Adverse Effects of a Clinically Relevant Dose of Hydroxyurea Used for the Treatment of Sickle Cell Disease on Male Fertility Endpoints

Two experiments were conducted to determine: 1) whether the adult male transgenic sickle cell mouse (Tg58 × Tg98; TSCM), exhibits the patterns of reproductive endpoints (hypogonadism) characteristic of men with sickle cell disease (SCD) and 2) whether hydroxyurea (HU) exacerbates this condition. In Experiment 1, blood samples were collected from adult age-matched TSCM and ICR mice (ICRM) (N = 10/group) for plasma testosterone measurements. Subsequently, mice were sacrificed, testes excised and weighed and stored spermatozoa recovered for the determination of sperm density, progressive motility and percentage of spermatozoa with normal morphology. In experiment 2, adult male TSCM were orally treated with 25 mg HU/kg body weight/day for 28 or 56 days. Control mice received the vehicle for HU (saline) as described above. At the end of the treatment periods, blood samples were collected for quantification of circulating testosterone. Subsequently, mice were sacrificed, testes and epididymides were recovered and weighed and one testis per mouse was subjected to histopathology. Stored spermatozoa were recovered for the determination of indices of sperm quality mentioned in Experiment 1. Testis weight, stored sperm density, progressive motility, percentage of spermatozoa with normal morphology and plasma testosterone concentrations of TSCM were significantly lower by 40, 65, 40, 69 and 66%, respectively than those of ICRM. These data indicate that adult TSCM used in this study suffered from hypogonadism, characteristically observed among adult male SCD patients. In Experiment 2, HU treatment significantly decreased testis weight on day 28, (0.09 ± 0.004g) that was further decreased on day 56 (0.06 ± 0.003g; treatment x time interaction) compared with controls (day 28, 0.15 ± 0.01g; day 56, 2, 0.16 ± 0.01g). Concomitant with a 52% shrinkage (P<0.001) in area of testes in 56 days of HU treatment, testes from HU-treated TSCM exhibited significant atrophic degeneration in the seminiferous tubules compared with controls. Furthermore, treated TSCM had only Sertoli cells and cell debris remaining in most of the seminiferous tubules in comparison with controls. Leydig cell prominence and hyperplasia were more evident (P<0.05) in the steroidogenic compartments of testes of HU-treated TSCM compared with controls. However, plasma testosterone concentrations were reduced by HU treatment (P<0.05; treatment x time interaction) compared with controls on the two time periods studied. Epididymides from HU-treated TSCM sustained a 25% shrinkage (P<0.05), along with 69 (P<0.005) and 95% reduction (P<0.005), in stored sperm density and sperm progressive motility (treatment x time interaction P<0.05), respectively on day 56 of treatment compared with controls. These data demonstrate that TSCM used in this study exhibited SCD-induced hypogonadism, thus authenticating their use for studying the effect of HU on male reproductive endpoints observed in SCD patients. Secondarily, our data show that HU treatment exacerbated the already SCD-induced hypogonadism to gonadal failure

The Moral & Ethical Imperatives to Achieve Health Equity

The annual lecture of the Phillips/C. J. “Pete” Silas Program in Ethics and Leadership was presented on September 19, 2018 from 3:00 p.m.- 4:00 p.m. in the Molecular Science and Engineering Building (MoSE), Room G011, Georgia Tech.Valerie Montgomery Rice, MD, FACOG, has served at the highest levels of patient care and medical research, as well as organizational management and public health policy. Marrying her management skills and strategic thinking to tackle challenging problems, she has a track record of redesigning complex organization’s management infrastructures to reflect the needs of evolving strategic environments and position the organization for success. Named the sixth president of Morehouse School of Medicine (MSM) and the first woman to lead the free-standing medical institution in 2014, Montgomery Rice serves as both the president and dean. A renowned infertility specialist and researcher, she previously served as dean and executive vice president for three years. Dedicated to the creation and advancement of health equity, she holds membership in many organizations and boards, including the National Academy of Medicine, National Center for Advancing Translational Sciences, Board of Directors for Kaiser Permanente School of Medicine, Board of Directors for The Nemours Foundation, Board of Directors for UnitedHealth Group, Ni-Q Medical Advisory Team, and the Association of American Medical Colleges Council of Deans. Montgomery Rice has received numerous accolades and honors. She was named to the Horatio Alger Association of Distinguished Americans and received the 2017 Horatio Alger Award. For two consecutive years (2016, 2017) Georgia Trend selected Montgomery Rice as one of the 100 Most Influential Georgians. Other honors include the following: Trumpet Vanguard Award (2015), The Dorothy Heights Crystal Stair Award (2014), National Coalition of 100 Black Women – Women of Impact (2014), YWCA – Women of Achievement (Atlanta-2014 and Nashville-2007), American Medical Women’s Association Elizabeth Blackwell Medal (2011) and Working Mother Media Multicultural Women’s Legacy Award (2011). A Georgia native, Montgomery Rice holds a bachelor’s degree in chemistry from the Georgia Institute of Technology, a medical degree from Harvard Medical School and an honorary degree from the University of Massachusetts Medical School. She completed her residency in obstetrics and gynecology at Emory University School of Medicine and her fellowship in reproductive endocrinology and infertility at Hutzel Hospital.Runtime: 54:29 minutesAs partisan politics becomes more and more entrenched in our society and continue to creep into the policy decisions that impact the everyday lives of individuals, the fight for health equity is becoming an increasingly moral one. This lecture evaluates the three main arguments for advancing health equity for all: the national security argument, the economic argument, and the moral argument. It will underscore the notion that while all three should have a place in societal discourse, it is the moral argument that should strike the most compelling chord. Key to this analysis is recognition of the alarming statistics that highlight the health disparities that many minority groups face in spite of the numerous resources that we have to offer as a country. This lecture concludes with a call to action, to champion the advancement of health equity, that should be heeded by all leaders and concerned citizens, as there are not only the moral and ethical imperatives compelling such, but also because it is inherently the American thing to do

