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Background Objective Methods Results Conclusions Commercial genome‐wide genotyping arrays have historically neglected coverage of genetic variation across populations.We aimed to create a multi‐ancestry genome‐wide array that would include a wide range of neuro‐specific genetic content to facilitate genetic research in neurological disorders across multiple ancestral groups, fostering diversity and inclusivity in research studies.We developed the Illumina NeuroBooster Array (NBA), a custom high‐throughput and cost‐effective platform on a backbone of 1,914,934 variants from the Infinium Global Diversity Array and added custom content comprising 95,273 variants associated with more than 70 neurological conditions or traits, and we further tested its performance on more than 2000 patient samples. This novel platform includes approximately 10,000 tagging variants to facilitate imputation and analyses of neurodegenerative disease–related genome‐wide association study loci across diverse populations.In this article, we describe NBA's potential as an efficient means for researchers to assess known and novel disease genetic associations in a multi‐ancestry framework. The NBA can identify rare genetic variants and accurately impute more than 15 million common variants across populations. Apart from enabling sample prioritization for further whole‐genome sequencing studies, we envisage that NBA will play a pivotal role in recruitment for interventional studies in the precision medicine space.From a broader perspective, the NBA serves as a promising means to foster collaborative research endeavors in the field of neurological disorders worldwide. Ultimately, this carefully designed tool is poised to make a substantial contribution to uncovering the genetic etiology underlying these debilitating conditions. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Background: Neurological diseases resulting from nervous system injuries can significantly impact nutritional status and the physical and cognitive capacities necessary for maintaining a sufficient diet. This study focuses on primary nutritional therapies for neurological illnesses. Methods: An integrative literature review was conducted using three databases: PePSIC, Medline, and LILACS. A comprehensive search strategy was employed, incorporating descriptors such as neuropathies, nutritional therapy, efficacy, and side effects. Results: After applying inclusion criteria, 175 relevant items were identified. While traditional medical interventions for neurological conditions typically involve medication, food therapy has shown promise in enhancing clinical outcomes and alleviating symptoms for certain diseases. Specifically, food therapy has been effective in improving the prognosis of adrenoleukodystrophy and mitigating symptoms of Wernicke-Korsakoff syndrome and epilepsy. Conclusion: Patients with neurological illnesses, such as adrenoleukodystrophy, Wernicke-Korsakoff syndrome, and epilepsy, may benefit from dietary interventions to improve prognosis and alleviate symptoms. Therefore, healthcare professionals should consider incorporating food therapy into the treatment plans for these conditions to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Neurological monogenic loss-of-function diseases are hereditary disorders resulting from gene mutations that decrease or abolish the normal function of the encoded protein. These conditions pose significant therapeutic challenges, which may be resolved through the development of innovative therapeutic strategies. RNA-based technologies, such as mRNA replacement therapy, have emerged as promising and increasingly viable treatments. Notably, mRNA therapy exhibits significant potential as a mutation-agnostic approach that can address virtually any monogenic loss-of-function disease. Therapeutic mRNA carries the information for a healthy copy of the defective protein, bypassing the problem of targeting specific genetic variants. Moreover, unlike conventional gene therapy, mRNA-based drugs are delivered through a simplified process that requires only transfer to the cytoplasm, thereby reducing the mutagenic risks related to DNA integration. Additionally, mRNA therapy exerts a transient effect on target cells, minimizing the risk of long-term unintended consequences. The remarkable success of mRNA technology for developing coronavirus disease 2019 vaccines has rekindled interest in mRNA as a cost-effective method for delivering therapeutic proteins. However, further optimization is required to enhance mRNA delivery, particularly to the CNS, while minimizing adverse drug reactions and toxicity. In this comprehensive review, we delve into past, present and ongoing applications of mRNA therapy for neurological monogenic loss-of-function diseases. We also discuss the promises and potential challenges presented by mRNA therapeutics in this rapidly advancing field. Ultimately, we underscore the full potential of mRNA therapy as a game-changing therapeutic approach for neurological disorders. [ABSTRACT FROM AUTHOR]

Modern medicine now has the capacity to improve therapy for many human diseases by introducing adult somatic stem cells that can repair or replace defective or damaged tissues. However, the area is still in an early phase of development, so all new applications must be carefully designed for maximal safety as well as effectiveness. [ABSTRACT FROM AUTHOR]

Observational studies have suggested that SARS-CoV-2 infection increases the risk of neurological diseases, but it remains unclear whether the association is causal. The present study aims to evaluate the causal relationships between SARS-CoV-2 infections and neurological diseases and analyzes the potential routes of SARS-CoV-2 entry at the cellular level. We performed Mendelian randomization (MR) analysis with CAUSE method to investigate causal relationship of SARS-CoV-2 infections with neurological diseases. Then, we conducted single-cell RNA sequencing (scRNA-seq) analysis to obtain evidence of potential neuroinvasion routes by measuring SARS-CoV-2 receptor expression in specific cell subtypes. Fast gene set enrichment analysis (fGSEA) was further performed to assess the pathogenesis of related diseases. The results showed that the COVID-19 is causally associated with manic (delta_elpd, − 0.1300, Z-score: − 2.4; P = 0.0082) and epilepsy (delta_elpd: − 2.20, Z-score: − 1.80; P = 0.038). However, no significant effects were observed for COVID-19 on other traits. Moreover, there are 23 cell subtypes identified through the scRNA-seq transcriptomics data of epilepsy, and SARS-CoV-2 receptor TTYH2 was found to be specifically expressed in oligodendrocyte and astrocyte cell subtypes. Furthermore, fGSEA analysis showed that the cell subtypes with receptor-specific expression was related to methylation of lysine 27 on histone H3 (H3K27ME3), neuronal system, aging brain, neurogenesis, and neuron projection. In summary, this study shows causal links between SARS-CoV-2 infections and neurological disorders such as epilepsy and manic, supported by MR and scRNA-seq analysis. These results should be considered in further studies and public health measures on COVID-19 and neurological diseases. [ABSTRACT FROM AUTHOR]

