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AbstractIschaemic stroke is a central nervous system disease with high morbidity, recurrence and mortality rates. Thrombolytic and neuroprotective therapies are the main therapeutic strategies for ischaemic stroke, however, the poor delivery efficiency of thrombolytic and neuroprotective drugs to the brain limits their clinical application. So far, the development of nanomedicine has brought opportunities for the above challenges, which can not only realise the effective accumulation of drugs in the target site, but also improve the pharmacokinetic behaviour of the drugs. Among the most rapidly developing nanoparticles, micelles gradually emerging as an effective strategy for ischaemic stroke treatment due to their own unique advantages. This review provided an overview of targeted and response-release micelles based on the physicochemical properties of the ischaemic stroke microenvironment, summarised the targeting strategies for delivering micellar formulations to the thrombus, blood-brain barrier, and brain parenchyma, and finally described the potentials and challenges of polymeric micelles in the treatment of ischaemic stroke. [ABSTRACT FROM AUTHOR]

Cinnamaldehyde (CA) is an active ingredient extracted from cinnamon and is widely used in the food industry as a natural additive. CA has a variety of biological functions, such as antibacterial, antioxidant, antiviral, and anticancer, as well as its role in regulating gut microbiota, have been well-established. Additionally, CA has shown positive effects on degenerative central nervous system diseases, cognitive impairment, arthritis, and ischemic reperfusion injury, and is widely used in the food industry and clinical medicine. However, its poor water solubility and easy oxidation have largely limited its broad application. To enhance the efficacy of CA delivery, innovative delivery systems have been developed. This review aims to compile the most recent literature on CA extraction methods, biological functions, delivery systems, and toxicology, highlighting the compound’s significance. By providing a comprehensive overview of CA, this review intends to serve as a valuable resource for the development and application of CA in both food and medical contexts. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsAutoimmune encephalitis (AE) is a group of autoimmune diseases targeting the central nervous system, characterized by severe clinical symptoms and substantial consumption of medical resources. Neuroinflammation plays a crucial role in disease progression, and detecting inflammatory responses can provide insights into disease status and disease severity. The systemic immune-inflammation index (SII), a novel marker of inflammatory status, has been rarely studied in AE.Retrospective analysis of data from AE patients admitted to the First Affiliated Hospital of Zhengzhou University between January 2019 and September 2023 was conducted. Univariate analysis and logistic regression were used to assess the association between SII and patient severity. Nomograms for predicting AE severity were established, and receiver operating characteristic (ROC) curves, concordance index (C-index), calibration curves, and decision curve analysis were employed to evaluate predictive accuracy. Additionally, the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score was used to assess patient severity.This study enrolled 157 patients, of whom 57 were classified as severe according to the CASE score. SII, cerebrospinal fluid (CSF) cell counts, disturbance of consciousness, and behavioural abnormalities independently associated with the occurrence of severe cases. The C-index of the nomograms was 0.87, indicating strong association with disease severity, as supported by the calibration. Additionally, SII levels were highest within seven days of onset and decreased after one month. In subgroup analyses of different antibodies, SII also associations with severe cases in NMDAR encephalitis.Higher SII levels are associated with an increased likelihood of developing severe AE, peaking within 7 days of disease onset and decreasing thereafter, potentially offering a prognostic marker to assess disease progression early in its course. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery (TDD) has gained clinical approval over several decades, with extensive research dedicated to novel drug and device development. Despite notable research progress, the market adoption of TDD devices has not met anticipated levels, with oral administration and injection remaining predominant delivery methods. To maximize the potential of TDD, we identify bottlenecks hindering its widespread clinical application and propose promising research avenues. We begin by analyzing stringent demands necessary to truly benefit patients, addressing significant challenges in biomechanics, nanomedicine, and flexible electronics. Subsequently, we delve into skin anatomy, enhancement strategies, nano-carriers, and their underlining mechanisms, highlighting the importance and framework of quantitative modeling. Based on these discussions, we highlight the core strength of TDD, such as automatic precise administration based on feedback and high delivery efficiencies, especially applicable to localized conditions (e.g., central nervous system diseases, tumors). Finally, we envision the future of intelligent TDD device and its operation scenario, aiming to steer research efforts toward faster translation of laboratory innovations into widely used products for sufferers. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a degenerative disease of the central nervous system. The pathogenesis is still not fully clear. One of the main histopathological manifestations is senile plaques formed by β-amyloid (Aβ) accumulation. Aβ is generated from the sequential proteolysis of amyloid precursor protein (APP) by β-secretase [i.e. β-site APP cleaving enzyme 1 (BACE1)] and γ-secretase, with a rate-limiting step controlled by BACE1 activity. Therefore, inhibiting BACE1 activity has become a potential therapeutic strategy for AD. The development of reliable detection methods for BACE1 activity plays an important role in early diagnosis of AD and evaluation of the therapeutic effect of new drugs for AD. This article has reviewed the recent advances in BACE1 activity detection techniques. The challenges of applying these analysis techniques to early clinical diagnosis of AD and development trends of the detection techniques have been prospected. [ABSTRACT FROM AUTHOR]

Background: MS (Multiple sclerosis) is a progressive neurologic disorder often appearing in the third decade of life. MS is the most frequent demyelinating disease of the central nervous system. The development of MS is influenced by environmental, genetic, and epigenetic factors. The bulk of the human transcriptome comprises lncRNAs, which play crucial regulatory roles. We aimed to assess the SNHG3 and BCYRN1 lncRNA expression in blood samples from MS patients and how these lncRNAs and disease activity are related. Methods: A total of 100 MS patients, including 8 primary progressive (PP), 82 relapsing-remitting (RR), and 10 secondary progressive (SP) MS, as well as 100 healthy controls, had their blood samples taken. Gene expression was assessed using quantitative real-time PCR. Recognizing the receiver operating characteristic (ROC) curve analysis, the diagnostic potential of lncRNA levels was evaluated. Results: Expressions of SNHG3 and BCYRN1 were found to have significantly increased (p < 0.0001). SNHG3 expression level showed significant differences compared to age groups and MS subtypes (p value = 0.001 and p value = 0.02). Furthermore, patients with a family history showed elevated BCYRN1 expression with a p value of 0.01. Considering the age factor, BCYRN1 exhibits altered expression levels in patient groups compared to healthy controls (p value 0.04). Additionally, the novel biomarkers SNHG3 and BCYRN1 can be used to diagnose MS (AUC = 0.97 and AUC = 0.88, respectively). Discussion: Increased levels of SNHG3 and BCYRN1 in the serum may serve as potential molecular biomarkers for the MS diagnosis. [ABSTRACT FROM AUTHOR]

AbstractIn recent times, the nasal region has emerged as a distinctive and dynamic environment where a myriad of microbial communities establish residence from infancy, persisting as both commensal and opportunistic pathogens throughout the lifespan. Understanding the coexistence of microorganisms in respiratory mucosal layers, their potential for infections, and the underlying molecular mechanisms shaping these interactions is crucial for developing efficient diagnostic and therapeutic interventions against respiratory and neurodegenerative diseases. Despite significant strides in understanding the olfactory system’s nexus with nasal microbiota, comprehensive correlations with neurological diseases still need to be discovered. The nasal microbiome, a sentinel in immune defense, orchestrates a delicate equilibrium that, when disrupted, can precipitate severe respiratory infections, including Chronic Rhinosinusitis, Chronic obstructive pulmonary disorder (COPD), and Asthma, and instigate a cascade effect on central nervous system diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Multiple sclerosis (MS). This review aims to redress this imbalance by meticulously exploring the anatomical and microbiological nuances of the nasal mucosal surface in health and disease. By delineating the molecular intricacies of these interactions, this review unravels the molecular mechanisms that govern the intricate nexus between nasal microbiota dysbiosis, olfactory dysfunction, and the progression of respiratory and neurological diseases. [ABSTRACT FROM AUTHOR]

