Mccarthyraun9637

Published by BMJ.OBJECTIVE To test the hypothesis that the pattern of serum biomarkers of disease activity and disability in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) will be different from those in neuromyelitis optica spectrum disorder (NMOSD) with anti-aquaporin-4 antibodies (AQP4-Abs). METHODS Using ultrasensitive single-molecule array assays, we measured neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and tau in the sera of consecutive patients with MOGAD (n = 16) and NMOSD with AQP4-Ab (n = 33). Serum biomarker levels were compared between patients in relapse and remission states, and correlations between the levels of these biomarkers and Expanded Disability Status Scale (EDSS) scores were analyzed within each group. RESULTS In the MOGAD group, the serum tau level was higher in a relapse state than in a remission state (relapse vs remission 0.5 [0.4-0.5] vs 0.2 [0.1-0.3] pg/mL, p = 0.027). Both serum levels of NfL and tau correlated with the EDSS score (NfL r = 0.684, p = 0.003; tau r = 0.524, p = 0.045). Meanwhile, in the NMOSD group, serum NfL and GFAP levels were higher in a relapse state than in a remission state (relapse vs remission NfL, 34.8 [12.2-62.3] vs 13.0 [11.3-20.0] pg/mL, p = 0.010; GFAP, 253.8 [150.6-303.0] vs 104.4 [93.9-127.9] pg/mL, p = 0.016). Only the serum GFAP level correlated with the EDSS score (r = 0.485, p = 0.012). CONCLUSION The pattern of serum biomarkers of disease activity and disability in MOGAD showed a distinct feature from those in NMOSD with AQP4-Ab, which implicates different pathogeneses between the 2 diseases. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. Eflornithine on behalf of the American Academy of Neurology.OBJECTIVE We examined the effect of glatiramer acetate (GA) on B-cell maturation, differentiation, and antigen presentation in MS and experimental autoimmune encephalomyelitis (EAE). METHODS A cross-sectional study of blood samples from 20 GA-treated and 18 untreated patients with MS was performed by flow cytometry; 6 GA-treated patients with MS were analyzed longitudinally. GA-mediated effects on B-cell antigen-presenting function were investigated in EAE, or, alternatively, B cells were treated with GA in vitro using vehicle as a control. RESULTS In MS, GA diminished transitional B-cell and plasmablast frequency, downregulated CD69, CD25, and CD95 expression, and decreased TNF-α production, whereas IL-10 secretion and MHC Class II expression were increased. In EAE, we observed an equivalent dampening of proinflammatory B-cell properties and an enhanced expression of MHC Class II. When used as antigen-presenting cells for activation of naive T cells, GA-treated B cells promoted development of regulatory T cells, whereas proinflammatory T-cell differentiation was diminished. CONCLUSIONS GA immune modulates B-cell function in EAE and MS and efficiently interferes with pathogenic B cell-T cell interaction. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.OBJECTIVE To quantify disease progression in individuals with Duchenne muscular dystrophy (DMD) using magnetic resonance biomarkers of leg muscles. METHODS MRI and magnetic resonance spectroscopy (MRS) biomarkers were acquired from 104 participants with DMD and 51 healthy controls using a prospective observational study design with patients with DMD followed up yearly for up to 6 years. Fat fractions (FFs) in vastus lateralis and soleus muscles were determined with 1H MRS. MRI quantitative T2 (qT2) values were measured for 3 muscles of the upper leg and 5 muscles of the lower leg. Longitudinal changes in biomarkers were modeled with a cumulative distribution function using a nonlinear mixed-effects approach. RESULTS MRS FF and MRI qT2 increased with DMD disease duration, with the progression time constants differing markedly between individuals and across muscles. The average age at half-maximal muscle involvement (μ) occurred 4.8 years earlier in vastus lateralis than soleus, and these measures were strongly associated with loss-of-ambulation age. Corticosteroid treatment was found to delay μ by 2.5 years on average across muscles, although there were marked differences between muscles with more slowly progressing muscles showing larger delay. CONCLUSIONS MRS FF and MRI qT2 provide sensitive noninvasive measures of DMD progression. Modeling changes in these biomarkers across multiple muscles can be used to detect and monitor the therapeutic effects of corticosteroids on disease progression and to provide prognostic information on functional outcomes. This modeling approach provides a method to transform these MRI biomarkers into well-understood metrics, allowing concise summaries of DMD disease progression at individual and population levels. CLINICALTRIALSGOV IDENTIFIER NCT01484678. © 2020 American Academy of Neurology.INTRODUCTION This study assessed whether initiating e-cigarette use increases the uptake of cigarette smoking in US adolescents compared with behavioural and synthetic controls. METHODS Data come from 78 265 adolescents in the National Youth Tobacco Survey (2014-2017) of whom 38 630 provided information about the first tobacco product they had used in 2014/15. Ever, past 30 day and established (30 day use and 100+ lifetime cigarettes) cigarette smoking was compared in adolescents who first used an e-cigarette (exposure group), a non-cigarette combustible (CT) or other non-combustible tobacco (NT) product (behavioural controls), and propensity score matched adolescents without initial e-cigarette use (synthetic controls). RESULTS Relative to behavioural controls, adolescents who tried e-cigarettes first were less likely to have ever smoked cigarettes (26% vs CT (42.4%; OR 0.48, 95% CI 0.40 to 0.57), or NT initiators (52.7%; OR 0.32, 95% CI 0.26 to 0.39)), to be past 30 day (6% vs CT (11.9%; OR 0.48, 95% CI 0.36 to 0.62), or NT initiators (20.0%; OR 0.26, 95% CI 0.19 to 0.35)) or be established cigarette smokers (0.7% vs CT (3.9%; OR 0.17, 95% CI 0.10 to 0.30), or NT initiators (8.4%; OR 0.08, 95% CI 0.04 to 0.13)). E-cigarette initiators were also less likely than synthetic controls (without initial e-cigarette use) to have ever smoked cigarettes (OR 0.76, 95% CI 0.62 to 0.93), be past 30 day (OR 0.71, 95% CI 0.55 to 0.91) or be established cigarette smokers (OR 0.26, 95% CI 0.13 to 0.51). CONCLUSION Less than 1% of US adolescents who use e-cigarettes first were established cigarette smokers. They were less likely to be smokers than adolescents who tried other combustible or non-combustible tobacco products first and propensity score matched adolescents without initial e-cigarette use. