7,219 results match your criteria Driving and Neurological Disease


Mitochondrial Transplantation Attenuates Brain Dysfunction in Sepsis by Driving Microglial M2 Polarization.

Mol Neurobiol 2020 Jul 1. Epub 2020 Jul 1.

Departments of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.

Activation of microglia and mitochondrial dysfunction are two major contributors to the pathogenesis of sepsis-associated brain dysfunction. Mitochondrial dysfunction can alter the immunological profile of microglia favoring to a pro-inflammatory phenotype. Mitochondrial transplantation, as an emerging mitochondria-targeted therapy, possesses considerable therapeutic potential in various central nervous system injuries or diseases. Read More

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http://dx.doi.org/10.1007/s12035-020-01994-3DOI Listing

Exposure to the heavy metal lead induces DNA copy number alterations in zebrafish cells.

Chem Res Toxicol 2020 Jun 22. Epub 2020 Jun 22.

DNA copy number variants (CNVs) are associated with the development of complex neurological diseases and disorders including autism spectrum disorder, schizophrenia, Alzheimer's disease, and Parkinson's disease. Exposure to multiple environmental chemicals including various heavy metals is suggested as a risk factor in these neurological diseases and disorders, but few studies have addressed if heavy metal exposure can result in de novo DNA copy number changes as a genetic mechanism contributing to these disease outcomes. In this study to further investigate the relationship between heavy metal exposure and de novo copy number alterations (CNAs), zebrafish fibroblast cells were exposed to the neurotoxicant lead (Pb). Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00156DOI Listing

Biophysical basis for Kv1.3 regulation of membrane potential changes induced by P2X4-mediated calcium entry in microglia.

Glia 2020 Jun 11. Epub 2020 Jun 11.

Department of Pharmacology, University of California, Davis, California, USA.

Microglia-mediated inflammation exerts adverse effects in ischemic stroke and in neurodegenerative disorders such as Alzheimer's disease (AD). Expression of the voltage-gated potassium channel Kv1.3 is required for microglia activation. Read More

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http://dx.doi.org/10.1002/glia.23847DOI Listing

Losing my licence meant I lost my independence.

Authors:
Zoe Barber

BMJ 2020 06 4;369:m1405. Epub 2020 Jun 4.

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http://dx.doi.org/10.1136/bmj.m1405DOI Listing

Predictors of the Best Outcomes Following Minimally Invasive Surgery for Grade 1 Degenerative Lumbar Spondylolisthesis.

Neurosurgery 2020 Jun 4. Epub 2020 Jun 4.

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California.

Background: The factors driving the best outcomes following minimally invasive surgery (MIS) for grade 1 degenerative lumbar spondylolisthesis are not clearly elucidated.

Objective: To investigate the factors that drive the best 24-mo patient-reported outcomes (PRO) following MIS surgery for grade 1 degenerative lumbar spondylolisthesis.

Methods: A total of 259 patients from the Quality Outcomes Database lumbar spondylolisthesis module underwent single-level surgery for degenerative grade 1 lumbar spondylolisthesis with MIS techniques (188 fusions, 72. Read More

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http://dx.doi.org/10.1093/neuros/nyaa206DOI Listing

Molecular networking in the neuronal ceroid lipofuscinoses: insights from mammalian models and the social amoeba Dictyostelium discoideum.

Authors:
Robert J Huber

J Biomed Sci 2020 May 20;27(1):64. Epub 2020 May 20.

Department of Biology, Trent University, 1600 West Bank Drive, Peterborough, Ontario, K9L 0G2, Canada.

The neuronal ceroid lipofuscinoses (NCLs), commonly known as Batten disease, belong to a family of neurological disorders that cause blindness, seizures, loss of motor function and cognitive ability, and premature death. There are 13 different subtypes of NCL that are associated with mutations in 13 genetically distinct genes (CLN1-CLN8, CLN10-CLN14). Similar clinical and pathological profiles of the different NCL subtypes suggest that common disease mechanisms may be involved. Read More

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http://dx.doi.org/10.1186/s12929-020-00653-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238602PMC

Exploring driving characteristics of fit- and unfit-to-drive neurological patients: a driving simulator study.

Traffic Inj Prev 2020 18;21(6):359-364. Epub 2020 May 18.

Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia.

To identify driving characteristics of fit-, unfit-, and conditionally fit-to-drive neurological patient populations using a driving simulator with three high-risk scenarios comprising rural, highway, and urban environments. The study included 91 neurological patients undergoing a multidisciplinary assessment for driver's license revalidation, consisting of a clinical, neuropsychological, functional, and on-road evaluation. The groups drove through three independent driving scenarios, during which a variety of measures describing reaction time, vehicular control, and traffic rule compliance were performed. Read More

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http://dx.doi.org/10.1080/15389588.2020.1764547DOI Listing
May 2020
1.286 Impact Factor

Acquired and inherited amyloidosis: Knowledge driving patients' care.