Pyruvate kinase M2 (PKM2) is a key rate-limiting enzyme in glycolysis. It is well known that PKM2 plays a vital role in the proliferation of tumor cells. However, PKM2 can also exert its biological functions by mediating multiple signaling pathways in neurological diseases, such as Alzheimer's disease (AD), cognitive dysfunction, ischemic stroke, post-stroke depression, cerebral small-vessel disease, hypoxic-ischemic encephalopathy, traumatic brain injury, spinal cord injury, Parkinson's disease (PD), epilepsy, neuropathic pain, and autoimmune diseases. In these diseases, PKM2 can exert various biological functions, including regulation of glycolysis, inflammatory responses, apoptosis, proliferation of cells, oxidative stress, mitochondrial dysfunction, or pathological autoimmune responses. Moreover, the complexity of PKM2's biological characteristics determines the diversity of its biological functions. However, the role of PKM2 is not entirely the same in different diseases or cells, which is related to its oligomerization, subcellular localization, and post-translational modifications. This article will focus on the biological characteristics of PKM2, the regulation of PKM2 expression, and the biological role of PKM2 in neurological diseases. With this review, we hope to have a better understanding of the molecular mechanisms of PKM2, which may help researchers develop therapeutic strategies in clinic. [ABSTRACT FROM AUTHOR]

Neurotrophins, particularly brain-derived neurotrophic factor (BDNF), act as key regulators of neuronal development, survival, and plasticity. BDNF is necessary for neuronal and functional maintenance in the striatum and the substantia nigra, both structures involved in the pathogenesis of Parkinson's Disease (PD). Depletion of BDNF leads to striatal degeneration and defects in the dendritic arborization of striatal neurons. Activation of tropomyosin receptor kinase B (TrkB) by BDNF is necessary for the induction of long-term potentiation (LTP), a form of synaptic plasticity, in the hippocampus and striatum. PD is characterized by the degeneration of nigrostriatal neurons and altered striatal plasticity has been implicated in the pathophysiology of PD motor symptoms, leading to imbalances in the basal ganglia motor pathways. Given its essential role in promoting neuronal survival and meditating synaptic plasticity in the motor system, BDNF might have an important impact on the pathophysiology of neurodegenerative diseases, such as PD. In this review, we focus on the role of BDNF in corticostriatal plasticity in movement disorders, including PD and dystonia. We discuss the mechanisms of how dopaminergic input modulates BDNF/TrkB signaling at corticostriatal synapses and the involvement of these mechanisms in neuronal function and synaptic plasticity. Evidence for alterations of BDNF and TrkB in PD patients and animal models are reviewed, and the potential of BDNF to act as a therapeutic agent is highlighted. Advancing our understanding of these mechanisms could pave the way toward innovative therapeutic strategies aiming at restoring neuroplasticity and enhancing motor function in these diseases. [ABSTRACT FROM AUTHOR]

Copper is a trace element required by the organism, but once the level of copper exceeds the threshold, it becomes toxic and even causes death. The underlying mechanisms of copper-induced death are inconclusive, with different studies showing different opinions on the mechanism of copper-induced death. Multiple investigations have shown that copper induces oxidative stress, endoplasmic reticulum stress, nucleolar stress, and proteasome inhibition, all of which can result in cell death. The latest research elucidates a copper-dependent death and denominates it as cuproptosis. Cuproptosis takes place through the combination of copper and lipoylated proteins of the tricarboxylic acid cycle, triggering agglomeration of lipoylated proteins and loss of iron-sulfur cluster proteins, leading to proteotoxic stress and ultimately death. Given the toxicity and necessity of copper, abnormal levels of copper lead to diseases such as neurological diseases and cancer. The development of cancer has a high demand for copper, neurological diseases involve the change of copper contents and the binding of copper to proteins. There is a close relationship between these two kinds of diseases and copper. Here, we summarize the mechanisms of copper-related death, and the association between copper and diseases, to better figure out the influence of copper in cell death and diseases, thus advancing the clinical remedy of these diseases. [ABSTRACT FROM AUTHOR]

