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Rurality, Infant Feeding Practices, And Perinatal Cardiovascular Health Behaviors, Elly Marie Marshall

Graduate Theses, Dissertations, and Problem Reports (ETD)

Introduction: Cardiovascular diseases are a leading cause of pregnancy-related deaths in the United States, with higher rates in rural areas. While limited healthcare access contributes to this disparity, other factors remain unclear. Breastfeeding provides long-term protection against cardiovascular disease, but modern infant feeding practices are complex and may impact maternal cardiovascular health (CVH) in unexpected ways. Healthy CVH behaviors of sufficient sleep duration, adequate physical activity, a healthy diet, and nicotine avoidance can enhance protection against future cardiovascular disease risk. Therefore, the aims of this dissertation are to 1) assess associations between rurality and first trimester CVH behaviors; 2) synthesize …

Oxytocin Dosing During Trial Of Labor After Cesarean To Minimize The Risk Of Uterine Rupture: A Systematic Review And Meta-Analysis, Pierpaolo Nicolì, Moti Gulersen, Jordan Beacham, Hila Hochler, Alessandra Familiari, Anna Locatelli, Cynthia Abraham, Ettore Cicinelli, Amerigo Vitagliano, Vincenzo Berghella

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: Oxytocin remains the mainstay for induction and for the management of labor arrest during trial of labor after cesarean (TOLAC). Therefore, the clinical question should be not whether to use oxytocin, but how to optimize its administration. This meta-analysis aimed to assess which oxytocin protocol, in terms of initial dose, amount of increase, timing to next increase, and maximum dose, may minimize the risk of uterine rupture (UR) during TOLAC.

DATA SOURCES: PubMed, Embase and Clinicaltrials.gov were searched up to September 21, 2024.

STUDY ELIGIBILITY CRITERIA: Randomized and nonrandomized studies evaluating the association between induction and/or augmentation with oxytocin …

The Psychiatric Burden Of Hidradenitis Suppurativa: A Trinetx Analysis Of Sex-Specific Disparities In Mental Health And Medication Use, Emily Sheetz, Julia Feord, Collette Sholi, Parker Adams, Tamas Gal, Susan G. Kornstein, Arturo Saavedra

Department of Medicine Faculty Publications

Background:

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition associated with physical and psychological burden. Prior research has shown increased rates of depression and anxiety among individuals with HS; however, sex-based disparities in the prevalence of these mental health conditions in patients with HS remain underexplored.

Objective:

To evaluate sex-based differences in the prevalence of major depressive disorder (MDD), generalized anxiety disorder (GAD), and the prescribing of antidepressants and anxiolytics among patients with HS.

Methods:

Using the TriNetX database, we identified patients over the age of 18 who had a recorded diagnosis of HS. Propensity score matching based on …

Upadacitinib For Recalcitrant Extraintestinal Crohn Disease, Avery H. Seward, Jeffrey P. Callen

Department of Medicine Faculty Publications

[Introduction] Crohn disease is a chronic inflammatory bowel disease that affects the gastrointestinal tract from the mouth to the anus. Extra-intestinal manifestations of Crohn disease are common, with the skin being the most commonly involved site.¹ Cutaneous manifestations of Crohn include lesions that directly extend from the bowel to the skin, whereas extraintestinal Crohn disease involves sites that do not directly extend from the bowel.¹ Extraintestinal Crohn disease is often resistant to treatments and often does not parallel the activity of the bowel disease.¹ There have only been 3 documented cases of extraintestinal Crohn disease responding to upadacitinib.²,³ We describe …

Combined Snare And Buddy-Balloon Strategy For Failed Valve Crossing In Valve-In-Valve Transcatheter Aortic Valve Replacement, Hira Sarfraz, Muhammad U. Javed, Parth K. Parikh, Joshua A. Cohen, Raymond L. Benza, Matthew R. Summers, Deepak R. Talreja

Department of Medicine Faculty Publications

Background

Retrograde valve crossing during valve-in-valve transcatheter aortic valve replacement (ViV TAVR) may fail despite modern delivery systems.

