Distinct plasma lipids predict axonal injury and multiple sclerosis activity.

Background: Lipids are of particular interest for the study of neuroinjury and neuroinflammation as structural lipids are major components of myelin, and a variety of lipid species modulate inflammation. In this study, we performed an in-depth lipidomics analysis to identify lipids associated with injury and disease activity.

Methods: Plasma samples were collected from paediatric-onset multiple sclerosis (MS) cases within 4 years of disease onset from 17 sites.

MOG CNS Autoimmunity and MOGAD.

At one time considered a possible form of neuromyelitis optica (NMO) spectrum disorder (NMOSD), it is now accepted that myelin oligodendrocyte glycoprotein (MOG) antibody (Ab)-associated disorder (MOGAD) is a distinct entity from either NMO or multiple sclerosis (MS) and represents a broad spectrum of clinical phenotypes. Whereas Abs targeting aquaporin-4 (AQP4) in NMO are pathogenic, the extent that anti-MOG Abs contribute to CNS damage in MOGAD is unclear. Both AQP4-specific Abs in NMO and MOG-specific Abs in MOGAD are predominantly IgG1, a T cell-dependent immunoglobulin (Ig) subclass.

Predictors of a relapsing course in myelin oligodendrocyte glycoprotein antibody-associated disease.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described demyelinating disorder, and children represent about 50% of all cases. Almost half of the patients experience relapses, but very few studies have evaluated predictors of relapse risk, challenging clinical management. The study aimed to identify predictors at MOGAD onset that are associated with a relapsing course.

Life-Threatening MOG Antibody-Associated Hemorrhagic ADEM With Elevated CSF IL-6.

Acute disseminated encephalomyelitis (ADEM) is one characteristic manifestation of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). A previously healthy man presented with retro-orbital headache and urinary retention 14 days after Tdap vaccination. Brain and spine MRI suggested a CNS demyelinating process.

Spatial habitat heterogeneity influences host-pathogen dynamics in a patchy population of Ranchman's tiger moth.

Host-pathogen dynamics are influenced by many factors that vary locally, but models of disease rarely consider dynamics across spatially heterogeneous environments. In addition, theory predicts that dispersal will influence host-pathogen dynamics of populations that are linked, although this has not been examined empirically in natural systems. We examined the spatial dynamics of a patchy population of tiger moths and its baculovirus pathogen, in which habitat type and weather influence dynamics.

T cell deletional tolerance restricts AQP4 but not MOG CNS autoimmunity.

Aquaporin-4 (AQP4)-specific Th17 cells are thought to have a central role in neuromyelitis optica (NMO) pathogenesis. When modeling NMO, only AQP4-reactive Th17 cells from AQP4-deficient (AQP4), but not wild-type (WT) mice, caused CNS autoimmunity in recipient WT mice, indicating that a tightly regulated mechanism normally ensures tolerance to AQP4. Here, we found that pathogenic AQP4 T cell epitopes bind MHC II with exceptionally high affinity.

Forest environmental frontiers around the globe: Old patterns and new trends in forest governance.

Forests are subject to a huge variety of often competing socio-economic demands and environmental change. This paper assesses the related conflicts that occur along what we label to be a "Global Forest Environmental Frontier". Assessing 11 contributions to a special issue on the same topic, it summarizes the main contents of these papers and concludes with an assessment of major trends.

Disturbance shapes the US forest governance frontier: A review and conceptual framework for understanding governance change.

Conflict in US forest management for decades centered around balancing demands from forested ecosystems, with a rise in place-based collaborative governance at the end of the twentieth century. By the early 2000s, it was becoming apparent that not only had the mix of players involved in forest management changed, but so had the playing field, as climate-driven disturbances such as wildfire and insect and disease outbreaks were becoming more extensive and severe. In this conceptual review paper, we argue that disturbance has become the most prominent driver of governance change on US national forests, but we also recognize that the governance responses to disturbance are shaped by variables such as discourses, institutional history and path dependence, and institutional innovation operating at different system levels.

Water Extract Shows Low Potential for Cytochrome P450-Mediated Drug Interactions.

(CA) shows considerable promise for development as a botanical drug for cognitive decline. Its primary bioactive components include triterpene glycosides asiaticoside and madecassoside and their corresponding aglycones asiatic acid and madecassic acid. Exploration of the bioactivity of CA's caffeoylquinic acids is ongoing.

Insulin-Like Growth Factors Are Key Regulators of T Helper 17 Regulatory T Cell Balance in Autoimmunity.

Appropriate balance of T helper 17 (Th17) and regulatory T (Treg) cells maintains immune tolerance and host defense. Disruption of Th17-Treg cell balance is implicated in a number of immune-mediated diseases, many of which display dysregulation of the insulin-like growth factor (IGF) system. Here, we show that, among effector T cell subsets, Th17 and Treg cells selectively expressed multiple components of the IGF system.

