Medical Sciences Commons^™

Data-Driven Identification Of Chemopreventive Agents For Breast Cancer, Deni̇z Can Güven, Cemal Orhan, Kazi̇m Şahi̇n, Fatih Mehmet Uçkun

Turkish Journal of Medical Sciences

Preclinical animal models of breast cancer provide the opportunity to identify chemopreventive drugs with single-agent activity as well as effective multi-modality regimens for primary as well as secondary prevention in high-risk persons. Our group has used the 7,12-dimethylbenz(a)anthracene (DMBA) mouse model of carcinogen-induced breast cancer to explore the clinical potential of two tyrosine kinase inhibitors and a nucleoside analog as chemopreventive agents. All three agents exhibited promising preclinical activity both as monotherapy and as components of combination therapy with the standard chemotherapy drug paclitaxel. The tumors developing despite chemoprevention were not only small and grew slowly, but they also displayed …

Thiol-Disulfide Homeostasis: An Integrated Approach With Biochemical And Clinical Aspects, Özcan Erel, Serpi̇l Erdoğan

Turkish Journal of Medical Sciences

Dynamic thiol-disulfide homeostasis (TDH) is a new area has begun to attract more scrutiny. Dynamic TDH is reversal of thiol oxidation in proteins and represents the status of thiols (-SH) and disulfides (-S-S-). Organic compounds containing the sulfhydryl group is called thiol, composed of sulfur and hydrogen atoms. Disulfides are the most important class of dynamic, redox responsive covalent bonds build in between two thiol groups. For many years, thiol levels were analyzed by several methods. During last years, measurements of disulfide levels have been analyzed by a novel automated method, developed by Erel and Neselioglu. In this method, addition …

Ankaferd Hemostat: From Molecules To Medicine, Rafi̇ye Çi̇ftçi̇ler, İbrahi̇m Celaletti̇n Haznedaroğlu

Turkish Journal of Medical Sciences

Ankaferd hemostat (ABS; Ankaferd Blood Stopper® , İstanbul, Turkey) is a hemostatic agent having an impact on red blood cell-fibrinogen interactions. The hemostatic effect of ABS depends upon the quick promotion of a protein network, particularly fibrinogen gamma, in relation to the erythrocyte aggregation. The entire physiological process involves ABS-induced formation of the protein network by vital erythrocyte aggregation. Vital erythrocyte aggregation occurs with the spectrine, ankyrin, and actin proteins on the membrane of the red blood cells. ABS notably affects cell metabolism and cell cycle mechanisms. Meanwhile, ABS has antiproliferative effects on cancer cells. The aim of this review …

Kinetics Of Notch Signaling During Osteoclastogenesis, Amber Larissa Framstad

EWU Masters Thesis Collection

Bone remodeling, the process of removing and replacing damaged bone matrix, is a dynamic physiological process essential to maintaining bone composition and integrity. Improper coordination of resorption and formation can lead to pathologic changes in bone composition and quality, as is seen in osteoporosis, a bone disorder most seen in post-metapausal women attributed to decreased estrogen levels. The Notch signal pathway is a highly conserved direct cell communication pathway known to regulate cell proliferation, differentiation and survival in many cell types including the differentiation of osteoclasts from bone marrow macrophages (BMMs). Osteoclastogenesis is initiated in BMMs by receptor activator of …

The Role Of Neural Precursor Cell Expressed Developmentally Down-Regulated Protein 9 In Enhanced Aggressiveness Of Hexavalent Chromium Transformed Bronchial Epithelial Cells, Peter Van Wie

Theses and Dissertations--Toxicology and Cancer Biology

Hexavalent chromium (Cr(VI)) is classified as a confirmed human carcinogen by the International Agency for Research and Cancer (IARC) and by the U.S. Environmental Protection Agency (EPA). Chronic exposure to (Cr(VI)) causes malignant cell transformation in human bronchial epithelial BEAS-2B cells. These Cr(VI)-transformed cells exhibit a highly aggressive phenotype including increased migration, invasion, and angiogenesis. The Cas family protein neuronal precursor developmentally down regulated protein 9 (NEDD9/Cas-L/HEF1) was dramatically overexpressed in Cr(VI)-transformed cells compared to normal BEAS-2B cells. Knockdown of NEDD9 by its shRNA reduced migration and invasion in vitro measured by migration and invasion assays. shNEDD9 reduced tumor formation …