Adult hippocampal neurogenesis (AHN) is affected by multiple factors, such as enriched environment, exercise, ageing, and neurodegenerative disorders. Neurodegenerative disorders can impair AHN, leading to progressive neuronal loss and cognitive decline. Compelling evidence suggests that individuals engaged in regular exercise exhibit higher production of proteins that are essential for AHN and memory. Interestingly, specific molecules that mediate the effects of exercise have shown effectiveness in promoting AHN and cognition in different transgenic animal models. Despite these advancements, the precise mechanisms by which exercise mimetics induce AHN remain partially understood. Recently, some novel exercise molecules have been tested and the underlying mechanisms have been proposed, involving intercommunications between multiple organs such as muscle-brain crosstalk, liver-brain crosstalk, and gut-brain crosstalk. In this review, we will discuss the current evidence regarding the effects and potential mechanisms of exercise mimetics on AHN and cognition in various neurological disorders. Opportunities, challenges, and future directions in this research field are also discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Brain age model, including estimated brain age and brain-predicted age difference (brain-PAD), has shown great potentials for serving as imaging markers for monitoring normal ageing, as well as for identifying the individuals in the pre-diagnostic phase of neurodegenerative diseases. PURPOSE: This study aimed to investigate the brain age models in normal ageing and mild cognitive impairments (MCI) converters and their values in classifying MCI conversion. METHODS: Pre-trained brain age model was constructed using the structural magnetic resonance imaging (MRI) data from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) project (N = 609). The tested brain age model was built using the baseline, 1-year and 3-year follow-up MRI data from normal ageing (NA) adults (n = 32) and MCI converters (n = 22) drew from the Open Access Series of Imaging Studies (OASIS-2). The quantitative measures of morphometry included total intracranial volume (TIV), gray matter volume (GMV) and cortical thickness. Brain age models were calculated based on the individual's morphometric features using the support vector machine (SVM) algorithm. RESULTS: With comparable chronological age, MCI converters showed significant increased TIV-based (Baseline: P = 0.021; 1-year follow-up: P = 0.037; 3-year follow-up: P = 0.001) and left GMV-based brain age than NA adults at all time points. Higher brain-PAD scores were associated with worse global cognition. Acceptable classification performance of TIV-based (AUC = 0.698) and left GMV-based brain age (AUC = 0.703) was found, which could differentiate the MCI converters from NA adults at the baseline. CONCLUSIONS: This is the first demonstration that MRI-informed brain age models exhibit feature-specific patterns. The greater GMV-based brain age observed in MCI converters may provide new evidence for identifying the individuals at the early stage of neurodegeneration. Our findings added value to existing quantitative imaging markers and might help to improve disease monitoring and accelerate personalized treatments in clinical practice. Plain Language Summary: Based on individual's MRI scans, brain age model has shown great potentials for serving as imaging markers for monitoring normal ageing (NA), as well as for identifying the ones in the pre-diagnostic phase of age-related neurodegenerative diseases. In this study, we investigated the brain age models in normal ageing and mild cognitive impairments (MCI) converters and their values in classifying MCI conversion. Pre-trained brain age model was constructed using the quantitative measures of morphometry included total intracranial volume (TIV), gray matter volume (GMV) and cortical thickness. With comparable chronological age, MCI converters showed significant increased brain age than NA adults at all time points. Higher brain age were associated with worse global cognition. This is the first demonstration that MRI-informed brain age models exhibit feature-specific patterns. The greater GMV-based brain age observed in MCI converters may provide new evidence for identifying the individuals at the early stage of neurodegeneration. Our findings added value to existing quantitative imaging markers and might help to improve disease monitoring and accelerate personalized treatments in clinical practice. [ABSTRACT FROM AUTHOR]

Huntingtin-associated protein 1 (HAP1) was the first protein discovered to interact with huntingtin. Besides brain, HAP1 is also expressed in the spinal cord, dorsal root ganglion, endocrine, and digestive systems. HAP1 has diverse functions involving in vesicular transport, receptor recycling, gene transcription, and signal transduction. HAP1 is strongly linked to several neurological diseases, including Huntington's disease, Alzheimer's disease, epilepsy, ischemic stroke, and depression. In addition, HAP1 has been proved to participate in cancers and diabetes mellitus. This article provides an overview of HAP1 regarding the tissue distribution, cell localization, functions, and offers fresh perspectives to investigate its role in diseases. [ABSTRACT FROM AUTHOR]

Objective: Accurate and reliable balance measures are important for prescribing fall prevention treatments and monitoring their effectiveness. Thus, we aimed to systematically review the psychometric properties of the Six-Spot Step Test, an increasingly used measure of dynamic balance. Data sources: A literature search using the free-text term "Six-Spot Step Test" was performed on 12 February 2024, in Medline, Embase, Rehabilitation & Sports Medicine and SPORTDiscus. Eligibility criteria were adults aged 18 or more, trials evaluating the psychometric properties of the Six-Spot Step Test, and English-language articles. Conference abstracts were excluded. Review methods: Two investigators screened and selected data independently and assessed the methodological quality and evidence using the COSMIN Risk of Bias checklist and modified GRADE approach. One investigator extracted study characteristics such as design, population and psychometric properties. Results: Of the 159 articles identified, 16, evaluating multiple measurement properties, were included in the final analysis. A total of 1319 people participated, including people affected by Stroke, multiple sclerosis, Parkison's disease, chronic inflammatory polyneuropathy and older adults with balance problems. Eight articles assessing reliability (n = 618, intraclass correlations coefficient ≥0.7, minimal detectable change = 22%) and 12 construct validity (n = 1082, 83% true hypothesis, area under the curve >0.7) exhibited sufficient methodological quality with high-level evidence, while two studies (n = 167) examining responsiveness showed very low evidence. Conclusion: Apart from responsiveness, robust evidence supports the reliability and validity of the Six-Spot Step Test for assessing dynamic balance in a specific group of individuals with neurological diseases and older adults. Further, it is considered feasible for clinical use. [ABSTRACT FROM AUTHOR]

