Medical Sciences Commons^™

Functional Neuroplasticity In The Nucleus Tractus Solitarius And Increased Risk Of Sudden Death In Mice With Acquired Temporal Lobe Epilepsy, Isabel D. Derera, Brian P. Delisle, Bret N. Smith

Physiology Faculty Publications

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in individuals with refractory acquired epilepsy. Cardiorespiratory failure is the most likely cause in most cases, and central autonomic dysfunction has been implicated as a contributing factor to SUDEP. Neurons of the nucleus tractus solitarius (NTS) in the brainstem vagal complex receive and integrate vagally mediated information regarding cardiorespiratory and other autonomic functions, and GABAergic inhibitory NTS neurons play an essential role in modulating autonomic output. We assessed the activity of GABAergic NTS neurons as a function of epilepsy development in the pilocarpine-induced status epilepticus (SE) model of …

Duodenal Varices: A Rare Cause Of Gastrointestinal Bleeding., Anam Malik Md, Abdul Aleem Md, Eric Nellis Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

Difatty Acyl-Conjugated Linear And Cyclic Peptides For Sirna Delivery, Hung Do, Meenakshi Sharma, Naglaa Salem El-Sayed, Parvin Mahdipoor, Emira Bousoik, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

A number of amphiphilic difatty acyl linear and cyclic R5K2 peptide conjugates were synthesized by solid-phase peptide methods to enhance the interaction with the hydrophobic cellular phospholipid bilayer and to improve siRNA delivery and silencing. Binding to siRNA molecules was significantly less for the cyclic peptide conjugates. A gradual decrease was observed in the particle size of the complexes with increasing peptide/siRNA ratio for most of the synthesized peptides, suggesting the complex formation. Most of the complexes showed a particle size of less than 200 nm, which is considered an appropriate size for in vitro siRNA delivery. A number of …

Intrinsic And Innate Defenses Of Neurons: Détente With The Herpesviruses, Lynn Enquist, David A. Leib

Dartmouth Scholarship

Neuroinvasive herpesviruses have evolved to efficiently infect and establish latency in neurons. The nervous system has limited capability to regenerate, so immune responses therein are carefully regulated to be nondestructive, with dependence on atypical intrinsic and innate defenses. In this article we review studies of some of these noncanonical defense pathways and how herpesvirus gene products counter them, highlighting the contributions that primary neuronal in vitro models have made to our understanding of this field.

Deletion Of The Nr4a Nuclear Receptor Nor1 In Hematopoietic Stem Cells Reduces Inflammation But Not Abdominal Aortic Aneurysm Formation, Hua Qing, Karrie L. Jones, Elizabeth B. Heywood, Hong Lu, Alan Daugherty, Dennis Bruemmer

Pharmacology and Nutritional Sciences Faculty Publications

Background: The NR4A3 orphan nuclear hormone receptor, NOR1, functions as a constitutively active transcription factor to regulate inflammation, proliferation, and cell survival during pathological vascular remodeling. Inflammatory processes represent key mechanisms leading to abdominal aortic aneurysm (AAA) formation. However, a role of NOR1 in AAA formation has not been investigated previously.

Methods: Inflammatory gene expression was analyzed in bone marrow-derived macrophages isolated from NOR1-deficient mice. Low-density lipoprotein receptor-deficient (LDLr^−/−) mice were irradiated and reconstituted with hematopoietic stem cells obtained from NOR1−/− or wild-type littermate mice. Animals were infused with angiotensin II and fed a diet enriched in saturated …

Parallelization Of A Three-Dimensional Full Multigrid Algorithm To Simulate Tumor Growth, Dylan Goodin, Chin F. Ng, Hermann B. Frieboes

Commonwealth Computational Summit

We present the performance gains of an openMP implementation of a fully adaptive nonlinear full multigrid (FMG) algorithm to simulate three-dimensional multispecies desmoplastic tumor growth on computer systems of varying processing capabilities. The FMG algorithm is applied to solve a recently published thermodynamic mixture model that uses a diffuse interface approach with fourth-order reaction-advection-diffusion PDEs (Cahn-Hilliard-type equations) that are coupled, nonlinear, and numerically stiff. The model includes multiple cell species and extracellular matrix (ECM), with adhesive and elastic energy contributions in chemical potential terms, as well as including blood and lymphatic vessels represented as continuous vasculatures. Advection-reaction-diffusion PDEs are employed …

