The Role of Mock Reviewing Sessions in the National Research Mentoring Network Strategic Empowerment Tailored for Health Equity Investigators: A Randomized Controlled Study.

The National Research Mentoring Network (NRMN) Strategic Empowerment Tailored for Health Equity Investigators (SETH) study evaluates the value of adding Developmental Network to Coaching in the career advancement of diverse Early-Stage Investigators (ESIs). Focused NIH-formatted Mock Reviewing Sessions (MRS) prior to the submission of grants can significantly enhance the scientific merits of an ESI's grant application. We evaluated the most prevalent design, analysis-related factors, and the likelihood of grant submissions and awards associated with going through MRS, using descriptive statistics, Chi-square, and logistic regression methods. A total of 62 out of 234 applications went through the MRS. There were 69.4% that pursued R grants, 22.6% career development (K) awards, and 8.0% other grant mechanisms. Comparing applications that underwent MRS versus those that did not (N = 172), 67.7% vs. 38.4% were submitted for funding (i.e., unadjusted difference of 29.3%; OR = 4.8, 95% CI = (2.4, 9.8), p-value < 0.0001). This indicates that, relative to those who did not undergo MRS, ESIs who did, were 4.8 times as likely to submit an application for funding. Also, ESIs in earlier cohorts (1-2) (a period that coincided with the pre COVID-19 era) as compared to those who were recruited at later cohorts (3-4) (i.e., during the peak of COVID-19 period) were 3.8 times as likely to submit grants (p-value < 0.0001). The most prevalent issues that were identified included insufficient statistical design considerations and plans (75%), conceptual framework (28.3%), specific aims (11.7%), evidence of significance (3.3%), and innovation (3.3%). MRS potentially enhances grant submissions for extramural funding and offers constructive feedback allowing for modifications that enhance the scientific merits of research grants.

Individual and Institutional Factors Contribute to Research Capacity Building for Early-Stage Investigators from Groups Underrepresented in Biomedical Research: A Qualitative Comparative Analysis.

BACKGROUND: Enhancement of diversity within the U.S. research workforce is a recognized need and priority at a national level. Existing comprehensive programs, such as the National Research Mentoring Network (NRMN) and Research Centers in Minority Institutions (RCMI), have the dual focus of building institutional research capacity and promoting investigator self-efficacy through mentoring and training. METHODS: A qualitative comparative analysis was used to identify the combination of factors that explain the success and failure to submit a grant proposal by investigators underrepresented in biomedical research from the RCMI and non-RCMI institutions. The records of 211 participants enrolled in the NRMN Strategic Empowerment Tailored for Health Equity Investigators (NRMN-SETH) program were reviewed, and data for 79 early-stage, underrepresented faculty investigators from RCMI (n = 23) and non-RCMI (n = 56) institutions were included. RESULTS: Institutional membership (RCMI vs. non-RCMI) was used as a possible predictive factor and emerged as a contributing factor for all of the analyses. Access to local mentors was predictive of a successful grant submission for RCMI investigators, while underrepresented investigators at non-RCMI institutions who succeeded with submitting grants still lacked access to local mentors. CONCLUSION: Institutional contexts contribute to the grant writing experiences of investigators underrepresented in biomedical research.

Mentor training for junior faculty: a brief evaluation report from the Georgia Clinical and Translational Science Alliance.

To provide a foundation for mentoring, junior faculty participated in a mentor training workshop informed by the Mentoring Clinical and Translational Researchers curriculum. The goal was to develop skills and behaviors that engender more rewarding and inclusive mentoring practices. Attendees responded to baseline and follow-up surveys assessing perceived mentoring skills. Follow-up surveys included closed- and open-ended questions about the value and satisfaction of the training, and intended behavior changes. Junior faculty respondents (n = 39) reported significantly higher overall mentoring skills after the training (t = -2.6, p = 0.012) with a medium effect size (Cohen's D = 0.59). Domains with statistically significant improvement from baseline to follow-up included aligning mentor-mentee expectations and assessing understanding. Thirty-eighty (97%) found the training valuable, and 32 (82%) indicated they would change mentoring-related behaviors because of the training. Intended behavior changes described in open-ended responses aligned with mentoring skills assessed (e.g., aligning expectations). An additional competency domain of evaluating mentoring relationships was also described. A mentor training workshop for junior faculty appeared to contribute to changes in mentoring skills and intended behaviors. Mentor training has the potential to enhance mentorship, which is critical to strengthening a diverse pipeline of clinical and translational science researchers.