The prevalence of neurological dieases, including neurodegenerative, neurotraumatic disorders, and neuroinflammatory conditions, has been rising due to global population and aging demographics. A key factor in the pathogenesis of these disorders is the hyperaccumulation of reactive oxygen and nitrogen species (RONS). Nanozymes have emerged as promising candidates for neurotherapeutic applications owing to their exceptional catalytic activity and stability. Of particular note is their ability to cross the blood‐brain barrier and counteract the production of reactive oxygen species via their enzyme‐mimicking characteristics. In this review, the latest advancements and theoretical knowledge in this research domain are summarized. Using the inherent functionalities of the Web of Science and bibliometric methodologies, annual publication trends are identified and extensively explored the most researched topics and neurological disorders in this field. The antioxidant reduction chemistry of the nanozymes is discussed, highlighting their ability to mimic natural oxidoreductase activity and inhibit RONS production at the source. Moreover, this review delves into the current limitations and future prospects of these mechanisms in addressing neurological disorders. The significant benefits and recent developments in the use of RONS‐regulating nanozymes for the treatment of neurological diseases are emphasized, offering insights into their therapeutic applications and broader implications for neurology. [ABSTRACT FROM AUTHOR]

In France, tens of thousands of people use a wheelchair. Driving powered wheelchairs (PWCs) present risks for users and their families. The risk of collision in PWC driver increases with severity of disability and may reduce their independence to drive. The European ADAPT project has developed a robotic assistance add-on for PWCs to prevent collisions and improve their driving performance. The aim of the SWADAPT2 study is to assess the benefit of this robotic assistance add-on arranged on a Standard Quickie Salsa M2 PWC in a population of PWC drivers with neurological disorders and driving difficulties. Eighteen (18) participants tested the system on three circuits of increasing difficulty, with and without the robotic assistance add-on. The benefit of the robotic assistance add-on was important especially on the more difficult circuits without impacting cognitive load or driving speed. The number of collisions was significantly reduced when using robotic assistance add-on from 2.16 to 0.36 on circuit 2 (p = 0.009) and from 7.3 to 1.33 on circuit 3 (p = 0.0009). Task load demand was not increased with the assistance. Finally, this system seems to be indicated to assist and improve driving safety for PWC drivers in driving difficulty. Evaluation was performed in controlled environments; therefore, further evaluation in real-world scenarios is needed to reach technology readiness. •This device is an effective technology to avoid collisions, especially for patients with neurological disorders in difficulty of driving. •Several use cases can be considered: –the equipment of drivers who are losing driving ability due to age evolution of their pathology, or anxiety –the equipment of users in driving training with difficulties, in order to facilitate access to users who are currently unable to drive. [ABSTRACT FROM AUTHOR]

Background: Sleep disorders significantly affect the quality of live and may impair cognitive development. Sleep disorders are reported to be common in chi ldr en wi th neurological diseases. However no report has evaluated the prevalence of sleep disorders among children chronic neurological diseases in Nigeria. This study therefore sort to determine the prevalence and types of sleep disorders among chi ldren wi th neurological diseases seen Child neurology clinic of University of Benin Teaching Hospital (UBTH), Benin City. Subjects and methods: This was a que s t ionna i r e ba s ed c ros s sectional study. Parents/caregivers of children attending the Child Neurology Clinic of UBTH were recruited and a structured questionnaire was administered to evaluate the presence of sleep disorders in the children they have brought to the clinic. Response scale ranged from never, rarely, occasional, frequent and very frequent. Children were judged to have sleep disorder if the symptom were present f requently or very frequently. Variables were aggregated as simple proportions and differences determine using chi-square test. Result:One hundred and fifty children aged 17years and below consisting of 98 (65.3%) males and 52 (34.7%) were evaluated. The most common sleep disorders found include restlessness during sleep 68.7%, frequent awakening 66.0%, snoring 57.3%, excessive day time sleepiness 53.3% and sleep walking among others. Sleep disorders were more common in boys than in girls and those aged 5 years and below than older children. Conclusion: Sleep disorders are very common among children with neurological diseases. These problems have great potential of fur ther impairing cognitive development and quality of life in these children.

Abstract Adult hippocampal neurogenesis (AHN) is affected by multiple factors, such as enriched environment, exercise, ageing, and neurodegenerative disorders. Neurodegenerative disorders can impair AHN, leading to progressive neuronal loss and cognitive decline. Compelling evidence suggests that individuals engaged in regular exercise exhibit higher production of proteins that are essential for AHN and memory. Interestingly, specific molecules that mediate the effects of exercise have shown effectiveness in promoting AHN and cognition in different transgenic animal models. Despite these advancements, the precise mechanisms by which exercise mimetics induce AHN remain partially understood. Recently, some novel exercise molecules have been tested and the underlying mechanisms have been proposed, involving intercommunications between multiple organs such as muscle-brain crosstalk, liver-brain crosstalk, and gut-brain crosstalk. In this review, we will discuss the current evidence regarding the effects and potential mechanisms of exercise mimetics on AHN and cognition in various neurological disorders. Opportunities, challenges, and future directions in this research field are also discussed.