AbstractOne of the most prevalent neurodegenerative diseases is Alzheimer’s disease (AD). The hallmarks of AD include the accumulation of amyloid plaques and neurofibrillary tangles, which cause related secondary diseases, progressive neurodegeneration, and ultimately death. The most prevalent cell type in the human central nervous system, astrocytes, are crucial for controlling neuronal function. Glial fibrillary acidic protein (GFAP) is released from tissue into the bloodstream due to astrocyte breakdown in neurological diseases. Increased levels of GFAP in the serum can function as blood markers and be an effective prognostic indicator to help diagnose neurological conditions early on, from stroke to neurodegenerative diseases. The human central nervous system (CNS) is greatly affected by diseases associated with blood GFAP levels. These include multiple sclerosis, intracerebral hemorrhage, glioblastoma multiforme, traumatic brain injuries, and neuromyelitis optica. GFAP demonstrates a strong diagnostic capacity for projecting outcomes following an injury. Furthermore, the increased ability to identify GFAP protein fragments helps facilitate treatment, as it allows continuous screening of CNS injuries and early identification of potential recurrences. GFAP has recently gained attention due to data showing that the plasma biomarker is effective in identifying AD pathology. AD accounts for 60–70% of the approximately 50 million people with dementia worldwide. It is critical to develop molecular markers for AD, whose number is expected to increase to about 3 times and affect humans by 2050, and to investigate possible targets to confirm their effectiveness in the early diagnosis of AD. In addition, most diagnostic methods currently used are image-based and do not detect early disease, i.e. before symptoms appear; thus, treatment options and outcomes are limited. Therefore, recently developed methods such as point-of-care (POC), on-site applications, and enzyme-linked immunosorbent assay-polymerase chain reaction (ELISA-PCR) that provide both faster and more accurate results are gaining importance. This systematic review summarizes published studies with different approaches such as immunosensor, lateral flow, POC, ELISA-PCR, and molecularly imprinted polymer using GFAP, a potential blood biomarker to detect neurological disorders. Here, we also provide an overview of current approaches, analysis methods, and different future detection strategies for GFAP, the most popular biosensing field. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) of unknown cause. Alterations in one-carbon metabolism have impact in the pathophysiology by genetic susceptibility to MS and increased the risk of MS. The aim of this study was to investigate the contribution of the gene polymorphism on Methylenetetrahydrofolate Reductase (MTHFR), Methionine Synthase Reductase (MTRR), Methionine Synthase (MTR) enzymes and of the essential factors (homocysteine, Hcy; cysteine, Cys; and vitamin B12, VitB12) in folate metabolism. Eligible MS patients (n = 147) and health controls (n = 127) were participated. The gene polymorphisms were analyzed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and the levels of plasma Hcy, Cys and VitB12 were measured by Enzyme Linked Immunuabsorbent Assay (ELISA). Our results showed that the levels of Hcy and VitB12 were lower and the levels of Cys were higher in MS compared to controls. The observation of high Cys values in all 3 gene polymorphisms suggests that the transsulfiration pathway of Hcy is directed towards Cys formation since the methionine synthesis pathway does not work. We could not find any association with all gene polymorphisms with the risk of MS. The T allele of MTHFR C677T and G allele of MTR A2756G are risk factors for serum Cys level on MS. As for MTR A2756G, serum vitB12 was observed in MS patients with G allele. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a central nervous system disease with the highest disability and mortality rate worldwide, and it is caused by a variety of factors. The most common medications for PD have side effects with limited therapeutic outcomes. Many studies have reported that chitosan oligosaccharide (COS) crossed blood-brain barrier to achieve a neuroprotective effect in PD. However, the role of COS in PD remains unclear. The present study demonstrated that COS increased dopaminergic neurons in the substantia nigra (SN) and ameliorated dyskinesia in a PD mouse model. Moreover, COS reduced gut microbial diversity and faecal short-chain fatty acids. Valeric acid supplementation enhanced the inflammatory response in the colon and SN, and it reversed COS - suppressed dopamine neurons damage. Autophagy was involved in COS modulating inflammation through valeric acid. These results suggest that COS reduces bacterial metabolites - valeric acid, which diminishes inflammation via activating autophagy, ultimately alleviating PD. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system. Oxidative stress via distinct pathobiological pathways plays a pivotal role in the formation and persistence of MS lesions. Acetyl-L-carnitine (ALC) facilitates the uptake of acetyl coenzyme-A into the mitochondria by a fatty acid oxidation process. ALC could be a therapeutic antioxidant in the myelin repair process. This study explored the potential neuroprotective effects of ALC in cuprizone (CPZ) intoxicated mice. Thirty male C57BL/6 mice were divided into three groups. The control animals received a normal diet. The CPZ and CPZ + ALC groups were fed with a 0.2% cuprizone diet for 12 weeks. In the CPZ + ALC group, animals received ALC (300 mg/kg/day) from the 10th -12th weeks. Animals were evaluated functionally by beam walking test (BWT) weekly. Eventually, the corpus callosum (CC) was extracted for histological, biochemical, and molecular studies. BWT data showed ALC significantly improves balance and gait in the demyelinating mouse model. Histological staining represented ALC effectively increased remyelination in the CC. Biochemical evaluations demonstrated ALC decreased the malondialdehyde level with a parallel increase in the reduced glutathione and catalase activity levels in the CC. Molecular analysis revealed that ALC significantly increased the expression of oligodendrocyte transcription-2 (Olig-2) and Poly lipoproteins (Plp) genes in the CC. ALC improved balance and motor coordination in the demyelinated mouse model. It may be by reducing the levels of free radicals and increasing the expression of Olig-2 and Plp as myelin-related genes. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system (CNS) due to an increase of abnormal peripherally auto-reactive T lymphocytes which elicit autoimmunity. The main pathophysiology of MS is myelin sheath damage by immune cells and a defect in the generation of myelin by oligodendrocytes. Macroautophagy/autophagy is a critical degradation process that eliminates dysfunctional or superfluous cellular components. Autophagy has the property of a double-edged sword in MS in that it may have both beneficial and detrimental effects on MS neuropathology. Therefore, this review illustrates the protective and harmful effects of autophagy with regard to this disease. Autophagy prevents the progression of MS by reducing oxidative stress and inflammatory disorders. In contrast, over-activated autophagy is associated with the progression of MS neuropathology and in this case the use of autophagy inhibitors may alleviate the pathogenesis of MS. Furthermore, autophagy provokes the activation of different immune and supporting cells that play an intricate role in the pathogenesis of MS. Autophagy functions in the modulation of MS neuropathology by regulating cell proliferation related to demyelination and remyelination. Autophagy enhances remyelination by increasing the activity of oligodendrocytes, and astrocytes. However, autophagy induces demyelination by activating microglia and T cells. In conclusion, specific autophagic activators of oligodendrocytes, and astrocytes, and specific autophagic inhibitors of dendritic cells (DCs), microglia and T cells induce protective effects against the pathogenesis of MS. Abbreviations: ALS: amyotrophic lateral sclerosis; APCs: antigen-presenting cells; BBB: blood-brain barrier; CSF: cerebrospinal fluid; CNS: central nervous system; DCs: dendritic cells; EAE: experimental autoimmune encephalomyelitis; ER: endoplasmic reticulum; LAP: LC3-associated phagocytosis; MS: multiple sclerosis; NCA: non-canonical autophagy; OCBs: oligoclonal bands; PBMCs: peripheral blood mononuclear cells; PD: Parkinson disease; ROS: reactive oxygen species; UPR: unfolded protein response [ABSTRACT FROM AUTHOR]

Astrocytes play an important role in the central nervous system, contributing to the development of and maintenance of synapses, recycling of neurotransmitters, and the integrity and function of the blood–brain barrier. Astrocytes are also linked to the pathophysiology of various neurodegenerative diseases. Astrocyte function and organization are tightly regulated by interactions mediated by the extracellular matrix (ECM). Engineered hydrogels can mimic key aspects of the ECM and can allow for systematic studies of ECM-related factors that govern astrocyte behaviour. In this study, we explore the interactions between neuroblastoma (SH-SY5Y) and glioblastoma (U87) cell lines and human fetal primary astrocytes (FPA) with a modular hyaluronan-based hydrogel system. Morphological analysis reveals that FPA have a higher degree of interactions with the hyaluronan-based gels compared to the cell lines. This interaction is enhanced by conjugation of cell-adhesion peptides (cRGD and IKVAV) to the hyaluronan backbone. These effects are retained and pronounced in 3D bioprinted structures. Bioprinted FPA using cRGD functionalized hyaluronan show extensive and defined protrusions and multiple connections between neighboring cells. Possibilities to tailor and optimize astrocyte-compatible ECM-mimicking hydrogels that can be processed by means of additive biofabrication can facilitate the development of advanced tissue and disease models of the central nervous system. [ABSTRACT FROM AUTHOR]

