Racial and Ethnic Representation in Peripheral Artery Disease Randomized Clinical Trials.

Clinical trial enrollment provides various benefits to study participants including early access to novel therapies that may potentially alter the trajectory of disease states. Trial sponsors benefit from enrolling demographically diverse trial participants enabling the trial outcomes to be generalizable to a larger proportion of the community at large. Despite these and other well-documented benefits, clinical trial enrollment for Black and Hispanic Americans as well as women continues to be low. Specific disease states such as PAD have a higher prevalence and clinical outcomes are relatively worse in Black Americans compared with non-Hispanic white Americans. The recruitment process for peripheral artery disease (PAD) clinical trials can be costly and challenging and usually comes at the expense of representation. Participant willingness and trust, engagement, and socioeconomic status play essential roles in the representation of underrepresented minority (URM) groups. Despite the contrary belief, URM groups such as Blacks and Hispanics are just as willing to participate in a clinical trial as non-Hispanic Whites. However, financial burdens, cultural barriers, and inadequate health literacy and education may impede URMs' access to clinical trials and medical care. Clinical trials' enrollment sites often pose transportation barriers and challenges that negatively impact creating a diverse study population. Lack of diversity among a trial population can stem from the stakeholder level, where corporate sponsors of academic readers do not consider diversity in clinical trials a priority due to false cost-benefit assumptions. The funding source may also impact the racial reporting or the results of a given trial. Industry-based trials have always been criticized for over-representing non-Hispanic White populations, driven by the desire to reach high completion rates with minimum financial burdens. Real efforts are warranted to ensure adequate minorities' representation in the PAD clinical trials and to the process toward the ultimate goal of developing more durable and effective PAD treatments that fit the needs of real-world populations.

A transgenic mouse line for assaying tissue-specific changes in endoplasmic reticulum proteostasis.

Maintenance of calcium homeostasis is important for proper endoplasmic reticulum (ER) function. When cellular stress conditions deplete the high concentration of calcium in the ER, ER-resident proteins are secreted into the extracellular space in a process called exodosis. Monitoring exodosis provides insight into changes in ER homeostasis and proteostasis resulting from cellular stress associated with ER calcium dysregulation. To monitor cell-type specific exodosis in the intact animal, we created a transgenic mouse line with a Gaussia luciferase (GLuc)-based, secreted ER calcium-modulated protein, SERCaMP, preceded by a LoxP-STOP-LoxP (LSL) sequence. The Cre-dependent LSL-SERCaMP mice were crossed with albumin (Alb)-Cre and dopamine transporter (DAT)-Cre mouse lines. GLuc-SERCaMP expression was characterized in mouse organs and extracellular fluids, and the secretion of GLuc-SERCaMP in response to cellular stress was monitored following pharmacological depletion of ER calcium. In LSL-SERCaMP × Alb-Cre mice, robust GLuc activity was observed only in the liver and blood, whereas in LSL-SERCaMP × DAT-Cre mice, GLuc activity was seen in midbrain dopaminergic neurons and tissue samples innervated by dopaminergic projections. After calcium depletion, we saw increased GLuc signal in the plasma and cerebrospinal fluid collected from the Alb-Cre and DAT-Cre crosses, respectively. This mouse model can be used to investigate the secretion of ER-resident proteins from specific cell and tissue types during disease pathogenesis and may aid in the identification of therapeutics and biomarkers of disease.

A case series of image-guided percutaneous drainage of abdominal aortic graft infection as bridge therapy.

INTRODUCTION: Aortic graft infection (AGI) is a rare complication following endovascular aneurysm repair and is associated with substantial morbidity and mortality. The traditional management of AGI is intravenous antibiotic therapy and surgical explantation. In this case series, percutaneous drainage was used as a bridge therapy in the treatment of AGI. METHODS: We report two cases, 78-year-old male and 57-year-old female, in whom image-guided percutaneous drainage was used to treat AGI in two contrasting contexts. Informed consent was obtained from both cases/relatives for publication. RESULTS: Both cases underwent successful percutaneous drainage of AGI utilized as a bridge therapy before definitive surgical reconstruction and graft explantation. Each patient had a different outcome. In the first case, the patient's comorbidities and severe disease state could not be overcome, resulting in his death. The second patient benefitted from the percutaneous drainage by allowing her more time ameliorate her malnutrition before definitive surgery. CONCLUSION: Data on the outcomes of percutaneous drainage of AGI is limited. The successful procedure described in this case series emphasizes the need to conduct more research to evaluate the safety and efficacy of this treatment approach before the surgical explantation.

The evolution of parasite host range in heterogeneous host populations.

Theory on the evolution of niche width argues that resource heterogeneity selects for niche breadth. For parasites, this theory predicts that parasite populations will evolve, or maintain, broader host ranges when selected in genetically diverse host populations relative to homogeneous host populations. To test this prediction, we selected the bacterial parasite Serratia marcescens to kill Caenorhabditis elegans in populations that were genetically heterogeneous (50% mix of two experimental genotypes) or homogeneous (100% of either genotype). After 20 rounds of selection, we compared the host range of selected parasites by measuring parasite fitness (i.e. virulence, the selected fitness trait) on the two focal host genotypes and on a novel host genotype. As predicted, heterogeneous host populations selected for parasites with a broader host range: these parasite populations gained or maintained virulence on all host genotypes. This result contrasted with selection in homogeneous populations of one host genotype. Here, host range contracted, with parasite populations gaining virulence on the focal host genotype and losing virulence on the novel host genotype. This pattern was not, however, repeated with selection in homogeneous populations of the second host genotype: these parasite populations did not gain virulence on the focal host genotype, nor did they lose virulence on the novel host genotype. Our results indicate that host heterogeneity can maintain broader host ranges in parasite populations. Individual host genotypes, however, vary in the degree to which they select for specialization in parasite populations.

Diversity, equity, and inclusion: one model to move from commitment to action in medical education.

The summer of 2020 riveted the attention of our nation with a sense of urgency to address structural racism. Cities declared racism a public health crisis, and organizations called for increased awareness of persistent historic racial inequities and advocacy for change. In medical education, students and institutional leaders felt compelled to transition from passive advocacy to energetic action in order to build a culture of anti-racism. In our institution, we applied J Mierke and V. Williamson's 6-step framework to achieve organizational culture change which is as follows: 1. Identify the catalyst for change; 2. Strategically plan for successful change; 3. Engage and empower organizational members; 4. Cultivate leaders at all levels; 5. Foster innovation, creativity, and risk-taking; 6. Monitor progress, measure success, and celebrate (even the small changes) along the way. In addition, we noted two key considerations for the success of the process: A. Transparency in communication, and B. Flexibility and adjustment to emerging situations. We share our approach using this framework which we believe is generalizable to other organizations. We draw from literature on organizational psychology and lastly call for the continuation and sustainability of the work that will continue to build a diverse, equitable, inclusive, antiracist and vibrant education community.