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Neuromodulation via Responsive Neurostimulation (RNS) or Deep Brain Stimulation (DBS) is an emerging treatment strategy for pediatric drug-resistant epilepsy (DRE). Knowledge gaps exist in patient selection, surgical technique, and perioperative care. Here, we use an expert survey to clarify practices. Thirty-two members of the Pediatric Epilepsy Research Consortium were surveyed using REDCap. Respondents were from 17 pediatric epilepsy centers (missing data in one): Four centers implant RNS only while 13 implant both RNS and DBS. Thirteen RNS programs commenced in or before 2020, and 10 of 12 DBS programs began thereafter. The busiest six centers implant 6-10 new RNS devices per year; all DBS programs implant 50%) was reported by 81% (13/16) of centers. RNS and DBS are rapidly evolving treatment modalities for safe and effective treatment of pediatric DRE. There is increasing interest in multicenter collaboration to gain knowledge and facilitate dialogue. PLAIN LANGUAGE SUMMARY: We surveyed 32 pediatric epilepsy centers in USA to highlight current practices of intracranial neuromodulation. Of the 17 that replied, we found that most centers are implanting thalamic targets in pediatric drug-resistant epilepsy using the RNS device. DBS device is starting to be used in pediatric epilepsy, especially after 2020. Different strategies for target identification are enumerated. This study serves as a starting point for future collaborative research.

Introduction: Mushroom toxicity is an important etiology of acute liver injury in a patient with gastrointestinal symptoms.Case Report: We present the case of a male patient presenting to the emergency department (ED) with gastrointestinal distress who was placed under ED observation for elevated liver function tests. During his hospital course, it was revealed he had consumed wild mushrooms believed to be Amanita phalloides.Conclusion: While mushroom ingestion and subsequent toxicity are rare, a high index of suspicion in foraging hobbyists is essential to arriving at the correct diagnosis and directing the patient to the appropriate management.

Abstract Following the approval of Epidiolex® (cannabidiol; CBD) for the treatment of seizures associated with Lennox–Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC), healthcare professionals (HCPs) have had substantial experience in treating patients with Epidiolex. However, confusion still remains among HCPs, caregivers, and patients regarding dosing, drug interactions, safety monitoring, and differentiation between Epidiolex and nonapproved CBD products. To establish consensus recommendations for Epidiolex treatment optimization in LGS, DS, and TSC, a panel of seven HCPs with expertise in epilepsy was convened. Panelists participated in a premeeting survey based on a literature review of Epidiolex for the treatment of LGS, DS, and TSC, and survey responses were compiled for discussion. A modified Delphi method was used to assess agreement among panelists regarding recommendation statements following two rounds of discussion. Panelists identified two broad themes – overcoming barriers to initiation and optimization of treatment for seizures associated with LGS, DS, and TSC – for consensus guidelines. Accurate identification of patients with these rare epilepsies is critical for optimization of Epidiolex treatment. Providers should differentiate Epidiolex from nonapproved CBD products and set expectations for the therapeutic effect and safety/tolerability of Epidiolex. Initial target dose and titration rate should be individualized by baseline variables, prior response to antiseizure medications, and therapeutic goals. Awareness of strategies to manage adverse events and concomitant medications, including drug–drug interactions, is critical. Tracking response to the maximum tolerated dose is an important measure of effectiveness. These consensus recommendations provide real‐world experience from neurology HCPs with experience in prescribing Epidiolex and can inform optimal use of Epidiolex for the treatment of seizures associated with LGS, DS, and TSC. Plain language summary Epidiolex® (cannabidiol) is approved for treating seizures in Lennox–Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. Although healthcare professionals have experience in treating patients with Epidiolex, there is a need for better understanding of dosing, drug interactions, and safety of this drug. Therefore, a group of epilepsy experts developed guidelines for best practices in Epidiolex treatment. Two main areas were identified: overcoming barriers to starting Epidiolex and considerations related to Epidiolex dosing. Within these areas, topics, including correct disease identification, managing adverse events, and determining individualized dose, were discussed. These guidelines provide real‐world experience to inform optimal Epidiolex use.