Impact of COVID-19 on the Research Career Advancement of Health Equity Scholars from Diverse Backgrounds.

The COVID-19 pandemic has significantly taxed scientific research and seems to have exacerbated existing inequities within the research field, particularly for early-stage investigators (ESIs). This study examines the effects of the COVID-19 pandemic on traditionally underrepresented ESIs enrolled in an NIH-supported study evaluating the effectiveness of developmental networks, grant writing coaching, and mentoring on research career advancement. The survey consisted of 24 closed-ended (quantitative) and 4 open-ended questions (qualitative) linked to a participant's ability to meet grant submission deadlines, research and professional development disruptions, stress level, career transition level, self-efficacy and management of scholarly tasks, and familial responsibilities. Results from 32 respondents (53%) suggest that COVID-19 adversely impacted the continuity of research (81%) and grant submissions (63%). On average, grant submissions were delayed by 6.69 months (i.e., greater than one grant cycle). We also conducted additional analyses characterizing nonresponse and found that there were no significant predictors of nonresponse, indicating a limited threat to the validity of our findings. The disruption caused by COVID-19 to the careers of ESIs from underrepresented groups in the biomedical workforce has been profound in the short term. The long-term consequences to the future success of these groups are unknown but is a worthwhile area of research and potential innovation.

Randomized Controlled Study to Test the Effectiveness of Developmental Network Coaching in the Career Advancement of Diverse Early-Stage Investigators (ESIs): Implementation Challenges and Lessons Learned.

Introduction: Adding developmental networks (DN) to grant-writing coaching can significantly enhance ESIs' research careers. Herein, we present study design, ESIs' characteristics and encountered challenges/lessons learned and their resolutions when deploying/implementing (a) NCR algorithm(s), (b) recruitment/retention and (c) implementing DN intervention. Methods: Nested Cluster Randomization (NCR) design governs this study implementation. The sample size is 220 ESIs intending to submit an NIH K, R, U, and/or Minority Supplement application(s). Primary outcome: intensity/sustainability of grant submission(s)/funding(s), measured by time to/between application(s). Outcome(s) analyses modes: summaries, Kaplan Meir and Cox proportional hazard models as a function of randomization groups and other predictors of outcomes. Results: In the present study, we recruited two cohorts of ESIs (N = 85): 39% African Americans, 18% Latinx, 18% Whites, 20% Asians and 6% Hawaiian/Pacific Islander/other ethnicities; 65% are women; 73% are assistant professors, 4% are Associate Professors and 23% are instructors/scientists/post-doctoral. Participants' disciplines: 32% basic/biomedical, 36% clinical/translational and 32% social/behavioral. Proposal(s) mechanisms: 61% research grants (R series), 31% career development (K series), 7% support of competitive research (SCORE) and 1% National Science Foundation applications. NCR did produce balance in the distribution of ESIs' demographics, sex at birth, ethnicity, professional appointments, background disciplines, and mechanism of sought funding. Lessons learned/challenges: NCR implementation was methodologically challenged during implementation by added constraints (e.g., assigning coaches to the same randomization arm of their participants as well as blinding them to ESIs' randomization group). Recruitment and retention were hampered by the COVID-19 pandemic and more progressive and innovative strategies were needed to heighten the visibility and outreach of this program. DN delivery was also affected by the pandemic and monitoring of ESIs' engagement and facilitation of communications interventions were needed. Resolution of these challenges effectively reconfigured NCR algorithms, recruitment/retention plans, and DN intervention delivery. We intend to recruit an additional 135 ESIs focusing on underrepresented scholars from RCMIs, CTSAs, and other programs. COVID-19 rendered this program 100% virtual, with recruitment/retention challenges and substantial disruption of ESIs' research. We may extend the grant writing period, coaching, and Mock Study Section support.

Challenges and Strategies of Successful Mentoring: The Perspective of LEADS Scholars and Mentors from Minority Serving Institutions.