Summary: Purpose: To identify what impacts the ketogenic diet (KD) may have on the outcomes of the highly prevalent neurological diseases (NDs) in the UK. These NDs are migraine, traumatic brain injury (TBI), stroke, fibromyalgia and restless legs syndrome (RLS). Additionally, if KD does impact the NDs outcomes, to identify by what biochemical mechanisms that does occur. Methods: Studies using KD as an intervention to treat NDs were identified through electronic database searches which comprise of 4 main themes (highly prevalent NDs, KD, neurological outcomes and biochemical mechanisms). Quality appraisal tools and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used to assess the quality of studies and evidence identified. Results: Twelve articles were identified and no studies for fibromyalgia and RLS. KD had positive impacts on all outcomes in migraine (attack frequency, duration, intensity, etc.) and stroke (balance & coordination, sensation, etc.). KD also had positive impacts on all outcomes in TBI ranging from physical, mental & behaviour and cognitive aspects, except no impact on “anxiety-like behaviour” and “brain oedema”. Improvement of mitochondria metabolism and reduction of neuroinflammation are the common biochemical mechanisms of KD improving the NDs outcomes. The specific mechanisms for migraine, TBI and stroke include inhibition of neuronal excitability, preservation of brain volume and increase in adenosine activity respectively. Conclusion: KD improved almost all outcomes in migraine, TBI and stroke by different biochemical mechanisms. However, cautions are needed to be taken while interpreting the results as RCTs on humans were lacking in this review.

Purpose: Childhood cancer survivors (CCS) have an increased risk of developing late chronic diseases, which can be influenced by the cancer type and its treatment. These chronic diseases can be severe and disabling, typically emerging years to decades after treatment. These deficits negatively impact quality of life, intelligence quotient, and memory. This study investigated how much the cancer type and treatment could affect the neurological hospitalisations in the French Childhood Cancer Survivors Study (FCCSS). Methods: We included 5579 childhood cancer survivors (CCS), diagnosed with solid tumours or lymphoma between 1945 and 2000, treated before 2001 and below the age of 21 years at initial treatment. The follow-up period was from 2006 to 2018. Hospitalisation data were obtained by linkage with the National Health Data System. We calculated the relative hospitalisation rate (RHRs) and absolute excess rate (AERs). Multivariable analyses were conducted using a Generalized Linear Model (GLM) with a Poisson distribution to estimate the association between neurological hospitalisation and patient characteristics. The expected number of hospitalisations served as an offset to compare the risk for FCCSS survivors with that of the reference population. Risk estimates were reported as relative risk (RR) with 95% confidence intervals. Results: The hospitalisation rate for CCS was 114.2 per 10,000 person-years (PY), compared to 48.4 in the reference population. The highest hospitalisation rates were observed for epilepsy (AER = 27.1 per 10000 PY, 95%CI: 23.5–31.2 and RHR = 5.1, 95%CI 4.4–5.7). In multivariable analyses, central nervous system (CNS) tumours survivors had the highest relative risk (RR) of hospitalisation (RR = 9.4, 95%CI: 6.7–13.1) followed by neuroblastoma survivors (RR = 2.5, 95%CI: 1.7–3.7). In the whole population, survivors who received radiation to the head and neck had a significantly higher risk of hospitalisation (RR = 3.9, 95%CI: 3.3–4.7) compared to those who did not receive radiotherapy. Conclusions: Head and neck irradiation was identified as a strong risk factor for hospitalisation. This underlines the importance of implementing specific neurologic surveillance programs for at-risk individuals. [ABSTRACT FROM AUTHOR]

Background: Women report a heightened concern of (breast) cancer, relative to other chronic conditions. This experimental study investigated whether such heightened concern may be a function of availability bias. Methods: participants (N = 750; 100% female) were randomly assigned to one of two experimental conditions: in the recall condition, they were asked to name the health condition they feared most; in the recognition condition, they picked the disease they feared most out of a list of chronic conditions. Results: The probability of selecting cancer as the most frightening disease varied as a function of experimental condition χ2 (10) = 112.13, p < 0.001. Participants in the recall condition were almost twice as likely to select cancer as the most frightening disease (N = 240, 59.10%) as those in the recognition condition (N = 121, 35.20%), who most frequently selected neurological diseases as the most threatening. The majority of participants believed that cancer was the disease receiving the most media attention (86.27%) (prior to the COVID-19 pandemic), and the one accounting for the highest number of deaths among Spanish females (63.50%). Conclusions: altogether, these results provide experimental evidence that availability bias may partly account for misperceptions and a heightened fear of cancer, which may narrow the scope of women’s information-seeking and health-preventive behaviors.

Cerebral veins are responsible for the outflow drainage of brain interstitial fluid (ISF). The importance of cerebral venous drainage has been emphasized in various neurological diseases. Impaired venous outflow may lead to brain edema, blood–brain barrier (BBB) disruption, inflammatory responses and hemorrhagic complications. With the development of imaging technologies, several imaging-based signs for venous assessment are proposed. Therapies targeting cerebral venous drainage have shown beneficial outcomes in cerebral venous sinus thrombosis (CVST) in clinic, however more insight into the cellular and molecular level should be elucidated. Here we review the pathological changes following cerebral venous drainage impairment, summary the advances in image-based evaluation, address the potential molecular mechanisms, and discuss venous drainage-focused therapies. A better understanding of cerebral venous drainage and its underlying mechanism will promote the pharmacological development and clinical management of CVST.

Background: Rare diseases, predominantly caused by genetic factors and often presenting neurological manifestations, are significantly underrepresented in research. This review addresses the urgent need for advanced research in rare neurological diseases (RNDs), which suffer from a data scarcity and diagnostic challenges. Bridging the gap in RND research is the integration of machine learning (ML) and omics technologies, offering potential insights into the genetic and molecular complexities of these conditions. Methods: We employed a structured search strategy, using a combination of machine learning and omics-related keywords, alongside the names and synonyms of 1840 RNDs as identified by Orphanet. Our inclusion criteria were limited to English language articles that utilized specific ML algorithms in the analysis of omics data related to RNDs. We excluded reviews and animal studies, focusing solely on studies with the clear application of ML in omics data to ensure the relevance and specificity of our research corpus. Results: The structured search revealed the growing use of machine learning algorithms for the discovery of biomarkers and diagnosis of rare neurological diseases (RNDs), with a primary focus on genomics and radiomics because genetic factors and imaging techniques play a crucial role in determining the severity of these diseases. With AI, we can improve diagnosis and mutation detection and develop personalized treatment plans. There are, however, several challenges, including small sample sizes, data heterogeneity, model interpretability, and the need for external validation studies. Conclusions: The sparse knowledge of valid biomarkers, disease pathogenesis, and treatments for rare diseases presents a significant challenge for RND research. The integration of omics and machine learning technologies, coupled with collaboration among stakeholders, is essential to develop personalized treatment plans and improve patient outcomes in this critical medical domain.