Case Summary

A 67-year-old man with a degenerated 27-mm Magna Ease bioprosthesis and unfavorable aortic geometry (kinked ascending aorta at a prior surgical graft site) underwent ViV TAVR, where retrograde valve crossing failed despite multiple stiff guidewires and snare traction alone. Successful delivery of a 29-mm Evolut FX+ was ultimately achieved by combining gooseneck-snare traction for coaxial realignment with a partially inflated Tyshak buddy balloon acting as a mechanical ramp across the surgical valve frame.

Discussion

This case demonstrates a structured, stepwise …

Selenium And Liver Steatosis And Fibrosis: Opposing Direct And Steatosis-Mediated Associations In A Large Cohort, Neda Rehan, Jubilee Benedict, Rehan Qayyum

Department of Medicine Faculty Publications

Background and Aims

Epidemiologic studies have reported conflicting associations between selenium exposure and liver disease. Whether selenium exerts opposing direct and steatosis-mediated effects on liver fibrosis is unknown. To evaluate the associations of blood selenium with elastography-defined hepatic steatosis and fibrosis and to determine whether hepatic steatosis mediates the relationship between selenium and fibrosis.

Methods

We conducted a cross-sectional analysis of adults aged >= 18 years in NHANES 2017-2023. Hepatic steatosis was assessed using the controlled attenuation parameter (CAP) and fibrosis using liver stiffness measurement (LSM). Blood selenium was categorized into quartiles. Survey-weighted multivariable linear regression and structural equation modeling …

Glucagon-Like Peptide Receptor Agonists (Glp-1ras) As Cardiovascular Risk Modifiers In Obstructive Sleep Apnea And Obesity: A Real-World Study, Jaeun Ahn, Junmin Song, Kyle Admire, Yu Chang, Kuan-Yu Chi, Nathaniel T. Gordon, Joshua M. Sill

Department of Medicine Faculty Publications

Introduction

Obstructive sleep apnea (OSA) is a well-established risk factor for cardiovascular disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated potential in reducing cardiovascular risk and improving OSA severity. However, a significant knowledge gap remains regarding the impact of GLP-1RAs on cardiovascular events in OSA patients.

Methods

We examined patients with a BMI over 30 diagnosed with OSA between January 2010 and November 2021 without a previous diagnosis of heart failure, pulmonary hypertension, or myocardial infarction. Two cohorts were created: those prescribed GLP-1RAs within 1 year of their OSA diagnosis and patients who were never prescribed GLP-1RAs. Propensity score matching …

Multiparametric Flow Cytometry Immune Profiling Of Pulmonary And Extra-Pulmonary Tuberculosis Reveals Distinct Blood-Based Biomarker Signatures, Kalaiarasan Ellappan, Prakash Babu Narasimhan, Harriet N. Garlant, Seshadri Vasan, Komal Jain, Saka Vinod Kumar, Vishnukanth Govindaraj, Vir Singh Negi, Karen E. Kempsell

Research outputs 2022 to 2026

This study investigated immune cell distributions, cell-specific immune markers, and selected biomarker targets in pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) using multiparametric flow cytometry (MFC). Whole blood was collected from 45 individuals, including healthy controls (HC), EPTB, and PTB patients (n = 15/group). Peripheral blood leukocytes were analysed by MFC to characterize CD4+ and CD8+ T cells, natural killer (NK), invariant NKT (iNKT) and NKT cells, classical (CM), intermediate (IM) and non-classical monocytes (NCM), and activated monocytes (AM). Expression of GBP1, CALCOCO2, IFIT3, SNX10, ARG1, PD-1, and PD-L1 was assessed across these immune subsets. Increased frequencies of NK, NKT, …

Understanding The Syphilis Resurgence Among Females Of Childbearing Age: Informing Prevention Efforts In New York State, Salvatore Currenti

Electronic Theses & Dissertations (2024 - present)

