Endothelial Cell-Derived Soluble CD200 Determines the Ability of Immune Cells to Cross the Blood-Brain Barrier.

The infiltration of immune cells into the central nervous system mediates the development of autoimmune neuroinflammatory diseases. We previously showed that the loss of either Fabp5 or calnexin causes resistance to the induction of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of multiple sclerosis (MS). Here we show that brain endothelial cells lacking either Fabp5 or calnexin have an increased abundance of cell surface CD200 and soluble CD200 (sCD200) as well as decreased T-cell adhesion. In a tissue culture model of the blood-brain barrier, antagonizing the interaction of CD200 and sCD200 with T-cell CD200 receptor (CD200R1) via anti-CD200 blocking antibodies or the RNAi-mediated inhibition of CD200 production by endothelial cells increased T-cell adhesion and transmigration across monolayers of endothelial cells. Our findings demonstrate that sCD200 produced by brain endothelial cells regulates immune cell trafficking through the blood-brain barrier and is primarily responsible for preventing activated T-cells from entering the brain.

Neurologic Complications in Hereditary Hemorrhagic Telangiectasia with Pulmonary Arteriovenous Malformations: A Systematic Review.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant multi-organ condition occurring with a 1 in 3800 prevalence in Alberta. This genetic disorder leads to vascular malformations in different organs including the lungs and brain, commonly affecting pulmonary vasculature leading to pulmonary arteriovenous malformations (PAVMs). PAVMs lead to right-to-left shunts, which may be associated with neurologic complications. We aimed to evaluate and summarize the reported neurologic manifestations of individuals with HHT with pre-existing PAVMs. METHODS: We performed a qualitative systematic review to determine available literature on neurological complications among patients with PAVMs and HHT. Published studies included observational studies, case studies, prospective studies, and cohort studies including search terms HHT, PAVMs, and various neurologic complications using MEDLINE and EMBASE. RESULTS: A total of 449 manuscripts were extracted including some duplicates of titles, abstracts, and text which were screened. Following this, 23 publications were identified for inclusion in the analysis. Most were case reports (n = 15). PAVMs were addressed in all these articles in association with various neurological conditions ranging from cerebral abscess, ischemic stroke, hemorrhagic stroke, embolic stroke, and migraines. CONCLUSION: Although HHT patients with PAVMs are at risk for a variety of neurological complications compared to those without PAVMs, the quality and volume of evidence characterizing this association is low. Individuals with PAVMs have a high prevalence of neurological manifestations such as cerebral abscess, transient ischemic attack, cerebral embolism, hemorrhage, and stroke. Mitigating stroke risk by implementing proper standardized screening techniques for PAVMs is invaluable in preventing increased mortality.

Magnesium Cobaltite Embedded in Corncob-Derived Nitrogen-Doped Carbon as a Cathode Catalyst for Power Generation in Microbial Fuel Cells.

Microbial fuel cells (MFCs) have drawn attention among renewable energy devices. High capital cost, poor durability, and slow oxygen reduction reaction (ORR) kinetics are the major hindrances in the commercialization of the technology. In this work, an environmentally benign approach is followed to synthesize a composite of magnesium cobaltite (MgCo2O4) embedded in nitrogen-doped carbon to optimize the performance of MFCs. Detailed characterization confirms the formation of MgCo2O4 nanostructures in the catalyst treated at 700 °C. Electrochemical studies suggest the superior performance of the MgCo2O4/NC-700 catalyst with a peak reduction current of -0.068 mA and a charge transfer resistance (Rct) of 40.5 Ω. The performance of the air cathodes is evaluated using activated sludge as inoculum in the anode chamber in single-chamber MFCs. The power output of MFC with MgCo2O4/NC-700 as an air cathode reaching 873.81 mW m-2 is 59.56 and 216.05% higher than those of MFCs with Pt/C (547.65 mW m-2) and Co/NC-700 (276.48 mW m-2) cathodes, respectively. These findings suggest that substituting magnesium in transition metal-nitrogen-carbon composites could help realize long-term application as air cathodes for power generation and wastewater treatment in MFCs.

Copper nanoparticles embedded in polyaniline derived nitrogen-doped carbon as electrocatalyst for bio-energy generation in microbial fuel cells.

Microbial fuel cells (SC-MFCs) have emerged as green energy devices to resolve the growing energy and environmental crisis. However, the technology's application depends on the sluggish oxygen reduction reaction (ORR) kinetics. Among the electrocatalysts explored, transition metal-nitrogen-carbon composites exhibit satisfactory ORR activity. Herein, we investigate the performance of copper-nitrogen-carbon (Cu/NC) electrocatalysts for ORR, highlighting the effect of temperature, role of nitrogen functionalities, and Cu-Nx sites in catalyst performance. Cu/NC-700 demonstrated satisfactory ORR activity with an onset potential of 0.7 V (vs. RHE) and a limiting current density of 3.4 mA cm-2. Cu/NC-700 modified MFC exhibited a maximum power density of 489.2 mW m-2, higher than NC-700 (107.3 mW m-2). These observations could result from synergistic interaction between copper and nitrogen atoms, high density of Cu-Nx sites, and high pyridinic-N content. Moreover, the catalyst exhibited superior stability, implying its use in long-term operations. The electrocatalytic performance of the catalyst suggests that copper-doped carbon catalysts could be potential metal-nitrogen-carbon material for scaled-up MFC applications.

Limited Utility of Chemotherapy for Pulmonary Langerhans Cell Histiocytosis Due to Unclear Diagnostic Criteria.

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease that affects young adults and is typically misdiagnosed or presents concurrently with more common respiratory conditions such as asthma or chronic obstructive lung disease (COPD). A combination of imaging, tissue biopsy, and clinical presentation is used for diagnosis since no definitive criteria have been established. Current standards are based on vague descriptors such as clustering of histologic markers but lack quantitative analysis. In this case report, we present a patient who was initially diagnosed with PLCH, but the lack of unanimity for diagnostic requirements led to conflicting diagnoses between institutions which may have prevented optimal care for the patient. The disparity limited new, alternative therapies for our patient that may have been beneficial since he was clinically not improving with smoking cessation and standard of care for obstructive lung diseases. However, quantitative endorsements for tissue analysis, such as requiring more than 30 Cd-1a stained Langerhans cells per high power field (HPF), may reduce discrepancies associated with current techniques. It is imperative that clear standards are established due to the unique treatment these patients require that is atypical from other pulmonary diseases such as asthma and COPD. New chemotherapeutic regimens such as cladribine and vemurafenib require oncologic care and have more broad side effects than typical pulmonary treatments, which emphasize the need for accurate diagnoses before starting treatment. Existing standards have created circumstances where PLCH is a differential but cannot be ruled out due to unclear criteria and limited research.