Medicine and Health Sciences Commons^™

An Ewas Of Dementia Biomarkers And Their Associations With Age, African Ancestry, And Ptsd, Mark W. Miller, Erika J. Wolf, Xiang Zhao, Mark W. Logue, Sage E. Hawn

Psychology Faculty Publications

Background

Large-scale cohort and epidemiological studies suggest that PTSD confers risk for dementia in later life but the biological mechanisms underlying this association remain unknown. This study examined this question by assessing the influences of PTSD, APOE ε4 genotypes, DNA methylation, and other variables on the age- and dementia-associated biomarkers Aβ40, Aβ42, GFAP, NfL, and pTau-181 measured in plasma. Our primary hypothesis was that PTSD would be associated with elevated levels of these markers.

Methods

Analyses were based on data from a PTSD-enriched cohort of 849 individuals. We began by performing factor analyses of the biomarkers, the results of which …

Plasma Protein Signatures Of Adult Asthma, Gordon J. Smilnak, Yura Lee, Abhijnan Chattopadhyay, Annah B. Wyss, Julie D. White, Sinjini Sikdar, Jianping Jin, Andrew J. Grant, Alison A. Motsinger-Reif, Jian-Liang Li, Mikyeong Lee, Bing Yu, Stephanie J. London

Mathematics & Statistics Faculty Publications

Background: Adult asthma is complex and incompletely understood. Plasma proteomics is an evolving technique that can both generate biomarkers and provide insights into disease mechanisms. We aimed to identify plasma proteomic signatures of adult asthma.

Methods: Protein abundance in plasma was measured in individuals from the Agricultural Lung Health Study (ALHS) (761 asthma, 1095 non-case) and the Atherosclerosis Risk in Communities study (470 asthma, 10,669 non-case) using the SOMAScan 5K array. Associations with asthma were estimated using covariate adjusted logistic regression and meta-analyzed using inverse-variance weighting. Additionally, in ALHS, we examined phenotypes based on both asthma and seroatopy (asthma with …

Recent Progress In Microrna Detection Using Integrated Electric Fields And Optical Detection Methods, Logeeshan Velmanickam, Dharmakeerthi Nawarathna

Electrical & Computer Engineering Faculty Publications

Low-cost, highly-sensitivity, and minimally invasive tests for the detection and monitoring of life-threatening diseases and disorders can reduce the worldwide disease burden. Despite a number of interdisciplinary research efforts, there are still challenges remaining to be addressed, so clinically significant amounts of relevant biomarkers in body fluids can be detected with low assay cost, high sensitivity, and speed at point-of-care settings. Although the conventional proteomic technologies have shown promise, their ability to detect all levels of disease progression from early to advanced stages is limited to a limited number of diseases. One potential avenue for early diagnosis is microRNA (miRNA). …

Comparison Between The Effects Of Acute Physical And Psychosocial Stress On Feedback-Based Learning, Xiao Yang, Brittany Nackley, Bruce H. Friedman

Psychology Faculty Publications

Stress modulates feedback-based learning, a process that has been implicated in declining mental function in aging and mental disorders. While acute physical and psychosocial stressors have been used interchangeably in studies on feedback-based learning, the two types of stressors involve distinct physiological and psychological processes. Whether the two types of stressors differentially influence feedback processing remains unclear. The present study compared the effects of physical and psychosocial stressors on feedback-based learning. Ninety-six subjects (Mage = 19.11 years; 50 female) completed either a cold pressor task (CPT) or mental arithmetic task (MAT), as the physical or psychosocial stressor, while electrocardiography and …

Metals And Metal Complexes In Diseases With A Focus On Covid-19: Facts And Opinions, Agnieszka Ścibior, Manuel Aureliano, Alvin A. Holder, Juan Llopis

Chemistry & Biochemistry Faculty Publications

In the present Special Issue on “Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions”, an attempt has been made to include reports updating our knowledge of elements considered to be potential candidates for therapeutic applications and certain metal-containing species, which are extensively being examined towards their potential biomedical use due to their specific physicochemical properties. The Special Issue compiles data on the role of metals in COVID-19 and focuses on other illnesses and biological processes that affect metal metabolism. It consists of eight manuscripts, including five review articles and three original research papers (Figure …