Syphilis is caused by Treponema pallidum and transmitted through direct contact with infected mucosal lesions and via vertical transmission during pregnancy (i.e., congenital). Transmission of syphilis to an infant during pregnancy (i.e., congenital syphilis [CS]) can lead to early fetal death, stillbirth, neonatal death, preterm birth, low birthweight, and congenital infection in infants. The United States (U.S.) is experiencing epidemic increases in both females of reproductive age with syphilis and infants with CS. In New York State (NYS), these trends have also occurred, especially after COVID-19 emergence, and increases in reported cases and incidence rates are comparable to national statistics. …

Neighborhood Socioeconomic Deprivation And Physical Activity Associate With Extracellular Vesicle Size And Cargo In A Community-Based Cohort Of Women, Yvonne Baumer, Elizabeth M. Aquino Peterson, Matthew R. Bavuso, Noel Miller, Cristhian A. Gutierrez-Huerta, Nithya P. Vijayakumar, Sam J. Neally, Kaveri Curlin, Valerie M. Mitchell, Billy S. Collins, Neelam R. Redekar, Subrata Paul, Anca D. Dobrian, Tiffany M. Powell-Wiley

Department of Biomedical and Translational Sciences Faculty Publications

African American (AA) women face disproportionate cardiovascular disease (CVD) risk due to adverse social determinants of health (SDoH), including lower socioeconomic status (SES). Physical activity (PA) and plasma extracellular vesicles (EVs) modulate CVD risk, but their relationships with SDoH remain unclear. This study examines associations between SDoH, PA, and plasma EVs in a Washington, DC-based cohort of at-risk AA women. Participants (N = 24, Age: 57 ± 12, BMI: 35 ± 6, ASCVD: 9 ± 5) joined the Step It Up Community-Engaged, Digital Health Physical Activity Intervention pilot study. EVs were isolated from fasting plasma samples. Multivariable regression, adjusted for …

Comparative Mass Spectrometry Analysis Of High And Low Centrifugation Extracellular Vesicle (Ev) Pellets From Healthy Urine Following Tamm-Horsfall Protein Removal, Dana Bielopolski, Luca Musante, Henrik Molina, Douglas Barrows, Samantha Upson, Lifang Yang, Thomas Carrol, Jonathan N. Tobin, Rhonda G. Kost, U. Erdbrügger

Department of Biomedical and Translational Sciences Faculty Publications

Objectives

Urinary extracellular vesicles (uEVs) are potential biomarkers for renal physiology and disease. Their isolation is challenged by Tamm-Horsfall protein (THP) contamination, particularly in high-speed ultracentrifugation (P100) fractions. Low-speed (P20) fractions contain biologically relevant uEVs, yet their proteomic composition is underexplored. This study evaluates strategies for THP removal to optimize mass spectrometry analysis and characterizes P20 and P100 uEV proteomes and its combination in healthy urine.

Methods

Urine from a healthy volunteer was processed via sequential centrifugation at 21,200 g (P20) and 164,244 g (P100). THP removal was performed using low ionic strength buffer (P20) and size-exclusion chromatography (P100). Western …

Inhibition Of Histone Demethylase Lsd1 Suppresses Cd47 Expression And Enhances Efficacy Of Cd47 Blockade In Breast Cancer, Fengjie Jiang, Yu Shen, Bing Li, Michael Henry, Nancy Davidson, Yi Huang

Department of Biomedical and Translational Sciences Faculty Publications

Background CD47 functions as a “don’t eat me” checkpoint, inhibiting macrophage-mediated phagocytosis in triple-negative breast cancer (TNBC). While anti-CD47 therapies can restore immune surveillance, their efficacy in TNBC is often limited by immune evasion and drug development challenges.

Methods We investigated the crosstalk between the histone demethylase lysine-specific demethylase 1 (LSD1) and CD47 signaling in TNBC using in silico datasets, isogenic cell lines, conditional BRCA1 knockout models, and syngeneic mouse models. Techniques such as immunohistochemistry, multiplex immunofluorescence, immunoprecipitation, protein ubiquitination, chromatin immunoprecipitation, chemotaxis, flow cytometry, and phagocytosis assays were employed to examine the epigenetic regulation of CD47 by LSD1 and …

