Medicine and Health Sciences Commons^™

Tamoxifen Activity Against Plasmodium In Vitro And In Mice, Ada Weinstock, Julio Gallego-Delgado, Cláudia Gomes, Julian Sherman, Cyrus Nikain, Sandra Gonzalez, Edward Fisher, Ana Rodriguez

Publications and Research

Background: Tamoxifen is an oestrogen receptor modulator that is widely used for the treatment of early stage breast cancer and reduction of recurrences. Tamoxifen is also used as a powerful research tool for controlling gene expression in the context of the Cre/loxP site-specific recombination system in conditional mutant mice.

Methods: To determine whether the administration of tamoxifen affects Plasmodium growth and/or disease outcome in malaria, in vitro studies assessing the effect of tamoxifen and its active metabolite 4-hydroxytamoxifen on Plasmodium falciparum blood stages were performed. Tamoxifen effects were also evaluated in vivo treating C57/B6 mice infected with Plasmodium berghei (ANKA …

Medical Dental Device: Biogeneric Implant Prototype, Ibeth Erazo, Aneeza Hussain, Renata Budny, Gaffar Gailani

Publications and Research

Teeth are lost due to tooth decay, injury, disease, or other causes. Today, dental implants extend the range of care to a variety of patients undergoing necessary prosthodontic rehabilitation. If the benefits of such treatments are to be maximized, then implants must be selected on logical basis and placed within the context of the full range of treatment modalities. However, modern dental implant systems are based on multiple components often leading to micro-movements which cause stress on the bone or bacterial infections, both of which compromise the success of osseointegration and consequently jeopardize the whole implant adaptation. Thus, a new …

Etiology And Clinical Patterns Of Uveitis At Three Ophthalmic Clinics In Tajikistan, Sayyora Yuldasheva, Saidbeg Satorov, Shekhratdzon Satorov, Vyacheslav Dushenkov

Publications and Research

A prospective observational study was conducted at three ophthalmic clinics to assess the clinical patterns and etiology of uveitis in the Central Asia Republic of Tajikistan. All patients underwent physical and ophthalmologic examinations. Extensive efforts were made to determine the etiology of uveitis, including workups for Behçet's Disease (BD) and Vogt–Koyanagi–Harada (VKH) syndrome. All patients were tested for the presence of HLA-B27. Presence and/or history of tuberculosis and syphilis were ruled out. HSV, CMV, Chlamydia trachomatis and HIV antibody titers were determined by ELISA. Uveitis was diagnosed in 51 patient ages 14 to 60 were with women accounted for 60.8%. …

Activation Of Lxrβ Inhibits Tumor Respiration And Is Synthetically Lethal With Bcl-Xl Inhibition, Trang Thi Thu Nguyen, Chiaki Tsuge Ishida, Enyuan Shang, Chang Shu, Consuelo Torrini, Yiru Zhang, Elena Bianchetti, Maria J. Sanchez-Quintero, Giulio Kleiner, Catarina M. Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Peter Canoll, Markus D. Siegelin

Publications and Research

Liver-X-receptor (LXR) agonists are known to bear anti-tumor activity. However, their efficacy is limited and additional insights regarding the underlying mechanism are necessary. By performing transcriptome analysis coupled with global polar metabolite screening, we show that LXR agonists, LXR623 and GW3965, enhance synergistically the anti-proliferative effect of BH3 mimetics in solid tumor malignancies, which is predominantly mediated by cell death with features of apoptosis and is rescued by exogenous cholesterol. Extracellular flux analysis and carbon tracing experiments (U-¹³C-glucose and U-¹³C-glutamine) reveal that within 5 h, activation of LXRβ results in reprogramming of tumor cell metabolism, leading …

Endothelial Iqgap1 Regulates Leukocyte Transmigration By Directing The Lbrc To The Site Of Diapedesis, David P. Sullivan, Prarthana J. Dalal, Fanny Jaulin, David B. Sacks, Geri Kreitzer, William A. Muller