Differentiation And Protective Capacity Of Virus-Specific Cd8, Vesselin T. Tomov, Olesya Palko, Chi Wai Lau, Ajinkya Pattekar, Yuhang Sun, Ralitza Tacheva, Bertram Bengsch, Sasikanth Manne, Gabriela L. Cosma, Laurence C. Eisenlohr, Timothy J. Nice, Herbert W. Virgin, E. John Wherry

Department of Microbiology and Immunology Faculty Papers

Noroviruses can establish chronic infections with active viral shedding in healthy humans but whether persistence is associated with adaptive immune dysfunction is unknown. We used genetically engineered strains of mouse norovirus (MNV) to investigate CD8⁺ T cell differentiation during chronic infection. We found that chronic infection drove MNV-specific tissue-resident memory (Trm) CD8⁺ T cells to a differentiation state resembling inflationary effector responses against latent cytomegalovirus with only limited evidence of exhaustion. These MNV-specific Trm cells remained highly functional yet appeared ignorant of ongoing viral replication. Pre-existing MNV-specific Trm cells provided partial protection against chronic infection but largely ceased …

Initial Experience Of A Community Gastroenterology Practice With Ultra-Slim Colonoscopy: A Case Series., Rajesh Essrani Md, Patrick Hickey Do, Hiral N. Shah Md, Paola Blanco Md

Department of Medicine

No abstract provided.

Unusual Case Of Obstructive Jaundice (Poster)., Rajesh Essrani Md, Eric Nellis Md, Patrick Hickey Do, Hiral N. Shah Md

Department of Medicine

No abstract provided.

Role Of 68ga-Dodatate Pet/Ct In Staging And Management Of Gastroenteropancreatic Neuroendocrine Tumor Management - A Case Series Report., Abdul Aleem Mbbs, Patrick Hickey Do, Shashin Shah Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

No Gastrointestinal Bleed Too Obscure: A Case Series Report Of Small Bowel Phlebectasias., Abdul Aleem Md, Anam Malik Md, Patrick Hickey Do, Anastasia Shnitser Md

Department of Medicine

No abstract provided.

Sex Differential In 15-Hydroxyprostaglandin Dehydrogenase Levels In The Lumen Of Human Intracranial Aneurysms., Nohra Chalouhi, Pascal Jabbour, Mario Zanaty, Robert M. Starke, James Torner, Daichi Nakagawa, David M. Hasan

Department of Neurosurgery Faculty Papers

BACKGROUND: Aspirin is a promising medical therapy for the prevention of intracranial aneurysm (IA) rupture. Recently, we found that men have a better response to aspirin than women. The purpose of this study was to determine whether a sex differential exists in the level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in the lumen of human IAs.

METHODS AND RESULTS: Consecutive patients undergoing coiling or stent-assisted coiling for a saccular IA at our institution were enrolled. Two samples (A and B) were collected from IA lumens, and the plasma level of 15-PGDH was measured using an ELISA-based method. The study included 38 patients, …

Spinal Excitability Changes After Transspinal And Transcortical Paired Associative Stimulation In Humans, Maria Knikou

Publications and Research

Paired associative stimulation (PAS) produces enduring neuroplasticity based on Hebbian associative plasticity. This study established the changes in spinal motoneuronal excitability by pairing transcortical and transspinal stimulation. Transcortical stimulation was delivered after (transspinal-transcortical PAS) or before (transcortical-transspinal PAS) transspinal stimulation. Before and after 40 minutes of each PAS protocol, spinal neural excitability was assessed based on the amplitude of the transspinal-evoked potentials (TEPs) recorded from ankle muscles of both legs at different stimulation intensities (recruitment input-output curve). Changes in TEPs amplitude in response to low-frequency stimulation and paired transspinal stimuli were also established before and after each PAS protocol. TEP …

Human Herpesvirus 8 Infects And Replicates In Langerhans Cells And Interstitial Dermal Dendritic Cells And Impairs Their Function., Giovanna Rappocciolo, Mariel Jais, Paolo A Piazza, Diana C Delucia, Frank J Jenkins, Charles R Rinaldo

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The predominant types of dendritic cells (DC) in the skin and mucosa are Langerhans cells (LC) and interstitial dermal DC (iDDC). LC and iDDC process cutaneous antigens and migrate out of the skin and mucosa to the draining lymph nodes to present antigens to T and B cells. Because of the strategic location of LC and iDDC and the ability of these cells to capture and process pathogens, we hypothesized that they could be infected with human herpesvirus 8 (HHV-8) (Kaposi's sarcoma [KS]-associated herpesvirus) and have an important role in the development of KS. We have previously shown that HHV-8 …

Angiocatheter Guided Closure Of Gastrocutaneous Fistula Tract In The Absence Of Fluoroscopy, Travis Magdaleno Md, Hiral N. Shah Md, Shashin Shah Md

Department of Medicine

No abstract provided.

