Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic α-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by α-syn preformed fibrils (PFF).
View Article and Find Full Text PDFUnlabelled: Intravenous (IV) vitamin C improves organ function and reduces inflammation in sepsis, an inflammatory state like the post-hematopoietic stem cell transplant (HCT) milieu. The safety and efficacy of parenteral vitamin C after allogeneic HCT were evaluated in a phase I/II trial. Clinical outcomes were compared with a propensity score - matched historical control.
View Article and Find Full Text PDFUnlabelled: Intravenous (IV) vitamin C improves organ function and reduces inflammation in sepsis, an inflammatory state like the post-hematopoietic stem cell transplant (SCT) milieu. The safety and efficacy of parenteral vitamin C after allogeneic hematopoietic stem cell transplant (HSCT) were evaluated in a phase I/II trial and clinical outcomes compared with a propensity score - matched historical control.
Methods: Patients with advanced hematologic malignancies were enrolled in a phase 2 clinical trial, receiving IV vitamin C, 50mg/kg/d, divided into 3 doses given on days 1-14 after HSCT, followed by 500 mg bid oral from day 15 until 6 months post-SCT.
Synucleinopathies are a set of devastating neurodegenerative diseases that share a pathologic accumulation of the protein α-synuclein (α-syn). This accumulation causes neuronal death resulting in irreversible dementia, deteriorating motor symptoms, and devastating cognitive decline. While the etiology of these conditions remains largely unknown, microglia, the resident immune cells of the central nervous system (CNS), have been consistently implicated in the pathogenesis of synucleinopathies.
View Article and Find Full Text PDFPurpose: To evaluate baseline characteristics, microbiological spectrum, management, and outcomes of patients with culture-proven fungal keratitis.
Methods: Retrospective review of all patients with culture-proven fungal keratitis seen over 6 years at a tertiary referral center.
Results: The present study included 62 eyes from 62 patients.
Neutralizing antibody responses gradually wane against several variants of concern (VOCs) after vaccination with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine messenger RNA-1273 (mRNA-1273). We evaluated the immune responses in nonhuman primates that received a primary vaccination series of mRNA-1273 and were boosted about 6 months later with either homologous mRNA-1273 or heterologous mRNA-1273.β, which encompasses the spike sequence of the B.
View Article and Find Full Text PDFUnlabelled: Neutralizing antibody responses gradually wane after vaccination with mRNA-1273 against several variants of concern (VOC), and additional boost vaccinations may be required to sustain immunity and protection. Here, we evaluated the immune responses in nonhuman primates that received 100 µg of mRNA-1273 vaccine at 0 and 4 weeks and were boosted at week 29 with mRNA-1273 (homologous) or mRNA-1273.β (heterologous), which encompasses the spike sequence of the B.
View Article and Find Full Text PDFB.1.351 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant most resistant to antibody neutralization.
View Article and Find Full Text PDFAggregation of misfolded α-synuclein (α-syn) is the major component of Lewy bodies and neurites in Parkinson's disease (PD) and related α-synucleinopathies. Some α-syn mutations (e.g.
View Article and Find Full Text PDFPurpose: To determine the prevalence and reasons for delays in diagnosis in patients with Acanthamoeba keratitis (AK) presenting to Wilmer Eye Institute, Baltimore, Maryland.
Methods: This retrospective study analysed all patients with culture-positive AK seen between 2012 and 2019 at a tertiary referral centre. Patient demographic information, clinical history, risk factors, symptom duration, referral patterns, slit lamp examination findings, visual acuity and need for surgery were collected.