1,383,347 results match your criteria Encephalopathy Hypertensive


Deep sequence modelling for Alzheimer's disease detection using MRI.

Comput Biol Med 2021 Jun 1;134:104537. Epub 2021 Jun 1.

School of Electrical Engineering and Computing, The University of Newcastle, NSW 2308, Australia.

Background: Alzheimer's disease (AD) is one of the deadliest diseases in developed countries. Treatments following early AD detection can significantly delay institutionalisation and extend patients' independence. There has been a growing focus on early AD detection using artificial intelligence. Read More

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Benzofuranyl-2-imidazoles as imidazoline I receptor ligands for Alzheimer's disease.

Eur J Med Chem 2021 May 20;222:113540. Epub 2021 May 20.

Laboratory of Medicinal Chemistry (Associated Unit to CSIC), Department of Pharmacology, Toxicology and Medicinal Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Biomedicine (IBUB), University of Barcelona, Av. Joan XXIII, 27-31, E-08028, Barcelona, Spain. Electronic address:

Recent findings unveil the pharmacological modulation of imidazoline I receptors (I-IR) as a novel strategy to face unmet medical neurodegenerative diseases. In this work, we report the chemical characterization, three-dimensional quantitative structure-activity relationship (3D-QSAR) and ADMET in silico of a family of benzofuranyl-2-imidazoles that exhibit affinity against human brain I-IR and most of them have been predicted to be brain permeable. Acute treatment in mice with 2-(2-benzofuranyl)-2-imidazole, known as LSL60101 (garsevil), showed non-warning properties in the ADMET studies and an optimal pharmacokinetic profile. Read More

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Differential expression of gut miRNAs in idiopathic Parkinson's disease.

Parkinsonism Relat Disord 2021 Jun 1;88:46-50. Epub 2021 Jun 1.

Department of Translational Brain Research, German Centre for Neurodegenerative Diseases (DZNE), Munich, Germany; Department of Neurology, Ludwig Maximilian University, Munich, Germany. Electronic address:

Objective: In the present work, we aimed to investigate the expression of microRNAs (miRNAs) in routine colonic biopsies obtained from patients with idiopathic Parkinson's disease (PD) and to address their value as a diagnostic biomarker for PD and their mechanistic contribution to PD onset and progression.

Methods: Patients with PD (n = 13) and healthy controls (n = 17) were prospectively recruited to undergo routine colonic biopsies for cancer screening. Total RNA was extracted from the biopsy material and the expression of miRNAs was quantified by Illumina High-Throughput Sequencing. Read More

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Differential lncRNA expression profiling of cognitive function in middle and old aged monozygotic twins using generalized association analysis.

J Psychiatr Res 2021 Jun 2;140:197-204. Epub 2021 Jun 2.

Unit of Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Denmark; Unit of Human Genetics, Department of Clinical Research, University of Southern Denmark, Denmark. Electronic address:

Cognitive impairment is the most prominent symptom in neurodegenerative disorders affecting quality of life and mortality. However, despite years of research, the molecular mechanism underlying the regulation of cognitive function and its impairment is poorly understood. This study aims to elucidate the role of long non-coding RNAs (lncRNAs) expression and lncRNA-mRNA interaction networks, by analyzing lncRNA expression in whole blood samples of 400 middle and old aged monozygotic twins in association with cognitive function using both linear models and a generalized correlation coefficient (GCC) to capture the diverse patterns of correlation. Read More

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Apolipoprotein A-I mimetic peptide inhibits atherosclerosis by increasing tetrahydrobiopterin via regulation of GTP-cyclohydrolase 1 and reducing uncoupled endothelial nitric oxide synthase activity.

Atherosclerosis 2021 May 31;328:83-91. Epub 2021 May 31.

Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, PR China; NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, PR China; Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, PR China; Guangdong Provincial Key Laboratory of Brain Function and Disease,Guangzhou, 510080, PR China. Electronic address:

Background And Aims: The apolipoprotein A-I mimetic peptide D-4F, among its anti-atherosclerotic effects, improves vasodilation through mechanisms not fully elucidated yet.

Methods: Low-density lipoprotein (LDL) receptor null (LDLr) mice were fed Western diet with or without D-4F. We then measured atherosclerotic lesion formation, endothelial nitric oxide synthase (eNOS) phosphorylation and its association with heat shock protein 90 (HSP90), nitric oxide (NO) and superoxide anion (O) production, and tetrahydrobiopterin (BH4) and GTP-cyclohydrolase 1 (GCH-1) concentration in the aorta. Read More

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Cross-cohort generalizability of deep and conventional machine learning for MRI-based diagnosis and prediction of Alzheimer's disease.

