Sociodemographic disadvantage in the burden of stress and academic performance in medical school: implications for diversity in medicine.

BACKGROUND: Nontraditional students bring to medicine inherent characteristics and perspectives that enrich the learning environment and contribute to expanding diversity in medicine. However, research has shown that these students, by virtue of their sociodemographic backgrounds, face unique challenges in medical education, which ultimately place them at a disadvantage compared to their peers. The purpose of this study is to explore relationships between sociodemographic characteristics, stress, and academic performance, in the context of outcomes that may be undermining efforts to diversify the physician workforce. METHODS: Using a retrospective observational cohort methodology, we examined institutional and USMLE exam performance data in conjunction with Perceived Stress Scale-4 survey results from six cohorts of students at Kirk Kerkorian School of Medicine at UNLV (n = 358). Using independent samples t-test, mean stress and academic performance were compared between four sociodemographic groups: first-generation college students, underrepresented in medicine (URM), socioeconomically disadvantaged, and age 30 + at matriculation. Results were considered significant where P ≤ .05. RESULTS: First-generation college students had significantly higher stress at the end of third year clerkships (mean 7.8 vs. 6.8, P* = .03). URM students had significantly lower scores on preclinical exams (mean 81.37 vs. 83.07, P* = .02). The students who were age 30 + at matriculation had significantly lower exam scores on all academic performance measures. CONCLUSION: Our results echo historic trends in academic performance for racial and ethnic minority students, and we present recent evidence of academic performance disparities based on age at matriculation. Residency program directors continue to use test scores as a primary metric to screen applicants and thus, poor academic performance has profound consequences on career trajectory. Finally, significantly higher stress in the first-generation students may be evidence of underlying psychological distress. Expanding the sociodemographic diversity among physicians, and by extension, medical students, has long been recognized as fundamental to addressing inequities in healthcare. However, results from our study suggest that aspects of medical education are unfavorable and disadvantageous for first-generation, URM, and older medical students. A deeper understanding of the interplay between sociodemographic characteristics and success in medical school is paramount as we pursue diversity in medicine.

Single-Cell RNA Sequencing Reveals Novel Genes Regulated by Hypoxia in the Lung Vasculature.

Pulmonary arterial hypertension (PAH) is a chronic progressive disease with significant morbidity and mortality. The disease is characterized by vascular remodeling that includes increased muscularization of distal blood vessels and vessel stiffening associated with changes in extracellular matrix deposition. In humans, chronic hypoxia causes PAH, and hypoxia-induced rodent models of PAH have been used for years to study the disease. With the development of single-cell RNA sequencing technology, it is now possible to examine hypoxia-dependent transcriptional changes in vivo at a cell-specific level. In this study, we used single-cell RNA sequencing to compare lungs from wild-type (Wt) mice exposed to hypoxia for 28 days to normoxia-treated control mice. We additionally examined mice deficient for Notch3, a smooth muscle-enriched gene linked to PAH. Data analysis revealed that hypoxia promoted cell number changes in immune and endothelial cell types in the lung, activated the innate immunity pathway, and resulted in specific changes in gene expression in vascular cells. Surprisingly, we found limited differences in lungs from mice deficient for Notch3 compared to Wt controls. These findings provide novel insight into the effects of chronic hypoxia exposure on gene expression and cell phenotypes in vivo and identify unique changes to cells of the vasculature.

miR-145 transgenic mice develop cardiopulmonary complications leading to postnatal death.

BACKGROUND: Both downregulation and elevation of microRNA miR-145 has been linked to an array of cardiopulmonary phenotypes, and a host of studies suggest that it is an important contributor in governing the differentiation of cardiac and vascular smooth muscle cell types. METHODS AND RESULTS: To better understand the role of elevated miR-145 in utero within the cardiopulmonary system, we utilized a transgene to overexpress miR-145 embryonically in mice and examined the consequences of this lineage-restricted enhanced expression. Overexpression of miR-145 has detrimental effects that manifest after birth as overexpressor mice are unable to survive beyond postnatal day 18. The miR-145 expressing mice exhibit respiratory distress and fail to thrive. Gross analysis revealed an enlarged right ventricle, and pulmonary dysplasia with vascular hypertrophy. Single cell sequencing of RNA derived from lungs of control and miR-145 transgenic mice demonstrated that miR-145 overexpression had global effects on the lung with an increase in immune cells and evidence of leukocyte extravasation associated with vascular inflammation. CONCLUSIONS: These data provide novel findings that demonstrate a pathological role for miR-145 in the cardiopulmonary system that extends beyond its normal function in governing smooth muscle differentiation.