J Peripher Nerv Syst 2020 Jun;25(2):85-101

National Reference Center for Familial Amyloid Polyneuropathy and Other Rare Neuropathies, APHP, Université Paris Saclay, INSERM U1195, Le Kremlin Bicêtre, France.

Until recently, systemic amyloidoses were regarded as ineluctably disabling and life-threatening diseases. However, this field has witnessed major advances in the last decade, with significant improvements in therapeutic options and in the availability of accurate and non-invasive diagnostic tools. Outstanding progress includes unprecedented hematological response rates provided by risk-adapted regimens in light chain (AL) amyloidosis and the approval of innovative pharmacological agents for both hereditary and wild-type transthyretin amyloidosis (ATTR). Read More

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http://dx.doi.org/10.1111/jns.12381DOI Listing

Clinical and patient determinants of changing therapy in relapsing-remitting multiple sclerosis (SWITCH study).

Mult Scler Relat Disord 2020 Jul 13;42:102124. Epub 2020 Apr 13.

Laboratory of Synaptic Immunopathology, Department of Systems Medicine, "Tor Vergata" University, Rome, Italy; Unit of Neurology - IRCCS Neuromed, Pozzilli, Isernia, Italy. Electronic address:

Background: clinical factors and frequency of disease-modifying therapy (DMT) changes/interruptions in relapsing-remitting multiple sclerosis (RRMS) patients have not been well defined. The aim of this study was to describe reasons of MS treatment modifications in a large cohort of Italian MS patients.

Methods: this multicenter, cross-sectional non interventional study (SWITCH) conducted at 28 Italian MS centers, screened, by visit/telephone contact between June 2016 and June 2017, all RRMS patients receiving stable DMT treatment and enrolled patients with change in DMT treatment. Read More

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http://dx.doi.org/10.1016/j.msard.2020.102124DOI Listing

Intestinal epithelial barrier and neuromuscular compartment in health and disease.

World J Gastroenterol 2020 Apr;26(14):1564-1579

Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy.

A number of digestive and extra-digestive disorders, including inflammatory bowel diseases, irritable bowel syndrome, intestinal infections, metabolic syndrome and neuropsychiatric disorders, share a set of clinical features at gastrointestinal level, such as infrequent bowel movements, abdominal distension, constipation and secretory dysfunctions. Several lines of evidence indicate that morphological and molecular changes in intestinal epithelial barrier and enteric neuromuscular compartment contribute to alterations of both bowel motor and secretory functions in digestive and extra-digestive diseases. The present review has been conceived to provide a comprehensive and critical overview of the available knowledge on the morphological and molecular changes occurring in intestinal epithelial barrier and enteric neuromuscular compartment in both digestive and extra-digestive diseases. Read More

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http://dx.doi.org/10.3748/wjg.v26.i14.1564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167418PMC

Ability of the Maze Navigation Test, Montreal Cognitive Assessment, and Trail Making Tests A & B to predict on-road driving performance in current drivers diagnosed with dementia.

N Z Med J 2020 04 24;133(1513):23-32. Epub 2020 Apr 24.

Senior Lecturer, University of Auckland.

Aim: This study aimed to evaluate the ability of the Maze Navigation Test (MNT), Montreal Cognitive Assessment (MoCA) and Trail Making Tests A & B (TMT A & B) to predict on-road driving performance in current drivers diagnosed with dementia.

Methods: Current drivers with a diagnosis of dementia in whom there were clinical concerns about their driving safety were invited to participate between December 2014 and February 2018. Participants completed the MNT, MoCA and TMT A & B, then underwent a blinded specialist Occupational Therapy & Rehabilitation Service (OTRS) off-road and on-road driving assessment. Read More

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BraInMap Elucidates the Macromolecular Connectivity Landscape of Mammalian Brain.

Cell Syst 2020 Apr;10(4):333-350.e14

Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Program in Bioinformatics, Boston University, Boston, MA, USA; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston University, Boston, MA, USA; Departments of Biochemistry and Biology, Boston University, Boston, MA, USA. Electronic address:

Connectivity webs mediate the unique biology of the mammalian brain. Yet, while cell circuit maps are increasingly available, knowledge of their underlying molecular networks remains limited. Here, we applied multi-dimensional biochemical fractionation with mass spectrometry and machine learning to survey endogenous macromolecules across the adult mouse brain. Read More

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http://dx.doi.org/10.1016/j.cels.2020.03.003DOI Listing

Partial loss of CFIm25 causes learning deficits and aberrant neuronal alternative polyadenylation.

Elife 2020 Apr 22;9. Epub 2020 Apr 22.

Program in Developmental Biology, Baylor College of Medicine, Houston, United States.