Refinement Of Saliva Microrna Biomarkers For Sports-Related Concussion, Steven D. Hicks, Cayce Onks, Raymond Y. Kim, Kevin J. Kim, Kevin J. Zhen, Jayson Loeffert, Andrea C. Loeffert, Robert P. Olympia, Gregory Fedorchak, Samantha Devita, Zofia Gagnon, Callan Mcloughlin, Miguel M. Madeira, Scott L. Zuckerman, Timothy Lee, Matthew Heller, Chuck Monteith, Thomas R. Campbell, Christopher Neville, Elise Fengler, Michael N. Dretsch

Rehabilitation Sciences Faculty Publications

Purpose

Recognizing sport-related concussion (SRC) is challenging and relies heavily on subjective symptom reports. An objective, biological marker could improve recognition and understanding of SRC. There is emerging evidence that salivary micro-ribonucleic acids (miRNAs) may serve as biomarkers of concussion; however, it remains unclear whether concussion-related miRNAs are impacted by exercise. We sought to determine whether 40 miRNAs previously implicated in concussion pathophysiology were affected by participation in a variety of contact and non-contact sports. Our goal was to refine a miRNA-based tool capable of identifying athletes with SRC without the confounding effects of exercise.

Methods

This case-control study harmonized …

Review Of Nighttime Temperature Effects On Long-Term Health Condition Through Sleep Studies, Sydnie Matkins

Modeling, Simulation and Visualization Student Capstone Conference

Over the past 40 years, there has been increasing interest in human sleep quality and duration. This nonsystematic review looked at over 80 peer-reviewed papers on the association among sleep, temperature, and long-term health conditions. Generally, warmer temperatures lend to poorer sleep quality, and poor sleep quality lend to mental illness and a higher risk of coronary heart disease and mortality. Future research should be to conduct a study that relies more on health records rather than questionnaires to accurately map current and future health quality.

A Single Bout Of Breast Milk Expression Does Not Increase Resting Metabolic Rate, Leryn J. Reynolds, Kayla R. Powell, Taskina Akhter, Hannah M. Twiddy, Patrick B. Wilson

Human Movement Sciences & Special Education Faculty Publications

Introduction: Breastfeeding women have elevated resting metabolic rate (RMR); however, whether a single bout of lactation increases RMR is unknown. This study aimed to determine if a single bout of lactation acutely increased RMR.

Methods: Twenty-two lactating women (age: 31 ± 0.9 year, body mass index: 27.3 ± 1.2 kg/m²) were recruited. RMR was assessed at baseline and at 1- and 2-h following breast milk expression.

Results: RMR was unchanged in lactating women following a single bout of lactation (baseline: 1437 ± 39; 1 h: 1425 ± 37 2 h: 1440 ± 31 kcal/day) (p > .05). RMR was …

Recent Advances In Research And Management Of Human Monkeypox Virus: An Emerging Global Health Threat, Parveen Kumar, Benu Chaudhary, Nishant Yadav, Sushma Devi, Ashutosh Pareek, Sujatha Alla, Fnu Kajal, Behdin Nowrouzi-Kia, Vijay Kumar Chattu, Madan Mohan Gupta

Engineering Management & Systems Engineering Faculty Publications

In 2003, the United States saw an epidemic of monkeypox that was later traced back to rodents of West Africa infected with the monkeypox virus (MPXV). Disease in the United States seemed less severe than the smallpox-like disease in the Democratic Republic of the Congo (DRC). In this study, researchers analyzed data from Central Africa: two distinct MPXV clades were confirmed by sequencing the genomes of MPXV isolates from Western Africa, the United States, and Central Africa. By comparing open reading frames across MPXV clades, scientists can infer which virus proteins might account for the observed variation in pathogenicity in …

Msdrp: A Deep Learning Model Based On Multisource Data For Predicting Drug Response, Haochen Zhao, Xiaoyu Zhang, Qichang Zhao, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Cancer heterogeneity drastically affects cancer therapeutic outcomes. Predicting drug response in vitro is expected to help formulate personalized therapy regimens. In recent years, several computational models based on machine learning and deep learning have been proposed to predict drug response in vitro. However, most of these methods capture drug features based on a single drug description (e.g. drug structure), without considering the relationships between drugs and biological entities (e.g. target, diseases, and side effects). Moreover, most of these methods collect features separately for drugs and cell lines but fail to consider the pairwise interactions between drugs and cell …

Multi-Ancestry Genome-Wide Association Analyses Improve Resolution Of Genes And Pathways Influencing Lung Function And Chronic Obstructive Pulmonary Disease Risk, Nick Shrine, Abril G. Izquierdo, Jing Chen, Richard Packer, Robert J. Hall, Anna L. Guyatt, Chiara Batini, Rebecca J. Thompson, Chandan Puvuluri, Vidhi Malik, Brian D. Hobbs, Matthew Moll, Wonji Kim, Ruth Tal-Singer, Per Bakke, Katherine A. Fawcett, Catherine John, Kayesha Coley, Noemi Nicole Piga, Sinjini Sikdar, Martin D. Tobin, Et Al.

