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Comparison of vaginal microbiome and symptoms in African American women with gynecologic cancers vs healthy controls

PI:  Deborah Watkins Bruner, RN, PhD, FAAN
Emory University
School of Nursing
Academic Advancement

Co-I: Kostas Konstantinidis, PhD
Associate Professor
Georgia Institute of Technology
School of Civil & Environmental Engineering
School of Biological Sciences (Adjunct)

Almost 800,000 women globally were diagnosed with gynecologic cancer (GyneCa) last year, of which endometrial (EndoCa) and cervical cancer (CervixCa) account for 75%. Recent U.S. statistics show almost 1 million survivors are living after these cancers. Women of African descent (Black) have the 2nd highest incidence of CervixCa but they have the highest death rates, and for EndoCa they have higher rates, more aggressive types, and poorer survival. Black women are also known to have distinct vaginal microbiome (VM) profiles associated with infections. To date, associations among the VM and cancer risk or treatment outcomes have not been studied. Of additional concern is that two-thirds of women who receive GyneCa treatments will be cured and live for decades with significant treatment-related symptoms including infections, vaginal spotting/bleeding on exam or sex, and painful sex. To address these significant issues, we collected preliminary data which demonstrate: 1) feasibility of our methods; 2) microbial pathogens associated with infection higher in Black patients post-treatment; 3) differences in VM profiles between GyneCa patients and healthy controls. We propose to conduct a secondary analysis to assess 42 Black women: 14 with GyneCa and 28 healthy Black controls to 1) evaluate differences in VM using metagenomics and 2) assess associations with poor outcomes after cancer treatments. Findings will help provide hypotheses for larger studies of risk factors for health disparities and poor outcomes in Black women and stimulate interventions (e.g., probiotics) to promote a healthier vaginal environment and minimize severe, often persistent symptoms in GyneCa survivors.

Validating a Scale to Measure Sexual Harassment in Jordan

PI:  Cari Jo Clark
Associate Professor
RSPH, Department of Global Health

Co-I: Kathryn M. Yount, PhD
Department of Sociology
Hubert Department of Global Health

Sexual harassment (SH) is prevalent worldwide and is associated with physical9  and mental harm and poor educational success for women. Our recently funded project, Ihtarmni (Respect Me), is the first test of a program to prevent SH in a Middle Eastern University setting. However, we have found that there is no validated measure of SH in a Middle Eastern context and formative research for our project at the University of Jordan (UJ), the site of the study, suggests that existing measures of SH, developed originally to examine SH in US-based places of employment may not be suitable to Jordan. Thus, it is urgent that we develop and test a measure of SH so that the team might measure true changes in SH that may come about from  students’ exposure to Ihtarmni. We propose to use our existing research infrastructure and team members in the US and in Jordan to adapt items from existing scales and to generate contextually relevant measures of SH victimization and perpetration. We will then test the adapted SH scales in interviews with a sample of university students (N=20) to make sure that items are measuring what we expect them to measure. We will make final adjustments to the scales and use them to estimate the extent of SH through an online survey administered to 1200 UJ students (600 men, 600 women).

Evaluating Satellite-based PM2.5 Air Quality Models in Urban East Asia

PI:  Yang Liu, PhD
Associate Professor
Emory University
Rollins School of Public Health

Co-I:  Avani Wildani, PhD
Assistant Professor
Emory University
Department of Math and Computer Science

The 2015 Global Burden of Diseases study estimated that exposure ambient fine particulate matter (PM2.5, airborne particles less than 2.5 micrometer in aerodynamic diameter) is responsible for 4.2 million deaths in 2015, overwhelmingly in low- and middle-income countries. However, these calculations were made by extrapolating the exposure-response functions derived in developed countries with much lower PM2.5 levels. Lack of reliable PM2.5 exposure estimates is a major hurdle to conducting PM2.5 health effects research, and most highly polluted cities in the developing world cannot afford large-scale routine ground monitoring.

