Medicine and Health Sciences Commons^™

Response Of Soil Nitrification To The Veterinary Pharmaceuticals Monensin, Ivermectin And Zinc Bacitracin, Magda A. Konopka

Electronic Thesis and Dissertation Repository

Pharmaceutical residues can reach agricultural land through amendment with animal or human waste. Since 2010, a series of replicated plots received annual applications of ivermectin, monensin and zinc bacitracin, either singly or in a mixture, at 0.1 mg/kg and 10 mg/kg concentrations. I collected soil samples before and after the fourth annual application of pharmaceuticals and assayed them for functional changes and amoA gene abundance, a gene needed for ammonia oxidation. In 2013, I exposed the soils to 100 mg/kg in a laboratory experiment which resulted in acceleration of nitrification. Under 10 mg/kg treatments in the field the abundance of …

Acquisition And Reconstruction Techniques For Fat Quantification Using Magnetic Resonance Imaging, Abraam S. Soliman

Electronic Thesis and Dissertation Repository

Quantifying the tissue fat concentration is important for several diseases in various organs including liver, heart, skeletal muscle and kidney. Uniquely, MRI can separate the signal from water and fat in-vivo, rendering it the most suitable imaging modality for non-invasive fat quantification. Chemical-shift-encoded MRI is commonly used for quantitative fat measurement due to its unique ability to generate a separate image for water and fat. The tissue fat concentration can be consequently estimated from the two images. However, several confounding factors can hinder the water/fat separation process, leading to incorrect estimation of fat concentration.

The inhomogeneities of the main …

A Ventilator Strategy Combining Low Tidal Volume Ventilation, Recruitment Maneuvers, And High Positive End-Expiratory Pressure Does Not Increase Sedative, Opioid, Or Neuromuscular Blocker Use In Adults With Acute Respiratory Distress Syndrome And May Improve Patient Comfort, Sangeeta Mehta, Deborah J. Cook, Yoanna Skrobik, John Muscedere

Anatomy and Cell Biology Publications

Background: The Lung Open Ventilation Study (LOV Study) compared a low tidal volume strategy with an experimental strategy combining low tidal volume, lung recruitment maneuvers, and higher plateau and positive end-expiratory pressures (PEEP) in adults with acute respiratory distress syndrome (ARDS). Herein, we compared sedative, opioid, and neuromuscular blocker (NMB) use among patients managed with the intervention and control strategies and clinicians' assessment of comfort in both groups. Methods: This was an observational substudy of the LOV Study, a randomized trial conducted in 30 intensive care units in Canada, Australia, and Saudi Arabia. In 16 centers, we recorded daily doses …

Induction Of Acute Lung Inflammation In Mice With Hemorrhagic Shock And Resuscitation: Role Of Hmgb1, Raymond L. C. Kao, Xuemei Xu, Anargyros Xenocostas, Neil Parry, Tina Mele, Claudio M. Martin, Tao Rui

Anatomy and Cell Biology Publications

Background: Hemorrhagic shock and resuscitation (HS/R) can induce multiple organ failure which is associated with high mortality. The lung is an organ commonly affected by the HS/R. Acute lung injury is a major cause of dysfunction in other organ systems. The objective of this study is to test the hypothesis that HS/R causes increased gut permeability which results in induction of high mobility group box1 protein (HMGB1) and further leads to the development of acute lung inflammation. Materials and methods: A mouse model of HS/R was employed in this study. Gut permeability and bacterial translocation were assessed with circulating FD4 …

Unique Functional Abnormalities In Youth With Combined Marijuana Use And Depression: An Fmri Study, Kristen A. Ford, Michael Wammes, Richard W. Neufeld, Derek Mitchell, Jean Theberge, Peter Williamson, Elizabeth A. Osuch

