Medicine and Health Sciences Commons^™

Near-Infrared Imaging Of Adoptive Immune Cell Therapy In Breast Cancer Model Using Cell Membrane Labeling, Fatma M. Youniss, Gobalakrishnan Sundaresan, Laura J. Graham, Li Wang, Collin R. Berry, Gajanan K. Dewkar, Purnima Jose, Harry D. Bear, Jamal Zweit

Radiology Publications

The overall objective of this study is to non-invasively image and assess tumor targeting and retention of directly labeled T-lymphocytes following their adoptive transfer in mice. T-lymphocytes obtained from draining lymph nodes of 4T1 (murine breast cancer cell) sensitized BALB/C mice were activated in-vitro with Bryostatin/Ionomycin for 18 hours, and were grown in the presence of Interleukin-2 for 6 days. T-lymphocytes were then directly labeled with 1,1-dioctadecyltetramethyl indotricarbocyanine Iodide (DiR), a lipophilic near infrared fluorescent dye that labels the cell membrane. Assays for viability, proliferation, and function of labeled T-lymphocytes showed that they were unaffected by DiR labeling. The DiR …

Headaches And Hemiparesis In An Immunocompetent Inmate, Andrea Gilbert Jelinek, Christine Fuller, Ahmet Baykal, Kimberly Stogner-Underwood, Hope Richard, Knarik Arkun

Pathology Publications

This is a case of a 22 year-old African American male inmate with no significant past medical history who regularly cleaned moldy bathrooms and showers during his incarceration. The patient presented with progressive development of left-sided weakness, dizziness, headaches, and vomiting over a two month period. In summary, we report this case to boost awareness of the potential for CNS phaeohyphomycosis infection to present as a clinical and radioimaging mimic of high grade glioma. Our patient, a previously healthy adult, is one of less than a dozen cases of cerebral phaeohyphomycosis due to Bipolaris documented in the literature, and is …

Measuring Hiv Stigma At The Family Level: Psychometric Assessment Of The Chinese Courtesy Stigma Scales (Ccsss), Hongjie Liu, Yongfang Xu, Yehuan Sun, Levent Dumenci

Social and Behavioral Sciences Publications

Courtesy stigma is the stigmatization a person perceives or experiences due to their association with a stigmatized individual or group. Most HIV-related stigma scales have been developed for people living with HIV/AIDS (PLWHAs), but not for their HIV-uninfected family members. To date, few measurement scales have been designed to measure the degree of stigma among both PLWHAs and their HIV-uninfected family members at the family level. We developed a set of courtesy stigma scales and estimated their reliability and validity from 256 PLWHAs and 256 of their HIV-uninfected family members. Exploratory and confirmatory factor analyses were performed in two independent …

Dvt Surveillance Program In The Icu: Analysis Of Cost-Effectiveness, Ajai K. Malhotra, Stephanie R. Goldberg, Laura Mclay, Nancy R. Martin, Luke G. Wolfe, Mark M. Levy, Vishal Khiatani, Todd C. Borchers, Therese M. Duane, Michel B. Aboutanos, Rao R. Ivatury

Biostatistics Publications

Background

Venous Thrombo-embolism (VTE – Deep venous thrombosis (DVT) and/or pulmonary embolism (PE) – in traumatized patients causes significant morbidity and mortality. The current study evaluates the effectiveness of DVT surveillance in reducing PE, and performs a cost-effectiveness analysis.

Methods

All traumatized patients admitted to the adult ICU underwent twice weekly DVT surveillance by bilateral lower extremity venous Duplex examination (48-month surveillance period – SP). The rates of DVT and PE were recorded and compared to the rates observed in the 36-month pre-surveillance period (PSP). All patients in both periods received mechanical and pharmacologic prophylaxis unless contraindicated. Total costs – …

Rare Variant Association Testing By Adaptive Combination Of P-Values, Wan-Yu Lin, Xiang-Yang Lou, Guimin Gao, Nianjun Liu

