Medicine and Health Sciences Commons^™

Interaction Between Cannabinoid System And Toll-Like Receptors Controls Inflammation, Kathleen L. Mccoy

Microbiology and Immunology Publications

Since the discovery of the endocannabinoid system consisting of cannabinoid receptors, endogenous ligands, and biosynthetic and metabolizing enzymes, interest has been renewed in investigating the promise of cannabinoids as therapeutic agents. Abundant evidence indicates that cannabinoids modulate immune responses. An inflammatory response is triggered when innate immune cells receive a danger signal provided by pathogen- or damage-associated molecular patterns engaging pattern-recognition receptors. Toll-like receptor family members are prominent pattern-recognition receptors expressed on innate immune cells. Cannabinoids suppress Toll-like receptor-mediated inflammatory responses. However, the relationship between the endocannabinoid system and innate immune system may not be one-sided. Innate immune cells express …

Interaction Between Cannabinoid System And Toll-Like Receptors Controls Inflammation, Kathleen L. Mccoy

Microbiology and Immunology Publications

Since the discovery of the endocannabinoid system consisting of cannabinoid receptors, endogenous ligands, and biosynthetic and metabolizing enzymes, interest has been renewed in investigating the promise of cannabinoids as therapeutic agents. Abundant evidence indicates that cannabinoids modulate immune responses. An inflammatory response is triggered when innate immune cells receive a danger signal provided by pathogen- or damage-associated molecular patterns engaging pattern-recognition receptors. Toll-like receptor family members are prominent pattern-recognition receptors expressed on innate immune cells. Cannabinoids suppress Toll-like receptor-mediated inflammatory responses. However, the relationship between the endocannabinoid system and innate immune system may not be one-sided. Innate immune cells express …

Clinically Relevant Investigation Of Flattening Filter-Free Skin Dose, Christopher L. Guy, Kishor Karki, Manju Sharma, Siyong Kim

Radiation Oncology Publications

As flattening filter-free (FFF) photon beams become readily available for treatment delivery in techniques such as SBRT, thorough investigation of skin dose from FFF photon beams is necessary under clinically relevant conditions. Using a parallel-plate PTW Markus chamber placed in a custom water-equivalent phantom, surface-dose measurements were taken at 2 × 2, 3 × 3, 4 × 4, 6 × 6, 8 × 8, 10 × 10, 20 × 20, and 30 × 30 cm2 field sizes, at 80, 90, and 100 cm source-to-surface distances (SSDs), and with fields defined by jaws and multileaf collimator (MLC) using multiple beam energies …

Allosteric Inhibition Of Factor Xiiia. Non-Saccharide Glycosaminoglycan Mimetics, But Not Glycosaminoglycans, Exhibit Promising Inhibition Profile, Rami A. Al-Horani, Rajesh Karuturi, Michael Lee, Daniel K. Afosa, Umesh R. Desai

Medicinal Chemistry Publications

Factor XIIIa (FXIIIa) is a transglutaminase that catalyzes the last step in the coagulation process. Orthostery is the only approach that has been exploited to design FXIIIa inhibitors. Yet, allosteric inhibition of FXIIIa is a paradigm that may offer a key advantage of controlled inhibition over orthosteric inhibition. Such an approach is likely to lead to novel FXIIIa inhibitors that do not carry bleeding risks. We reasoned that targeting a collection of basic amino acid residues distant from FXIIIa’s active site by using sulfated glycosaminoglycans (GAGs) or non-saccharide GAG mimetics (NSGMs) would lead to the discovery of the first allosteric …

Effects Of Inositol(S) In Women With Pcos: A Systematic Review Of Randomized Controlled Trials, Vittorio Unfer, John E. Nestler, Zdravko A. Kamenov, Nikos Prapas, Fabio Facchinetti

Obstetrics and Gynecology Publications

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, with complex etiology and pathophysiology, which remains poorly understood. It affects about 5–10% of women of reproductive age who typically suffer from obesity, hyperandrogenism, ovarian dysfunction, and menstrual irregularity. Indeed, PCOS is the most common cause of anovulatory infertility in industrialized nations, and it is associated with insulin resistance, type 2 diabetes mellitus, and increased cardiovascular risk. Although insulin resistance is not included as a criterion for diagnosis, it is a critical pathological condition of PCOS. The purpose of this systematic review is the analysis of recent randomized clinical trials of …

Virginia Dental Journal (Vol. 93, No. 4, 2016)

Virginia Dental Journal

No abstract provided.

