Neurological Disorders Research Articles

Health status and quality of life before critical illness: Northern Finland Birth Cohort 1966 study.

Previous findings support the claim intensive care unit (ICU) patients have a higher rate of comorbidities and reduction of health- and functional status compared with the normal population. In this prospective observational study, our aim was to determine those health-related factors at the age of 31 years which were associated with a later critical illness among previously un-hospitalized individuals by exploring data obtained from the Northern Finland Birth Cohort 1966 (NFBC1966). NFBC1966 is a Finnish birth cohort, which includes 12,058 live births with expected dates of delivery during 1966. The study was conducted among cohort participants who had not been hospitalized for any reason before the cohort follow-up visit at the age of 31. The study group included NFBC1966 participants who were admitted to the ICU of the Oulu University Hospital. The control group included participants who were treated for any reason in regular hospital wards. The data considering the participants' health status and behavior at the age of 31 were collected from the NFBC1966 database. The gathering of ICU and hospitalization data was concluded on December 31, 2016. 849 NFBC1966 participants met the inclusion criteria: 69 were treated in the ICU (study group) and 780 on regular hospital wards (controls). In the study group, the rate of neurological diseases (26% vs. 16%, 95% CI: -21.8%, -0.2%), malignancy (3% vs. 0.7%, 95% CI: -9.7%, 0.0%), alcohol abuse (4.5% vs. 1%, 95% CI: -11.5%, -0.3%) and smoking (77% vs. 65%, 95% CI: -21.6%, -0.3%) were higher compared with the control group. The patients in the ICU group were also more prone to violent injuries, (17% vs. 7%, 95% CI: -20.2%, -1.9%), practiced less hard physical activity (65% vs. 78%, 95% CI: 2.1%, 25.3%) and had lower maximal muscle strength according to the hand grip test (30 vs. 34 kg, 95% CI: -8.2, 8.6 kg). In this study examining previously un-hospitalized patients, the main factors associated with future critical illness were neurological comorbidities, malignancy, alcohol misuse, smoking, low maximum muscle strength, and less frequent physical exercise compared with those with hospitalization not requiring ICU admission.

Evaluation of Glymphatic System Development in Neonatal Brain via Diffusion Analysis along the Perivascular Space Index.

Glymphatic system is a recently discovered macroscopic waste clearance system associated with numerous neurological diseases. However, little is known about glymphatic system development in neonates. We sought to evaluate diffusion along the perivascular space (ALPS) index, a proxy for glymphatic system function, in neonates and investigate its potential associations with maturation, sex, and preterm birth. Diffusion magnetic resonance imaging (MRI) data in 418 neonates, including 92 preterm neonates (57 males) and 326 term neonates (175 males), from the Developing Human Connectome Project were used for evaluating ALPS index. Linear regression modeling was performed to assess group differences in the ALPS index according to preterm birth and sex. Pearson's and partial correlation analysis were performed to assess the association between the ALPS index and gestational age (GA) as well as postmenstrual age (PMA) at MRI. Moderation analysis was performed to assess the moderation effect of preterm birth on the relationship between the ALPS index and PMA. Compared to term neonates, preterm neonates exhibited lower ALPS indices (p < 0.001). The ALPS index positively correlated with PMA (p = 0.004) and GA (p < 0.001). Preterm birth (p = 0.013) had a significant moderation effect on the relationship between the ALPS index and PMA. Sex had no significant direct effect (p = 0.639) or moderation effect (p = 0.333) on ALPS index. Glymphatic system development is a dynamic process in neonates, which can be moderated by preterm birth, the ALPS index could serve as a sensitive biomarker for monitoring this process. ANN NEUROL 2024;96:970-980.

Tandem mass tag-based proteomics reveals the antiepileptic mechanism of steroidal saponins from Anemarrhena asphodeloides in Kainic acid induced epileptic rat model.