Development Of Pancreatic Cancer During Novel Therapy For Head And Neck Cancer With Pembrolizumab: A Case Report, Travis Magdaleno Md, Patrick Hickey Do, Shashin Shah Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

Glycolytic Reprogramming Through Pck2 Regulates Tumor Initiation Of Prostate Cancer Cells, Jiangsha Zhao, Jieran Li, Teresa W.M. Fan, Steven X. Hou

Toxicology and Cancer Biology Faculty Publications

Tumor-initiating cells (TICs) play important roles in tumor progression and metastasis. Identifying the factors regulating TICs may open new avenues in cancer therapy. Here, we show that TIC-enriched prostate cancer cell clones use more glucose and secrete more lactate than TIC-low clones. We determined that elevated levels of phosphoenolpyruvate carboxykinase isoform 2 (PCK2) are critical for the metabolic switch and the maintenance of TICs in prostate cancer. Information from prostate cancer patient databases revealed that higher PCK2 levels correlated with more aggressive tumors and lower survival rates. PCK2 knockdown resulted in low TIC numbers, increased cytosolic acetyl-CoA and cellular protein …

Analytics For Non-Invasive Skin Imaging And Actinic Damage, Christina E. Borchers

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Epstein-Barr Virus Mucocutaneous Colonic Ulcer In An Immunocompetent Patient., Travis Magdaleno Md, Eric Nellis Md, Paola Blanco Md

Department of Medicine

No abstract provided.

No Difference In Myosin Kinetics And Spatial Distribution Of The Lever Arm In The Left And Right Ventricles Of Human Hearts, Divya Duggal, S. Requena, Janhavi Nagwekar, Sangram Raut, Ryan Rich, Hriday Das, Vipul Patel, Ignacy Gryczynski, Rafal Fudala, Zygmunt Gryczynski, Cheavar Blair, Kenneth S. Campbell, Julian Borejdo

Physiology Faculty Publications

The systemic circulation offers larger resistance to the blood flow than the pulmonary system. Consequently, the left ventricle (LV) must pump blood with more force than the right ventricle (RV). The question arises whether the stronger pumping action of the LV is due to a more efficient action of left ventricular myosin, or whether it is due to the morphological differences between ventricles. Such a question cannot be answered by studying the entire ventricles or myocytes because any observed differences would be wiped out by averaging the information obtained from trillions of myosin molecules present in a ventricle or myocyte. …

Cheating The Cheaters: Spatial Dynamics In The Evolutionary Stability Of Antibiotic Resistance, Devin Akman

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

A New Approach For Modeling Of Tumor Volume With Nonlinear Discrete Fractional Equations, Ferhan Atici, Mustafa Atici, Ngoc Nguyen, Dana Marshall

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Complex Interplay Of Kinetic Factors Governs The Synergistic Properties Of Hiv-1 Entry Inhibitors., Koree W. Ahn, Michael J. Root

Department of Biochemistry and Molecular Biology Faculty Papers

The homotrimeric HIV-1 envelope glycoprotein (Env) undergoes receptor-triggered structural changes that mediate viral entry through membrane fusion. This process is inhibited by chemokine receptor antagonists (CoRAs) that block Env-receptor interactions and by fusion inhibitors (FIs) that disrupt Env conformational transitions. Synergy between CoRAs and FIs has been attributed to a CoRA-dependent decrease in the rate of viral membrane fusion that extends the lifetime of the intermediate state targeted by FIs. Here, we demonstrated that the magnitude of CoRA/FI synergy unexpectedly depends on FI-binding affinity and the stoichiometry of chemokine receptor binding to trimeric Env. For C-peptide FIs (clinically represented by …

Development Of A Concussion Pathway In Acute Care., Katharine Bell Ms, Otr/L, Cbis, Alisha Unternahrer Ms, Otr/L

Department of Medicine

No abstract provided.

Role Of Microglial Amylin Receptors In Mediating Beta Amyloid (Aβ)-Induced Inflammation, Wen Fu, Vlatka Vukojevic, Aarti Patel, Rania Soudy, David Mactavish, David Westaway, Kamaljit Kaur, Valeri Goncharuk, Jack Jhamandas

Pharmacy Faculty Articles and Research

Background: Neuroinflammation in the brain consequent to activation of microglia is viewed as an important component of Alzheimer’s disease (AD) pathology. Amyloid beta (Aβ) protein is known to activate microglia and unleash an inflammatory cascade that eventually results in neuronal dysfunction and death. In this study, we sought to identify the presence of amylin receptors on human fetal and murine microglia and determine whether Aβ activation of the inflammasome complex and subsequent release of cytokines is mediated through these receptors.