Aim: Tuberculous meningitis is an infectious disease of the central nervous system caused by Mycobacterium tuberculosis (M. tuberculosis). It mainly involves the meninges and brain parenchyma, as well as the spinal cord and meninges; Disability and mortality rates are high. In recent years, due to the increase of drug-resistant tuberculosis patients, population mobility and the prevalence of acquired immune deficiency syndrome, the incidence rate of tuberculosis has increased significantly, and tuberculous meningitis has also increased. Methods: At present, tuberculosis is still a worldwide infectious disease that seriously threatens human health, especially in underdeveloped and developing countries. China is the largest developing country in the world with a large population. Results: The situation of tuberculosis prevention and control is grim. Its disability rate is the highest in tuberculosis infection. In addition to the common non-specific manifestations, tuberculous meningoencephalitis may also have rare manifestations of stroke, hearing loss and visual loss. Conclusion: Understanding and timely improvement of corresponding examinations and targeted treatment will help improve the prognosis of patients. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is a chronic, demyelinating inflammatory disease of the central nervous system. Medication persistence is defined as an interval between the initiation and last dose of the applied medication and presents a useful surrogate marker of a stable disease course. This observational study aimed to evaluate medication persistence and discontinuation reasons in Slovenian people with multiple sclerosis treated with dimethyl fumarate. Our retrospective cohort study evaluated people with relapsing-remitting multiple sclerosis treated with dimethyl fumarate as an initial monotherapy or switched from injectable disease-modifying therapy medication between 2014 and 2021. Medication dispenses were extracted from the Slovenian National Institute of Public Health Outpatient Medication Database. The medication persistence criterion was based on the treatment gap. Patients exceeding a 60-day gap were considered nonpersistent. The median time to discontinuation was assessed using survival analyses. Considering discontinuation reasons, patients were further divided into safety and inefficacy groups. Due to the high probability of adverse effects, patients exceeding a 60-day gap were included in the safety group, but definite discontinuation reason remains unknown. The impact of covariates was evaluated by Cox regression. A total of 269 patients were included (183 women, mean age 37 years). During the 7-year follow-up period, 123 (45.7%) patients discontinued treatment. The median time to discontinuation was 5.6 years. After 1, 2, and 5 years of treatment, 84%, 77%, and 57% of patients were found to be persistent, respectively. All patients older than 30 years (p = 0.0013) and among them, those in the inefficacy group (p = 0.037) were more likely to be persistent. The results of our study proved a high persistence rate among our patients. The most frequent discontinuation reason was gastrointestinal adverse effects. Medication persistence requires interventions in younger patients with an unstable disease course. [ABSTRACT FROM AUTHOR]

To evaluate the clinical utility of metagenomic next-generation sequencing (mNGS) for the diagnosis of central nervous system infections (CNSI). Cerebrospinal fluid (CSF) from 54 patients who were high-level clinical suspicion of CNSI was collected and sent for mNGS and conventional tests from January 2019 to March 2022. Twenty out of 54 patients were diagnosed with CNSI and 34 non-CNSI. Among the 34 non-CNSI, one was false positive by mNGS. Among the 20 CNSI, 11 had presumed viral encephalitis and/or meningitis, 5 had presumed bacterial meningitis, 2 had presumed TMB, 1 had Crytococcus meningitis and 1 had neurosyphilis. The sensitivity of viral encephalitis and/or meningitis was 0.73 (8/11); 10 virus were detected; 9/10 was dsDNA; 1/10 was ssRNA. SSRN ranged from 1 to 13. The accuracy rate was 0.4, the accuracy rate was positively correlated with SSRN (r = 0.738, P = 0.015), SSRN ≥ 1, the accuracy rate was 0.4; SSRN ≥ 3, the accuracy rate was 0.66; SSRN ≥ 4, the accuracy rate was 0.75; SSRN ≥ 6, the accuracy rate was 1. The sensitivity of bacterial meningitis was 1. Seven kinds of bacteria were detected, among which 3/7 were gram positive, 3/7 were gram negative, and 1/7 was infected NTM (nontuberculous mycobacteria). The accuracy rate was 0.43 (3/7). The sensitivity of TBM was 0.66 (2/3), the accuracy rate was 1. The sensitivity of Crytococcus meningitis was 1, the accuracy rate was 0.5. PPV (positive predictive value) of mNGS was 0.94, NPV (negative predictive value) of mNGS was 0.89, specificity was 0.97 and sensitivity was 0.8. The AUG for CSF mNGS diagnosis of CNSI was 0.89 (95% CI = 0.78–0.99) Headache, meningeal irritation sign and image of meninges abnormal were correlated with the sensitivity of mNGS (r = 0.451, 0.313, 0.446; p = 0.001, 0.021, 0.001); CSF Glucose and CSF Chloride were negatively correlated with sensitivity of mNGS (r = -0.395, −0.462; p = 0.003, ＜ 0.001). mNGS is a detection means with high sensitivity, wide coverage and strong timeliness, which can help clinicians to identify the pathogen diagnosis quickly, conduct targeted anti-infection treatment early and reduce antibiotic abuse. The pathogen which causing low CSF Glucose, low CSF Chloride or meninges infections was more likely to be detected by mNGS. It may be related to growth and structural characteristics of the pathogen and blood–brain barrier damage. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is involved in the pathogenesis of multiple sclerosis (MS), a severe autoimmune demyelinating disease of the central nervous system. The gene polymorphism Cdx-2 (rs11568820, G/A) seriously influences the trancriptional activity of the vitamin D receptor (VDR) that binds the vitamin D responsive elements of target genes including HLA-DRB1*15. The aim of the present study in Slovaks was to analyse the association of Cdx-2 variants with the risk of MS and disability progression, and to assess the DRB1*15:01 allele as a possible confounding factor. In total, 493 MS patients and 417 healthy controls were involved in this study. The genotyping of Cdx-2 was performed using restriction analysis; DRB1*15:01 positivity was determined by a high-resolution melting analysis of its surrogate marker rs3135388 (G/A). Our results did not prove any allelic association between Cdx-2 and a risk of MS (minor allele A − 0.181 in patients vs. 0.161 in controls, OR = 1.15,.95 CI = 0.90–1.47, p = 0.289). The logistic regression analysis, adjusted for sex and age, showed no differences in Cdx-2 genotype counts when using an additive, dominant or recessive genetic model (p = 0.351, 0.150, 0.240 respectively). The Cdx-2 variants were also not associated with disease disability progression, evaluated using the Multiple Sclerosis Severity Score. The HLA-DRB1*15:01 allele was found to strongly increase the risk of MS in our study (0.300 in patients vs. 0.101 in controls, OR = 3.83,.95 CI = 2.94–4.99, p = 1.016 × 10−26, dominant genetic model OR = 4.62,.95 CI = 3.40–6.26, p = 9.1 × 10−23). In summary, we found the Cdx-2 as a single genetic marker not to be associated with MS development or progression in Slovaks, independently of HLA-DRB1*15:01 status. [ABSTRACT FROM AUTHOR]