We previously showed that -spanning copy-number variations (CNVs) are associated with intellectual disability (Gennarino et al., 2015). However, the patients' CNVs also included other genes. Read More

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http://dx.doi.org/10.7554/eLife.50895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176433PMC

Genome-wide association studies and Mendelian randomization analyses for leisure sedentary behaviours.

Nat Commun 2020 Apr 21;11(1):1770. Epub 2020 Apr 21.

Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB, Groningen, The Netherlands.

Leisure sedentary behaviours are associated with increased risk of cardiovascular disease, but whether this relationship is causal is unknown. The aim of this study is to identify genetic determinants associated with leisure sedentary behaviours and to estimate the potential causal effect on coronary artery disease (CAD). Genome wide association analyses of leisure television watching, leisure computer use and driving behaviour in the UK Biobank identify 145, 36 and 4 genetic loci (P < 1×10), respectively. Read More

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http://dx.doi.org/10.1038/s41467-020-15553-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174427PMC

Human Response and Injury Resulting from Head Impacts with Unmanned Aircraft Systems.

Stapp Car Crash J 2019 Nov;63:29-64

Aerospace Research Center, The Ohio State University.

Unmanned aircraft systems (UAS), commonly known as drones, are part of a new and budding industry in the United States. Economic and public benefits associated with UAS use across multiple commercial sectors are driving new regulations which alter the stringent laws currently restricting UAS flights over people. As new regulations are enacted and more UAS populate the national airspace, there is a need to both understand and quantify the risk associated with UAS impacts with the uninvolved public. Read More

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November 2019

Glioma-Induced Alterations in Neuronal Activity and Neurovascular Coupling during Disease Progression.

Cell Rep 2020 Apr;31(2):107500

Laboratory for Functional Optical Imaging, Zuckerman Mind Brain Behavior Institute, Departments of Biomedical Engineering and Radiology, Columbia University, New York, NY 10027, USA. Electronic address:

Diffusely infiltrating gliomas are known to cause alterations in cortical function, vascular disruption, and seizures. These neurological complications present major clinical challenges, yet their underlying mechanisms and causal relationships to disease progression are poorly characterized. Here, we follow glioma progression in awake Thy1-GCaMP6f mice using in vivo wide-field optical mapping to monitor alterations in both neuronal activity and functional hemodynamics. Read More

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http://dx.doi.org/10.1016/j.celrep.2020.03.064DOI Listing

Characterization of the SIM-A9 cell line as a model of activated microglia in the context of neuropathic pain.

PLoS One 2020 14;15(4):e0231597. Epub 2020 Apr 14.

Graduate School of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, Pittsburgh, PA, United States of America.

Resident microglia of the central nervous system are being increasingly recognized as key players in diseases such as neuropathic pain. Biochemical and behavioral studies in neuropathic pain rodent models have documented compelling evidence of the critical role of ATP mediated-P2X4R-brain-derived neurotrophic factor (BDNF) signaling pathway in the initiation and maintenance of pain hypersensitivity, a feature driving neuropathic pain-related behavior. The goal of this study was to develop and characterize an in vitro cell line model of activated microglia that can be subsequently utilized for screening neuropathic pain therapeutics. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231597PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156095PMC

Diagnosis and Management of Obstructive Sleep Apnea: A Review.

JAMA 2020 04;323(14):1389-1400

Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland.

Importance: Obstructive sleep apnea (OSA) affects 17% of women and 34% of men in the US and has a similar prevalence in other countries. This review provides an update on the diagnosis and treatment of OSA.

Observations: The most common presenting symptom of OSA is excessive sleepiness, although this symptom is reported by as few as 15% to 50% of people with OSA in the general population. Read More

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http://dx.doi.org/10.1001/jama.2020.3514DOI Listing

A Comprehensive Review of Brain Connectomics and Imaging to Improve Deep Brain Stimulation Outcomes.

Mov Disord 2020 May 12;35(5):741-751. Epub 2020 Apr 12.

Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida, USA.

DBS is an effective neuromodulatory therapy that has been applied in various conditions, including PD, essential tremor, dystonia, Tourette syndrome, and other movement disorders. There have also been recent examples of applications in epilepsy, chronic pain, and neuropsychiatric conditions. Innovations in neuroimaging technology have been driving connectomics, an emerging whole-brain network approach to neuroscience. Read More

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http://dx.doi.org/10.1002/mds.28045DOI Listing
May 2020
5.680 Impact Factor

Transcriptomic analysis of brain tissues identifies a role for CCAAT enhancer binding protein β in HIV-associated neurocognitive disorder.

J Neuroinflammation 2020 Apr 11;17(1):112. Epub 2020 Apr 11.

Department of Psychiatry, School of Medicine, University of California San Diego, 9500 Gilman Dr., BSB 3009, San Diego, La Jolla, CA, 92093-0603, USA.