Expert Consensus On Osteoporosis Risk Management In Patients With Sleep Disorders, Siqi Leng, Jinming Yang, Yuming Jin, Jie Shi, Ye Zhang, Junying Zhou, Lusi Tan, Taomei Li, Peiyan Ni, Kejia Hu, Yuan Shi, Jiamin Liao, Yun Li, Pei Xue, Christian Benedict, Alexandros N. Vgontzas, Michael Furian, Talant Sooronbaev, Naima Covassin, Virend K. Somers, Zhoulong Yu, Hongqiang Sun, Xiao Tan, Jihui Zhang, Yun Kwok Wing, Yue Leng, Larry D. Sanford, Michael V. Vitiello, Katie L. Stone, Rong Ren, Lin Lu, Xiangdong Tang

Department of Biomedical and Translational Sciences Faculty Publications

A rate-limiting step in the prevention and early intervention of osteoporosis is identifying its asymptomatic onset. Accumulating evidence shows that sleep disorders are associated with an increased risk of osteoporosis. Given their early detectable and modifiable nature, integrating sleep disorder management into osteoporosis prevention and care pathways offers a novel approach for enhancing skeletal health. This expert consensus represents a collaborative effort by specialists in sleep medicine and orthopedics from across the world, integrating epidemiological, mechanistic, and interventional evidence to provide general guidance for prevention and clinical practice, and to foster multidisciplinary collaboration in the management of sleep disorders and …

Ornithine Metabolism In Retinal Pigment Epithelium And Retina And Implications In Gyrate Atrophy, Artjola Puja

Graduate Theses, Dissertations, and Problem Reports (ETD)

Ornithine aminotransferase (OAT) is a mitochondrial enzyme that regulates ornithine metabolism by converting ornithine to pyrroline-5-carboxylate, a precursor for proline and glutamate synthesis. Deficiency of OAT causes systemic ornithine accumulation and leads to gyrate atrophy (GA) of the choroid and retina, a hereditary disorder characterized by progressive chorioretinal degeneration and irreversible vision loss. Chorioretinal atrophy typically starts at the mid-peripheral retina and progresses toward the macula. Although elevated ornithine is considered toxic to the eye, how ornithine is metabolized in ocular tissues and why OAT deficiency causes selective, region-specific vulnerability remain unclear. We combined ex vivo and in vivo stable …

The Gendered Heart: Closing The Gender Gap In Heart Disease Diagnosis And Treatment, Aiden Varghese

UROP Posters

Cardiovascular disease (CVD) continues to be the primary cause of death for both men and women in the United States, being characterized and treated in a historically male-centric manner. This research paper will address the disparities in risk factors for heart disease between genders, gender differences in diagnosis, and gender differences in management/treatment, thereby demonstrating the critical importance of incorporating sex specific factors into the field of cardiology. It has been demonstrated that lifestyle changes such as physical activity and smoking cessation can reduce CVD risk universally. This signifies a necessary shift toward being proactive in the prevention of CVD. …

Acute Lower Leg Transcutaneous Electrical Nerve Stimulation Increases Leg Blood Flow And Exercise Capacity In Patients With Peripheral Arterial Disease, Thomas K. Pellinger, Catherine B. Neighbors, Joshua C. Hefta, Patrick H. Luo, Carl B. Suarez, Erotokritos T. Varlas, Grant H. Simmons, Brett J. Wong

EVMS School of Health Professions Faculty Publications

We tested the hypothesis that two different durations of lower leg transcutaneous electrical nerve stimulation (TENS) increase post-TENS popliteal artery blood flow (PABF), popliteal vascular conductance (PVC), and 6-min walk distance (6MWD) in patients with peripheral artery disease (PAD). Seven subjects (5 male, 2 female) with PAD (67.9 ± 7.4 years; claudication: ankle-brachial index (ABI) < 0.90) participated in three randomized treatment sessions: control or bilateral TENS (3.0 Hz burst mode, 250 µs) for either 15 or 45 min. PABF (Doppler ultrasound) was measured before and after treatment. 6MWD and time/distance to claudication onset were measured 25 min post-treatment during each session. PABF, PVC and 6MWD increased after both 15 and 45 min of TENS (P < 0.05, post-TENS vs. pre-TENS baseline/control). Our preliminary results suggest that as little as 15 min of lower leg TENS increases leg blood flow and exercise capacity in individuals with PAD.