Publications and Research

Transendothelial migration (TEM) of leukocytes across the endothelium is critical for inflammation. In the endothelium, TEM requires the coordination of membrane movements and cytoskeletal interactions, including, prominently, recruitment of the lateral border recycling compartment (LBRC). The scaffold protein IQGAP1 was recently identified in a screen for LBRC-interacting proteins. Knockdown of endothelial IQGAP1 disrupted the directed movement of the LBRC and substantially reduced leukocyte TEM. Expression of truncated IQGAP1 constructs demonstrated that the calponin homology domain is required for IQGAP1 localization to endothelial borders and that the IQ domain, on the same IQGAP1 polypeptide, is required for its function in TEM. …

Cc Chemokine Ccl1 Receptor Ccr8 Mediates Conversion Of Mesenchymal Stem Cells To Embryoid Bodies Expressing Foxp3+Ccr8+ Regulatory T Cells, Nasreen Haque, Tuteja Akaash, Niloufar Haque

Publications and Research

Embryoid bodies (EBs) are three dimensional aggregates of pluripotent stem cells primarily used to investigate morphogenesis and cell toxicity, are also attractive tools in regenerative medicine. While embryonic stem cells (ESCs) and induced pluripotent cells (IPSCs) have been shown to form EBs in mouse, primate and humans, EB formation have not been previously demonstrated in mesenchymal stem cells (MSCs). Here we show that rat MSCs form EBs; which express regulatory T cell (Treg) marker Foxp3 and CC chemokine CCL1 receptor CCR8. We show a novel method for formation of EBs from MSCs under stress and demonstrate that the induction of …

Competitive Frontoparietal Interactions Mediate Implicit Inferences, Martijn E. Wokke, Tony Ro

Publications and Research

Frequent experience with regularities in our environment allows us to use predictive information to guide our decision process. However, contingencies in our environment are not always explicitly present and sometimes need to be inferred. Heretofore, it remained unknown how predictive information guides decision-making when explicit knowledge is absent and how the brain shapes such implicit inferences. In the present experiment, 17 human participants (9 females) performed a discrimination task in which a target stimulus was preceded by a predictive cue. Critically, participants had no explicit knowledge that some of the cues signaled an upcoming target, allowing us to investigate how …

Activation Of Lxr Receptors And Inhibition Of Trap1 Causes Synthetic Lethality In Solid Tumors, Trang Thi Thu Nguyen, Chiaki Tsuge Ishida, Enyuan Shang, Chang Shu, Elena Bianchetti, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

Cholesterol is a pivotal factor for cancer cells to entertain their relentless growth. In this case, we provide a novel strategy to inhibit tumor growth by simultaneous activation of liver-X-receptors and interference with Tumor Necrosis Factor Receptor-associated Protein 1 (TRAP1). Informed by a transcriptomic and subsequent gene set enrichment analysis, we demonstrate that inhibition of TRAP1 results in suppression of the cholesterol synthesis pathway in stem-like and established glioblastoma (GBM) cells by destabilizing the transcription factor SREBP2. Notably, TRAP1 inhibition induced cell death, which was rescued by cholesterol and mevalonate. Activation of liver X receptor (LXR) by a clinically validated …

Extreme Events Reveal An Alimentary Limit On Sustained Maximal Human Energy Expenditure, Caitlin Thurber, Lara R. Dugas, Cara Ocobock, Bryce Carlson, John R. Speakman, Herman Pontzer

Publications and Research

The limits on maximum sustained energy expenditure are unclear but are of interest because they constrain reproduction, thermoregulation, and physical activity. Here, we show that sustained expenditure in humans, measured as maximum sustained metabolic scope (SusMS), is a function of event duration. We compiled measurements of total energy expenditure (TEE) and basal metabolic rate (BMR) from human endurance events and added new data from adults running ~250 km/week for 20 weeks in a transcontinental race. For events lasting 0.5 to 250+ days, SusMS decreases curvilinearly with event duration, plateauing below 3× BMR. This relationship differs from that of shorter events …

