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"Chen, John"
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Optic neuritis and autoimmune optic neuropathies: advances in diagnosis and treatment
Optic neuritis is an inflammatory optic neuropathy that is commonly indicative of autoimmune neurological disorders including multiple sclerosis, myelin-oligodendrocyte glycoprotein antibody-associated disease, and neuromyelitis optica spectrum disorder. Early clinical recognition of optic neuritis is important in determining the potential aetiology, which has bearing on prognosis and treatment. Regaining high-contrast visual acuity is common in people with idiopathic optic neuritis and multiple sclerosis-associated optic neuritis; however, residual deficits in contrast sensitivity, binocular vision, and motion perception might impair vision-specific quality-of-life metrics. In contrast, recovery of visual acuity can be poorer and optic nerve atrophy more severe in individuals who are seropositive for antibodies to myelin oligodendrocyte glycoprotein, AQP4, and CRMP5 than in individuals with typical optic neuritis from idiopathic or multiple-sclerosis associated optic neuritis. Key clinical, imaging, and laboratory findings differentiate these disorders, allowing clinicians to focus their diagnostic studies and optimise acute and preventive treatments. Guided by early and accurate diagnosis of optic neuritis subtypes, the timely use of high-dose corticosteroids and, in some instances, plasmapheresis could prevent loss of high-contrast vision, improve contrast sensitivity, and preserve colour vision and visual fields. Advancements in our knowledge, diagnosis, and treatment of optic neuritis will ultimately improve our understanding of autoimmune neurological disorders, improve clinical trial design, and spearhead therapeutic innovation.
Journal Article
The neuro-ophthalmological manifestations of NMOSD and MOGAD—a comprehensive review
Optic neuritis (ON) is one of the most frequently seen neuro-ophthalmic causes of vision loss worldwide. Typical ON is often idiopathic or seen in patients with multiple sclerosis, which is well described in the landmark clinical trial, the Optic Neuritis Treatment Trial (ONTT). However, since the completion of the ONTT, there has been the discovery of aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibodies, which are biomarkers for neuromyelitis optica spectrum disorder (NMOSD) and MOG antibody-associated disease (MOGAD), respectively. These disorders are associated with atypical ON that was not well characterised in the ONTT. The severity, rate of recurrence and overall outcome differs in these two entities requiring prompt and accurate diagnosis and management. This review will summarise the characteristic neuro-ophthalmological signs in NMOSD and MOGAD, serological markers and radiographic findings, as well as acute and long-term therapies used for these disorders.
Journal Article
Fantastic Four : the complete collection. Vol. 1
\"Legendary writer Jonathan Hickman's sprawling, landmark Fantastic Four run begins here! Dark Reign strikes Marvel's first family in an explosive way - with HAMMER agents attacking the Baxter Building! But as Reed Richards builds a bridge across the multiverse to learn how to solve everything, he finds more than he bargained for... what is the Council? The FF deal with the Wizard and the Mole Man, a familiar visitor arrives from the future with a mysterious message, and the team journeys deep beneath the Earth, under the sea and to the moon--where they learn a startling secret about the history of the Inhumans. It's superior super hero storytelling as only Jonathan Hickman can deliver it!\"-- Page [4] of cover.
Book
Dancing with the stars: Benefits of a star employee's temporary absence for organizational performance
Research Summary: While research has focused primarily on stars as individual contributors, we examine organizational situations where stars must work closely with non-stars. We argue that, in such situations, building teamwork around a star is an exercise in learning under complexity. In response, organizations prioritize interactions involving the star to simplify learning. This simplification, however, creates organizational myopia. We claim that a star's temporary absence helps the organization overcome myopia by triggering a search for new routines. When he returns, the organization may combine these new routines with pre-absence routines to improve teamwork and performance. We exploit injuries to star players in the National Basketball Association as an exogenous shock and find that on average, teams perform better after a star's return than before his absence. Managerial Summary: This study examines the effect of the temporary absence of a star evidence that a star employee's temporary absence helps the organization overcome an over-reliance on the star and improve teamwork. Improved teamwork, in turn, enables the organization to perform better upon the star's return than it did prior to his absence. This result suggests that organizations might want to revisit the tendency to view stars as too valuable to lose, even for a short time. In particular, organizations may want to pull stars from ongoing projects and encourage them to attend professional development programs. A star's temporary absence and return from such a program improves not only the star's skills but also the organization's teamwork.
