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Browsing by Author "Almodovar, Sharilyn"
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Item Impact of human immunodeficiency virus on pulmonary vascular disease(Magdi Yacoub Institute, 2021-06-30) Kumar, Ashok; Mahajan, Aatish; Salazar, Ethan A.; Pruitt, Kevin; Guzman, Christian Arce; Clauss, Matthias A.; Almodovar, Sharilyn; Dhillon, Navneet K.; Medicine, School of MedicineWith the advent of anti-retroviral therapy, non-AIDS-related comorbidities have increased in people living with HIV. Among these comorbidities, pulmonary hypertension (PH) is one of the most common causes of morbidity and mortality. Although chronic HIV-1 infection is independently associated with the development of pulmonary arterial hypertension, PH in people living with HIV may also be the outcome of various co-morbidities commonly observed in these individuals including chronic obstructive pulmonary disease, left heart disease and co-infections. In addition, the association of these co-morbidities and other risk factors, such as illicit drug use, can exacerbate the development of pulmonary vascular disease. This review will focus on these complex interactions contributing to PH development and exacerbation in HIV patients. We also examine the interactions of HIV proteins, including Nef, Tat, and gp120 in the pulmonary vasculature and how these proteins alter the endothelial and smooth muscle function by transforming them into susceptible PH phenotype. The review also discusses the available infectious and non-infectious animal models to study HIV-associated PAH, highlighting the advantages and disadvantages of each model, along with their ability to mimic the clinical manifestations of HIV-PAH.Item Mice with humanized immune system as novel models to study HIV-associated pulmonary hypertension(Frontiers Media, 2022-08-05) Rodriguez-Irizarry, Valerie J.; Schneider, Alina C.; Ahle, Daniel; Smith, Justin M.; Suarez-Martinez, Edu B.; Salazar, Ethan A.; McDaniel Mims, Brianyell; Rasha, Fahmida; Moussa, Hanna; Moustaïd-Moussa, Naima; Pruitt, Kevin; Fonseca, Marcelo; Henriquez, Mauricio; Clauss, Matthias A.; Grisham, Matthew B.; Almodovar, Sharilyn; Medicine, School of MedicinePeople living with HIV and who receive antiretroviral therapy have a significantly improved lifespan, compared to the early days without therapy. Unfortunately, persisting viral replication in the lungs sustains chronic inflammation, which may cause pulmonary vascular dysfunction and ultimate life-threatening Pulmonary Hypertension (PH). The mechanisms involved in the progression of HIV and PH remain unclear. The study of HIV-PH is limited due to the lack of tractable animal models that recapitulate infection and pathobiological aspects of PH. On one hand, mice with humanized immune systems (hu-mice) are highly relevant to HIV research but their suitability for HIV-PH research deserves investigation. On another hand, the Hypoxia-Sugen is a well-established model for experimental PH that combines hypoxia with the VEGF antagonist SU5416. To test the suitability of hu-mice, we combined HIV with either SU5416 or hypoxia. Using right heart catheterization, we found that combining HIV+SU5416 exacerbated PH. HIV infection increases human pro-inflammatory cytokines in the lungs, compared to uninfected mice. Histopathological examinations showed pulmonary vascular inflammation with arterial muscularization in HIV-PH. We also found an increase in endothelial-monocyte activating polypeptide II (EMAP II) when combining HIV+SU5416. Therefore, combinations of HIV with SU5416 or hypoxia recapitulate PH in hu-mice, creating well-suited models for infectious mechanistic pulmonary vascular research in small animals.Item National Heart, Lung, and Blood Institute Workshop Summary: Enhancing Opportunities for Training and Retention of a Diverse Biomedical Workforce(American Thoracic Society, 2016-04) Duncan, Gregg A.; Lockett, Angelia; Villegas, Leah R.; Almodovar, Sharilyn; Gomez, Jose L.; Flores, Sonia C.; Wilkes, David S.; Tigno, Xenia T.; Microbiology and Immunology, School of MedicineRATIONALE: Committed to its mission of conducting and supporting research that addresses the health needs of all sectors of the nation's population, the Division of Lung Diseases, National Heart, Lung, and Blood Institute of the National Institutes of Health (NHLBI/NIH) seeks to identify issues that impact the training and retention of underrepresented individuals in the biomedical research workforce. OBJECTIVES: Early-stage investigators who received grant support through the NIH Research Supplements to Promote Diversity in Health Related Research Program were invited to a workshop held in Bethesda, Maryland in June, 2015, in order to (1) assess the effectiveness of the current NHLBI diversity program, (2) improve its strategies towards achieving its goal, and (3) provide guidance to assist the transition of diversity supplement recipients to independent NIH grant support. METHODS: Workshop participants participated in five independent focus groups to discuss specific topics affecting underrepresented individuals in the biomedical sciences: (1) Socioeconomic barriers to success for diverse research scientists; (2) role of the academic research community in promoting diversity; (3) life beyond a research project grant: non-primary investigator career paths in research; (4) facilitating career development of diverse independent research scientists through NHLBI diversity programs; and (5) effectiveness of current NHLBI programs for promoting diversity of the biomedical workforce. MEASUREMENTS AND MAIN RESULTS: Several key issues experienced by young, underrepresented biomedical scientists were identified, and solutions were proposed to improve on training and career development for diverse students, from the high school to postdoctoral trainee level, and address limitations of currently available diversity programs. Although some of the challenges mentioned, such as cost of living, limited parental leave, and insecure extramural funding, are also likely faced by nonminority scientists, these issues are magnified among diversity scientists and are complicated by unique circumstances in this group, such as limited exposure to science at a young age, absence of role models and mentors from underrepresented backgrounds, and social norms that relegate their career endeavors, particularly among women, to being subordinate to their expected cultural role. CONCLUSIONS: The factors influencing the participation of underrepresented minorities in the biomedical workforce are complex and span several continuous or overlapping stages in the professional development of scientists from these groups. Therefore, a multipronged approach is needed to enable the professional development and retention of underrepresented minorities in biomedical research. This approach should address both individual and social factors and should involve funding agencies, academic institutions, mentoring teams, professional societies, and peer collaboration. Implementation of some of the recommendations, such as access to child care, institutional support and health benefits for trainees, teaching and entrepreneurial opportunities, grant-writing webinars, and pre-NIH career development (Pre-K) pilot programs would not only benefit biomedical scientists from underrepresented groups but also improve the situation of nondiverse junior scientists. However, other issues, such as opportunities for early exposure to science of disadvantaged/minority groups, and identifying mentors/life coaches/peer mentors who come from similar cultural backgrounds and vantage points, are unique to this group.