Abstract The unfavorable prognosis of many neurological conditions could be attributed to limited tissue regeneration in central nervous system (CNS) and overwhelming inflammation, while liver X receptor (LXR) may regulate both processes due to its pivotal role in cholesterol metabolism and inflammatory response, and thus receives increasing attentions from neuroscientists and clinicians. Here, we summarize the signal transduction of LXR pathway, discuss the therapeutic potentials of LXR agonists based on preclinical data using different disease models, and analyze the dilemma and possible resolutions for clinical translation to encourage further investigations of LXR related therapies in CNS disorders. Graphical Abstract

Background: Rare diseases, predominantly caused by genetic factors and often presenting neurological manifestations, are significantly underrepresented in research. This review addresses the urgent need for advanced research in rare neurological diseases (RNDs), which suffer from a data scarcity and diagnostic challenges. Bridging the gap in RND research is the integration of machine learning (ML) and omics technologies, offering potential insights into the genetic and molecular complexities of these conditions. Methods: We employed a structured search strategy, using a combination of machine learning and omics-related keywords, alongside the names and synonyms of 1840 RNDs as identified by Orphanet. Our inclusion criteria were limited to English language articles that utilized specific ML algorithms in the analysis of omics data related to RNDs. We excluded reviews and animal studies, focusing solely on studies with the clear application of ML in omics data to ensure the relevance and specificity of our research corpus. Results: The structured search revealed the growing use of machine learning algorithms for the discovery of biomarkers and diagnosis of rare neurological diseases (RNDs), with a primary focus on genomics and radiomics because genetic factors and imaging techniques play a crucial role in determining the severity of these diseases. With AI, we can improve diagnosis and mutation detection and develop personalized treatment plans. There are, however, several challenges, including small sample sizes, data heterogeneity, model interpretability, and the need for external validation studies. Conclusions: The sparse knowledge of valid biomarkers, disease pathogenesis, and treatments for rare diseases presents a significant challenge for RND research. The integration of omics and machine learning technologies, coupled with collaboration among stakeholders, is essential to develop personalized treatment plans and improve patient outcomes in this critical medical domain. [ABSTRACT FROM AUTHOR]

The therapeutic effects of curcumin and its derivatives, based on research in recent years, are limited by their low bioavailability. To improve bioavailability and develop the medical field of application, different delivery systems have been developed that are adapted to certain environments or the proposed target type. This study presents some half-curcuminoids prepared by the condensation of acetylacetone with 4-hydroxybenzaldehyde (C1), 4-hydroxy-3-methoxybenzaldehyde (C2), 4-acetamidobenzaldehyde (C3), or 4-diethylaminobenzaldehyde (C4), at microwaves as a simple, solvent-free, and eco-friendly method. The four compounds obtained were characterized in terms of morphostructural and photophysical properties. Following the predictions of theoretical studies on the biological activities related to the molecular structure, in vitro tests were performed for compounds C1–C3 to evaluate the antitumor properties and for C4's possible applications in the treatment of neurological diseases. The four compounds were encapsulated in two types of hydrogel matrices. First, the alginate–glucosamine network was generated and then the curcumin analogs were loaded (G1, G3, G5–G7, and G9). The second type of hydrogels was obtained by loading the active compound together with the generation of the hydrogel carrier matrices, by simply dissolving (G4 and G10) or by chemically binding half-curcuminoid derivatives to glucosamine (G2 and G8). Thus, two types of curcumin analog delivery systems were obtained, which could be applied in various types of medical treatments. [ABSTRACT FROM AUTHOR]

