Digital Commons Network^™

Differential Iron Regulatory Genetics In 2d & 3d Culture Of Breast Cancer Cells, Tyler Hanna, Suzy Torti Ph. D, Frank Torti M.D., Mph, Nicole Farra Ph. D.

Honors Scholar Theses

The iron regulatory axis has consistently been shown to be perturbed in cancer cell lines relative to non-cancerous cell lines. As cancer cells rapidly divide and grow, they require iron to fuel many intracellular processes, including DNA replication and protein synthesis. Three-dimensional cell culture is an increasingly popular method of culture that purportedly more accurately mimics the in vivo microenvironment of cancers over traditional two-dimensional culture. This project was prompted by previous lab results to investigate differential iron regulatory gene expression in 2D and 3D spheroid culture models. We replicated the findings that the gene hepcidin is induced in 3D …

Xerostomia: A Comprehensive Review, Danevin Putrus

Honors College Theses

This thesis will be highlighting the condition known as Xerostomia. Xerostomia is the condition also known as “dry mouth”. This condition affects many people all throughout the world with symptoms causing bad breath, discomfort, difficulty speaking and many other. The seriousness of this condition can lead to cardiovascular disease, dementia, respiratory infections, diabetes mellitus, rheumatoid arthritis, and even cancer (Absolutedental.com). Currently there is not any one specific solution for the condition although many have been proposed. Throughout the thesis I will closely examine former research studies, current solutions proposed, and propose my own study and solution based on research and …

Comparative Plasma Proteomics In Muscle Atrophy Induced By Cancer Cachexia And Hindlimb Unloading, Kirsten Rene Dunlap

Graduate Theses and Dissertations

Introduction: Muscle atrophy results from a dysfunction in protein turnover that leads to loss of mass and function and occurs concurrently with multiple pathologies such as cancer and extended bed rest. Atrophy reduces overall quality of life while increasing morbidity and mortality. Currently, efficacious therapeutic interventions to treat and prevent muscle wasting in all its forms are lacking, however if conserved mechanisms can be identified between wasting conditions, this would aid in the development of multipurpose therapeutics to ameliorate this pathology. Purpose: To examine circulating factors present across atrophic pathologies. Methods: 35 male C57BL/6J mice were assigned to hindlimb unloading …

Transcriptional Influence Of Retinoic Acid And Its Effects On Angiogenesis Of Murine Salivary Glands., Isaac Feinn

College of Arts & Sciences Senior Theses

Salivary gland hypofunction is a major disorder of salivary glands, and can arise either from diseases such as xerostomia, or from defective epithelial morphogenesis during embryogenesis. Hundreds of thousands of individuals suffer from dry mouth, and there is currently no restorative therapy for these patients. Investigation of salivary gland developmental biology will inform regenerative therapies. Currently it is known that retinoic acid (RA), the biologically active form of Vitamin A, is required for proper development of the salivary gland, but little is known about its cellular mechanism regulating organogenesis. This study sought to analyze salivary gland development in Rdh10 knock …

Post Lumbar-Puncture Headache Experience In A Community Hospital (Peach) Study, Melissa Kessel, Caroline Knight, Robert Stein

MaineHealth Maine Medical Center

Introduction:

Post lumbar puncture (LP) headaches have been reported to occur in 10 to 30% of patients . The incidence of post-LP headaches at Pen Bay Medical Center (PBMC) was unknown prior to this study. This study was undertaken to attempt to understand the local experience with this procedural complication.

The Effect Of Glucosamine, Chondroitin And Harpagophytum Procumbens On Femoral Hyaline Cartilage Thickness In Patients With Knee Osteoarthritis– An Mri Versus Ultrasonography Study, Florentin Ananu Vreju, Paulina Lucia Ciurea, Anca Rosu, Beatrice Andreea Chisalau, Cristina Dorina Parvanescu, Sineta Cristina Firulescu, Adina Turcu Stiolica, Andreea Lili Barbulescu, Stefan Cristian Dinescu, Cristiana Iulia Dumitrescu, Roxana Mihaela Dumitrascu, Cristina Criveanu, Lucretiu Radu, Mihai Tusaliu, Daniela Dumitrescu