Journal Article
Avengers Academy : the complete collection. Vol. 2
The Avengers Academy faces Fear Itself! No, not prom night - though they have to survive that too, when the Sinister Six crash the party! We mean actual Fear Itself, as the Serpent's army assaults the Marvel Universe and the squad must battle the possessed, hammer-wielding versions of Titania and the Absorbing Man! Meanwhile, as Speedball returns to the scene of his greatest failure, can he rally the town of Stamford against the Serpent and finally earn forgiveness from its people - or himself? Plus, the students get schooled by a substitute teacher - the Amazing Spider-Man - but their lesson is interrupted by Psycho-Man! And as Hank Pym relocates the Academy to California, they come under attack by...the West Coast Avengers?!
Book
Measuring Myeloperoxidase Activity in Biological Samples
Enzymatic activity measurements of the highly oxidative enzyme myeloperoxidase (MPO), which is implicated in many diseases, are widely used in the literature, but often suffer from nonspecificity and lack of uniformity. Thus, validation and standardization are needed to establish a robust method that is highly specific, sensitive, and reproducible for assaying MPO activity in biological samples.
We found conflicting results between in vivo molecular MR imaging of MPO, which measures extracellular activity, and commonly used in vitro MPO activity assays. Thus, we established and validated a protocol to obtain extra- and intracellular MPO from murine organs. To validate the MPO activity assays, three different classes of MPO activity assays were used in spike and recovery experiments. However, these assay methods yielded inconsistent results, likely because of interfering substances and other peroxidases present in tissue extracts. To circumvent this, we first captured MPO with an antibody. The MPO activity of the resultant samples was assessed by ADHP and validated against samples from MPO-knockout mice in murine disease models of multiple sclerosis, steatohepatitis, and myocardial infarction. We found the measurements performed using this protocol to be highly specific and reproducible, and when performed using ADHP, to be highly sensitive over a broad range. In addition, we found that intracellular MPO activity correlated well with tissue neutrophil content, and can be used as a marker to assess neutrophil infiltration in the tissue.
We validated a highly specific and sensitive assay protocol that should be used as the standard method for all MPO activity assays in biological samples. We also established a method to obtain extra- and intracellular MPO from murine organs. Extracellular MPO activity gives an estimate of the oxidative stress in inflammatory diseases, while intracellular MPO activity correlates well with tissue neutrophil content. A detailed step-by-step protocol is provided.
Journal Article
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): current understanding and challenges
New diagnostic criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have recently been proposed, distinguishing this syndrome from other inflammatory diseases of the central nervous system. Seropositivity status for MOG-IgG autoantibodies is important for diagnosing MOGAD, but only in the context of robust clinical characterization and cautious interpretation of neuroimaging. Over the last several years, access to cell-based assay (CBA) techniques has improved diagnostic accuracy, yet the positive predictive value of serum MOG-IgG values varies with the prevalence of MOGAD in any given patient population. For this reason, possible alternative diagnoses need to be considered, and low MOG-IgG titers need to be carefully weighted. In this review, cardinal clinical features of MOGAD are discussed. Key challenges to the current understanding of MOGAD are also highlighted, including uncertainty regarding the specificity and pathogenicity of MOG autoantibodies, the need to identify immunopathologic targets for future therapies, the quest to validate biomarkers that facilitate diagnosis and detect disease activity, and the importance of deciphering which patients with MOGAD require long-term immunotherapy.
Journal Article
The prevalence of mild cognitive impairment by aspects of social isolation
This study describes the prevalence of mild cognitive impairment (MCI) across different aspects of social isolation among adults 65 years or older.
In this cross-sectional study, we utilized the Wave 3 data from the National Social Life, Health, and Aging Project (NSHAP). MCI was defined as a Montreal Cognitive Assessment (MoCA) score less than 23. Prevalence of MCI was calculated for above and below average social disconnectedness (SD), perceived isolation (PI), and demographic variables age, gender, race/ethnicity, education, and household income.
The overall prevalence [and 95% confidence interval] of MCI was 27.5% [25.5-29.6]. The high prevalence of MCI was found in those who had above average SD (32.0% [29.1-34.9]), above average PI (33.3% [29.7-36.8]), were older in age (43.1% [38.9-47.3]), male (28.7% [25.9-31.5]), Black (61.1% [52.5-69.6]), had less than a high school education (66.3% [58.9-73.8]), or were in the lowest income group (46.2% [39.7-52.7]). Those with above average SD or PI had a higher prevalence of MCI in almost all demographics, compared to those with below average SD or PI. Those who were Black or African American or had less than a high school education did not have a greater prevalence of MCI when SD was above average.
This current study adds to the body of literature that links SD and PI to MCI and sheds light on the possible existing socio-demographic disparities. Groups with greater than average SD or PI tend to have a higher prevalence of MCI. Further studies are needed to establish a causal association of SD and PI with MCI.
Journal Article