Mentoring continues to be a salient conversation in academia among junior and senior faculty and administrators. Mentors provide guidance and structure to junior faculty so that they can meet their academic and professional goals. Mentors also convey skills in balancing life and academic pursuits. Therefore, the purpose of this descriptive study was to provide additional insight from a training program called Leading Emerging and Diverse Scientists to Success (LEADS) regarding successful strategies and challenges of mentoring relating to lessons learned from the scholars and mentees' perspective. The LEADS program provided multiple training platforms to increase skills and knowledge regarding research to promote expertise in grant writing and submission for funding opportunities among diverse scientists. These findings reinforce the knowledge about the value of a mentor in helping define the research pathway of their mentee and underscoring the importance of mentoring.

Association between MTNR1B polymorphisms and obesity in African American: findings from the Jackson Heart Study.

BACKGROUND: Melatonin is a hormone that is secreted at night by the pineal gland. It exerts its function by binding to the MT1 and MT2 receptors, which are encoded by the MTNR1A and MTNR1B genes, respectively. Previous studies reveal that MTNR1B variants are associated with insulin secretion impairments and an increased body mass index (BMI) in individuals of European and Asian ancestries. Obesity is highly prevalent in the US and disproportionately affects African Americans. Here, we hypothesized that common single nucleotide polymorphisms (SNPs) imputed in 1000 Genomes in the MTNR1B gene are associated with adiposity in African American adult men and women and that the association is modified by insomnia. METHODS: We used an additive genetic model to describe the association between the adiposity traits (BMI and waist circumference) and selected MTNR1B variants in 3,029 Jackson Heart Study participants, with an average age of 55.13 ± 12.84 years, and 62% were women. We regressed the adiposity measures on the estimated allelic or genotypic dosage at every selected SNP and adjusted for age, sex, population stratification, and insomnia. Thirty common SNPs, spanning the MTNR1B gene, with a minor allele frequency ≥ 5%, a call rate ≥ 90%, a Hardy-Weinberg equilibrium p value > 10-6, were available for the analysis. RESULTS: The allele T of rs76371840 was associated with adiposity (OR = 1.47 [1.13-1.82]; PFDR-adjusted = 0.0499), and the allele A of rs8192552 showed a significant association with waist circumference (ß = 0.023 ± 0.007; PFDR-adjusted = 0.0077) after correcting for multiple testing. When insomnia was included in the adiposity analysis model, the following four variants became significantly associated with adiposity: rs6483208; rs4388843; rs4601728; and rs12804291. CONCLUSIONS: Our data indicate that polymorphisms in the MTNR1B gene are associated with obesity traits in African Americans. To the best of our knowledge, this is the first study to explore the effect of insomnia on the association between the circadian MTNR1B genetic variants and metabolic traits in an African American sample population. We observed that insomnia affected the association between the MTNR1B variants and adiposity.

Morehouse Choice Accountable Care Organization and Education System (MCACO-ES): Integrated Model Delivering Equitable Quality Care.

Accountable Care Organizations (ACOs) seek sustainable innovation through the testing of new care delivery methods that promote shared goals among value-based health care collaborators. The Morehouse Choice Accountable Care Organization and Education System (MCACO-ES), or (M-ACO) is a physician led integrated delivery model participating in the Medicare Shared Savings Program (MSSP) offered through the Centers for Medicare and Medicaid Services (CMS) Innovation Center. The MSSP establishes incentivized, performance-based payment models for qualifying health care organizations serving traditional Medicare beneficiaries that promote collaborative efficiency models designed to mitigate fragmented and insufficient access to health care, reduce unnecessary cost, and improve clinical outcomes. The M-ACO integration model is administered through participant organizations that include a multi-site community based academic practice, independent physician practices, and federally qualified health center systems (FQHCs). This manuscript aims to present a descriptive and exploratory assessment of health care programs and related innovation methods that validate M-ACO as a reliable simulator to implement, evaluate, and refine M-ACO's integration model to render value-based performance outcomes over time. A part of the research approach also includes early outcomes and lessons learned advancing the framework for ongoing testing of M-ACO's integration model across independently owned, rural, and urban health care locations that predominantly serve low-income, traditional Medicare beneficiaries, (including those who also qualify for Medicaid benefits (also referred to as "dual eligibles"). M-ACO seeks to determine how integration potentially impacts targeted performance results. As a simulator to test value-based innovation and related clinical and business practices, M-ACO uses enterprise-level data and advanced analytics to measure certain areas, including: 1) health program insight and effectiveness; 2) optimal implementation process and workflows that align primary care with specialists to expand access to care; 3) chronic care management/coordination deployment as an effective extender service to physicians and patients risk stratified based on defined clinical and social determinant criteria; 4) adoption of technology tools for patient outreach and engagement, including a mobile application for remote biometric monitoring and telemedicine; and 5) use of structured communication platforms that enable practitioner engagement and ongoing training regarding the shift from volume to value-based care delivery.