Biostatistics Publications

With the development of next-generation sequencing technology, there is a great demand for powerful statistical methods to detect rare variants (minor allele frequencies (MAFs)-MidPmethod (Cheung et al., 2012, Genet Epidemiol 36: 675–685) and propose an approach (named ‘adaptive combination of P-values for rare variant association testing’, abbreviated as ‘ADA’) that adaptively combines per-site P-values with the weights based on MAFs. Before combining P-values, we first imposed a truncation threshold upon the per-site P-values, to guard against the noise caused by the inclusion of neutral variants. ThisADA method is shown to outperform popular burden …

A New Powerful Nonparametric Rank Test For Ordered Alternative Problem, Guogen Shan, Daniel Young, Le Kang

Biostatistics Publications

We propose a new nonparametric test for ordered alternative problem based on the rank difference between two observations from different groups. These groups are assumed to be independent from each other. The exact mean and variance of the test statistic under the null distribution are derived, and its asymptotic distribution is proven to be normal. Furthermore, an extensive power comparison between the new test and other commonly used tests shows that the new test is generally more powerful than others under various conditions, including the same type of distribution, and mixed distributions. A real example from an anti-hypertensive drug trial …

A New Powerful Nonparametric Rank Test For Ordered Alternative Problem, Guogen Shan, Daniel Young, Le Kang

Biostatistics Publications

We propose a new nonparametric test for ordered alternative problem based on the rank difference between two observations from different groups. These groups are assumed to be independent from each other. The exact mean and variance of the test statistic under the null distribution are derived, and its asymptotic distribution is proven to be normal. Furthermore, an extensive power comparison between the new test and other commonly used tests shows that the new test is generally more powerful than others under various conditions, including the same type of distribution, and mixed distributions. A real example from an anti-hypertensive drug trial …

Associations Between Childhood Body Size, Composition, Blood Pressure And Adult Cardiac Structure: The Fels Longitudinal Study, Roy T. Sabo, Miao-Shan Yen, Stephen Daniels, Shumei S. Sun

Biostatistics Publications

Objectives

To determine whether childhood body size, composition and blood pressure are associated with adult cardiac structure by estimating childhood “age of divergence.”

Methods

385 female and 312 male participants in the Fels Longitudinal Study had echocardiographic measurements of left ventricular mass, relative wall thickness, and interventricular septal thickness. Also available were anthropometric measurements of body mass index, waist circumference, percentage body fat, fat free mass, total body fat, and systolic and diastolic blood pressures, taken in both childhood and adulthood. The age of divergence is estimated as the lowest age at which childhood measurements are significantly different between patients …

Job Attributes, Job Satisfaction And The Return To Health After Breast Cancer Diagnosis And Treatment, Andrew J. Barnes, Nicholas Robert, Cathy J. Bradley

Health Policy Publications

Background: As detection and treatment of cancer has advanced, the number of working age women with breast cancer has increased. This study provides new information on the intersection of breast cancer treatment and job tasks and how, together, they impact employed and newly diagnosed women.

Methods: The sample comprised 493 employed women within two months of initiating treatment. Job satisfaction and demands were assessed by pre-diagnosis recall along with measures of mental and physical health and assessed again nine months after initiating treatment. Using seemingly unrelated regression, we tested the effect of job tasks and satisfaction on mental and …

Polypectomy Techniques, Endoscopist Characteristics, And Serious Gastrointestinal Adverse Events, Askar S. Chukmaitov, Cathy J. Bradley, Bassam Dahman, Umaporn Siangphoe, Doumit Bouhaidar, Joan L. Warren

Health Policy Publications

Background: A use of polypectomy techniques by endoscopist specialty (primary care, surgery, and gastroenterology) and experience (volume), and associations with serious gastrointestinal adverse events, were examined.

Methods: A retrospective follow-up study with ambulatory surgery and hospital discharge datasets from Florida, 1999-2001, was used. Thirty-day hospitalizations due to colonic perforations and gastrointestinal bleeding were investigated for 323,585 patients.

