameters in a mouse model of accelerated aging. Seventy-two (72) male mice were randomly assigned to the blank control group (BC), negative control group (NC), and four similar microalgae extract of PT groups (branded as BrainPhytTM) with different human equivalent doses. From day 01 to day 51, mice in the BC group were injected with a 0.9% normal saline solution, while mice in all other groups were subcutaneously injected with D-galactose (D-Gal) at a dose of 150 mg/kg once per day, five days per week. Results indicated that, for the three higher microalgae extract of PT dose groups, spatial cognitive function, swim latency, and step-through latency impairments induced by chronic D-Gal intoxication were significantly and fully inhibited, with mean values similar to those in the BC group during each day of testing. Similar benefits were observed in biochemical analysis, specifically regarding brain and plasma levels of lipid peroxidation, TNF-α, and IL-6 markers. These data underscore the positive effects of a standardized extract of PT containing 2% FX on cognitive function parameters such as spatial working memory, long-term memory, and short-term memory through the regulation of oxidative stress and inflammation pathways.

The orbitofrontal cortex (OFC) area plays a critical role in human brain functions. However, susceptibility differences between paranasal sinuses and nasal cavity tissues often cause local field variations in the OFC during MRI, resulting in image distortions and signal loss. In this paper, we introduce a subject-friendly neck passive shim solution aimed at enhancing field homogeneity in the brain, specifically in the OFC region. Utilizing 3D gradient-echo pulse sequences, main magnetic field (B0) maps of four subjects’ brains were acquired at 4T MRI. Subsequently, these maps were decomposed into spherical harmonic coefficients and averaged. Optimal positions for placing shim elements on a semi-cylindrical surface, positioned slightly above the neck and below the chin, were computed. The findings indicate a substantial enhancement in B0 homogeneity, particularly within the OFC region, through the integration of this semi-cylindrical passive shim system in conjunction with first and second-order active shimming.

Background: Increase of collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. We hypothesized that COL I/COL III ratio is increased in the brain arteriovenous malformations (bAVMs), which is associated with bAVM hemorrhage. Method: Surgically resected human bAVM samples and mouse bAVMs induced in three transgenic mouse lines with activin receptor-like kinase 1 or endoglin deletion in the endothelial cells or in the brain focally. Colony-stimulating factor receptor inhibitor was used to transiently deplete microglia. COL I and COL III levels, hemorrhage, and gene expression in bAVMs were analyzed. Results: The COL I and COL III levels and the COL I/COL III ratio were higher on human and mouse bAVMs than controls, which was associated with bAVM hemorrhage. Col I and Col III mRNAs were also increased in mouse bAVMs. The degree of microhemorrhage in mouse bAVMs was positively correlated with Col I/Col III ratios. Transient depletion of microglia reduced Col I/Col III ratio and microhemorrhage in mouse bAVMs. Conclusion: COL I/COL III ratio are increased in bAVM vessels, which is associated with bAVM hemorrhage. Depletion of microglia reduces Col I/Col III ratio and hemorrhage in mice bAVMs.

Background: Aging rate is affected by genetic changes, epigenetic modifications, oxidative stress, inflammation, lifestyle and environmental factors. In accelerated aging (AA), biological age exceeds the chronological one. Objective: To undertake a critical reappraisal of the AA concept and to reveal its weaknesses and limitations. Methods: We reviewed over 300 recent articles dealing with physiology of brain aging and pathophysiology of neurodegeneration. Results: (1) Organ systems age at different rates, which interferes with application of the AA concept to individual organs. (2) Aging rate can be decelerated due to individual structure–functional reserves built with cognitive, physical training or pharmacological interventions. (3) The AA concept lacks standardised terminology and methodology. (4) Specific molecular biomarkers (MBM) reflect aging. To consolidate the AA theory, researchers should validate numerous MBM candidates. (5) Aging factors, mechanisms and the exact nature of their biological outcomes are not well understood. Conclusion: Although considered as a perspective theory, the AA concept has serious limitations and it requires an update.

