Opportunities for Expanding Access to Veterinary Care: Lessons From COVID-19.

The COVID-19 pandemic impacted people and professions around the world, including veterinary medicine. The epidemiology of SARS-CoV-2 broadened the definition of vulnerability in human populations, and the virus' economic impacts exacerbated well-established financial barriers to providing equal access to medical care. The objective of this study was to explore how the pandemic was impacting access to companion animal care in the months March-September of 2020, with a focus on traditionally vulnerable as well as newly vulnerable populations. Additionally, this study sought to identify areas on which the veterinary profession can focus in order to help increase access to veterinary care, including the veterinary school curriculum, continuing education, and telemedicine. We conducted surveys and interviews with animal owners (n = 1009), veterinarians and clinic staff (n = 516), and access to veterinary care organizations (n = 17). Collectively, these responses highlighted how the COVID-19 pandemic created new, and amplified existing, issues with accessing and providing veterinary care. Three critical themes arose; (1) opportunities for further learning for the veterinary profession; including curricula around telemedicine, financially resilient business models and understanding health disparities and vulnerable populations; (2) a need for a network of collaboration and communication across veterinary clinics and access to care organizations and (3) future preparedness for health, economic or other crises response. Overall, the pandemic emphasized the complexity of access to care, as well as the role of veterinarians in public health. This information can be used to develop strategies to aid in increased access to veterinary care now and in the face of future disasters.

Environmental Sustainability in Veterinary Medicine: An Opportunity for Teaching Hospitals.

Climate change is one of the greatest public health threats of the twenty-first century. Recent surveys of veterinary students and practicing veterinarians have highlighted their concerns about the impacts of climate change on animal health and a strong desire to be knowledgeable about the practice and promotion of environmental sustainability within clinical practice. Most American Veterinary Medical Association (AVMA)-accredited veterinary schools have a veterinary teaching hospital (VTH) where veterinary students receive their core clinical education. Given this, VTHs may provide opportunities for students to learn how veterinary clinics can decrease their environmental footprint and actions they could incorporate into their future clinical work. To assess the feasibility of and support for introducing environmentally sustainable practices into VTHs, we distributed an anonymous online survey to all AVMA-accredited veterinary schools with an associated VTH. Responses were received from 843 individuals representing 23 VTHs in 7 countries. While the overwhelming majority of responding personnel believe this is an important topic, there is little evidence that sustainable behaviors are being practiced or showcased within VTHs. Respondents were most interested in working to increase recycling and reduce general waste and energy consumption within their hospitals. In addition to a lack of educational resources, funding was a commonly identified barrier to incorporating more environmentally sustainable practices. These results add to the growing evidence that enhanced incorporation of sustainability into veterinary medical education at all stages is needed and that VTHs provide a unique opportunity to lead by example.

Linking Endoplasmic Reticular Stress and Alternative Splicing.

RNA splicing patterns in antibody-secreting cells are shaped by endoplasmic reticulum stress, ELL2 (eleven-nineteen lysine-rich leukemia gene 2) induction, and changes in the levels of snRNAs. Endoplasmic reticulum stress induces the unfolded protein response comprising a highly conserved set of genes crucial for cell survival; among these is Ire1, whose auto-phosphorylation drives it to acquire a regulated mRNA decay activity. The mRNA-modifying function of phosphorylated Ire1 non-canonically splices Xbp1 mRNA and yet degrades other cellular mRNAs with related motifs. Naïve splenic B cells will activate Ire1 phosphorylation early on after lipopolysaccharide (LPS) stimulation, within 18 h; large-scale changes in mRNA content and splicing patterns result. Inhibition of the mRNA-degradation function of Ire1 is correlated with further differences in the splicing patterns and a reduction in the mRNA factors for snRNA transcription. Some of the >4000 splicing changes seen at 18 h after LPS stimulation persist into the late stages of antibody secretion, up to 72 h. Meanwhile some early splicing changes are supplanted by new splicing changes introduced by the up-regulation of ELL2, a transcription elongation factor. ELL2 is necessary for immunoglobulin secretion and does this by changing mRNA processing patterns of immunoglobulin heavy chain and >5000 other genes.

RNA Splicing in the Transition from B Cells to Antibody-Secreting Cells: The Influences of ELL2, Small Nuclear RNA, and Endoplasmic Reticulum Stress.

In the transition from B cells to Ab-secreting cells (ASCs) many genes are induced, such as ELL2, Irf4, Prdm1, Xbp1, whereas other mRNAs do not change in abundance. Nonetheless, using splicing array technology and mouse splenic B cells plus or minus LPS, we found that induced and "uninduced" genes can show large differences in splicing patterns between the cell stages, which could influence ASC development. We found that ∼55% of these splicing changes depend on ELL2, a transcription elongation factor that influences expression levels and splicing patterns of ASC signature genes, genes in the cell-cycle and N-glycan biosynthesis and processing pathways, and the secretory versus membrane forms of the IgH mRNA. Some of these changes occur when ELL2 binds directly to the genes encoding those mRNAs, whereas some of the changes are indirect. To attempt to account for the changes that occur in RNA splicing before or without ELL2 induction, we examined the amount of the small nuclear RNA molecules and found that they were significantly decreased within 18 h of LPS stimulation and stayed low until 72 h. Correlating with this, at 18 h after LPS, endoplasmic reticulum stress and Ire1 phosphorylation are induced. Inhibiting the regulated Ire1-dependent mRNA decay with 4u8C correlates with the reduction in small nuclear RNA and changes in the normal splicing patterns at 18 h. Thus, we conclude that the RNA splicing patterns in ASCs are shaped early by endoplasmic reticulum stress and Ire1 phosphorylation and later by ELL2 induction.