Power Equation for Predicting the Risk of Central Nervous System Oxygen Toxicity at Rest
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ABSTRACT:
SUBMITTER: Aviner B
PROVIDER: S-EPMC7461992 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:The brown ghost knifefish (Apteronotus leptorhynchus) is a weakly electric teleost fish of particular interest as a model organism for a variety of research areas in neuroscience, including neurophysiology, neuroethology, and neurobiology. This versatile model system has been more recently used in the study of central nervous system development and regeneration during adulthood, as well as in the study of vertebrate aging and senescence. Despite substantial scientific interest in this species, no genomic resources are currently available. After evaluating several trimming and transcript reconstruction strategies, de novo assembly using Trinity uncovered at least 11,847 unique components (“genes”) containing full or near-full length protein sequences based on alignment to a reference set of known Actinopterygii protein sequences, with as many as 42,459 components containing at least a partial protein-coding sequence, providing broad coverage of the proteome. Shotgun proteomics confirmed translation of open reading frames from over 2,000 transcripts, including alternative splice variants. Assignment of tandem mass spectra obtained was shown to be greatly improved with the assembly compared with using databases of sequences from closely related organisms.
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Project description:Purpose of reviewCentral nervous system (CNS) tuberculosis is the most devastating form of tuberculosis (TB), with mortality and or neurological sequelae in over half of individuals. We reviewed original research and systematic reviews published since 1 January 2019 for new developments in CNS TB pathophysiology, diagnosis, management and prognosis.Recent findingsInsight in the pathophysiology is increasing steadily since the landmark studies in 1933, focussing on granuloma type classification, the relevance of the M. tuberculosis bacterial burden and the wide range of immunological responses. Although Xpert/RIF has been recommended by the WHO for extrapulmonary TB diagnosis, culture is still needed to increase the sensitivity of TB meningitis diagnosis. Sequential MRIs can improve understanding of neurological deficits at baseline and during treatment. Pharmacokinetic/pharmacodynamic modelling suggests that higher doses of rifampicin and isoniazid in TB meningitis could improve survival.SummaryRecent studies in the field of CNS-TB have largely focussed on TB meningitis. The outcome may improve by optimizing treatment dosing. This needs to be confirmed in clinical trials. Due to the important role of inflammation, these trials should be used as the platform to study the inflammatory and metabolomic responses. This could improve understanding of the biology of this disease and improve patient outlook by enabling individualised host-directed therapy.
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Project description:PurposeSecond primary (SP) neoplasms of the central nervous system (CNS) among cancer survivors are devastating but poorly understood processes. The absolute risk, or true incidence, of developing an SP CNS tumor among cancer survivors is not well characterized.Methods and materialsPatients diagnosed with cancer between 1975 and 2016 were queried using the Surveillance, Epidemiology, and End Results Program. Cumulative incidence rates (CIRs) were estimated using competitive risk analysis. The effects of covariates were assessed using multivariate competitive risk regression.ResultsMore than 3.8 million patient records were extracted. The absolute risk of developing an SP CNS neoplasm at 25 years was highest among long-term survivors of CNS cancers (CIR, 6.6%). Cranial radiation increased the incidence of SP tumors in pediatric patients (25-year CIR, 5.7% vs 1.1%; P = .0012) but not adults (25-year CIR, 5.8% vs 5.0%; P = .66). Multivariate cumulative risk regression identified radiation among pediatric patients as the greatest risk for an increased CIR (subdistribution hazard ratio, 2.50; 95% CI, 1.86-3.38; P = 2e-9). Meningiomas (42.9% vs 24.1%; P = 2e-7) and glioblastomas (20.5% vs 14.5%; P = .046) represented a greater proportion of the SP CNS tumors in those who received cranial irradiation. The median age of an SP diagnosis was decreased among those who received prior radiation (41 years [interquartile range (IQR), 30-65 years] vs 49 years [IQR, 30-65 years]; P = 7e-5).ConclusionsThe risk of developing a second primary CNS neoplasm is elevated in patients with a prior CNS cancer independent of treatment history. The association between cranial radiation therapy and risk for subsequent cancers may be limited to the pediatric population.
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