Epilepsy (EP) is one of the most common neurological diseases in the world. Anemarrhena asphodeloides Bunge. (AA), as a typical heat-cleaning medicine, has been proven to possess the antiepileptic effect in clinical and experimental studies. Anemarrhena asphodeloides steroidal saponins (AAS) are main components. However, the therapeutic effects and underlying mechanisms of AAS against EP are not been fully elucidated. In this study, 63 steroidal saponins were discovered in AAS by UPLC-Q-TOF/MS analysis. Pharmacological and behavioral analysis demonstrated that AAS could significantly lower the Racine classification and reduce the frequency of generalized spike rhythm the rate of tetanic seizures in kainic acid-induced epileptic rats. Hematoxylin and eosin and Nissl staining-indicated AAS could significantly improve hippocampal injury and neuron loss in epileptic rats. TMT proteomic analysis discovered 26 different expressed proteins (DEPs), which were identified as the rescue proteins. After bioinformatic analysis, Heat Shock Protein 90 Alpha Family Class B Member 1 (Hsp90ab1) and Tyrosine 3-Monooxygenase (Ywhab) were screened as key DEPs and verified by western blotting. AAS could significantly inhibited the up-regulation of Hsp90ab1 and Ywhab in EP rats; these two proteins might be the key targets of AAS in treating EP.

Recent Advancements and SAR Studies of Synthetic Coumarins as MAO-B Inhibitors: An Updated Review.

The oxidative deamination of a wide range of endogenous and exogenous amines is catalyzed by a family of enzymes known as monoamine oxidases (MAOs), which are reliant on flavin-adenine dinucleotides. Numerous neurological conditions, such as Parkinson's disease (PD) and Alzheimer's disease (AD), are significantly correlated with changes in the amounts of biogenic amines in the brain caused by MAO. Hydrogen peroxide, reactive oxygen species, and ammonia, among other toxic consequences of this oxidative breakdown, can harm brain cells' mitochondria and cause oxidative damage. The prime objective of this review article was to highlight and conclude the recent advancements in structure-activity relationships of synthetic derivatives of coumarins for MAO-B inhibition, published in the last five years' research articles. The literature (between 2019 and 2023) was searched from platforms like Science Direct, Google Scholar, PubMed, etc. After going through the literature, we have found a number of coumarin derivatives being synthesized by researchers for the inhibition of MAO-B for the management of diseases associated with the enzyme such as Alzheimer's Disease and Parkinson's Disease. The effect of these coumarin derivatives on the enzyme depends on the substitutions associated with the structure. The structure-activity relationships of the synthetic coumarin derivatives that are popular nowadays have been described and summarized in the current study. The results revealed the updated review on SAR studies of synthetic coumarins as MAO-B inhibitors, specifically for Alzheimer's Disease and Parkinson's Disease. The patents reported on coumarin derivatives as MAO-B inhibitors were also highlighted. Recently, coumarins, a large class of chemicals with both natural and synthetic sources, have drawn a lot of attention because of the vast range of biological actions they have that are linked to neurological problems. Numerous studies have demonstrated that chemically produced and naturally occurring coumarin analogs both exhibited strong MAO-B inhibitory action. Coumarins bind to MAO-B reversibly thereby preventing the breakdown of neurotransmitters like dopamine leading to the inhibition of the enzyme A number of MAO-B blockers have been proven to be efficient therapies for treating neurological diseases like Alzheimer's Disease and Parkinson's Disease. To combat these illnesses, there is still an urgent need to find effective treatment compounds.

Targeting GM2 Ganglioside Accumulation in Dementia: Current Therapeutic Approaches and Future Directions.

Dementia in neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB) is a progressive neurological condition affecting millions worldwide. The amphiphilic molecule GM2 gangliosides are abundant in the human brain and play important roles in neuronal development, intercellular recognition, myelin stabilization, and signal transduction. GM2 ganglioside's degradation requires hexosaminidase A (HexA), a heterodimer composed of an α subunit encoded by HEXA and a β subunit encoded by HEXB. The hydrolysis of GM2 also requires a non-enzymatic protein, the GM2 activator protein (GM2-AP), encoded by GM2A. Pathogenic mutations of HEXA, HEXB, and GM2A are responsible for autosomal recessive diseases known as GM2 gangliosidosis, caused by the excessive intralysosomal accumulation of GM2 gangliosides. In AD, PD and DLB, GM2 ganglioside accumulation is reported to facilitate Aβ and α-synuclein aggregation into toxic oligomers and plaques through activation of downstream signaling pathways, such as protein kinase C (PKC) and oxidative stress factors. This review explored the potential role of GM2 ganglioside alteration in toxic protein aggregations and its related signaling pathways leading to neurodegenerative diseases. Further review explored potential therapeutic approaches, which include synthetic and phytomolecules targeting GM2 ganglioside accumulation in the brain, holding a promise for providing new and effective management for dementia.