The Coulter Principle: For The Good Of Humankind, Marshall Graham

Theses and Dissertations--History

The atomic bombings of Hiroshima and Nagasaki in August 1945 made Wallace H. Coulter abruptly comprehend the critical need for rapid and accurate blood-cell counts in providing care for victims of radiation exposure. This thesis documents the unwritten story of his journey from that comprehension through his invention and implementation of the Coulter Principle, its commercialization in the first widely available automated blood-cell counter, and elaboration of that ground-breaking counter into increasingly sophisticated instrumentation for analysis not only of blood cells, but of particles involved in many other scientific disciplines. International cold-war politics and the burgeoning of increasingly powerful nuclear …

Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Correlating The Physicochemical Properties Of Magnesium Stearate With Tablet Dissolution And Lubrication, Julie L. Calahan

Theses and Dissertations--Pharmacy

Magnesium stearate (MgSt) is the most commonly used pharmaceutical excipient and is present in over half the tablet formulations on the market. In spite of its popularity as an effective lubricant, it has been repeatedly recognized that there is significant variability between MgSt samples, which can cause inconsistent lubrication between batches of MgSt. The hypothesis of this research is that the batch-to-batch variability in tablet lubrication and dissolution observed in tablet formulations containing different MgSt samples can be correlated with differences in MgSt physicochemical properties (fatty acid salt composition, crystal hydrate form, particle size and surface area). Developing correlations between …

Elucidating Molecular Function Of Mithramycin And Analogues For The Treatment Of Ews-Ets Expressing Cancers, Reiya Hayden

Theses and Dissertations--Pharmacy

Introduction: Chromosomal translocations are common in cancer. In many cancers such as prostate cancer, leukemia and Ewing sarcoma, chromosomal translocations are the main driver of malignancy. Ewing sarcoma is a cancer diagnosed mostly in children and adolescents that has very grim outcomes for patients with metastasis and recurrent disease. Malignancy in Ewing sarcoma is due to EWS-FLI1, an aberrant transcription factor that is the result of a chromosomal translocation. EWS-FLI1 is the main driver of oncogenesis in Ewing sarcoma and has been the target of many drugs developed to treat the disease. Mithramycin (MTM) was identified as a potent inhibitor …

Functional Impact Of Angiotensinogen Specific Domains On Angiotensin Ii-Mediated Functions, Chia-Hua Wu

Theses and Dissertations--Pharmacology and Nutritional Sciences

Angiotensinogen (AGT) is the only substrate for all angiotensin peptides in the renin angiotensin system (RAS). Cleavage of AGT by renin is a rate-limiting step of angiotensin peptides productions in the RAS and regulates angiotensin peptides-associated pathophysiological functions. Only ten N-terminal residues are cleaved by renin and the functions of remaining part of AGT protein, which is called des(angiotensin I)AGT, remain unclear. Despite of pivotal roles of AGT in the RAS, studies related to how AGT is metabolized and how des(angiotensin I)AGT regulates AGT functions or AngII-mediated functions are limited.

Renin cleavage of AGT shows species specificity. It has been …

Apoe As A Metabolic Regulator In Humans, Mice, And Astrocytes, Brandon C. Farmer

Theses and Dissertations--Physiology

Altered metabolic pathways appear to play central roles in the pathophysiology of late-onset Alzheimer’s disease (AD). Carrier status of the E4 allele of the APOE gene is the strongest genetic risk factor for late-onset AD, and increasing evidence suggests that E4 carriers may be at an increased risk for neurodegeneration based on inherent metabolic impairments. A new appreciation is forming for the role of APOE in cerebral metabolism, and how nutritional factors may impact this role. In chapter 1, the literature on nutritional interventions in E4 carriers aimed at mitigating disease risk is reviewed. Studies investigating the mechanism by which …

