Potent neutralizing human monoclonal antibodies protect from inhalational Rift Valley fever virus.

Rift Valley fever (RVF) is an emerging arboviral disease affecting both humans and livestock. In humans, RVF displays a spectrum of clinical manifestations, including encephalitis. To date, there are no FDA-approved vaccines or therapeutics for human use, although several are in pre-clinical development. Few small animal models of RVF encephalitis exist, further complicating countermeasure assessment. Human mAbs RVFV-140, RVFV-268 and RVFV-379 are recombinant potently neutralizing antibodies that prevent infection by binding the RVFV surface glycoproteins. Previous studies showed that both RVFV-268 and RVFV-140 improve survival in a lethal mouse model of disease, and RVFV-268 has prevented vertical transmission in a pregnant rat model of infection. Despite these successes, evaluation of mAbs in the context of brain disease has been limited. This is the first study to assess neutralizing antibodies for prevention of RVF neurologic disease using a rat model. Administration of RVFV-140, RVFV-268, or RVFV-379 twenty-four hours prior to aerosol exposure to the virulent ZH501 strain of RVFV results in substantially enhanced survival and lack of neurological signs of disease. These results using a stringent and highly lethal aerosol infection model supports the potential use of human mAbs to prevent the development of RVF encephalitis.

Quantifying instability in neurological disorders EEG based on phase space DTM function.

Classifying individuals with neurological disorders and healthy subjects using EEG is a crucial area of research. The current feature extraction approach focuses on the frequency domain features in each of the EEG frequency bands and functional brain networks. In recent years, researchers have discovered and extensively studied stability differences in the electroencephalograms (EEG) of patients with neurological disorders. Based on this, this paper proposes a feature descriptor to characterize EEG instability. The proposed method starts by forming a signal point cloud through Phase Space Reconstruction (PSR). Subsequently, a pseudo-metric space is constructed, and pseudo-distances are calculated based on the consistent measure of the point cloud. Finally, Distance to Measure (DTM) Function are generated to replace the distance function in the original metric space. We calculated the relative distances in the point cloud by measuring signal similarity and, based on this, summarized the point cloud structures formed by EEG with different stabilities after PSR. This process demonstrated that Multivariate Kernel Density Estimation (MKDE) based on a Gaussian kernel can effectively separate the mappings of different stable components within the signal in the phase space. The two average DTM values are then proposed as feature descriptors for EEG instability.In the validation phase, the proposed feature descriptor is tested on three typical neurological disorders: epilepsy, Alzheimer's disease, and Parkinson's disease, using the Bonn dataset, CHB-MIT, the Florida State University dataset, and the Iowa State University dataset. DTM values are used as feature inputs for four different machine learning classifiers, and The results show that the best classification accuracy of the proposed method reaches 98.00 %, 96.25 %, 96.71 % and 95.34 % respectively, outperforming commonly used nonlinear descriptors. Finally, the proposed method is tested and analyzed using noisy signals, demonstrating its robustness compared to other methods.

Beyond movement: Headache in patients with functional movement disorders.

OBJECTIVE: To evaluate headache comorbidity in a cohort of patients with functional movement disorders by assessing the prevalence, clinical characteristics, and temporal relationship of headache with the onset of functional symptoms. BACKGROUND: Functional movement disorders are common and potentially treatable. Although headache is frequent in these patients, few studies have evaluated their headache features. METHODS: This observational cohort study included consecutive patients with functional movement disorders evaluated in our Functional Movement Disorders Unit between October 2021 and November 2022. Clinical and demographic features from clinical charts were reviewed, and patients completed a self-administered questionnaire designed by the authors that included headache characteristics, disease duration, treatments received, and the Headache Impact Test-6. Headache type was classified as per the Classification of Headache Disorders, third edition (ICHD-3). RESULTS: A total of 51 patients with functional movement disorders were included. Of those, 40 (78%) reported having recurrent headache. Headache intensity was moderate-severe in 33/40 (83%), and about two-thirds experienced headache >9 days/month. Disability secondary to headache was high (median [interquartile range] Headache Impact Test-6 score 62 [49-66]). Based on the ICHD-3, 23/40 (58%) of patients with headache met the criteria for migraine or probable migraine, 11/40 (27%) for tension-type headache, two of 40 (5%) for new daily persistent headache, and one of 40 (3%) for primary exercise headache, while three of 40 (7%) were unclassifiable. The onset of headache occurred before the functional movement disorder in 28/40 (70%), after the functional movement disorder in five of 40 (12%), and simultaneously in six of 40 (15%). In this last group, four of the six (67%) patients described a daily headache from the onset, and two met the criteria for new daily persistent headache. CONCLUSIONS: Headache is a frequent condition in patients with functional movement disorders and an additional burden of disability beyond their motor symptoms. We found that, besides migraine and tension-type headache, new daily persistent headache may be a comorbid phenotype in patients with functional movement disorders and should be further studied in larger prospective studies.

