Pathological Activity Research Articles

Advancing Alzheimer's disease pharmacotherapy: efficacy of glucocorticoid modulation with dazucorilant (CORT113176) in preclinical mouse models.

Exposure to chronic stress and high levels of glucocorticoid hormones in adulthood has been associated with cognitive deficits and increased risk of Alzheimer's disease (AD). Dazucorilant has recently emerged as a selective glucocorticoid receptor (NR3C1) modulator, exhibiting efficacy in counteracting amyloid-β toxicity in an acute model of AD. We aim to assess the therapeutic potential of dazucorilant in reversing amyloid and tau pathologies through the inhibition of glucocorticoid receptor pathological activity, and providing additional evidence for its consideration in AD treatment. The efficacy of dazucorilant was evaluated in two transgenic mouse models of amyloid pathology. The slowly progressing J20 and the aggressively pathological 5xFAD mice. Behavioural analysis was conducted to evaluate welfare, cognitive performances and anxiety levels. The activity of the glucocorticoid receptor system, neuroinflammation, amyloid burden and tau phosphorylation were examined in hippocampi. In both AD models, chronic treatment with dazucorilant improved working and long-term spatial memories along with the inhibition of glucocorticoid receptor-dependent pathogenic processes and the normalization of plasma glucocorticoid levels. Dazucorilant treatment also resulted in a reduction in tau hyperphosphorylation and amyloid production and aggregation. Additionally, dazucorilant seemed to mediate a specific re-localization of activated glial cells onto amyloid plaques in J20 mice, suggesting a restoration of physiological neuroinflammatory processes. Dazucorilant exhibited sustained disease-modifying effects in two AD models. Given that this compound has demonstrated safety and tolerability in human subjects, our results provide pre-clinical support for conducting clinical trials to evaluate its potential in AD.

Schwann cells in regeneration and cancer

Schwann cells are specific peripheral glial cells with remarkable plasticity following peripheral nerve injury. Injury responses stimulate c-Jun activation in Schwann cells, drive epithelial-mesenchymal transition and cellular phenotypic changes, and induce the generation of reprogrammed repair Schwann cells to orchestrate peripheral nerve regeneration process. Schwann cells and/or Schwann cell-derived molecules are commonly used as supporting cells and/or neurotrophic factors to construct Schwann cell-based tissue-engineered nerve grafts for repairing severe peripheral nerve injury with long defects. Transplantation of Schwann cells and/or Schwann cell-derived molecules also serves as a helpful approach for the treatment of other injured tissues, such as the spinal cord, skin, digit tip, and bone. Schwann cells are not only associated with tissue regeneration but also involved in tumorigenesis and tumor progression. Schwann cells are the major cellular component of neurofibromatosis type 1 and the sole cell type in neurofibromatosis type 2 and schwannomatosis. In addition, Schwann cells also function as an important player in the tumor microenvironment and aid in the growth and invasiveness of many other solid cancers. In the present review, we outline the physiological and pathological activities of Schwann cells and discuss the functional roles of Schwann cells in homeostasis, regeneration, and cancer.

Inhibition of high glucose-induced cardiac fibroblast activation: an effective treatment for diabetic cardiomyopathy using Chinese herbal medicine

Diabetic cardiomyopathy (DCM) is one of the common diabetic microangiopathy in clinical practice. In the early stage of the disease, there are no obvious clinical symptoms. In the middle and late stages, MF, arrhythmia, and even heart failure may occur, affecting the life and health of patients. MF, as one of the pathological features of DCM at the end stage, is the key factor of poor prognosis leading to ventricular wall stiffness and heart failure, which affects the clinical process and outcome of patients. The development of MF in a high glucose environment involves multiple complex fibrogenic pathways that work together to activate fibroblasts, thereby promoting MF. Indeed, aberrant activation of cardiac fibroblasts (CFs) is a key factor in MF. Therefore, inhibiting the activation of CFs may become a new strategy for the treatment of DCM. Previous studies have shown that Chinese herbal medicine (CHM) has potential in the treatment of DCM. In this review, we first introduced the physiology and function of CFs and discussed the conditions for the pathological activation of CFs in the process of diabetes, and then systematically summarized the effects of CHM on the activation of CFs by controlling the production of advanced glycosylation end products, oxidative stress and inflammation. This review will illustrate the potential of CHM to inhibit the activation of CFs and provide new ideas for the treatment of DCM.