Achieving Health Equity with e-Healthystrides©: Patient Perspectives of a Consumer Health Information Technology Application.

Objective: We describe the implementation, clinical outcomes and participant perspectives for e-Healthystrides©. Setting: Three independent ambulatory clinics and an historic African American (AA) church. Participants: Adults with diagnosed diabetes mellitus type 2. Intervention: e-Healthystrides© health coach facilitated intervention. Primary outcome: Acquisition of three new self-management behaviors. Secondary outcomes: Blood pressure, blood glucose, A1c, attrition rate and participant perspectives of e-Healthystrides©. Methods: A convergent parallel mixed method design was used in both pilot studies. Results: Two hundred and sixty-four participants, aged ~62±16 years, enrolled. Attrition at 52 weeks varied 50%-90% by site. Low engagement users were defined mainly by anxiety with putting health information online. The primary outcome was achieved in 36% of our participants, with the top 3 self-management behaviors acquired being: reducing risk (24.5%); healthy eating (23.7%); and monitoring (16.4%). Problem solving had the lowest rate of achievement (.91%). Blood pressure improved significantly at all sites at 12 weeks and at clinics A,B,C at 52 weeks. Blood glucose improved at 12 weeks: clinic A (P=.0001), B (P=.003), C (P=.001) and D (P=.03); but, at 52 weeks, only clinics A (P=<.0001) and B (P=.0001). Participants felt empowered by features of e-Healthystrides©. Engagement with health coaches and peers was highly valued. Conclusions: e-Healthystrides© is effective for self-management behavior change. Participants showed the best success with healthy coping, healthy eating, and monitoring behaviors. They felt empowered by access to health information and valued interaction with coaches and peers. Our findings support strong relational/social network strategy with a role for coaches as guides (apomediaries) who facilitate skill acquisition using technology.

The Association of Black Cardiologists (ABC) Cardiovascular Implementation Study (CVIS): A Research Registry Integrating Social Determinants to Support Care for Underserved Patients.

African Americans, other minorities and underserved populations are consistently under- represented in clinical trials. Such underrepresentation results in a gap in the evidence base, and health disparities. The ABC Cardiovascular Implementation Study (CVIS) is a comprehensive prospective cohort registry that integrates social determinants of health. ABC CVIS uses real world clinical practice data to address critical gaps in care by facilitating robust participation of African Americans and other minorities in clinical trials. ABC CVIS will include diverse patients from collaborating ABC member private practices, as well as patients from academic health centers and Federally Qualified Health Centers (FQHCs). This paper describes the rationale and design of the ABC CVIS Registry. The registry will: (1) prospectively collect socio-demographic, clinical and biospecimen data from enrolled adults, adolescents and children with prioritized cardiovascular diseases; (2) Evaluate the safety and clinical outcomes of new therapeutic agents, including post marketing surveillance and pharmacovigilance; (3) Support National Institutes of Health (NIH) and industry sponsored research; (4) Support Quality Measures standards from the Center for Medicare and Medicaid Services (CMS) and Commercial Health Plans. The registry will utilize novel data and technology tools to facilitate mobile health technology application programming interface (API) to health system or practice electronic health records (EHR). Long term, CVIS will become the most comprehensive patient registry for underserved diverse patients with cardiovascular disease (CVD) and co morbid conditions, providing real world data to address health disparities. At least 10,000 patients will be enrolled from 50 sites across the United States.

A federated EHR network data completeness tracking system.

