Associations between Faculty Vitality and Burnout in the COVID-19 Era: the Experience of One Institution

Introduction: Faculty vitality is the ideal synergy between engaged faculty and mission-driven institutions that generates a fruitful environment for academic productivity, career satisfaction, and fulfillment of shared goals. The COVID-19 pandemic has introduced unprecedented disruptions to faculty vitality, with profound perturbations to individual and institutional support networks. However, the extent of this impact is unclear, as are strategies to mitigate loss of faculty vitality and prevent burnout. Methods: We developed a survey instrument to evaluate the impact of COVID-19 on faculty vitality and burnout at a mid-sized, Midwestern academic institution affiliated with a university hospital. Survey items focused on individual and institutional factors that are predictive of faculty vitality, organized around themes of work-life integration, professional engagement, and institutional support. The survey also evaluated the impact of interventions implemented in response to the pandemic on faculty burnout. Results: One hundred and thirty-eight clinical and basic science faculty participated in the survey. Female faculty are less satisfied with work-life integration since the onset of the pandemic. Almost all (98.2%) faculty respondents experienced detriments to their professional development, and 38% believed their research was affected. Faculty of color experienced more detrimental effects on their professional development. Self-reported burnout increased from 23.6% before to 44.8% after the pandemic. Burnout was associated with lack of career development opportunities, whereas career satisfaction and utilization of university support efforts were protective. Conclusion: Faculty vitality has decreased since the pandemic began, but institutional support can mitigate these detrimental effects. Additional research on the efficacy of interventions to support female faculty, early-career researchers, and under-represented minorities in medicine is needed

The absence of myocardial calcium-independent phospholipase a2γ results in impaired prostaglandin e2 production and decreased survival in mice with acute trypanosoma cruzi infection

Cardiomyopathy is a serious complication of Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi. The parasite often infects cardiac myocytes, causing the release of inflammatory mediators, including eicosanoids. A recent study from our laboratory demonstrated that calcium-independent phospholipase A(2)γ (iPLA(2)γ) accounts for the majority of PLA(2) activity in rabbit ventricular myocytes and is responsible for arachidonic acid (AA) and prostaglandin E(2) (PGE(2)) release. Thus, we hypothesized that cardiac iPLA(2)γ contributes to eicosanoid production in T. cruzi infection. Inhibition of the isoform iPLA(2)γ or iPLA(2)β, with the R or S enantiomer of bromoenol lactone (BEL), respectively, demonstrated that iPLA(2)γ is the predominant isoform in immortalized mouse cardiac myocytes (HL-1 cells). Stimulation of HL-1 cells with thrombin, a serine protease associated with microthrombus formation in Chagas' disease and a known activator of iPLA(2), increased AA and PGE(2) release, accompanied by platelet-activating factor (PAF) production. Similarly, T. cruzi infection resulted in increased AA and PGE(2) release over time that was inhibited by pretreatment with (R)-BEL. Further, T. cruzi-infected iPLA(2)γ-knockout (KO) mice had lower survival rates and increased tissue parasitism compared to wild-type (WT) mice, suggesting that iPLA(2)γ-KO mice were more susceptible to infection than WT mice. A significant increase in iPLA(2) activity was observed in WT mice following infection, whereas iPLA(2)γ-KO mice showed no alteration in cardiac iPLA(2) activity and produced less PGE(2). In summary, these studies demonstrate that T. cruzi infection activates cardiac myocyte iPLA(2)γ, resulting in increased AA and PGE(2) release, mediators that may be essential for host survival during acute infection. Thus, these studies suggest that iPLA(2)γ plays a cardioprotective role during the acute stage of Chagas' disease

Absence of calcium‐independent phospholipase A2β impairs platelet‐activating factor production and inflammatory cell recruitment in Trypanosoma cruzi‐infected endothelial cells