Anatomy and Cell Biology Publications

Prior research has shown a relationship between early onset marijuana (MJ) use and depression; however, this relationship is complex and poorly understood. Here, we utilized passive music listening and fMRI to examine functional brain activation to a rewarding stimulus in 75 participants [healthy controls (HC), patients with major depressive disorder (MDD), frequent MJ users, and the combination of MDD and MJ (MDD?+?MJ)]. For each participant, a preferred and neutral piece of instrumental music was determined (utilizing ratings on a standardized scale), and each completed two 6-min fMRI scans of a passive music listening task. Data underwent pre-processing and 61 participants …

Cardiac Fibroblasts Contribute To Myocardial Dysfunction In Mice With Sepsis: The Role Of Nlrp3 Inflammasome Activation, Wenbo Zhang, Xuemei Xu, Raymond Kao, Tina Mele, Peter Kvietys, Claudio M. Martin, Tao Rui

Anatomy and Cell Biology Publications

Myocardial contractile dysfunction in sepsis is associated with the increased morbidity and mortality. Although the underlying mechanisms of the cardiac depression have not been fully elucidated, an exaggerated inflammatory response is believed to be responsible. Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome is an intracellular platform that is involved in the maturation and release of interleukin (IL)-1 beta. The aim of the present study is to evaluate whether sepsis activates NLRP3 inflammasome/caspase-1/IL-1 beta pathway in cardiac fibroblasts (CFs) and whether this cytokine can subsequently impact the function of cardiomyocytes (cardiac fibroblast-myocyte crosstalk). We show that treatment of …

Comparing Moral Judgments Of Patients With Frontotemporal Dementia And Frontal Stroke, Sandra Baez, Blas Couto, Teresa Torralva, Luciano A. Sposato, David Huepe, Patricia Montañes, Pablo Reyes, Diana Matallana, Nora S. Vigliecca, Andrea Slachevsky, Facundo Manes, Agustin Ibanez

Anatomy and Cell Biology Publications

Importance Several clinical reports have stated that patients with prefrontal lesions or patients with the behavioral variant of frontotemporal dementia share social cognition impairments. Moral reasoning is impaired in both conditions but there have been few investigations that directly compare this domain in the 2 groups.

Observations This work compared the moral judgments of these patient groups using a task designed to disentangle the contributions of intentions and outcomes in moral judgment. For both disorders, patients judged scenarios where the protagonists believed that they would cause harm but did not as being more permissible than the control group. Moreover, patients …

Olanzapine-Induced Methylation Alters Cadherin Gene Families And Associated Pathways Implicated In Psychosis, Melkaye G. Melka, Christina A Castellani, Nagalingam Rajakumar, Richard O'Reilly, Shiva M Singh

Biology Publications

BACKGROUND: The complex aetiology of most mental disorders involves gene-environment interactions that may operate using epigenetic mechanisms particularly DNA methylation. It may explain many of the features seen in mental disorders including transmission, expression and antipsychotic treatment responses. This report deals with the assessment of DNA methylation in response to an antipsychotic drug (olanzapine) on brain (cerebellum and hippocampus), and liver as a non-neural reference in a rat model. The study focuses on the Cadherin/protocadherins encoded by a multi-gene family that serve as adhesion molecules and are involved in cell-cell communication in the mammalian brain. A number of these molecules …

Identification And Characterization Of Cysteine Protease Genes In Tobacco For Use In Recombinant Protein Production, Kishor Duwadi

Electronic Thesis and Dissertation Repository

Plants are an attractive host system for pharmaceutical protein production. Many therapeutic proteins have been produced and scaled up in plants at a low cost compared to the conventional microbial and animal based systems. The main technical challenge during this process is to produce sufficient level of proteins in plants. Low yield is generally caused by proteolytic degradation during expression and downstream processing of recombinant proteins. The yield of a human therapeutic protein interleukin (IL) -10 produced in transgenic tobacco leaves was found to be below the critical level, and is potentially due to degradation by tobacco cysteine proteases (CysPs). …

The Effects Of Oar-Shaft Stiffness And Length On Rowing Biomechanics, Brock Laschowski

