A training programme for novice extracorporeal resuscitation providers.

Introduction: The use of extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest is increasing globally. However, providing equity of access to all patients is challenging, and to date, access has been limited to inner city areas surrounding major hospitals. To increase the availability of ECPR in our jurisdiction, we sought to train pre-hospital physicians with no experience in extracorporeal membrane oxygenation cardiopulmonary resuscitation (ECPR). To enable this, we sort to develop and teach a syllabus that would provide novice ECPR providers the skill to perform ECPR safely and effectively in the pre-hospital environment. Methods: This training programme consisted of 11 pre-hospital physicians and six critical care paramedics. All participants had no prior hospital experience instituting or managing ECPR patients. The training programme was multimodal utilising a porcine model of heart failure to teach time pressured dynamic physiological troubleshooting, cadaver labs to teach cannulation, didactic teaching and simulation. Key knowledge and skill domains were identified. Each learning framework was built upon with a final focus on integrating all skill domains required to successfully initiate ECPR. Results: The training program was completed from February 2022 to August 2023. Knowledge progression was assessed at key stages via written and practical examination. Each participant demonstrated clear knowledge and skill progression at the key stages of the training programme. At the end of the training programme, participants met the pre-defined standards to progress to ECPR provision in the pre-hospital environment. Conclusion: We present a training program for novice ECPR providers performing ECPR in the pre-hospital setting. The outcomes of this training program can provide a training framework for both novices, low volume ECMO centres and pre-hospital clinicians.

Four-dimensional nuclear speckle phase separation dynamics regulate proteostasis.

Phase separation and biorhythms control biological processes in the spatial and temporal dimensions, respectively, but mechanisms of four-dimensional integration remain elusive. Here, we identified an evolutionarily conserved XBP1s-SON axis that establishes a cell-autonomous mammalian 12-hour ultradian rhythm of nuclear speckle liquid-liquid phase separation (LLPS) dynamics, separate from both the 24-hour circadian clock and the cell cycle. Higher expression of nuclear speckle scaffolding protein SON, observed at early morning/early afternoon, generates diffuse and fluid nuclear speckles, increases their interactions with chromatin proactively, transcriptionally amplifies the unfolded protein response, and protects against proteome stress, whereas the opposites are observed following reduced SON level at early evening/late morning. Correlative Son and proteostasis gene expression dynamics are further observed across the entire mouse life span. Our results suggest that by modulating the temporal dynamics of proteostasis, the nuclear speckle LLPS may represent a previously unidentified (chrono)-therapeutic target for pathologies associated with dysregulated proteostasis.

Equine Arteritis Virus Elicits a Mucosal Antibody Response in the Reproductive Tract of Persistently Infected Stallions.

Equine arteritis virus (EAV) has the ability to establish persistent infection in the reproductive tract of the stallion (carrier) and is continuously shed in its semen. We have recently demonstrated that EAV persists within stromal cells and a subset of lymphocytes in the stallion accessory sex glands in the presence of a significant local inflammatory response. In the present study, we demonstrated that EAV elicits a mucosal antibody response in the reproductive tract during persistent infection with homing of plasma cells into accessory sex glands. The EAV-specific immunoglobulin isotypes in seminal plasma included IgA, IgG1, IgG3/5, and IgG4/7. Interestingly, seminal plasma IgG1 and IgG4/7 possessed virus-neutralizing activity, while seminal plasma IgA and IgG3/5 did not. However, virus-neutralizing IgG1 and IgG4/7 in seminal plasma were not effective in preventing viral infectivity. In addition, the serological response was primarily mediated by virus-specific IgM and IgG1, while virus-specific serum IgA, IgG3/5, IgG4/7, and IgG6 isotype responses were not detected. This is the first report characterizing the immunoglobulin isotypes in equine serum and seminal plasma in response to EAV infection. The findings presented herein suggest that while a broader immunoglobulin isotype diversity is elicited in seminal plasma, EAV has the ability to persist in the reproductive tract, in spite of local mucosal antibody and inflammatory responses. This study provides further evidence that EAV employs complex immune evasion mechanisms during persistence in the reproductive tract that warrant further investigation.

Dietary Carotenoid Supplementation Enhances the Cutaneous Bacterial Communities of the Critically Endangered Southern Corroboree Frog (Pseudophryne corroboree).

The rapid spread of infectious disease has resulted in the decline of animal populations globally. Amphibians support a diversity of microbial symbionts on their skin surface that help to inhibit pathogen colonisation and reduce disease susceptibility and virulence. These cutaneous microbial communities represent an important component of amphibian immune defence, however, very little is known about the environmental factors that influence the cutaneous microbiome. Here, we characterise the cutaneous bacterial communities of a captive colony of the critically endangered Australian southern corroboree frog, Pseudophyrne corroboree, and examine the effect of dietary carotenoid supplementation on bacterial abundance, species richness and community composition. Individuals receiving a carotenoid-supplemented diet exhibited significantly higher bacterial abundance and species richness as well as an altered bacterial community composition compared to individuals that did not receive dietary carotenoids. Our findings suggest that dietary carotenoid supplementation enhances the cutaneous bacteria community of the southern corroboree frog and regulates the presence of bacteria species within the cutaneous microbiome. Our study is the second to demonstrate that carotenoid supplementation can improve amphibian cutaneous bacterial community dynamics, drawing attention to the possibility that dietary manipulation may assist with the ex situ management of endangered species and improve resilience to lethal pathogens such as Batrachochytrium dendrobatidis (Bd).