Eutherians have 11 retrotransposon Gag-like (RTL)/sushi-ichi retrotransposon homolog (SIRH) genes presumably derived from a certain retrovirus. Accumulating evidence indicates that the RTL/SIRH genes play a variety of roles in the current mammalian developmental system, such as in the placenta, brain and innate immune system in a eutherian-specific manner. It has been shown that the functional role of Paternally Expressed 10 (PEG10) in placental formation is unique to the therian mammals, as are the eutherian-specific roles of PEG10 and PEG11/RTL1 in maintaining the fetal capillary network and the endocrine regulation of RTL7/SIRH7 (aka Leucine Zipper Down-Regulated in Cancer 1 (LDOCK1)) in the placenta. In the brain, PEG11/RTL1 is expressed in the corticospinal tract and hippocampal commissure, mammalian-specific structures, and in the corpus callosum, a eutherian-specific structure. Unexpectedly, at least three RTL/SIRH genes, RTL5/SIRH8, RTL6/SIRH3 and RTL9/SIRH10, play important roles in combating a variety of pathogens, viruses, bacteria and fungi, respectively, suggesting that the innate immunity system of the brain in eutherians has been enhanced by the emergence of these new components. In this review, we will summarize the function of 10 out of the 11 RTL/SIRH genes and discuss their roles in eutherian development and evolution.

Postural instability (PI) in Parkinson’s disease (PD) exposes patients to increased risk of falls (RF). Although dopaminergic therapy and deep brain stimulation (DBS) improve motor performance in advanced PD patients, their effects on PI and RF are not clear. PI and RF were assessed by a stabilometric platform in 6 advanced PD patients. Patients were evaluated on and off dopaminergic medication and four DBS conditions: bilateral-DBS, DBS of the more- or less-affected side and DBS-off. Dopaminergic medication alone worsened PI and RF, DBS alone worsened RF, and no medication/DBS combination produced an improvement in postural control with respect to the OFF-medication/DBS-off condition. When ON-medication, PI and RF significantly improved after turning the DBS on, regardless of medication condition. Among DBS conditions, bilateral-DBS provided the maximal improvement of PI and RF when ON medication, and minimal worsening of PI and RF when OFF medication, whereas patients performed worse when in most-affected side DBS condition. These results can help in developing the best therapeutic strategy for postural disorders in patients with advanced PD.

Bone marrow mononuclear cells (BMMNCs) have emerged as a potential therapeutic strategy for various incurable conditions including autism spectrum disorder (ASD). To study its safety and efficacy, we analyzed 1011 patients who underwent intrathecal administration of autologous BMMNCs along with neurorehabilitation. At mean follow-up of 19.3 months after intervention, 90.6% patients showed overall improvement. Improvements were observed in attention concentration, command following, eye contact, sitting tolerance, social interaction, hyperactivity, communication, speech, aggressiveness, stereotypical and self-injurious behavior. Statistically significant changes were observed in scores of Indian Scale of Autism Assessment and Childhood Autism Rating Scale (p<0.05). On subgroup analysis, improvements were recorded irrespective of age and disease severity and better outcome was observed in patients who took multiple doses of cell therapy compared to single dose. Comparative Brain PET-CT scan of 401 patients showed improved brain metabolism after the intervention. No major adverse events were reported. Only 9 out of 1011 patients experienced seizures which were managed using medications. 4 out of 9 had history of seizures while 5 had normal EEG with no history. However, improvements were still observed in these 9 patients. Thus, intrathecal transplantation of autologous BMMNCs along with neurorehabilitation is safe and efficacious in patients with ASD.

Background: This study investigated the incidence, characteristics and functional outcomes associated with unplanned Acute Care Unit Readmissions (ACUR) during inpatient traumatic brain injury (TBI) rehabilitation in an Asian cohort. Methods: Retrospective review of electronic medical records from single rehabilitation unit was conducted from 1 Jan 2012 to 31 Dec 2014. Inclusion criteria were first TBI, aged &gt;18 years, admitted &lt; 6 months of TBI. ACUR were characterized into either of neurological, medical or neurosurgical subtypes. The main outcome measure was discharge Functional Independence Measure (FIM). Secondary outcomes included rehabilitation length of stay (RLOS). Results: Of 121 eligible TBI records, the incidence of ACUR was 14% (n=17), comprising neurologic (76.5%) and medical (23.5%) subtypes, occurring at median of 13 days (IQR 6, 28.5) after rehabilitation admission. Patients without ACUR had significantly higher admission mean (SD) FIM score compared to those with ACUR (FIM ACUR-negative 63.4 (21.1) vs FIM ACUR-positive 50.53(25.4), P =0.026). Significantly lower discharge FIM was noted in those with ACUR compared to those without. (FIM ACUR-positive 65.8(31.4) vs FIM ACUR-negative 85.4 (21.1), P = 0.023) Furthermore, a significant near-doubling of RLOS was noted in ACUR patients compared to non-ACUR counterparts [ACUR-positive median 55 days (IQR 34.50, 87.50) vs ACUR-negative median 28 days (IQR 16.25, 40.00), P = 0.002]. Conclusion: This study highlights the significant negative functional impact and lengthening of rehabilitation duration of ACUR on inpatient rehabilitation outcome for TBI.

