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Background Objective Methods Results Conclusion Understanding the neural mechanisms underlying migraine and other primary headache disorders is critical for the development of long‐term cures. Magnetoencephalography (MEG), an imaging modality that measures neuronal currents and cortical excitability with high temporal and superior spatial resolution, has been increasingly used in neurological research. Initial MEG studies showed promise in directly recording cortical spreading depression—a cortical correlate of migraine with aura. However, lately MEG technology has highly evolved with greater potential to reveal underlying pathophysiology of migraine and primary headache disorders, and aid in the identification of biomarkers.To systematically review the use of MEG in migraine and other primary headache disorders and summarize findings.We conducted a systematic search and selection of MEG studies in migraine and primary headache disorders from inception until June 8, 2023, in Medline, Embase, Cochrane, and Scopus databases. Peer‐reviewed English articles reporting the use of MEG for clinical or research purposes in migraine and primary headache disorders were selected.We found 560 articles and included 38 in this review after screening. Twelve studies investigated resting‐state, while others investigated a sensory modality using an evoked or event‐related paradigm with a total of 35 cohort and 3 case studies. Thirty‐two studies focused exclusively on migraine, while the rest reported other primary headache disorders.The findings show an evolution of MEG from a 7‐ to a 306‐channel system and analysis evolving from sensor‐level evoked responses to more advanced source‐level connectivity measures. A relatively few MEG studies portrayed migraine and primary headache disorders as a sensory abnormality, especially of the visual system. We found heterogeneity in the datasets, data reporting standards (due to constantly evolving MEG technology and analysis methods), and patient characteristics. Studies were inadequately powered and there was no evidence of blinding procedures to avoid selection bias in case–control studies, which could have led to false‐positive findings. More studies are needed to investigate the affective–cognitive aspects that exacerbate pain and disability in migraine and primary headache disorders. [ABSTRACT FROM AUTHOR]

Objectives: A deep knowledge of the surgical anatomy of the target area is mandatory for a successful operative procedure. For this purpose, over the years, many teaching and learning methods have been described, from the most ancient cadaveric dissection to the most recent virtual reality, each with their respective pros and cons. Photogrammetry, an emergent technique, allows for the creation of three-dimensional (3D) models and reconstructions. Thanks to the spreading of photogrammetry nowadays it is possible to generate these models using professional software or even smartphone apps. This study aims to compare the neuroanatomical photogrammetric models generated by the two most utilized smartphone applications in this domain, Metascan and 3D-Scanner, through quantitative analysis. Methods: Two human head specimens (four sides) were examined. Anatomical dissection was segmented into five stages to systematically expose well-defined structures. After each stage, a photogrammetric model was generated using two prominent smartphone applications. These models were then subjected to both quantitative and qualitative analysis, with a specific focus on comparing the mesh density as a measure of model resolution and accuracy. Appropriate consent was obtained for the publication of the cadaver's image. Results: The quantitative analysis revealed that the models generated by Metascan app consistently demonstrated superior mesh density compared to those from 3D-Scanner, indicating a higher level of detail and potential for precise anatomical representation. Conclusion: Enabling depth perception, capturing high-quality images, offering flexibility in viewpoints: photogrammetry provides researchers with unprecedented opportunities to explore and understand the intricate and magnificent structure of the brain. However, it is of paramount importance to develop and apply rigorous quality control systems to ensure data integrity and reliability of findings in neurological research. This study has demonstrated the superiority of Metascan in processing photogrammetric models for neuroanatomical studies. [ABSTRACT FROM AUTHOR]