Research in the past decade has shown that satellite remote sensing data, especially aerosol optical depth (AOD), can be a promising solution to this great challenge. Various statistical and machine learning models have been developed using satellite data to estimate PM2.5 levels. However, most of such work has been done in the US at very low PM2.5 levels instead of the developing worlds with high pollution levels and high population density. In this applied study, we propose to transfer the satellite PM2.5 models developed in the US to two East Asian urban regions. We aim to answer two important and practical questions: (1) would these models developed using local inputs perform as well as those supported by US data sources? and (2) how would model accuracy improve with more ground measurements? In addition to advancing our knowledge of PM2.5 in these understudied regions, we also expect to use the findings of this project as preliminary results for future extramural grant proposals.

The time of Aids: What Happened Here, the Power of Human Resilience, and the Progress and Discoveries that Resulted

PI:  Cindy Powell, MD, MPH
Assistant Professor
School of Medicine
Emory Critical Care Center
Division of Pulmonary, Allergy, and Critical Care Medicine

Co-PI:  Robert E. Schmidt Barracano, MFA
Professor and Director of Production
Department of Film and Media

Hiv first appeared in 1981 when the New York Times published “Rare Cancer Seen in 41 Homosexuals,” describing a series of cases with Kaposi’s sarcoma. That weekend, many of the same lesions were found by gay men themselves as they desperately searched their bodies for signs of the disease (1). It was the beginning of the AIDS epidemic that would go on to claim millions of lives worldwide, and it would change literally everything about modern life, from the most intimate details of our relationships to the way the medical community and society as a whole confront disease epidemics in general. AIDS also coincided in time with the development of electronic devices that would go on to record the full impact of the tragedy and broadcast it on the newly created 24 hour news channels. As a result, much has been published about the epidemic. What has not been told is the story of the south, and of Atlanta in particular, of how its medical centers were overwhelmed with the sick, how ordinary people, including many in training to become the next generation of health care providers, would rise up to confront this enemy. It felt to many of them like swimming into a tsunami. The purpose of this project is to document these stories and to use them to shed light on what happened, on the human resilience it highlighted, and on how it shaped our medical advancements and our society at large up to the present time.

Prophylactic Progesterone Treatment for Neonatal Anesthesia Neuroinflammation

PI: Jessica Raper, PhD
Research Assistant Professor
Yerkes Primate Research Center
Co-PI: Iqbal Sayeed, PhD
Assistant Professor
School of Medicine
Emergency Medicine

Although anesthetic drugs are safe and effective, recent concern have been raised that anesthetics may cause neurotoxicity in the developing brain. Animal studies demonstrate anesthesia-induced neuro-inflammation and -toxicity, whereas epidemiological studies demonstrate increased risk for learning disabilities and ADHD in children who receive three or more anesthetic exposures before four years old. Considering that over 6 million children need to undergo general anesthesia every year, there is a great need to find a treatment that will mitigate the neurocognitive effects of early anesthesia exposure. Substantial body of preclinical work demonstrates the neuroprotective and restorative effect of progesterone in several experimental models of brain injury. In this URC proposal, we seek to evaluate anesthesia-induced neuroinflammation and long-term neurocognitive changes in a rodent model of repeated neonatal sevoflurane exposure. Next, we will examine whether the prophylactic progesterone treatment dampens neuroinflammation and attenuates neurological/functional deficit caused by repeated sevoflurane exposure. We hypothesize that pretreatment with progesterone will reduce microglia activation in the brain (neuroinflammatory marker) and protect the hippocampus from ultrastructure damage induced by repeated anesthesia exposure. In addition, we anticipate that progesterone will result in no observable difference in anxiety behavior nor impairments in learning and memory tasks compared to controls. This project will provide proof of concept that progesterone can protect against anesthesia-induced neuroinflammation. These preliminary data will also provide a basis for a larger-scale study to extend findings into a nonhuman primate model of anesthesia neuroinflammation, which will provide a key step toward translational use in humans.