OBJECTIVE: The study sought to design, pilot, and evaluate a federated data completeness tracking system (CTX) for assessing completeness in research data extracted from electronic health record data across the Accessible Research Commons for Health (ARCH) Clinical Data Research Network. MATERIALS AND METHODS: The CTX applies a systems-based approach to design workflow and technology for assessing completeness across distributed electronic health record data repositories participating in a queryable, federated network. The CTX invokes 2 positive feedback loops that utilize open source tools (DQe-c and Vue) to integrate technology and human actors in a system geared for increasing capacity and taking action. A pilot implementation of the system involved 6 ARCH partner sites between January 2017 and May 2018. RESULTS: The ARCH CTX has enabled the network to monitor and, if needed, adjust its data management processes to maintain complete datasets for secondary use. The system allows the network and its partner sites to profile data completeness both at the network and partner site levels. Interactive visualizations presenting the current state of completeness in the context of the entire network as well as changes in completeness across time were valued among the CTX user base. DISCUSSION: Distributed clinical data networks are complex systems. Top-down approaches that solely rely on technology to report data completeness may be necessary but not sufficient for improving completeness (and quality) of data in large-scale clinical data networks. Improving and maintaining complete (high-quality) data in such complex environments entails sociotechnical systems that exploit technology and empower human actors to engage in the process of high-quality data curating. CONCLUSIONS: The CTX has increased the network's capacity to rapidly identify data completeness issues and empowered ARCH partner sites to get involved in improving the completeness of respective data in their repositories.

Developing a Training Program to Diversify the Biomedical Research Workforce.

The National Institutes of Health has made considerable investments to diversify the biomedical research workforce. Towards this goal, the authors partnered with representatives from several minority-serving institutions (MSIs) to develop training for the next generation of researchers. To ensure the most effective training program, the authors conducted a needs assessment with junior and senior investigators from the partnering MSIs. In 2016, the authors conducted focus groups and interviews with 23 junior investigators as well as in-depth interviews with 6 senior investigators from the partnering institutions with the goal of identifying specific areas of training and support that would help junior investigators at MSIs develop and sustain research careers. The data were transcribed and coded, and thematic analysis was conducted. The authors determined four areas in which training and support were needed: training in the "informal curriculum" (skills not covered in traditional clinical research courses), protected time for research training, opportunities to create career-advancing work products, and networking opportunities. The themes that were identified informed the development of the LEADS (Leading Emerging and Diverse Scientists to Success) program. The program consists of 10 instructor-led online modules each lasting approximately one month in duration with weekly synchronous sessions. Scholars are expected to be able to devote at least 20% of their time to the program.

Using a Virtual Community (the Health Equity Learning Collaboratory) to Support Early-Stage Investigators Pursuing Grant Funding.

Junior investigators often have limited access to networks of scientific experts and resources that facilitate competitive grant submissions. Since environments in which scientists are trained are critically important for long-term success, we built and tested a virtual environment for early-stage investigators (ESIs) working on grant proposals. The aim of this study was to evaluate the virtual community's influence on grant submission patterns among participants from underrepresented groups. As part of a grant writing coaching model, junior investigators were recruited into a professional development program designed to develop competitive grantsmanship skills. Designed by the Research Resources and Outreach Core (RROC) of the National Research Mentoring Network (NRMN), the Health Equity Learning Collaboratory (EQ-Collaboratory) provided a virtual community for social support, accountability, constructive feedback, and access to peer networks to help investigators overcome barriers to grant submission. This study assessed differences in outcomes for participants who completed the training within the EQ-Collaboratory compared to those who did not. The analyzed data revealed a statistically significant difference in the average time to submission for participants enrolled in the EQ-Collaboratory. EQ-Collaboratory ESIs submitted proposals 148.6 days earlier, (p < 0.0001). The results suggest that a supportive virtual environment can help investigators more quickly overcome barriers to grant submission.

DEMOCRATIZING DISCOVERY HEALTH WITH N=Me.