The scoping review was undertaken to explore comorbidities in infants and children with neonatal brachial plexus palsy (NBPP). The purpose of the review was to inform physical and occupational therapy screening of multiple body systems during the examination of children with NBPP. EBSCO Discovery and EMBASE electronic databases were searched for reports published between January 1996 and September 2021 describing comorbidities in children with NBPP between birth and 18 years. Key data pertaining to comorbidity prevalence, risk factors, clinical features, and associated outcomes were extracted and charted by one researcher and confirmed by a second researcher. Thirty-six articles were included in the scoping review. Fourteen comorbidities were identified across the musculoskeletal, neurological, cardiopulmonary, and integumentary systems and the communication domain. The most prevalent comorbidities were clavicle fractures, plagiocephaly, torticollis, high body mass index, and language delays. The least prevalent comorbidity was facial nerve palsy. Physical and occupational therapists can use knowledge of comorbidities in infants and children with NBPP for multisystem screening during the examination. A thorough history can identify risk factors for comorbidities. Detection of comorbidities during screening allows for timely specialty referrals to optimize care. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is an inflammatory, autoimmune, and progressive neurodegenerative disease of the central nervous system with an unknown etiology. Based on the gender differences in epidemiological, clinical, and pathological features of multiple sclerosis, the role of sex hormones and their receptors in this disease has been considered. A single nucleotide polymorphism located in the exon 4 of progesterone receptor, rs1042838 (G/T -Val660Leu), was associated with reduced progesterone receptor activity. We aimed to investigate the association of this polymorphism with the risk of multiple sclerosis. A total of 426 individuals were included in the present study, including 200 patients and 226 age and sex adjusted healthy controls in Iranian population. The target SNP was genotyped using PCR-RFLP, and statistical analysis was performed using SPSS 21.0 and by ꭓ2 and logistic regression tests. The results showed that the allele T acts as a risk allele, so that the genotypes TG and TT significantly increase RRMS susceptibility compared to the genotype GG. Our data suggest that Val660Leu polymorphism might be a risk factor for the development of RRMS. [ABSTRACT FROM AUTHOR]

Neurological disorders are associated with very high rates of depression and anxiety, which significantly increase disease burden, but remain an area of considerable unmet need. Psychological therapies, especially those based on the principles of cognitive and behavioural therapy, appear to be efficacious for improving both mental health (e.g., depression and anxiety) and functional outcomes (e.g., sleep, fatigue) in patients with a variety of neurological disorders. However, access to these therapies is limited. Neuropsychologists rarely have the capacity to deliver ongoing psychological therapy and there appears to be a lack of community psychologist that specialise in this area. This commentary argues that these barriers need to be addressed and psychologists should play a greater role in reducing the burden of neurological disorders. One step towards this is building the confidence and competence of psychologists to effectively work with patients with neurological symptoms, especially common cognitive difficulties (e.g., inattention, poor memory, slower processing speed). Thus, this commentary provides a practical guide for modifying psychological therapies for adults with neurological disorders, including principles of compensatory cognitive rehabilitation. It aims to provide principles to help maximise engagement, learning and retention of psychological concepts and ultimately to encourage more psychologists to work with this under-served group. What is already known about this topic: Depression and anxiety are common in neurological disorders but often go untreated. Psychological therapies can improve mental health and functional outcomes across neurological disorders, but access to these interventions is very limited. Neuropsychologists report a lack of confidence providing ongoing psychological interventions for mental health, and identifying community psychologists specialising in neurology is challenging. What this topic adds: A discussion of the mental health burden of neurological disorders and role of psychological therapy. A guide to modifying psychological therapies for adults with neurological disorders, especially for cognitive difficulties. Tips for maximising engagement, learning and retention within therapy to support effective work with people with neurological disorders. [ABSTRACT FROM AUTHOR]

Cerebral microbleeds (CMBs) are subclinical lesions of the brain parenchyma and an important marker for the clinical diagnosis of central nervous system vascular disease. However, the relationship between CMBs and cerebral infarction, cerebral hemorrhage, and cognitive impairment remains unclear. In order to explore the cognitive function and risk factors of patients with acute cerebral infarction (ACI) complicated with cerebral microbleeds, 190 patients with ACI were collected. The patients were divided into groups with CMBs (n = 108) and groups without CMBs (n = 82) according to the presence or absence of CMBs. The general data, various examination indicators, Montreal Cognitive Assessment Scale (MoCA) scores of the two groups of patients were analyzed. Sixty healthy controls who underwent physical examination in our hospital during the same period were included as the healthy control group. ACI patients with CMBs had significantly higher rates of leukoaraiosis, hyperhomocysteinemia, hypercholesterolemia, and hypertension. Cognitive function was significantly lower in ACI patients with CMBs. Serum D-dimer, serum high-sensitivity C-reactive protein, serum neuron-specific enolase, and serum S100β of ACI patients with CMBs were all negatively correlated with their MoCA scores. ACI patients with CMBs tended to have lower cognitive abilities than ACI patients without CMBs. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1(GLP-1) is a multifunctional polypeptide throughout the lifespan via activating Glucagon-like peptide-1 receptor (GLP-1R).GLP-1 can affect food ingestion, enhance the secretion of insulin from pancreatic islets induced by glucose and be utilized to treat type 2 diabetes mellitus(T2DM).But, accumulating evidences from the decades suggest that activation GLP-1R can not only regulate the blood glucose, but also sustain the homeostasis of intracellular environment and protect neuron from various damaged responses such as oxidative stress, inflammation, excitotoxicity, ischemia and so on. And more and more pre-clinical and clinical studies identified that GLP-1 and its analogues may play a significant role in improving multiple central nervous system (CNS) diseases including neurodegenerative diseases, epilepsy, mental disorders, ischemic stroke, hemorrhagic stroke, traumatic brain injury, spinal cord injury, chronic pain, addictive disorders, other diseases neurological complications and so on. In order to better reveal the relationship between GLP-1/GLP-1R axis and the growth, development and survival of neurons, herein, this review is aimed to summarize the multi-function of GLP-1/GLP-1R axis in CNS diseases. [ABSTRACT FROM AUTHOR]

Background and purpose: Parkinson's disease is a common degenerative disease of the central nervous system with complex pathogenesis. More and more studies have found that inflammatory response promotes the occurrence and development of the disease, in which the activation of microglia plays an important role. PGC-1α (peroxisome proliferator activated receptor-γ coactivator-1α) is the main factor in mitochondrial biogenetic, and is closely related to the inflammatory response. Our immunofluorescence test results showed that PGC-1α and microglia (Iba1) have double-labeled phenomenon. The expression of microglia in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) group increased, and PGC-1α/Iba1 double label increased. To test whether lowering the expression of PGC-1α can reduce the activation of microglia and protect the substantia nigra dopaminergic neurons, we constructed PGC-1α interference lentivirus. Methods: Immunofluorescence, western blot, and ELISA were used to detect microglial phenotype. Results: The results showed that PGC-1α interfering with lentivirus can transfect microglial cells in substantia nigra, and the PGC-1α protein level decreased in substantia nigra accordingly; TH protein expression had no statistical difference compared with MPTP group; PGC-1α interfering lentivirus reduced microglia number and activation, and at the same time the expression of iNOS and Arg1 significantly reduced compared with MPTP group. The IL-6 expression in blood detected using ELISA was significantly reduced compared with MPTP group. Conclusion: PGC-1α downregulation inhibited microglia activity, and both M1 and M2 microglial activities are reduced. [ABSTRACT FROM AUTHOR]

This study aimed to systematically assess the impact of clinical and demographic variables on the diagnostic yield of Whole Exome Sequencing (WES) when applied to children with Autism Spectrum Disorder (ASD) from a consanguineous population. Ninety-seven children were included in the analysis, 63% were male and 37% were females. 77.3% had a suspected syndromic aetiology of which 68% had co-existent central nervous system (CNS) clinical features, while 69% had other systems involved. The diagnostic yield of WES in our cohort with ASD was 34%. Children with seizures were more likely to have positive WES results (46% vs. 31%, p = 0.042). Probands with suspected syndromic ASD aetiology showed no significant differential impact on the diagnostic yield of WES. [ABSTRACT FROM AUTHOR]

