Yanyi Sun

(MMSc-IMM) Interferon Response Inhibits Trophoblast Fusion and Increase Placenta Permeability During Maternal Immune Activation

The placenta is a temporary organ that forms in the uterus during pregnancy, which provides nutrients and oxygen to the fetus through the umbilical cord. It also works as a barrier that separates the maternal and fetal circulations, protecting fetus from pathogens from the maternal side or maternal immune attack. Maternal immune activation during gestation is associated with adverse outcomes in offspring (1). Studies using rodent models suggest that inflammatory responses at the placenta contribute to growth restriction and even fetal demise (2 , 3). Yet it remains unclear how placental inflammation could be harmful to the fetus. Here, we investigated the permeability of placenta using a mouse model. Data shows that the mouse placenta became leakier during maternal immune activation, which might be able to mediate infiltration of potentially harmful substances into fetal circulation. Trophoblast is the main cell type that makes up the maternal-fetal barrier at the placenta. Some of these cells undergo cell fusion and form syncytia, which reduces cell-cell junction and contribute to the barrier function of the placenta. In vitro cell assay indicates that interferons, which is a group of cytokines produced by host cells as a defensive response to viruses, could inhibit trophoblast fusion. Taken together, our study suggests that reduced syncytia formation caused by interferon responses could contribute to the increase of placental permeability during maternal immune activation, which exposes the fetus to the danger outside of the conceptus.

1 Maternal-Fetal Inflammation in the Placenta and the Developmental Origins of Health and Disease

2 Type I interferons instigate fetal demise after Zika virus infection

3 The placental interleukin-6 signaling controls fetal brain development and behavior

Zachary Whaley

(MMSc-MedEd) Mindsets of General Surgery Residents and Faculty

Authors: Zachary Whaley, MD, Deanna Palenzuela, MD Emil Petrusa, PhD, Surgical Mindsets Research Team, Roy Phitayakorn, MD

Background: Mindset is a psychological construct describing individuals’ beliefs about their potential to change their ability level and is often referred to as either Growth or Fixed. Mindset is considered an important aspect of learning in children and undergraduate students, but there is little investigation of its importance at the GME level.

Methods: We surveyed surgical residents (n=83) and attendings (n=86) at four academic general surgery programs using a modified version of the original mindset assessment, which uses a scale from 1-7 with higher scores indicating more growth-oriented mindsets. We used statistical analysis to characterize the distribution of mindsets and possible contributing factors.

Results: Response rate was 169/602 (n=83 residents and 86 attendings; 38% and 23% respectively). The survey had high internal consistency (α = 0.87). Average resident and attending mindset scores were identical (5.7±0.9), and there was a statistically significant difference in average mindset scores of different programs (5.3 to 6.0, p<0.001). Within individual programs, there was no statistically significant difference between mindset score of attendings and that of residents. Linear regression of mindset subgroups demonstrated a significant contribution to general mindset score from the mindset score for surgical skill (p<0.001), but patient care skill was not statistically significant (p=0.07). Differences between sub-group mindsets scores were also statistically significant (5.2 to 6.2, p<0.001). Multivariable linear regression demonstrated significantly more growth mindset in residents and attendings that self-identify as male versus female (5.6 vs 5.9, p=0.019), but no significant difference in mindset scores by race (p=0.662).

Discussion: On average, residents and attendings demonstrate similarly high growth mindset scores as opposed to a balance of fixed versus growth noted in other learners. Interestingly, mindset scores varied significantly by program and gender. Further research is needed to better understand these associations and the effect of mindset on other important learning outcomes.

Jingyao