Electronic Thesis and Dissertation Repository

This work investigates the effects of oar-shaft stiffness and length on rowing biomechanics. The mechanical properties of the oar-shafts were examined using an end-loaded cantilever system, and theoretical relations were proposed between the mechanics of the oar-shafts and rowing performance. On-water experiments were subsequently conducted and rowing biomechanics measured via the PowerLine Rowing Instrumentation System. The PowerLine system measures force and oar angle on the oarlock, as well as proper boat acceleration. The convergent validity and test-retest reliability of the PowerLine force measurements were determined prior to the on-water experiments. Thereafter, rowers were tested over a set distance using oar-shafts …

Transcriptional Regulation Of Peptidylarginine Deiminase Type Iv: Implications For Rheumatoid Arthritis, Ali Abbas

Electronic Thesis and Dissertation Repository

High titers of anti-citrullinated protein antibodies have been detected in sera of rheumatoid arthritis (RA) patients, implicating citrullinating enzymes in the pathogenesis of RA. Peptidylarginine deiminase type IV (PAD4) is a member of the PAD family of enzymes that catalyze the post- translational modification of arginine to citrulline and has been linked with RA. However, little is known about its transcriptional regulation. Therefore, our aim was to determine how transcription of PAD4 is activated in the myeloid lineage. Using bioinformatics, a potential nuclear factor kappa B (NF-kB) binding site was identified on the PAD4 promoter. Luciferase assays were used to …

Complexity And Familiarity Enhance Single-Trial Detectability Of Imagined Movements With Electroencephalography, Raechelle M. Gibson, Srivas Chennu, Adrian M. Owen, Damian Cruse

Anatomy and Cell Biology Publications

Objective: We sought to determine whether the sensorimotor rhythms (SMR) elicited during motor imagery (MI) of complex and familiar actions could be more reliably detected with electroencephalography (EEG), and subsequently classified on a single-trial basis, than those elicited during relatively simpler imagined actions. Methods: Groups of healthy volunteers, including experienced pianists and ice hockey players, performed MI of varying complexity and familiarity. Their electroencephalograms were recorded and compared using brain-computer interface (BCI) approaches and spectral analyses. Results: Relative to simple MI, significantly more participants produced classifiable SMR for complex MI. During MI of performance of a complex musical piece, the …

Genomic Predictors Of Drug Response To The Alpha-Specific Phosphoinositol 3-Kinase (Pi3ka-Alpha) Inhibitor Byl719 In Head And Neck Cancers, Giananthony T. Rizzo

Electronic Thesis and Dissertation Repository

PIK3CA is the only frequently mutated, druggable oncogene in head and neck squamous cell cancer (HNSCC), with PIK3CA point mutations and gene amplification rates of 17.5% and 40% respectively, with higher rates in HPV-positive disease. The objective of this research was to determine the effects of BYL719, an α-specific PI3K inhibitor in HNSCC cell lines.

All cell lines with PIK3CA hotspot point mutations or gene amplifications will be sensitive to BYL719.

Twenty-eight HNSCC cell lines were subjected to increasing concentrations of BYL719 and cell viability was measured over time. Cell lines were screened for activating PIK3CA hotspot mutations and amplifications …

Probiotic Therapy For Heart Failure: Investigating The Potential Anti-Hypertrophic Properties Of Probiotics, Grace L. Ettinger

Electronic Thesis and Dissertation Repository

Heart failure patients face a five-year 50% mortality rate, due to impaired cardiac function and hypertrophy of the heart. Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Considering the established cardiovascular benefits of some probiotics, including reduction of cholesterol and hypertension, it was hypothesized that probiotics can improve outcomes of heart failure. Probiotics or controls were administered orally to an animal model for heart failure. Those receiving probiotics showed a significant improvement in cardiac hypertrophy and an attenuation of heart failure compared to control. No changes in gut microbial composition occurred. …

A Non-Contrast Magnetic Resonance Imaging Technique To Assess Blood-Brain Barrier Permeability, Harini Pandithasekera