Background: Neurological disorders have had a substantial rise the last three decades, imposing substantial burdens on both patients and healthcare costs. Consequently, the demand for high-quality research has become crucial for exploring effective treatment options. However, current neurology research has some limitations in terms of transparency, reproducibility, and reporting bias. The adoption of reporting guidelines (RGs) and trial registration policies has been proven to address these issues and improve research quality in other medical disciplines. It is unclear the extent to which these policies are being endorsed by neurology journals. Therefore, our study aims to evaluate the publishing policies of top neurology journals regarding RGs and trial registration. Methods: For this cross-sectional study, neurology journals were identified using the 2021 Scopus CiteScore Tool. The top 100 journals were listed and screened for eligibility for our study. In a masked, duplicate fashion, investigators extracted data on journal characteristics, policies on RGs, and policies on trial registration using information from each journal's Instruction for Authors webpage. Additionally, investigators contacted journal editors to ensure information was current and accurate. No human participants were involved in this study. Our data collection and analyses were performed from December 14, 2022, to January 9, 2023. Results: Of the 356 neurology journals identified, the top 100 were included into our sample. The five-year impact of these journals ranged from 50.844 to 2.226 (mean [SD], 7.82 [7.01]). Twenty-five (25.0%) journals did not require or recommend a single RG within their Instructions for Authors webpage, and a third (33.0%) did not require or recommend clinical trial registration. The most frequently mentioned RGs were CONSORT (64.6%), PRISMA (52.5%), and ARRIVE (53.1%). The least mentioned RG was QUOROM (1.0%), followed by MOOSE (9.0%), and SQUIRE (17.9%). Conclusions: While many top neurology journals endorse the use of RGs and trial registries, there are still areas where their adoption can be improved. Addressing these shortcomings leads to further advancements in the field of neurology, resulting in higher-quality research and better outcomes for patients. [ABSTRACT FROM AUTHOR]

Neuroprotection aims to safeguard neurons from damage caused by various factors like stress, potentially leading to the rescue, recovery, or regeneration of the nervous system and its functions [J Clin Neurosci. 2002;9(1):4–8]. Conversely, neuroplasticity refers to the brain's ability to adapt and change throughout life, involving structural and functional alterations in cells and synaptic transmission [Neural Plast. 2014;2014:541870]. Neuroprotection is a broad and multidisciplinary field encompassing various approaches and strategies aimed at preserving and promoting neuronal health. It is a critical area of research in neuroscience and neurology, with the potential to lead to new therapies for a wide range of neurological disorders and conditions. Neuroprotection can take various forms and may involve pharmacological agents, lifestyle modifications, or behavioral interventions. Accordingly, also the perspective and the meaning of neuroprotection differs due to different angles of interpretation. The primary interpretation is from the pharmacological point of view since the most consistent data come from this field. In addition, we will discuss also alternative, yet less considered, perspectives on neuroprotection, focusing on specific neuroprotective targets, interactions with surrounding microglia, different levels of neuroprotective effects, the reversive/adaptative dimension, and its use as anticipatory/prophylactic intervention. [ABSTRACT FROM AUTHOR]

Background: Bone‐derived protein osteocalcin, which has beneficial effects on brain function, may be a future research direction for neurological disorders. A growing body of evidence suggests a link between osteocalcin and neurological disorders, but the exact relationship is contradictory and unclear. Scope of Review: The aim of this review is to summarize the current research on the interaction between osteocalcin and the central nervous system and to propose some speculative future research directions. Major Conclusions: In the normal central nervous system, osteocalcin is involved in neuronal structure, neuroprotection, and the regulation of cognition and anxiety. Studies on osteocalcin‐related abnormalities in the central nervous system are divided into animal model studies and human studies, depending on the subject. In humans, the link between osteocalcin and brain function is inconsistent. These conflicting data may be due to methodological inconsistencies. By reviewing the related literature on osteocalcin, some comorbidities of the bone and nervous system and future research directions related to osteocalcin are proposed. [ABSTRACT FROM AUTHOR]

In this roundup, associate editor Nicholas Gerbis summarizes notable recent developments in scientific research, selected from reports compiled in the free electronic newsletter Sigma Xi SmartBrief: www.smartbrief.com/sigmaxi/ Bricks, Frogs Beat [...]

The Neurology Awareness and Research Foundation (NARF) has established a Community Welfare Clinic called the Brain and Heart Clinic in Gulistan-e-Jauhar, Karachi. The clinic aims to provide treatment to patients suffering from heart and brain diseases, epilepsy, diabetes, stroke, headache, and memory impairment disorders. The president of NARF, Prof. Muhammad Wasay, emphasized the importance of disease prevention through screenings for blood pressure, diabetes, and cholesterol. NARF plans to establish more clinics in different parts of the city to provide free or subsidized treatment, as well as tobacco cessation clinics and rehabilitation facilities. The clinics will also serve as referral centers and provide computerized data for research purposes. Since its inception in 2007, NARF has focused on creating awareness, educating doctors and the public, and providing free treatment and medicines through medical camps in remote areas. The foundation aims to provide treatment to those in need and raise awareness about neurology and its related sub-specialties. [Extracted from the article]