Background: HIV-associated neurocognitive disorders (HAND) persist in the era of combined antiretroviral therapy (ART) despite reductions in viral load (VL) and overall disease severity. The mechanisms underlying HAND in the ART era are not well understood but are likely multifactorial, involving alterations in common pathways such as inflammation, autophagy, neurogenesis, and mitochondrial function. Newly developed omics approaches hold potential to identify mechanisms driving neuropathogenesis of HIV in the ART era. Read More

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http://dx.doi.org/10.1186/s12974-020-01781-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149918PMC

Chronic inflammation mediates brain injury in HIV infection: relevance for cure strategies.

Curr Opin Neurol 2020 Jun;33(3):397-404

Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.

Purpose Of Review: Chronic inflammation is a major component of HIV infection, the effects of which can be devastating in the central nervous system (CNS). Protecting the brain is, therefore, critical as efforts proceed to cure HIV infection by reactivating latent viral reservoirs and driving immune responses. We review the clinical presentation and pathology findings of inflammatory processes in the CNS in patients managed with ART and the drivers of these processes. Read More

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http://dx.doi.org/10.1097/WCO.0000000000000807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331798PMC

Development of disease-modifying drugs for frontotemporal dementia spectrum disorders.

Nat Rev Neurol 2020 04 23;16(4):213-228. Epub 2020 Mar 23.

Department of Research and Development, Chiesi Farmaceutici, Parma, Italy.

Frontotemporal dementia (FTD) encompasses a spectrum of clinical syndromes characterized by progressive executive, behavioural and language dysfunction. The various FTD spectrum disorders are associated with brain accumulation of different proteins: tau, the transactive response DNA binding protein of 43 kDa (TDP43), or fused in sarcoma (FUS) protein, Ewing sarcoma protein and TATA-binding protein-associated factor 15 (TAF15) (collectively known as FET proteins). Approximately 60% of patients with FTD have autosomal dominant mutations in C9orf72, GRN or MAPT genes. Read More

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http://dx.doi.org/10.1038/s41582-020-0330-xDOI Listing
April 2020
15.358 Impact Factor

HJ22, a Novel derivative of piperine, Attenuates ibotenic acid-induced cognitive impairment, oxidativestress, apoptosis and inflammation via inhibiting the protein-protein interaction of Keap1-Nrf2.

Int Immunopharmacol 2020 Jun 16;83:106383. Epub 2020 Mar 16.

Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address:

Kelch-like ECH-associated protein (Keap1)-nuclear factor erythroid-2-related factor 2 (Nrf2) protein-protein interaction has become an important drug target for the treatment of Alzheimer's disease. In this study, we found a novel piperine derivative (HJ22) synthesized by our group with great ability to bind to Keap-1 and activate Keap1-Nrf2-ARE signaling pathway in vitro, driving us to investigate the beneficial effects of HJ22 on ibotenic acid (IBO)-induced neurological disorders in rats and underlying mechanisms. Interestingly, HJ22 significantly ameliorated IBO-induced cognitive impairment in Morris water maze, Y-maze and passive avoidance tests. Read More

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http://dx.doi.org/10.1016/j.intimp.2020.106383DOI Listing

Long-term exposure to lead reduces antioxidant capacity and triggers motor neurons degeneration and demyelination in spinal cord of adult rats.

Ecotoxicol Environ Saf 2020 May 6;194:110358. Epub 2020 Mar 6.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, State of Pará, Brazil. Electronic address:

Lead is a toxic metal found in environment with great neurotoxic potential. The main effect is associated with impairments in hippocampus and cerebellum, driving to cognitive and motor dysfunctions, however, there is a lack of evidences about the effects over the spinal cord. In this way, we aimed to investigate in vivo the effects of long-term exposure to lead acetate in oxidative biochemistry and morphology of rats' spinal cord. Read More

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http://dx.doi.org/10.1016/j.ecoenv.2020.110358DOI Listing

Neuroactive steroids alphaxalone and CDNC24 are effective hypnotics and potentiators of GABA currents, but are not neurotoxic to the developing rat brain.

Br J Anaesth 2020 05 6;124(5):603-613. Epub 2020 Mar 6.

Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address:

Background: The most currently used general anaesthetics are potent potentiators of γ-aminobutyric acid A (GABA) receptors and are invariably neurotoxic during the early stages of brain development in preclinical animal models. As causality between GABA potentiation and anaesthetic-induced developmental neurotoxicity has not been established, the question remains whether GABAergic activity is crucial for promoting/enhancing neurotoxicity. Using the neurosteroid analogue, (3α,5α)-3-hydroxy-13,24-cyclo-18,21-dinorchol-22-en-24-ol (CDNC24), which potentiates recombinant GABA receptors, we examined whether this potentiation is the driving force in inducing neurotoxicity during development. Read More

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http://dx.doi.org/10.1016/j.bja.2020.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222221PMC

Inflammation in Neurological Disorders: The Thin Boundary Between Brain and Periphery.