Mathematics & Statistics Faculty Publications

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of …

Population Variations Of Cheiloscopy Patterns: A Cross-Sectional Observation Pilot Study, Emily Smith Regan, Brenda T. Bradshaw, Ann M. Bruhn, Walter Melvin, Sinjini Sikdar

Dental Hygiene Faculty Publications

Purpose Lip prints are unique and have potential for use as a human identifier. The purpose of this study was to observe possible cheiloscopy differences of individuals with and without parafunctional oral habits such as smoking, vaping, playing a wind instrument or using an asthma inhaler.

Methods This IRB approved blinded cross-sectional observation pilot study collected lip prints from sixty-six individuals, three of which were excluded. Participants cleansed their lips, then lipstick was applied to the vermillion zones of the upper and lower lips. Adhesive tape was applied to the lips and prints were transferred to white bond paper for …

Adaptive Critic Network For Person Tracking Using 3d Skeleton Data, Joseph G. Zalameda, Alex Glandon, Khan M. Iftekharuddin, Mohammad S. Alam (Ed.), Vijayan K. Asari (Ed.)

Electrical & Computer Engineering Faculty Publications

Analysis of human gait using 3-dimensional co-occurrence skeleton joints extracted from Lidar sensor data has been shown a viable method for predicting person identity. The co-occurrence based networks rely on the spatial changes between frames of each joint in the skeleton data sequence. Normally, this data is obtained using a Lidar skeleton extraction method to estimate these co-occurrence features from raw Lidar frames, which can be prone to incorrect joint estimations when part of the body is occluded. These datasets can also be time consuming and expensive to collect and typically offer a small number of samples for training and …

Npgreat: Assembly Of The Human Subtelomere Regions With The Use Of Ultralong Nanopore Reads And Linked Reads, Eleni Adam, Desh Ranjan, Harold Riethman

Computer Science Faculty Publications

Background: Human subtelomeric DNA regulates the length and stability of adjacent telomeres that are critical for cellular function, and contains many gene/pseudogene families. Large evolutionarily recent segmental duplications and associated structural variation in human subtelomeres has made complete sequencing and assembly of these regions difficult to impossible for many loci, complicating or precluding a wide range of genetic analyses to investigate their function.

Results: We present a hybrid assembly method, NanoPore Guided REgional Assembly Tool (NPGREAT), which combines Linked-Read data with mapped ultralong nanopore reads spanning subtelomeric segmental duplications to potentially overcome these difficulties. Linked-Read sets of DNA sequences identified …

T-Cell Antigen Receptors In Multiple Sclerosis, Lisa Lanée Keyes Jones

Biomedical Sciences Theses & Dissertations

Multiple Sclerosis (MS) is T-cell mediated autoimmune disease characterized by inflammation, demyelination, and degeneration of axons in the brain and spinal cord. A T cell-mediated immune response in MS is directed against myelin components and possibly other antigens in genetically susceptible individuals and is triggered by a viral infection. The T-cell antigen receptor (TCR) on T cells is responsible for antigen recognition and determines specificity. Our overall hypothesis is to determine whether clonally expanded T cells in patients with MS recognize viral or self-antigens and to determine whether molecular mimicry is involved in the development of the disease. To study …

Modification Of The Tumor Microenvironment Enhances Anti-Pd-1 Immunotherapy In Metastatic Melanoma, Guilan Shi, Megan Scott, Cathryn G. Mangiamele, Richard Heller