O-05 A RARE CAUSE OF BILATERAL GIANT ADRENAL MASS: PRIMARY ADRENAL LYMPHOMA

Abstract Introduction Primary adrenal lymphoma (PAL) is an extremely rare form of non-Hodgkin lymphoma, representing less than 1% of cases. It is usually bilateral, unlike secondary adrenal lymphoma, which is often unilateral. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of PAL, making up about 70% of cases. PAL primarily affects older patients and lacks distinct nodular lesions, making diagnosis difficult; pathological examination is essential for confirmation. Clinical Case A 62-year-old male patient with no known comorbidities presented with symptoms of night sweats, weight loss (approximately 10 kg over the past month), and general weakness persisting for the past two months. Physical examination revealed decreased breath sounds in the bilateral lower lung fields and a dullness to percussion over Traube's space on abdominal examination. No other pathological findings were noted. Vital signs were in normal range. Laboratory evaluation showed normocytic anemia, thrombocytopenia, and hypercalcemia with suppressed parathyroid hormone levels. Additionally, lactate dehydrogenase levels were elevated (see Table 1). A thoracic, abdominal, and pelvic computed tomography (CT) scan was performed to assess for malignancy. The CT scan revealed a solid mass lesion measuring approximately 11 x 18 x 10 cm with an average density of 50 HU, exhibiting non-homogeneous contrast enhancement. This lesion is located in the bilateral adrenal regions and show confluent extension anterior to the abdominal aorta (see Figure 1). Subsequently, the patient underwent hormonal analysis to assess adrenal function and an 18F-FDG PET/CT scan was planned. Hormonal analysis indicated that the adrenal mass was non-functional, with preserved adrenal gland function (see Table 2). The PET/CT scan showed intense pathological activity accumulation in the adrenal mass lesion (SUVmax: 25.9) and diffuse increased activity in the bone marrow. Following this, both bone marrow and adrenal mass biopsies were performed. The bone marrow biopsy did not reveal infiltrative pathology. However, the biopsy of the adrenal mass was reported as aggressive mature large B-cell lymphoma. Primary bilateral adrenal lymphoma was diagnosed. The patient was evaluated by hematology and subsequently initiated on R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy. Following six cycles of R-CHOP, the suprarenal mass is completely resolved. However, during follow-up one year later, the disease relapsed with a cranial mass. Conclusion PAL is a rare extranodal non-Hodgkin's lymphoma, predominantly affecting males around 70 years old. It usually presents with large bilateral adrenal masses and can cause primary adrenal insufficiency (PAI) in up to 70% of cases. Diagnosis is confirmed by histology after imaging. Treatment typically involves a combination of surgery, chemotherapy, and/or radiotherapy, with PAI requiring hormone replacement therapy.Figure 1:Imaging of the Tumor Lesion Before and After Chemotherapya/b) Pre/Post-Chemotherapy PET/CT Imaging, c/d) Pre/Post-Chemotherapy CT Imaging Table 1:Patient’s laboratory parameters Table 2:Patient’s adrenal function assessment(Values marked with an asterisk (*) were measured in a 24-hour urine collection, while the other values were measured in plasma.) (DHEAS: Dehydroepiandrosterone sulfate)

Ultrasound Evaluation of Upper Limb Sublesional Muscle Morphology in Cervical Spinal Cord Injury.