Electronic Thesis and Dissertation Repository

The Blood-brain barrier (BBB) regulates the entry of compounds between the blood and the brain, thus plays an important role in brain homeostasis. Studies indicate in disease states such as Alzheimer’s the BBB integrity is compromised. The motive of this project is to investigate the sensitivity of the diffusion-weighted arterial spin labeling (DW-ASL) technique to detect water exchange. Testing the sensitivity requires a reliable method of opening the barrier at specific locations of the brain. Here, a unique technology named focused ultrasound (FUS) has been used to mimic a compromised BBB environment.

A series of experiments were conducted in a …

Cholinergic Signaling Exerts Protective Effects In Models Of Sympathetic Hyperactivity-Induced Cardiac Dysfunction, Mariana Gavioli, Aline Lara, Pedro W. M. Almeida, Augusto Martins Lima, Denis D. Damasceno, Cibele Rocha-Resende, Marina Ladeira, Rodrigo R. Resende, Patricia M. Martinelli, Marcos Barrouin Melo, Patricia C. Brum, Marco Antonio Peliky Fontes, Robson A. Souza Santos, Marco A. M. Prado, Silvia Guatimosim

Anatomy and Cell Biology Publications

Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i) the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO), and ii) the alpha(2A)/alpha(2C)-drenergic receptor knockout (KO) mice that lack pre-synaptic adrenergic receptors. …

Quantifying The Effect Of Age And Contraction Mode On The Force-Velocity-Power Relationship In The Knee Extensors, Justin R. Paturel

Electronic Thesis and Dissertation Repository

PURPOSE: To assess and compare the force-velocity-power relationship (F-V-P) using isotonic and isokinetic knee extensions in 11 younger (19-30y) and 11 older (69-81y) men. METHODS: The construction of the F-V-P curves were attained with each participant performing maximal, explosive knee extensions at 8 different loads (isotonic) and 8 different velocities (isokinetic) on a Cybex HUMAC NORM dynamometer. Maximal voluntary contraction (MVC or P_o), maximal shortening velocity (V_max), maximum power, optimal torque (P_opt) and velocity (V_opt) were assessed and compared. RESULTS: The older men were 43% weaker, 18% slower and ~54% less powerful …

The Neural Correlates Of Regulating Positive And Negative Emotions In Medication-Free Major Depression, Steven G. Greening, Elizabeth A. Osuch, Peter C. Williamson, Derek G. V. Mitchell

Anatomy and Cell Biology Publications

Depressive cognitive schemas play an important role in the emergence and persistence of major depressive disorder (MDD). The current study adapted emotion regulation techniques to reflect elements of cognitive behavioural therapy (CBT) and related psychotherapies to delineate neurocognitive abnormalities associated with modulating the negative cognitive style in MDD. Nineteen non-medicated patients with MDD and 19 matched controls reduced negative or enhanced positive feelings elicited by emotional scenes while undergoing functional magnetic resonance imaging. Although both groups showed significant emotion regulation success as measured by subjective ratings of affect, the controls were significantly better at modulating both negative and positive emotion. …

Economic Evaluation Of Potential Applications Of Gene Expression Profiling In Clinical Oncology, Malek Hannouf

Electronic Thesis and Dissertation Repository

Histopathological analysis of tumor is currently the main tool used to guide cancer management. Gene expression profiling may provide additional valuable information for both classification and prognostication of individual tumors. A number of gene expression profiling assays have been developed recently to inform therapy decisions in women with early stage breast cancer and help identify the primary tumor site in patients with metastatic cancer of unknown primary. The impact of these assays on health and economic outcomes, if introduced into general practice, has not been determined. I aimed to conduct an economic evaluation of regulatory-approved gene expression profiling assays for …

The Effects Of Ocean Acidification And Eutrophication On The Growth, Lipid Composition And Toxicity Of The Marine Raphidophyte Heterosigma Akashiwo., Julia Rose Matheson

