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Lancet (London, England) Jan 2021Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and... (Review)
Review
Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.
Topics: Central Nervous System Viral Diseases; Child; Enterovirus Infections; Global Health; Humans; Magnetic Resonance Imaging; Muscle Hypotonia; Muscle Weakness; Myelitis; Neuromuscular Diseases; Patient Outcome Assessment
PubMed: 33357469
DOI: 10.1016/S0140-6736(20)32723-9 -
Nature Sep 2019Elucidating the cellular architecture of the human cerebral cortex is central to understanding our cognitive abilities and susceptibility to disease. Here we used... (Comparative Study)
Comparative Study
Elucidating the cellular architecture of the human cerebral cortex is central to understanding our cognitive abilities and susceptibility to disease. Here we used single-nucleus RNA-sequencing analysis to perform a comprehensive study of cell types in the middle temporal gyrus of human cortex. We identified a highly diverse set of excitatory and inhibitory neuron types that are mostly sparse, with excitatory types being less layer-restricted than expected. Comparison to similar mouse cortex single-cell RNA-sequencing datasets revealed a surprisingly well-conserved cellular architecture that enables matching of homologous types and predictions of properties of human cell types. Despite this general conservation, we also found extensive differences between homologous human and mouse cell types, including marked alterations in proportions, laminar distributions, gene expression and morphology. These species-specific features emphasize the importance of directly studying human brain.
Topics: Adolescent; Adult; Aged; Animals; Astrocytes; Biological Evolution; Cerebral Cortex; Female; Humans; Male; Mice; Middle Aged; Neural Inhibition; Neurons; Principal Component Analysis; RNA-Seq; Single-Cell Analysis; Species Specificity; Transcriptome; Young Adult
PubMed: 31435019
DOI: 10.1038/s41586-019-1506-7 -
Nature May 2022The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced after infection... (Review)
Review
The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced after infection or vaccination. To address the public health threat caused by the increasing SARS-CoV-2 genomic diversity, the National Institute of Allergy and Infectious Diseases within the National Institutes of Health established the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme. This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants that could potentially affect the transmission, virulence, and resistance to infection- and vaccine-induced immunity. The SAVE programme is a critical data-generating component of the US Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines and therapeutics, and for communicating public health risk. Here we describe the coordinated approach used to identify and curate data about emerging variants, their impact on immunity and effects on vaccine protection using animal models. We report the development of reagents, methodologies, models and notable findings facilitated by this collaborative approach and identify future challenges. This programme is a template for the response to rapidly evolving pathogens with pandemic potential by monitoring viral evolution in the human population to identify variants that could reduce the effectiveness of countermeasures.
Topics: Animals; Biological Evolution; COVID-19; COVID-19 Vaccines; Humans; National Institute of Allergy and Infectious Diseases (U.S.); Pandemics; Pharmacogenomic Variants; SARS-CoV-2; United States; Virulence
PubMed: 35361968
DOI: 10.1038/s41586-022-04690-5 -
Nature Medicine May 2021Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in...
Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.
Topics: Angiotensin-Converting Enzyme 2; Asymptomatic Infections; COVID-19; Humans; Mouth; SARS-CoV-2; Saliva; Serine Endopeptidases; Taste Disorders; Virus Replication
PubMed: 33767405
DOI: 10.1038/s41591-021-01296-8 -
Cell Host & Microbe Dec 2022The monkeypox virus (MPXV) outbreak confirmed in May 2022 in non-endemic countries is raising concern about the pandemic potential of novel orthopoxviruses. Little is...
The monkeypox virus (MPXV) outbreak confirmed in May 2022 in non-endemic countries is raising concern about the pandemic potential of novel orthopoxviruses. Little is known regarding MPXV immunity in the context of MPXV infection or vaccination with vaccinia-based vaccines (VACV). As with vaccinia, T cells are likely to provide an important contribution to overall immunity to MPXV. Here, we leveraged the epitope information available in the Immune Epitope Database (IEDB) on VACV to predict potential MPXV targets recognized by CD4 and CD8 T cell responses. We found a high degree of conservation between VACV epitopes and MPXV and defined T cell immunodominant targets. These analyses enabled the design of peptide pools able to experimentally detect VACV-specific T cell responses and MPXV cross-reactive T cells in a cohort of vaccinated individuals. Our findings will facilitate the monitoring of cellular immunity following MPXV infection and vaccination.
Topics: Humans; Vaccinia virus; Monkeypox virus; Vaccinia; Mpox (monkeypox); Epitopes
PubMed: 36463861
DOI: 10.1016/j.chom.2022.11.003 -
Journal of Virology Aug 2022Human enterovirus D68 (EV-D68) is a globally reemerging respiratory pathogen that is associated with the development of acute flaccid myelitis (AFM) in children.... (Review)
Review
Human enterovirus D68 (EV-D68) is a globally reemerging respiratory pathogen that is associated with the development of acute flaccid myelitis (AFM) in children. Currently, there are no approved vaccines or treatments for EV-D68 infection, and there is a paucity of data related to the virus and host-specific factors that predict disease severity and progression to the neurologic syndrome. EV-D68 infection of various animal models has served as an important platform for characterization and comparison of disease pathogenesis between historic and contemporary isolates. Still, there are significant gaps in our knowledge of EV-D68 pathogenesis that constrain the development and evaluation of targeted vaccines and antiviral therapies. Continued refinement and characterization of animal models that faithfully reproduce key elements of EV-D68 infection and disease is essential for ensuring public health preparedness for future EV-D68 outbreaks.
Topics: Animals; Antiviral Agents; Central Nervous System Viral Diseases; Child; Disease Outbreaks; Disease Progression; Enterovirus D, Human; Enterovirus Infections; Humans; Models, Animal; Myelitis; Viral Vaccines
PubMed: 35852353
DOI: 10.1128/jvi.00833-22 -
Database : the Journal of Biological... Jul 2021The Ontology for Biomedical Investigations (OBI) underwent a focused review of assay term annotations, logic and hierarchy with a goal to improve and standardize these... (Review)
Review
The Ontology for Biomedical Investigations (OBI) underwent a focused review of assay term annotations, logic and hierarchy with a goal to improve and standardize these terms. As a result, inconsistencies in W3C Web Ontology Language (OWL) expressions were identified and corrected, and additionally, standardized design patterns and a formalized template to maintain them were developed. We describe here this informative and productive process to describe the specific benefits and obstacles for OBI and the universal lessons for similar projects.
Topics: Biological Ontologies; Language; Reference Standards
PubMed: 34244718
DOI: 10.1093/database/baab040 -
Life (Basel, Switzerland) Jun 2023Scoliosis and Scheuermann's disease are common spinal deformities that affect a substantial population, particularly adolescents, often impacting their quality of life.... (Review)
Review
Scoliosis and Scheuermann's disease are common spinal deformities that affect a substantial population, particularly adolescents, often impacting their quality of life. This comprehensive review aims to present a detailed understanding of these conditions, their diagnosis, and various treatment strategies. Through an extensive exploration of current literature, the review discusses the etiology of these spinal deformities and the use of diagnostic tools such as X-rays and MRI. It further delves into the range of treatment options available, from conservative approaches such as physiotherapy and bracing to more invasive surgical interventions. The review underscores the necessity of an individualized treatment approach, taking into account factors such as the patient's age, the severity of the curvature, and overall health. This all-encompassing perspective on scoliosis and Scheuermann's disease will aid in evidence-based decision making in their management with the goal of improving patient outcomes.
PubMed: 37374124
DOI: 10.3390/life13061341