Neurological Biomarker Profiles in Royal Canadian Air Force (RCAF) Pilots and Aircrew.

Background/objectives: Military aviators can be exposed to extreme physiological stressors, including decompression stress, G-forces, as well as intermittent hypoxia and/or hyperoxia, which may contribute to neurobiological dysfunction/damage. This study aimed to investigate the levels of neurological biomarkers in military aviators to assess the potential risk of long-term brain injury and neurodegeneration.

Methods: This cross-sectional study involved 48 Canadian Armed Forces (CAF) aviators and 48 non-aviator CAF controls.

Effects of an Extreme Weather Event on Primate Populations.

Objectives: With contemporary, human-induced climate change at a crisis point, extreme weather events (e.g., cyclones, heatwaves, floods) are becoming more frequent, intense, and difficult to predict.

Blood-based diagnosis of pediatric tuberculosis: a prospective cohort study in South Africa and Dominican Republic.

Objectives: Pediatric tuberculosis (TB) diagnosis is complicated by challenges in obtaining invasive respiratory specimens that frequently contain few Mycobacterium tuberculosis (Mtb) bacilli. We report the diagnostic performance of an Mtb antigen-derived peptide (MAP-TB) assay and its ability to monitor TB treatment response.

Methods: Study cohorts enrolled children who presented with presumptive TB at two hospitals in South Africa from 2012 to 2017 (157 children aged <13 years) and at community-based clinics in the Dominican Republic from 2019 to 2023 (101 children aged <18 years).

In situ staining with antibodies cross-reactive in pigs, cattle, and white-tailed deer facilitates understanding of biological tissue status and immunopathology.

Identifying cellular markers within archived formalin-fixed, paraffin-embedded (FFPE) tissues is critical for understanding tissue landscapes impacting animal health, but in situ detection methods are limited in veterinary species by a restricted toolbox of species-compatible immunoreagents. We identify antibodies with conserved in situ reactivity to IBA-1 (macrophages/dendritic cells), CD3ε (T cells), Pax5 (B cells), Ki-67 (cycling cells), and cytokeratin type I/II (epithelial cells) in FFPE tissues of pigs, cattle, and white-tailed deer. Multiplexed brightfield detection (IBA-1/CD3ε/Pax5) in lymph nodes of all three species demonstrated species-specific and species-conserved features of cellular architecture.

Structure-Based Discovery and Development of Highly Potent Dihydroorotate Dehydrogenase Inhibitors for Malaria Chemoprevention.

Malaria remains a serious global health challenge, yet treatment and control programs are threatened by drug resistance. Dihydroorotate dehydrogenase (DHODH) was clinically validated as a target for treatment and prevention of malaria through human studies with DSM265, but currently no drugs against this target are in clinical use. We used structure-based computational tools including free energy perturbation (FEP+) to discover highly ligand efficient, potent, and selective pyrazole-based DHODH inhibitors through a scaffold hop from a pyrrole-based series.