Upper limb paralysis is arguably the most limiting consequence of cervical spinal cord injury (cSCI). There is limited knowledge regarding the early structural changes of muscles implicated in grasp/pinch function and upper extremity nerve transfer surgeries. We evaluated: (1) muscle size and echo intensity (EI) in subacute cSCI (2-6 months) and (2) the influence of lower motor neuron (LMN) damage on these ultrasound parameters. Cross-sectional B-mode images were captured bilaterally in individuals with cSCI (injury duration: 3.3 ± 1.2 months; C4-C6 injury levels; American Spinal Injuries Association Impairment Scale A-C; 45.7 ± 13.7 years; 3 females, 14 males) for biceps brachii (BB), extensor carpi ulnaris, extensor indicis proprius, flexor pollicis longus (FPL), and first dorsal interosseous. Each limb was analyzed as an independent event (n = 34). Cross-sectional area (CSA), thickness (MT), and EI were compared to healthy controls (HC). BB and FPL concentric needle electromyography (EMG) data were also obtained. Abnormal LMN health was defined by the presence of pathological spontaneous activity. Relative to HC, forearm and hand muscle size were 15%-41% lower (p < 0.05), while EI was 21%-40% higher (p < 0.05); no significant differences were observed for sublesional BB muscles (n = 16) (p > 0.05). Muscles demonstrating abnormal LMN health displayed reduced BB MT and elevated FPL EI (p < 0.05). These results underscore the substantial changes in forearm and hand muscle morphology within the subacute period after cSCI, with preliminary evidence suggesting that these changes are influenced by LMN damage.

PRMT5 Inhibition Reduces Hyperinflammation in a Murine Model of Secondary Hemophagocytic Lymphohistiocytosis (HLH).

Hemophagocytic lymphohistiocytosis (HLH) is a rare but aggressive and potentially lethal hyperinflammatory syndrome characterized by pathologic immune activation and excessive production of proinflammatory cytokines leading to tissue damage and multisystem organ failure. There is an urgent need for the discovery of novel targets and development of therapeutic strategies to treat this rare but deadly syndrome. Protein Arginine Methyltransferase 5 (PRMT5) mediates T cell-based inflammatory responses, making it a potential actionable target for the treatment of HLH. Using CPG-1826 and anti-IL10R antibody, we induced murine secondary HLH in vivo with a marked expansion of splenic myeloid cell subsets and concurrent reduction of T and NK cell populations. PRMT5 expression was significantly upregulated in splenic T and NK lymphocytes as well as monocytes and dendritic cells in mice with HLH (p<0.05). Treatment with PRT382, a potent and selective PRMT5 inhibitor, significantly reduced physical signs of secondary HLH, including splenomegaly, hepatomegaly and anemia (p<0.0001 in each case), when compared to untreated mice. Inflammatory cytokines known to drive hyperinflammation in HLH, including IFNγ and IL-6 were reduced to healthy levels with PRT382 treatment (p>0.999 for both). PRT382 treatment also reduced the expansion of myeloid cell populations (p<0.0001) in mice with HLH, compared to untreated mice, while restoring T and NK cell numbers (p<0.001 for both). These results identify PRMT5 as a promising target for the management of secondary HLH and justify further exploration in this and other models of hyperinflammation.

Mapping Pituitary Neuroendocrine Tumors: An Annotated MRI Dataset Profiling Tumor and Carotid Characteristics

Pituitary neuroendocrine tumors remain one of the most common intracranial tumors. While radiomic research related to pituitary tumors is progressing, public data sets for external validation remain scarce. We introduce an open dataset comprising high-resolution T1 contrast-enhanced MR scans of 136 patients with pituitary tumors, annotated for tumor segmentation and accompanied by clinical, radiological and pathological metadata. This diverse dataset captures variations in tumor size, location, and pathological activity, essential for understanding this complex condition. Expert annotations of both the tumor and adjacent carotid arteries ensure precise delineation, facilitating the development of automated segmentation algorithms. Our initiative addresses the need for standardized data in pituitary oncology, fosters collaboration and innovation, and enables the development and benchmarking of workflows that utilize pituitary radiomics for treatment planning and outcome prediction.

Biological function and mechanism of NAT10 in cancer.