Mechanism-Driven Therapy For Diabetic Cardiovascular Disease, Fabian Sanchis-Gomar, Carl J. Lavie, Salvatore Carbone, Ian J. Neeland

EVMS School of Health Professions Faculty Publications

[Introduction] Diabetic cardiovascular disease is a network disorder, not a glucose-only complication

Diabetes accelerates cardiovascular (CV) target-organ damage through multiple interacting biological modules that amplify risk even when glycemia is modestly controlled^[1]. These modules include (i) adipose tissue dysfunction with altered adipokine secretion and immune-cell infiltration; (ii) ectopic lipid deposition in liver, myocardium, and perivascular/epicardial fat (iii) endothelial dysfunction with impaired nitric oxide bioavailability and heightened oxidative stress (iv) chronic kidney disease (CKD)-mediated volume, pressure, and uremic-toxin stress, and (v) autonomic and neurohormonal activation that promotes hypertension, arrhythmias, and remodeling^[1]. The clinical spectrum includes macrovascular disease …

Development Of A Semi-Mechanistic Population Pharmacokinetic Model For Predicting Tenofovir Disoproxil Fumarate And Tenofovir Alafenamide Exposure In Plasma And Cellular Matrices During Pregnancy And Postpartum, Yifan Yu, Kristina M. Brooks, Gustavo F. Doncel, Brookie M. Best, Mark A. Marzinke, Mark Mirochnick, Peter Anderson, Landon Myer, Connie Celum, Renee Heffron, Jenell Coleman, Dvora Joseph Davey, Craig W. Hendrix, Jeremiah D. Momper, Robert Bies, Rachel K. Scott

CONRAD Publications

Background and Objective

Tenofovir (TFV)-based regimens are backbones of both HIV treatment and pre-exposure prophylaxis during pregnancy. Multiple studies have shown up to one-third decreases in dried blood spot tenofovir-diphosphate concentrations during pregnancy among participants taking tenofovir disoproxil fumarate (TDF). Currently, there are no mechanism-based models describing the pharmacokinetics of tenofovir diphosphate (the active anabolite) in peripheral blood mononuclear cells (PBMCs) of pregnant individuals receiving TDF or tenofovir alafenamide (TAF), and the mechanisms behind observed differences between dried blood spots and PBMCs remain unclear.

Methods

To address this gap, we developed a semi-mechanistic model to simultaneously describe the pharmacokinetics of …

A Comparison Of F/Taf And F/Tdf As Hiv Pre-Exposure Prophylaxis In A Predominantly Cisgender Women Population In East And South Africa: A Randomised, Factorial, Non-Inferiority Trial, Sheena Mccormack, David Dunn, Sylvia Kusemererwa, Patricia Munseri, Nishanta Singh, Wiston William, Gertrude Mutonyi, Henry Bern, Lauriane Goldwirt, Cherry Kingsley, Arne Kkroidl, Christian Holm Hansen, Song Ding, Rachel Kawuma, Mary Amondi, Ubaldo Bahemuka, Deus Buma, Daniel Clutterbuck, Zakir Gaffoor, Angus Jennings, Agricola Joachim, Ayoub Kakande, Berna Kalanzi, Abisai Kisinda, Mabela Matsoso, Thomas Miller, Neetha Mmedsci Morar, Jacqueline Musau, Jane Nabbuto, Ayanda Nzuza, Doreen Pamba, Simona Salomone, Thandiwe Sithole, Edith Tarimo, Kubashni Woeber, Kundai Chinyenze, Glenda Gray, Eligius Lyamuya, Muhammad Bakari, Said Aboud, Lucas Maganga, Gustavo Doncel, Janet Seeley, Jonathan Weber, Pontiano Kaleebu, Julie Fox, Eugene Ruzagira, On Behalf Of The Prepvacc Study Group

CONRAD Publications

Background:

F/TAF was shown to be non-inferior to F/TDF as pre-exposure prophylaxis (PrEP) in men, but approval was not extended to cisgender women. We report the results of PrEPVacc, in which a predominantly female population was randomly allocated to receive daily oral F/TDF or F/TAF for ∼6 months within a HIV-1 prophylactic vaccine trial.