Neuronal connectivity, behavioral, and transcriptional alterations associated with the loss of MARK2.

Neuronal connectivity is essential for adaptive brain responses and can be modulated by dendritic spine plasticity and the intrinsic excitability of individual neurons. Dysregulation of these processes can lead to aberrant neuronal activity, which has been associated with numerous neurological disorders including autism, epilepsy, and Alzheimer's disease. Nonetheless, the molecular mechanisms underlying abnormal neuronal connectivity remain unclear. We previously found that the serine/threonine kinase Microtubule Affinity Regulating Kinase 2 (MARK2), also known as Partitioning Defective 1b (Par1b), is important for the formation of dendritic spines invitro. However, despite its genetic association with several neurological disorders, the invivo impact of MARK2 on neuronal connectivity and cognitive functions remains unclear. Here, we demonstrate that the loss of MARK2 invivo results in changes to dendritic spine morphology, which in turn leads to a decrease in excitatory synaptic transmission. Additionally, the loss of MARK2 produces substantial impairments in learning and memory, reduced anxiety, and defective social behavior. Notably, MARK2 deficiency results in heightened seizure susceptibility. Consistent with this observation, electrophysiological analysis of hippocampal slices indicates underlying neuronal hyperexcitability in MARK2-deficient neurons. Finally, RNAseq analysis reveals transcriptional changes in genes regulating synaptic transmission and ion homeostasis. These results underscore the invivo role of MARK2 in governing synaptic connectivity, neuronal excitability, and cognitive functions.

The Role of Gut Microbioma in Human Health: Exploring the Impact on Metabolism, Immunity, and Neurological Disorders

Abstract: The human microbiota has been progressively accepted for its role in sustaining overall health and well-being. The gut microflora vigorously communicates with the host metabolic system that exert influence on the progression, maturation, immune cells development and immune homeostasis maintenance. For the proper functioning of the immune system a diversified and steady gut microflora is needed, while “Dysbiosis” or an imbalance in the gut microbioma will lead to autoimmune and inflammatory diseases. The gut microbiota provides shape to our immune response and contribute to host protection against pathogen or bacterium through mechanisms such as the transformation of pro- inflammatory cytokine production, regulatory T-cell inductor and by intestinal mucosaql barrier. In addition to gut microbiota can affect our neurological function and play a key role in the pathogenesis of psychological disorders such as autism, depression, anxiety, Parkinson and Alzheimer’s disease. Gut microbiota can regulate neurological disorders by supplementing them with fecal transplantation, probiotics and antibiotics. An important parameter to consider gut microbioma disorder is Firmicutes/ Bacteroidetes.

The Future of OOC on Neurological Diseases - Alzheimer's

Abstract: Neurological Diseases such as Alzheimer's and Parkinsons' have been deemed incurable diseases. The complexity of the human brain is an obstacle for scientists to understand how treatments could interact with human brain microenvironments. To this date, researchers have used traditional modeling methods, such as in vitro cell culture and in vivo animal models. These methods are unable to showcase the different layers of the blood-brain barrier or accurately represent the cellular interactions within the brain. The proposed solution is a new research technology, organ on a chip, a multi-organ system connected with microfluidics. This review explores the organ on a chip, what it is made for, and how it is the future of drug development. In addition, we explore the lymphatic system and the different organ-on-a-chip models that can simulate the lymphatic system and BBB. Organ on a chip has the potential to help efficiently develop drugs and treatment, which has the potential to improve neurological disease conditions.