Bioelectrics Publications

Resistance to checkpoint-blockade treatments is a challenge in the clinic. Both primary and acquired resistance have become major obstacles, greatly limiting the long-lasting effects and wide application of blockade therapy. Many patients with metastatic melanoma eventually require further therapy. The absence of T-cell infiltration to the tumor site is a well-accepted contributor limiting immune checkpoint inhibitor efficacy. In this study, we combined intratumoral injection of plasmid IL-12 with electrotransfer and anti-PD-1 in metastatic B16F10 melanoma tumor model to increase tumor-infiltrating lymphocytes and improve therapeutic efficacy. We showed that effective anti-tumor responses required a subset of tumor-infiltrating CD8⁺ and CD4 …

Medical Manikin Augmented Reality Simulation (M2ars), Pauline Delacruz, Jacob Gibson, Daniel Howard, Jaclyn Peacock, Kendall Robbins

Modeling, Simulation and Visualization Student Capstone Conference

The Medical Manikin Augmented Reality Simulation (M2ARS) is an augmented reality simulation application built for the Microsoft HoloLens 2 that uses the principles of anatomy transfer to overlay human anatomical structures onto a medical manikin digitally. These structures currently consist of the skeletal, muscular, and circulatory systems. In addition, a model of the lungs and an animated heart are also available within the simulation. M2ARS allows the user to view these structures in a manner that is both visually and spatially accurate to the human body. This application contains two modes; an augmented reality mode, which uses a manikin, and …

Pulmonary Function And Blood Dna Methylation: A Multiancestry Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Tianxiao Huan, Daniel L. Mccartney, Geetha Chittoor, Maaike De Vries, Lies Lahousse, Jennifer N. Nguyen, Jennifer A. Brody, Juan Castillo-Fernandez, Natalie Terzikhan, Cancan Qi, Roby Joehanes, Josine L. Min, Gordon J. Smilnak, Jessica R. Shaw, Chen Xi Yang, Elena Colicino, Thanh T. Hoang, Mairead L. Bermingham, Hanfei Xu, Anne E. Justice, Cheng-Jian Xu, Stephen S. Rich, Simon R. Cox, Judith M. Vonk, Ivana Prokić, Nona Sotoodehnia, Pei-Chien Tsai, Joel D. Schwartz, Janice M. Leung, Sinjini Sikdar, Rosie M. Walker, Sarah E. Harris, Diana A. Van Der Plaat, David J. Van Den Berg, Traci M. Bartz, Tim D. Spector, Pantel S. Vokonas, Riccardo E. Marioni, Adele M. Taylor, Yongmei Liu, R. Graham Barr, Leslie A. Lange, Andrea A. Baccarelli, Ma'en Obeidat, Myriam Fornage, Tianyuan Wang, James M. Ward, Alison A. Motsinger-Reif, Gibran Hemani, Gerard H. Koppelman, Jordana T. Bell, Sina A. Gharib, Guy Brusselle, H. Marike Boezen, Kari E. North, Daniel Levy, Kathryn L. Evans, Josée Dupris, Charles E. Breeze, Ani Manichaikul, Stephanie J. London

Mathematics & Statistics Faculty Publications

Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication.

Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function.

Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV₁, FVC, and FEV₁/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics.

Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery …

Robust Meta-Analysis For Large-Scale Genomic Experiments Based On An Empirical Approach, Sinjini Sikdar

Mathematics & Statistics Faculty Publications

BACKGROUND: Recent high-throughput technologies have opened avenues for simultaneous analyses of thousands of genes. With the availability of a multitude of public databases, one can easily access multiple genomic study results where each study comprises of significance testing results of thousands of genes. Researchers currently tend to combine this genomic information from these multiple studies in the form of a meta-analysis. As the number of genes involved is very large, the classical meta-analysis approaches need to be updated to acknowledge this large-scale aspect of the data.

METHODS: In this article, we discuss how application of standard theoretical null distributional assumptions …

Plasmonic-Based Biosensor For The Early Diagnosis Of Prostate Cancer, Thakshila Liyanage, Bayan Alharbi, Linh Quan, Aurora Esquela-Kerscher, Gymama Slaughter

Bioelectrics Publications

A tapered optical fiber (TOF) plasmonic biosensor was fabricated and used for the sensitive detection of a panel of microRNAs (miRNAs) in human serum obtained from noncancer and prostate cancer (PCa) patients. Oncogenic and tumor suppressor miRNAs let7a, let-7c, miR-200b, miR-141, and miR-21 were tested as predictive cancer biomarkers since multianalyte detection minimizes false-positive and false-negative rates and establishes a strong foundation for early PCa diagnosis. The biosensing platform integrates metallic gold triangular nanoprisms (AuTNPs) laminated on the TOF to excite surface plasmon waves in the supporting metallic layer and enhance the evanescent mode of the fiber surface. …