Results: Primary care endoscopists and surgeons used hot biopsy forceps/ablation, while gastroenterologists provided snare polypectomy or complex colonoscopy. Low-volume endoscopists were more likely to use simpler rather than complex procedures. For hot forceps/ablation and snare polypectomy, low- and medium-volume endoscopists reported higher …

Determinants Of Coverage Decisions In Health Insurance Marketplaces: Consumers' Decision-Making Abilities And The Amount Of Information In Their Choice Environment, Andrew J. Barnes, Yaniv Hanoch, Thomas Rice

Health Policy Publications

Objective

To investigate the determinants and quality of coverage decisions among uninsured choosing plans in a hypothetical health insurance marketplace.

Study Setting

Two samples of uninsured individuals: one from an Internet-based sample comprised largely of young, healthy, tech-savvy individuals (n = 276), and the other from low-income, rural Virginians (n = 161).

Study Design

We assessed whether health insurance comprehension, numeracy, choice consistency, and the number of plan choices were associated with participants' ability to choose a cost-minimizing plan, given their expected health care needs (defined as choosing a plan costing no more than $500 in excess of the total …

From Listening To Experiencing: Changing Evidence-Based Pharmacy Library Instruction, Barbara A. Wright, Jennifer A. Mcdaniel

VCU Libraries Faculty and Staff Presentations

OBJECTIVE: Adapt bibliographic instruction from a traditional 50-minute lecture format to a hands-on, small group approach to more closely align with a team-based assignment.

METHODS: First year students in the School of Pharmacy's PharmD program are assigned to teams and work together on projects for lecture-based courses. In the second year, they are introduced to Team-Based Learning (TBL). To improve library instruction for first year students, two librarians used a team-based approach with hands-on examination of pharmacy resources to provide a better student learning experience than the traditional 50-minute lecture. Librarians led 90 minute interactive sessions for two teams for …

Examining A Link Between Paraquat, Alpha-Synuclein Fibrillation And Neurodegeneration: A Review, Nikhil Ailaney

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Parkinson’s disease is a chronic and progressive motor system disorder that is caused by the degeneration of dopaminergic neurons in the central nervous system. At the molecular level, Parkinson’s disease works by decreasing the concentrations of the neurotransmitter dopamine, a chemical messenger involved in motor messaging, within the central nervous system. Low levels of dopamine in the central nervous system causes motor system dysfunction because the insufficient levels of dopamine lead to an inability for neurons to successfully transmit motor messages. At the organismal level, Parkinson’s disease causes tremors, Bradykinesia, and rigidity. These symptoms ultimately lead to a diminished quality …

Understanding Nicotine Addition: Dependency As A Result Of Maladaptive Brain Structure, Nate Thomas

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Nicotine addiction is the most prevalent, destructive dependency found in our culture. Despite its well-documented damaging health risks, nicotine use is still widely accepted and could be conceptualized as a social epidemic. Much of this acceptance may stem from nicotine’s lack of debilitating cognitive effects, as compared to those of other abused drugs. However, what may reign dominantly over nicotine’s legality is simple cultural precedent: tobacco has never been illegal and holds a place in human history. Therefore, attempting to alter this would prove highly unpopular and unsuccessful. This macroscopic irrationality, a blind favor for cultural precedents, parallels the irrational …

Selective Activation Of Htrpv1 By N-Geranyl Cyclopropylcarboxamide, An Amiloride-Insensitive Salt Taste Enhancer, Min Jung Kim, Hee Jin Son, Yiseul Kim, Hae-Jin Kweon, Byung-Chang Suh, Vijay Lyall, Mee-Ra Rhyu

Physiology and Biophysics Publications and Presentations

TRPV1t, a variant of the transient receptor potential vanilloid-1 (TRPV1) has been proposed as a constitutively active, non-selective cation channel as a putative amiloride-insensitive salt taste receptor and shares many properties with TRPV1. Based on our previous chorda tympani taste nerve recordings in rodents and human sensory evaluations, we proposed that N-geranylcyclopropylcarboxamide (NGCC), a novel synthetic compound, acts as a salt taste enhancer by modulating the amiloride/benzamil-insensitive Na+ entry pathways. As an extension of this work, we investigated NGCC-induced human TRPV1 (hTRPV1) activation using a Ca2+-flux signaling assay in cultured cells. NGCC enhanced Ca2+ influx in hTRPV1-expressing cells in …