Health 360x is a mobile health application and social platform that integrates self-monitoring and decision support for preventive health. We studied 240 diabetic patients in primary care practices and a church community in metropolitan Atlanta. Health coaches were trained on the Health 360x curriculum, which was adapted from the American Association of Diabetes Educators. Participants worked with the health coaches to set goals for diabetes self-management. The intervention included weekly coaching for 12 weeks and online peer networking. Outcome variables included blood pressure, physical activity, and blood glucose that showed significant improvement at 12 weeks and 12 months compared to baseline. Focus group testing revealed that references for empowerment and engagement were associated with positive clinical outcomes. Barriers to adoption and use of the technology were inability to use the internet and concern about privacy and security of health data. Future efforts will integrate a multidisciplinary training dashboard with considerable attention to education on security features including data encryption and sign-on verification.

Promoting Diversity in the Clinical and Translational Research Workforce.

The positive impact of diversity in increasing the effectiveness of the research workforce has been undeniably demonstrated to be an essential element for achieving health equity. Diversity is also instrumental for the research workforce to advance discovery, eliminate health disparities, improve minority health and achieve effective patient-centered outcomes in the quest for better health. One of the sustainable ways to achieve diversity in the workforce is through training, education and career development of all interested individuals including minority, underserved, underrepresented and populations with special needs. A Hispanic public, academic health center, and a historically black private medical school, have joined efforts in this article to share their experiences in addressing diversity in the clinical and translational research workforce with grant support from the National Institutes of Health. The purpose of this paper is to describe how diversity has been achieved through a concerted effort to recruit and develop underrepresented junior faculty and doctoral candidates for successful careers in clinical and translational research focused on health disparities and minority health. We describe Initiatives designed to achieve diversity in recruitment and development of research teams, together with an evaluation of outcomes to determine the success of the program and its participants.

Detection of HIV-1 and Human Proteins in Urinary Extracellular Vesicles from HIV+ Patients.

BACKGROUND: Extracellular vesicles (EVs) are membrane bound, secreted by cells, and detected in bodily fluids, including urine, and contain proteins, RNA, and DNA. Our goal was to identify HIV and human proteins (HPs) in urinary EVs from HIV+ patients and compare them to HIV- samples. METHODS: Urine samples were collected from HIV+ (n = 35) and HIV- (n = 12) individuals. EVs were isolated by ultrafiltration and characterized using transmission electron microscopy, tandem mass spectrometry (LC/MS/MS), and nanoparticle tracking analysis (NTA). Western blots confirmed the presence of HIV proteins. Gene ontology (GO) analysis was performed using FunRich and HIV Human Interaction database (HHID). RESULTS: EVs from urine were 30-400 nm in size. More EVs were in HIV+ patients, P < 0.05, by NTA. HIV+ samples had 14,475 HPs using LC/MS/MS, while only 111 were in HIV-. HPs in the EVs were of exosomal origin. LC/MS/MS showed all HIV+ samples contained at least one HIV protein. GO analysis showed differences in proteins between HIV+ and HIV- samples and more than 50% of the published HPs in the HHID interacted with EV HIV proteins. CONCLUSION: Differences in the proteomic profile of EVs from HIV+ versus HIV- samples were found. HIV and HPs in EVs could be used to detect infection and/or diagnose HIV disease syndromes.

Building Diverse Careers in Clinical and Translational Research: Evaluation of a Certificate Program in Translational Research.

Introduction: The Certificate Program in Translational Research (CPTR) at the Georgia Clinical and Translational Science Alliance provides PhD students, post-doctoral fellows and faculty with didactic, mentored, and experiential training in clinical and translational research. Methods: Quantitative evaluation includes tracking trainee competency, publications, grants and careers in clinical and translational research. Qualitative evaluation includes interviews with trainees about program experiences. Results: The CPTR provided knowledge and skills in clinical and translational research through coursework, clinical rotation, and collaboration with interdisciplinary scientists. Trainees reported increased confidence in 22 program competencies. Trainees have published more than 290 peer-reviewed articles and received over four million dollars in grants from the NIH, over $15 from the U.S. Department of Defense, and more than $300,000 from foundations. Trainees who completed the program remained in clinical and translational research. Conclusions: Programs like the CPTR are needed to train investigators to advance biomedical discoveries into population health.

Quercetin reduces hydroxyurea induced cytotoxicity in immortalized mouse aortic endothelial cells.