Reduction Of Plasmid Vector Backbone Length Enhances Reporter Gene Expression, Carly Boye, Sezgi Arpag, Michael Francis, Scott Declemente, Aislin West, Richard Heller, Anna Bulysheva

Electrical & Computer Engineering Faculty Publications

Gene therapy has a wide range of applications for various types of pathologies. Viral methods of gene delivery provide high levels of gene expression but have various safety concerns. Non-viral methods are largely known to provide lower levels of expression. We aim to address this issue by using plasmid DNA with smaller backbones to increase gene expression levels when delivered using non-viral methods. In this study we compare gene expression levels between two vectors with firefly luciferase encoding gene insert using liposome complexes and gene electrotransfer as delivery methods. A 2-fold reduction in plasmid vector backbone size, disproportionately enhanced gene …

Gene Electrotransfer Of Fgf2 Enhances Collagen Scaffold Biocompatibility, Carly Boye, Kyle Cristensen, Kamal Asadipour, Scott Declemente, Michael Francis, Anna Bulysheva

Electrical & Computer Engineering Faculty Publications

Tendon injuries are a common athletic injury that have been increasing in prevalence. While there are current clinical treatments for tendon injuries, they have relatively long recovery times and often do not restore native function of the tendon. In the current study, gene electrotransfer (GET) parameters for delivery to the skin were optimized with monophasic and biphasic pulses with reporter and effector genes towards optimizing underlying tendon healing. Tissue twitching and damage, as well as gene expression and distribution were evaluated. Bioprinted collagen scaffolds, mimicking healthy tendon structure were then implanted subcutaneously for biocompatibility and angiogenesis analyses when combined with …

The Investigations Of Nps Modulated Immunity And Immunometabolism, Brittney Leigh Ruedlinger

Biomedical Sciences Theses & Dissertations

Cancers remain in the top noncommunicable diseases responsible for premature mortality. The heterogeneity among cancers and within tumors makes treating them ever more challenging. Our misfortune for developing cures is mocked by cancer, with the lowest probability of success (PoS) through clinical trials and FDA approval. At the basic level, there are generally two broad gaps impeding cancer eradication: the unidentified shared mechanism(s) exploited by all cancers and the therapeutic approach to intervene. Nanosecond pulse stimulation (NPS) offers a unique approach since its broad impacts intersect those often hijacked by oncogenesis. Metabolic pathways, known for dysfunctions among cancers, share a …

The Impact Of Nanopulse Treatment On The Tumor Microenvironment In Breast Cancer: Overturning The Treg Immunosuppressive Dominance, Anthony Nanajian

Biomedical Sciences Theses & Dissertations

Nanopulse treatment (NPT) is a high-power electric engineering modality that has been shown to be an effective local tumor treatment approach in multiple cancer models. Our previous studies on the orthotopic 4T1-luc breast cancer model demonstrated that NPT ablated local tumors. The treatment consequently conferred protection against a second live tumor challenge and minimized spontaneous metastasis. This study aims to understand how NPT mounts a potent immune response in a predominantly immunosuppressive tumor.

NPT changed the local and systemic dynamics of immunosuppressive cells by significantly reducing the numbers of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages …

Cold Atmospheric-Pressure Plasma Caused Protein Damage In Methicillin-Resistant Staphylococcus Aureus Cells In Biofilms, Li Guo, Lu Yang, Yu Qi, Gulimire Niyazi, Lingling Huang, Lu Gou, Zifeng Wang, Lei Zhang, Dingxin Liu, Xiaohua Wang, Hailan Chen, Michael G. Kong

Bioelectrics Publications

Biofilms formed by multidrug-resistant bacteria are a major cause of hospital-acquired infections. Cold atmospheric-pressure plasma (CAP) is attractive for sterilization, especially to disrupt biofilms formed by multidrug-resistant bacteria. However, the underlying molecular mechanism is not clear. In this study, CAP effectively reduced the living cells in the biofilms formed by methicillin-resistant Staphylococcus aureus, and 6 min treatment with CAP reduced the S. aureus cells in biofilms by 3.5 log₁₀. The treatment with CAP caused the polymerization of SaFtsZ and SaClpP proteins in the S. aureus cells of the biofilms. In vitro analysis demonstrated that recombinant SaFtsZ lost …