Recent Advances in the Synthesis of Antioxidant Derivatives: Pharmacological Insights for Neurological Disorders.

Neurological disorders, characterized by oxidative stress (OS) and inflammation, have become a major global health concern. Redox reactions play a vital role in regulating the balance of the neuronal microenvironment. Specifically, the imbalance leads to a significant weakening of the organism's natural defensive mechanisms. This, in turn, causes the development of harmful oxidative stress, which plays a crucial role in the onset and progression of neurodegenerative dis-eases. The quest for effective therapeutic agents has led to significant advancements in the syn-thesis of antioxidant derivatives. This review provides a comprehensive overview of the recent developments in the use of novel antioxidant compounds with potential pharmacological applica-tions in the management of neurological disorders. The discussed compounds encompass a di-verse range of chemical structures, including polyphenols, vitamins, flavonoids, and hybrid mole-cules, highlighting their varied mechanisms of action. This review also focuses on the mechanism of oxidative stress in developing neurodegenerative disease. The neuroprotective effects of these antioxidant derivatives are explored in the context of specific neurological disorders, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. The ultimate goal is to pro-vide effective treatments for these debilitating conditions and improve the quality of life for pa-tients.

Neuromicrobiology Comes of Age: The Multifaceted Interactions between the Microbiome and the Nervous System.

The past decade has seen an explosion in our knowledge about the interactions between gut microbiota, the central nervous system, and the immune system. The gut-brain axis has recently gained much attention due to its role in regulating host physiology. This review explores recent findings concerning potential pathways linking the gut-brain axis to the initiation, pathophysiology, and development of neurological disorders. Our objective of this work is to uncover causative factors and pinpoint particular pathways and therapeutic targets that may facilitate the translation of experimental animal research into practical applications for human patients. We highlight three distinct yet interrelated mechanisms: (1) disruptions of both the intestinal and blood-brain barriers, (2) persistent neuroinflammation, and (3) the role of the vagus nerve.

From inflammatory signaling to neuronal damage: Exploring NLR inflammasomes in ageing neurological disorders.

The persistence of neuronal degeneration and damage is a major obstacle in ageing medicine. Nucleotide-binding oligomerization domain (NOD)-like receptors detect environmental stressors and trigger the maturation and secretion of pro-inflammatory cytokines that can cause neuronal damage and accelerate cell death. NLR (NOD-like receptors) inflammasomes are protein complexes that contain NOD-like receptors. Studying the role of NLR inflammasomes in ageing-related neurological disorders can provide valuable insights into the mechanisms of neurodegeneration. This includes investigating their activation of inflammasomes, transcription, and capacity to promote or inhibit inflammatory signaling, as well as exploring strategies to regulate NLR inflammasomes levels. This review summarizes the use of NLR inflammasomes in guiding neuronal degeneration and injury during the ageing process, covering several neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, and peripheral neuropathies. To improve the quality of life and slow the progression of neurological damage, NLR-based treatment strategies, including inhibitor-related therapies and physical therapy, are presented. Additionally, important connections between age-related neurological disorders and NLR inflammasomes are highlighted to guide future research and facilitate the development of new treatment options.

Revolutionizing Neurology: The Role of Artificial Intelligence in Advancing Diagnosis and Treatment.

