Burnout among emergency physicians working at a large tertiary centre in Ontario

BACKGROUND: Emergency medicine (EM) is a high-stress specialty. Work related stress and burnout have been reported to negatively impact physician-patient interactions, overall physician mental and physical health, and most importantly, patient outcomes. We assessed the rates of burnout among emergency physicians (EPs) at our centre. METHODS: A local cross-sectional study to assess burnout among adult and pediatric EPs, fellows and residents was conducted at three Emergency Departments (EDs) at a single institution in Canada. The anonymous online survey encompassed demographics, the validated MBI tool (Maslach Burnout Inventory) and additional questions aimed at identifying determinants of EP burnout. Each respondent’s three MBI scale scores, (Emotional Exhaustion, Depersonalization and Personal Accomplishment), were calculated as described in the MBI manual. Descriptive statistics were calculated and relationships between risk factors and burnout scores were examined using t-tests, one-way ANOVAs, and/or regression analyses where appropriate. RESULTS: The survey had a 72% (84/118) response rate. Results indicated a high degree of burnout among EPs with 66.2% of respondents meeting the cutoff for burnout. Physicians who were single, female, CCFP-EM trained and those having fewer years of practice were identified to have higher burnout scores. We did not identify any factors to be predictive or any associated with Personal Accomplishment. CONCLUSION: Consistent with previous literature, EPs at this institution were shown to be at risk for moderate to severe burnout. Despite this, they showed high feelings of personal accomplishment. This study suggests that opportunities exist for wellness programs targeted at identified high risk groups

The 17th Rocky Mountain Virology Association Meeting

Since 2000, scientists and students from the greater Rocky Mountain region, along with invited speakers, both national and international, have gathered at the Mountain Campus of Colorado State University to discuss their area of study, present recent findings, establish or strengthen collaborations, and mentor the next generation of virologists and prionologists through formal presentations and informal discussions concerning science, grantsmanship and network development. This year, approximately 100 people attended the 17th annual Rocky Mountain Virology Association meeting, that began with a keynote presentation, and featured 29 oral and 35 poster presentations covering RNA and DNA viruses, prions, virus-host interactions and guides to successful mentorship. Since the keynote address focused on the structure and function of Zika and related flaviviruses, a special session was held to discuss RNA control. The secluded meeting at the foot of the Colorado Rocky Mountains gave ample time for in-depth discussions amid the peak of fall colors in the aspen groves while the random bear provided excitement. On behalf of the Rocky Mountain Virology Association, this report summarizes the \u3e50 reports

The 20th Anniversary Meeting of the Rocky Mountain Virology Association

Due to the COVID-19 pandemic and multiple devastating forest fires, the 2020 meeting of the Rocky Mountain Virology Association was held virtually. The three-day gathering featured talks describing recent advances in virology and prion research. The keynote presentation described the measles virus paradox of immune suppression and life-long immunity. Special invited speakers presented information concerning visualizing antiviral effector cell biology in mucosal tissues, uncovering the T-cell tropism of Epstein-Barr virus type 2, a history and current survey of coronavirus spike proteins, a summary of Zika virus vaccination and immunity, the innate immune response to flavivirus infections, a discussion concerning prion disease as it relates to multiple system atrophy, and clues for discussing virology with the non-virologist. On behalf of the Rocky Mountain Virology Association, this report summarizes selected presentations

New Coordinative Compounds with 4-(4’-pyridyl)pyridinium Disubstituted Monoylides

The complexes with manganese(II), iron(II), cobalt(II), nickel(II) and copper(II) of 2-(4, 4’-bipyridin-1-ium-1-yl)-1-(4-bromophenylamino)-3-(4-methoxyphenyl)-3-oxo-1-thioxopropan-2-ide (ylide, Y) were synthesized and characterized. The obtained compounds with 1 : 2 metal/ligand ratios have been characterized by FTIR, UV Vis spectroscopy, ESI MS spectrometry, molecular conductance, magnetic measurements and thermal analysis. The ylide ligand forms chelates with metallic (II) ions through their amide nitrogen and oxygen atoms

Vector Competence of American Mosquitoes for Three Strains of Zika Virus

In 2015, Zika virus (ZIKV; Flaviviridae; Flavivirus) emerged in the Americas, causing millions of infections in dozens of countries. The rapid spread of the virus and the association with disease outcomes such as Guillain-Barré syndrome and microcephaly make understanding transmission dynamics essential. Currently, there are no reports of vector competence (VC) of American mosquitoes for ZIKV isolates from the Americas. Further, it is not clear whether ZIKV strains from other genetic lineages can be transmitted by American Aedes aegypti populations, and whether the scope of the current epidemic is in part facilitated by viral factors such as enhanced replicative fitness or increased vector competence. Therefore, we characterized replication of three ZIKV strains, one from each of the three phylogenetic clades in several cell lines and assessed their abilities to be transmitted by Ae. aegypti mosquitoes. Additionally, laboratory colonies of different Culex spp. were infected with an American outbreak strain of ZIKV to assess VC. Replication rates were variable and depended on virus strain, cell line and MOI. African strains used in this study outcompeted the American strain in vitro in both mammalian and mosquito cell culture. West and East African strains of ZIKV tested here were more efficiently transmitted by Ae. aegypti from Mexico than was the currently circulating American strain of the Asian lineage. Long-established laboratory colonies of Culex mosquitoes were not efficient ZIKV vectors. These data demonstrate the capacity for additional ZIKV strains to infect and replicate in American Aedes mosquitoes and suggest that neither enhanced virus replicative fitness nor virus adaptation to local vector mosquitoes seems likely to explain the extent and intensity of ZIKV transmission in the Americas

Structural Studies of West Nile Virus in Complex with Neutralizing Antibodies.