Abstract Efficient detection of the magnetic state is a critical step towards useful antiferromagnet-based spintronic devices. Recently, finite tunneling magnetoresistance (TMR) has been demonstrated in tunnel junctions with antiferromagnetic electrodes, however, these studies have been mostly limited to junctions with two identical antiferromagnet (AFM) electrodes, where the matching of the spin-split Fermi surfaces played critical role. It remains unclear if AFMs can provide a finite net spin polarization, and hence be used as a spin polarizer or detector. In this work, we experimentally fabricate single-sided antiferromagnetic tunnel junctions consisting of one AFM electrode (Mn3Sn) and one ferromagnet (FM) electrode (CoFeB), where the spin polarized tunneling transport from AFM is detected by the FM layer. We observe a high TMR at cryogenic temperature (>100% at 10 K) in these asymmetric AFM tunnel junctions, suggesting a large effective spin polarization from Mn3Sn despite its nearly vanishing magnetization. The large TMR is consistent with recent theoretical studies where the broken symmetry in non-collinear AFMs is predicted to lift the spin degeneracy in the band structure. Our work provides strong evidence that spin polarized electrical transport can be achieved from AFMs.

Using data from 11 institutions, the authors investigate enrollments in intermediate microeconomics to determine characteristics of successful and unsuccessful students and follow the retake behavior of unsuccessful students. Successful students are significantly different from unsuccessful ones, and unsuccessful students differ by type (unsuccessful completers vs. withdrawers). Aptitude is a strong predictor of success but not of retake. Having taken or concurrently taking intermediate macro reduces the likelihood of withdrawal and increases that of retake. Proficiency in calculus reduces the likelihood of unsuccessful completion but is uncorrelated with withdrawal and retake. Predictors of unsuccessful completion, withdrawal, and retake are similar in direction and significance for males and females, although magnitudes differ. URM students are more likely than white and Asian students to earn less than a C-.

This article's authors use student transcript data to identify differences in the study of economics among Black students at HBCUs and PWIs. The data show that a higher fraction of Black students at HBCUs initially intend to study economics, relative to those at PWIs (4.0% vs. 1.3% of micro principles enrollees) and persist in the major (9.4% vs. 3.8%). Logit analysis suggests that (1) academically stronger Black students are less likely to persist to an economics degree at both institution types and (2) Black female students at HBCUs are as equally likely to persist to a degree in economics as their male counterparts while those at PWIs are less likely to persist. Additional research is needed to determine the causal factors responsible for these outcomes.

Abstract Background Colonic diverticulosis, the most common lesion found in routine colonoscopy, affects more than 50% of individuals aged ≥ 60 years. Emerging evidence suggest that dysbiosis of gut microbiota may play an important role in the pathophysiology of diverticular disease. However, specific changes in microbial species and metabolic functions in asymptomatic diverticulosis remain unknown. Methods In a cohort of US adults undergoing screening colonoscopy, we analyzed the gut microbiota using shotgun metagenomic sequencing. Demographic factors, lifestyle, and medication use were assessed using a baseline questionnaire administered prior to colonoscopy. Taxonomic structures and metabolic pathway abundances were determined using MetaPhlAn3 and HUMAnN3. We used multivariate association with linear models to identify microbial species and metabolic pathways that were significantly different between asymptomatic diverticulosis and controls, while adjusting for confounders selected a priori including age at colonoscopy, sex, body mass index (BMI), and dietary pattern. Results Among 684 individuals undergoing a screening colonoscopy, 284 (42%) had diverticulosis. Gut microbiome composition explained 1.9% variation in the disease status of asymptomatic diverticulosis. We observed no significant differences in the overall diversity of gut microbiome between asymptomatic diverticulosis and controls. However, microbial species Bifidobacterium pseudocatenulatum and Prevotella copri were significantly enriched in controls (q value = 0.19 and 0.14, respectively), whereas Roseburia intestinalis, Dorea sp. CAG:317, and Clostridium sp. CAG: 299 were more abundant in those with diverticulosis (q values = 0.17, 0.24, and 0.10, respectively). We observed that the relationship between BMI and diverticulosis appeared to be limited to carriers of Bifidobacterium pseudocatenulatum and Roseburia intestinalis (P interaction = 0.09). Conclusions Our study provides the first large-scale evidence supporting taxonomic and functional shifts of the gut microbiome in individuals with asymptomatic diverticulosis. The suggestive interaction between gut microbiota and BMI on prevalent diverticulosis deserves future investigations.