Medical Literary Messenger (Vol. 3, No. 2, Spring/Summer 2016)

Medical Literary Messenger

Exposure / Dan Campion -- The Second Floor Shop B / Hil Scott -- Incubator Memory / Meridian Johnson -- Take Me to Richmond / Derick Nelson Jenkins -- Destination Unknown / Derick Nelson Jenkins -- Symmetry / Derick Nelson Jenkins -- The Aide / Erika D. Price -- Subconscious / David Yoffe -- What My Uncle is Thinking / Tamsyn Brennan -- Progression / E. F. Schraeder -- Waiting / Justin Nicholes -- Only 1,482 Steps From the Massey Cancer Center Entrance / Dodge Havens -- At Hardy-Owen Funeral Home, Conveniently Located on Dixie Highway / Monique Kluczykowski -- …

Medical Literary Messenger (Vol. 4, No. 1, Fall/Winter 2016)

Medical Literary Messenger

Irene—London, December 2006 / Katharine Harer -- Today / Antonia Lewandowski -- The Bench / Richard LeBlond -- illustration / Alana Barrett -- After Reading Elizabeth Bishop’s “In the Waiting Room” / Nina Bannett -- How to Open Your Eyes / Angus Woodward -- Stage 3 / Amanda Gomez -- NeuroSkull / Alana Barrett -- It / Grace Fryberger -- The Mammogram, Part II / Katharine Harer -- Old and New / Derick Nelson Jenkins -- The Innoculation / Simon Friedman -- illustrations / Alana Barrett -- Shocking / Phyllis Price -- Boutique Hotel / Lynn Ciesielski -- A Sleeping …

Mir-9 Acts As An Oncomir In Prostate Cancer Through Multiple Pathways That Drive Tumour Progression And Metastasis, S. J. Seashols-Williams, W. Budd, G. C. Clark, Q. Wu, R. Daniel, E. Dragoescu, Z. E. Zehner

Biochemistry and Molecular Biology Publications

Identification of dysregulated microRNAs (miRNAs) in prostate cancer is critical not only for diagnosis, but also differentiation between the aggressive and indolent forms of the disease. miR-9 was identified as an oncomiR through both miRNA panel RT-qPCR as well as high-throughput sequencing analysis of the human P69 prostate cell line as compared to its highly tumorigenic and metastatic subline M12, and found to be consistently upregulated in other prostate cell lines including DU-145 and PC3. While miR-9 has been characterized as dysregulated either as an oncomiR or tumour suppressor in a variety of other cancers including breast, ovarian, and nasopharyngeal …

Exploration Of Bivalent Ligands Targeting Putative Mu Opioid Receptor And Chemokine Receptor Ccr5 Dimerization, Christopher K. Arnatt, Bethany A. Falls, Yunyun Yuan, Thomas J. Raborg, Ruturaj R. Masvekar, Nazira El-Hage, Dana E. Selley, Anthony V. Nicola, Pamela E. Knapp, Kurt F. Hauser, Yan Zhang

Medicinal Chemistry Publications

Modern antiretroviral therapies have provided HIV-1 infected patients longer lifespans and better quality of life. However, several neurological complications are now being seen in these patients due to HIV-1 associated injury of neurons by infected microglia and astrocytes. In addition, these effects can be further exacerbated with opiate use and abuse. One possible mechanism for such potentiation effects of opiates is the interaction of the mu opioid receptor (MOR) with the chemokine receptor CCR5 (CCR5), a known HIV-1 co-receptor, to form MOR-CCR5 heterodimer. In an attempt to understand this putative interaction and its relevance to neuroAIDS, we designed and synthesized …

Speaking Up: Using Ostes To Understand How Medical Students Address Professionalism Lapses, Constance R. Tucker, Beth A. Choby, Andrew Moore, Robert Scott Parker Ii, Benjamin R. Zambetti, Sarah Naids, Jillian Scott, Jennifer Loome, Sierra Gaffney

Publications from the Office of the Dean

Background: Objective-structured teaching encounters (OSTEs) are used across many disciplines to assess teaching ability. The OSTE detailed in this paper assesses 191 fourth-year medical students’ (M4) ability to identify and address lapses in professionalism based on Association of American Medical Colleges’ professionalism competencies. The research questions addressed are:

• How frequently do M4s address professionalism lapses observed during an OSTE?
• What factors influence whether M4s provide feedback when they observe professionalism lapses in an OSTE?