Neuroimage Clin 2021 Jun 4;31:102712. Epub 2021 Jun 4.

Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.

This work validates the generalizability of MRI-based classification of Alzheimer's disease (AD) patients and controls (CN) to an external data set and to the task of prediction of conversion to AD in individuals with mild cognitive impairment (MCI). We used a conventional support vector machine (SVM) and a deep convolutional neural network (CNN) approach based on structural MRI scans that underwent either minimal pre-processing or more extensive pre-processing into modulated gray matter (GM) maps. Classifiers were optimized and evaluated using cross-validation in the Alzheimer's Disease Neuroimaging Initiative (ADNI; 334 AD, 520 CN). Read More

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Consistent Alterations of Human Fecal Microbes after Transplantation into Germ-free Mice.

Genomics Proteomics Bioinformatics 2021 Jun 9. Epub 2021 Jun 9.

MOE Key Laboratory of Molecular Biophysics, Hubei Key Laboratory of Bioinformatics and Molecular-imaging, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; College of Life Science, Henan Normal University, Xinxiang 453007, China. Electronic address:

Fecal microbiota transplantation (FMT) of human fecal samples into germ-free (GF) mice is useful for establishing causal relationships between the gut microbiota and human phenotypes. However, due to the intrinsic differences between human and mouse intestines and the different diets of the two organisms, it may not be possible to replicate human phenotypes in mice through FMT; similarly, treatments that are effective in mouse models may not be effective in humans. In this study, we aimed to identify human gut microbes that undergo significant and consistent changes (i. Read More

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Family-based exome sequencing identifies RBM45 as a possible candidate gene for frontotemporal dementia and amyotrophic lateral sclerosis.

Neurobiol Dis 2021 Jun 9:105421. Epub 2021 Jun 9.

Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. Electronic address:

Neurodegenerative disorders like frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are pathologically characterized by toxic protein deposition in the cytoplasm or nucleus of affected neurons and glial cells. Many of these aggregated proteins belong to the class of RNA binding proteins (RBP), and, when mutated, account for a significant subset of familial ALS and FTD cases. Here, we present first genetic evidence for the RBP gene RBM45 in the FTD-ALS spectrum. Read More

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Glucose metabolic crosstalk and regulation in brain function and diseases.

Prog Neurobiol 2021 Jun 9:102089. Epub 2021 Jun 9.

Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, 21201, United States; Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD, 21201, United States; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, United States; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, United States; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, United States. Electronic address:

Brain glucose metabolism, including glycolysis, the pentose phosphate pathway, and glycogen turnover, produces ATP for energetic support and provides the precursors for the synthesis of biological macromolecules. Although glucose metabolism in neurons and astrocytes has been extensively studied, the glucose metabolism of microglia and oligodendrocytes, and their interactions with neurons and astrocytes, remain critical to understand brain function. Brain regions with heterogeneous cell composition and cell-type-specific profiles of glucose metabolism suggest that metabolic networks within the brain are complex. Read More

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Prognostic performance of seven biomarkers compared to liver biopsy in early alcohol-related liver disease.

J Hepatol 2021 Jun 9. Epub 2021 Jun 9.

Department of Gastroenterology and Hepatology, Odense University Hospital, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.

Background & Aims: Alcohol is the most common cause of liver-related mortality and morbidity. We therefore aimed to assess and compare the prognostic performance of elastography and blood-based markers to predict time to the first liver-related event, severe infection, and all-cause mortality in patients with a history of excess drinking.

Methods: Prospective cohort study of patients with early, compensated alcohol-related liver disease. Read More

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Peripherally active dextromethorphan derivatives lower blood glucose levels by targeting pancreatic islets.

Cell Chem Biol 2021 Jun 2. Epub 2021 Jun 2.

Institute for Vascular and Islet Cell Biology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at Heinrich Heine University, 40225 Düsseldorf, Germany; Institute of Metabolic Physiology, Heinrich Heine University, 40225 Düsseldorf, Germany; Center of Competence for Innovative Diabetes Therapy (KomIT), German Diabetes Center (DDZ), 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Helmholtz Zentrum München, 85764 Neuherberg, Germany. Electronic address:

Dextromethorphan (DXM) acts as cough suppressant via its central action. Cell-protective effects of this drug have been reported in peripheral tissues, making DXM potentially useful for treatment of several common human diseases, such as type 2 diabetes mellitus (T2DM). Pancreatic islets are among the peripheral tissues that positively respond to DXM, and anti-diabetic effects of DXM were observed in two placebo-controlled, randomized clinical trials in humans with T2DM. Read More

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From Kuru to Alzheimer: a personal outlook.