Journal of Mind and Medical Sciences

Background: the evaluation of cartilage thickness has become possible with new techniques such as musculoskeletal ultrasonography (US) and magnetic resonance imagining (MRI), making the evaluation of the treatment response and the progression of the disease more accurate. Objective: to evaluate the efficacy of a Symptomatic Slow Acting Drug for Osteoarthritis using both US and MRI for measuring cartilage thickness at baseline and after 1 year. Methods: The study included the clinical evaluation of 20 patients at baseline, at 6 and 12 months as well as imaging exams (US and MRI) at baseline and after 1 year. Measurements …

Microbiota Signatures In Type-2 Diabetic Patients With Chronic Kidney Disease - A Pilot Study, Gratiela P. Gradisteanu, Roxana A. Stoica, Laura Petcu, Ariana Picu, Adrian P. Suceveanu, Teodor Salmen, Diana S. Stefan, Cristian Serafinceanu, Mariana Carmen Chifiriuc, Anca P. Stoian

Journal of Mind and Medical Sciences

The human microbiota is paramount for normal host physiology. Altered host-microbiome interactions are part of the pathogenesis of numerous common ailments. Currently, much emphasis is placed on the involvement of the microbiome in the pathogenesis of type-2 diabetes mellitus (T2DM), impaired glucose tolerance, and other metabolic disorders (i.e. obesity). Several studies found highly significant correlations of specific intestinal bacteria with T2DM. A better understanding of the role of the microbiome in diabetes and its complications might provide new insights in the development of new therapeutic principles.

Our pilot study investigates the microbiota patterns in Romanian type-2 diabetic patients with diabetic …

Physical Exercise – The Friend Or The Enemy Of The Patient With Pulmonary Tuberculosis?, Victoria Maria Ruta, Teodora Gabriela Alexescu, Simina Tarmure, Vasile Negrean, Monica Carmen Pop, Nicoleta Motoc, Iulia Olimpia Pfingstgraf, Mirela Georgiana Perne, Lorena Ciumarnean, Simona Valeria Clichici, Adina Milena Man

Journal of Mind and Medical Sciences

Introduction. Tuberculosis, a major cause of morbidity and mortality, is the second cause of death from an infectious disease, after HIV/AIDS. Each second, a new infection occurs around the globe. Pulmonary tuberculosis can equally affect a performance athlete as well as an aspiring athlete. Physical exercise must be individualized and customized. Pulmonary rehabilitation guides 3 recommend types of exercises for patients with obstructive pathology: stretching, cardiovascular exercise or aerobics. Exercises must be started under medical supervision and must be interrupted if: the ventricular altitude increases above the maximum estimated level for the age, oxygen saturation (SaO2). Aim. The current review …

A Background Of The Opioid Epidemic And Its Relationship To The Medicaid Expansion, Er Yearn Jang

Senior Honors Theses

Despite the recent increase in public awareness of the opioid epidemic, the background of this epidemic is still disappointingly unknown to the public. The opioid epidemic is a national crisis which impacts, not only individuals’ wellbeing but the economy of the United States. The federal government sought to mitigate it through the enactment of the Patient Protection and Affordable Care Act. The Medicaid expansion, which was built into this law, sparked controversy; controversy which has yet to be solved to this day. Going forward, the knowledge we gather from examining the connection between this epidemic and the Medicaid expansion will …

Ucp1 Expression-Associated Gene Signatures Of Human Epicardial Adipose Tissue., Kanta Chechi, Jinchu Vijay, Pierre Voisine, Patrick Mathieu, Yohan Bossé, Andre Tchernof, Elin Grundberg, Denis Richard

Manuscripts, Articles, Book Chapters and Other Papers

Multiple reports of uncoupling protein 1 (UCP1) expression have established its presence in human epicardial adipose tissue (eAT). Its functional relevance to eAT, however, remains largely unknown. In a recent study, we reported that adrenergic stimulation of eAT was associated with downregulation of secreted proteins involved in oxidative stress-related and immune-related pathways. Here, we explored the UCP1-associated features of human eAT using next-generation deep sequencing. Paired biopsies of eAT, mediastinal adipose tissue (mAT), and subcutaneous adipose tissue (sAT) obtained from cardiac surgery patients, with specific criteria of high and low expression of UCP1 in eAT, were subjected to RNA sequencing. …

