SUMMARY Iron regulatory proteins 1 and 2 (Irps) post-transcriptionally control the expression of transcripts that contain iron responsive element (IRE) sequences, including ferritin, ferroportin, transferrin receptor and hypoxia inducible factor 2α (HIF2α). We report here that mice with targeted deletion of Irp1 developed pulmonary hypertension and polycythemia that was exacerbated by a low iron diet. Hematocrits increased to 65% in iron-starved mice, and many polycythemic mice died of abdominal hemorrhages. Irp1 deletion enhanced HIF2α protein expression in kidneys of Irp1−/− mice, which led to increased erythropoietin (EPO) expression, polycythemia and concomitant tissue iron deficiency. Increased HIF2α expression in pulmonary endothelial cells induced high expression of endothelin-1, likely contributing to the pulmonary hypertension of Irp1−/− mice. Our results reveal why anemia is an early physiological consequence of iron deficiency, highlight the physiological significance of Irp1 in regulating erythropoiesis and iron distribution, and provide important insights into the molecular pathogenesis of pulmonary hypertension.

Taking a holistic approach to examining parents' experiences and support needs has enabled their changing needs to be highlighted across key care transitions within hospital and community settings and the service implications identified. Improvements in care co-ordination across care transitions are needed to ensure continuity of care and integration of support.

Background Finite clinical data and understanding of COVID-19 immunopathology has led to limited, opinion-based recommendations for management of immune-mediated inflammatory disease (IMID) patients on immunosuppressive (IS) therapeutics. Objective Determine if IS therapeutic type impacts COVID-19 risk among IMID patients. Methods We conducted a retrospective cohort analysis of Henry Ford Health System (HFHS) patients tested for COVID-19 between February 1 st and April 18 th , 2020 treated with IS medication for IMID. Therapeutic class of IS medication, comorbidities, and demographic factors were combined into multivariate models to determine predictors of COVID-19 infection, admission, ventilation, and mortality. Results Of 213 IMID patients, 36.2% tested positive for COVID-19, who had no greater odds of being hospitalized or requiring ventilation relative to the general population. No IS therapeutic worsened the course of disease after multivariate correction, though multi-drug regimens and biologics predicted an increased and decreased rate of hospitalization, respectively, with the latter driven by TNFα inhibitors. Limitations A single-center study somewhat limits generalization to community-based settings. Only patients tested for COVID-19 were analyzed. Conclusion IS therapies for IMIDs are not associated with a significantly greater risk of SARS-CoV-2 or severe sequelae when controlling for other factors, and TNFα inhibitors may decrease odds of severe infection.

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