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Anti‐NMDAR encephalitis (NMDARE) is an autoantibody‐mediated disorder characterized by seizures, movement disorders, neurocognitive deficits, and psychosis, but the complete phenotypic heterogeneity, and outcomes are incompletely understood in children. This single‐center retrospective analysis of NMDARE at the largest pediatric hospital in the United States between 2009 and 2024 screened 115 patients diagnosed with NMDARE. 103 had sufficient clinical data available for analyses. Two‐thirds were Hispanic, disproportionate to the Houston metro area demographics, and Hispanic patients had a higher CSF white cell count and antibody titer. Approximately one‐half of the patients with idiopathic NMDARE presented with a focal cortical phenotype that localized to the perisylvian region as initial symptomology, which we describe as a “perisylvian phenotype.” Patients with teratomas had more severe early symptoms, earlier lumbar punctures, higher CSF white cell counts, earlier treatment, and longer hospital durations than HSVE and idiopathic patients. CSF antibody titers directly correlated to hospital length of stay and mRS at presentation through 12‐month follow up, and normal routine CSF studies and brain MRI delayed initiation of first‐line immunotherapy. These novel and corroborating observations serve as the foundation for future studies on early focal neurological deficits (i.e., perisylvian phenotype) that must be addressed by clinicians to prevent delay in care.

Pediatric new drug trials are federally mandated, but family perspectives in multiple sclerosis (MS) research are limited. Due to MS chronicity and long-term medical system involvement, we obtained family views on research priorities and optimized methods for future studies. Focus groups were convened with families impacted by pediatric-onset MS. Recruitment included those followed by the Network of Pediatric MS Centers, geographically disparate locations, and centers’ voluntary election. Study questions included: healthcare experiences, clinical trials perspectives, cognitive/psychosocial/educational outcomes, disease course and disability accrual. All subjects supported future clinical studies. Patients highlighted contribution to knowledge base but were wary of experimental medication and disease-course impeding activities. Parents underscored medication delivery modalities, side-effects, and limiting children’s discomfort. All wanted study relevance made explicit. Suggested future study design elements included: providing compensation, limiting assumptions regarding outcome linkages, understanding study-related psychological impacts, and reducing participation burdens. Rare disease research can assist general medicine diagnosis and referral. Variable study designs and explicit rationale may augment participation. Closing the pediatric research gap requires family engagement in the research process.

ObjectiveThe role of diet in multiple sclerosis (MS) course remains largely unknown. Children with MS have a higher relapse rate compared with MS in adults. Thus, studying the effect of diet on relapse rate in this age group is likely to provide more robust answers.MethodsThis is a multicentre study done at 11 paediatric MS centres in the USA. Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) with disease onset before 18 years of age and duration of less than 4 years were included in this study. Dietary intake during the week before enrolment was assessed with the validated Block Kids Food Screener. The outcome of the study was time from enrolment to the next relapse. 219 patients with paediatric RRMS or CIS were enrolled. Each 10% increase in energy intake from fat increased the hazard of relapse by 56% (adjusted HR 1.56, 95% CI 1.05 to 2.31, p=0.027), and in particular each 10% increase in saturated fat tripled this hazard (adjusted HR: 3.37, 95% CI 1.34 to 8.43, p=0.009). In contrast, each additional one cup equivalent of vegetable decreased the hazard of relapse by 50% (adjusted HR: 0.50, 95% CI 0.27 to 0.91, p=0.024). These associations remained with mutual adjustment and persisted when adjusting for baseline 25(OH) vitamin D serum level. Other studied nutrients were not associated with relapse.ConclusionsThis study suggests that in children with MS, high energy intake from fat, especially saturated fat, may increase the hazard to relapse, while vegetable intake may be independently protective.

BackgroundWe previously reported an association between household chemical exposures and an increased risk of paediatric-onset multiple sclerosis.MethodsUsing a case–control paediatric multiple sclerosis study, gene–environment interaction between exposure to household chemicals and genotypes for risk of paediatric-onset multiple sclerosis was estimated.Genetic risk factors of interest included the two major HLA multiple sclerosis risk factors, the presence of DRB1*15 and the absence of A*02, and multiple sclerosis risk variants within the metabolic pathways of common household toxic chemicals, including IL-6 (rs2069852), BCL-2 (rs2187163) and NFKB1 (rs7665090).Results490 paediatric-onset multiple sclerosis cases and 716 controls were included in the analyses. Exposures to insect repellent for ticks or mosquitos (OR 1.47, 95% CI 1.06 to 2.04, p=0.019), weed control products (OR 2.15, 95% CI 1.51 to 3.07, p<0.001) and plant/tree insect or disease control products (OR 3.25, 95% CI 1.92 to 5.49, p<0.001) were associated with increased odds of paediatric-onset multiple sclerosis. There was significant additive interaction between exposure to weed control products and NFKB1 SNP GG (attributable proportions (AP) 0.48, 95% CI 0.10 to 0.87), and exposure to plant or disease control products and absence of HLA-A*02 (AP 0.56; 95% CI 0.03 to 1.08). There was a multiplicative interaction between exposure to weed control products and NFKB1 SNP GG genotype (OR 2.30, 95% CI 1.00 to 5.30) but not for other exposures and risk variants. No interactions were found with IL-6 and BCL-2 SNP GG genotypes.ConclusionsThe presence of gene–environment interactions with household toxins supports their possible causal role in paediatric-onset multiple sclerosis.