Lack Of Negatively Charged Residues At The External Mouth Of Kir2.2 Channels Enable The Voltage-Dependent Block By External Mg2+, Junwei Li, Xiaoxiao Xie, Jun Liu, Hui Yu, Suhua Zhang, Yong Zhan, Hailin Zhang, Diomedes E. Logothetis, Hailong An

Physiology and Biophysics Publications and Presentations

Kir channels display voltage-dependent block by cytosolic cations such as Mg2+ and polyamines that causes inward rectification. In fact, cations can regulate K channel activity from both the extracellular and intracellular sides. Previous studies have provided insight into the up-regulation of Kir channel activity by extracellular K+ concentration. In contrast, extracellular Mg2+ has been found to reduce the amplitude of the single-channel current at milimolar concentrations. However, little is known about the molecular mechanism of Kir channel blockade by external Mg2+ and the relationship between the Mg2+ blockade and activity potentiation by permeant K+ ions. In this study, we applied …

Suppression Of The Pi3k Pathway In Vivo Reduces Cystitis-Induced Bladder Hypertrophy And Restores Bladder Capacity Examined By Magnetic Resonance Imaging, Zhongwei Qiao, Chunmei Xia, Shanwei Shen, Frank D. Corwin, Miao Liu, Ruijuan Guan, John R. Grider, Li-Ya Qiao

Physiology and Biophysics Publications and Presentations

This study utilized magnetic resonance imaging (MRI) to monitor the real-time status of the urinary bladder in normal and diseased states following cyclophosphamide (CYP)-induced cystitis, and also examined the role of the phosphoinositide 3-kinase (PI3K) pathway in the regulation of urinary bladder hypertrophy in vivo. Our results showed that under MRI visualization the urinary bladder wall was significantly thickened at 8 h and 48 h post CYP injection. The intravesical volume of the urinary bladder was also markedly reduced. Treatment of the cystitis animals with a specific PI3K inhibitor LY294002 reduced cystitis-induced bladder wall thickening and enlarged the intravesical volumes. …

Effect Of Enac Modulators On Rat Neural Responses To Nacl, Shobha Mummalaneni, Jie Qian, Tam-Hao T. Phan, Mee-Ra Rhyu, Gerard L. Heck, John A. Desimone, Vijay Lyall

Physiology and Biophysics Publications and Presentations

The effects of small molecule ENaC activators N,N,N-trimethyl-2-((4-methyl-2-((4-methyl-1H-indol-3-yl)thio)pentanoyl)oxy)ethanaminiumiodide (Compound 1) and N-(2-hydroxyethyl)-4-methyl-2-((4-methyl-1H-indol-3-yl)thio)pentanamide(Compound 2), were tested on the benzamil (Bz)-sensitive NaCl chorda tympani (CT) taste nerve response under open-circuit conditions and under ±60 mV applied lingual voltage-clamp, and compared with the effects of known physiological activators (8-CPT-cAMP, BAPTA-AM, and alkaline pH), and an inhibitor (ionomycin+Ca2+) of ENaC. The NaCl CT response was enhanced at −60 mV and suppressed at +60 mV. In every case the CT response (r) versus voltage (V) curve was linear. All ENaC activators increased the open-circuit response (ro) and the voltage …

A Model Of The Effect Of Uncertainty On The C Elegans L2/L2d Decision, Leon Avery

Physiology and Biophysics Publications and Presentations

Abstract

At the end of the first larval stage, the C elegans larva chooses between two developmental pathways, an L2 committed to reproductive development and an L2d, which has the option of undergoing reproductive development or entering the dauer diapause. I develop a quantitative model of this choice using mathematical tools developed for pricing financial options. The model predicts that the optimal decision must take into account not only the expected potential for reproductive growth, but also the uncertainty in that expected potential. Because the L2d has more flexibility than the L2, it is favored in unpredictable environments. I estimate …