N-acetyltransferase 10 (NAT10) is a nucleolar acetyltransferase with an acetylation catalytic function and can bind various protein and RNA molecules. As the N4-acetylcytidine (ac4C) "writer" enzyme, NAT10 is reportedly involved in a variety of physiological and pathological activities. Currently, the NAT10-related molecular mechanisms in various cancers are not fully understood. In this review, we first describe the cellular localization of NAT10 and then summarize its numerous biological functions. NAT10 is involved in various biological processes by mediating the acetylation of different proteins and RNAs. These biological functions are also associated with cancer progression and patient prognosis. We also review the mechanisms by which NAT10 plays roles in various cancer types. NAT10 can affect tumor cell proliferation, metastasis, and stress tolerance through its acetyltransferase properties. Further research into NAT10 functions and expression regulation in tumors will help explore its future potential in cancer diagnosis, treatment, and prognosis.

Wnt signaling drives stromal inflammation in inflammatory arthritis.

The concept that fibroblasts are critical mediators of inflammation is an emerging paradigm. In rheumatoid arthritis (RA), they are the main producers of IL-6 as well as a host of other cytokines and chemokines. Their pathologic activation also directly causes cartilage and bone degradation. Yet, therapeutic agents specifically targeting fibroblasts are not available. Here, we find that Wnt receptors and modulators are predominantly expressed in stromal populations in the synovium. Importantly, non-canonical Wnt activation induces robust inflammatory gene expression including an abundance of cytokines and chemokines in synovial fibroblasts in vitro . Strikingly, the addition of Wnt ligands or inhibition of Wnt secretion exacerbates or reduces arthritis severity, respectively, in vivo in a murine model of inflammatory arthritis. These observations are relevant in human disease, as Wnt activation signatures are enhanced in fibroblasts derived from inflamed RA synovial tissue as well as fibroblasts across other inflammatory diseases. Together, these findings implicate Wnt signaling as a major driver of fibroblast-mediated inflammation and joint pathology. They further suggest that targeting the Wnt pathway is a therapeutically relevant approach to rheumatoid arthritis, particularly in patients who do not respond to conventional treatments and who often express fibroblast-predominant synovial phenotypes.

CHARACTERISTICS OF THE FUNCTIONAL STATUS OF MASTICULING MUSCLES ACCORDING TO ELECTROMYOGRAPHY DATA IN PATIENTS WITH BRUXISM UNDER THE INFLUENCE OF REHABILITATION INTERVENTION

Purpose: to evaluate the effectiveness of the developed physical therapy program based on the parameters of the electromyographic study of the masticatory muscles of patients with bruxism. Material. The control group consisted of 32 people without burdened dental status. Group 1 consisted of 31 people with bruxism, which was corrected with individual relaxing splints. Group 2 consisted of 32 people with bruxism, in whom, in addition to splints, a physical therapy program was applied - therapeutic exercises, massage, post-isometric relaxation, kinesiological taping for masticatory muscles, muscles of the face, neck, cervical collar zone, back, shoulder, electromyostimulation of masticatory muscles; autorelaxation sessions according to Schultz; patient education. The purpose of the program was: normalization of the strength and tone of the muscles of the face and neck; reduction of discomfort; improvement of chewing function; improving the quality of life. The effectiveness of the program was evaluated based on the results of electromyography. Results. In patients with bruxism, signs of bilateral increased bioelectric activity of the masticatory and temporal muscles at rest and during functional load were determined by their average amplitude, with the preference of masticatory muscle activity when determining symmetry indices based on the results of electromyography. The program of complex physical therapy demonstrated a statistically significantly better effect (p&lt;0.05) on the studied indicators of bioelectric activity of the masticatory and temporal muscles compared to the group of patients who underwent rehabilitation with the use of passive splint therapy. During the re-examination, it was established that in both studied groups there was an improvement in the condition of the patients relative to the initial level, but with an advantage in the individuals of group 2. At rest, the activity of the masticatory muscles on the right side decreased statistically significantly (p&lt;0.05) compared to the initial level in group 1 by 23.8%, group 2 by 47.4%; on the left side – by 22.6% and 41.7%, respectively. The average activity of the temporal muscles in group 1 did not change (p&gt;0.05); in group 2, it decreased on the right side by 25.9%, on the left side by 33.3% (p&lt;0.05). Indices of symmetry of masticatory and temporal muscle activity at rest continued to characterize the relatively symmetrical tension of these groups; there was a decrease in the activity preference of masticatory muscles over temporal muscles - in group 1 by 18.5%, in group 2 - by 23.3% (р&lt;0.05). A statistically significant improvement compared to the initial result (p&lt;0.05) was achieved in both groups according to the results with functional load. The improvement of activity of the masticatory muscles on the right side was 23.1% in group 1, 23.5% in group 2 (р&lt;0.05); from the left - 46.8% and 48.8%, respectively (p&lt;0.05). The reduction of excessive bioelectric activity due to CA of the temporal muscles was 16.1% on the right side in group 1, 14.0% on the left side, and 36.1% and 40.9%, respectively, in group 2 (р&lt;0.05). Symmetry of occlusion also improved - in group 1 by 9.7%, in group 2 - by 15.1%. Conclusions. Means of physical therapy improve the effectiveness of dental interventions, therefore, it is advisable to use them to reduce the severity of pathological high bioelectric activity of the masticatory muscles, which is the basis for improving the functioning of the orofacial zone in patients with bruxism.