Authors:
Maurizio Brunori

Protein Sci 2021 Jun 12. Epub 2021 Jun 12.

Accademia Nazionale dei Lincei and Dipartimento di Scienze Biochimiche "A. Rossi Fanelli," Sapienza Università di Roma, Rome, Italy.

Seventy years ago we learned from Chris Anfinsen that the stereochemical code necessary to fold a protein is embedded into its amino acid sequence. In water, protein morphogenesis is a spontaneous reversible process leading from an ensemble of disordered structures to the ordered functionally competent protein; conforming to Aristotle's definition of substance, the synolon of matter and form. The overall process of folding is generally consistent with a two state transition between the native and the denatured protein: not only the denatured state is an ensemble of several structures, but also the native protein populates distinct functionally relevant conformational (sub)states. Read More

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Blood-brain barrier leakage and perivascular collagen accumulation precede microvessel rarefaction and memory impairment in a chronic hypertension animal model.

Metab Brain Dis 2021 Jun 12. Epub 2021 Jun 12.

Koç University Research Center for Translational Medicine, Istanbul, Turkey.

Hypertension (HT) is one of the main causes of vascular dementia, lead to cognitive decline. Here, we investigated the relationship between cerebral microvessels, pericytes, extracellular matrix (ECM) accumulation, blood-brain barrier (BBB) breakdown, and memory impairment at mid-life in a chronic hypertension animal model. Spontaneously hypertensive rats (SHRs) (n = 20) are chosen for the model and age matched Wistar rats (n = 16) as controls. Read More

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Neurogenesis in the adult Drosophila brain.

Genetics 2021 Jun 12. Epub 2021 Jun 12.

Genetics Graduate Training Program, University of Wisconsin-Madison, School of Medicine and Public Health, 1111 Highland Avenue, Madison, WI 53705, USA.

Neurodegenerative diseases such as Alzheimer's and Parkinson's currently affect ∼25 million people worldwide (Erkkinen et al. 2018). The global incidence of traumatic brain injury (TBI) is estimated at ∼70 million/year (Dewan et al. Read More

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Likelihood-based tests for detecting circadian rhythmicity and differential circadian patterns in transcriptomic applications.

Brief Bioinform 2021 Jun 12. Epub 2021 Jun 12.

Department of Biostatistics at the University of Florida, Gainesville, FL, 32608, USA.

Circadian rhythmicity in transcriptomic profiles has been shown in many physiological processes, and the disruption of circadian patterns has been found to associate with several diseases. In this paper, we developed a series of likelihood-based methods to detect (i) circadian rhythmicity (denoted as LR_rhythmicity) and (ii) differential circadian patterns comparing two experimental conditions (denoted as LR_diff). In terms of circadian rhythmicity detection, we demonstrated that our proposed LR_rhythmicity could better control the type I error rate compared to existing methods under a wide variety of simulation settings. Read More

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Increased risk of short-term depressive disorder after Helicobacter pylori eradication: A population-based nested cohort study.

Helicobacter 2021 Jun 11:e12824. Epub 2021 Jun 11.

Institute of Brain Science, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan.

Background: Depressive disorder is a major psychiatric illness, and a disturbed brain-gut-microbiome axis may contribute to its pathophysiology. Chronic Helicobacter pylori (H. pylori) infections are common in the general population and using multiple antibiotics is required for its eradication, which is associated with gut dysbiosis and may lead to depression. Read More

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Chronic restraint stress induces changes in the cerebral Galpha 12/13 and Rho-GTPase signaling network.

Pharmacol Rep 2021 Jun 11. Epub 2021 Jun 11.

Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland.

Background: Evidence indicates that Gα12, Gα13, and its downstream effectors, RhoA and Rac1, regulate neuronal morphology affected by stress. This study was aimed at investigating whether repeated stress influences the expression of proteins related to the Gα12/13 intracellular signaling pathway in selected brain regions sensitive to the effects of stress. Furthermore, the therapeutic impact of β(1)adrenergic receptors (β1AR) blockade was assessed. Read More

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Prediction of post TIPS hepatic encephalopathy: are we there yet?

