Acid sphingomyelinase deficiency (ASMD) is a rare progressive genetic disorder caused by pathogenic variants in the gene causing low or absent activity of the enzyme acid sphingomyelinase, resulting in subsequent accumulation of its substrate, sphingomyelin. Signs and symptoms of excessive lysosomal sphingomyelin storage, such as hepatosplenomegaly and pulmonary impairment, and in a subset of patients, progressive neurological manifestations, have long been recognized as hallmarks of the disease. Uncontrolled accumulation of sphingomyelin has important and complex downstream metabolic and immunologic consequences that contribute to the disease burden.
View Article and Find Full Text PDFGeneral anesthesia induces a reversible loss of consciousness (LOC), a state that is characterized by the inability to feel pain. Identifying LOC in animals poses unique challenges, because the method most commonly used in humans, responding to questions, cannot be used in animals. For over a century, loss of righting reflex (LORR) has been used to assess LOC in animals.
View Article and Find Full Text PDFDue to global climate change resulting in extreme temperature fluctuations, it becomes increasingly necessary to explore the natural genetic variation in model crops such as rice to facilitate the breeding of climate-resilient cultivars. To uncover genomic regions in rice involved in managing cold stress tolerance responses and to identify associated cold tolerance genes, two inbred line populations developed from crosses between cold-tolerant and cold-sensitive parents were used for quantitative trait locus (QTL) mapping of two traits: degree of membrane damage after 1 week of cold exposure quantified as percent electrolyte leakage (EL) and percent low-temperature seedling survivability (LTSS) after 1 week of recovery growth. This revealed four EL QTL and 12 LTSS QTL, all overlapping with larger QTL regions previously uncovered by genome-wide association study (GWAS) mapping approaches.
View Article and Find Full Text PDFBackground: The contribution of artefenomel to the clinical and parasiticidal activity of ferroquine and artefenomel in combination in uncomplicated Plasmodium falciparum malaria was investigated.
Methods: This Phase 2a, randomized, open-label, parallel-group study was conducted from 11th September 2018 to 6th November 2019 across seven centres in Benin, Burkina Faso, Gabon, Kenya, and Uganda. Patients aged ≥ 14-69 years with microscopically confirmed infection (≥ 3000 to ≤ 50,000 parasites/µL blood) were randomized 1:1:1:1 to 400 mg ferroquine, or 400 mg ferroquine plus artefenomel 300, 600, or 1000 mg, administered as a single oral dose.
Background: Monoclonal antibodies targeting IgE, interleukin-4 and -13, and interleukin-5 are effective in treating severe type 2 asthma, but new targets are needed. Itepekimab is a new monoclonal antibody against the upstream alarmin interleukin-33. The efficacy and safety of itepekimab as monotherapy, as well as in combination with dupilumab, in patients with asthma are unclear.
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