Electronic Thesis and Dissertation Repository

Anthropogenic forcing, such as ocean acidification caused by rising carbon dioxide emissions, and eutrophication due to increased nutrient loadings in run-off, are causing major changes to the biogeochemistry of the oceans. As a consequence, coastal phytoplankton are susceptible to altered biogeochemical environments. This study examined the effect of a lower pH and increased levels of nutrients on the common coastal harmful alga, Heterosigma akashiwo. Growth rates, maximal cell yields, neutral lipid accumulation and toxicity of cells grown under various pH and nutrients regimes were measured. H. akashiwo growth was near maximal when grown at lower pH levels. There was …

Effect Of Ascorbate On Coagulation And Fibrinolytic Factors In The Septic Microvasculature, Scott Swarbreck

Electronic Thesis and Dissertation Repository

Sepsis, a systemic inflammatory response to an infection, is a significant cause of morbidity and mortality worldwide. The microcirculation during sepsis fails, in part, due to microthrombosis and the resulting plugging of capillaries, precipitating organ failure. Intravenous injection of ascorbate has been shown to reduce capillary plugging, however the mechanism of this protective effect is unclear. We hypothesized that ascorbate-mediated destabilization of the microthrombi through promoting fibrinolysis could contribute to this protection.

We showed that streptokinase, a pro-fibrinolytic agent, reduced the capillary plugging to a similar degree as ascorbate. This similarity provided the impetus for studying the effect of ascorbate …

Interesting Shapes Of Vegetables: Is It A Strategy To Promote Consumption Among Preschool Children?, Salma H. Alhabshi

Electronic Thesis and Dissertation Repository

This study highlighted the low intake of vegetables by preschool children and determined whether changing the shape of vegetables increased their level of consumption. A new strategy of repeated exposure to interesting-shaped vegetables was a step aimed at increasing vegetable consumption by increasing the fun element in having vegetables as snacks. Vegetables are the less desirable food in comparison to more attractive unhealthy choices available to children, and discovering a strategy to promote vegetables is considered an important step in nutrition. The primary aim was to explore the effect of repeated exposure (eight times) of shaped vegetables on consumption by …

Development Of Non-Covalent Functionalization Of Carbon Nanotubes For Sirna Delivery, King Sun Siu

Electronic Thesis and Dissertation Repository

RNA interference (RNAi) therapy is promising for treating various diseases but the delivery of small interfering RNA (siRNA) is difficult. To overcome the technical difficulties of siRNA delivery, an efficient and targeted delivery of siRNA is required for efficient RNAi therapy. Single-walled carbon nanotubes (CNT) has been used for nucleic acid delivery such as siRNA delivery. It has been found that CNT can gain entry into the cells by a diffusion-like mechanism which was called “nano-needle”. However, the solubility of CNT is low in most of the solvents including water. Functionalization of CNT can be carried out to enhance the …

Functional Anatomy Of The Anconeus: Muscle Architecture And Motor Unit Number Estimation, Daniel E. Stevens

Electronic Thesis and Dissertation Repository

Exploring muscle architecture in vivo and estimating the number of MUs in the human anconeus muscle have important implications related to the neuromuscular function of this muscle as a model for study in health and disease. The two studies presented in this thesis investigate the functional anatomy of the anconeus in 10 healthy young men (25±3y).

Ultrasound imaging has facilitated the measure of the architectural variables, fascicle length (L_F) and pennation angle (PA), in many human skeletal muscles in vivo. However, the functional anatomy of the anconeus has been investigated mainly from cadavers exclusively. Thus, the purpose …

Reciprocity In Microbiome And Immune System Interactions And Its Implications In Disease And Health., Enayat Nikoopour, Bhagirath Singh