Circle of Willis and Its Anatomical Relevance

The Circle of Willis is an arterial network located at the base of the brain, formed by the interconnection of the anterior, middle, and posterior cerebral arteries, along with the anterior and posterior communicating arteries. It connects the internal carotid arteries to the vertebral arteries, allowing the distribution of cerebral blood flow. Its significance lies in its ability to offer an alternative pathway in cases of arterial obstruction, helping to prevent cerebral ischemia. However, anatomical variations of this structure are common, and only 20% to 25% of the population has a "complete" or symmetrical configuration. Such variations can influence the risk of cerebrovascular diseases, such as stroke, as they may compromise the efficiency of the compensatory mechanism. These anatomical variations have a direct impact on the diagnosis and treatment of neurological conditions. The integrity of the Circle of Willis can influence the severity of symptoms in cases of ischemic strokes, as well as affect aneurysm formation and its clinical implications. Advances in imaging techniques, such as CT angiography and magnetic resonance imaging, have enabled more accurate diagnoses and the development of more effective treatments for conditions associated with the Circle of Willis, making its anatomical understanding essential for the prevention and management of cerebrovascular diseases.

Potential Risks Associated With Long-term Use of Proton Pump Inhibitors and the Maintenance Treatment Modality for Patients With Mild Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) significantly affects the health-related quality of life and healthcare costs. The prevalence of this disease is increasing in Asia, leading to a rapid increase in the demand of proton pump inhibitors (PPIs). Despite effective symptom management during initial treatment, relapse rates after PPI cessation remain high in patients with GERD, warranting longterm maintenance therapy. Concerns regarding potential side effects related to the long-term use of PPIs are escalating with increased usage. Studies have reported diverse side effects of PPIs, such as increased fracture risk, cardiovascular concerns, enteric infections, neurological diseases, and potential associations with gastric cancer. However, definitive causal relationships remain unclear. This review comprehensively summarizes the latest knowledge on the potential risks associated with long-term use of PPIs. Continuous or noncontinuous therapy can be used as a maintenance treatment modality for GERD. For patients with mild GERD, including those with nonerosive and mildly erosive reflux disease, on-demand therapy following a sufficient period of continuous maintenance therapy is recommended as a long-term maintenance treatment option.

Machine learning techniques for diagnosis of rare diseases from medical images

Introduction/Background: Rare diseases are life-threatening or chronically debilitating conditions that affect a small percentage of the population. Early and accurate diagnosis of rare diseases is challenging due to their complexity and limited understanding. Conventional diagnostic methods are often inadequate, time-consuming, and expensive. Machine learning (ML) has emerged as a promising technique for the analysis of medical images to support the diagnosis of various diseases including rare disorders. ML algorithms can learn complex patterns from large medical imaging datasets to aid clinicians in disease diagnosis, prognosis, and detection of complications. Materials and Methods: A structured search was conducted in electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar to identify peer-reviewed articles published between 2013 to 2023 related to ML-based diagnosis of rare diseases from medical images. A total of 187 articles were identified after removing duplicates. The titles and abstracts of retrieved articles were screened to determine their relevance based on the research objective. Finally, 51 full-text articles were selected for the final review. The key data extracted from selected studies included diseases, imaging modalities, ML algorithms, performance metrics, datasets, and limitations. Results: Most studies evaluated deep learning-based ML techniques, with convolutional neural networks (CNN) being the most applied algorithm. CNNs were mainly used to classify rare diseases based on specific imaging features in X-rays, CT, and MRI scans. Diseases frequently investigated included cardiovascular, neurological, and rare genetic disorders. Publicly available datasets such as Deep Lesion, MSD, and ChestX-ray14 were commonly utilized. Most studies reported high classification accuracy ranging from 80-95% on test datasets. However, limited generalizability due to small private datasets and lack of external validation were limitations. Discussion: The results demonstrate the potential of deep learning for the image-based diagnosis of rare diseases. Features learned from large imaging data sets enabled CNNs to distinguish subtle abnormalities. Hybrid models combining CNNs with other techniques like recurrent neural networks further improved performance. Overall, ML showed promise as a decision support tool. However, more multi-center validation studies are needed using larger and diverse datasets before clinical adoption. Standardization of performance metrics and reporting is also required to establish reliability and generalizability. Conclusion: This comprehensive review provided insights into ongoing research applying ML to medical images for rare disease diagnosis. While initial results are encouraging, further work is still necessary before ML can be reliably used in clinical decision making. Larger collaborative efforts and open-source datasets are needed to advance the field. Standardization of ML frameworks can also promote reproducible research and comparison of different methodologies.