Treatment-Induced Breast Cancer Dormancy And Relapse, Rebecca Keim

Theses and Dissertations

When breast tumor cells encounter stress due to cancer therapies, they may enter a dormant state, escaping from treatment-induced apoptosis. Dormant cells may eventually regain proliferative capabilities and cause recurrent metastatic disease, which is the leading cause of mortality in breast cancer patients. We sought to determine if a high dose of radiation therapy (RT) or combined chemo-immunotherapy, with and without the blockade of autophagy by chloroquine (CQ), could overcome treatment-induced tumor dormancy or relapse. We found that autophagy contributes in part to treatment-induced tumor dormancy. We also found that three therapeutic strategies were successful in inhibiting or preventing tumor …

Epigenetic Alterations Of Toll-Like Receptors By Tet2 In Spontaneous Preterm Labor, Anuja Chumble

Theses and Dissertations

Increasing evidence implicates the presence of bacteria in intrauterine tissues as an important risk factor for spontaneous preterm labor. Epigenetic alterations of innate immunity genes may increase the mother’s sensitivity to subclinical levels of bacteria. This study examined the presence of TET2, TLR-2, and TLR-9 in intrauterine tissue, and evaluated whether epigenetic alterations of these genes, as well as IL-8, changed their expression in human decidual tissue and a macrophage cell culture. Immunohistochemicalstaining was used to detect the presence of these proteins in intrauterine tissue. Gene expression changes were evaluated in stimulated monocytes and macrophages. Fluorescence immunohistochemistry was used to …

Application Of Marginal Structural Models In Pharmacoepidemiologic Studies, Shibing Yang

Theses and Dissertations

Background: Inverse-probability-of-treatment-weighted estimation (IPTW) of marginal structural models was proposed to adjust for time-varying confounders that are influenced by prior treatment use. It is unknown whether pharmacoepidemiologic studies that applied IPTW conformed to the recommendations proposed by methodological studies. In addition, no previous study has compared the performance of different analytic strategies adopted in IPTW analyses. Objectives: This project aims 1) to review the reporting practice of pharmacoepidemiologic studies that applied IPTW, 2) to compare the validity and precision of several approaches to constructing weight, 3) to use IPTW to estimate the effectiveness of glucosamine and chondroitin in treating osteoarthritis. …

Characterization Of Putative Porphyromonas Gingivalis Rna-Binding Proteins, Holly Dwyer

Theses and Dissertations

Porphyromonas gingivalis (P. gingivalis) is a gram-negative, anaerobic bacterium recognized as a major player in progression of periodontal disease. P. gingivalis survives in the oral cavity while being exposed to dynamic environmental conditions such as pH, temperature, nutrient availability and host immune responses such as oxygen tension and nitrosative stress. Survival and pathogenesis of P. gingivalis in the oral cavity require mechanisms to regulate gene expression in response to the extracellular signals. Little is known about the regulatory mechanisms of P. gingivalis in the oral cavity, so it is important to investigate and characterize these regulatory mechanisms. Adaptation to environmental …

Modulation Of Cns Neurotransmitter Levels And Associated Behaviors In Organic Anion Transporter 1 (Slc22a6) And Organic Anion Transporter 3 (Slc22a8) Knockout Mice, Christine Farthing

Theses and Dissertations

According to the World Health Organization, mental disorders represent the leading cause of disability in the US generating ~58 billion dollars in medical costs annually. Additionally, among the US population, ~40 million adults suffer from an anxiety disorder and ~14 million suffer from a major depressive disorder. The association between the persistence of these neurobehavioral conditions and central nervous system (CNS) levels of biogenic amines and metabolites has been studied for half a century. Further, a number of drugs interfering with neurotransmission/metabolism are used clinically for treatment of these disorders. Recently, some members of the solute carrier (SLC) superfamily, the …

Quantitative Mass Spectrometric Investigations Of Protein Biomarkers: Serum Thymidine Kinase 1 And Human Osteopontin, Morse Faria

Theses and Dissertations

Mass spectrometry is being increasingly used in biomarker research mainly due to its ability to achieve high selectivity coupled with high sensitivity. This dissertation focuses on quantitative mass spectrometric investigations of two protein biomarkers i.e. serum thymidine kinase 1 (TK1) and human osteopontin (OPN).