Adolescent seizure impacts oligodendrocyte maturation, neuronal-glial circuit Formation, and myelination in the mammalian forebrain.

Oligodendrocyte progenitor cells differentiate into oligodendrocytes, which myelinate axons during development and following demyelinating injury. However, the mechanisms that drive the timing and specificity of developmental myelination are not well understood. We hypothesized that oligodendrocyte progenitor cell proliferation and differentiation would be affected by pathological neuronal activity during adolescent development when developmental myelination is occurring and that this would also impact neuron-to-oligodendrocyte progenitor cell connectivity and myelination. We used kainic acid to induce a seizure in mice, treating equal numbers of males and females, in sample sizes of at least five animals. We found that the seizures led to increased cell death overall, specifically in the oligodendrocyte-lineage cells. We found that both oligodendrocyte progenitor cell proliferation and overall numbers increased, and the number of mature oligodendrocytes decreased. We found a decrease in myelin in the cerebral cortex, corpus callosum, and hippocampus after a seizure. We observed an increase in demyelinating lesions, but no change in neuronal process length, in brains after seizure, suggesting that the demyelination was due primarily to the loss of both oligodendrocyte-lineage cells. We found that Kir4.1 potassium channel expression on oligodendrocyte progenitor cells decreased after seizure, but not mature oligodendrocytes. Finally, we found a decrease in neuron-to-oligodendrocyte progenitor cell connections in seizure mice compared to controls. These findings provide insight into the response of the adolescent brain to seizure activity, as well as how seizures affect oligodendrocyte development, neuronal-glial connections, and myelin formation.

Early therapy initiation is crucial in chronic inflammatory demyelinating polyneuropathy: prospective multimodal data from the German INHIBIT registry

BackgroundDiagnosing chronic inflammatory demyelinating polyneuropathy (CIDP) can be challenging, leading to delays in initiating therapy. As disability in CIDP is mainly dependent on axonal damage, the impact of delayed immunotherapy remains unclear. We multimodally investigated the clinical outcomes of patients with early CIDP regarding different treatment strategies and time points.MethodsPatients with CIDP diagnosis within 1 year before study inclusion were systematically selected from the prospective Immune-mediated Neuropathies Biobank (INHIBIT) registry. Clinical and therapeutic data, and findings from nerve conduction study (NCS), and nerve and muscle ultrasound were correlated at inclusion and 12 months later. The patient outcomes were compared between immunotherapies. The effect of timing immunotherapy on clinical outcomes was determined using regression analysis.ResultsIn total, 30 patients were included (time from diagnosis to inclusion 22 ± 19 weeks). Low amplitudes of compound muscle potential were significantly associated with pathological spontaneous activity (PSA, r = 0.467) and correlated with the Heckmatt scale (rSp = 0.391). All three parameters were significantly associated with higher overall disability sum scores (NCS score rSp = 0.581, PSA r = 0.385, Heckmatt scale rSp = 0.472). The delays in initiating therapy resulted in progression of axonal damage (rSp = 0.467) and disability (R2 = 0.200). The combination of first-line therapies led to reduced disability progression (r = 0.773), while second-line therapies resulted in improved overall axonal damage (r = 0.467).ConclusionsAxonal damage occurs early and is the main cause of clinical disabilities. Prompt initiation of therapy is crucial to prevent axonal damage and thereby disability progression. A comprehensive therapeutic approach, including a combination of first- or second-line therapies, may improve long-term outcomes.