Uncontrolled and fast cell proliferation is the cause of brain tumors. Early cancer detection is vitally important in order to save many lives. Brain tumors can be divided into several categories depending on the kind, place of origin, pace of development, and stage of progression; as a result, tumor classification is crucial for targeted therapy. The aim of brain tumor segmentation is to accurately delineate the areas of the brain. A specialist with a thorough understanding of brain illnesses must manually identify the proper type of brain tumor. Additionally, processing a lot of images takes time and is tiresome. Therefore, automatic segmentation and classification techniques are required to speed up and enhance the diagnosis of brain tumors. Tumors can be quickly and safely detected by brain scans using imaging modalities, including computed tomography (CT), magnetic resonance imaging (MRI), and others. Machine learning (ML) and artificial intelligence (AI) have shown promise in the development of algorithms that aid in automatic classification and segmentation utilizing various imaging modalities. This review discussed various types of brain tumors, publicly accessible datasets, enhancement methods, segmentation, feature extraction, classification, machine learning techniques, and deep learning, learning through transfer, for the study of brain tumors.

Judo is a popular Japanese martial art and an Olympic sport. Recently, an increasing interest has been observed in the application of judo as a multicomponent exercise, with a growing body of evidence showing that multicomponent exercise improves physical and cognitive performance in older adults. Therefore, this review highlights the benefits of judo training in preventing physical and cognitive decline in older adults. Specifically, first, this review outlines the basic characteristics of judo (philosophy, match, and training). Next, previous studies investigating the effects of judo training on physical and cognitive aspects of older adults are reviewed. Thereafter, the brain mechanisms underlying the effects of judo training in improving physical and cognitive performance are discussed. Throughout this review, judo training demonstrated some positive effects on physical (gait and balance, among others) and cognitive (memory and executive function) function in older adults. These positive effects are attributed to a variety of changes in the brain (e.g., increased neurotrophic factor expression and increased cerebral blood flow, among others), that affect different brain regions and networks both functionally and structurally. From these findings, this review concludes that judo training can be an effective way to maintain and prevent physical and cognitive decline in older adults.

In this work, we developed a highly sensitive multiplexed immunosensor for direct simultaneous detection of both N-terminal Natriuretic Peptide (NT-proBNP) and Cortisol in human artificial saliva (AS). The developed biosensor platform based on silicon nitride was composed from four gold working microelectrodes (WEs) and an integrated counter and reference electrode. Gold WEs were biofunctionalized through carboxyl diazonium (4-APA) to immobilize both anti- NT-proBNP and anti-Cortisol antibodies for simultaneous detection. The electroaddressing of the 4-APA onto the gold WE surfaces was realized by cyclic voltammetry (CV), while the interaction between antibodies and antigens in PBS was monitored by electrochemical impedance spectroscopy (EIS). The antigen detection in human AS was realized by EIS combined with the standard addition method. The immunesensor was highly sensitive and selective toward the corresponding biomarkers in both PBS and artificial human saliva as well as in the presence of other potential interfering biomarkers such as tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10). The limit of detection (LOD) was at 0.2pg/mL for NT-proBNP within the range 0.03 to 0.9pg/mL, while the LOD for Cortisol was 0.06 ng/mL within the range 0.02 to 0.6 ng/mL for Cortisol in artificial saliva. The developed immunosensor is very promising for significant detection time reducing as it allows the simultaneous detection of various biomarkers.