Setting:

Five study sites in three African countries (Uganda, Tanzania, South Africa).

Methods:

The two regimens were compared by the averted infections ratio (AIR) - the proportion of infections averted by F/TAF relative to F/TDF. The counterfactual HIV incidence, an essential component of this metric, was …

Longitudinal Changes In Plasma Biomarkers Of Immune Activation, Neuronal Inflammation And Injury In Persons With Hiv Initiating Art, Merle Henderson, Peter Dutey-Magni, Carolina Herrera, Wolfgang Stöhr, Alejandro Arenas-Pinto, Owen Swann, Amanda Heslegrave, Henrik Zetterberg, John Tregoning, Sarah Fidler, François Raffi, Andrea Calcagno, Ab Babiker, Alan Winston

CONRAD Publications

Background

Data on changes in biomarkers of brain health, and their associations with cognitive function in adults commencing either dual- or triple-antiretroviral therapy (ART) are sparse.

Methods

Plasma biomarkers (neurofilament light [NfL], glial fibrillary acidic protein [GFAP], sCD14, CXCL10, neopterin and IL-6) were measured at baseline and after 96 weeks on ART in individuals randomized to darunavir/ritonavir and either tenofovir-DF/emtricitabine (triple-ART, n = 119) or raltegravir (dual-ART, n = 119) in NEAT-001/ANRS143. Regression models examined associations of baseline and week-96 biomarker concentrations with HIV clinical parameters, composite cognitive test scores (Standardized neuropsychological test [NPZ], 7-domains) and treatment arm.

Results

In …

Formulation Development Of Topical Inserts Containing Doxycycline And Doxycycline Combined With Tenofovir Alafenamide And Elvitegravir For The Prevention Of Sexually Transmitted Infections, Vivek Agrahari, M. Melissa Peet, Jasmin Monpara, Rijo John, Sriramakamal Jonnalagadda, Pardeep K. Gupta, Meredith R. Clark, Gustavo F. Doncel

CONRAD Publications

Despite advances in oral and injectable HIV prevention options and oral prophylaxis for sexually transmitted infections (STIs) of bacterial origin, there remains a critical need for effective on-demand topical (vaginal and rectal) products for pre- and post-exposure prophylaxis (PrEP and PEP). To fill this gap, we have developed single and first-in-kind multi-active topical inserts for bacterial STIs and HIV/STIs prevention. We have formulated two different inserts, one containing doxycycline (DOX) at 10, 50, and 100 mg doses for bacterial STI prevention, and a multipurpose prevention product (TED insert) that combines DOX (10 mg) with the antiretrovirals tenofovir alafenamide (TAF; 20 …

Partial Post-Exposure Protection By Topical Inserts Containing Tenofovir Alafenamide Fumarate/Elvitegravir In A Macaque Model Of Rectal Simian Hiv (Shiv) Infection, Natalia Makarova, Tyana Singletary, M. Melissa Peet, Kristen Kelley, Ryan Johnson, Vivek Agrahari, Maria Mendoza, Yi Pan, Walid Heneine, Meredith R. Clark, J. Gerardo García Lerma, Gustavo F. Doncel, James W. Smith

CONRAD Publications

On-demand topical inserts for HIV prevention may be a good option for people who have a low frequency of sexual activity. We recently demonstrated in a preclinical macaque model that rectal application of inserts containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) conferred protection against SHIV infection (93% efficacy) when applied as pre-exposure prophylaxis 4 hours before SHIV exposure. Here, we show that the same inserts provide significant postexposure protection (82.9% efficacy) when applied 4 hours after SHIV exposure. Our findings further support the ongoing clinical development of TAF/EVG inserts for on-demand HIV prevention.