A NEW ROLE FOR KYNURENINE METABOLISM IN THE AGE-ASSOCIATED DECLINE OF THE BACTERIAL IMMUNE RESPONSE

Abstract Tryptophan metabolism through the kynurenine pathway becomes dysregulated during normal aging and is implicated in age-associated disease, including chronic inflammation, atherosclerosis, neurodegeneration, and cancer. Kynurenine pathway enzymes and metabolites influence a range of molecular processes critical to healthy aging, including regulation of inflammatory and immune responses. Kynurenine metabolism is active in immune cells and activated in response to proinflammatory cytokine signaling. We previously determined that elevating physiological levels of the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3HAA) via either direct supplementation or inhibition of the enzyme that degrades 3HAA, 3HAA dioxygenase (HAAO), extends lifespan and delays age-associated health decline in both Caenorhabditis elegans and mice. Published work suggests that 3HAA is anti-inflammatory in mammals, for example by reducing the ratio of activated to regulatory T cells and inhibiting pathological activation of macrophages. In recent work, we find that elevating physiological 3HAA can beneficially enhance the immune response of C. elegans to bacterial pathogens during aging. 3HAA is sufficient to kill bacterial and inhibit bacterial growth in culture. When HAAO is inhibited in C. elegans, 3HAA accumulates in lysosome related organelles (LROs) in the intestinal cells, the same subcellular compartment that contains engulfed bacteria. LROs are a cellular repository for both iron and zinc, and we further find that iron chelation or zinc supplementation dramatically enhances the bactericidal properties of 3HAA. Here we present a mechanistic model in which age-dependent accumulation of 3HAA in intestinal LROs combines with zinc to enhance bacterial resistance with age in C. elegans.

Non-conventional deep brain stimulation in a network model of movement disorders

Conventional deep brain stimulation (DBS) for movement disorders is a well-established clinical treatment. Over the last few decades, over 200,000 people have been treated by DBS worldwide for several neurological conditions, including Parkinson's disease and Essential Tremor. DBS involves implanting electrodes into disorder-specific targets in the brain and applying an electric current. Although the hardware has developed in recent years, the clinically used stimulation pattern has remained as a regular frequency square pulse. Recent studies have suggested that phase-locking, coordinated reset or irregular patterns may be as or more effective at desynchronising the pathological neural activity. Such studies have shown efficacy using detailed neuron models or highly simplified networks and considered one frequency band. We previously described a population level model which generates oscillatory activity in both the beta band (20 Hz) and the tremor band (4 Hz). Here we use this model to look at the impact of applying regular, irregular and phase dependent bursts of stimulation, and show how this influences both tremor- and beta-band activity. We found that bursts are as or more effective at suppressing the pathological oscillations compared to continuous DBS. Importantly however, at higher amplitudes we found that the stimulus drove the network activity, as seen previously. Strikingly, this suppression was most apparent for the tremor band oscillations, with beta band pathological activity being more resistant to the burst stimulation compared to continuous, conventional DBS. Furthermore, our simulations showed that phase-locked bursts of stimulation did not convey much improvement on regular bursts of oscillation. Using a genetic algorithm optimisation approach to find the best stimulation parameters for regular, irregular and phase-locked bursts, we confirmed that tremor band oscillations could be more readily suppressed. Our results allow exploration of stimulation mechanisms at the network level to formulate testable predictions regarding parameter settings in DBS.