Abstract Objective To evaluate the Refractory Epilepsy Screening Tool for Lennox–Gastaut Syndrome (REST‐LGS) for real‐world identification of LGS in adults and to develop a scoring system for the tool. Methods A retrospective chart review of adults with drug resistant epilepsy (DRE) and intellectual development disorder (IDD) was conducted by 2 primary care providers blinded to diagnosis. The REST‐LGS was designed via the Modified Delphi Consensus and was previously validated. This tool consists of 8 criteria (4 major, 4 minor) considered indicative of LGS. To account for missing data in the earlier validation study and to evaluate applicability in a real‐world setting, the REST‐LGS was refined to include a scoring system in which major criteria were more heavily weighted than minor criteria, producing categories of “likely” (>11 points), “possible” (8–11 points), and “unlikely” (

Abstract Background Sudden unexpected death in epilepsy (SUDEP) is the most common cause of epilepsy‐related mortality. Although most witnessed SUDEPs follow seizures, mechanisms are uncertain. Investigations into the pathophysiology of SUDEP have relied on models and rare recordings of brain function at the time of the event. The brain‐responsive neurostimulation (RNS) device from Neuropace offers a therapeutic option for drug‐refractory epilepsy (DRE), enabling the recording of brain activity and the preemptive termination of seizures. Therefore, patients who experience SUDEP while being treated with an RNS device can provide insights into neural activity at the moment of this event. Objective We report the history and electrocorticographic (ECoG) recordings of a patient with DRE who experienced SUDEP years after RNS placement. Patient History A girl with Phelan–McDermid syndrome and Lennox–Gastaut syndrome had an RNS device implanted at the age of 14 to treat DRE. Initially, electrodes were positioned in the right orbitofrontal (OF) and right premotor frontal regions, with the OF lead later changed to the centromedian thalamic nucleus. At age 19, the patient was found unconscious and in cardiac arrest by her parents. Although spontaneous circulation returned en route to the hospital, the patient did not regain consciousness and died. Subsequent analysis of ECoGs from RNS recordings at the time of death indicated seizure onset in the right premotor frontal cortex, which persisted despite seizure termination attempts by the RNS. Conclusions We present a patient with SUDEP associated with the onset of RNS‐refractory seizures. The significance of this report is highlighted by the rarity of literature on neuronal function at the time of SUDEP. Moreover, it underscores the potential for devices capable of monitoring ECoG activity to shed light on the mechanisms underlying SUDEP and to inform interventions.

Abstract Bacterial contamination is the most prevalent infectious complication of blood transfusion in the developed world. To mitigate this, several ultraviolet light-based pathogen reduction technologies (PRTs), some of which require photo-chemicals, have been developed to minimize infection transmission. Relative to UV light, visible 405-nm light is safer and has shown potential to be developed as a PRT for the in situ treatment of ex vivo human plasma and platelet concentrates, without the need for photo-chemicals. This study investigates the effect of 405-nm light on human plasma, with focus on the compatibility of antimicrobial light doses with essential plasma clotting factors. To determine an effective antimicrobial dose that is compatible with plasma, prebagged human plasma (up to 300 mL) was seeded with common microbial contaminants and treated with increasing doses of 405-nm light (16 mW cm−2; ≤ 403 J cm−2). Post-exposure plasma protein integrity was investigated using an AOPP assay, in vitro coagulation tests, and ELISA-based measurement of fibrinogen and Protein S. Microbial contamination in 300 mL prebagged human plasma was significantly reduced (P ≤ 0.05) after exposure to ≤ 288 J cm−2, with microbial loads reduced by > 96.2%. This dose did not significantly affect the plasma protein quality parameters tested (P > 0.05). Increased doses (≥ 345 J cm−2) resulted in a 4.3% increase in clot times with no statistically significant change in protein activity or levels. Overall, this study has demonstrated that the effective microbicidal 405 light dose shows little to no negative effect on plasma quality.