Antioxid Redox Signal 2020 Jul 9;33(3):191-210. Epub 2020 Apr 9.

Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy.

Accumulating evidence suggests that inflammation is a major contributor in the pathogenesis of several highly prevalent, but also rare, neurological diseases. In particular, the neurodegenerative processes of Alzheimer's disease (AD), vascular dementia (VAD), Parkinson's disease (PD), and multiple sclerosis (MS) are fueled by neuroinflammation, which, in turn, is accompanied by a parallel systemic immune dysregulation. This cross-talk between periphery and the brain becomes substantial when the bloodbrain barrier loses its integrity, as often occurs in the course of these diseases. Read More

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http://dx.doi.org/10.1089/ars.2020.8076DOI Listing

TREM-1 activation is a potential key regulator in driving severe pathogenesis of enterovirus A71 infection.

Sci Rep 2020 Mar 2;10(1):3810. Epub 2020 Mar 2.

Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore.

Hand, foot and mouth disease (HFMD), caused by enterovirus A71 (EV-A71), presents mild to severe disease, and sometimes fatal neurological and respiratory manifestations. However, reasons for the severe pathogenesis remain undefined. To investigate this, infection and viral kinetics of EV-A71 isolates from clinical disease (mild, moderate and severe) from Sarawak, Malaysia, were characterised in human rhabdomyosarcoma (RD), neuroblastoma (SH-SY5Y) and peripheral blood mononuclear cells (PBMCs). Read More

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http://dx.doi.org/10.1038/s41598-020-60761-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052206PMC
March 2020
5.078 Impact Factor

Immune and Apoptosis Mechanisms Regulating Placental Development and Vascularization in Preeclampsia.

Front Physiol 2020 11;11:98. Epub 2020 Feb 11.

Laboratory of Maternal-Child Health, Centre de Recherche de l'Hôpital du Sacré-Coeur de Montréal, Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-de-l'Île-de-Montréal, Montreal, QC, Canada.

Preeclampsia is the most severe type of hypertensive disorder of pregnancy, affecting one in 10 pregnancies worldwide and increasing significantly maternal and neonatal morbidity and mortality. Women developing preeclampsia display an array of symptoms encompassing uncontrolled hypertension and proteinuria, with neurological symptoms including seizures at the end of pregnancy. The main causes of preeclampsia are still unknown. Read More

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http://dx.doi.org/10.3389/fphys.2020.00098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026478PMC
February 2020

Amyloid-β and Tau at the Crossroads of Alzheimer's Disease.

Adv Exp Med Biol 2019 ;1184:187-203

Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.

Alzheimer's disease (AD) is the most common form of dementia characterized neuropathologically by senile plaques and neurofibrillary tangles (NFTs). Early breakthroughs in AD research led to the discovery of amyloid-β as the major component of senile plaques and tau protein as the major component of NFTs. Shortly following the identification of the amyloid-β (Aβ) peptide was the discovery that a genetic mutation in the amyloid precursor protein (APP), a type1 transmembrane protein, can be a cause of autosomal dominant familial AD (fAD). Read More

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http://dx.doi.org/10.1007/978-981-32-9358-8_16DOI Listing

Biased M1-muscarinic-receptor-mutant mice inform the design of next-generation drugs.

Nat Chem Biol 2020 03 20;16(3):240-249. Epub 2020 Feb 20.

The Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

Cholinesterase inhibitors, the current frontline symptomatic treatment for Alzheimer's disease (AD), are associated with low efficacy and adverse effects. M1 muscarinic acetylcholine receptors (M1 mAChRs) represent a potential alternate therapeutic target; however, drug discovery programs focused on this G protein-coupled receptor (GPCR) have failed, largely due to cholinergic adverse responses. Employing novel chemogenetic and phosphorylation-deficient, G protein-biased, mouse models, paired with a toolbox of probe molecules, we establish previously unappreciated pharmacologically targetable M1 mAChR neurological processes, including anxiety-like behaviors and hyper-locomotion. Read More

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http://dx.doi.org/10.1038/s41589-019-0453-9DOI Listing

Tracking intratumoral heterogeneity in glioblastoma via regularized classification of single-cell RNA-Seq data.

BMC Bioinformatics 2020 Feb 18;21(1):59. Epub 2020 Feb 18.

INESC-ID, Instituto Superior Técnico, Universidade de Lisboa, Rua Alves Redol 9, Lisboa, 1000-029, Portugal.