The quality and quantity of clozapine safety monitoring considerably differs among South American countries and mainly focus on hematological surveillance. Few studies have been conducted on other clozapine-related adverse effects (ADRs) and mainly refer to case reports and literature reviews. We retrieved thirty-nine publications on clozapine related ADRs others than neutropenia. Studies in Brazil and Venezuela accounted for 67 % of all the publications, and 8 out of 12 countries published 2 or less manuscripts. Only Chile offers serum clozapine level measurement in public institutions. Given the recently recognized role of ethnicity, gender, smoking, obesity drug interactions in optimal clozapine administration, modernization of clozapine clinical use and research in psychiatry and neurology most be broadcasted and stimulated in South American countries. [ABSTRACT FROM AUTHOR]

Handedness, a complex human aspect that reflects the functional lateralization of the hemispheres, also interacts with the immune system. This study aimed to expand the knowledge of the lateralization of hand, foot, and eye activities in patients with immune-mediated (IM) or other (noIM) neurological diseases and to clarify the properties of the Edinburgh Handedness Inventory (EHI) in an Italian population. Three hundred thirty-four patients with IM or noIM diseases affecting the brain or spine and peripheral nervous system were interviewed about stressful events preceding the disease, subjective handedness, and familiarity for left-handedness or ambidexterity. The patients and 40 healthy subjects underwent EHI examination. In the whole group of participants, 24 items of the EHI were classified into five factors (Hand Transitive, Hand Refined, Hand Median, Foot, Eye), demonstrating good reliability and validity. Chronological age had a significant influence on hand and foot EHI factors and the laterality quotient (LQ), particularly on writing and painting. In the patient groups, EHI factors and the LQ were also predicted by age of disease onset, duration of disease, and family history of left-handedness or ambidexterity. No differences were found between patients and healthy subjects, but pencil use scored significantly lower in patients with IM diseases than in those with noIM brain diseases. These results demonstrate that the lateralization of hand and foot activities is not a fixed human aspect, but that it can change throughout life, especially for abstract and symbolic activities. Chronic neurological diseases can cause changes in handedness. This may explain why, unlike systemic immunological diseases, IM neurological diseases are not closely associated with left-handedness. In these patients, the long version of the EHI is appropriate for determining the lateralization of body activities to contextualize the neurological picture; therefore, these findings extend the Italian normative data sets. [ABSTRACT FROM AUTHOR]

Neurological conditions are the leading cause of disability and mortality combined, demanding innovative, scalable, and sustainable solutions. Brain health has become a global priority with adoption of the World Health Organization's Intersectoral Global Action Plan in 2022. Simultaneously, rapid advancements in artificial intelligence (AI) are revolutionizing neurological research and practice. This scoping review of 66 original articles explores the value of AI in neurology and brain health, systematizing the landscape for emergent clinical opportunities and future trends across the care trajectory: prevention, risk stratification, early detection, diagnosis, management, and rehabilitation. AI's potential to advance personalized precision neurology and global brain health directives hinges on resolving core challenges across four pillars—models, data, feasibility/equity, and regulation/innovation—through concerted pursuit of targeted recommendations. Paramount actions include swift, ethical, equity-focused integration of novel technologies into clinical workflows, mitigating data-related issues, counteracting digital inequity gaps, and establishing robust governance frameworks balancing safety and innovation. [ABSTRACT FROM AUTHOR]

Underserved and underrepresented populations have historically been excluded from neurological research. This lack of representation has implications for translation of research findings into clinical practice given the impact of social determinants of health on neurological disease risk, progression, and outcomes. Lack of inclusion in research is driven by individual-, investigator-, and study-level barriers as well as larger systemic injustices (e.g., structural racism, discriminatory practices). Although strategies to increase inclusion of underserved and underrepresented populations have been put forth, numerous questions remain about the most effective methodology. In this article, we highlight inclusivity patterns and gaps among the most common neurological conditions and propose best practices informed by our own experiences in engagement of local community organizations and collaboration efforts to increase underserved and underrepresented population participation in neurological research. [ABSTRACT FROM AUTHOR]