Generation of transgenic mice that conditionally express microRNA miR-145.

MicroRNAs are modulators of cellular phenotypes and their functions contribute to development, homeostasis, and disease. miR-145 is a conserved microRNA that has been implicated in regulating an array of phenotypes. These include supporting smooth muscle differentiation, repression of stem cell pluripotency, and inhibition of tumor growth and metastasis. Previously, our lab demonstrated that miR-145 acts to suppress cardiac fibrosis through inhibition of the TGF-ß signaling pathway. The range of effects that miR-145 has on different cell types makes it an attractive microRNA for further study. Here we describe the generation of transgenic mice that conditionally express miR-145 through Cre recombinase-mediated activation. Characterization of individual founder lines indicates that overexpression of miR-145 in the developing cardiovascular system has detrimental effects, with three independent miR-145 transgenic lines exhibiting Cre-dependent lethality. Expression analysis demonstrates that the transgene is robustly expressed and our analysis reveals a novel downstream target of miR-145, Tnnt2. The miR-145 transgenic mice represent a valuable tool to understand the role of miR-145 in diverse cell types and to address its potential as a therapeutic mediator for the treatment of disease.

Qualitative case study investigating PAX-good behaviour game in first nations communities: insight into school personnel's perspectives in implementing a whole school approach to promote youth mental health.

OBJECTIVES: PAX-Good Behaviour Game (PAX-GBG) is associated with improved mental health among youth. First Nations community members decided on a whole school approach to facilitate PAX-GBG implementation, by offering intervention training to all staff members in their schools. Our objective is to gain a greater understanding of how this approach was viewed by school personnel, in order to improve implementation in remote and northern First Nations communities. DESIGN: We conducted a qualitative case study using semi-structured interviews. SETTING: Interviews were conducted in First Nations schools located in northern Manitoba, Canada, in February 2018. PARTICIPANTS: We used purposive sampling in selecting the 23 school staff from First Nations communities. INTERVENTION: PAX-GBG is a mental health promotion intervention that teachers deliver in the classroom alongside normal instructional activities. It was implemented school-wide over 4 months from October 2017 to February 2018. OUTCOME MEASURES: We inquired about the participants' perception of PAX-GBG and the whole school approach. We applied an iterative coding system, identified recurring ideas and classified the ideas into major categories. RESULTS: Implementing the PAX-GBG whole school approach improved students' behaviour and created a positive school environment. Students were learning self-regulation, had quieter voices and demonstrated awareness of the PAX-GBG strategies. All teachers interviewed had used the programme. Support from school administrators and having all school personnel use the programme consistently were facilitators to successful implementation. Challenges included the timing of training, lack of clarity in how to implement and implementing among students in older grades and those with special needs. CONCLUSIONS: The whole school approach to implementing PAX-GBG was viewed as an acceptable and feasible way to extend the reach of PAX-GBG in order to promote the mental health of First Nations youth. Recommendations included ensuring school leadership support, changes to the training and cultural and literacy adaptations.

Affordable hands-on DNA sequencing and genotyping: an exercise for teaching DNA analysis to undergraduates.

In this report, we describe a 5-week laboratory exercise for undergraduate biology and biochemistry students in which students learn to sequence DNA and to genotype their DNA for selected single nucleotide polymorphisms (SNPs). Students use miniaturized DNA sequencing gels that require approximately 8 min to run. The students perform G, A, T, C Sanger sequencing reactions. They prepare and run the gels, perform Southern blots (which require only 10 min), and detect sequencing ladders using a colorimetric detection system. Students enlarge their sequencing ladders from digital images of their small nylon membranes, and read the sequence manually. They compare their reads with the actual DNA sequence using BLAST2. After mastering the DNA sequencing system, students prepare their own DNA from a cheek swab, polymerase chain reaction-amplify a region of their DNA that encompasses a SNP of interest, and perform sequencing to determine their genotype at the SNP position. A family pedigree can also be constructed. The SNP chosen by the instructor was rs17822931, which is in the ABCC11 gene and is the determinant of human earwax type. Genotypes at the rs178229931 site vary in different ethnic populations.