Background: Women report a heightened concern of (breast) cancer, relative to other chronic conditions. This experimental study investigated whether such heightened concern may be a function of availability bias. Methods: participants (N = 750; 100% female) were randomly assigned to one of two experimental conditions: in the recall condition, they were asked to name the health condition they feared most; in the recognition condition, they picked the disease they feared most out of a list of chronic conditions. Results: The probability of selecting cancer as the most frightening disease varied as a function of experimental condition χ2 (10) = 112.13, p < 0.001. Participants in the recall condition were almost twice as likely to select cancer as the most frightening disease (N = 240, 59.10%) as those in the recognition condition (N = 121, 35.20%), who most frequently selected neurological diseases as the most threatening. The majority of participants believed that cancer was the disease receiving the most media attention (86.27%) (prior to the COVID-19 pandemic), and the one accounting for the highest number of deaths among Spanish females (63.50%). Conclusions: altogether, these results provide experimental evidence that availability bias may partly account for misperceptions and a heightened fear of cancer, which may narrow the scope of women's information-seeking and health-preventive behaviors. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to raise awareness toward early diagnosis, effective treatment, and prevention of respiratory complications in patients with neurological diseases. The goal is to improve patients' overall condition and reduce mortality rates. Materials and Methods: This study is a prospective observational study conducted at Damascus Hospital, Damascus, Syria, from October 2022 to March 2023. It includes (100) patients diagnosed with neurological diseases who developed respiratory complications. Their ages ranged from 18 to 89 years, with an equal gender distribution. Data analysis was performed using SPSS statistics version 19. Results: This study revealed that cerebrovascular accidents cause aspiration pneumonia. The most frequent chest X-ray and thoracic computed tomography findings showed pulmonary densities and infiltrates. Subsequently, arterial blood gas results showed type 2 respiratory failure. Many patients experienced regression of respiratory complications, and the mortality rate was low, indicating the efficacy of treatments. Conclusion: Respiratory complications significantly contribute to mortality in patients with neurological diseases. The study emphasizes the importance of early diagnosis and preventive measures such as elevating the patient's bed and periodic suctioning of secretions. Placing patients in specialized neurological intensive care units for tailored treatment is advised. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are multipotent stromal cells with the ability to self-renew and multi-directional differentiation potential. Exogenously administered MSCs can migrate to damaged tissue sites and participate in the repair of damaged tissues. A large number of pre-clinical studies and clinical trials have demonstrated that MSCs have the potential to treat the abnormalities of congenital nervous system and neurodegenerative diseases. Therefore, MSCs hold great promise in the treatment of neurological diseases. Here, we summarize and highlight current progress in the understanding of the underlying mechanisms and strategies of MSC application in neurological diseases. [ABSTRACT FROM AUTHOR]

As an essential trace element for organisms, zinc participates in various physiological processes, such as RNA transcription, DNA replication, cell proliferation, and cell differentiation. The destruction of zinc homeostasis is associated with various diseases. Zinc homeostasis is controlled by the cooperative action of zinc transporter proteins that are responsible for the influx and efflux of zinc. Zinc transporter proteins are mainly categorized into two families: Zrt/Irt‐like protein (SLC39A/ZIP) family and zinc transporter (SLC30A/ZNT) family. ZIP transporters contain 14 members, namely ZIP1‐14, which can be further divided into four subfamilies. Currently, ZIP transporters‐regulated zinc homeostasis is one of the research hotspots. Cumulative evidence suggests that ZIP transporters‐regulated zinc homeostasis may cause physiological dysfunction and contribute to the onset and progression of diverse diseases, such as cancers, neurological diseases, and cardiovascular diseases. In this review, we initially discuss the structure and distribution of ZIP transporters. Furthermore, we comprehensively review the latest research progress of ZIP transporters‐regulated zinc homeostasis in diseases, providing a new perspective into new therapeutic targets for treating related diseases. [ABSTRACT FROM AUTHOR]

Background: Most neurological diseases have no curative treatment; therefore, focusing on prevention is key. Continuous research to uncover the protective and risk factors associated with different neurological diseases is crucial to successfully inform prevention strategies. eHealth has been showing promising advantages in healthcare and public health and may therefore be relevant to facilitate epidemiological studies. Objective: In this study, we performed a Delphi consensus exercise to identify the key screening tests to inform the development of a digital neurological examination tool for epidemiological research. Methods: Twelve panellists (six experts in neurological examination, five experts in data collection—two were also experts in the neurological examination, and three experts in participant experience) of different nationalities joined the Delphi exercise. Experts in the neurological examination provided a selection of items that allow ruling out neurological impairment and can be performed by trained health workers. The items were then rated by them and other experts in terms of their feasibility and acceptability. Results: Ten tests and seven anamnestic questions were included in the final set of screening items for the digital neurological examination. Three tests and five anamnestic questions were excluded from the final selection due to their low ratings on feasibility. Conclusion: This work identifies the key feasible and acceptable screening tests and anamnestic questions to build an electronic tool for performing the neurological examination, in the absence of a neurologist. [ABSTRACT FROM AUTHOR]

Background: Neurological diseases are becoming a more significant burden, and taking action on this developing issue is urgent. Developing solutions for these conditions using stem cell-based regenerative medicine is growing in appeal. Multipotent cells, or mesenchymal stromal cells, are used to treat various illnesses. The bone marrow (BM) and peripheral blood are the residence of mesenchymal stem cells (MSCs), also known as marrow stromal cells. By producing different integrins, growth factors, cytokines, and adhesion molecules, MSCs help hematopoiesis. Additionally, depending on the lineage of the MSCs, it will be possible to differentiate them. According to in vivo studies, injected MSCs have been identified in the host's adipose tissue, articular cartilage, lung, perivascular regions of the central nervous system. The preclinical and early clinical research on MSC therapy for neurological diseases like stroke, amyotrophic lateral sclerosis, multiple system atrophy, Parkinson's disease, and Alzheimer's disease is summarized in this article. Conclusions: Much is still unclear, despite the rise in clinical trials of MSCbased treatments for neurological illnesses during the past ten years and experimental investigations utilizing animal models. Therefore, more study is required to assess and quantify the hazards associated with cell-based versus cell-free treatments, create new methods for obtaining larger numbers of healthy cells, and lessen the variability of outcomes caused by the inherent heterogeneity of MSCs. [ABSTRACT FROM AUTHOR]