Proof-Of-Concept Development And Preclinical Evaluation Of A Microarray Patch Platform For Codelivery Of Multiple Broadly Neutralizing Antibodies For Hiv Prevention, M. Melissa Peet, Vivek Agrahari, Parbeen Singh, Lam Luong Hoai Nguyen, Louise A. Ouattara, Eun Sung Yang, Carolina Herrera, Amarendra Pegu, Theodore C. Pierson, Thanh D. Nguyen, Gustavo F. Doncel

CONRAD Publications

Broadly neutralizing antibodies (bnAbs) are advancing as a preventative or treatment option for HIV infection, but currently must be administered parenterally, typically as a large injection or infusion, an invasive method of delivery, especially for the pediatric population. Here, we present proof-of-concept data on a minimally invasive microneedle (MN) patch platform codelivering three bnAbs, PGT121, VRC07-523LS, and PGDM1400LS, from separate MN patch units or pixels. Each 1 cm² patch pixel, fabricated via solvent casting, contained ∼2 mg of one bnAb. In ex vivo porcine skin tests, the MNs effectively penetrated the skin. When tested in vitro in PBS buffer, MNs …

Micrornas Regulated By Pregnancy Target Antiviral And Cancer Immunity Overlapping With The Hiv Interactome, Paula F. T. Cezar-De-Mello, Jonathan M. Dreyfuss, Pai-Lien Chen, Hidemi Yamamoto, Xiaoming Gao, Hui Pan, Charles Morrison, Gustavo F. Doncel, Robert L. Barbieri, Raina N. Fichorova

CONRAD Publications

Innate immunity predictors of HIV-1 risk and pathogenesis vary with reproductive hormones, pregnancy, and lactation, yet the underlying mechanisms remain unclear. We hypothesized that pregnancy-associated physiological adaptations alter systemic microRNA (miRNA) expression, thereby regulating immunity, pathogenesis and susceptibility to infection. We analyzed 174 serum samples from 88 participants in a longitudinal cohort from Uganda and Zimbabwe across pre-pregnancy (PP), pregnancy (P), and postpartum breastfeeding (BF). Cell-free peripheral blood miRNAs (n = 2083) were profiled using HTG EdgeSeq. Pregnancy-specific miRNAs were identified by intersecting differentially expressed (DE) miRNAs from P vs. PP and P vs. BF comparisons. miRNA targets and pathways …

Antiviral Activity And Mucosal Safety Of Novel Human-Milk-Inspired Antimicrobial Peptides, Nazita Yousefieh, Louise A. Ouattara, Maimoona Bhutta, Ishita M. Shah, Carolina Herrera, Gustavo F. Doncel

CONRAD Publications

Background: Sexually transmitted infections (STIs) remain a major global health concern, with over one million new curable cases reported daily and limited long-term treatment options. Additionally, there are limited treatment options for women with bacterial vaginosis (BV), a dysbiotic condition predisposing them to STIs. Computationally designed human-milk-inspired antimicrobial peptides (AMPs) are promising candidates for novel antiviral and antibacterial therapies. This study evaluated the cervicovaginal mucosal safety and antiviral activity of three human-milk-inspired AMPs (MAT-006, UCD-MAT-001, and UCD-MAT-002) previously shown to exhibit antimicrobial activity against BV-causing pathogens. Methods: AMP cytotoxicity and inflammatory responses were assessed in relevant genital tract cell lines …

Predicting Oral Hiv Pre-Exposure Prophylaxis Efficacy In Cisgender Women Across Pregnancy And Postpartum, Yifan Yu, Kristina M. Brooks, Gustavo F. Doncel, Brookie M. Best, Mark A. Marzinke, Mark Mirochnick, Peter L. Anderson, Landon Myer, Connie Celum, Renee Heffron, Jenell Coleman, Dvora L. Joseph Davey, Lanxin Zhang, Max Von Kleist, Craig W. Hendrix, Jeremiah D. Momper, Robert Bies, Rachel K. Scott

CONRAD Publications

Cisgender women face an increased risk of HIV acquisition during pregnancy and postpartum. Oral pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate (F/TDF) is recommended in pregnancy despite limited published pharmacokinetic (PK) and efficacy data during pregnancy. Altered PK during pregnancy may reduce prophylactic efficacy and necessitate higher adherence. Tenofovir alafenamide (TAF) is a newer tenofovir prodrug with higher tenofovir diphosphate (TFV-DP) exposure in peripheral blood mononuclear cells (PBMCs), but the prophylactic efficacy of F/TAF across different reproductive stages in women is understudied. We adapted a multiscale modeling framework to predict the prophylactic efficacy of F/TDF and F/TAF across …