Artificial intelligence (AI) has emerged as a powerful tool in the field of neurology, significantly impacting the diagnosis and treatment of neurological disorders. Recent technological breakthroughs have given us access to a plethora of information relevant to many aspects of neurology. Neuroscience and AI share a long history of collaboration. Along with great potential, we encounter obstacles relating to data quality, ethics, and inherent difficulty in applying data science in healthcare. Neurological disorders pose intricate challenges due to their complex manifestations and variability. Automating image interpretation tasks, AI algorithms accurately identify brain structures and detect abnormalities. This accelerates diagnosis and reduces the workload on medical professionals. Treatment optimization benefits from AI simulations that model different scenarios and predict outcomes. These AI systems can currently perform many of the sophisticated perceptual and cognitive capacities of biological systems, such as object identification and decision making. Furthermore, AI is rapidly being used as a tool in neuroscience research, altering our understanding of brain functioning. It has the ability to revolutionize healthcare as we know it into a system in which humans and robots collaborate to deliver better care for our patients. Image analysis activities such as recognizing particular brain regions, calculating changes in brain volume over time, and detecting abnormalities in brain scans can be automated by AI systems. This lessens the strain on radiologists and neurologists while improving diagnostic accuracy and efficiency. It is now obvious that cutting-edge artificial intelligence models combined with high-quality clinical data will lead to enhanced prognostic and diagnostic models in neurological illness, permitting expert-level clinical decision aids across healthcare settings. In conclusion, AI's integration into neurology has revolutionized diagnosis, treatment, and research. As AI technologies advance, they promise to unravel the complexities of neurological disorders further, leading to improved patient care and quality of life. The symbiosis of AI and neurology offers a glimpse into a future where innovation and compassion converge to reshape neurological healthcare. This abstract provides a concise overview of the role of AI in neurology and its transformative potential.

The role of hydrogen sulfide regulation of ferroptosis in different diseases.

Ferroptosis is a programmed cell death that relies on iron and lipid peroxidation. It differs from other forms of programmed cell death such as necrosis, apoptosis and autophagy. More and more evidence indicates that ferroptosis participates in many types of diseases, such as neurodegenerative diseases, ischemia-reperfusion injury, cardiovascular diseases and so on. Hence, clarifying the role and mechanism of ferroptosis in diseases is of great significance for further understanding the pathogenesis and treatment of some diseases. Hydrogen sulfide (H2S) is a colorless and flammable gas with the smell of rotten eggs. Many years ago, H2S was considered as a toxic gas. however, in recent years, increasing evidence indicates that it is the third important gas signaling molecule after nitric oxide and carbon monoxide. H2S has various physiological and pathological functions such as antioxidant stress, anti-inflammatory, anti-apoptotic and anti-tumor, and can participate in various diseases. It has been reported that H2S regulation of ferroptosis plays an important role in many types of diseases, however, the related mechanisms are not fully clear. In this review, we reviewed the recent literature about the role of H2S regulation of ferroptosis in diseases, and analyzed the relevant mechanisms, hoping to provide references for future in-depth researches.

Primary cilia formation requires the Leigh syndrome-associated mitochondrial protein NDUFAF2.

Mitochondria-related neurodegenerative diseases have been implicated in the disruption of primary cilia function. Mutation in an intrinsic mitochondrial complex I component NDUFAF2 has been identified in Leigh syndrome, a severe inherited mitochondriopathy. Mutations in ARMC9, which encodes a basal body protein, cause Joubert syndrome, a ciliopathy with defects in the brain, kidney, and eye. Here, we report a mechanistic link between mitochondria metabolism and primary cilia signaling. We discovered that loss of NDUFAF2 caused both mitochondrial and ciliary defects in vitro and in vivo and identified NDUFAF2 as a binding partner for ARMC9. We also found that NDUFAF2 was both necessary and sufficient for cilia formation and that exogenous expression of NDUFAF2 rescued the ciliary and mitochondrial defects observed in cells from patients with known ARMC9 deficiency. NAD+ supplementation restored mitochondrial and ciliary dysfunction in ARMC9-deficient cells and zebrafish and ameliorated the ocular motility and motor deficits of a patient with ARMC9 deficiency. The present results provide a compelling mechanistic link, supported by evidence from human studies, between primary cilia and mitochondrial signaling. Importantly, our findings have significant implications for the development of therapeutic approaches targeting ciliopathies.