Methods: Standardized patients (SPs) and standardized learners (SLs) were recruited and trained to participate in a standardized encounter with specific cognitive, social, and behavioral …

Bone - Prosthesis Junction For Active Tendon Implants: A Biomechanical Comparison Of Two Fixation Techniques, Imran Khatri, Jennifer S. Wayne Phd

MD Student Summer Research Fellowship Program Posters

End-to-end repair of damaged tendon is not possible in many instances of injury. Staged flexor tendon reconstruction has been proven to be a valuable method of addressing complex flexor tendon injuries when the patient presents late, has failed primary repair, or the injury mandates it (1). Silicone implants have been used for two-stage flexor tendon reconstructions with reports of long-term use as active implants (2,3). Implants have been reported functional approximately one year post-surgery with some still in use up to 25 years after reconstruction (4). This suggests the potential of the implant serving as a permanent prosthesis. The biomechanical …

Family-Centered Rounds And Medical Student Performance On The Nbme Pediatrics Subject (Shelf) Examination: A Retrospective Cohort Study, Tiffany N. Kimbrough, Victor Heh, N. Romesh Wijesooriya, Michael S. Ryan

Pediatrics Publications

Objective

To determine the association between family-centered rounds (FCR) and medical student knowledge acquisition as assessed by the National Board of Medical Examiners (NBME) pediatric subject (shelf) exam.

Methods

A retrospective cohort study was conducted of third-year medical students who graduated from Virginia Commonwealth University School of Medicine between 2009 and 2014. This timeframe represented the transition from ‘traditional’ rounds to FCR on the pediatric inpatient unit. Data collected included demographics, United States Medical Licensing Examination (USMLE) Step 1 and 2 scores, and NBME subject examinations in pediatrics (PSE), medicine (MSE), and surgery (SSE).

Results

Eight hundred and sixteen participants …

Metabolism And Metabolic Inhibition Of Xanthotoxol In Human Liver Microsomes, Zhongnv Ma, Xianbao Shi, Gang Zhang, Feng Guo, Lina Shan, Jiqun Cai

Medicinal Chemistry Publications

Cytochrome p450 (CYP450) enzymes are predominantly involved in Phase I metabolism of xenobiotics. In this study, the CYP450 isoforms involved in xanthotoxol metabolism were identified using recombinant CYP450s. In addition, the inhibitory effects of xanthotoxol on eight CYP450 isoforms and its pharmacokinetic parameters were determined using human liver microsomes. CYP1A2, one of CYP450s, played a key role in the metabolism of xanthotoxol compared to other CYP450s. Xanthotoxol showed stronger inhibition on CYP3A4 and CYP1A2 compared to other isoenzymes with the IC50 of 7.43 μM for CYP3A4 and 27.82 μM for CYP1A2. The values of inhibition kinetic parameters (Ki) were 21.15 …

Virginia Dental Journal (Vol. 93, No. 2, 2016)

Virginia Dental Journal

No abstract provided.

Pharmacological Blockade Of The Calcium Plateau Provides Neuroprotection Following Organophosphate Paraoxon Induced Status Epilepticus In Rats, Laxmikant S. Deshpande, Robert E. Blair, Beverly A. Huang, Kristin F. Phillips, Robert J. Delorenzo

Neurology Publications

Organophosphate (OP) compounds which include nerve agents and pesticides are considered chemical threat agents. Currently approved antidotes are crucial in limiting OP mediated acute mortality. However, survivors of lethal OP exposure exhibit delayed neuronal injury and chronic behavioral morbidities. In this study, we investigated neuroprotective capabilities of dantrolene and carisbamate in a rat survival model of paraoxon (POX) induced status epilepticus (SE). Significant elevations in hippocampal calcium levels were observed 48-h post POX SE survival, and treatment with dantrolene (10 mg/kg, i.m.) and carisbamate (90 mg/kg, i.m.) lowered these protracted calcium elevations. POX SE induced delayed neuronal injury …