Objective: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that frequently affects cognition. Persons with MS (PwMS) complain of difficulties with prospective memory (PM), the capacity to remember to perform an intended action at the appropriate moment in the future. The objective of this study was to assess the clinical utility of the Miami Prospective Memory Test (MPMT) in detecting PM deficits in MS. The test is brief, easy to administer and accessible, and allows direct comparison between scores on event- and time-based conditions. A secondary objective was to examine the relationship between PM performance and cognitive functioning. Method: Eighty-four PwMS between 27 and 78 years old were compared to 50 age-, sex- and education-matched healthy adults on the MPMT. Results: Time-based (TB) scores, but not event-based (EB) scores, were significantly lower in PwMS than in healthy adults. The MPMT showed good internal consistency, and correlations were found with disability assessed by the Expanded Disability Status Scale (EDSS). PM was also correlated with memory and executive/attention functioning. Conclusions: This study supports the clinical utility of the MPMT in assessing the presence of PM deficits in PwMS especially under TB constraints. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system mediated by antibodies targeting the aquaporin-4 (AQP4) water channel expressed on astrocytes. The binding of specific antibodies to AQP4 causes complement-dependent cytotoxicity, leading to inflammation and demyelination. Several recent phase 2 and 3 randomized placebo-controlled trials showed the efficacy and safety of monoclonal antibody therapies targeting B-cells, interleukin-6 receptor, and complement. Current biologic treatments for NMOSD and developments therein, and unresolved issues in NMOSD treatment. New biologic treatments demonstrate high efficacy and good safety for patients with AQP4-IgG-positive NMOSD. The optimal therapeutics for seronegative NMOSD, pediatric patients, and female patients who are pregnant or wish to be are unclear, and further research is needed. Also, real-world studies of new biological agents and the data on the durability of their beneficial effects and their long-term safety are required. Effective rescue therapy for an acute attack is critical given permanent disability in NMOSD is attack-related, and biologic agents that treat acute attack are emerging. If such treatments are to become widely applied, studies on the most cost-effective treatment strategies are needed. [ABSTRACT FROM AUTHOR]

Demyelinating diseases of the central nervous system (CNS) often have neuro-ophthalmological manifestations, and retinal examination can be helpful in making the diagnosis. The latest iteration of optical coherence tomography (OCT)-based criteria for optic neuritis in multiple sclerosis has been developed in the research realm, but its application to clinical practice, and to the more uncommon demyelinating diseases requires further study. The ability to use OCT data to distinguish between various CNS demyelinating disorders could provide additional paraclinical tools to accurately diagnose patients. Furthermore, neuro-ophthalmological testing can define the extent of inflammatory damage in the CNS, independent of patient-reported history. New referrals for OCT at a tertiary multiple sclerosis and neuro-immunology referral centre (n = 167) were analysed retrospectively for the self-reporting of optic neuritis, serological test results, and diagnosis. Only approximately 30% of patients with a clinical history of unilateral optic neuritis solely had a unilateral optic neuropathy, nearly 40% of those subjects actually having evidence of bilateral optic neuropathies. Roughly 30% of patients reporting a history of bilateral optic neuritis did not have any evidence of structural disease, with 20% of these patients having a separate, intervenable diagnosis noted on macular scans. OCT is a useful adjunct diagnostic tool in the evaluation of demyelinating disease and has the ability to aid in a more accurate diagnosis for patients. Application of the international interocular difference thresholds to a clinical patient population generally reproduces the original results, emphasising their appropriateness. The analysis distinguishing the demyelinating diseases needs to be replicated in a blinded, multi-centre setting. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a serious central nervous system disease, and secondary injury, including oxidative stress, the inflammatory response and accompanying neuronal apoptosis, will aggravate the condition. Due to the existence of the blood-spinal cord barrier (BSCB), the existing drugs for SCI treatment are difficulty to reach the injury site and thus their efficacy is limited. In this study, we designed chitosan-modified hollow manganese dioxide nanoparticles (CM) for the delivery of resveratrol to help it pass through the BSCB. Resveratrol (Res), a poorly soluble drug, was adsorbed into CM with a particle size of approximately 130 nm via the adsorption method, and the drug loading reached 21.39 ± 2.53%. In vitro dissolution experiment, the Res release of the loaded sample (CMR) showed slowly release behavior and reached about 87% at 36 h. In vitro at the cellular level and in vivo at the animal level experiments demonstrated that CMR could alleviate significantly oxidative stress by reducing level of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and increasing glutathione peroxidase (GSH) level. Additionally, immunofluorescence (iNOS, IL-1ß, and Cl caspase-3) and western blot (iNOS, cox-2, IL-1ß, IL-10, Cl caspase-3, bax, and bcl-2) were used to detect the expression of related factors, which verified that CMR could also reduce inflammation and neuronal apoptosis. These results indicated that CM, as a potential central nervous system drug delivery material, was suitable for SCI treatment. [ABSTRACT FROM AUTHOR]

The blood-brain barrier (BBB) is a protective barrier for brain safety, but it is also a major obstacle to the delivery of drugs to the cerebral parenchyma such as the hippocampus, hindering the treatment of central nervous system diseases such as Alzheimer's disease (AD). In this work, an anti-AD brain-targeted nanodrug delivery system by co-loading icariin (ICA) and tanshinone IIA (TSIIA) into Aniopep-2-modified long-circulating (Ang2-ICA/TSIIA) liposomes was developed. Low-density lipoprotein receptorrelated protein-1 (LRP1) was a receptor overexpressed on the BBB. Angiopep-2, a specific ligand of LRP1, exhibited a high binding efficiency with LRP1. Additionally, ICA and TSIIA, drugs with neuroprotective effects are loaded into the liposomes, so that the liposomes not only have an effective BBB penetration effect, but also have a potential anti-AD effect. The prepared Ang2-ICA/TSIIA liposomes appeared narrow dispersity and good stability with a diameter of 110nm, and a round morphology. Cell uptake observations, BBB models in vitro, and imaging analysis in vivo showed that Ang2-ICA/TSIIA liposomes not only penetrate the BBB through endocytosis, but also accumulate in N2a cells or brain tissue. The pharmacodynamic analysis in vivo demonstrated that Ang2-ICA/TSIIA liposomes could improve AD-like pathological features in APP/PS1 mice, including inhibiting neuroinflammation and oxidative stress, reducing apoptosis, protecting neurons, and improving cognitive function. Therefore, Ang2-ICA/TSIIA liposomes are considered a potentially effective therapeutic strategy for AD. [ABSTRACT FROM AUTHOR]

This study is a secondary analysis of data from a mixed methods exploration of fatigue in people with multiple sclerosis (MS), a chronic autoimmune disease affecting the central nervous system. During initial analysis, worry emerged during discussions of the fatigue experience. The purpose of this study is to explore worry in relationship to exercise and physical activity behavior. Mixed methods were used to address the research question. 55 people with MS provided demographic and survey data (habitual physical activity, body perception, functioning). 35 participated in semi-structured interviews on the topics of fatigue, body sensations, emotions, and their effects on physical activity. Qualitative data were analyzed utilizing constructivist grounded theory. Quantitative data were analyzed utilizing multiple regression. Qualitative theory described participants' thoughts and experiences regarding the consequences of fatigue during activity, and how they appear to influence subsequent actions. Worry played a critical role in thought processes regarding physical activity. Aspects of body perception were weak quantitative predictors of physical activity behavior after control of physical functionality. The most significant finding of this study was the description and dialogue about worry as a factor that shapes perceptions of the benefits and value of exercise and physical activity. Physical activity practitioners could benefit from seeking to understand physical-activity-related worry when examining physical activity behavior and designing programming. [ABSTRACT FROM AUTHOR]

Secretory carrier membrane proteins (SCAMPs) constitute a group of membrane transport proteins in plants, insects and mammals. The mammalian genome contains five types of SCAMP genes, namely, SCAMP1-SCAMP5. SCAMPs participate in the vesicle cycling fusion of vesicles and cell membranes and play roles in regulating exocytosis and endocytosis, activating synaptic function and transmitting nerve signals. Among these proteins, SCAMP5 is highly expressed in the brain and has direct or indirect effects on the function of the central nervous system. This paper may allow us to better understand the role of SCAMP5 in the central nervous system diseases. SCAMP5 regulates membrane transport, controls the exocytosis of SVs and is related to secretion carrier and membrane function. In addition, SCAMP5 plays a major role in the normal maintenance of the physiological functions of nerve cells. This article summarizes the effects of SCAMP5 on nerve cell exocytosis, endocytosis and synaptic function, as well as the relationship between SCAMP5 and various neurological diseases, to better understand the role of SCAMP5 in the pathogenesis of neurological diseases. Through PubMed, this paper examined and analyzed the role of SCAMP5 in the central nervous system, as well as the relationship between SCAMP5 and various neurological diseases using the key terms "secretory carrier membrane proteins"," SCAMP5"," exocytosis"," endocytosis", "synaptic function", "central nervous system diseases" up to 01 March 2022. SCAMP5 regulates membrane transport, controls the exocytosis of SVs and is related to secretion carrier and membrane function. In addition, SCAMP5 plays a major role in the normal maintenance of the physiological functions of nerve cells. This article summarizes the effects of SCAMP5 on nerve cell exocytosis, endocytosis and synaptic function, as well as the relationship between SCAMP5 and various neurological diseases, to better understand the role of SCAMP5 in the pathogenesis of neurological diseases. [ABSTRACT FROM AUTHOR]