Cells in the brain are surrounded by extracellular space (ECS), which forms porous nets and interconnected routes for molecule transportation. Our view of brain ECS has changed from a largely static compartment to dynamic and diverse structures that actively regulate neural activity and brain states. Emerging evidence supports that dysregulation of brain ECS contributes to the pathogenesis and development of many neurological disorders, highlighting the importance of therapeutic modulation of brain ECS function. Here, we aim to provide an overview of the regulation and dysfunction of ECS in healthy and pathological brains, as well as advanced tools to investigate properties of brain ECS. This review emphasizes modulation methods to manipulate ECS with implications to restore their function in brain diseases. Highlights: • Up-to-date overview of the regulation of brain ECS in health and disease. • Recent advances in detecting the biophysical properties, function, and dynamic changes of brain ECS are reviewed. • Advanced pharmacological and physical methods to manipulate brain ECS, which provides therapeutic potentials for treating neurological disorders. [ABSTRACT FROM AUTHOR]

Copyright of Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas is the property of Universidad de Santiago de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), stroke, and aneurysms, are characterized by the abnormal accumulation and aggregation of disease-causing proteins in the brain and spinal cord. Recent research suggests that proteins linked to these conditions can be secreted and transferred among cells using exosomes. The transmission of abnormal protein buildup and the gradual degeneration in the brains of impacted individuals might be supported by these exosomes. Furthermore, it has been reported that neuroprotective functions can also be attributed to exosomes in neurodegenerative diseases. The potential neuroprotective functions may play a role in preventing the formation of aggregates and abnormal accumulation of proteins associated with the disease. The present review summarizes the roles of exosomes in neurodegenerative diseases as well as elucidating their therapeutic potential in AD, PD, ALS, HD, stroke, and aneurysms. By elucidating these two aspects of exosomes, valuable insights into potential therapeutic targets for treating neurodegenerative diseases may be provided. [ABSTRACT FROM AUTHOR]

The unfavorable prognosis of many neurological conditions could be attributed to limited tissue regeneration in central nervous system (CNS) and overwhelming inflammation, while liver X receptor (LXR) may regulate both processes due to its pivotal role in cholesterol metabolism and inflammatory response, and thus receives increasing attentions from neuroscientists and clinicians. Here, we summarize the signal transduction of LXR pathway, discuss the therapeutic potentials of LXR agonists based on preclinical data using different disease models, and analyze the dilemma and possible resolutions for clinical translation to encourage further investigations of LXR related therapies in CNS disorders. [ABSTRACT FROM AUTHOR]

• Discovering putative biomarkers that point to the interaction between AUD and NDs. • To identify the synergistic effects and targets of AUD on the progression of NDs. • Exploring proinflammatory responses was the significant pathways in AUD and NDs. • Identifying hub proteins (CCL2, IL1B, and TH etc.) for therapeutic targets. • Determining several TFs and miRNAs to understand the gene regulation patterns. Clinical investigations showed that individuals with Alcohol Use Disorder (AUD) have worse Neurological Disease (ND) development, pointing to possible pathogenic relationships between AUD and NDs. It remains difficult to identify risk factors that are predisposing between AUD and NDs. In order to fix these issues, we created the bioinformatics pipeline and network-based approaches for employing unbiased methods to discover genes abnormally stated in both AUD and NDs and to pinpoint some of the common molecular pathways that might underlie AUD and ND interaction. We found 100 differentially expressed genes (DEGs) in both the AUD and ND patient's tissue samples. The most important Gene Ontology (GO) terms and metabolic pathways, including positive control of cytotoxicity caused by T cells, proinflammatory responses, antigen processing and presentation, and platelet-triggered interactions with vascular and circulating cell pathways were then extracted using the overlapped DEGs. Protein-protein interaction analysis was used to identify hub proteins, including CCL2, IL1B, TH, MYCN, HLA-DRB1, SLC17A7, and HNF4A, in the pathways that have been reported as playing a function in these disorders. We determined several TFs (HNF4A, C4A, HLA-B, SNCA, HLA-DMB, SLC17A7, HLA-DRB1, HLA-C, HLA-A, and HLA-DPB1) and potential miRNAs (hsa-mir-34a-5p, hsa-mir-34c-5p, hsa-mir-449a, hsa-mir-155-5p, and hsa-mir-1-3p) were crucial for regulating the expression of AUD and ND which could serve as prospective targets for treatment. Our methodologies discovered unique putative biomarkers that point to the interaction between AUD and various neurological disorders, as well as pathways that could one day be the focus of therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Tear fluid (TF) production is an important component of normal ocular function. It is regulated by parasympathetic and sympathetic innervation. Because parasympathetic nerve fibers originate in the brainstem, pathology in this brain region may affect TF production. For example, a reduction in TF production has been described in patients with Parkinson's disease (PD). Methods: TF was collected at one center from 772 individuals, 708 of which were patients with different neurological diseases, and 64 healthy controls. Wetting lengths (WL) were recorded using Schirmer test strips with a collection time of 10 min. Results: WL correlated negatively with age and was significantly reduced in subgroups of patients with neurodegenerative diseases (NDDs) (PD, Amyotrophic lateral sclerosis (ALS), other motor neuron diseases (MNDs)), as well as inflammatory/autoimmune/infectious central nervous system (CNS) diseases and vascular CNS diseases (VCDs), even if corrected for age or sex. While temperature had a significant negative effect on TF production, other environmental factors, such as hours of sunlight and humidity, did not. Conclusion: WL was altered in many neurological diseases compared to healthy controls. Most importantly, we observed a reduction of WL in NDDs, independent of age or sex. This study highlights the potential of WL as an easily obtainable parameter and suggests functional alterations in the autonomic innervation in various neurological disorders. [ABSTRACT FROM AUTHOR]

Copyright of Kranion is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)