Impaired Immunological Synapse In Sperm Associated Antigen 6 (Spag6) Deficient Mice, Lauren Folgosa Cooley, Mohey Eldin El Shikh, Wei Li, Rebecca C. Keim, Zhengang Zhang, Jerome F. Strauss, Zhibing Zhang, Daniel H. Conrad

Microbiology and Immunology Publications

Sperm associated antigen 6 (SPAG6), a component of the central apparatus of the “9 + 2” axoneme, plays a central role in ciliary and flagellar motility; but, its contribution to adaptive immunity and immune system development is completely unknown. While immune cells lack a cilium, the immunological synapse is a surrogate cilium as it utilizes the same machinery as ciliogenesis including the nucleation of microtubules at the centrosome. This prompted our hypothesis that SPAG6 critically regulates the formation and function of immunological synapses. Using bone marrow reconstitution studies of adult WT mice, we demonstrate that SPAG6 is expressed in primary …

The Prostaglandin E2-Ep3 Receptor Axis Regulates Anaplasma Phagocytophilum-Mediated Nlrc4 Inflammasome Activation, Xiaowei Wang, Dana K. Shaw, Holly L. Hammond, Fayyaz S. Sutterwala, Manira Rayamajhi, Kari Ann Shirey, Darren J. Perkins, Joseph V. Bonventre, Thangam S. Velayutham, Sean M. Evans, Kyle G. Rodino, Lauren Viebrock, Karen M. Scanlon, Nicholas H. Carbonetti, Jason A. Carlyon, Edward A. Miao, Jere W. Mcbride, Michail Kotsyfakis, Joao H. F. Pedra

Microbiology and Immunology Publications

Rickettsial agents are sensed by pattern recognition receptors but lack pathogen-associated molecular patterns commonly observed in facultative intracellular bacteria. Due to these molecular features, the order Rickettsiales can be used to uncover broader principles of bacterial immunity. Here, we used the bacterium Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, to reveal a novel microbial surveillance system. Mechanistically, we discovered that upon A. phagocytophilum infection, cytosolic phospholipase A2 cleaves arachidonic acid from phospholipids, which is converted to the eicosanoid prostaglandin E2 (PGE2) via cyclooxygenase 2 (COX2) and the membrane associated prostaglandin E synthase-1 (mPGES-1). PGE2-EP3 receptor signaling leads …

Does The Addition Of Standard Systematic Biopsies To Targeted Prostate Biopsies Influence Treatment Choices For Patients And Clinicians?, William Behl, Jinxing Yu Md

MD Student Summer Research Fellowship Program Posters

Addition of standard systematic prostate biopsy to targeted biopsy in patients with elevated PSA and no prior systematic prostate biopsy within the preceding 3 years detected PCa GS ≥ 7 on the opposite side of the prostate from the target lesions (with no significant abnormalities on mp-MRI) in 13% of patients. This result may influence treatment choices, particularly for those patients considering focal therapy for PCa.

First Trimester Vaginal Microbiome As Pregnancy Outcome Predictor, Sarah K. Rozycki, Jennifer M. Fettwis

MD Student Summer Research Fellowship Program Posters

• We have developed clinical definiKons of healthy and complicated pregnancies based on pathologies that will be used in future VaHMP studies.

• Although one study7 found dysbioKc vagitypes in all three semesters of women who had PPROM, none of our PPROM subjects had a BVAB1 vagitype, and there were equal Gardnerella vaginalis vagitypes in both the controls and subjects who had PPROM (Fig. 2).

• While there were more PPROM subjects with Lactobacillus iners vagitypes, this Lactobacillus is less protecKve as it can coexist with pathogenic anaerobic bacteria.