Physiological Effects During Aerobatic Flights On Science Astronaut Candidates, Pedro Llanos, Diego M. Garcia

Publications

Spaceflight is considered the last frontier in terms of science, technology, and engineering. But it is also the next frontier in terms of human physiology and performance. After more than 200,000 years humans have evolved under earth’s gravity and atmospheric conditions, spaceflight poses environmental stresses for which human physiology is not adapted. Hypoxia, accelerations, and radiation are among such stressors, our research involves suborbital flights aiming to develop effective countermeasures in order to assure sustainable human space presence. The physiologic baseline of spaceflight participants is subject to great variability driven by age, gender, fitness, and metabolic reserve. The objective of …

Physiological Effects On Scientist Astronaut Candidates: Hypobaric Training Assessment, Pedro Llanos, Diego Garcia

Publications

This paper is addressed to expanding our understanding of the effects of hypoxia training on our bodies to better model its dynamics and leverage some of its implications and effects on human health. Hypoxia training is a recommended practice for military and civilian pilots that allow them to recognize their early hypoxia signs and symptoms, and Scientist Astronaut Candidates (SACs) who underwent hypobaric hypoxia (HH) exposure as part of a training activity for prospective suborbital flight applications. This observational-analytical study describes physiologic responses and symptoms experienced by a SAC group before, during and after HH exposure and proposes a model …

A Review Of The Influence Of Fathers On Children's Eating Behaviours And Dietary Intake, Stephanie Rahill, Aileen Kennedy, John Kearney

Articles

The role of fathers in child rearing has changed in recent years due to an increase in maternal employment. Despite this, the majority of research has focused on maternal influences and behaviours in relation to child feeding. Therefore, the aims of the narrative review were: 1) to examine the role and responsibility of fathers in child feeding and the factors associated with paternal responsibility in child feeding; 2) to establish how paternal modelling, paternal diets, and paternal feeding practices relate to children's eating behaviours and dietary intake; and 3) to explore the role of maternal perceptions on paternal feeding roles, …

Editorial: Human-Nature Interactions: Perspectives On Conceptual And Methodological Issues, Tadhg Macintyre, Jürgen Beckmann, Giovanna Calogiuri, Aoife Donnelly, Marc Jones, Christopher R. Madan, Noel Brick, Christopher Gidlow, Mike Rogerson, Mark Nieuwenhuijsen

Articles

Urban agglomerations expose citizens to ever-increasing risks from heat, air pollution, noise stress, and reduced nature connectedness. Concurrently, accumulating evidence suggests various health benefits by exposure to urban natural spaces (World Health Organization, 2016a; Bratman et al., 2019). Existing research suggests an array of benefits of contact with nature which are linked to physical activity (e.g., green exercise), active travel, and residential proximity to greenspace. Psychological benefits appear to be related to mood, well-being, attention and pro-environmental behavior; physiological benefits have been described in terms of increased physical activity, improved cardiovascular parameters, reduced stress hormones, and enhanced immune resources (Bowler …

Scrambling The Skin: A Psychophysical Study Of Adaptation To Scrambled Tactile Apparent Motion, Tatjana Seizova-Cajic, Sandra Ludvigsson, Birger Sourander, Melinda Popov, Janet L. Taylor

Research outputs 2014 to 2021

Copyright: © 2020 Seizova-Cajic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. An age-old hypothesis proposes that object motion across the receptor surface organizes sensory maps (Lotze, 19th century). Skin patches learn their relative positions from the order in which they are stimulated during motion events. We propose that reversing the local motion within a global motion sequence (‘motion scrambling’) provides a good test for this idea, and present results of the …

Brainwave Nets: Are Sparse Dynamic Models Susceptible To Brain Manipulation Experimentation?, Diego C. Nascimento, Marco A. Pinto-Orellana, Joao P. Leite, Dylan J. Edwards, Francisco Louzada, Taiza E.G. Santos