Population-Based Analysis of 6534 Seizure Emergency Cases from Emergency Medical Services Data.

INTRODUCTION: Seizures are common reasons to call an ambulance, and this study aims to analyze the burden of seizures in the prehospital setting based on incidence, hospital admission rate, and costs. METHODS: This was a population-based, cross-sectional analysis of prehospital emergency medical services (EMS) data on suspected seizure cases from the federal state of Hesse, Germany, in 2019. RESULTS: A total of 6534 suspected seizure cases were identified, of which most were those with a known seizure disorder. Incidence rate for epilepsy-related seizures (ES; pediatric epilepsy, first seizure [1stS], seizure with known seizure disorder [SEPI]) was 205.7 per 100,000 inhabitants and incidence rate for pediatric febrile seizures (PFS) was 36.7 per 100,000 inhabitants, corresponding to 171,275 ES and 28,500 PFS (99.3% < 18 years) cases in Germany. A prehospital EMS physician was involved in 40.0% (SEPI) to 54.4% (PFS) of suspected seizure cases. Depending on the type of seizure, 70.7% (SEPI) to 80.9% (1stS) were admitted to hospital for inpatient stay of ≥ 24 h. An additional 4% (PFS) to 16% (1stS) of cases needed immediate intervention at hospital. Prehospital EMS staff needed 8:24 min:s (SD 7:24; n = 5004) after the emergency call to arrive at the scene of the ES and 10:58 min:s (SD 27:39; n = 321) for PFS. ES and PFS cases caused estimated costs of 48.5 and 8.1 million euros for Germany in 2019, respectively, not including hospital treatment-related costs. CONCLUSION: This study identified a high number of suspected seizure-related emergency cases and proportion of patients admitted to hospitals, as well as high associated costs in Germany.

New variants expand the neurological phenotype of COQ7 deficiency.

The protein encoded by COQ7 is required for CoQ10 synthesis in humans, hydroxylating 3-demethoxyubiquinol (DMQ10) in the second to last steps of the pathway. COQ7 mutations lead to a primary CoQ10 deficiency syndrome associated with a pleiotropic neurological disorder. This study shows the clinical, physiological, and molecular characterization of four new cases of CoQ10 primary deficiency caused by five mutations in COQ7, three of which have not yet been described, inducing mitochondrial dysfunction in all patients. However, the specific combination of the identified variants in each patient generated precise pathophysiological and molecular alterations in fibroblasts, which would explain the differential in vitro response to supplementation therapy. Our results suggest that COQ7 dysfunction could be caused by specific structural changes that affect the interaction with COQ9 required for the DMQ10 presentation to COQ7, the substrate access to the active site, and the maintenance of the active site structure. Remarkably, patients' fibroblasts share transcriptional remodeling, supporting a modification of energy metabolism towards glycolysis, which could be an adaptive mechanism against CoQ10 deficiency. However, transcriptional analysis of mitochondria-associated pathways showed distinct and dramatic differences between patient fibroblasts, which correlated with the extent of pathophysiological and neurological alterations observed in the probands. Overall, this study suggests that the combination of precise genetic diagnostics and the availability of new structural models of human proteins could help explain the origin of phenotypic pleiotropy observed in some genetic diseases and the different responses to available therapies.

The yield of genetic workup for middle-aged and elderly patients with neurological disorders in a real-world setting.