Effects Of An Early-Onset Hfd On Hepatic Functioning In A 3xtg Model Of Ad, Matthias Hirst

Graduate Theses, Dissertations, and Problem Reports (ETD)

Background: Approximately 1 billion people currently live with obesity. Driven by factors such as a high-fat diet (HFD), this pathology can have drastic effects throughout the body, with the liver in particular being a main target of its downstream consequences. Although it is capable of storing lipids, excess fat can conglomerate in the liver and contribute to various hepatic pathologies. A specific pattern of hepatic dysfunction seen in response to an HFD is increased acetylation of mitochondrial proteins. Further, expression and activity of insulin-degrading enzyme (IDE), involved in the degradation of Aβ, are altered in response to an HFD. Aβ …

Integrating Genetic Modifier Genotype With Serum Proteomics In Duchenne Muscular Dystrophy Clinical Trials Links Ltbp4 Genetic Modifier To Il-23/Cd93 Pathways In Muscle, Utkarsh J. Dang, Yuan Fang, Daniele Sabbatini, Elena Pegoraro, Luca Bello, Paula R. Clemens, Michela Guglieri, John Van Den Anker, Jesse Damsker, Laura Hagerty, Yetrib Hathout, Michael Ziemba, Lauren Morgenroth, Surajit Bhattacharya, Kanneboyina Nagaraju, Jyoti K. Jaiswal, Eric P. Hoffman

Mathematics & Statistics Faculty Publications

Genetic modifiers of Duchenne muscular dystrophy (DMD) that alter disease severity or response to therapy have been reported using natural history or registry data sets of older corticosteroid-treated patients. We tested associations of genetic modifiers on motor function outcomes in young (4 to <  7 years) steroid naïve clinical trial participants. Participants in clinical trials (VBP15-002/003 [n = 48]; VBP15-004 [n = 121]; DNA available for n = 110) were genotyped for eight published genetic modifier loci, and associations of genotypes with baseline motor function defined via an age-adjusted linear model. Corticosteroid drug response was modeled by genotype-stratified placebo vs. steroid treatment at 12- and 24-weeks posttreatment (mixed model for repeated measures). …

Politics Of A Silent Pandemic: Antimicrobial Resistance And State Capacity In India And Nigeria, Mia Kelly

CMC Senior Theses

Antimicrobial Resistance (AMR) has emerged as one of the most pressing yet widely underestimated health threats of the 21st century; this thesis explores the potentially devastating global impact of this “silent pandemic”, exposing how deeply health outcomes depend on political choices, regulatory capacity, and economic constraints. Although the danger of spreading drug-resistant pathogens is now widely acknowledged in both the scientific and political communities, states differ in their abilities to contain the issue, with low- and middle-income countries facing the greatest obstacles to national action plan implementation. This thesis investigates these disparities through a comparison of India and Nigeria, two …

Roles Of Cytokines In Modulating Trypanosoma Brucei Rhodesiense Infection Outcomes In Vervet Monkeys, Clarah Jebet, John Kibuthu Thuita, Daniel Masiga, Benedict Owino Orindi, John Oidho, Mark C. Field, Enock Matovu, Vincent Owino Adung’A

All Peer-Reviewed Publications

Introduction:

Human African trypanosomiasis (HAT), caused by Trypanosoma brucei rhodesiense, is categorized as acute due to rapid disease progression but presents varying clinical outcomes. Although the mechanisms underpinning differential clinical progression are poorly understood, both host and parasite factors are implicated. Therefore, we sought to elucidate roles of primate host factors in mediating varying T. b. rhodesiense infection outcomes.

Methods:

Here, we assessed the roles of selected host cytokines in disease progression using a tsetse-mediated infection in a non-human primate (NHP) vervet monkey model that closely mimics HAT and natural infection. We quantified eight cytokines, including TNF-α, IFN-γ, IL-10, IL-6, …