Research outputs 2014 to 2021

© Copyright © 2020 Nascimento, Pinto-Orellana, Leite, Edwards, Louzada and Santos. Sparse time series models have shown promise in estimating contemporaneous and ongoing brain connectivity. This paper was motivated by a neuroscience experiment using EEG signals as the outcome of our established interventional protocol, a new method in neurorehabilitation toward developing a treatment for visual verticality disorder in post-stroke patients. To analyze the [complex outcome measure (EEG)] that reflects neural-network functioning and processing in more specific ways regarding traditional analyses, we make a comparison among sparse time series models (classic VAR, GLASSO, TSCGM, and TSCGM-modified with non-linear and iterative optimizations) …

Tripping Over The Other: Could Psychedelics Increase Empathy?, Emily Blatchford, Stephen Bright, Liam Engel

Research outputs 2014 to 2021

There is increasing evidence that psychedelic-assisted psychotherapy is effective for a range of psy-chological conditions. There are likely numerous mechanisms of action that contribute to these clinicaleffects. One such mechanism of action might involve psychedelics increasing levels of empathicfunctioning. This paper synthesises research concerning the relationship between psychedelics andempathy, emphasising neuroscientific and clinical contexts. We conclude that neuropsychological andclinical evidence imply psychedelics could lead to increased empathic functioning. The effects of psy-chedelics on the 5-HT system, default mode network, neural connectivity and ego dissolution areimplicated in these changes. Changes in empathic functioning also likely relate to increases in thepersonality trait …

Rna Sequencing Of Human Peripheral Nerve In Response To Injury: Distinctive Analysis Of The Nerve Repair Pathways., Andrew S. Welleford, Jorge E. Quintero, Nader El Seblani, Eric Blalock, Sumedha Gunewardena, Steven M. Shapiro, Sean M. Riordan, Peter Huettl, Zain Guduru, John A. Stanford, Craig G. Van Horne, Greg A. Gerhardt

Manuscripts, Articles, Book Chapters and Other Papers

The development of regenerative therapies for central nervous system diseases can likely benefit from an understanding of the peripheral nervous system repair process, particularly in identifying potential gene pathways involved in human nerve repair. This study employed RNA sequencing (RNA-seq) technology to analyze the whole transcriptome profile of the human peripheral nerve in response to an injury. The distal sural nerve was exposed, completely transected, and a 1 to 2 cm section of nerve fascicles was collected for RNA-seq from six participants with Parkinson's disease, ranging in age between 53 and 70 yr. Two weeks after the initial injury, another …

Letter To The Editor - Awareness Of Stroke Among Patients Attending Primary Healthcare Services In Abha, Southwestern Saudi Arabia, Ismail A. Khatri

Neurosciences

No abstract provided.

Awareness Of Patients With Multiple Sclerosis In Saudi Arabia Regarding The Relationship Between Smoking And Multiple Sclerosis, Faizan Z. Kashoo, Mazen Alqahtani, Fuzail Ahmad

Neurosciences

No abstract provided.

Generation Of Induced Pluripotent Stem Cells From Blood Cell Of Glucose-6-Phosphate Dehydrogenase (G6pd) Deficiency, Malinee Tongbaen

Chulalongkorn University Theses and Dissertations (Chula ETD)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common genetic enzyme disorder that affects more than 400 million people worldwide. Insufficient of G6PD enzyme or defect in enzyme activity can cause acute hemolysis after exposure to oxidative stress. The disease model used for pathogenesis study underlying oxidative damage or drug screening in G6PD deficient patients is still needed. In vitro generation of human-induced pluripotent stem cells (iPSCs) afford the potential source of the disease model in medical research. This study aimed to generate the iPSCs derived from G6PD deficient-subjects for used as a specific-disease model. The G6PD-derived iPSCs were generated from …

Ketamine Vs Placebo For Depression, Austin Strosser

Capstone Showcase

Depression is a disease that effects millions of patients and has a variety of symptoms. It is primarily defined by depressed mood and anhedonia. The first line treatment for depression is SSRI medications. These medications have several side effects and are not effective for a large number of patients. Therefore, this study was done to review ketamine as a new treatment option for depression and see how it compares to a placebo.

