Annual review of pathology
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Nearly all infectious agents contain DNA or RNA genomes, making sequencing an attractive approach for pathogen detection. The cost of high-throughput or next-generation sequencing has been reduced by several orders of magnitude since its advent in 2004, and it has emerged as an enabling technological platform for the detection and taxonomic characterization of microorganisms in clinical samples from patients. ⋯ The review covers ( a) next-generation sequencing technologies and common platforms, ( b) next-generation sequencing assay workflows in the clinical microbiology laboratory, ( c) bioinformatics analysis of metagenomic next-generation sequencing data, ( d) validation and use of metagenomic next-generation sequencing for diagnosing infectious diseases, and ( e) significant case reports and studies in this area. Next-generation sequencing is a new technology that has the promise to enhance our ability to diagnose, interrogate, and track infectious diseases.
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Review
The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future.
The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudolymphatic function in the brain. ⋯ Here, we review the role of the glymphatic pathway in CNS physiology, the factors known to regulate glymphatic flow, and the pathologic processes in which a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, are also discussed.
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For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. ⋯ Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations.
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Gliomas are the most common primary human brain tumors and occur in both adults and children. Over the past few years, systematic large-scale genomic and epigenomic profiling has provided unprecedented insight into their pathogenesis, uncovering alterations in an unanticipated number of genes and regulatory elements. In this review, we discuss recent discoveries about the genomics and epigenomics of adult and pediatric gliomas and highlight how some of the founding genetic mutations reshape the cancer epigenome. These studies provide an in-depth view of the molecular routes leading to glioma development, offer insight into the cancer stem cell model, help refine classifications, and should lay the foundation for improved clinical care.
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Almost a century ago, the first clinical account of the punch-drunk syndrome emerged, describing chronic neurological and neuropsychiatric sequelae occurring in former boxers. Thereafter, throughout the twentieth century, further reports added to our understanding of the neuropathological consequences of a career in boxing, leading to descriptions of a distinct neurodegenerative pathology, termed dementia pugilistica. During the past decade, growing recognition of this pathology in autopsy studies of nonboxers who were exposed to repetitive, mild traumatic brain injury, or to a single, moderate or severe traumatic brain injury, has led to an awareness that it is exposure to traumatic brain injury that carries with it a risk of this neurodegenerative disease, not the sport or the circumstance in which the injury is sustained. Furthermore, the neuropathology of the neurodegeneration that occurs after traumatic brain injury, now termed chronic traumatic encephalopathy, is acknowledged as being a complex, mixed, but distinctive pathology, the detail of which is reviewed in this article.