• “Candidatus Mycoplasma girerdii”, Lactobacillus jensenii, and Ureaplasma were significantly associated …

Tumor-Reactive Immune Cells Protect Against Metastatic Tumor And Induce Immunoediting Of Indolent But Not Quiescent Tumor Cells, Kyle K. Payne, Rebecca Keim, Laura Graham, Michael O. Idowu, Wen Wan, Xiang-Yang Wang, Amir A. Toor, Harry D. Bear, Masoud H. Manjili

Massey Comprehensive Cancer Center Publications

Two major barriers to cancer immunotherapy include tumor-induced immune suppression mediated by myeloid-derived suppressor cells and poor immunogenicity of the tumor-expressing self-antigens. To overcome these barriers, we reprogrammed tumor-immune cell cross-talk by combined use of decitabine and adoptive immunotherapy, containing tumor-sensitized T cells and CD25⁺ NKT cells. Decitabine functioned to induce the expression of highly immunogenic cancer testis antigens in the tumor, while also reducing the frequency of myeloid-derived suppressor cells and the presence of CD25⁺ NKT cells rendered T cells, resistant to remaining myeloid-derived suppressor cells. This combinatorial therapy significantly prolonged survival of animals bearing metastatic tumor …

Development Of A Translational Model To Screen Medications For Cocaine Use Disorder I: Choice Between Cocaine And Food In Rhesus Monkeys, Amy R. Johnson

Pharmacology and Toxicology Publications

Background

Homologous cocaine self-administration procedures in laboratory animals and humans may facilitate translational research for medications development to treat cocaine dependence. This study, therefore, sought to establish choice between cocaine and an alternative reinforcer in rhesus monkeys responding under a procedure back-translated from previous human studies and homologous to a human laboratory procedure described in a companion paper.

Methods

Four rhesus monkeys with chronic indwelling intravenous catheters had access to cocaine injections (0, 0.043, 0.14, or 0.43 mg/kg/injection) and food (0, 1, 3, or 10 1 g banana-flavored food pellets). During daily 5 h sessions, a single cocaine dose and …

Substance Use And Depression Symptomatology: Measurement Invariance Of The Beck Depression Inventory (Bdi-Ii) Among Non-Users And Frequent-Users Of Alcohol, Nicotine And Cannabis, Ashlee A. Moore, Michael C. Neale, Judy L. Silberg, Brad Verhulst

Psychiatry Publications

Depression is a highly heterogeneous condition, and identifying how symptoms present in various groups may greatly increase our understanding of its etiology. Importantly, Major Depressive Disorder is strongly linked with Substance Use Disorders, which may ameliorate or exacerbate specific depression symptoms. It is therefore quite plausible that depression may present with different symptom profiles depending on an individual’s substance use status. Given these observations, it is important to examine the underlying construct of depression in groups of substance users compared to non-users. In this study we use a non-clinical sample to examine the measurement structure of the Beck Depression Inventory …

Art And Medicine: A Collaborative Project Between Virginia Commonwealth University In Qatar And Weill Cornell Medicine In Qatar, Amy J. Andres, Thomas R. Himsworth, Alan Weber, Stephen Scott

VCU Libraries Faculty and Staff Publications

Four faculty researchers, two from Virginia Commonwealth University in Qatar, and two from Weill Cornell Medicine in Qatar developed a one semester workshop-based course in Qatar exploring the connections between art and medicine in a contemporary context. Students (6 art / 6 medicine) were enrolled in the course. The course included presentations by clinicians, medical engineers, artists, computing engineers, an art historian, a graphic designer, a painter, and other experts from the fields of art, design, and medicine. To measure the student experience of interdisciplinarity, the faculty researchers employed a mixed methods approach involving psychometric tests and observational ethnography. Data …

Saudi Scd Patients’ Symptoms And Quality Of Life Relative To The Number Of Ed Visits, Anwar E. Ahmed, Ahmed S. Alaskar, Donna K. Mcclish, Yosra Z. Ali, Mohammed H. Aldughither, Ahmad M. Al-Suliman, Hafiz M. Malhan

Biostatistics Publications

Background

Individuals living with sickle cell disease (SCD) have significantly increased emergency department (ED) use compared to the general population. In Saudi Arabia, health care is free for all individuals and therefore has no bearing on increased ED visits. However, little is known about the relationship between quality of life (QoL) and frequency of acute care utilization in this patient population.