West Nile virus (WNV) is a positive strand RNA virus in the family Flaviviridae, which includes members such as dengue, Japanese encephalitis, tick-borne encephalitis, yellow fever and Hepatitis C. As with other members of the genus, it is arthropod transmitted and has recently established itself as an endemic virus in the United States. Although most infections are asymptomatic, clinical manifestations of WNV include encephalitis and death. We have been interested in investigating the nature of the immune response with particular emphasis on the role of antibodies in reducing the level of infection. We have used a combination of techniques, but primarily structure, as a tool to probe the nature of antibody-mediated virus neutralization. Our results suggest that neutralization of virus particles is more complex than originally envisioned, with multiple mechanisms utilized. Using a combination of X-ray crystallography and cryo-electron microscopy, several virus-antibody complexes have been determined at pseudo-atomic resolution. These studies suggest the following: 1) flavivirus particles exhibit dynamic motions or breathing that transiently expose cryptic epitopes; 2) although there are 180 potential binding sites for each monoclonal antibody the quasi-equivalent nature of the virion usually permits only a subset of sites to be utilized; 3) the availability of these sites, the epitope itself, and the avidity of antibody directly influence the mechanism of neutralization; and 4) particles thought to be incapable of infecting cells, so-called immature viruses, may play a critical role in immune surveillance and reactivity. The structure of the flavivirus virion and complexes of monoclonal antibodies will be presented along with data to support mechanisms antibody-mediated flavivirus neutralizatio

Dengue viruses cleave STING in humans but not in nonhuman primates, their presumed natural reservoir.

Human dengue viruses emerged from primate reservoirs, yet paradoxically dengue does not reach high titers in primate models. This presents a unique opportunity to examine the genetics of spillover versus reservoir hosts. The dengue virus 2 (DENV2) - encoded protease cleaves human STING, reducing type I interferon production and boosting viral titers in humans. We find that both human and sylvatic (reservoir) dengue viruses universally cleave human STING, but not the STING of primates implicated as reservoir species. The special ability of dengue to cleave STING is thus specific to humans and a few closely related ape species. Conversion of residues 78/79 to the human-encoded 'RG' renders all primate (and mouse) STINGs sensitive to viral cleavage. Dengue viruses may have evolved to increase viral titers in the dense and vast human population, while maintaining decreased titers and pathogenicity in the more rare animals that serve as their sustaining reservoir in nature

Glutamine supports pancreatic cancer growth through a Kras-regulated metabolic pathway

Cancer cells exhibit metabolic dependencies that distinguish them from their normal counterparts1. Among these addictions is an increased utilization of the amino acid glutamine (Gln) to fuel anabolic processes2. Indeed, the spectrum of Gln-dependent tumors and the mechanisms whereby Gln supports cancer metabolism remain areas of active investigation. Here we report the identification of a non-canonical pathway of Gln utilization in human pancreatic ductal adenocarcinoma (PDAC) cells that is required for tumor growth. While most cells utilize glutamate dehydrogenase (GLUD1) to convert Gln-derived glutamate (Glu) into α-ketoglutarate in the mitochondria to fuel the tricarboxylic acid (TCA) cycle, PDAC relies on a distinct pathway to fuel the TCA cycle such that Gln-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate (OAA) by aspartate transaminase (GOT1). Subsequently, this OAA is converted into malate and then pyruvate, ostensibly increasing the NADPH/NADP+ ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as Gln deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, we establish that the reprogramming of Gln metabolism is mediated by oncogenic Kras, the signature genetic alteration in PDAC, via the transcriptional upregulation and repression of key metabolic enzymes in this pathway. The essentiality of this pathway in PDAC and the fact that it is dispensable in normal cells may provide novel therapeutic approaches to treat these refractory tumors

Variation in Competence for ZIKV Transmission by Aedes aegypti and Aedes albopictus in Mexico

BACKGROUND: ZIKV is a new addition to the arboviruses circulating in the New World, with more than 1 million cases since its introduction in 2015. A growing number of studies have reported vector competence (VC) of Aedes mosquitoes from several areas of the world for ZIKV transmission. Some studies have used New World mosquitoes from disparate regions and concluded that these have a variable but relatively low competence for the Asian lineage of ZIKV. METHODOLOGY/PRINCIPAL FINDINGS: Ten Aedes aegypti (L) and three Ae. albopictus (Skuse) collections made in 2016 from throughout Mexico were analyzed for ZIKV (PRVABC59-Asian lineage) VC. Mexican Ae. aegypti had high rates of midgut infection (MIR), dissemination (DIR) and salivary gland infection (SGIR) but low to moderate transmission rates (TR). It is unclear whether this low TR was due to heritable salivary gland escape barriers or to underestimating the amount of virus in saliva due to the loss of virus during filtering and random losses on surfaces when working with small volumes. VC varied among collections, geographic regions and whether the collection was made north or south of the Neovolcanic axis (NVA). The four rates were consistently lower in northeastern Mexico, highest in collections along the Pacific coast and intermediate in the Yucatan. All rates were lowest north of the NVA. It was difficult to assess VC in Ae. albopictus because rates varied depending upon the number of generations in the laboratory. CONCLUSIONS/SIGNIFICANCE: Mexican Ae. aegypti and Ae. albopictus are competent vectors of ZIKV. There is however large variance in vector competence among geographic sites and regions. At 14 days post infection, TR varied from 8-51% in Ae. aegypti and from 2-26% in Ae. albopictus