Multiple Sclerosis (MS), the leading cause of non-traumatic neurological disability in young adults, is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). Due to the poor accessibility to the target organ, CNS-confined processes underpinning the later progressive form of MS remain elusive thereby limiting treatment options. We aimed to examine DNA methylation, a stable epigenetic mark of genome activity, in glial cells to capture relevant molecular changes underlying MS neuropathology. We profiled DNA methylation in nuclei of non-neuronal cells, isolated from 38 post-mortem normal-appearing white matter (NAWM) specimens of MS patients (n = 8) in comparison to white matter of control individuals (n = 14), using Infinium MethylationEPIC BeadChip. We identified 1,226 significant (genome-wide adjusted P-value < 0.05) differentially methylated positions (DMPs) between MS patients and controls. Functional annotation of the altered DMP-genes uncovered alterations of processes related to cellular motility, cytoskeleton dynamics, metabolic processes, synaptic support, neuroinflammation and signaling, such as Wnt and TGF-β pathways. A fraction of the affected genes displayed transcriptional differences in the brain of MS patients, as reported by publically available transcriptomic data. Cell type-restricted annotation of DMP-genes attributed alterations of cytoskeleton rearrangement and extracellular matrix remodelling to all glial cell types, while some processes, including ion transport, Wnt/TGF-β signaling and immune processes were more specifically linked to oligodendrocytes, astrocytes and microglial cells, respectively. Our findings strongly suggest that NAWM glial cells are highly altered, even in the absence of lesional insult, collectively exhibiting a multicellular reaction in response to diffuse inflammation. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the patient perspective of their experiences of daily life after spasticity-correcting surgery for disabling upper limb (UL) spasticity after spinal cord injury (SCI) and stroke. Eight patients with UL spasticity resulting from SCI (n= 6) or stroke (n= 2) were interviewed 6–9 months after spasticity-correcting surgery. A phenomenographic approach was used to analyze the interviews. Five themes emerged from the interviews: (1) bodily changes, such as increased muscle strength, range of motion, and reduced muscle-hypertonicity; (2) improved occupational performance, facilitating tasks, mobility, and self-care; (3) regained control, explicating the perception of regaining bodily control and a more adaptable body; (4) enhanced interpersonal interactions, entailing the sense of being more comfortable undertaking social activities and personal interactions; and (5) enhanced psychological well-being, including having more energy, increased self-esteem, and greater happiness after surgery. The participants experienced improvements in their everyday lives, including body functions, activities, social life, and psychological well-being. The benefits derived from surgery made activities easier, increased occupational performance, allowed patients regain their roles and interpersonal interactions, and enhanced their psychological well-being. Spasticity-correcting surgery benefits patients by improving bodily functions, which in turn, enable gains in activities, social life, and psychological well-being. Patients' experiences of increased body functions, such as enhanced mobility and reduced muscle hypertonicity, appear to increase the sense of bodily control. The surgery can increase participation and psychological well-being, even for patients whose functional or activity level did not improve after the treatment. The benefits expressed by the individuals in this study can be used to inform, planning, and in discussion with patients and other healthcare professionals about interventions targeting spasticity. [ABSTRACT FROM AUTHOR]

Psoriasis is an inflammatory, chronic and immune-mediated disease that can affect the skin and joints. Pro-inflammatory cytokines have a dominant role in the pathogenesis of this heterogeneous disease in which the IL-23/IL-17 axis plays a crucial role. The IL-17 family is involved in numerous processes such as immune defense, intestinal disorders and diseases of the central nervous system. In psoriasis, in particular, many cytokines belonging to the IL-17 family are involved in the inflammatory cascade underlying the disease. The knowledge of the mechanisms and pathways behind psoriasis is crucial for the development of new target therapies. We focused on IL-17 biology in order to understand why biological drugs against this cytokine are an effective treatment for moderate to severe psoriasis. Clinical trials results of ixekizumab, brodalumab, secukinumab and bimekizumab have been presented. Il-17 inhibitors are a very fast and effective treatment against psoriasis; however, fungal infections can occur during their use, due to IL-17 biological functions. Therefore, it should be mandatory to choose the right patients to treat with these monoclonal antibodies in order to have a tailored target therapy for each patient. [ABSTRACT FROM AUTHOR]

As a committed step in the urea cycle, arginase cleaves l-arginine to form l-ornithine and urea. l-Ornithine is essential to: cell proliferation, collagen formation and other physiological functions, while the urea cycle itself converts highly toxic ammonia to urea for excretion. Recently, arginase was exploited as an efficient catalyst for the environmentally friendly synthesis of l-ornithine, an abundant nonprotein amino acid that is widely employed as a food supplement and nutrition product. It was also proposed as an arginine-reducing agent in order to treat arginase deficiency and to be a means of depleting arginine to treat arginine auxotrophic tumors. Targeting arginase inhibitors of the arginase/ornithine pathway offers great promise as a therapy for: cardiovascular, central nervous system diseases and cancers with high arginase expression. In this review, recent advances in the characteristics, structure, catalytic mechanism and preparation of arginase were summarized, with a focus being placed on the biotechnical and medical applications of arginase. In particular, perspectives have been presented on the challenges and opportunities for the environmentally friendly utilization of arginase during l-ornithine production and in therapies. [ABSTRACT FROM AUTHOR]

Herpes simplex encephalitis (HSE), mainly caused by herpes simplex virus type 1 (HSV-1), is a severe central nervous system disease commonly followed by cognitive impairment, behavioral changes, and focal neurological signs. Although increasing evidence implicates the central role of microglia in HSE progression, the intrinsic restrictors or the acquired environmental factors that balance the beneficial or detrimental immune responses in microglia remain unclear. In a recent study, we find that a gut microbial metabolite activates mitophagy to regulate microglia-mediated neuroinflammation and to mitigate HSE progression. HSV-1 neurotropic infection causes gut microbiota dysbiosis and microglial antiviral immune response, whereas depletion of gut microbiota by oral antibiotics treatment further results in hyperactivated microglia and exacerbated HSE pathology. Notably, exogenous administration of nicotinamide n-oxide (NAMO), an oxidative product of nicotinamide mainly produced by intestinal neomycin-sensitive bacteria, especially Lactobacillus gasseri and Lactobacillus reuteri, can significantly suppress HSE progression. Mechanistically, HSV-1 infection causes mitochondrial dysfunction and impairs mitophagy to activate microglia and promote proinflammatory cytokine production, whereas NAMO restores NAD+-dependent mitophagy to restrain microglial over-activation and to prevent HSV-1 early infection in neuronal cells. This work reveals a novel function of gut microbial metabolites as intrinsic regulators of microglia homeostasis and neuroinflammation via mitophagy. Abbreviations: AD: Alzheimer disease; ABX: antibiotics; HSE: herpes simplex encephalitis; HSV-1: herpes simplex virus type 1; NAD+: nicotinamide adenine dinucleotide; NAMO: nicotinamide n-oxide; SCFAs: short-chain fatty acids. [ABSTRACT FROM AUTHOR]

Uncaria rhynchophylla (UR) belongs to the Rubiaceae family, and its dried hooks are usually used in traditional medicine. It is effective in treating diseases related to the central nervous system. This study aimed to evaluate the safety of UR extract, investigate its antimutagenic and antioxidative activities, and elucidate its active components. Extraction and fractionation of the UR extract resulted in yields of 6.71%, 0.037%, 0.042%, 0.152%, 0.332%, and 5.132%, for hexane, ether, DCM, EtOAC, and aqueous fractions, respectively. The four indole alkaloids, total phenolic content (TPC), and total flavonoid content (TFC) of UR extract and its subfractions were measured. Alkaloid content was highest in the UR extract. TPC was the highest in the EtOAC fraction (373.7 ± 20.9 mg gallic acid equivalent (GAE)/g), whereas TFC was the highest in the UR extract (33.5 ± 2.4 mg quercetin equivalent (QE)/g). To assess the safety of UR extract mutagenicity, cytotoxicity, and oxidative stress inducibility assays were performed. The UR extract (2000 µg/plate) showed excellent antimutagenic activity (above 90%) against BaP in both TA98 and TA100 strains. The UR extract exhibited efficient DPPH (RC50 239.2 ± 16.5 µg/mL) and ABTS scavenging activity (RC50 458.7 ± 25.0 µg/mL). The UR extract (150 µg/mL) showed cytoprotective activity (65.6% ± 9.2%) against t-BHP. Among the subfractions, the EtOAC fraction possessed the strongest activities, overall. UR generally showed excellent biological activity at nontoxic concentrations (determined in vitro in current work), although the chemical composition of UR requires further investigation prior to its potential future use. [ABSTRACT FROM AUTHOR]