Stunting And Combined Overweight With Stunting Among Schoolchildren In Kuwait: Trends Over A 13-Year Period, Abdullah Al-Taiar, Nawal Alqaoud, Reem Sharaf Alddin, Faheema Alanezi, Monica Subhakaran, Anne Dumadag, Ahmed N. Albatineh

Community & Environmental Health Faculty Publications

Objectives: This study aimed to investigate the sex- and age-specific trends of stunting and combined overweight with stunting among schoolchildren over a 13-year period in Kuwait. Subjects and Methods: The Kuwait Nutrition Surveillance System objectively measured the height of 172,573 schoolchildren (5–19 years) over a 13-year period (2007–2019). Data on gender and date of birth were extracted from school records. Stunting was defined as height 2 standard deviations (SD) below the World Health Organization growth reference median. Logistic regression models were used to examine the trends of stunting over the study period while stratifying by gender. Results: In males, the …

Fmri Feature Extraction Model For Adhd Classification Using Convolutional Neural Network, Senuri De Silva, Sanuwani Udara Dayarathna, Gangani Ariyarathne, Dulani Meedeniya, Sampath Jayarathna

Computer Science Faculty Publications

Biomedical intelligence provides a predictive mechanism for the automatic diagnosis of diseases and disorders. With the advancements of computational biology, neuroimaging techniques have been used extensively in clinical data analysis. Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder, with the symptomology of inattention, impulsivity, and hyperactivity, in which early diagnosis is crucial to prevent unwelcome outcomes. This study addresses ADHD identification using functional magnetic resonance imaging (fMRI) data for the resting state brain by evaluating multiple feature extraction methods. The features of seed-based correlation (SBC), fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) are comparatively applied to …

Il-15/Il-15rα Heterodimeric Complex As Cancer Immunotherapy In Murine Breast Cancer Models, Siqi Guo, Ronald B. Smeltz, Anthony Nanajian, Richard Heller

Bioelectrics Publications

Interleukin 15 (IL-15) has been evaluated as a potential treatment for solid tumors in clinical trials, but the effectiveness of systemic IL-15 administration as a monotherapy has not been realized. IL-15 receptor alpha (IL-15Rα) can stabilize IL-15 and enhance its bioactivity. The goal of this study was to examine the activity of IL-15/IL-15Rα complex (IL-15cx) to CD8(+) T cells and evaluate its potential efficacy in murine breast cancer models. The antitumor efficacy was studied in mouse mammary carcinoma models (Her2/neu transgenic and 4T1-luc mammary cancers) treated with systemic recombinant protein with/without the depletion of myeloid-derived suppressor cells or intra-tumoral gene …

Moderate Heat-Assisted Gene Electrotransfer For Cutaneous Delivery Of A Dna Vaccine Against Hepatitis B Virus, Chelsea Edelblute, Cathryn Mangiamele, Richard Heller

Bioelectrics Publications

An estimated 350 million people are living with chronic Hepatitis B virus (HBV) worldwide. Preventative HBV vaccination in infants has reduced the disease burden; however, insufficient immunization programs and access obstacles leave vulnerable populations at risk for infection in endemic regions. Gene electrotransfer (GET) using a noninvasive multielectrode array (MEA) provides an alternative platform for DNA vaccination in the skin. DNA vaccines are nonlive and nonreplicating and temperature stable unlike their counterparts. In addition, their simple engineering allows them to be manufactured quickly at a low cost. In the current work, we present the combination of GET and moderate heating …

Moderate Heat-Assisted Gene Electrotransfer As A Potential Delivery Approach For Protein Replacement Therapy Through The Skin, Chelsea Edelblute, Cathryn Mangiamele, Richard Heller

Bioelectrics Publications

Gene-based approaches for protein replacement therapies have the potential to reduce the number of administrations. Our previous work demonstrated that expression could be enhanced and/or the applied voltage reduced by preheating the tissue prior to pulse administration. In the current study, we utilized our 16-pin multi-electrode array (MEA) and incorporated nine optical fibers, connected to an infrared laser, between each set of four electrodes to heat the tissue to 43 °C. For proof of principle, a guinea pig model was used to test delivery of reporter genes. We observed that when the skin was preheated, it was possible to achieve …