The Henry M. Jackson Foundation

Identification of the diverse animal hosts responsible for spill-over events from animals to humans is crucial for comprehending the transmission patterns of emerging infectious diseases, which pose significant public health risks. To better characterize potential animal hosts of Lassa virus (LASV), we assessed domestic and non-domestic animals from 2021-2022 in four locations in southern Nigeria with reported cases of Lassa fever (LF). Birds, lizards, and domestic mammals (dogs, pigs, cattle and goats) were screened using RT-qPCR, and whole genome sequencing was performed for lineage identification on selected LASV positive samples. Animals were also screened for exposure to LASV by enzyme-linked immunosorbent assay (ELISA). Among these animals, lizards had the highest positivity rate by PCR. Genomic sequencing of samples in most infected animals showed sub-lineage 2 g of LASV. Seropositivity was highest among cattle and lowest in pigs. Though the specific impact these additional hosts may have in the broader virus-host context are still unknown - specifically relating to pathogen diversity, evolution, and transmission - the detection of LASV in non-rodent hosts living in proximity to confirmed human LF cases suggests their involvement during transmission as potential reservoirs. Additional epidemiological data comparing viral genomes from humans and animals, as well as those circulating within the environment will be critical in understanding LASV transmission dynamics and will ultimately guide the development of countermeasures for this zoonotic health threat.

Concussion has been described in the United States (US) collegiate student-athlete population, but female-specific findings are often underrepresented and underreported. Our study aimed to describe female collegiate student-athletes' initial injury characteristics and return to activity outcomes following concussion. Female collegiate student-athletes (n = 1393) from 30-US institutions experienced a concussion and completed standardized, multimodal concussion assessments from pre-injury through unrestricted return to play (uRTP) in this prospective, longitudinal cohort study. Initial injury presentation characteristics, assessment, and return to activity outcomes [<48-h (acute), return to learn, initiate return to play (iRTP), uRTP] were collected. We used descriptive statistics to report injury characteristics, return to activity outcomes, and post-injury assessment performance change categorization (worsened, unchanged, improved) based on change score confidence rank criteria across sport contact classifications [contact (n = 661), limited (n = 446), non-contact (n = 286)]. The median (25th to 75th percentile) days to return to learn was 6.0 (3.0-10.0), iRTP was 8.1 (4.8-13.8), and uRTP was 14.8 (9.9-24.0), but varied by contact classification. Across contact levels, the majority experienced worse SCAT total symptom severity (72.8-82.6%), ImPACT reaction time (91.2-92.6%), and BSI-18 total score (45.2-51.8%) acutely relative to baseline, but unchanged BESS total errors (58.0-60.9%), SAC total score (71.5-76.1%), and remaining ImPACT domains (50.6-66.5%). Our findings provide robust estimates of the typical female collegiate student-athlete presentation and recovery trajectory following concussion, with overall similar findings to the limited female collegiate student-athlete literature. Overall varying confidence rank classification was observed acutely. Our findings provide clinically-relevant insights for athletes, clinicians, researchers, and policymakers to inform efforts specific to females experiencing concussion.

Mitochondrial dysfunction is implicated in heat-induced skeletal muscle (SKM) injury and its underlying mechanisms remain unclear. Evidence suggests that cellular ions and molecules, including divalent cations and adenine nucleotides, are involved in the regulation of mitochondrial function. In this study, we examined Ca2+, Mg2+, and NAD+ levels in mouse C2C12 myoblasts and SKM in response to heat exposure. During heat exposure, mitochondrial Ca2+ levels increased significantly, whereas cytosolic Ca2+ levels remained unaltered. The mitochondrial Ca2+ levels in the SKM of heat-exposed mice were 28% higher compared to control mice. No changes in cytosolic Ca2+ were detected between the two groups. Following heat exposure, cytosolic and mitochondrial Mg2+ levels were reduced by 47% and 23% in C2C12 myoblasts, and by 51% and 44% in mouse SKMs, respectively. In addition, heat exposure decreased mitochondrial NAD+ levels by 32% and 26% in C2C12 myoblasts and mouse SKMs, respectively. Treatment with the NAD+ precursor nicotinamide riboside (NR) partially prevented heat-induced depletion of NAD+. Additionally, NR significantly reduced heat-increased mitochondrial fission, mitochondrial depolarization, and apoptosis in C2C12 myoblasts and mouse SKMs. No effects of NR on heat-induced changes in intracellular Ca2+ and Mg2+ levels were observed. This study provides in vitro and in vivo evidence that acute heat stress causes alterations in mitochondrial Ca2+, Mg2+, and NAD+ homeostasis. Our results suggest mitochondrial NAD+ homeostasis as a therapeutic target for the prevention of heat-induced SKM injury.