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Omalizumab Implementation in Practice: Lessons Learned From the OUtMATCH Study.
J Allergy Clin Immunol Pract
November 2024
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Md.
Article Synopsis
- In February 2024, the FDA approved omalizumab for food allergy treatment, following positive results from the OUtMATCH phase 3 clinical trial.
- The trial showed significant effectiveness in desensitizing patients to multiple allergens, although some participants did not respond and fewer tolerated all three food allergens compared to single ones.
- Clinicians are expected to have questions about patient selection and treatment management, indicating a need for further research to enhance real-world application and ensure high-quality outcomes.
Structural basis of CDNF interaction with the UPR regulator GRP78.
Nat Commun
September 2024
Herantis Pharma Plc, FI-02600, Espoo, Finland.
Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that is a disease-modifying drug candidate for Parkinson's disease. CDNF has pleiotropic protective effects on stressed cells, but its mechanism of action remains incompletely understood. Here, we use state-of-the-art advanced structural techniques to resolve the structural basis of CDNF interaction with GRP78, the master regulator of the unfolded protein response (UPR) pathway.
View Article and Find Full Text PDFIL-4 drives exhaustion of CD8 CART cells.
Nat Commun
September 2024
T Cell Engineering, Mayo Clinic, Rochester, MN, USA.
Durable response to chimeric antigen receptor T (CART) cell therapy remains limited in part due to CART cell exhaustion. Here, we investigate the regulation of CART cell exhaustion with three independent approaches including: a genome-wide CRISPR knockout screen using an in vitro model for exhaustion, RNA and ATAC sequencing on baseline and exhausted CART cells, and RNA and ATAC sequencing on pre-infusion CART cell products from responders and non-responders in the ZUMA-1 clinical trial. Each of these approaches identify interleukin (IL)-4 as a regulator of CART cell dysfunction.
View Article and Find Full Text PDFDuring aging, the spine undergoes degenerative changes, particularly with vertebral endplate bone expansion and sclerosis, that is associated with nonspecific low back pain (LBP). We reported that parathyroid hormone (PTH) treatment could reduce vertebral endplate sclerosis and improve pain behaviors in aging, SM/J and young lumbar spine instability (LSI) mice. Aberrant innervation noted in the vertebral body and endplate during spinal degeneration was reduced with PTH treatment in aging and LSI mice as quantified by PGP9.
View Article and Find Full Text PDFKetone monoester attenuates oxygen desaturation during weighted ruck exercise under acute hypoxic exposure but does not impact cognitive performance.
Exp Physiol
October 2024
Healthspan, Resilience and Performance Research, Florida Institute for Human and Machine Cognition, Pensacola, Florida, USA.
Acute ingestion of exogenous ketone supplements in the form of a (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (R-BD R-βHB) ketone monoester (KME) can attenuate declines in oxygen availability during hypoxic exposure and might impact cognitive performance at rest and in response to moderate-intensity exercise. In a single-blind randomized crossover design, 16 males performed assessments of cognitive performance before and during hypoxic exposure with moderate exercise [2 × 20 min weighted ruck (∼22 kg) at 3.2 km/h at 10% incline] in a normobaric altitude chamber (4572 m, 11.
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