The advent of Induced Pluripotent Stem Cells (iPSCs) has revolutionized neuroscience research. This groundbreaking innovation has facilitated the development of three-dimensional (3D) neural organoids, which closely mimicked the intricate structure and diverse functions of the human brain, providing an unprecedented platform for the in-depth study and understanding of neurological phenomena. However, these organoids lack key components of the neural microenvironment, particularly immune cells like microglia, thereby limiting their applicability in neuroinflammation research. Recent advancements focused on addressing this gap by integrating iPSC-derived microglia into neural organoids, thereby creating an immunized microenvironment that more accurately reflects human central neural tissue. This review explores the latest developments in this field, emphasizing the interaction between microglia and neurons within immunized neural organoids and highlights how this integrated approach not only enhances our understanding of neuroinflammatory processes but also opens new avenues in regenerative medicine. [ABSTRACT FROM AUTHOR]

Background and purpose: Neurological disorders constitute a significant portion of the global disease burden, affecting >30% of the world's population. This prevalence poses a substantial threat to global health in the foreseeable future. A lack of awareness regarding this high burden of neurological diseases has led to their underrecognition, underappreciation, and insufficient funding. Establishing a strategic and comprehensive research agenda for brain‐related studies is a crucial step towards aligning research objectives among all pertinent stakeholders and fostering greater societal awareness. Methods: A scoping literature review was undertaken by a working group from the European Academy of Neurology (EAN) to identify any existing research agendas relevant to neurology. Additionally, a specialized survey was conducted among all EAN scientific panels, including neurologists and patients, inquiring about their perspectives on the current research priorities and gaps in neurology. Results: The review revealed the absence of a unified, overarching brain research agenda. Existing research agendas predominantly focus on specialized topics within neurology, resulting in an imbalance in the number of agendas across subspecialties. The survey indicated a prioritization of neurological disorders and research gaps. Conclusions: Building upon the findings from the review and survey, key components for a strategic and comprehensive neurological research agenda in Europe were delineated. This research agenda serves as a valuable prioritization tool for neuroscientific researchers, as well as for clinicians, donors, and funding agencies in the field of neurology. It offers essential guidance for creating a roadmap for research and clinical advancement, ultimately leading to heightened awareness and reduced burden of neurological disorders. [ABSTRACT FROM AUTHOR]

Sex, sexuality, and gender diversity is understudied and underserved in neurology. Neurology research inclusive of LGBTQIA+ (lesbian, gay, bisexual, transgender, queer, intersex, asexual) people is limited. Existing research struggles with a paucity of neurology studies collecting sex, sexuality, and gender diverse (SSGD) data, conflation of sex and gender, lack of precision in measures, neglect of younger and older populations, nebulous benefit to community, and absent intersectionality. Future directions in SSGD neurology research include precise and community‐based measurements, respect for LGBTQIA+ colleagues, and the application of minority stress models. All patients stand to benefit from research that elucidates how SSGD variables influence neurological health. ANN NEUROL 2024;95:421–431 [ABSTRACT FROM AUTHOR]

The rapidly accelerating translation of biomedical advances is leading to revolutionary therapies that are often inaccessible to historically marginalized populations. We identified and synthesized recent guidelines and statements to propose 7 strategies to integrate equity within translational research in neurology: (1) learn history; (2) learn about upstream forces; (3) diversify and liberate; (4) change narratives and adopt best communication practices; (5) study social drivers of health and lived experiences; (6) leverage health technologies; and (7) build, sustain, and lead culturally humble teams. We propose that equity should be a major goal of translational research, equally important as safety and efficacy. ANN NEUROL 2024;95:432–441 [ABSTRACT FROM AUTHOR]