Hepatol Int 2021 Jun 11. Epub 2021 Jun 11.

Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110029, India.

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Distinct basal brain functional activity and connectivity in the emotional-arousal network and thalamus in patients with functional constipation associated with anxiety and/or depressive disorders.

Psychosom Med 2021 Jun 11. Epub 2021 Jun 11.

Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, China Department of Radiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi 710038, China Department of Psychiatry, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.

Objective: Functional constipation (FC) is a common gastrointestinal disorder. Anxiety and/or depressive disorders are common in patients with FC (FCAD). Brain dysfunction may play a role in FC, but the contribution of comorbid anxiety and/or depression in patients with FC is poorly understood. Read More

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Postmortem whole-genome sequencing on a dried blood spot identifies a novel homozygous SUOX variant causing isolated sulfite oxidase deficiency.

Cold Spring Harb Mol Case Stud 2021 Jun 11;7(3). Epub 2021 Jun 11.

Rady Children's Institute for Genomic Medicine, San Diego, California 92123, USA.

Rapid whole-genome sequencing (rWGS) has shown that genetic diseases are a common cause of infant mortality in neonatal intensive care units. Dried blood spots collected for newborn screening allow investigation of causes of infant mortality that were not diagnosed during life. Here, we present a neonate who developed seizures and encephalopathy on the third day of life that was refractory to antiepileptic medications. Read More

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Severe multisystem pathology, metabolic acidosis, mitochondrial dysfunction, and early death associated with an X-linked variant.

Cold Spring Harb Mol Case Stud 2021 Jun 11;7(3). Epub 2021 Jun 11.

Greenwood Genetic Center, Greenwood, South Carolina 29646, USA.

Variants in the X-linked gene (apoptosis-inducing factor mitochondria-associated 1) are associated with a highly variable clinical presentation that encompasses motor neuropathy, ataxia, encephalopathies, deafness, and cognitive impairment. encodes a mitochondrial flavin adenine dinucleotide (FAD)-dependent nicotinamide adenine dinucleotide (NADH) oxidoreductase, with roles in the regulation of respiratory complex assembly and function, production of reactive oxygen species, and the coordination of a caspase-independent type of apoptosis known as parthanatos. In this report, we describe a missense variant (absent in reference population databases; c. Read More

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The spectrum of acute leukoencephalopathy with restricted diffusion (ALERD): A case series and review of literature.

Eur J Paediatr Neurol 2021 Jun 6;33:86-93. Epub 2021 Jun 6.

Department of Pediatric Neurology, Rainbow Children's Hospital, Hyderabad, Telangana, India. Electronic address:

Introduction: The clinico-etiological spectrum of Acute leukoencephalopathy with restricted diffusion (ALERD) is not well known in Indian population. This is likely to vary between populations and ethnicities.

Methods: We retrospectively reviewed the clinicoetiological spectrum of ALERD at a tertiary care pediatric center, and described the clinical, imaging, etiological spectrum and short-term outcomes. Read More

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Age-related amyloidosis outside the brain: A state-of-the-art review.

Ageing Res Rev 2021 Jun 8:101388. Epub 2021 Jun 8.

Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. Electronic address:

Inside and outside the brain, accumulation of amyloid fibrils plays key roles in the pathogenesis of fatal age-related diseases such as Alzheimer's and Parkinson's diseases and wild-type transthyretin amyloidosis. Although the incidence of all amyloidoses increases with age, for some types of amyloidosis aging is known as the main direct risk factor, and these types are typically diseases of elderly people. More than 10 different precursor proteins are known to cause age-associated amyloidosis; these proteins include amyloid β protein, α-synuclein, transthyretin, islet amyloid polypeptide, atrial natriuretic factor, and the newly discovered epidermal growth factor-containing fibulin-like extracellular matrix protein 1. Read More

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T2 heterogeneity as an in vivo marker of microstructural integrity in medial temporal lobe subfields in ageing and mild cognitive impairment.

Neuroimage 2021 Jun 9;238:118214. Epub 2021 Jun 9.

Bristol Medical School, University of Bristol, Institute of Clinical Neurosciences, Learning & Research Building at Southmead Hospital, Bristol BS10 5NB, UK; Clinical Neurosciences, North Bristol NHS Trust, Bristol, UK.