Methods

A cross-sectional study was conducted on 366 patients with SCD who attended the outpatient department at King Fahad Hospital, Hofuf, Saudi Arabia. Data were collected through self-administered surveys, which included: demographics, SCD-related ED visits, clinical issues, and QoL …

Methods For Evaluating Respondent Attrition In Web-Based Surveys, Camille J. Hochheimer, Roy T. Sabo, Alex H. Krist, Teresa Day, John Cyrus, Steven H. Woolf

Biostatistics Publications

Background: Electronic surveys are convenient, cost effective, and increasingly popular tools for collecting information. While the online platform allows researchers to recruit and enroll more participants, there is an increased risk of participant dropout in Web-based research. Often, these dropout trends are simply reported, adjusted for, or ignored altogether.

Objective: To propose a conceptual framework that analyzes respondent attrition and demonstrates the utility of these methods with existing survey data.

Methods: First, we suggest visualization of attrition trends using bar charts and survival curves. Next, we propose a generalized linear mixed model (GLMM) to detect or confirm …

Proton Pump Inhibitors Are Associated With Increased Risk Of Development Of Chronic Kidney Disease, Pradeep Arora, Anu Gupta, Mojgan Golzy, Nilang Patel, Randolph L. Carter, Kabir Jalal, James W. Lohr

Biostatistics Publications

Background

Acute interstitial nephritis secondary to proton pump inhibitors (PPIs) frequently goes undiagnosed due to its subacute clinical presentation, which may later present as chronic kidney disease (CKD). We investigated the association of PPI use with the development of CKD and death.

Methods

Two separate retrospective case–control study designs were employed with a prospective logistic regression analysis of data to evaluate the association of development of CKD and death with PPI use. The population included 99,269 patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008. For evaluation of the CKD outcome, 22,807 with preexisting CKD at …

Improving Sensitivity Of Linear Regression-Based Cell Type-Specific Differential Expression Deconvolution With Per-Gene Vs. Global Significance Threshold, Edmund R. Glass, Mikhail G. Dozmorov

Biostatistics Publications

Background

The goal of many human disease-oriented studies is to detect molecular mechanisms different between healthy controls and patients. Yet, commonly used gene expression measurements from blood samples suffer from variability of cell composition. This variability hinders the detection of differentially expressed genes and is often ignored. Combined with cell counts, heterogeneous gene expression may provide deeper insights into the gene expression differences on the cell type-specific level.

Published computational methods use linear regression to estimate cell type-specific differential expression, and a global cutoff to judge significance, such as False Discovery Rate (FDR). Yet, they do not consider many artifacts …

African-American Patients With Cancer Talking About Clinical Trials (Tact) With Oncologists During Consultations: Evaluating The Efficacy Of Tailored Health Messages In A Randomised Controlled Trial—The Tact Study Protocol, R F. Brown, R Davis, M Wilson Genderson, S Grant, D Cadet, M Lessard, J Alpert, J Ward, G Ginder

Health Policy Publications

Introduction Low rates of accrual of African-American (AA) patients with cancer to therapeutic clinical trials (CTs) represent a serious and modifiable racial disparity in healthcare that impedes the development of promising cancer therapies. Suboptimal physician–patient consultation communication is a barrier to the accrual of patients with cancer of any race, but communication difficulties are compounded with AA patients. Providing tailored health messages (THM) to AA patients and their physician about CTs has the potential to improve communication, lower barriers to accrual and ameliorate health disparities.

Objective (1) Demonstrate the efficacy of THM to increase patient activation as measured by direct …

Dna Methylation Of Regulatory Regions Of Imprinted Genes At Birth And Its Relation To Infant Temperament, Bernard F. Fuemmeler, Chien-Ti Lee, Adelheid Soubry, Edwin S. Iversen, Zhiqing Huang, Amy P. Murtha, Joellen M. Schildkraut, Randy L. Jirtle, Susan K. Murphy, Cathrine Hoyo

Health Policy Publications

Background: DNA methylation of the differentially methylated regions (DMRs) of imprinted genes is relevant to neurodevelopment.

Methods: DNA methylation status of the DMRs of nine imprinted genes in umbilical cord blood leukocytes was analyzed in relation to infant behaviors and temperament (n = 158).

Results: MEG3 DMR levels were positively associated with internalizing (β = 0.15, P = 0.044) and surgency (β = 0.19, P = 0.018) behaviors, after adjusting for birth weight, gender, gestational age at birth, maternal age at delivery, race/ethnicity, education level, smoking status, parity, and a history of anxiety or depression. Higher methylation levels at the …