Hybrid microfluidics model of human airway inflammation by transmigrated blood leukocytes

PI:  Rabindra Tirouvanziam, PhD
Assistant Professor
School of Medicine
Department of Pediatrics, PACS Division

Co-PI:  Shuichi Takayama, PhD
School of Medicine
Department of Biomedical Engineering

Inflammatory airway diseases (IADs) cause significant morbidity and mortality worldwide. Examples of IAD include asthma, the leading chronic condition in children; chronic obstructive pulmonary disease (COPD), the third leading cause of adult deaths; and cystic fibrosis (CF), the most common genetic disease in Caucasians. A hallmark of IADs is the recruitment of blood leukocytes through the airway epithelium, and into the lumen. Therein, leukocytes are exposed to various cues (from the epithelium, and from leukocytes recruited earlier) that cause them to undergo pathological changes. These changes often result in reduced protective antimicrobial functions, and enhanced self-injurious oxidative, proteolytic, and pro-inflammatory signaling. Interactions between airway epithelium and transmigrated leukocytes are dynamic and complex, and there currently lacks models capable of mimicking them accurately, in ways that would enable development of better drugs for intractable IADs such as asthma, COPD, and CF. To tackle this unmet need, we will leverage complementary expertise and innovations of the Tirouvanziam (human airway immunology) and Takayama (lung-on-a-chip) groups in a new collaboration. Our objective is to deliver the first-of-its kind hybrid microfluidics model incorporating a human airway epithelium grown at air-liquid interface on the underside of a porous  matrix, with apical flow of blood leukocytes enabling transepithelial migration into the lumen. This model will be validated by real-time microscopy and multimodal endpoint analysis by physiological and phenotypic assays. This interdisciplinary pilot study will open avenues for extramural proposals relevant to translational airway biology and bioengineering, both research areas in which our laboratories hold successful track records. This interdisciplinary pilot study will open avenues for extramural proposals relevant to translational airway biology and bioengineering, both research areas in which our laboratories hold successful track records.

Feasibility of Closed-Loop Deep Brain Stimulation to Treat Sleepiness and Cataplexy in a Mouse Model of Human Narcolepsy Type 1

PI: Jon T. Willie, M.D., Ph.D.
Assistant Professor
School of Medicine
Laboratory for Behavioral Neuromodulation
Department of Neurosurgery

Co-PI:  Babak Mahmoudi, Ph.D.
Assistant Professor
Georgia Institute of Technology
Emory University School of Medicine
Departments of Biomedical Engineering and Biomedical Informatics

Narcolepsy type 1 is a brain disorder associated with excessive sleepiness and attacks of paralysis triggered by emotion (cataplexy). Electrical signals from the brain and muscles during cataplexy show features of rapid-eye-movement (REM) sleep and other abnormal signals occurring during wake. Narcolepsy is caused by loss of a specific group of wake-active excitatory brain cells (orexin neurons) in the hypothalamus, a deep brain structure. There is currently no cure, but genetically modified mice with absence of orexin neurons provide a validated model in which experimental therapies can be tested. We are interested in determining whether direct electrical stimulation (deep brain stimulation, DBS), which provides benefit for other neurological disorders, could also benefit narcolepsy. First, we will use narcoleptic mice implanted with brain recording electrodes to prove that abnormal brain signals can specifically predict and detect abnormal behavior (sleep attacks and cataplexy). Then, we will use stimulation electrodes in different candidate brain regions related to emotion and arousal to immediately improve alertness and reverse cataplexy when these symptoms are observed to occur. Finally, we will develop real-time computer analysis of brain recordings to control stimulation (closed-loop DBS) in freely-behaving narcoleptic mice to prevent narcolepsy symptoms continuously in real time. This pilot study will test the feasibility of a novel translational therapy (DBS for sleep-wake and arousal disorders), which represents a completely novel indication for DBS. This work would advance neuroscience and   have translational therapeutic implications for narcolepsy, primary hypersomnia, and post-traumatic stress disorder, which are all conditions treated at Emory.