Annotated interictal discharges in intracranial EEG sleep data and related machine learning detection scheme

Interictal epileptiform discharges (IEDs) such as spikes and sharp waves represent pathological electrophysiological activities occurring in epilepsy patients between seizures. IEDs occur preferentially during non-rapid eye movement (NREM) sleep and are associated with impaired memory and cognition. Despite growing interest, most studies involving IED detections rely on visual annotations or employ simple amplitude threshold approaches. Alternatively, advanced computerized detection methods are not standardized or publicly available. To address this gap, we introduce a novel dataset comprising multichannel intracranial electroencephalography (iEEG) data recorded at two medical centers during overnight sleep with IED annotations performed by expert neurologists. Utilizing these annotations to train machine learning models via a gradient-boosting algorithm, we demonstrate automated IED detection with high precision (94.4%) and sensitivity (94.3%) that can generalize across individuals and surpass performance of a leading commercial software. The dataset featuring multi-channel annotations with sub-second resolution including hippocampus and medial temporal lobe (MTL) regions is made publicly available, together with the detection algorithm, to advance research on detection methodology, epilepsy, sleep, and cognition.

Impact of Sliding Window Overlap Ratio on EEG-Based ASD Diagnosis Using Brain Hemisphere Energy and Machine Learning

Early screening is a key component of intensive intervention therapy and rehabilitation for children with autism spectrum disorder (ASD). Electroencephalogram (EEG) signals provide real-time, high-sensitivity monitoring of pathological activities in children with ASD. This study used a dataset of 52 samples with 19-channel sleep data and proposed a new approach to diagnosing ASD based on energy differences between the left and right hemispheres of the brain. The preprocessing stage included decimation, band-pass filtering to remove unwanted frequencies, artifact subspace reconstruction to eliminate artifacts, and amplitude normalization to preserve the relative relationships between the signal features, which were crucial for the subsequent analysis and classification. Five band-pass filters were applied to decomposing the EEG signals. For each decomposed band, the signals from each brain hemisphere were analyzed separately by calculating the peak sensor’s envelope and obtaining the mean envelope for each hemisphere, resulting in two mean signals (right and left). Features were extracted using a sliding window approach applied to the mean signals of each hemisphere, with varying overlap ratios (12.5% to 87.5%, in 12.5% steps). The maximum, mean, and minimum energy values were used individually as features. Three types of SVM kernels—linear (L), the radial basis function (RBF), and quadratic—were employed for classification. The proposed method achieved the highest accuracy, sensitivity, and F1-score of 91.7%, 91.4%, and 91.6%, respectively, in the Theta band using SVM-L with the maximum energy features and the maximum overlap ratio.

Intranasal Delivery of Lithium Salt Suppresses Inflammatory Pyroptosis in the brain and Ameliorates Memory Loss and Depression-like Behavior in 5XFAD mice.

This study compares the changes in lithium concentrations in the brain and blood following the administration of intranasal or oral lithium chloride (LiCl) dissolved in either Ryanodex Formulation Vehicle (RFV) or water, as well as the therapeutic effectiveness and side effects of intranasal versus oral lithium chloride (LiCl) in RFV, and their mechanisms for inhibiting inflammation and pyroptosis in 5xFAD Alzheimers Disease (AD) mice brains. In comparison to oral LiCl in RFV, intranasal LiCl in RFV decreased lithium blood concentrations but increased brain concentrations and duration, resulting in a significantly higher brain/blood lithium concentration ratio than intranasal LiCl in water or oral LiCl in RFV in young adult mice. Intranasal LiCl in RFV robustly protects both memory loss and depressive behavior in both young and old 5xFAD mice, with no side effects or thyroid/kidney toxicity. In fact, intranasal LiCl in RFV protects against age-dependent kidney function impairment in 5xFAD mice. This lithium mediated neuroprotection was associated with its potent effects on the inhibition of InsP3R-1 Ca2+ channel receptor increase, ameliorating pathological inflammation and activation of the pyroptosis pathway, and the associated loss of synapse proteins. Intranasal LiCl in RFV could become an effective and potent inhibitor of pathological inflammation/pyroptosis in the CNS and treat both dementia and depression with no or minimal side effects/organ toxicity, particular in AD.