Genetic workup is becoming increasingly common in the clinical assessment of neurological disorders. We evaluated its yield among middle-aged and elderly neurological patients, in a real-world context. This retrospective study included 368 consecutive Israeli patients aged 50 years and older (202 [54.9%] males), who were referred to a single neurogenetics clinic between 2017 and mid-2023. All had neurological disorders, without a previous molecular diagnosis. Demographic, clinical and genetic data were collected from medical records. The mean age at first genetic counseling at the clinic was 62.3 ± 7.8 years (range 50-85 years), and the main indications for referral were neuromuscular, movement and cerebrovascular disorders, as well as cognitive impairment and dementia. Out of the 368 patients, 245 (66.6%) underwent genetic testing that included exome sequencing (ES), analysis of nucleotide repeat expansions, detection of specific mutations, targeted gene panel sequencing or chromosomal microarray analysis. Overall, 80 patients (21.7%) received a molecular diagnosis due to 36 conditions, accounting for 32.7% of the patients who performed genetic testing. The diagnostic rates were highest for neuromuscular (58/186 patients [31.2%] in this group, 39.2% of 148 tested individuals) and movement disorders (14/79 [17.7%] patients, 29.2% of 48 tested), but lower for other disorders. Testing of nucleotide repeat expansions and ES provided a diagnosis to 28/73 (38.4%) and 19/132 (14.4%) individuals, respectively. Based on our findings, genetic workup and testing are useful in the diagnostic process of neurological patients aged ≥50 years, in particular for those with neuromuscular and movement disorders.

Nursing practices on sexual health for people with neurological disorders: A narrative review.

AIMS: To identify and describe nursing practices on the sexual health of people with neurological disorders. DESIGN: Narrative review. METHODS: Data were extracted from 1 January 2002, to 20 May 2021. Inclusion criteria were nursing practices, sexual health and people with neurological disorders. The main outcome measures were: context of nursing practice implementation (assumptions, knowledge, strategies and skills), facilitators of and barriers to addressing and treating the sexual health of people with neurological disorders, and benefits of nursing practices in sexual health. PRISMA reporting guidelines were used. DATA SOURCES: PubMed, Embase, ScienceDirect and CINAHL. RESULTS: In total, 926 articles were identified and nine were included. The involvement of nurses was recommended in most studies. Assumptions about the impact of neurology on sexuality and nurse's role in sexual healthcare, biopsychosocial knowledge, and skills (ethical, interpersonal, and technical) were highlighted. We found that the modes of knowledge proposed by Carper were mobilized in an unequal way. Sexual difficulties were the key focus and eroticization concerns were not addressed in any of the articles. CONCLUSION: Several studies advocate nursing intervention; however, few accurately present, detail and evaluate sexual health nursing practices of patients with neurological pathologies. Literature describes practices structured around disorders rather than the potentials, fails to address the brake of eroticism and provides little information on the results of interventions. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Developing teaching programs on sexual health in nursing programs may be necessary if nurses are to support a diverse range of patients in an inclusive and positive manner. These programs should highlight the domain-specific knowledge that is mobilized. IMPACT: Sexual health is a fundamental human right. Alterations in the nervous system have shown to affect sexual health, however, it is not often discussed among patients with neurological disorders, who are rarely provided with sexual health counselling. Our findings may impact healthcare professionals engaged in care with these patients. REPORTING METHOD: PRISMA. No patient or public contribution.

Autism-associated neuroligin-3 deficiency in medial septum causes social deficits and sleep loss in mice.

Patients with autism spectrum disorder (ASD) frequently experience sleep disturbance. Genetic mutations in Neuroligin-3 (NLG3) genes are highly correlative with ASD and sleep disturbance. However, the cellular and neural circuit bases of this correlation remain elusive. Here, we find the conditional knockout of NLG3 (NLG3-CKO) in the medial septum (MS) impairs social memory and reduces sleep. NLG3 knockout in MS causes hyperactivity of MS-GABA neurons during social avoidance and wakefulness. Activation of MSGABA neurons induces social memory deficits and sleep loss in C57BL/6 mice. In contrast, inactivation of these neurons ameliorates social memory deficits and sleep loss in NLG3-CKO mice. Sleep deprivation leads to social memory deficits, while social isolation causes sleep loss, both resulting in a reduction of NLG3 expression and an increase in activity of GABAergic neurons in MS from C57BL/6 mice. Furthermore, MS-GABA-innervated CA2 neurons specifically regulate social memory without impacting sleep, whereas MSGABA-innervating neurons in the preoptic area selectively control sleep without affecting social behavior. Together, these findings demonstrate that the hyperactive MS-GABA neurons impair social memory and disrupt sleep resulting from NLG3 knockout in MS, and achieve the modality specificity through their divergent downstream targets.