Background: Understanding cellular and molecular heterogeneity in glioblastoma (GBM), the most common and aggressive primary brain malignancy, is a crucial step towards the development of effective therapies. Besides the inter-patient variability, the presence of multiple cell populations within tumors calls for the need to develop modeling strategies able to extract the molecular signatures driving tumor evolution and treatment failure. With the advances in single-cell RNA Sequencing (scRNA-Seq), tumors can now be dissected at the cell level, unveiling information from their life history to their clinical implications. Read More

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http://dx.doi.org/10.1186/s12859-020-3390-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029554PMC
February 2020

A slipped-CAG DNA-binding small molecule induces trinucleotide-repeat contractions in vivo.

Nat Genet 2020 02 14;52(2):146-159. Epub 2020 Feb 14.

Program of Genetics & Genome Biology, The Hospital for Sick Children, The Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada.

In many repeat diseases, such as Huntington's disease (HD), ongoing repeat expansions in affected tissues contribute to disease onset, progression and severity. Inducing contractions of expanded repeats by exogenous agents is not yet possible. Traditional approaches would target proteins driving repeat mutations. Read More

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http://dx.doi.org/10.1038/s41588-019-0575-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043212PMC
February 2020

Bioenergetic restoration and neuroprotection after therapeutic targeting of mitoNEET: New mechanism of pioglitazone following traumatic brain injury.

Exp Neurol 2020 May 10;327:113243. Epub 2020 Feb 10.

Spinal Cord & Brain Injury Research Center, University of Kentucky, Lexington, KY 40536, USA; Department of Neuroscience, University of Kentucky, Lexington, KY 40536, USA; Lexington VA Healthcare System, Lexington, KY 40502, USA. Electronic address:

Mitochondrial dysfunction is a pivotal event in many neurodegenerative disease states including traumatic brain injury (TBI) and spinal cord injury (SCI). One possible mechanism driving mitochondrial dysfunction is glutamate excitotoxicity leading to Ca-overload in neuronal or glial mitochondria. Therapies that reduce calcium overload and enhance bioenergetics have been shown to improve neurological outcomes. Read More

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http://dx.doi.org/10.1016/j.expneurol.2020.113243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089834PMC
May 2020
4.696 Impact Factor

A Network-Based Bioinformatics Approach to Identify Molecular Biomarkers for Type 2 Diabetes that Are Linked to the Progression of Neurological Diseases.

Int J Environ Res Public Health 2020 02 6;17(3). Epub 2020 Feb 6.

Bone Biology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.

Neurological diseases (NDs) are progressive disorders, the progression of which can be significantly affected by a range of common diseases that present as comorbidities. Clinical studies, including epidemiological and neuropathological analyses, indicate that patients with type 2 diabetes (T2D) have worse progression of NDs, suggesting pathogenic links between NDs and T2D. However, finding causal or predisposing factors that link T2D and NDs remains challenging. Read More

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http://dx.doi.org/10.3390/ijerph17031035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037290PMC
February 2020
2.063 Impact Factor

New Potential Axes of HIV Neuropathogenesis with Relevance to Biomarkers and Treatment.

Curr Top Behav Neurosci 2020 Feb 11. Epub 2020 Feb 11.

Applied Neurosciences Program, Peter Duncan Neurosciences Research Unit, St. Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia.

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) affect approximately half of people living with HIV despite viral suppression with antiretroviral therapies and represent a major cause of morbidity. HAND affects activities of daily living including driving, using the Internet and, importantly, maintaining drug adherence. Whilst viral suppression with antiretroviral therapies (ART) has reduced the incidence of severe dementia, mild neurocognitive impairments continue to remain prevalent. Read More

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http://dx.doi.org/10.1007/7854_2019_126DOI Listing
February 2020

Parkinson's disease and spirituality.

NeuroRehabilitation 2020 ;46(1):31-39

Faraday Institute for Science and Religion, Cambridge, UK.

Objective: To assess the claim that Parkinson's disease (PD) specifically reduces religiosity religious faith and spirituality.

Methods: A longitudinal case-control study over 12 months of spirituality in 42 patients with idiopathic PD and 39 disease controls matched for age, gender, educational attainment and disability. There was no selection on grounds of religious affiliation. Read More

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http://dx.doi.org/10.3233/NRE-192947DOI Listing
January 2020

Lysosome and Inflammatory Defects in GBA1-Mutant Astrocytes Are Normalized by LRRK2 Inhibition.

Mov Disord 2020 May 8;35(5):760-773. Epub 2020 Feb 8.

Ann Romney Center for Neurological Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Background: Autosomal recessive mutations in the glucocerebrosidase gene, Beta-glucocerebrosidase 1 (GBA1), cause the lysosomal storage disorder Gaucher's disease. Heterozygous carriers of most GBA1 mutations have dramatically increased Parkinson's disease (PD) risk, but the mechanisms and cells affected remain unknown. Glucocerebrosidase expression is relatively enriched in astrocytes, yet the impact of its mutation in these cells has not yet been addressed. Read More

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http://dx.doi.org/10.1002/mds.27994DOI Listing

Sensitivity study on seat belt system key factors in terms of disabled driver behavior during frontal crash.