The 2014 Minority Health and Health Disparities Grantees’ Conference

Health disparities have been defined as a particular type of health difference closely linked with social, economic and/or environmental disadvantage. The National Institute on Minority Health and Health Disparities (NIMHD) at the National Institutes of Health, has a comprehensive portfolio of grants that fund scientific research to improve racial/ethnic minority health and eliminate health disparities. The 2014 Minority Health and Health Disparities Grantees’ Conference highlighted excellence and innovation in biological, environmental, sociocultural, clinical and behavioral research supported by NIMHD. This special issue of the International Journal of Environmental Research and Public Health includes peer-reviewed publications from investigators who participated in this conference

Bringing New Minds and New Methods to Bridging Health Disparity and Equity

No abstract available

Aspirin Blocks EGF-stimulated Cell Viability in a COX-1 Dependent Manner in Ovarian Cancer Cells

licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2013.07.08; Accepted: 2013.09.20; Published: 2013.09.27 Objective: Although aspirin has been associated with a reduction of the risk of cancer when used as a nonsteroidal anti-inflammatory drug, its use to reduce the risk of ovarian cancer is controversial. Ovarian cancer cells usually express high levels of cyclooxygenase-1 (COX)-1. Because aspirin is a rather selective inhibitor of COX-1, the ability of aspirin to reduce the risk of ovarian cancer may be dependent on the level of COX-1 expression in those cells. Furthermore, epidermal growth factor receptor (EGFR) is frequently overexpressed in the malignant phenotype of ovarian cancer leading to increased cell proliferation and survival. Here we investigated if aspirin attenuates EGFR-activated ovarian cancer cell growth in a COX-1 dependent manner. Methods: Cell viability assays and Western blot analyses were used to determine the effect of aspirin on EGF-stimulated cell proliferation. Gene silencing and gene expression techniques were employed to knockdown or to express COX-1, respectively

Evaluation of Quantra Hologic Volumetric Computerized Breast Density Software in Comparison With Manual Interpretation in a Diverse Population

Objective: Increased mammographic breast density is a well-established risk factor for breast cancer development, regardless of age or ethnic background. The current gold standard for categorizing breast density consists of a radiologist estimation of percent density according to the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) criteria. This study compares paired qualitative interpretations of breast density on digital mammograms with quantitative measurement of density using Hologic’s Food and Drug Administration–approved R2 Quantra volumetric breast density assessment tool. Our goal was to find the best cutoff value of Quantra-calculated breast density for stratifying patients accurately into high-risk and low-risk breast density categories. Methods: Screening digital mammograms from 385 subjects, aged 18 to 64 years, were evaluated. These mammograms were interpreted by a radiologist using the ACR’s BI-RADS density method, and had quantitative density measured using the R2 Quantra breast density assessment tool. The appropriate cutoff for breast density–based risk stratification using Quantra software was calculated using manually determined BI-RADS scores as a gold standard, in which scores of D3/D4 denoted high-risk densities and D1/D2 denoted low-risk densities. Results: The best cutoff value for risk stratification using Quantra-calculated breast density was found to be 14.0%, yielding a sensitivity of 65%, specificity of 77%, and positive and negative predictive values of 75% and 69%, respectively. Under bootstrap analysis, the best cutoff value had a mean ± SD of 13.70% ± 0.89%. Conclusions: Our study is the first to publish on a North American population that assesses the accuracy of the R2 Quantra system at breast density stratification. Quantitative breast density measures will improve accuracy and reliability of density determination, assisting future researchers to accurately calculate breast cancer risks associated with density increase

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&rsquo;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&rsquo;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 &ldquo;dual eligibles&rdquo;). 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