Triple Negative Breast Cancer (TNBC), indicated by the absence of estrogen, progesterone and human epidermal growth factor receptor 2 (HER2), is the most aggressive form of breast cancer characterized by high rates of metastasis and low survival. Among those diagnosed with TNBC, 34% contain Inhibitor of Growth 4 (ING4) deletion that is associated with poor patient outcomes. We previously showed that ING4 negatively regulates NF-B in breast cancer. Previous studies show parthenolide, a compound found in feverfew (Tanacetum parthenium) to inhibit NF-B in cervical and gastric cancer. We hypothesized that parthenolide inhibits cytokine-induced activation of NF-B in ING4 deficient TNBC cells. To test the hypothesis, previously established vectors, v2, ING4 wildtype and v2h1, ING4-deleted were synthesized in MDA-MB 231, a TNBC cell line, using a CRISPR/Cas9 system. Inflammatory cytokines, IL-1 and TNF, were tested in ING4 wildtype or ING4 deleted cells for elicited phosphorylation of NF-B, proliferation, and migration in the presence or absence of parthenolide. The results showed that TNF or IL-1 induced translocation phosphorylation of NF-B regardless of ING4 deletion. ING4 inhibited proinflammatory cytokine induced pp65, consistent with previous studies demonstrating the negative regulation of NF-B in ING4-sufficent cell lines. We found the optimal working dose of parthenolide, 100nM, had no effect on cell proliferation in the presence or absence of IL-1. Parthenolide inhibited IL-1induced phosphorylation of NF-B regardless of ING4 deletion. Parthenolide inhibited TNF-induced phosphorylation of NF-B in ING4-deleted cell lines. Moreover, parthenolide induced migration of TNBC cells regardless of ING4 presence of absence. TNF and parthenolide treated samples in ING4-deleted cell lines were found to inhibit cell migration to basal level. These results demonstrate the difference in inhibitory mechanism of parthenolide in induced phosphorylation of NF-B through proinflammatory cytokines TNF or IL-1This is demonstrated by the exclusivity of parthenolide inhibition of TNF induced phosphorylation of NF-B in ING4-deleted TNBC cell line. In contrast, parthenolide inhibition of IL-1 induced phosphorylation of NF-B occurred regardless of ING4 deletion. These results may inhibit parthenolide as an alternative to those with ING4-deleted TNBC due to its role in inducing cancer phenotype cell migration.

Stress is a necessary and functional part of human physiology. From responding to life-threatening situations to getting people out of bed in the morning, stress serves a major purpose in human survival. However, when consistent and high levels of stress are experienced, it can pose a threat to human health. One of the major mediators of physiological stress is a hormone called cortisol. Cortisol is a well-defined substance and its function in normal physiology is well understood. Scientific research indicates that consistent and high levels of this hormone may be an aid in cancer’s ability to evade the human immune response. Despite this, there is not much known about its relationship with cancer. I used immunofluorescence to determine cell-to-cell variability of vimentin expression and DNA content for cells that were exposed to cortisol at consistent and frequent doses overtime and those not exposed to cortisol to determine if cortisol altered the variability of vimentin expression and DNA content. I observed no change in the variability in vimentin expression across both cell conditions. I did observe variability in DNA content across both cell conditions, with more variability in the population affected by cortisol. These results suggest that there might be a relationship between the stress induced by cortisol, taking place at the genomic level but may have no impact on specific protein expression. Potential implications of the research conducted are looks to preventative medicine in the context of stress experienced by members of marginalized groups as a way of preventing cancer development.

There is increasing interest in understanding how active learning affects students’ mental health as science courses transition from traditional lecture to active learning. Prior research has found that active learning can both alleviate and exacerbate undergraduate mental health problems. Existing studies have only examined the relationship between active learning and anxiety. No studies have examined the relationship between active learning and undergraduate depression. To address this gap in the literature, we conducted hour-long exploratory interviews with 29 students with depression who had taken active learning science courses across six U.S. institutions. We probed what aspects of active learning practices exacerbate or alleviate depressive symptoms and how students’ depression affects their experiences in active learning. We found that aspects of active learning practices exacerbate and alleviate students’ depressive symptoms, and depression negatively impacts students’ experiences in active learning. The underlying aspects of active learning practices that impact students’ depression fall into four overarching categories: inherently social, inherently engaging, opportunities to compare selves to others, and opportunities to validate or invalidate intelligence. We hope that by better understanding the experiences of undergraduates with depression in active learning courses we can create more inclusive learning environments for these students.

Mental health conditions can impact college students’ social and academic achievements. As such, students may disclose mental illnesses on medical school applications. Yet, no study has investigated to what extent disclosure of a mental health condition impacts medical school acceptance. We designed an audit study to address this gap. We surveyed 99 potential admissions committee members from at least 43 unique M.D.-granting schools in the U.S. Participants rated a fictitious portion of a medical school application on acceptability, competence, and likeability. They were randomly assigned to a condition: an application that explained a low semester GPA due to a mental health condition, an application that explained a low semester GPA due to a physical health condition, or an application that had a low semester GPA but did not describe any health condition. Using ANOVAs, multinomial regression, and open-coding, we found that committee members do not rate applications lower when a mental health condition is revealed. When asked about their concerns regarding the application, 27.0% of participants who received an application that revealed a mental health condition mentioned it as a concern; 14.7% of participants who received an application that revealed a physical health condition mentioned it as a concern. Committee members were also asked about when revealing a mental health condition would be beneficial and when it would be detrimental. This work indicates that medical school admissions committee members do not exhibit a bias towards mental health conditions and provides recommendations on how to discuss mental illness on medical school applications.