In this feature, Rob Jenkins, Public Policy Fellow at the Wilson Center, speaks with Nimo Hassan, Executive Director of the Somali NGO Consortium and Board Chair of the International Council [...]

Abstract Neuromodulation via Responsive Neurostimulation (RNS) or Deep Brain Stimulation (DBS) is an emerging treatment strategy for pediatric drug‐resistant epilepsy (DRE). Knowledge gaps exist in patient selection, surgical technique, and perioperative care. Here, we use an expert survey to clarify practices. Thirty‐two members of the Pediatric Epilepsy Research Consortium were surveyed using REDCap. Respondents were from 17 pediatric epilepsy centers (missing data in one): Four centers implant RNS only while 13 implant both RNS and DBS. Thirteen RNS programs commenced in or before 2020, and 10 of 12 DBS programs began thereafter. The busiest six centers implant 6–10 new RNS devices per year; all DBS programs implant 50%) was reported by 81% (13/16) of centers. RNS and DBS are rapidly evolving treatment modalities for safe and effective treatment of pediatric DRE. There is increasing interest in multicenter collaboration to gain knowledge and facilitate dialogue. Plain language summary We surveyed 32 pediatric epilepsy centers in USA to highlight current practices of intracranial neuromodulation. Of the 17 that replied, we found that most centers are implanting thalamic targets in pediatric drug‐resistant epilepsy using the RNS device. DBS device is starting to be used in pediatric epilepsy, especially after 2020. Different strategies for target identification are enumerated. This study serves as a starting point for future collaborative research.

BackgroundChronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are characterized by shared exposures and clinical features, but distinct genetic and pathologic features exist. These features have not been well-studied using large-scale gene expression datasets. We hypothesized that there are divergent gene, pathway, and cellular signatures between COPD and IPF.MethodsWe performed RNA-sequencing on lung tissues from individuals with IPF (n = 231) and COPD (n = 377) compared to control (n = 267), defined as individuals with normal spirometry. We grouped the overlapping differential expression gene sets based on direction of expression and examined the resultant sets for genes of interest, pathway enrichment, and cell composition. Using gene set variation analysis, we validated the overlap group gene sets in independent COPD and IPF data sets.ResultsWe found 5010 genes differentially expressed between COPD and control, and 11,454 genes differentially expressed between IPF and control (1% false discovery rate). 3846 genes overlapped between IPF and COPD. Several pathways were enriched for genes upregulated in COPD and downregulated in IPF; however, no pathways were enriched for genes downregulated in COPD and upregulated in IPF. There were many myeloid cell genes with increased expression in COPD but decreased in IPF. We found that the genes upregulated in COPD but downregulated in IPF were associated with lower lung function in the independent validation cohorts.ConclusionsWe identified a divergent gene expression signature between COPD and IPF, with increased expression in COPD and decreased in IPF. This signature is associated with worse lung function in both COPD and IPF.

Introduction: Mushroom toxicity is an important etiology of acute liver injury in a patient with gastrointestinal symptoms. Case Report: We present the case of a male patient presenting to the emergency department (ED) with gastrointestinal distress who was placed under ED observation for elevated liver function tests. During his hospital course, it was revealed he had consumed wild mushrooms believed to be Amanita phalloides. Conclusion: While mushroom ingestion and subsequent toxicity are rare, a high index of suspicion in foraging hobbyists is essential to arriving at the correct diagnosis and directing the patient to the appropriate management.