Ludwig Edinger (1855–1918) is often perceived as a functional neuroanatomist who primarily followed traditional lines of microscopic research. That he was a rather fascinating innovator in the history of neurology at the turn from the nineteenth to the twentieth century has, however, gone quite unnoticed. Edinger's career and his pronounced hopes for future investigative progress in neurological work mark an important shift, one away from traditional research styles connected to department-based approaches towards a multi-perspective and quite advanced form of interdisciplinary scientific work. Being conceptually influenced by the Austrian neuroanatomist Heinrich Obersteiner (1847–1922) and his foundation of the Neurological Institute in Vienna in 1882, Edinger established a multi-faceted brain research program. It was linked to an institutional setting of laboratory analysis and clinical research that paved the way for a new type of interdisciplinarity. After completion of his medical training, which brought him in working relationships with illustrious clinicians such as Friedrich von Recklinghausen (1810–1879) and Adolf Kussmaul (1822–1902), Edinger settled in 1883 as one of the first clinically working neurologists in the German city of Frankfurt/Main. Here, he began to collaborate with the neuropathologist Carl Weigert (1845–1904), who worked at the independent research institute of the Senckenbergische Anatomie. Since 1902, Edinger came to organize the anatomical collections and equipment for a new brain research laboratory in the recently constructed Senckenbergische Pathologie. It was later renamed the "Neurological Institute", and became an early interdisciplinary working place for the study of the human nervous system in its comparative, morphological, experimental, and clinical dimensions. Even after Edinger's death and under the austere circumstances of the Weimar Period, altogether three serviceable divisions continued with fruitful research activities in close alignment: the unit of comparative neurology, the unit of neuropsychology and neuropathology (headed by holist neurologist Kurt Goldstein, 1865–1965), and an associated unit of paleoneurology (chaired by Ludwig Edinger's daughter Tilly, 1897–1967, who later became a pioneering neuropaleontologist at Harvard University). It was especially the close vicinity of the clinic that attracted Edinger's attention and led him to conceive a successful model of neurological research, joining together different scientific perspectives in a unique and visibly modern form. [ABSTRACT FROM AUTHOR]

Copy number variation (CNV) at 7q11.23 causes Williams-Beuren syndrome (WBS) and 7q microduplication syndrome (7Dup), neurodevelopmental disorders (NDDs) featuring intellectual disability accompanied by symmetrically opposite neurocognitive features. Although significant progress has been made in understanding the molecular mechanisms underlying 7q11.23- related pathophysiology, the propagation of CNV dosage across gene expression layers and their interplay remains elusive. Here we uncovered 7q11.23 dosage-dependent symmetrically opposite dynamics in neuronal differentiation and intrinsic excitability. By integrating transcriptomics, translatomics, and proteomics of patient-derived and isogenic induced neurons, we found that genes related to neuronal transmission follow 7q11.23 dosage and are transcriptionally controlled, while translational factors and ribosomal genes are posttranscriptionally buffered. Consistently, we found phosphorylated RPS6 (p-RPS6) downregulated in WBS and upregulated in 7Dup. Surprisingly, p-4EBP was changed in the opposite direction, reflecting dosage- specific changes in total 4EBP levels. This highlights different dosage-sensitive dyregulations of the mTOR pathway as well as distinct roles of p-RPS6 and p-4EBP during neurogenesis. Our work demonstrates the importance of multiscale disease modeling across molecular and functional layers, uncovers the pathophysiological relevance of ribosomal biogenesis in a paradigmatic pair of NDDs, and uncouples the roles of p-RPS6 and p-4EBP as mechanistically actionable relays in NDDs., Introduction With over a thousand associated genes and an increasing number of polygenic risk variants, neurodevelopmental disorders (NDDs), in particular autism spectrum disorder (ASD) and intellectual disability (ID), continue to [...]

Background: To assess the state of neurological scientific research in Italy in the time interval 2020–2023. Methods: Elsevier's modular integrated platform "SciVal" was used to analyze bibliometric research products starting from scientific production data uploaded onto Scopus. We considered the research area "Neurology" in the 01/01/2020–14/06/2023 time interval, and the following variables were extracted: number of published studies, number of citations, Field-Weighted Citation Impact, and percentage of international collaborations. The contribution of Italian scientists to the neurological research was compared to that of the other nations. Results: Research identified 90,633 scientific papers in the neurological area worldwide, with a total of 472,750 citations. The products assigned to Italian groups were 6670 (53,587 citations, Field-Weighted Citation Impact 1.68, 41% international collaborations). Conclusions: According to the present study, Italian neurological research 2020 to 2023 ranks fifth globally and third in Europe. [ABSTRACT FROM AUTHOR]