Reduction of AMPA receptor activity on mature oligodendrocytes attenuates loss of myelinated axons in autoimmune neuroinflammation.

Glutamate dysregulation occurs in multiple sclerosis (MS), but whether excitotoxic mechanisms in mature oligodendrocytes contribute to demyelination and axonal injury is unexplored. Although current treatments modulate the immune system, long-term disability ensues, highlighting the need for neuroprotection. Glutamate is elevated before T2-visible white matter lesions appear in MS.

Batf Pioneers the Reorganization of Chromatin in Developing Effector T Cells via Ets1-Dependent Recruitment of Ctcf.

The basic leucine zipper transcription factor activating transcription factor-like (Batf) contributes to transcriptional programming of multiple effector T cells and is required for T helper 17 (Th17) and T follicular helper (Tfh) cell development. Here, we examine mechanisms by which Batf initiates gene transcription in developing effector CD4 T cells. We find that, in addition to its pioneering function, Batf controls developmentally regulated recruitment of the architectural factor Ctcf to promote chromatin looping that is associated with lineage-specific gene transcription.

Preferences for interventions designed to increase cervical screening uptake in non-attending young women: How findings from a discrete choice experiment compare with observed behaviours in a trial.

Background: Young women's attendance at cervical screening in the UK is continuing to fall, and the incidence of invasive cervical cancer is rising.

Objectives: We assessed the preferences of non-attending young women for alternative ways of delivering cervical screening.

Design: Postal discrete choice experiment (DCE) conducted during the STRATEGIC study of interventions for increasing cervical screening uptake.

Medicaid and CHIP Child Health Beneficiary Incentives: Program Landscape and Stakeholder Insights.

Objectives: To describe the landscape of Medicaid and the Children's Health Insurance Program beneficiary incentive programs for child health and garner key stakeholder insights on incentive program rationale, child and family engagement, and program evaluation.

Methods: We identified beneficiary health incentive programs from 2005 to 2018 through a search of peer-reviewed and publicly available documents and through semistructured interviews with 80 key stakeholders (Medicaid and managed-care leadership, program evaluators, patient advocates, etc). This study highlights insights from 23 of these stakeholders with expertise on programs targeting child health (<18 years old) to understand program rationale, beneficiary engagement, and program evaluation.

Correlation of DOTATOC Uptake and Pathologic Grade in Neuroendocrine Tumors.

Objectives: Gallium (Ga)-DOTATOC is a somatostatin analog used to detect neuroendocrine tumors (NETs). Ki-67 proliferation index (Ki-67 PI) has been established as a prognostic factor in NETs. We aimed to evaluate whether a correlation exists between Ki-67 PI and somatostatin receptor positron emission tomography (SSTR-PET) uptake.

Adolescent and Young Adult Recreational, Occupational, and Transportation Activity: Activity Recommendation and Weight Status Relationships.

Purpose: Physical activity can occur in many settings, or domains, including recreation, occupation, and transportation. We described patterns of adolescent and young adult (YA) activity in each domain, and the extent that accounting for different domains impacts activity recommendation adherence. We also examined activity domain associations with weight status.

Engaging Beneficiaries In Medicaid Programs That Incentivize Health-Promoting Behaviors.

Medicaid programs are increasingly adopting incentive programs to improve health behaviors among beneficiaries. There is limited evidence on what incentives are being offered to Medicaid beneficiaries, how programs are engaging beneficiaries, and how programs are evaluated. In 2017-18 we synthesized available information on these programs and interviewed eighty policy stakeholders to identify the rationale behind key program design decisions and stakeholders' recommendations for beneficiary engagement and program evaluation.

A cluster randomized trial of strategies to increase uptake amongst young women invited for their first cervical screen: The STRATEGIC trial.

Objectives To measure the feasibility and effectiveness of interventions to increase cervical screening uptake amongst young women. Methods A two-phase cluster randomized trial conducted in general practices in the NHS Cervical Screening Programme. In Phase 1, women in practices randomized to intervention due for their first invitation to cervical screening received a pre-invitation leaflet and, separately, access to online booking.

Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination.

A major hallmark of the autoimmune demyelinating disease multiple sclerosis (MS) is immune cell infiltration into the brain and spinal cord resulting in myelin destruction, which not only slows conduction of nerve impulses, but causes axonal injury resulting in motor and cognitive decline. Current treatments for MS focus on attenuating immune cell infiltration into the central nervous system (CNS). These treatments decrease the number of relapses, improving quality of life, but do not completely eliminate relapses so long-term disability is not improved.