Acta Bioeng Biomech 2019 ;21(4):169-180

Military University of Technology, Faculty of Mechanical Engineering, Warsaw, Poland.

Purpose: Each year, many cars (in Poland approximately three hundred) are adopted for disabled driver, to enable them to drive the car independently. The purpose of the paper is to assess the key factors which significantly influence the disabled driver behavior during a frontal crash and have the biggest impact on the safety factors.

Methods: To achieve the purpose of the paper, the finite element method was used. Read More

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Chimeric antigen receptor T-cell therapy in patients with neurologic comorbidities.

Pediatr Blood Cancer 2020 04 4;67(4):e28199. Epub 2020 Feb 4.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Chimeric antigen receptor T cells (CAR-T) are an effective and potentially durable treatment for refractory and multiply relapsed B-cell acute lymphoblastic leukemia. Neurotoxicity is frequent after CAR-T cell therapy. Mechanisms driving neurotoxicity are incompletely understood, and symptoms can range from transient and mild to severe and life-threatening. Read More

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http://dx.doi.org/10.1002/pbc.28199DOI Listing

Arginine π-stacking drives binding to fibrils of the Alzheimer protein Tau.

Nat Commun 2020 Jan 29;11(1):571. Epub 2020 Jan 29.

Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.

Aggregation of the Tau protein into fibrils defines progression of neurodegenerative diseases, including Alzheimer's Disease. The molecular basis for potentially toxic reactions of Tau aggregates is poorly understood. Here we show that π-stacking by Arginine side-chains drives protein binding to Tau fibrils. Read More

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http://dx.doi.org/10.1038/s41467-019-13745-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989696PMC
January 2020

Characterization of a nap1l1 transgenic reporter in zebrafish.

Gene 2020 Apr 24;735:144388. Epub 2020 Jan 24.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Sciences, Fudan University, Shanghai 200032, PR China. Electronic address:

Nap1l1 gene encodes a tissue specific nucleosome assembly protein and is essential for tissue development. Here, we report the generation and characterization of a nap1l1 transgenic reporter in zebrafish model. We showed that a 5-kilobase (kb) genomic fragment immediately upstream of the nap1l1 gene transcription initiation site is capable of targeting the nucleic enhanced green fluorescence protein (EGFP) expression initially to central nervous system and subsequently to lateral line neuromasts, cardiomyocytes, and paraxial vessels, where the endogenous nap1l1 normally expresses with only a few exception. Read More

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http://dx.doi.org/10.1016/j.gene.2020.144388DOI Listing

Mutational landscape screening of methylene tetrahydrofolate reductase to predict homocystinuria associated variants: An integrative computational approach.

Mutat Res 2020 Jan - Apr;819-820:111687. Epub 2020 Jan 16.

Centre for Bioinformatics, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Vision Research Foundation, Sankara Nethralaya, Chennai, 600 006, Tamil Nadu, India. Electronic address:

Methylene tetrahydrofolate reductase (MTHFR) is a flavoprotein, involved in one-carbon pathway and is responsible for folate and homocysteine metabolism. Regulation of MTHFR is pivotal for maintaining the cellular concentrations of methionine and SAM (S-adenosyl methionine) which are essential for the synthesis of nucleotides and amino acids, respectively. Therefore, mutations in MTHFR leads to its dysfunction resulting in conditions like homocystinuria, cardiovascular diseases, and neural tube defects in infants. Read More

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http://dx.doi.org/10.1016/j.mrfmmm.2020.111687DOI Listing

On Smartphone Sensability of Bi-Phasic User Intoxication Levels from Diverse Walk Types in Standardized Field Sobriety Tests.

Conf Proc IEEE Eng Med Biol Soc 2019 07;2019:3279-3285

Intoxicated driving causes 10,000 deaths annually. Smartphone sensing of user gait (walk) to identify intoxicated users in order to prevent drunk driving, have recently emerged. Such systems gather motion sensor (accelerometer and gyroscope) data from the users' smartphone as they walk and classify them using machine or deep learning. Read More

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http://dx.doi.org/10.1109/EMBC.2019.8857214DOI Listing

Experimentally Modifiable Parameters and Their Relation to the Tonic Vibration Reflex in Chronic Hemiparetic Stroke.

Conf Proc IEEE Eng Med Biol Soc 2019 07;2019:2302-2306

The tonic vibration reflex (TVR), a reflexive muscle contraction resulting from muscle or tendon vibration, is a useful tool in assessing spinal motoneuron excitability, particularly in hyperexcitable conditions, such as in chronic hemiparetic stroke. The influence of experimental parameters, for example the type of vibratory stimulus and limb configuration, and their interactions on the TVR response in chronic stroke is unknown, yet this knowledge is crucial for designing experiments with reliable TVR responses. Therefore, we conducted a screening experiment of six potential driving factors affecting the TVR response, with a D-optimal split plot fractional design matrix consisting of thirty-two combinations for each of the four participants with chronic hemiparetic stroke. Read More

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http://dx.doi.org/10.1109/EMBC.2019.8857014DOI Listing

Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis.