Brain temperature, brain metabolites, and immune system phenotypes in temporal lobe epilepsy.

Epileptogenesis is linked to neuroinflammation. We hypothesized that local heat production caused by neuroinflammation can be visualized non-invasively invivo via brain magnetic resonance spectroscopic imaging (MRSI) and MRSI-thermometry (MRSI-t) and that there is a relationship in patients with temporal lobe epilepsy (TLE) between MRSI-t and brain metabolites choline and myo-inositol and between neuroimaging and cellular and serum biomarkers of inflammation. Thirty-six (36) participants, 18 with temporal lobe epilepsy (13 females) and 18 age-matched healthy controls (nine females), were enrolled prospectively and underwent MRSI/MRSI-t; TLE participants also provided blood samples. Temperature was measured using creatine as a reference metabolite. Analysis of Functional NeuroImages 3dttest++ tool was used to analyze voxel-level group differences in temperature, choline, and myo-inositol. Associations with immune cell subsets, cytokines, and chemokines related to inflammation were quantified using correlation coefficients with significant relationships as noted. Patients with TLE showed elevated temperature, choline, and myo-inositol in the temporal lobes. Higher brain temperature was associated with higher levels of cytokines and chemokines, including GM-CSF, TNF, IL-1β, and IL - 12p70, and lower frequency of immune cells including CD3+ T-cells, CD4+ T-cells, CD8+ T-cells, and classical monocytes. Higher choline was associated with higher levels of the cytokines including LT-α, IL-13, and IL-4, and higher myo-inositol was associated with a higher frequency of CD4+ T-cell and CD19+ B-cell subsets and higher levels of cytokines and chemokines including LT-α, IL-13, and CCL3. This study, for the first time, showed that in temporal lobes of patients with TLE temperature and metabolite changes correlate with cellular and serum biomarkers of inflammation. Our results provide support for further development of MRSI-t as a measure of neuroinflammation in epilepsy and potentially other neurological disorders and as an investigative and clinical tool. Neuroinflammation is associated with excessive heat production which can be visualized with magnetic resonance spectroscopic imaging and thermometry (MRSI-t). We prospectively investigated the relationship between MRSI-t and cellular and serum measures of peripheral inflammation in patients with temporal lobe epilepsy (TLE); we compared the results of MRSI-t in patients with TLE to healthy controls. We showed a relationship between the temperature elevations in TLE and elevations of various measures of peripheral inflammation. Our results support further development of MRSI-t as a measure of neuroinflammation in epilepsy and potentially other neurological disorders and as an investigative and clinical tool.

Functional outcomes in children and adolescents with neurodisability accessing music therapy: A scoping review.

To determine the evidence for functional outcomes experienced by a population with paediatric neurodisability (such as acquired brain injury, cerebral palsy, spinal cord injury, and other neurological disorders), who access music therapy through neurorehabilitation services across the rehabilitation spectrum. Using scoping review methodology of the JBI and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), a systematic search was conducted across eight databases and expert knowledge users were consulted. Articles were screened by title and abstract, and data from eligible studies were categorized using the International Classification of Functioning, Disability and Health: Children and Youth version (ICF-CY). From 1726 records identified, 53 eligible primary sources were included in the synthesis. Most literature (n = 30) related to children and adolescents with an acquired or traumatic brain injury. Physical functionwas the most frequently reported outcome across sources(n = 27), followed by communication (n = 25), social (n = 22), cognitive (n = 17), emotional (n = 13), psychological (n = 13), behavioural (n = 8), and sensory (n = 5). Evidence for functional outcomes experienced by children and adolescents accessing music therapy as part of their neurorehabilitation is limited. More than half of the included sources were clinical descriptions with small samples. High-quality studies involving children, adolescents, families, and interprofessional teams are needed to identify the most effective music therapy methods and techniques for functional outcomes in paediatric neurodisability.