Research Progress in the Field of Hydrogen Sulfide Donors in the Last Five Years.

Hydrogen sulfide (H2S) serves as the third gasotransmitter, crucial in various physiological processes involving its production and metabolism. Elevated levels of H2S can result in acute or chronic poisoning, whereas lower concentrations are involved in regulating diverse physiological and pathological activities within the human body. Moreover, it actively participates in maintaining normal cellular function by exerting cell protection and anti-apoptotic effects. In recent years, extensive research has been conducted to explore the physiological significance of H2S and its potential applications in developing prodrugs. To further unravel the biological and clinical potential of H2S, H2S donors have gained widespread utilization. These compounds facilitate our understanding of the specific functional aspects governed by H2S and hold promise as potential therapeutic agents. Therefore, it is necessary to study H2S as a delivery vehicle at the cellular and in vivo levels. This review provides an overview of advancements made over the past five years regarding H2S donors and their applications in biology, encompassing indirectly released donors of carbonyl sulfide (COS), directly released small molecule donors, Nanocomposite scaffolds, and hydrogels.

Endothelial molecule levels (VCAM-1, ICAM-1) in uncomplicated malaria cases in Lagos, Nigeria

Background. Elevated endothelial activation markers are linked to malaria syndromes due to the sequestration of Plasmodium falciparum-infected red blood cells in deep tissue vessels. This study evaluated vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) levels in uncomplicated malaria and their association with host factors. Methods. A cross-sectional study was conducted in four health facilities in Ikorodu, Lagos State, Nigeria. Blood samples from children and adults were screened for malaria via microscopy, and plasma ICAM-1 and VCAM-1 levels were measured using ELISA. Results. ICAM-1 (1.03 × 106 ± 20,689.2 pg/ml) and VCAM-1 (1.11 × 106 pg/ml; range: 3,725–6,273,725 pg/ml) levels were significantly higher in malaria-positive cases compared to controls (p &lt; 0.01). The geometric mean parasite density was 11,183 parasites/μl, but ICAM-1 and VCAM-1 levels did not correlate with parasite density (p &gt; 0.1). Packed cell volume (PCV) was significantly lower in malaria-positive cases (p = 0.042), with ICAM-1 and VCAM-1 negatively correlating with PCV (p &lt; 0.05). Both markers were also inversely associated with age (p &lt; 0.05). Conclusion. VCAM-1 and ICAM-1 levels are elevated in uncomplicated malaria, independent of parasite density but negatively associated with PCV and age, highlighting the role of endothelial activation in malaria pathology.

Expansion of epileptogenic networks via neuroplasticity in neural mass models.

Neuroplasticity refers to functional and structural changes in brain regions in response to healthy and pathological activity. Activity dependent plasticity induced by epileptic activity can involve healthy brain regions into the epileptogenic network by perturbing their excitation/inhibition balance. In this article, we present a new neural mass model, which accounts for neuroplasticity, for investigating the possible mechanisms underlying the epileptogenic network expansion. Our multiple-timescale model is inspired by physiological calcium-mediated synaptic plasticity and pathological extrasynaptic N-methyl-D-aspartate (NMDA) dependent plasticity dynamics. The model highlights that synaptic plasticity at excitatory connections and structural changes in the inhibitory system can transform a healthy region into a secondary epileptic focus under recurrent seizures and interictal activity occurring in the primary focus. Our results suggest that the latent period of this transformation can provide a window of opportunity to prevent the expansion of epileptogenic networks, formation of an epileptic focus, or other comorbidities associated with epileptic activity.