Steroid Receptor Coactivator-1 Modulates The Function Of Pomc Neurons And Energy Homeostasis, Yongjie Yang, Agatha A Van Der Klaauw, Liangru Zhu, Tessa M Cacciottolo, Yanlin He, Lukas K J Stadler, Chunmei Wang, Pingwen Xu, Kenji Saito, Antentor Hinton, Xiaofeng Yan, Julia M Keogh, Elana Henning, Matthew C Banton, Audrey E Hendricks, Elena G Bochukova, Vanisha Mistry, Katherine L Lawler, Lan Liao, Jianming Xu, Stephen O'Rahilly, Qingchun Tong, Uk10k Consortium, Inês Barroso, Bert W O'Malley, I Sadaf Farooqi, Yong Xu

Children’s Nutrition Research Center Staff Publications

Hypothalamic neurons expressing the anorectic peptide Pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here, we show that Steroid Receptor Coactivator-1 (SRC-1) interacts with a target of leptin receptor activation, phosphorylated STAT3, to potentiate Pomc transcription. Deletion of SRC-1 in Pomc neurons in mice attenuates their depolarization by leptin, decreases Pomc expression and increases food intake leading to high-fat diet-induced obesity. In humans, fifteen rare heterozygous variants in SRC-1 found in severely obese individuals impair leptin-mediated Pomc reporter activity in cells, whilst four variants found in non-obese controls do not. In a knock-in mouse model of a loss of function …

Severe Anion Gap Metabolic Acidosis Associated With Initiation Of A Very Low-Carbohydrate Diet., Sijan Basnet, Niranjan Tachamo, Salik Nazir, Rashmi Dhital, Asad Jehangir, Anthony Donato

Reading Hospital Internal Medicine Residency

Low carbohydrate diets have been popularized as an effective solution for weight loss. Although rare, life-threatening anion gap metabolic acidosis has been reported in patients on these diets. We present a case of a 31-year-old man with atypical symptoms of chest pain and shortness of breath found to have severe metabolic acidosis after starting low carbohydrate diet for a week.

Changes In Mitochondrial Protein Expression In Human Cd4 + T Cells During The Initiation And Progression Of Diabetes, Alanna Keady

Health Sciences Student Work

Introduction: Chronic sterile inflammation that underlies obesity can promote unhealthy cellular changes eventually leading to a decline in metabolic health and type-2 diabetes. Dysregulation of cellular processes during the initiation and progression of obesity can impair inflammatory homeostasis leading to a proinflammatory Th17 cytokine profile by CD4 + Tcells. Our ongoing research efforts are to understand the mechanistic link between the changes in a cellular housekeeping process known as autophagy and the regulation of Th17 cytokines in obese non diabetic and diabetic subjects. Methods: We assessed cellular protein expression and colocalization using immunoblotting, immunofluorescence, flow cytometry and ELISA assays. Results: …

The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue

Senior Theses

Phenylketonuria, now known as phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder of metabolism affecting approximately one in every 15,000 infants born in the United States. Patients have nonfunctional PAH enzyme secondary to one or more genetic mutations. The enzyme deficit results in destructive supraphysiologic blood phenylalanine levels upon consumption of the essential dietary amino acid phenylalanine. Current standards of care mitigate signs and symptoms of the disorder, but do not approach a cure. The methods for creating a prototype pharmabiotic as an innovative treatment strategy for PAH deficiency are described herein.

DNA molecular cloning techniques were utilized to engineer …

Is Breastfeeding Truly Best? Evolutionary, Physiological, & Cultural Factors That Shape Breastfeeding Practices, Emily J. Green 19

Honor Scholar Theses

No abstract provided.