Background As little is known of association(s) between gut microbiota profiles and host immunological markers, we explored these in children with and without multiple sclerosis (MS). Methods Children ≤18 years provided stool and blood. MS cases were within 2-years of onset. Fecal 16S rRNA gene profiles were generated on an Illumina Miseq platform. Peripheral blood mononuclear cells were isolated, and Treg (CD4 + CD25 hi CD127 low FoxP3 + ) frequency and CD4 + T-cell intracellular cytokine production evaluated by flow cytometry. Associations between microbiota diversity, phylum-level abundances and immune markers were explored using Pearson’s correlation and adjusted linear regression. Results Twenty-four children (15 relapsing-remitting, nine controls), averaging 12.6 years were included. Seven were on a disease-modifying drug (DMD) at sample collection. Although immune markers (e.g. Th2, Th17, Tregs) did not differ between cases and controls ( p  > 0.05), divergent gut microbiota associations occurred; richness correlated positively with Th17 for cases ( r  = +0.665, p  = 0.018), not controls ( r  = −0.644, p  = 0.061). Bacteroidetes inversely associated with Th17 for cases ( r  = −0.719, p  = 0.008), not controls ( r  = +0.320, p  = 0.401). Fusobacteria correlated with Tregs for controls ( r  = +0.829, p  = 0.006), not cases ( r  = −0.069, p  = 0.808). Conclusions Our observations motivate further exploration to understand disruption of the microbiota-immune balance so early in the MS course.

Background We previously identified air quality as a risk factor of interest for pediatric multiple sclerosis. The purpose of this study is to more closely examine the association between the six criteria air pollutants and pediatric MS as well as identify specific areas of toxic release using data from the Toxic Release Inventory. Methods Pediatric MS cases (N = 290) and healthy controls (N = 442) were included as part of an ongoing case–control study. We used the National Emissions Inventory system to estimate particulate exposure by county of residence for each participant. Proximity to Toxic Release Inventory (TRI) sites was also assessed using ArcGIS mapping tools. Risk‐Screening Environmental Indicators (RSEI) classified counties at risk to exposure of environmental toxic releases. Results Fine particulate matter (PM2.5), carbon monoxide (CO), sulfur dioxide (SO2), and lead air emissions were associated with increased odds for pediatric MS (P < 0.01) for those residing within 20 miles of an MS center. Most study participants (75%) resided within 5 miles of at least one TRI site; however, the mean total pounds of stack air releases was higher for sites near MS cases (81,000 tons) compared to those near healthy controls (35,000 tons, P = 0.002). Average RSEI scores did not differ significantly between cases and controls. Conclusion Out of several air pollutants examined, we show that fine particulate matter and three other criteria pollutants (SO2, CO, and lead) were statistically associated with higher odds for pediatric MS.

After a long history of overexploitation, increasing efforts to restore marine ecosystems and rebuild fisheries are under way. Here, we analyze current trends from a fisheries and conservation perspective. In 5 of 10 well-studied ecosystems, the average exploitation rate has recently declined and is now at or below the rate predicted to achieve maximum sustainable yield for seven systems. Yet 63% of assessed fish stocks worldwide still require rebuilding, and even lower exploitation rates are needed to reverse the collapse of vulnerable species. Combined fisheries and conservation objectives can be achieved by merging diverse management actions, including catch restrictions, gear modification, and closed areas, depending on local context. Impacts of international fleets and the lack of alternatives to fishing complicate prospects for rebuilding fisheries in many poorer regions, highlighting the need for a global perspective on rebuilding marine resources.

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.

Elucidating the sites and mechanisms of sRAGE action in the healthy state is vital to better understand the biological importance of the receptor for advanced glycation end products (RAGE). Previous studies in animal models of disease have demonstrated that exogenous sRAGE has an anti-inflammatory effect, which has been reasoned to arise from sequestration of pro-inflammatory ligands away from membrane-bound RAGE isoforms. We show here that sRAGE exhibits in vitro binding with high affinity and reversibly to extracellular matrix components collagen I, collagen IV, and laminin. Soluble RAGE administered intratracheally, intravenously, or intraperitoneally, does not distribute in a specific fashion to any healthy mouse tissue, suggesting against the existence of accessible sRAGE sinks and receptors in the healthy mouse. Intratracheal administration is the only effective means of delivering exogenous sRAGE to the lung, the organ in which RAGE is most highly expressed; clearance of sRAGE from lung does not differ appreciably from that of albumin.

Biomass from cellulosic bioenergy crops is expected to play a substantial role in future energy systems, especially if climate policy aims at stabilizing greenhouse gas concentration at low levels. However, the potential of bioenergy for climate change mitigation remains unclear due to large uncertainties about future agricultural yield improvements and land availability for biomass plantations. This letter, by applying a modelling framework with detailed economic representation of the land and energy sector, explores the cost-effective contribution of bioenergy to a low-carbon transition, paying special attention to implications for the land system. In this modelling framework, bioenergy competes directly with other energy technology options on the basis of costs, including implicit costs due to biophysical constraints on land and water availability. As a result, we find that bioenergy from specialized grassy and woody bioenergy crops, such as Miscanthus or poplar, can contribute approximately 100 EJ in 2055 and up to 300 EJ of primary energy in 2095. Protecting natural forests decreases biomass availability for energy production in the medium, but not in the long run. Reducing the land available for agricultural use can partially be compensated for by means of higher rates of technological change in agriculture. In addition, our trade-off analysis indicates that forest protection combined with large-scale cultivation of dedicated bioenergy is likely to affect bioenergy potentials, but also to increase global food prices and increase water scarcity. Therefore, integrated policies for energy, land use and water management are needed.