Stem cell therapies for neurological disorders: current progress, challenges, and future perspectives.

Stem cell-based therapies have emerged as a promising approach for treating various neurological disorders by harnessing the regenerative potential of stem cells to restore damaged neural tissue and circuitry. This comprehensive review provides an in-depth analysis of the current state of stem cell applications in primary neurological conditions, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI), and other related disorders. The review begins with a detailed introduction to stem cell biology, discussing the types, sources, and mechanisms of action of stem cells in neurological therapies. It then critically examines the preclinical evidence from animal models and early human trials investigating the safety, feasibility, and efficacy of different stem cell types, such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs). While ESCs have been studied extensively in preclinical models, clinical trials have primarily focused on adult stem cells such as MSCs and NSCs, as well as iPSCs and their derivatives. We critically assess the current state of research for each cell type, highlighting their potential applications and limitations in different neurological conditions. The review synthesizes key findings from recent, high-quality studies for each neurological condition, discussing cell manufacturing, delivery methods, and therapeutic outcomes. While the potential of stem cells to replace lost neurons and directly reconstruct neural circuits is highlighted, the review emphasizes the critical role of paracrine and immunomodulatory mechanisms in mediating the therapeutic effects of stem cells in most neurological disorders. The article also explores the challenges and limitations associated with translating stem cell therapies into clinical practice, including issues related to cell sourcing, scalability, safety, and regulatory considerations. Furthermore, it discusses future directions and opportunities for advancing stem cell-based treatments, such as gene editing, biomaterials, personalized iPSC-derived therapies, and novel delivery strategies. The review concludes by emphasizing the transformative potential of stem cell therapies in revolutionizing the treatment of neurological disorders while acknowledging the need for rigorous clinical trials, standardized protocols, and multidisciplinary collaboration to realize their full therapeutic promise.

Serum neurofilament light chain levels are associated with depression among US adults: a cross-sectional analysis among US adults, 2013-2014.

BACKGROUND: Serum neurofilament light chain (sNfL) has been identified as a biomarker for neurologic diseases. However, sNfL remains unknown to be responsible for depression. AIMS: The aim of this research was to explore the relationship between sNfL levels and depression in US adults. METHODS: In this cross-sectional survey of the general population, we investigated representative data involving 10,175 participants from the 2013-2014 cycle of the National Health and Nutrition Examination Survey (NHANES). Depression was diagnosed using the Patient Health Questionnaire-9 (PHQ-9). The effect of related factors on depression was analyzed by conducting a univariate analysis. Stratified analysis was utilized to detect the stability and sensitivity of the relationship. After adjusting for race, education, marital status, smoking status, body mass index (BMI), sleep duration, income, and a history of hypertension, sedentary behavior and stroke, multivariable linear regression was performed to demonstrate the correlation between sNfL and depression. RESULTS: A total of 1301 individuals between the ages of 20 and 75 were involved in this investigation, of which 108 (8.3%) were diagnosed with depression. A significant positive correlation between sNfL and depression among adults in the US was observed by conducting univariable analyses. After adjusting for confounding factors, the multivariate analyses indicated that elevated sNfL levels might play a pivotal role in the development of depression (odds ratio (OR) = 3.0; 95% confidence interval (CI): (1.5, 6.1), P = 0.002). CONCLUSION: These results indicated that sNfL is closely linked to depression in a nationally representative individual. However, further studies are needed to confirm the biological mechanism as well as the clinical implications of sNfL and depression.

Exploring Microorganisms Associated to Acute Febrile Illness and Severe Neurological Disorders of Unknown Origin: A Nanopore Metagenomics Approach.