Methods: The presence of dimeric components of the amylin receptor (calcitonin receptor and receptor activity modifying protein 3) …

Zenker’S Diverticulum And Squamous Esophageal Cancer: A Case Report, Ion Dina, Octav Ginghina, Corina D. Toderescu, Cristian Bălălău, Bianca Galateanu, Carolina Negrei, Claudia Iacobescu

Journal of Mind and Medical Sciences

Zenker’s diverticulum represents a rare esophageal lesion developed especially in the elderly population due to herniation of esophageal mucosa above the cricopharyngeus muscle. The condition leads to food retention, regurgitation, aspiration, and dysphagia in affected patients. Progressive dysphagia also characterizes malignant diseases of the esophagus like squamous esophageal carcinoma that typically appears in male patients in the seventh decade of life, with a history of cigarette smoking and alcohol abuse. We report a case of a male patient who presented with dysphagia for both solids and liquids along with significant weight loss, and who was diagnosed with medium esophageal cancer …

Therapeutic Challenges In A Case Of Psoriasis With Nail Onset, Mădălina I. Mitran, Cristina I. Mitran, Maria I. Sârbu, Vasile Benea, Mircea Tampa, Simona R. Georgescu

Journal of Mind and Medical Sciences

Nail psoriasis affects a large number of patients with psoriasis and has a major psychosocial impact. Furthermore, it may be regarded as a predictor of more severe forms of psoriasis and early sign of psoriatic arthritis. The clinical presentations vary depending on the structure affected (nail matrix or nail bed), the nail lesions may range from minor to severe, but they are not specific. Treatment is a challenge, in most cases the lesions being resistant to therapy. We present a rare case of psoriasis with nail onset in a 59-year-old woman. The nail involvement confined to the fingernails was severe, …

Protective Role Of S-Adenosylmethionine Against Fructose-Induced Oxidative Damage In Obesity, Kameliya Zh Bratoeva, Mariya A. Radanova, Albena V. Merdzhanova, Ivan S. Donev

Journal of Mind and Medical Sciences

Introduction. It has been shown that S-adenosylmethionine (S-AMe) stimulates glutathione synthesis and increases cell resistance to the cytotoxic action of free radicals and pro-inflammatory cytokines. The aim of this study was to determine the effect of S-adenosylmethionine on the oxidative stress in adipose tissue in a model of fructose-induced obesity. Methods. The study was performed on male Wistar rats divided into 3 groups: control, fructose fed (HFD) (35%, 16 weeks), and HFD + S-AMe (20 mg/kg). We examined the changes in the ratio of retroperitoneal adipose tissue weight / body weight; levels of reduced glutathione (GSH) and malondialdehyde (MDA) in …

Cesarean Scar Defects And Placental Abnormalities – A 3 Year Survey Study, Denisa Oana Bălălău, Nicolae Bacalbașa, Anca D. Stănescu

Journal of Mind and Medical Sciences

The placenta is an essential organ for embryonic and fetal development, ensuring nutrient uptake, gas exchange (via the mother's blood supply), waste elimination, thermo-regulation, immunological and hormonal factors, etc. The most common placental abnormalities are represented by placenta previa, and a morbidly adherent placenta (in the form of accreta, increta, and percreta placenta). This study was performed on a sample of 99 patients diagnosed with abnormalities of placentation who underwent cesarian delivery during a period of 3 years in Bucur Maternity Hospital. Seven patients were diagnosed with morbidly adherent placenta (5 accreta and 2 percreta subtypes), the others having placenta …

Emergency Surgery And Limitation Of Therapeutic Effort In Relation To Neurologic Deterioration In Elderly Patients – A Survey Of European Surgeons, Mihai Paduraru, Luca Ponchietti, Isidro M. Casas, Jorge Pereira, Aitor Landaluce-Olavarria, Diego Mariani

Journal of Mind and Medical Sciences

Background. In emergency surgery, a very heterogeneous approach is required in the decision making process, especially when considering the patient’s postoperative quality of life as well as medical, ethical, and legal factors. In some cases, the presence of an Advance Directive (AD) form may potentially help resolve the surgeon’s dilemma. Objectives. The primary objective of this survey was to investigate the opinions of surgeons across a representative cross-section of European countries regarding the decision making process using a specific case scenario so as to identify similarities and differences in practice. A secondary objective was to identify the possibility of establishing …