Background. Multiple sclerosis (MS) is an autoimmune and demyelination disease of the central nervous system that causes progressive accumulation of disability over time. Recent studies have highlighted the correlation between metabolic disorders and cognitive dysfunctions. The present study aims to evaluate the correlation between components of the lipid profile and cognitive dysfunctions in patients affected by MS. Methods. 90 MS inpatients were included in this study. We divided the sample into three subgroups to evaluate the influence of the presence of dyslipidemia: G1 (patients with dyslipidemia), G2 (patients without dyslipidemia), G3 (patients with a higher than normal lipid value). Patients underwent rehabilitation treatment which included conventional physiotherapy, speech therapy, psychological support, cognitive rehabilitation, nutritional therapy, robotic rehabilitation, cognitive rehabilitation, and virtual reality. Results. The results showed that the three subgroups had a significant improvement in global cognitive functioning (MOCA p < 0.00), working memory (BRB-NV SRT-LTS p < 0.00) and in attention process (BRB-NV SDMT p < 0.00). Only in the G2, we observed a significant improvement in visuospatial abilities (RAO SPART p < 0.00). Moreover, we found that the cholesterol was negatively correlated with the cognitive functioning score of the patients after rehabilitation and the EDSS score. While the triglyceride scores were negatively correlated with the working memory score before and after rehabilitation. BMI scores were negatively correlated with the visuospatial ability score. Conclusion. Investigating these aspects could help in managing patients, preventing alterations that compromise the patient's quality of life. [ABSTRACT FROM AUTHOR]

Central nervous system infectious disease caused by the multidrug-resistant Acinetobacter baumannii (AB) seriously threatens human life in clinic. Tigecycline has good sensitivity in killing AB, but due to its wide tissue distribution and blood-brain barrier, concentration in cerebrospinal fluid is low, therefore, the clinical effect is limited. Herein, we designed micro-bubbled tigecycline, aimed to enhance its anti-MDRAB effects under ultrasound. The lipid microbubbles with different ratios of lipids to drugs (a ratio of 10:1, 20:1, and 40:1) were prepared by the mechanical shaking method. The morphology, zeta potential and particle size of microbubbles were tested to screen out the much better formulation. Encapsulation efficiency and drug loading amount were determined by ultracentrifugation combined with high-performance liquid chromatography. Then the in vitro antibacterial activity against AB was conducted using the selected ultrasound-activated microbubble. Results showed the selected microbubbles with high encapsulation efficiency and good stability. The mechanical shaking method is feasible for preparation of drug-loaded and ultrasound-activated lipid microbubbles. Using 0.2 mg/mL microbubbles, combined with 1 MHz, 2.5 W/cm2 and 1 min of ultrasound exhibited a potent anit-AB in vitro. This study indicates that tigecycline treatment in form of ultrasound-activated microbubble is a promising strategy against AB infections. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by progressive cognitive and memory-related impairment. However, current therapeutic treatments have not proved sufficiently effective, mainly due to the complicated pathogenesis of the disease. In this study, a nano-formulation of graphene oxide (GO) loaded with dauricine (Dau) was investigated in terms of the combined anti-inflammatory and anti-oxidative stress effects of Dau and the inhibition of misfolding and aggregation of the amyloid-b (Ab) protein by GO. Both in vivo and in vitro models were induced using Ab1-42, and the formulation was administered nasally in mice. The results showed that GO loaded with Dau greatly reduced oxidative stress through increasing superoxide dismutase levels and decreasing reactive oxygen species and malondialdehyde levels in vitro; it also alleviated the cognitive memory deficits and brain glial cell activation in mice with Ab1-42-induced AD. This proved that GO loaded with Dau could protect against Ab1-42-induced oxidative damage and apoptosis in both in vitro and in vivo AD models; therefore, GO loaded with Dau has the potential to be an effective and agent for the rapid treatment of AD. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis along with its animal model, experimental autoimmune encephalomyelitis (EAE), are chronic inflammatory and degenerative diseases of the central nervous system (CNS). Due to the unknown cause of the disease, the most common treatments of MS are targeted for the reduction of inflammation and the repairment of CNS tissue damage, especially myelin restoration. Due to the immune protective nature of herbs, it may be useful to evaluate the impact of herbs in the diet regimen of MS patients along with their immune-mediated effects. The purpose of this study was to investigate the effect of an aqueous extract of Artemisia dracunculus (Tarragon) on the treatment of EAE in C57BL/6 mice. Methods: In this experimental study, mice were divided into the following control, untreated EAE, and A. dracunculus treated EAE groups. EAE was induced by myelin oligodendrocyte glycoprotein (MOG35-55) in female C57BL/6 mice. The symptoms of the disease and the weight of the mice were recorded daily. On day 33 after EAE induction, the mice were sacrificed and the specimens were collected. Cell proliferation and cytokine release (TGF-β, IL-17 and IL-23) from mice cultured spleen cells was measured by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and ELISA respectively. Results: Administration of the extract of A. dracunculus mitigated EAE symptoms (P < 0.05). Furthermore, there was a reduction in the levels of inflammatory cytokines including IL-17 (P = 0.009) and IL-23 (P = 0.012) and confirmed increased serum antioxidant levels in A. dracunculus treated EAE mice (P = 0.008). Conclusions: These observations indicate that A. dracunculus extracts could reduce inflammatory cytokines and attenuate certain signs of EAE, suggesting the potential of a useful adjuvant therapy for MS. [ABSTRACT FROM AUTHOR]

Multiple Sclerosis (MS) is a chronic autoimmune and neurodegenerative disease of the central nervous system with a course dependent on early treatment response. Increasing evidence also suggests that despite eliminating disease activity (relapses and lesions), many patients continue to accrue disability, highlighting the need for a more comprehensive definition of treatment success. Optimizing disability outcome measures, as well as continuously improving our understanding of neuroinflammatory and neurodegenerative biomarkers is required. This review describes the challenges inherent in classifying and monitoring disease phenotype in MS. The review also provides an assessment of clinical, radiological, and blood biomarker tools for current and future practice. Emerging MRI techniques and standardized patient outcome assessments will increase the accuracy of initial diagnosis and understanding of disease progression. [ABSTRACT FROM AUTHOR]

The increasing popularity of exergaming (exercise and gaming) has already emerged in the rehabilitation setting to help individuals develop, maintain, and restore maximum body movement and physical function. However, there is a lack of attention to the risk of sustaining injuries associated with exergaming. While there are reports of potential harm or injuries for patients using this intervention, ergonomics has still not been given attention or consideration in the deliverance of exergaming during rehabilitation. The primary aim of this review is to identify the ergonomic considerations in the delivery of exergaming in rehabilitation. The secondary aim is to review the outcome measures used in the results of exergaming to patients with neurologic and orthopedic conditions from the literature gathered and appraised. The study will use a systematic review design to identify the ergonomic considerations and outcome measures in the delivery of exergaming and rehabilitation of neurologic and orthopedic patients by using only randomized controlled trial studies. Centre for Evidence-based Medicine of Oxford University will be used to appraise the reliability and validity of the chosen article and the Mendeley software, Rayyan QCRI application, and a spreadsheet software will be used in the inclusion, critical appraisal, and data gathering process to ensure objectivity. Preferred Reporting Items for Systematic Reviews (PRISMA) will be provided for visualization of the study acquisition and selection process. The extracted data will undergo analysis and will then determine the ergonomic considerations and outcome measures utilized in the studies reviewed. [ABSTRACT FROM AUTHOR]