Effects Of The Kcnq Channel Opener Ezogabine On Functional Connectivity Of The Ventral Striatum And Clinical Symptoms In Patients With Major Depressive Disorder, Aaron Tan, Sara Costi, Laurel S. Morris, Nicholas T. Van Dam, Marin Kautz, Alexis E. Whitton, Allyson K. Friedman, Katherine A. Collins, Gabriella Ahle, Nisha Chadha, Brian Do, Diego A. Pizzagalli, Dan V. Iosifescu, Eric J. Nestler, Ming-Hu Han, James W. Murrough

Publications and Research

Major depressive disorder (MDD) is a leading cause of disability worldwide, yet current treatment strategies remain limited in their mechanistic diversity. Recent evidence has highlighted a promising novel pharmaceutical target—the KCNQ-type potassium channel—for the treatment of depressive disorders, which may exert a therapeutic effect via functional changes within the brain reward system, including the ventral striatum. The current study assessed the effects of the KCNQ channel opener ezogabine (also known as retigabine) on reward circuitry and clinical symptoms in patients with MDD. Eighteen medication-free individuals with MDD currently in a major depressive episode were enrolled in an open-label study and …

Modeling Changes In Cellular Micro-Environment In Mild To Moderate Head Trauma, Xiangfu Zhang, Subhendra N. Sarkar Phd, Rt

Publications and Research

Our work aims to connect and model multiple small, inter-related tissue injuries as a consequence of mild traumatic brain injuries (mTBI). It has been shown that frontal and temporal lobes are vulnerable regions for brain traumatic injury. A brain injury from a blow or high-speed impact can cause undersurface of the frontal and temporal lobes to deform against the anterior and cranial fossae. This deformation can often trigger damage to the cerebral vasculature, which is ill-understood and can result in chronic damage to larger vessels over time. These physiological injuries can be manifested psychologically; such as patients’ sleep-wake disturbances. The …

Effects Of Vitamin D3 And Its Chemical Analogs On The Growth Of Hodgkin’S Lymphoma, In Vitro, Rajendra Ghardbaran, Bo Zhang, Luis Valerio, Onyekwere Onwumere, Madeline Wong, Jason Mighty, Stephen Redenti

Publications and Research

Objective: Vitamin D receptor (VDR) activities have been noted for a number of B cell malignancies which showed varying sensitivities to vitamin D3 (1,25-dihydroxyvitamin D3, VD3, calcitriol) and its synthetic analogs. The objective of this study was to address the potential effects of VD3 and vitamin D3 analogs (VDAs) on the growth of Hodgkin’s lymphoma (HL), a malignant pathology of B cell origin, in vitro.

Results: Immunofluorescence staining showed the expression of VDR by primary Hodgkin’s (H) and Reed–Sternberg (RS)—HRS-tumor cells in HL histological sections. Western blot analyses revealed expression of VDR in the HL cell lines Hs445, HDLM2, KMH2, …

Case Presentation On Congestive Heart Failure And Pulmonary Edema, Tetiana Soloviova, Denise Aris

Publications and Research

No abstract provided.

Transspinal Stimulation Increases Motoneuron Output Of Multiple Segments In Human Spinal Cord Injury, Lynda M. Murray, Maria Knikou

Publications and Research

Targeted neuromodulation strategies that strengthen neuronal activity are in great need for restoring sensorimotor function after chronic spinal cord injury (SCI). In this study, we established changes in the motoneuron output of individuals with and without SCI after repeated noninvasive transspinal stimulation at rest over the thoracolumbar enlargement, the spinal location of leg motor circuits. Cases of motor incomplete and complete SCI were included to delineate potential differences when corticospinal motor drive is minimal. All 10 SCI and 10 healthy control subjects received daily monophasic transspinal stimuli of 1-ms duration at 0.2 Hz at right soleus transspinal evoked potential (TEP) …