Editorial: Epigenetic modification in neurological diseases

Editorial: Epigenetic modification in neurological diseases

The role of surgery in recurrent local cerebral metastases: a multi-institutional retrospective analysis.

Local recurrent brain metastases are defined as lesions that recur in the brain at the same site after a previous local therapy. In patients already submitted to surgery, a second operation may be potentially challenging due to scar formation, infiltration of cerebral vessels or eloquent brain areas and local effect of previous radiotherapy. The aim of this study is to retrospectively review the results and complications of a second surgical treatment in a series of local recurrent lesions and to review the literature on this topic. 37 patients submitted to surgery for a local, histologically confirmed, recurrent brain metastases between 2000 and 2022 were retrospectively analyzed with respect to the following parameters: age, histology, anatomic location, time to recurrence, previous radiotherapy, size of recurrent tumors, preoperative and postoperative Karnofsky Performance Status(KPS) score, recursive partitioning analysis (RPA) class and graded prognostic assessment (GPA) score, surgery-related complications and the presence of further cerebral metastases. Overall survival (OS) was calculated using the Kaplan-Meier method. A multivariate Cox proportional hazard model was developed using stepwise regression (forwards selection) with predictive variables that were significant in the univariate analyses. A significant improvement of post-operative KPS status was obtained after second surgery. At multivariate analysis better results in terms of OS were achieved in patients with a pre-operative KPS ≥ 70 and in patients who had received radiotherapy after the initial surgery. No significant postoperative complications related to previous treatments were observed. Surgical resection of local recurrent brain metastases may improve patients ́ neurologic conditions allowing more time for systemic therapies to act with a low incidence of surgery-related morbidity and mortality. However, careful patient selection with a fair pre-operative clinical status seems mandatory to achieve the best post-operative results, since uniform treatment-paradigms cannot be established yet, due to the highly heterogeneous patient cohort.

Mapping the evolving trend of research on leukocyte telomere length: a text-mining study

BackgroundSubstantial evidence indicates that measuring leukocyte telomere length (LTL) is a useful tool that may be considered as a valuable biomarker of individual biological age, correlating with numerous chronic disorders. However, to date, there has been a lack of in-depth understanding regarding the current landscape and forthcoming developments in the LTL field. Therefore, this study aimed to utilize bibliometric methods to summarize the knowledge structure, current focus, and emerging directions in this field.MethodScientific publications on LTL spanning the period from 2000 to 2022 were acquired from the Web of Science Core Collection database. Several bibliometric tools including CiteSpace, VOSviewer, and an online website were utilized for bibliometric analysis. The primary evaluations encompassed investigating the major contributors and their collaborative relationships among countries/regions, institutions, and authors, conducting co-citation analyses of authors, journals, as well as reference, examining reference bursts, as well as performing co-occurrence analyses of keywords.ResultsThere are 1818 papers with 66,668 citations identified. Both the annual publication and citation counts on LTL exhibited significant upward trends. The United States emerged as the most prominent contributor, as evidenced by the greatest volume of papers and the highest H-index value. University of California San Francisco and Aviv A were identified as the most productive institution and author in this domain, respectively. Reference analysis revealed that longitudinal study and mendelian randomization study are the most concerned research method in this field recently. Keywords analysis showed that the most concerned diseases in LTL fields were aging, inflammation, cardiovascular diseases, endocrine diseases, neurological and psychiatric diseases, and cancers. In addition, the following research directions such as “COPD”, “mendelian randomization”, “adiposity”, “colorectal cancer”, “National Health and Nutrition Examination Survey (NHNES)”, “telomerase reverse transcriptase”, “pregnancy” have garnered increasing attention in recent times and hold the potential to evolve into research foci in the foreseeable future.ConclusionThis is the first bibliometric study that provides comprehensive overview of LTL research. The findings of this study could become valuable references for investigators to explore and address the current and emerging challenges in LTL research.

MicroRNA-Targeted Gene Regulation in Salivary Gland Tissue of De Novo Parkinson's Disease Patients.