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.BACKGROUND In the United States, transgender youth are at especially high risk for HIV infection. Literature regarding HIV prevention strategies for this vulnerable, often-hidden population is scant. Before effective, population-based HIV prevention strategies may be adequately developed, it is necessary to first enhance the contextual understanding of transgender youth HIV risk and experiences with HIV preventive services. METHODS Two 3-day, online, asynchronous focus groups were conducted with transgender youth from across the United States to better understand participant HIV risk and experiences with HIV preventive services. Participants were recruited by using online advertisements posted via youth organizations. Qualitative data were analyzed by using content analysis. RESULTS A total of 30 transgender youth participated. The average age was 18.6 years, and youth reported a wide range of gender identities (eg, 27% were transgender male, 17% were transgender female, and 27% used ≥1 term) and sexual orientations. Four themes emerged (1) barriers to self-efficacy in sexual decision-making; (2) safety concerns, fear, and other challenges in forming romantic and/or sexual relationships; (3) need for support and education; and (4) desire for affirmative and culturally competent experiences and interactions (eg, home, school, and health care). CONCLUSIONS Youth discussed experiences and perspectives related to their gender identities, sexual health education, and HIV preventive services. Findings should inform intervention development to improve support and/or services, including the following (1) increasing provider knowledge and skills to provide gender-affirming care, (2) addressing barriers to services (eg, accessibility and affordability as well as stigma and discrimination), and (3) expanding sexual health education to be inclusive of all gender identities, sexual orientations, and definitions of sex and sexual activity. Copyright © 2020 by the American Academy of Pediatrics.An increasing number of studies highlight common brain regions and processes in mediating conscious sensory experience. While most studies have been performed in the visual modality, it is implicitly assumed that similar processes are involved in other sensory modalities. However, the existence of supramodal neural processes related to conscious perception has not been convincingly shown so far. Here, we aim to directly address this issue by investigating whether neural correlates of conscious perception in one modality can predict conscious perception in a different modality. In two separate experiments, we presented participants with successive blocks of near-threshold tasks involving subjective reports of tactile, visual, or auditory stimuli during the same magnetoencephalography (MEG) acquisition. Using decoding analysis in the poststimulus period between sensory modalities, our first experiment uncovered supramodal spatiotemporal neural activity patterns predicting conscious perception of the feeble stimulation. Strikingly, these supramodal patterns included activity in primary sensory regions not directly relevant to the task (e.g., neural activity in visual cortex predicting conscious perception of auditory near-threshold stimulation). We carefully replicate our results in a control experiment that furthermore show that the relevant patterns are independent of the type of report (i.e., whether conscious perception was reported by pressing or withholding a button press). Using standard paradigms for probing neural correlates of conscious perception, our findings reveal a common signature of conscious access across sensory modalities and illustrate the temporally late and widespread broadcasting of neural representations, even into task-unrelated primary sensory processing regions. Copyright © 2020 the Author(s). Published by PNAS.Temporal dynamics of urban warming have been extensively studied at the diurnal scale, but the impact of background climate on the observed seasonality of surface urban heat islands (SUHIs) remains largely unexplored. On seasonal time scales, the intensity of urban-rural surface temperature differences ([Formula see text]) exhibits distinctive hysteretic cycles whose shape and looping direction vary across climatic zones. These observations highlight possible delays underlying the dynamics of the coupled urban-biosphere system. However, a general argument explaining the observed hysteretic patterns remains elusive. A coarse-grained model of SUHI coupled with a stochastic soil water balance is developed to demonstrate that the time lags between radiation forcing, air temperature, and rainfall generate a rate-dependent hysteresis, explaining the observed seasonal variations of [Formula see text] If solar radiation is in phase with water availability, summer conditions cause strong SUHI intensities due to high rural evaporative cooling.