The Comparative Efficacy Of Amantadine Vs. Lcig Therapy For The Treatment Of Levodopa-Induced Dyskinesia In Patients With Advanced Parkinson's Disease, Katelynn Timony

Capstone Showcase

Introduction: Though levodopa-carbidopa therapy remains the gold standard of Parkinson’s disease (PD) treatment to this day, patients often experience increased dyskinetic activity as a result of long-term treatment; known as levodopa-induced dyskinesia (LID); the mechanism of which is not completely understood. In this review, the efficacy of two adjunct treatments for LID are compared: 1) the concomitant administration of amantadine, an antiviral medication with antidyskinetic properties; and 2) a new form of levodopa administration in the form of an intestinal gel delivered straight via a device much like an insulin pump.

Methods: Two systematic literature searches of primary, peer-reviewed articles …

The Effects Of Autophagy And Senescence On Sensitivity To Cisplatin In Head And Neck Cancer, Zara H. Siddiqui

Theses and Dissertations

While current treatments in cancer, such as chemotherapy and radiation, can generally be effective in eliminating disease in patients, there also exists the possibility of recurrence of cancer cells over time. In patients diagnosed with locally advanced head and neck carcinoma, about 50-60% develop a loco-regional recurrence within two years, and 20-30% of patients develop metastatic disease at distant sites in the body [5]. On a cellular level, one mechanism for this survival may be that natural mechanisms such as autophagy and senescence play a role in allowing cells to survive after undergoing treatment. One standard of care chemotherapy for …

Exploring The Heteromeric Interface Of The 5-Ht2a-Mglu2 Receptor Complex, Mohamed Aarif Abdul Kareem

Theses and Dissertations

Schizophrenia is a serious mental disorder characteristic of several neurotransmitters including dopamine, serotonin, and glutamate being in imbalance. Early therapies focused solely on dopamine antagonism and second-generation antipsychotics focused on the dopamine and serotonin systems and their respective G protein coupled receptor (GPCR) proteins. Although debate for dimerization of certain classes of GPCR exist, the establishment of an mGlu2-5-HT_2A heterocomplex, which is implicated in schizophrenia is of interest. Previous studies have used a mutation-based approach to identify transmembrane domain 4 (TM4) as the domain responsible in mGlu2 for mediating heteromerization before narrowing down the individual amino acids responsible for …

The Quantified Elf, Umico Niwa

Theses and Dissertations

The Quantified Elf is an ongoing collection of scientific, medical, archaeological articles and excerpts from my personal journal. It is a way by which I explore the various ways Western notions of personhood subsume human life into constructs of sexuality and gender, overlooking the various other modes of unbridled existence: plant, microbial. fungal, animal, celestial bodies. The speculative medical papers propose novel forms of body modification to combat gender dysphoria.

Modeling Gardnerella Host-Pathogen Interaction: Characterization Of Vaginolysin And The Opacity Phenotype, Erin M. Garcia

Theses and Dissertations

Bacterial vaginosis (BV) describes a dysbiotic state of the vaginal mucosa, during which the dominance by beneficial lactobacilli species is lost, the vaginal pH increases, and the flora comprising the vaginal microbiome becomes more diverse. Bacterial taxa associated with this dysbiotic state interact to form a dense polymicrobial biofilm on the surface of the vaginal epithelium. This shift in the vaginal microflora is clinically important, even when symptoms are not noted, as women with BV are at increased risk for acquisition of other sexually transmitted infections, including HIV, and are more than two times as likely to experience preterm birth. …

An Identification Of Tgf-B'S Role In Ischemic Cholangiopathy, Courtney Chmielewski

Theses and Dissertations

Organ transplants are a necessary intervention for many diseases that result in end stage organ failure. The donation pool cannot match the demands of the transplant list, so expanding the pool to include donation after cardiac death (DCD) is desired. However, there are increased odds of graft failure and ischemic cholangiopathy leading to inferior outcomes when DCD livers are used. Ischemic cholangiopathy consists of multiple diffuse strictures and fibrosis of the bile ducts leading to a loss of epithelialization and fibrosis. The cellular mechanism is proposed to be epithelial-to-mesenchymal transition (EMT). TGF-�� is seen as a key initiator of EMT, …