Long-Term Use Of Antibiotics And Risk Of Colorectal Adenoma, Yin Cao, Kana Wu, Raaj Mehta, David A. Drew, Mingyang Song, Paul Lochhead, Long H. Nguyen, Jacques Izard, Charles S. Fuchs, Wendy S. Garrett, Curtis Huttenhower, Shuji Ogino, Edward L. Giovannucci, Andrew T. Chan

Department of Food Science and Technology: Faculty Publications

Objective: Recent evidence suggests that antibiotic use, which alters the gut microbiome, is associated with an increased risk of colorectal cancer. However, the association between antibiotic use and risk of colorectal adenoma, the precursor for the majority of colorectal cancers, has not been investigated.

Design: We prospectively evaluated the association between antibiotic use at age 20–39 and 40–59 (assessed in 2004) and recent antibiotic use (assessed in 2008) with risk of subsequent colorectal adenoma among 16,642 women aged ≥ 60 enrolled in the Nurses’ Health Study who underwent at least one colonoscopy through 2010. We used multivariate logistic …

Characterizing Aft1/2-Grx3/4 Interaction And The Role Of Bol2 During Iron Regulation In Saccharomyces Cerevisiae, William Rivers

Senior Theses

Iron dysregulation has been linked to a variety of human diseases, such as anemia, Friedreich’s ataxia, X-linked sideroblastic anemia, sideroblastic-like microcytic anemia, and myopathy. Thus, it is vitally important to understand the mechanisms for regulating intracellular iron. Here, we use fluorescence microscopy techniques in live cells to study interactions of the yeast proteins Grx3/4, Aft1/2, and Bol2, which have been shown to be involved in turning off iron import when the cell has adequate iron. Modified versions of genes encoding these proteins have been incorporated into several yeast backgrounds to use fluorescence to monitor interactions under varying iron levels.

Probiotic Administration As An Adjuvant Therapeutic Treatment For Anxiety, Depression, And Cognitive Impairment Among Hypothyroid Patients, Erin R. Gorman

Selected Honors Theses

Hypothyroidism is a form of thyroid dysfunction that occurs when the thyroid gland does not make and secrete enough thyroid hormones to regulate certain processes in the body. Because thyroid hormones take part in many bodily functions, hypothyroidism can cause a large range of symptoms. Current research indicates that some strains of probiotics have beneficial effects on certain neurological and inflammatory diseases, leading to the impression that they can be used therapeutically for effective treatment of different mental health issues such as anxiety, stress, depression, and impaired memory. Because hypothyroidism often leads to such mental symptoms, it may be possible …

Coming Together To Define Membrane Contact Sites., Luca Scorrano, Maria Antonietta De Matteis, Scott Emr, Francesca Giordano, György Hajnóczky, Benoît Kornmann, Laura L. Lackner, Tim P. Levine, Luca Pellegrini, Karin Reinisch, Rosario Rizzuto, Thomas Simmen, Harald Stenmark, Christian Ungermann, Maya Schuldiner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Close proximities between organelles have been described for decades. However, only recently a specific field dealing with organelle communication at membrane contact sites has gained wide acceptance, attracting scientists from multiple areas of cell biology. The diversity of approaches warrants a unified vocabulary for the field. Such definitions would facilitate laying the foundations of this field, streamlining communication and resolving semantic controversies. This opinion, written by a panel of experts in the field, aims to provide this burgeoning area with guidelines for the experimental definition and analysis of contact sites. It also includes suggestions on how to operationally and tractably …

Aortoduodenal Fistula Forms From Primary Aortic Stump Graft In A Two-Time Multi-Visceral Transplant Patient With Presentation Of Gastrointestinal Bleed And Bowel Perforation: A Case Report, Brielle Corrente

Graduate Student Research Symposium

Usually not diagnosed until open laparotomy, aortoduodenalfistulas (ADF) are one of the rarest complications of intestinal transplant surgery. With an incidence rate of only 0.04% at autopsy and only 250 documented cases since the early 1800’s, aortoduodenal fistulas are the most deadly complications of intestinal transplantation with a mortality rate of 100% without surgical intervention. A 39 year old, two-time multi-visceral transplant African American female patient suffered from a primary aortoduodenal fistula formation in a primary modified multi-visceral transplant aortic stump graft site. With emergency open laparotomy repair, revascularization of the secondary multi-visceral transplant was performed, saving the life of …