Both acute and chronic phases of Trypanosoma cruzi (T. cruzi) infection are characterized by tissue inflammation, mainly in the heart. A key step in the inflammatory process is the transmigration of inflammatory cells across the endothelium to underlying infected tissues. We observed increased arachidonic acid release and platelet‐activating factor (PAF) production in human coronary artery endothelial cells (HCAEC) at up to 96 h of T. cruzi infection. Arachidonic acid release is mediated by activation of the calcium‐independent phospholipase A(2) (iPLA(2)) isoforms iPLA(2)β and iPLA(2)γ, whereas PAF production was dependent upon iPLA(2)β activation alone. Trypanosoma cruzi infection also resulted in increased cell surface expression of adhesion molecules. Increased adherence of inflammatory cells to T. cruzi‐infected endothelium was blocked by inhibition of endothelial cell iPLA(2)β or by blocking the PAF receptor on inflammatory cells. This suggests that PAF, in combination with adhesion molecules, might contribute to parasite clearing in the heart by recruiting inflammatory cells to the endothelium

Tryptase activates calcium-independent phospholipase A2 and releases PGE2 in airway epithelial cells

Human small airway epithelial cells (HSAEC) form the boundary between the external environmental allergens and the internal lung milieu. Mast cells are present in human lung tissue interspersed within the pulmonary epithelium and can secrete a host of pre- and newly formed mediators from their granules, which may propagate small airway inflammation. In this study, tryptase stimulation of HSAEC increased membrane-associated, calcium-independent phospholipase A2γ (iPLA2γ) activity, resulting in increased arachidonic acid and PGE2 release. These responses were inhibited by pretreating HSAEC with the iPLA2-selective inhibitor bromoenol lactone. The tryptase-stimulated PGE2 production was inhibited by treating HSAEC with the cyclooxygenase (COX)-1-selective inhibitor SC-560 and the nonselective COX inhibitor aspirin but not by the COX-2-selective inhibitor CAY10404, indicating that the early release of arachidonic acid is metabolized by constitutive COX-1 to form PGE2 in tryptase-stimulated HSAEC. Additionally, platelet-activating factor production and neutrophil adherence to tryptase-stimulated HSAEC was also increased. This complex response can set up a cascade of inflammatory mediator production in small airways. We speculate that selective inhibition of iPLA2γ-mediated phospholipid hydrolysis may prove beneficial in inflammatory airway diseases

Impaired Expression of Prostaglandin E2 (PGE2) Synthesis and Degradation Enzymes during Differentiation of Immortalized Urothelial Cells from Patients with Interstitial Cystitis/Painful Bladder Syndrome.

The differentiated superficial cells of the urothelium restrict urine flow into the bladder wall. We have demonstrated that urothelial cells isolated from bladders of patients with interstitial cystitis/painful bladder syndrome (IC/PBS) fail to release PGE2 in response to tryptase. This study examines the expression of PGE2 synthesis and degradation enzymes in urothelial cells during differentiation.We measured immunoprotein expression of cyclooxygenase-2 (COX-2), prostaglandin E2 synthase (PGES) and 15-hydroxyprostaglandin dehydrogenase (PGDH) in human urothelial cells and in immortalized urothelial cells isolated from the bladders of IC/PBS patients or normal subjects during stratification and differentiation produced by increased calcium and fetal bovine serum (Ca/FBS) in the culture medium for 1, 3 and 7 days.PGES immunoprotein expression increased during differentiation in normal and IC/PBS urothelial cells. COX-2 expression also increased in cells from normal patients following differentiation. Remarkably, no COX-2 expression was detectable in urothelial cells isolated from 3 out of 4 IC/PBS patients. PGDH immunoprotein expression decreased in normal cells after 1 and 3 days of Ca/FBS addition, but returned to normal after 7 days. PGDH expression was unchanged during differentiation at 1 and 3 days, but was more than 2-fold higher at 7 days compared to day 0 in the IC/PBS cells. Urothelial cells isolated from IC/PBS patients demonstrated no PGE2 release in response to tryptase under any of the experimental conditions studied.Taken together, our results indicate that PGE2 release is compromised during stratification and differentiation in IC/PBS urothelium and may contribute to impaired barrier function