A better understanding of early brain changes that precede loss of independence in diseases like Alzheimer's disease (AD) is critical for development of disease-modifying therapies. Quantitative MRI, such as T2 relaxometry, can identify microstructural changes relevant to early stages of pathology. Recent evidence suggests heterogeneity of T2 may be a more informative MRI measure of early pathology than absolute T2. Read More

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The distinct and overlapping brain networks supporting semantic and spatial constructive scene processing.

Neuropsychologia 2021 Jun 8:107912. Epub 2021 Jun 8.

Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3AR, UK. Electronic address:

Scene imagery features prominently when we recall autobiographical memories, imagine the future and navigate around in the world. Consequently, in this study we sought to better understand how scene representations are supported by the brain. Processing scenes involves a variety of cognitive processes that in the real world are highly interactive. Read More

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SIRT1/PGC-1α signaling activation by mangiferin attenuates cerebral hypoxia/reoxygenation injury in neuroblastoma cells.

Eur J Pharmacol 2021 Jun 8:174236. Epub 2021 Jun 8.

Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, School of Life Sciences and Medicine, Northwest University, 10 Fengcheng Three Road, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education. Faculty of Life Sciences, Northwest University, 229 Taibai North Road, Xi'an, China. Electronic address:

Ischemia reperfusion injury (IRI) is associated with poor prognoses in the setting of ischemic brain diseases. Silence information regulator 1 (SIRT1) is a member of the third class of nicotinamide adenine dinucleotide (NAD)-dependent sirtuins. Recently, the role of SIRT1/peroxisome proliferators-activated receptor-γ coactivator 1α (PGC-1α) pathway in organ (especially the brain) protection under various pathological conditions has been widely investigated. Read More

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Extension of retinofugal projections in an assembled model of human pluripotent stem cell-derived organoids.

Stem Cell Reports 2021 May 27. Epub 2021 May 27.

Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis IN, USA; Department of Ophthalmology, Indiana University School of Medicine, Indianapolis IN, USA. Electronic address:

The development of the visual system involves the coordination of spatial and temporal events to specify the organization of varied cell types, including the elongation of axons from retinal ganglion cells (RGCs) to post-synaptic targets in the brain. Retinal organoids recapitulate many features of retinal development, yet have lacked downstream targets into which RGC axons extend, limiting the ability to model projections of the human visual system. To address these issues, retinal organoids were generated and organized into an in vitro assembloid model of the visual system with cortical and thalamic organoids. Read More

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Persistent visual dysfunction following PRES due to COVID-19: Case series and literature review.

Eur J Neurol 2021 Jun 11. Epub 2021 Jun 11.

Department of Ophthalmology, Colorado University School of Medicine, 1675 North Aurora Ct. F731, Aurora, CO, 80045, USA.

Background: The full spectrum of neurological sequelae in COVID-19 is beginning to emerge. SARS-CoV-2 has the potential to cause both direct and indirect brain vascular endothelial damage through infection and inflammation that may result in long-term neurological signs and symptoms. We sought to illuminate persistent neuro-ophthalmological deficits that may be seen following posterior reversible encephalopathy syndrome (PRES) due to COVID-19. Read More

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Combining MGMT promoter pyrosequencing and protein expression to optimize prognosis stratification in glioblastoma.

Cancer Sci 2021 Jun 11. Epub 2021 Jun 11.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Institute for Brain Disorders and Beijing Key Laboratory of Brain Tumor, Beijing, China.

Pyrosequencing (PSQ) represents the golden standard for MGMT promoter status determination. Binary interpretation of results based on the threshold from the average of several CpGs tested would neglect the existence of the "gray zone". How to define the gray zone and reclassify patients in this subgroup remains to be elucidated. Read More

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Repurposing of Clinically Approved Poly-(Adp-Ribose) Polymerase Inhibitors For The Therapy of Sepsis.

Shock 2021 Jun 10. Epub 2021 Jun 10.

Division of Infectious Diseases, Escola Paulista de Medicina, Universidade Federal de Sao Paulo - Sao Paulo - Brazil Laboratory of Medical Research - Faculty of Medicine of the University of São Paulo-USP, São Paulo, Brazil Chair of Pharmacology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.

Abstract: Sepsis' pathogenesis involves multiple mechanisms that lead to a dysregulation of the host's response. Significant efforts have been made in search of interventions that can reverse this situation and increase patient survival. Poly (ADP-polymerase) (PARP) is a constitutive nuclear and mitochondrial enzyme, which functions as a co-activator and co-repressor of gene transcription, thus regulating the production of inflammatory mediators. Read More

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