Does Family Communication Matter? Exploring Knowledge Of Breast Cancer Genetics In Cancer Families, Deborah Himes, Sarah H. Davis, Jane Lassetter Phd, Rn, Neil E. Peterson, Margaret F. Clayton, Wendy C. Birmingham, Anita Y. Kinney

Faculty Publications

Purpose: Knowledge of breast cancer genetics is critical for those at increased hereditary risk who must make decisions about breast cancer screening options. This descriptive study explored theory-based relationships among cognitive and emotional variables related to knowledge of breast cancer genetics in cancer families. Methods: Participants included first-degree relatives of women with breast cancer who had received genetic counseling and testing. Study participants themselves did not have breast cancer and had not received genetic counseling or testing. Data were collected by telephone interviews and surveys. Variables analyzed included numeracy, health literacy, cancer-related distress, age, education, and the reported amount of …

Dissecting Features Of Epigenetic Variants Underlying Cardiometabolic Risk Using Full-Resolution Epigenome Profiling In Regulatory Elements., Fiona Allum, Åsa K. Hedman, Xiaojian Shao, Warren A. Cheung, Jinchu Vijay, Frédéric Guénard, Tony Kwan, Marie-Michelle Simon, Bing Ge, Cristiano Moura, Elodie Boulier, Lars Rönnblom, Sasha Bernatsky, Mark Lathrop, Mark I. Mccarthy, Panos Deloukas, André Tchernof, T Pastinen, Marie-Claude Vohl, Elin Grundberg

Manuscripts, Articles, Book Chapters and Other Papers

Sparse profiling of CpG methylation in blood by microarrays has identified epigenetic links to common diseases. Here we apply methylC-capture sequencing (MCC-Seq) in a clinical population of ~200 adipose tissue and matched blood samples (Ntotal~400), providing high-resolution methylation profiling (>1.3 M CpGs) at regulatory elements. We link methylation to cardiometabolic risk through associations to circulating plasma lipid levels and identify lipid-associated CpGs with unique localization patterns in regulatory elements. We show distinct features of tissue-specific versus tissue-independent lipid-linked regulatory regions by contrasting with parallel assessments in ~800 independent adipose tissue and blood samples from the general population. We follow-up …

Can Assisted Reproductive Technologies Help Conserve 300 Million Years Of Evolution? A First Attempt At Developing These Technologies For Male Reptiles, Sean M. Perry

LSU Doctoral Dissertations

Biodiversity loss is the most critical environmental problem threatening ecosystem, animal, and human health today. Increases in extinction rates have been observed over the past 50 years, with reptile losses occurring twelve times faster than traditional extinction rates. This demonstrated biodiversity loss is secondary to climate change, habitat destruction, infectious disease, invasive species, poaching, and unsustainable trade. Approximately 20% of all reptiles are threatened with extinction and population declines are approaching rates similar to the current amphibian extinction crisis. Preventing the extinction of reptiles will require humans to acknowledge these losses and develop plans to preserve these evolutionary sentinel species. …

Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

The past two decades have witnessed significant advances in high-throughput ``omics" technologies such as genomics, proteomics, metabolomics, transcriptomics and radiomics. These technologies have enabled simultaneous measurement of the expression levels of tens of thousands of features from individual patient samples and have generated enormous amounts of data that require analysis and interpretation. One specific area of interest has been in studying the relationship between these features and patient outcomes, such as overall and recurrence-free survival, with the goal of developing a predictive ``omics" profile. Large-scale studies often suffer from the presence of a large fraction of censored observations and potential …

An Investigation Of Stimulants: Reviewing Their Effects On The Brain, Including Memory And Microglia, Michael Douchey