Biotransformed Metabolites Of The Hop Prenylflavanone Isoxanthohumol, Hyun Jung Kim, Soon-Ho Yim, Fubo Han, Bok Yun Kang, Hyun Jin Choi, Da-Woon Jung, Darren R. Williams, Kirk R. Gustafson, Edward J. Kennelly, Ik-Soo Lee

Publications and Research

A metabolic conversion study on microbes is known as one of the most useful tools to predict the xenobiotic metabolism of organic compounds in mammalian systems. The microbial biotransformation of isoxanthohumol (1), a major hop prenylflavanone in beer, has resulted in the production of three diastereomeric pairs of oxygenated metabolites (2–7). The microbial metabolites of 1 were formed by epoxidation or hydroxylation of the prenyl group, and HPLC, NMR, and CD analyses revealed that all of the products were diastereomeric pairs composed of (2S)- and (2R)- isomers. The structures of these metabolic compounds were elucidated to be (2S,200S)- and (2R,200S)-40 …

Model-Based Methods To Translate Adolescent Medicine Trials Network For Hiv/Aids Interventions Findings Into Policy Recommendations: Rationale And Protocol For A Modeling Core (Atn 161), Anne M. Neilan, Kunjal Patel, Allison L. Agwu, Ingrid V. Bassett, K. Rivet Amico, Catherine M. Crespi, Aditya H. Gaur, Keith J. Horvath, Kimberly A. Powers, H. Jonathon Rendina, Lisa B. Hightow-Weidman, Xiaoming Li, Sylvie Naar, Sharon Nachman, Jeffrey T. Parsons, Kit N. Simpson, Bonita F. Stanton, Kenneth A. Freedberg, Audrey C. Bangs, Michael G. Hudgens, Andrea L. Ciaranello

Publications and Research

BACKGROUND: The United States Centers for Disease Control and Prevention estimates that approximately 60,000 US youth are living with HIV. US youth living with HIV (YLWH) have poorer outcomes compared with adults, including lower rates of diagnosis, engagement, retention, and virologic suppression. With Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) support, new trials of youth-centered interventions to improve retention in care and medication adherence among YLWH are underway.

OBJECTIVE: This study aimed to use a computer simulation model, the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-Adolescent Model, to evaluate selected ongoing and forthcoming ATN interventions to improve viral load suppression …

Spinal Matrix Metalloproteinase 8 Regulates Pain After Peripheral Trauma, Maral Tajerian, J. David Clark

Publications and Research

It is well documented that pain chronification requires a host of plastic mechanisms at the spinal cord (SC) level, including alterations in neuronal and glial structure and function. Such cellular plasticity necessitates the existence of a plastic extracellular matrix(ECM). Here, we describe a key role for ECM remodeling in the regulation of chronic pain following peripheral injury. Three weeks following tibia fracture in mice, we show increased levels of MMP8 in the SC. Furthermore, we show that the pharmacological or genetic downregulation of MMP8 ameliorates the pain phenotype observed after injury. These results delineate an extracellular mechanism for pain chronification, …

Resistance Training Volume Enhances Muscle Hypertrophy But Not Strength In Trained Men, Brad J. Schoenfeld, Bret Contreras, James Krieger, Jozo Grgic, Kenneth Delcastillo, Ramon Belliard, Andrew Alto

Publications and Research

Purpose: The purpose of this study was to evaluate muscular adaptations between low-, moderate-, and high-volume resistance training protocols in resistance-trained men.

Methods: Thirty-four healthy resistance-trained men were randomly assigned to one of three experimental groups: a low-volume group performing one set per exercise per training session (n = 11), a moderate-volume group performing three sets per exercise per training session (n = 12), or a high-volume group performing five sets per exercise per training session (n = 11). Training for all routines consisted of three weekly sessions performed on nonconsecutive days for 8 wk. Muscular strength was evaluated with …