Abstract Bovine tuberculosis is an infectious disease of global significance that remains endemic in many countries. Mycobacterium bovis infection in cattle is characterized by a cell-mediated immune response (CMI) that precedes humoral responses, however the timing and trajectories of CMI and antibody responses determined by newer generation assays remain undefined. Here we used defined-antigen interferon-gamma release assays (IGRA) and an eleven-antigen multiplex ELISA (Enferplex TB test) alongside traditional tuberculin-based IGRA and IDEXX M. bovis antibody tests to assess immune trajectories following experimental M. bovis infection of cattle. The results show CMI responses developed as early as two-weeks post-infection, with all infected cattle testing positive three weeks post-infection. Interestingly, 6 of 8 infected animals were serologically positive with the Enferplex TB assay as early as 4 weeks post-infection. As expected, application of the tuberculin skin test enhanced subsequent serological reactivity. Infrequent M. bovis faecal shedding was observed but was uncorrelated with observed immune trajectories. Together, the results show that early antibody responses to M. bovis infection are detectable in some individuals and highlight an urgent need to identify biomarkers that better predict infection outcomes, particularly for application in low-and-middle income countries where test-and-slaughter based control methods are largely unfeasible.

Background: Cell-based therapies for drug-resistant epilepsy using induced pluripotent stem cell-derived inhibitory interneurons are now in early-phase clinical trials, building on findings from trials in Parkinson’s disease (PD) and Huntington’s disease (HD). Graft rejection and the need for immunosuppressive therapy post-transplantation pose potential barriers to more epilepsy patients becoming potential candidates for inhibitory interneurons transplantation surgery. Objectives: The present literature review weighs the evidence for and against human leukocyte antigen (HLA)-mediated graft rejection in PD and HD and examines the potential advantages and drawbacks to five broad approaches to cell-based therapies, including autologous cell culture and transplantation, in vivo reprogramming of glial cells using viral vectors, allogeneic transplantation using off-the-shelf cell lines, transplantation using inhibitory interneurons cultured from HLA-matched cell lines, and the use of hypoimmunogenic-induced pluripotent stem cell-derived inhibitory interneurons. The impact of surgical technique and associated needle trauma on graft rejection is also discussed. Methods: Non-systematic literature review. Results: While cell-based therapies have enjoyed early successes in treating a host of central nervous system disorders, the immunologic reaction against surgical procedures and implanted materials has remained a major obstacle. Conclusions: Adapting cell-based therapies using iPSC-derived inhibitory interneurons for epilepsy surgery will similarly require surmounting the challenge of immunogenicity.

Anophthalmia and microphthalmia (A/M) are rare birth defects affecting up to 2 per 10,000 live births. These conditions are manifested by the absence of an eye or reduced eye volumes within the orbit leading to vision loss. Although clinical case series suggest a strong genetic component in A/M, few systematic investigations have been conducted on potential genetic contributions owing to low population prevalence. To overcome this challenge, we utilized DNA samples and data collected as part of the National Birth Defects Prevention Study (NBDPS). The NBDPS employed multi-center ascertainment of infants affected by A/M. We performed exome sequencing on 67 family trios and identified numerous genes affected by rare deleterious nonsense and missense variants in this cohort, including de novo variants. We identified 9 nonsense changes and 86 missense variants that are absent from the reference human population (Genome Aggregation Database), and we suggest that these are high priority candidate genes for A/M. We also performed literature curation, single cell transcriptome comparisons, and molecular pathway analysis on the candidate genes and performed protein structure modeling to determine the potential pathogenic variant consequences on PAX6 in this disease.

Past survey evidence shows little change in how economists teach, but the pandemic forced change upon faculty. This survey investigates what that change looked like, whether faculty feel that the changes were for the better or worse for themselves and their students, and what changes faculty will continue post-pandemic.