Acute febrile illness (AFI) and severe neurological disorders (SNDs) often present diagnostic challenges due to their potential origins from a wide range of infectious agents. Nanopore metagenomics is emerging as a powerful tool for identifying the microorganisms potentially responsible for these undiagnosed clinical cases. In this study, we aim to shed light on the etiological agents underlying AFI and SND cases that conventional diagnostic methods have not been able to fully elucidate. Our approach involved analyzing samples from fourteen hospitalized patients using a comprehensive nanopore metagenomic approach. This process included RNA extraction and enrichment using the SMART-9N protocol, followed by nanopore sequencing. Subsequent steps involved quality control, host DNA/cDNA removal, de novo genome assembly, and taxonomic classification. Our findings in AFI cases revealed a spectrum of disease-associated microbes, including Escherichia coli, Streptococcus sp., Human Immunodeficiency Virus 1 (Subtype B), and Human Pegivirus. Similarly, SND cases revealed the presence of pathogens such as Escherichia coli, Clostridium sp., and Dengue virus type 2 (Genotype-II lineage). This study employed a metagenomic analysis method, demonstrating its efficiency and adaptability in pathogen identification. Our investigation successfully identified pathogens likely associated with AFI and SNDs, underscoring the feasibility of retrieving near-complete genomes from RNA viruses. These findings offer promising prospects for advancing our understanding and control of infectious diseases, by facilitating detailed genomic analysis which is critical for developing targeted interventions and therapeutic strategies.

Vitamin D in Central Nervous System: Implications for Neurological Disorders.

Vitamin D, obtained from diet or synthesized internally as cholecalciferol and ergocalciferol, influences bodily functions through its most active metabolite and the vitamin D receptor. Recent research has uncovered multiple roles for vitamin D in the central nervous system, impacting neural development and maturation, regulating the dopaminergic system, and controlling the synthesis of neural growth factors. This review thoroughly examines these connections and investigates the consequences of vitamin D deficiency in neurological disorders, particularly neurodegenerative diseases. The potential benefits of vitamin D supplementation in alleviating symptoms of these diseases are evaluated alongside a discussion of the controversial findings from previous intervention studies. The importance of interpreting these results cautiously is emphasised. Furthermore, the article proposes that additional randomised and well-designed trials are essential for gaining a deeper understanding of the potential therapeutic advantages of vitamin D supplementation for neurological disorders. Ultimately, this review highlights the critical role of vitamin D in neurological well-being and highlights the need for further research to enhance our understanding of its function in the brain.

How to design optimal brain stimulation to modulate phase-amplitude coupling?

Objective.Phase-amplitude coupling (PAC), the coupling of the amplitude of a faster brain rhythm to the phase of a slower brain rhythm, plays a significant role in brain activity and has been implicated in various neurological disorders. For example, in Parkinson's disease, PAC between the beta (13-30 Hz) and gamma (30-100 Hz) rhythms in the motor cortex is exaggerated, while in Alzheimer's disease, PAC between the theta (4-8 Hz) and gamma rhythms is diminished. Modulating PAC (i.e. reducing or enhancing PAC) using brain stimulation could therefore open new therapeutic avenues. However, while it has been previously reported that phase-locked stimulation can increase PAC, it is unclear what the optimal stimulation strategy to modulate PAC might be. Here, we provide a theoretical framework to narrow down the experimental optimisation of stimulation aimed at modulating PAC, which would otherwise rely on trial and error.Approach.We make analytical predictions using a Stuart-Landau model, and confirm these predictions in a more realistic model of coupled neural populations.Main results.Our framework specifies the critical Fourier coefficients of the stimulation waveform which should be tuned to optimally modulate PAC. Depending on the characteristics of the amplitude response curve of the fast population, these components may include the slow frequency, the fast frequency, combinations of these, as well as their harmonics. We also show that the optimal balance of energy between these Fourier components depends on the relative strength of the endogenous slow and fast rhythms, and that the alignment of fast components with the fast rhythm should change throughout the slow cycle. Furthermore, we identify the conditions requiring to phase-lock stimulation to the fast and/or slow rhythms.Significance.Together, our theoretical framework lays the foundation for guiding the development of innovative and more effective brain stimulation aimed at modulating PAC for therapeutic benefit.