First part of this research was focused on developing a liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for measuring the activity of TK1 in serum by monitoring the conversion of a TK1 specific exogenous substrate, 3’-deoxy-3’-fluorothymidine (FLT), to its mono-phosphorylated form 3’-deoxy-3’-fluorothymidine monophosphate (FLT-MP). A method to quantify FLT-MP on LC-MS/MS was developed and …

Statistical Modeling Of Interfractional Tissue Deformation And Its Application In Radiation Therapy Planning, Douglas J. Vile

Theses and Dissertations

In radiation therapy, interfraction organ motion introduces a level of geometric uncertainty into the planning process. Plans, which are typically based upon a single instance of anatomy, must be robust against daily anatomical variations. For this problem, a model of the magnitude, direction, and likelihood of deformation is useful. In this thesis, principal component analysis (PCA) is used to statistically model the 3D organ motion for 19 prostate cancer patients, each with 8-13 fractional computed tomography (CT) images. Deformable image registration and the resultant displacement vector fields (DVFs) are used to quantify the interfraction systematic and random motion. By applying …

Examining The Sensory Characteristics Of Preschool Children With Retentive Fecal Incontinence, Isabelle Beaudry-Bellefeuille

Theses and Dissertations

Occupational therapists are concerned with individuals´ abilities to engage in daily occupations. When a daily activity such as bowel management is problematic, participation in key occupations can be limited. Retentive fecal incontinence is a common disorder in children. Behavior seems to be partly responsible for this condition. Occupational therapists have hypothesized that some behaviors could be related to sensory over-responsivity. This study investigated the relationship between retentive fecal incontinence and sensory over-responsivity and examined the Toileting Habit Profile Questionnaire, a tool designed to screen for toileting difficulties. The study showed that a group of children (n=16) with retentive fecal incontinence …

Completely Intracorporeal Robotic-Assisted Laparoscopic Ileovesicostomy, Maryellen T. Dolat, Greg Wade, B. Mayer Grob, Lance J. Hampton, Adam P. Klausner

Surgery Publications

We present a report of a completely intracorporeal robotic-assisted laparoscopic ileovesicostomy with long term follow-up. The patient was a 55-year-old man with paraplegia secondary to tropical spastic paresis resulting neurogenic bladder dysfunction. The procedure was performed using a da Vinci Surgical system (Intuitive Surgical, Sunnyvale, CA) and took 330 minutes with an estimated blood loss of 100 mL. The patient recovered without perioperative complications. He continues to have low pressure drainage without urethral incontinence over two years postoperatively.

Donor Heart Utilization Following Cardiopulmonary Arrest And Resuscitation: Influence Of Donor Characteristics And Wait Times In Transplant Regions, Mohammed Quader, Luke Wolfe, Gundars Katlaps, Vigneshwar Kasirajan

Surgery Publications

Background. Procurement of hearts from cardiopulmonary arrest and resuscitated (CPR) donors for transplantation is suboptimal. We studied the influences of donor factors and regional wait times on CPR donor heart utilization. Methods. From UNOS database (1998 to 2012), we identified 44,744 heart donors, of which 4,964 (11%) received CPR. Based on procurement of heart for transplantation, CPR donors were divided into hearts procured (HP) and hearts not procured (HNP) groups. Logistic regression analysis was used to identify predictors of heart procurement. Results. Of the 4,964 CPR donors, 1,427 (28.8%) were in the HP group. Donor characteristics that favored heart procurement …

Is The Consistency More Important Than The Ingredients For Treatment? Case Report For Eosinophilic Esophagitis, Dan W. Parrish, Shashank Sharma, Santhosh Kumar

Surgery Publications

Eosinophilic Esophagitis seems to be an ever-changing disease, from patient-to-patient and from year-to-year in the same patient. Improvements in these patients’ lives have been made with the realization that elimination of dietary antigens helped with symptom relief and treatment with topical steroids assisted in eradication of esophageal eosinophils.

This case study has two very important aspects that should be emphasized. The first is the realization that it may be consistency of the steroid mixture rather than the ingredients that infer the effectiveness of the EoE treatment, and the second aspect is the willingness of the medical team to listen to …