Although α-synucleinopathy has been confirmed in the submandibular gland (SMG) tissue of Parkinson's disease (PD) patients, in-depth disease-related molecular research, such as tissue-specific transcriptional signals, has not been performed. In the present study, disease-relevant tissue-specific transcriptional signals in SMG tissue from PD patients were investigated to identify potential diagnostic, prognostic, and pathophysiologic biomarkers. Here, seven de novo drug-naïve PD patients and six age- and sex-matched individuals without neurological or psychological diseases were enrolled. Total RNA sequencing (RNA-seq) and total small RNA-seq (smRNA-seq) were performed on SMG tissue and blood samples, with 26 RNA-seq and 26 smRNA-seq samples used for the final analysis. Differentially expressed genes (DEGs) and microRNAs in SMG tissue and blood from PD patients were obtained and their functional integration and interaction network were analyzed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the DEGs interacted with cytokine-, inflammation-, and immune-related pathways. Synphilin-1 expression was significantly downregulated in SMG tissue of PD patients, and α-synuclein expression did not significantly differ between PD patients and controls in either SMG tissue or blood. Fifteen tissue-specific miRNA signals in SMG tissue were identified that showed better diagnostic ability compared with those in blood samples. The correlation between DEGs and environmental factors appeared altered in PD patients. The results indicated the DEGs and microRNA signatures identified in SMG tissue may be promising diagnostic and prognostic biomarkers. These molecular insights offer potential avenues for the development of novel therapeutic strategies targeting the underlying disease mechanisms in PD patients.

MRI and CT compatible asymmetric bilayer hydrogel electrodes for EEG-based brain activity monitoring

The exploration of multi-dimensional brain activity with high temporal and spatial resolution is of great significance in the diagnosis of neurological disease and the study of brain science. Although the integration of electroencephalogram (EEG) with magnetic resonance imaging (MRI) and computed tomography (CT) provides a potential solution to achieve a brain-functional image with high spatiotemporal resolution, the critical issues of interface stability and magnetic compatibility remain challenging. Therefore, in this research, we proposed a conductive hydrogel EEG electrode with an asymmetrical bilayer structure, which shows the potential to overcome the challenges. Benefiting from the bilayer structure with different moduli, the hydrogel electrode exhibits high biological and mechanical compatibility with the heterogeneous brain-electrode interface. As a result, the impedance can be reduced compared with conventional metal electrodes. In addition, the hydrogel-based ionic conductive electrodes, which are free from metal conductors, are compatible with MRI and CT. Therefore, they can obtain high spatiotemporal resolution multi-dimensional brain information in clinical settings. The research outcome provides a new approach for establishing a platform for early diagnosis of brain diseases and the study of brain science.

Conservative, physical and surgical interventions for managing faecal incontinence and constipation in adults with central neurological diseases.

Conservative, physical and surgical interventions for managing faecal incontinence and constipation in adults with central neurological diseases.

Intracranial inoculation rapidly induces Nipah virus encephalitis in Syrian hamsters.

Nipah virus (NiV) is a highly pathogenic Paramyxovirus associated with outbreaks in Malaysia, Bangladesh, and India with high mortality rates. NiV infection causes fatal respiratory and neurological disease. The majority of survivors suffer from long-term neurological sequelae or late onset and relapsed encephalitis. The pathogenesis of neurological disease is complex and has not been able to be studied in current animal models as they are skewed towards the development of lethal respiratory disease rather than neurological disease. Although NiV neurological disease can be observed in animal models, there is currently no model where the majority of animals consistently develop neurological disease. Here, we developed a new Syrian hamster (Mesocricetus auratus) model to mimic neurological disease in humans. Hamsters were inoculated intracranially in the cerebellomedullary cistern with different doses of NiV, strain Malaysia. Intracranial NiV inoculation in the cerebellomedullary cistern resulted in a rapid progression towards severe neurological disease requiring euthanasia. High Nipah viral loads were detected in the brains, and NiV spread from the CNS to the lungs. Histopathologic examination of the brain showed ischemic necrosis, often accompanied by marked edema and hemorrhage. NiV antigen was detected primarily in meninges and cerebellum, but rarely observed in brain parenchyma. These histological lesions were different from the typical lesions observed in NiV-infected humans. Thus, despite the consistent development of neurological disease, intracranial inoculation does not result in a model representative of NiV neurological disease.