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

Thrombin Induces Macrophage Migration Inhibitory Factor Release and Upregulation in Urothelium: A Possible Contribution to Bladder Inflammation

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine expressed by urothelial cells that mediates bladder inflammation. We investigated the effect of stimulation with thrombin, a Protease Activated Receptor-1 (PAR1) agonist, on MIF release and MIF mRNA upregulation in urothelial cells.MIF and PAR1 expression was examined in normal human immortalized urothelial cells (UROtsa) using real-time RT-PCR, Western blotting and dual immunostaining. MIF and PAR1 immunostaining was also examined in rat urothelium. The effect of thrombin stimulation (100 nM) on urothelial MIF release was examined in UROtsa cells (in vitro) and in rats (in vivo). UROtsa cells were stimulated with thrombin, culture media were collected at different time points and MIF amounts were determined by ELISA. Pentobarbital anesthetized rats received intravesical saline (control), thrombin, or thrombin +2% lidocaine (to block nerve activity) for 1 hr, intraluminal fluid was collected and MIF amounts determined by ELISA. Bladder or UROtsa MIF mRNA was measured using real time RT-PCR.UROtsa cells constitutively express MIF and PAR1 and immunostaining for both was observed in these cells and in the basal and intermediate layers of rat urothelium. Thrombin stimulation of urothelial cells resulted in a concentration- and time-dependent increase in MIF release both in vitro (UROtsa; 2.8-fold increase at 1 hr) and in vivo (rat; 4.5-fold) while heat-inactivated thrombin had no effect. In rats, thrombin-induced MIF release was reduced but not abolished by intravesical lidocaine treatment. Thrombin also upregulated MIF mRNA in UROtsa cells (3.3-fold increase) and in the rat bladder (2-fold increase) where the effect was reduced (1.4-fold) by lidocaine treatment.Urothelial cells express both MIF and PAR1. Activation of urothelial PAR1 receptors, either by locally generated thrombin or proteases present in the urine, may mediate bladder inflammation by inducing urothelial MIF release and upregulating urothelial MIF expression

Recent insights into cigarette smoking as a lifestyle risk factor for breast cancer

Shannon Kispert, Jane McHowat Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO, USA Abstract: There have been many cohort studies published reviewing the epidemiological evidence that links breast cancer to cigarette smoking, yet the underlying mechanisms are largely unknown and research studies are few and incomplete. Although cohort studies are important in establishing a connection between breast cancer and cigarette smoking, basic science research is necessary to prove the relationship and to highlight potential interventions and drug targets that can be used to manage the disease. This subject has been controversial for many decades; however, there has been a recent resurgence in interest because of the widespread acknowledgment of the role lifestyle choices play in cancer development and progression. This review will detail the current statistics associated with cigarette smoking and discuss recent cohort and basic research studies that highlight the association of cigarette smoking and breast cancer initiation and progression. Keywords: metastasis, tobacco, tumor growt