BACKGROUND: Chronic inflammation is a characteristic of sickle cell disease (SCD), and is invariably associated with vascular endothelial injury. Hydroxyurea (HU), a naturally cytotoxic chemotherapeutic agent, is the only FDA drug approved for SCD, and is therefore naturally cytotoxic. Quercetin (QCT) is a dietary flavonoid found ubiquitously in plants and foods that have anti-oxidative and anti-inflammatory characteristics. Our hypothesis is that dietary QCT will decrease cytotoxic effects of lipopolysaccharide (LPS) and HU induced vascular cell damage. METHODS: Lipopolysaccharide (LPS) was used to induce inflammation in immortalized mouse aortic endothelial cells (iMAECs), providing an in vitro model of inflamed endothelial cells. The cells were exposed to LPS throughout the entire experiment. Interventions included treating the LPS exposed cells with QCT, HU, or QCT + HU over 50 hours. The 50-hour period included 24 hours of varying treatments, followed by two hours of hypoxic exposure and then 24 hours under normal aerobic exposure. RESULTS: LDH level was significantly higher for LPS treated versus untreated cells (P = 0.0004). LPS plus 30 micromole QCT reduced the LDH (p = 0.1, trend), whereas LPS plus 100 micromoles HU, significantly increased LDH (p = 0.0004). However, LPS plus treatment with 30 micromoles QCT/100 micromoles HU, significantly reduced LDH, compared with HU alone (p = 0.0002). DISCUSSION: These results suggest that quercetin may be effective against vascular endothelial cell damage for iMAECs in vitro. In particular, it shows promise in preventing HU-induced cytotoxicity, surprisingly found from these results. This latter finding is important, and should be given more consideration, since HU is the only FDA-approved drug for treating sickle cell patients, and its use is rapidly increasing.

Type II Endometrial Cancer Overexpresses NILCO: A Preliminary Evaluation.

OBJECTIVE: The expression of NILCO molecules (Notch, IL-1, and leptin crosstalk outcome) and the association with obesity were investigated in types I and II endometrial cancer (EmCa). Additionally, the involvement of NILCO in leptin-induced invasiveness of EmCa cells was investigated. METHODS: The expression of NILCO mRNAs and proteins were analyzed in EmCa from African-American (n = 29) and Chinese patients (tissue array, n = 120 cases). The role of NILCO in leptin-induced invasion of Ishikawa and An3ca EmCa cells was investigated using Notch, IL-1, and leptin signaling inhibitors. RESULTS: NILCO molecules were expressed higher in type II EmCa, regardless of ethnic background or obesity status of patients. NILCO proteins were mainly localized in the cellular membrane and cytoplasm of type II EmCa. Additionally, EmCa from obese African-American patients showed higher levels of NILCO molecules than EmCa from lean patients. Notably, leptin-induced EmCa cell invasion was abrogated by NILCO inhibitors. CONCLUSION: Type II EmCa expressed higher NILCO molecules, which may suggest it is involved in the progression of the more aggressive EmCa phenotype. Obesity was associated with higher expression of NILCO molecules in EmCa. Leptin-induced cell invasion was dependent on NILCO. Hence, NILCO might be involved in tumor progression and could represent a new target/biomarker for type II EmCa.

Matrix Signaling Subsequent to a Myocardial Infarction: A Proteomic Profile of Tissue Factor Microparticles.

This study investigated the release and proteomic profile of tissue factor microparticles (TFMPs) prospectively (up to 6 months) following a myocardial infarction (MI) in a chronic porcine model to establish their utility in tracking cellular level activities that predict physiologic outcomes. Our animal groups (n = 6 to 8 each) consisted of control, noninfarcted (negative control); infarcted only (positive control); and infarcted animals treated with cardiac resynchronization therapy (CRT) and a ß-blocker (BB) (metoprolol succinate). The authors found different protein profiles in TFMPs between the control, infarcted only group, and the CRT + BB treated group with predictive impact on the outward phenotype of pathological remodeling after an MI within and between groups. This novel approach of monitoring cellular level activities by profiling the content of TFMPs has the potential of addressing a shortfall of the current crop of cardiac biomarkers, which is the inability to capture composite molecular changes associated with chronic maladaptive signaling in a spatial and temporal manner.