Nat Commun 2020 01 14;11(1):247. Epub 2020 Jan 14.

Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.

Cerebrospinal fluid (CSF) protects the central nervous system (CNS) and analyzing CSF aids the diagnosis of CNS diseases, but our understanding of CSF leukocytes remains superficial. Here, using single cell transcriptomics, we identify a specific location-associated composition and transcriptome of CSF leukocytes. Multiple sclerosis (MS) - an autoimmune disease of the CNS - increases transcriptional diversity in blood, but increases cell type diversity in CSF including a higher abundance of cytotoxic phenotype T helper cells. Read More

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http://dx.doi.org/10.1038/s41467-019-14118-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959356PMC
January 2020

Intraocular scattering as a predictor of driving performance in older adults with cataracts.

PLoS One 2020 14;15(1):e0227892. Epub 2020 Jan 14.

Department of Optics, Laboratory of Vision Sciences and Applications, University of Granada, Spain.

Cataracts can limit a person's ability to perform vision-dependent tasks safely, affecting the quality of life of older people. This study examines the relationship between visual function and driving, by studying which visual parameters might be important for predicting driving performance in older drivers with and without cataracts, ascertaining whether the objective measurement of intraocular scattering should be considered in assessment procedures for older drivers. This cross-sectional study involved a total of 20 older drivers (10 patients with bilateral cataracts and 10 control subjects). Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227892PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959599PMC

Symptomatic Brain Hemorrhages from Cavernous Angioma After Botulinum Toxin Injections, a Role of TLR/MEKK3 Mechanism? Case Report and Review of the Literature.

World Neurosurg 2020 Apr 7;136:7-11. Epub 2020 Jan 7.

Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine and Biological Sciences, Chicago, Illinois, USA. Electronic address:

Background: Cavernous angiomas (CAs) are vascular malformations that may result in stroke.

Case Description: Herein, we evaluate a CA patient with chronic migraine who experienced 2 documented symptomatic hemorrhages after receiving respective high doses of botulinum toxin (Btx).

Conclusions: Recently, bacterial lipopolysaccharide has been reported to contribute to CA development through Toll-like receptor signaling, causing hemorrhagic angiogenic proliferation. Read More

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http://dx.doi.org/10.1016/j.wneu.2019.12.172DOI Listing

Longitudinal Associations of 12th-Grade Binge Drinking With Risky Driving and High-Risk Drinking.

Pediatrics 2020 02 6;145(2). Epub 2020 Jan 6.

Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland; and.

Objective: To study the longitudinal associations of 12th-grade binge drinking with driving while impaired (DWI), riding with an impaired driver (RWI), blackouts, extreme binge drinking, and risky driving (self-reported Checkpoints Risky Driving Scale) among emerging adults up to 4 years after leaving high school.

Methods: The data were all 7 waves (W 1 to W 7 of the NEXT Generation Health Study; a US nationally representative study ( = 2785) with a probability cohort of 10th-graders (mean age = 16.2 years; SE = 0. Read More

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http://dx.doi.org/10.1542/peds.2018-4095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993274PMC
February 2020

ELF5 modulates the estrogen receptor cistrome in breast cancer.

PLoS Genet 2020 01 2;16(1):e1008531. Epub 2020 Jan 2.

Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Victoria Street Darlinghurst Sydney, NSW, Australia.

Acquired resistance to endocrine therapy is responsible for half of the therapeutic failures in the treatment of breast cancer. Recent findings have implicated increased expression of the ETS transcription factor ELF5 as a potential modulator of estrogen action and driver of endocrine resistance, and here we provide the first insight into the mechanisms by which ELF5 modulates estrogen sensitivity. Using chromatin immunoprecipitation sequencing we found that ELF5 binding overlapped with FOXA1 and ER at super enhancers, enhancers and promoters, and when elevated, caused FOXA1 and ER to bind to new regions of the genome, in a pattern that replicated the alterations to the ER/FOXA1 cistrome caused by the acquisition of resistance to endocrine therapy. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959601PMC
January 2020

A systems approach identifies Enhancer of Zeste Homolog 2 (EZH2) as a protective factor in epilepsy.

PLoS One 2019 31;14(12):e0226733. Epub 2019 Dec 31.

Department of Neuroscience, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.

Complex neurological conditions can give rise to large scale transcriptomic changes that drive disease progression. It is likely that alterations in one or a few transcription factors or cofactors underlie these transcriptomic alterations. Identifying the driving transcription factors/cofactors is a non-trivial problem and a limiting step in the understanding of neurological disorders. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226733PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938365PMC