Microbiology & Immunology Publications

Adaptation of the whole microbial normal flora residing in a host to its natural habitat over an evolutionary period has resulted in peaceful coexistence with mutual benefits for both microbiota and host in steady state. This symbiotic relationship between host and microbiota has a significant impact on shaping the immune response in the host to achieve an immune tolerance to microbiota but retaining the ability to respond to invading pathogens. Perturbation of this balance by manipulation of microbial communities in the host can lead to immune dysregulation and susceptibility to diseases. By studying the host in the absence of microbiota …

Skin Disease And Non-Syndromic Hearing Loss-Linked Cx30 Mutations Exhibit Several Distinct Cellular Pathologies, Amy Berger, John Kelly, Patrick Lajoie, Qing Shao, Dale Laird

Anatomy and Cell Biology Publications

Connexin 30 (Cx30), a member of the large gap junction protein family, plays a role in the homeostasis of the epidermis and inner ear through gap junctional intercellular communication (GJIC). Here, we investigated the underlying mechanisms of four autosomal dominant Cx30 gene mutations linked to hearing loss and/or various skin diseases. First, the T5M mutant linked to non-syndromic hearing loss formed functional gap junction channels and hemichannels, similar to wild type Cx30. The loss-of-function V37E mutant associated with Clouston syndrome or keratitis-ichthyosis-deafness syndrome was retained in the endoplasmic reticulum and significantly induced apoptosis. The G59R mutant linked to Vohwinkel and …

Recent Advances In The Molecular Characterization Of Circulating Tumor Cells, Lori E. Lowes, Alison L. Allan

Anatomy and Cell Biology Publications

Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch((R)) system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs …

Adaptation Of Semiautomated Circulating Tumor Cell (Ctc) Assays For Clinical And Preclinical Research Applications, Lori E. Lowes, Benjamin D. Hedley, Michael Keeney, Alison L. Allan

Anatomy and Cell Biology Publications

The majority of cancer-related deaths occur subsequent to the development of metastatic disease. This highly lethal disease stage is associated with the presence of circulating tumor cells (CTCs). These rare cells have been demonstrated to be of clinical significance in metastatic breast, prostate, and colorectal cancers. The current gold standard in clinical CTC detection and enumeration is the FDA-cleared CellSearch system (CSS). This manuscript outlines the standard protocol utilized by this platform as well as two additional adapted protocols that describe the detailed process of user-defined marker optimization for protein characterization of patient CTCs and a comparable protocol for CTC …

Activation Of Mglur2/3 Receptors In The Ventral Prefrontal Cortex Reverses Sensorimotor Gating Deficits Induced By A Systemic Nmda Receptor Antagonist, Bridget Valsamis, Michael Chang, Marei Typlt, Susanne Schmid

Anatomy and Cell Biology Publications

Prepulse inhibition (PPI) of acoustic startle is an operational measure of sensorimotor gating, which is disrupted in schizophrenia. NMDA receptor (NMDAR) antagonist induced PPI disruption has become an important pharmacological model for schizophrenia; however, knowledge of the underlying mechanism remains incomplete. This study examines the role of NMDAR in the caudal pontine reticular nucleus (PnC) and the medial prefrontal cortex (mPFC) in NMDARs antagonist induced PPI deficits, as well as the NMDA receptor subtypes involved. We administered the NMDA antagonist MK-801 locally into the caudal pontine reticular formation (PnC), where the PPI mediating pathway converges with the primary startle pathway, …

The Role Of Oxygen Tension And Insulin-Like Growth Factor Signaling In The Placental Mesenchymal Stem Cell Fate, Amer Youssef

Electronic Thesis and Dissertation Repository

The human placenta of different gestational ages is a readily available source for isolation of adult mesenchymal stem cell (MSC) for potential use in regenerative therapies. The chorionic villous region, the largest component of a placenta that interfaces with the maternal circulation, is a rich source of placental MSCs (PMSCs). To remain multipotent, PMSCs are best maintained in culture conditions that mimic the in vivo microenvironment. Insulin like growth factors (IGFs, IGF-I and -II) and oxygen tension are two of the most important microenvironmental factors in the placenta. They are of low concentration or tension respectively, at early gestation, and …