UNO Student Research and Creative Activity Fair

Stimulants are a class of drugs that have a variety of effects on the brain, including changes in receptor activity in the brain areas responsible for- memory, attention, emotion, motor control, and the reward pathway. Stimulants may be generally classified by their availability. For example, prescription stimulants, which include drugs such as methylphenidate (Concerta™, Ritalin™) and mixed amphetamine salts (Adderall™), must be prescribed by medical professionals. Another regulated stimulant, albeit one available without a prescription, is nicotine; a highly addictive chemical that is age-restricted by the U.S. federal government. Nicotine is found in tobacco products, and in tobacco-free alternatives including …

Relationship Between Dietary Intake And Obesity Among A Group Of Primary School-Aged Children In Cairo Governorate, Ahmed S. Marei, Hany H. El-Gazzar, Khaled Elkelany, Mohamed F. Al Soda, Saher A. Khairy, Salwa M. Saleh, Mahmood D. Al-Mendalawi

Journal of Medicine in Scientific Research

No abstract provided.

Saturated Fatty Acid Activates T Cell Inflammation Through A Nicotinamide Nucleotide Transhydrogenase (Nnt)-Dependent Mechanism, Grace Mccambridge, Madhur Agrawal, Alanna Keady, Philip A. Kern, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Pharmacology and Nutritional Sciences Faculty Publications

Circulating fatty acids (FAs) increase with obesity and can drive mitochondrial damage and inflammation. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial protein that positively regulates nicotinamide adenine dinucleotide phosphate (NADPH), a key mediator of energy transduction and redox homeostasis. The role that NNT-regulated bioenergetics play in the inflammatory response of immune cells in obesity is untested. Our objective was to determine how free fatty acids (FFAs) regulate inflammation through impacts on mitochondria and redox homeostasis of peripheral blood mononuclear cells (PBMCs). PBMCs from lean subjects were activated with a T cell-specific stimulus in the presence or absence of generally pro-inflammatory …

Early Progression Of Krabbe Disease In Patients With Symptom Onset Between 0 And 5 Months., Maria L. Beltran-Quintero, Nicholas A. Bascou, Michele D. Poe, David A. Wenger, Carlos A. Saavedra-Matiz, Matthew J. Nichols, Maria L. Escolar

Department of Neurology Faculty Papers

BACKGROUND: Krabbe disease is a rare neurological disorder caused by a deficiency in the lysosomal enzyme, β-galactocerebrosidase, resulting in demyelination of the central and peripheral nervous systems. If left without treatment, Krabbe disease results in progressive neurodegeneration with reduced quality of life and early death. The purpose of this prospective study was to describe the natural progression of early onset Krabbe disease in a large cohort of patients.

METHODS: Patients with early onset Krabbe disease were prospectively evaluated between 1999 and 2018. Data sources included diagnostic testing, parent questionnaires, standardized multidisciplinary neurodevelopmental assessments, and neuroradiological and neurophysiological tests.

RESULTS: We …

Student-Faculty Collaborative Research Grant Report, Megan Bestwick

Post-Grant Reports

Mitochondria are essential organelles in most eukaryotic cells because of their role in metabolism and the production of ATP by the oxidative phosphorylation (OXPHOS) pathway, as well as other key cellular processes. Metal cofactors, such as copper (Cu) and iron (Fe), are incorporated into OXPHOS protein complexes of yeast located within the inner membrane of the mitochondria. Misincorporation or modulation of these available metals in mitochondrial enzymes leads to the production of reactive oxygen species (ROS). ROS are reactive molecules containing oxygen such as peroxides, superoxide, and hydroxyl radicals. Yeast are a good model for studying aging and the effect …

Innovation And Competition In Advanced Therapy Medicinal Products, Enrique Seoane-Vazquez, Vaishali Shukla, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

"Advanced therapy medicinal products (ATMPs), including gene therapy, cell therapy, and tissue engineering products, represent a paradigm shift in health care as they have great potential for preventing and treating many diseases (Food and Drug Administration (FDA), 2013). By way of example, only 367 (8.0%) of the 4,603 rare diseases and conditions listed by the NIH Genetic and Rare Diseases Information Center had at least one FDA-approved drug therapy in early 2018. An estimated 3,038 (66.0%) of those rare diseases and conditions are congenital and genetic diseases that could potentially be treated by gene therapy. There are already ATMPs under …