A majority of stroke patients have persisting upper extremity impairments, with a large number of individuals who do not regain the ability to reach and manipulate everyday objects despite receiving prolonged and intensive therapy. Varied interventions have been employed to improve reaching functions. However, there is a lack of a comprehensive and updated review of all the interventions that can be used to improve upper extremity reaching function in stroke. To review the existing interventions aimed to improve upper extremity reaching function in persons with stroke. Studies with quantitative, qualitative, and mixed methods design which have employed interventions to improve upper extremity reaching function following stroke and have been published from database inception to 25th February 2021 in English. The proposed scoping review will follow the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist and will be conducted as per the methodological framework proposed by Arksey and O'Malley. A database-specific search strategy will be used in four electronic databases (MEDLINE, Scopus, CINAHL, Web of Science) and four grey literature platforms (ProQuest, MedNAR, OpenGrey, New York Academy of Medicine). The screening and extraction of data from eligible studies will be done independently by two reviewers. The extracted data will be presented with the help of tables and visual representation. Previously conducted reviews have enumerated the various types of interventions that have been used to improve upper extremity reaching function, but are incomprehensive and in need of an update. This review will provide an overview of all the therapeutic interventions which might aid in clinical decision making during stroke rehabilitation. [ABSTRACT FROM AUTHOR]

Spasticity is a motor disorder often associated with decreased ROM, ADL performance, and QOL. DN has shown potential to improve spasticity by stimulating spastic muscle tissue with a stainless steel monofilament needle. To determine the effects of dry needling (DN) on muscle spasticity in adults with neurological disorders. Literature search of Cochrane, CINAHL, Google Scholar, and ProQuest was conducted. Search limits: English, journals, human subjects, 2009–2019. Selection criteria: Adults 18+ with neurological disorders and interventions included dry needling as treatment for spasticity. Two reviewers, for methodological quality based on Oxford Levels of Evidence, independently assessed each study. Ten articles met the selection criteria, all showing reductions in spasticity. Secondary outcomes were reported with improvements at the impairment level including muscle length, range of motion, pain, and motor performance (Fugl-Meyer motor subscale); and at the functional level including hand dexterity (box and block test), balance (computerized dynamic posturography) and mobility (TUG). There is low to moderate evidence in support of using DN to decrease spasticity in adults with neurological disorders, specifically in those with a history of stroke. Limitations included lack of follow-up and small sample sizes. Further high-level research is required to determine long-term outcomes of DN in spastic muscles. There was a short-term decrease in spasticity of target muscles after the performance of DN. Evidence included improvements at the impairment and functional levels after the use of DN. DN poses as a safe, feasible option to improve spasticity and impact other targeted outcomes in adults with neurological disorders. [ABSTRACT FROM AUTHOR]

Treatment of central nervous system (CNS) demyelination is greatly hindered by lack of the knowledge regarding to underlying molecular mechanisms as well as therapeutic agents. Here, we report a novel small molecule agent, gastrodin (GAS), which can significantly promote CNS myelination in in vivo mice models. By using high-throughput sequencing analysis, we discover a key long non-coding RNA Gm7237 that can enhance CNS myelination and is up-regulated by GAS. Through using bioinformatic analysis and experimental validations, we further unravel that microRNA-142a (miR-142a) and its target myelin gene regulatory factor (MRF) is under the direct regulation by Gm7237. Finally, we demonstrate that Gm7237/miR-142a/MRF axis is the key pathway involved in CNS myelination mediated by GAS. Overall, our results provide not only a novel agent for therapeutic treatment of CNS demyelination but also a molecular basis responsible for GAS-promoted CNS myelination. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite pulmonary impairments being the most prevalent, extra-pulmonary manifestations of COVID-19 are abundant. Confirmed COVID-19 cases have now surpassed 57.8 million worldwide as of 22 November 2020. With estimated case fatality rates (number of deaths from COVID-19 divided by number of confirmed COVID-19 cases) varying between 1 and 7%, there will be a large population of recovered COVID-19 patients that may acquire a multitude of long-term health consequences. While the multi-organ manifestations of COVID-19 are now well-documented, the potential long-term implications of these manifestations remain to be uncovered. In this review, we turn to previous similar coronaviruses (i.e. SARS-CoV-1 and Middle East respiratory syndrome coronavirus [MERS-CoV]) in combination with known health implications of SARS-CoV-2 infection to predict potential long-term effects of COVID-19, including pulmonary, cardiovascular, hematologic, renal, central nervous system, gastrointestinal, and psychosocial manifestations, in addition to the well-known post-intensive care syndrome. It is necessary to monitor COVID-19 patients after discharge to understand the breadth and severity of long-term effects. This can be accomplished by repurposing or initiating large cohort studies to not only focus on the long-term consequences of SARS-CoV-2 infection, but also on acquired immune function as well as ethno-racial group and household income disparities in COVID-19 cases and hospitalizations. The future for COVID-19 survivors remains uncertain, and if this virus circulates among us for years to come, long-term effects may accumulate exponentially. [ABSTRACT FROM AUTHOR]

Multiple Sclerosis (MS) is an inflammatory degenerative disease of the central nervous system. Cognitive impairment is a frequent feature of MS at both the earlier and later stages of the disease, and it tends to worsen over time. Cognitive rehabilitation (CR) is becoming a standard component of neurorehabilitation in patients with MS. The aim of this study is to evaluate the effect of computerized CR, by using the Italian software ERICA, on cognitive and daily life performance in MS patients with mild to moderate cognitive impairment. We studied 40 individuals affected by MS, randomized into either traditional CR group (TCRG: n = 20), which performed a conventional cognitive training, or the computer-assisted CR group (CCRG: n = 20), which performed PC-based CR. The cognitive dysfunctions were investigated through a complete neuropsychological battery, administered before (T0) and after (T1) each different training. Both the trainings were well-tolerated and led to improvement in cognitive function. Notably, the CCRG had a significant effect in improving memory, attention, and processing speed, as compared to TCRG. ERICA training could be a valuable tool for the CR in patients affected by MS. Further studied are needed to confirm these promising results and evaluate the long-term effects. [ABSTRACT FROM AUTHOR]

Like patients with AQP4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD), the therapy of MOGAD patients with interferon beta-1a or glatiramer acetate for classic MS failed (ARR 1.5). I Michael S. Vaphiades i Paediatric multiple sclerosis and antibody-associated demyelination: clinical, imaging, and b... Fadda G, Armangue T, Hacohen Y, Chitnis T, Banwell B. Paediatric multiple sclerosis and antibody-associated demyelination: clinical, imaging, and biological considerations for diagnosis and care. I Neurology i . 2020;95(23):e3124-e3128. doi: 10.1212/WNL.0000000000010847 The authors retrospectively studied 145 consecutive patients with aquaporin-4 (AQP4) antibody-seropositive neuromyelitis optica spectrum disorder (NMOSD) who had serial brain MRI scans over an interval of at least 1 year during relapse-free period after immunosuppressive therapy. The authors concluded that asymptomatic brain lesions are rarely observed on conventional MRI in clinically stable AQP4 antibody-seropositive NMOSD patients after immunosuppressive therapy and brain MRI lesions characteristic of NMOSD are not seen in the relapse-free period. [Extracted from the article]

Treatment of Central Pain Syndrome (CPS) is known to be extremely challenging. Current therapies are unsatisfactory as patients report only mild to moderate pain relief. We report a case of using ketamine as a patient-controlled analgesia (PCA) for the treatment of CPS. A 58-year-old male with CPS presented with severe generalized body pain refractory to multiple pharmacological interventions. He was started on a basal infusion rate at 0.3 mg/kg/h with a ketamine PCA bolus of 10 mg with a 10-minute lockout period. Over the next 7 days, the basal infusion rate was titrated up to 2.1 mg/kg/h relative to the number of times the patient pressed the PCA. At the end of the trial, the patient reported 0/10 pain with lightheadedness on the first day being the only side effect reported. He was discharged home with his regular pain regimen, with significant decrease in pain over the next few months. Rather than trying to establish a "one size fits all" protocol for ketamine infusions, this case illustrates a shift in pain management focus by allowing patients to self-titrate and demonstrates the potential for using ketamine PCA as a treatment option for CPS. [ABSTRACT FROM AUTHOR]