RESUMEN
Coronavirus disease 2019 (COVID-19; severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] has dislocated clinical services and postgraduate training. To better understand and to document these impacts, we contacted anaesthesia trainees and trainers across six continents and collated their experiences during the pandemic. All aspects of training programmes have been affected. Trainees report that reduced caseload, sub-specialty experience, and supervised procedures are impairing learning. Cancelled educational activities, postponed examinations, and altered rotations threaten progression through training. Job prospects and international opportunities are downgraded. Work-related anxieties about provision of personal protective equipment, and risks to self and to colleagues are superimposed on concerns for family and friends and domestic disruption. These seismic changes have had consequences for well-being and mental health. In response, anaesthetists have developed innovations in teaching and trainee support. New technologies support trainer-trainee interactions, with a focus on e-learning. National training bodies and medical regulators that specify training and oversee assessment of trainees and their progression have provided flexibility in their requirements. Within anaesthesia departments, support transcends grades and job titles with lessons for the future. Attention to wellness, awareness of mental health issues and multimodal support can attenuate but not eliminate trainee distress.
Asunto(s)
Anestesiología/educación , Anestesistas/educación , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Actitud del Personal de Salud , COVID-19 , Curriculum , Grupos Diagnósticos Relacionados , Educación de Postgrado en Medicina , Humanos , Salud Mental , Equipo de Protección Personal , Estudiantes de Medicina/psicología , EnseñanzaRESUMEN
Yersinia pestis, the causative agent of bubonic and pneumonic plague, is typically a zoonotic vector-borne disease of wild rodents. Bacterial biofilm formation in the proventriculus of the flea contributes to chronic infection of fleas and facilitates efficient disease transmission. However prior to biofilm formation, ingested bacteria must survive within the flea midgut, and yet little is known about vector-pathogen interactions that are required for flea gut colonization. Here we establish a Drosophila melanogaster model system to gain insight into Y. pestis colonization of the insect vector. We show that Y. pestis establishes a stable infection in the anterior midgut of fly larvae, and we used this model system to study the roles of genes involved in biofilm production and/or resistance to gut immunity stressors. We find that PhoP and GmhA both contribute to colonization and resistance to antimicrobial peptides in flies, and furthermore, the data suggest biofilm formation may afford protection against antimicrobial peptides. Production of reactive oxygen species in the fly gut, as in fleas, also serves to limit bacterial infection, and OxyR mediates Y. pestis survival in both insect models. Overall, our data establish the fruit fly as an informative model to elucidate the relationship between Y. pestis and its flea vector.
Asunto(s)
Sistema Digestivo/inmunología , Sistema Digestivo/microbiología , Resistencia a la Enfermedad/inmunología , Drosophila melanogaster/inmunología , Drosophila melanogaster/microbiología , Inmunidad Innata , Yersinia pestis/fisiología , Animales , Péptidos Catiónicos Antimicrobianos/biosíntesis , Biopelículas , Recuento de Colonia Microbiana , Sistema Digestivo/parasitología , Drosophila melanogaster/parasitología , Larva/microbiología , Larva/parasitología , Mutación/genética , Especies Reactivas de Oxígeno/metabolismo , Siphonaptera/fisiologíaRESUMEN
Jarid2 was recently identified as an important component of the mammalian Polycomb repressive complex 2 (PRC2), where it has a major effect on PRC2 recruitment in mouse embryonic stem cells. Although Jarid2 is conserved in Drosophila, it has not previously been implicated in Polycomb (Pc) regulation. Therefore, we purified Drosophila Jarid2 and its associated proteins and found that Jarid2 associates with all of the known canonical PRC2 components, demonstrating a conserved physical interaction with PRC2 in flies and mammals. Furthermore, in vivo studies with Jarid2 mutants in flies demonstrate that among several histone modifications tested, only methylation of histone 3 at K27 (H3K27), the mark implemented by PRC2, was affected. Genome-wide profiling of Jarid2, Su(z)12 (Suppressor of zeste 12), and H3K27me3 occupancy by chromatin immunoprecipitation with sequencing (ChIP-seq) indicates that Jarid2 and Su(z)12 have very similar distribution patterns on chromatin. However, Jarid2 and Su(z)12 occupancy levels at some genes are significantly different, with Jarid2 being present at relatively low levels at many Pc response elements (PREs) of certain Homeobox (Hox) genes, providing a rationale for why Jarid2 was never identified in Pc screens. Gene expression analyses show that Jarid2 and E(z) (Enhancer of zeste, a canonical PRC2 component) are not only required for transcriptional repression but might also function in active transcription. Identification of Jarid2 as a conserved PRC2 interactor in flies provides an opportunity to begin to probe some of its novel functions in Drosophila development.