Background: Neurological disorders remain a worldwide concern due to their increasing prevalence and mortality, combined with the lack of available treatment, in most cases. Exploring protective and risk factors associated with the development of neurological disorders will allow for improving prevention strategies. However, ascertaining neurological outcomes in population-based studies can be both complex and costly. The application of eHealth tools in research may contribute to lowering the costs and increase accessibility. The aim of this systematic review is to map existing eHealth tools assessing neurological signs and/or symptoms for epidemiological research. Methods: Four search engines (PubMed, Web of Science, Scopus & EBSCOHost) were used to retrieve articles on the development, validation, or implementation of eHealth tools to assess neurological signs and/or symptoms. The clinical and technical properties of the software tools were summarised. Due to high numbers, only software tools are presented here. Findings: A total of 42 tools were retrieved. These captured signs and/or symptoms belonging to four neurological domains: cognitive function, motor function, cranial nerves, and gait and coordination. An additional fifth category of composite tools was added. Most of the tools were available in English and were developed for smartphone device, with the remaining tools being available as web-based platforms. Less than half of the captured tools were fully validated, and only approximately half were still active at the time of data collection. Interpretation: The identified tools often presented limitations either due to language barriers or lack of proper validation. Maintenance and durability of most tools were low. The present mapping exercise offers a detailed guide for epidemiologists to identify the most appropriate eHealth tool for their research. Funding: The current study was funded by a PhD position at the University of Groningen. No additional funding was acquired. [ABSTRACT FROM AUTHOR]

This document contains abstracts from various articles and workshops related to brain impairment and neurological research. The articles cover topics such as the association between traumatic brain injury (TBI) and mental health outcomes, the impact of brain atrophy on interoception and emotion recognition, and the volumetric trajectories of amygdala subnuclei in frontotemporal dementia. The workshops focus on engaging with First Nations communities, technological interventions for cognitive impairments, reducing emotion dysregulation after brain injury, and understanding ADHD symptoms and interventions. The articles and workshops provide valuable insights into disability and rehabilitation, highlighting the need for improved support and inclusion. [Extracted from the article]

This document emphasizes the significance of translational research in understanding and treating neurological and psychiatric diseases. It discusses the importance of in vivo and in vitro models in studying the complex mechanisms of these conditions. The document also highlights the role of sex/gender and aging in the development of neuropsychiatric disorders. The research topic includes 25 papers that cover various topics, such as novel preclinical models, research techniques, and the potential of stem-cell-based therapies. These papers provide valuable insights into the underlying pathology of neurological and psychiatric diseases and offer potential avenues for new treatments. The document also discusses the importance of preclinical models in advancing research on these disorders, identifying potential biomarkers, and discovering innovative treatments. It emphasizes the role of neuropharmacological research in developing therapeutic agents and the significance of advanced imaging techniques in studying brain structure and function. The ultimate goal is to improve the quality of life for individuals with these complex mental health conditions through personalized care and support. [Extracted from the article]

Over the past 20 years, several eye-tracking technologies have been developed. This article aims to present a new type of eye tracker capable of producing detailed information on eye and head movements using an array of magnetoresistive detectors fixed on the patient's head and a small magnet inserted into a contact lens, adapted to the curvature of the cornea of the subject. The software used for data analysis can combine or compare eye and head movements and can represent them as 2D or 3D images. Preliminary data involve an initial patient who was asked to perform several tasks to establish the accuracy, reliability, and tolerance of the magnetic eye tracker and software. The tasks included assessment of saccadic eye movements and pursuit, "drawing" alphabetic shapes or letters, and reading. Finally, a Head Impulse Test (HIT) was performed to estimate the VOR gain, comparing the standard deviation established via vHIT with that established via this magnetic eye tracker (mHIT). This prototypical device is minimally invasive, lightweight, relatively cheap, and tolerable, with a high degree of reliability and precision. All these characteristics could lead to the future use of the magnetic eye tracker in neurological and otoneurological fields. [ABSTRACT FROM AUTHOR]

Background: The degree of blood pH affects the fundamental function of vitamin D, which is to maintain calcium and phosphorus as well as many other biochemical, neurological, and behavioural activities the difference in blood pH impacts the levels of calcium and vitamin D in the blood, and it is also in charge of ensuring that calcium levels are suitable and constant. Objective: that blood pH affects the basic function of calcium and phosphorus and vitamin D, the difference in pH affects calcium and vitamin D levels in the blood and is also responsible for keeping calcium levels appropriate and stable. Methods: 7 groups composed of 35 mature female rats were divided at random. Results: After 24 hours, none of the animals died. While stress activity increased with alkaline water, vitamin D3 and calcium levels increased in the acid water group while their concentration decreased with prednisolone, while calcium levels did not change in the alkaline water group. The animals in the two groups of vitamin D3 and acidified water with or without prednisolone moved less in the open field. Along with increased oxidative stress, vitamin D3 with acid water also inhibited cholinesterase activity. The lipid profile in the blood is impacted by the vitamin D3 group in both acidic and alkaline water. Conclusion: Prednisolone reduces serum levels of vitamin D3. And that acidic water directly affects the toxicity of vitamin D3, while alkaline water significantly reduces toxicity. [ABSTRACT FROM AUTHOR]

In this study, I use a representative survey from the German Twin Family Panel (N = 5,472) to examine the extent to which genetic and environmental factors account for time spent playing video games on personal computers and gaming consoles. Results show that genetic variation among twins explains a non-trivial amount of variation in video game play. Through ACE modeling techniques, I find that between 25% to 39% of the total variance in time spent playing video games can be attributed to shared genetic traits with the remainder explained by shared environmental factors (e.g., parenting and culture) and environmental attributes unique to individuals. This study and its findings provide a starting point for future genetic and neurological research on video game use and effects. [ABSTRACT FROM AUTHOR]

Vascular aging affects multiple organ systems, Including the brain, where It can lead to vascular dementia. However, a concrete understanding of how aging specifically affects the brain vasculature, along with molecular readouts, remains vastly incomplete. Here, we demonstrate that aging is associated with a marked decline in Notch3 signaling in both murine and human brain vessels. To clarify the consequences of Notch3 loss in the brain vasculature, we used single-cell transcriptomics and found that Notch3 inactivation alters regulation of calcium and contractile function and promotes a notable increase in extracellular matrix. These alterations adversely impact vascular reactivity, manifesting as dilation, tortuosity, microaneurysms, and decreased cerebral blood flow, as observed by MRI. Combined, these vascular impairments hinder glymphatic flow and result in buildup of glycosaminoglycans within the brain parenchyma. Remarkably, this phenomenon mirrors a key pathological feature found in brains of patients with CADASIL, a hereditary vascular dementia associated with NOTCH3 missense mutations. Additionally, single-cell RNA sequencing of the neuronal compartment in aging Notch3- null mice unveiled patterns reminiscent of those observed in neurodegenerative diseases. These findings offer direct evidence that age-related NOTCH3 deficiencies trigger a progressive decline in vascular function, subsequently affecting glymphatic flow and culminating in neurodegeneration., Introduction Aging introduces a series of complex molecular, structural, and functional changes to blood vessels, with important consequences for organ physiology (1). In the brain, compromised vascular function can trigger [...]

Recent studies using cell type-specific knockout mouse models have improved our understanding of the pathophysiological relevance of suppressor of lin-12-like-HMG-CoA reductase degradation 1 (SEL1L- HRD1) endoplasmic reticulum- associated (ER-associated) degradation (ERAD); however, its importance in humans remains unclear, as no disease variant has been identified. Here, we report the identification of 3 biallelic missense variants of SEL1L and HRD1 (or SYVN1) in 6 children from 3 independent families presenting with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, hypotonia, and/or ataxia. These SEL1L (p.Gly585Asp, p.Met528Arg) and HRD1 (p.Pro398Leu) variants were hypomorphic and impaired ERAD function at distinct steps of ERAD, including substrate recruitment (SEL1L p.Gly585Asp), SEL1L-HRD1 complex formation (SEL1L p.Met528Arg), and HRD1 activity (HRD1 p.Pro398Leu). Our study not only provides insights into the structure-function relationship of SEL1L-HRD1 ERAD, but also establishes the importance of SEL1L-HRD1 ERAD in humans., Introduction Nascent membrane or secretory proteins are synthesized and folded in the endoplasmic reticulum (ER), which is prone to misfolding. Such misfolding may have pathogenic consequences if not cleared effectively [...]