Diseases Commons^™

A Lin28b Tumor-Specific Transcript In Cancer, Weijie Guo, Zhixiang Hu, Yichao Bao, Yuchen Li, Shengli Li, Qiupeng Zheng, Dongbin Lyu, Di Chen, Tao Yu, Yan Li, Xiaodong Zhu, Jie Ding, Yingjun Zhao, Xianghuo He, Shenglin Huang

Markey Cancer Center Faculty Publications

The diversity and complexity of the cancer transcriptome may contain transcripts unique to the tumor environment. Here, we report a LIN28B variant, LIN28B-TST, which is specifically expressed in hepatocellular carcinoma (HCC) and many other cancer types. Expression of LIN28B-TST is associated with significantly poor prognosis in HCC patients. LIN28B-TST initiates from a de novo alternative transcription initiation site that harbors a strong promoter regulated by NFYA but not c-Myc. Demethylation of the LIN28B-TST promoter might be a prerequisite for its transcription and transcriptional regulation. LIN28B-TST encodes a protein isoform with additional N-terminal amino acids and is critical for cancer …

Outcomes Of A Pharmacist-Managed Clinic For Underserved Persons With Unmanaged Type 2 Diabetes Mellitus, Ashley L. Lefebvre, Andrew R. Zullo, Ruth Dapaah-Afriyie, Christina M. Collins, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background

A multidisciplinary approach is recommended for the management of type 2 diabetes mellitus (DM).

Aim

To evaluate the impact of a pharmacist intervention on haemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), and diabetes-related hospitalisations in an underserved cohort with unmanaged type 2 DM.

Methods

This analysis was a retrospective cohort study. Criteria for inclusion were persons with unmanaged type 2 DM defined as HbA1c values ≥8% at time of enrolment, ≥18 years old, and enrolment in a pharmacist-managed clinic for ≥12 months. Pre- and post-intervention differences in HbA1c, SBP and DBP values were assessed using …

Repeat-Associated Non-Aug (Ran) Translation And Other Molecular Mechanisms In Fragile X Tremor Ataxia Syndrome, M. Rebecca Glineburg, Peter K. Todd, Nicolas Charlet-Berguerand, Chantal Sellier

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset inherited neurodegenerative disorder characterized by progressive intention tremor, gait ataxia and dementia associated with mild brain atrophy. The cause of FXTAS is a premutation expansion, of 55 to 200 CGG repeats localized within the 5′UTR of FMR1. These repeats are transcribed in the sense and antisense directions into mutants RNAs, which have increased expression in FXTAS. Furthermore, CGG sense and CCG antisense expanded repeats are translated into novel proteins despite their localization in putatively non-coding regions of the transcript. Here we focus on two proposed disease mechanisms for FXTAS: 1) RNA …

Relationship Between The Dimerization Of Thyroglobulin And Its Ability To Form Triiodothyronine, Cintia E. Citterio, Yoshiaki Morishita, Nada Dakka, Balaji Veluswamy, Peter Arvan

Pharmacy Faculty Articles and Research

Thyroglobulin (TG) is the most abundant thyroid gland protein, a dimeric iodoglycoprotein (660 kDa). TG serves as the protein precursor in the synthesis of thyroid hormones tetraiodothyronine (T₄) and triiodothyronine (T₃). The primary site for T₃ synthesis in TG involves an iodotyrosine acceptor at the antepenultimate Tyr residue (at the extreme carboxyl terminus of the protein). The carboxyl-terminal region of TG comprises a cholinesterase-like (ChEL) domain followed by a short unique tail sequence. Despite many studies, the monoiodotyrosine donor residue needed for the coupling reaction to create T₃ at this evolutionarily conserved …

Drug Repurposing For Schistosomiasis: Combinations Of Drugs Or Biomolecules., Maria João Gouveia, Paul J Brindley, Fátima Gärtner, José M Correia Da Costa, Nuno Vale

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosomiasis is a major neglected tropical disease. Control of schistosomiasis currently relies on a single drug, praziquantel, and despite its efficacy against the all schistosome species that parasitize humans, it displays some problematic drawbacks and alone is ineffective in counteracting adverse pathologies associated with infection. Moreover, due to the development of the potential emergence of PZQ-resistant strains, the search for additional or alternative antischistosomal drugs have become a public health priority. The current drug discovery for schistosomiasis has been slow and uninspiring. By contrast, repurposing of existing approved drugs may offer a safe, rapid and cost-effective alternative. Combined treatment with …

Faith In Each Other: Sticking Together Through The Challenges Of Huntington's Disease, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Motivators For Alzheimer's Disease Clinical Trial Participation, Shoshana H. Bardach, Sarah D. Holmes, Gregory A. Jicha

Graduate Center for Gerontology Faculty Publications

Background

Alzheimer’s disease (AD) research progress is impeded due to participant recruitment challenges. This study seeks to better understand, from the perspective of individuals engaged in clinical trials (CTs), research motivations.

Methods

Participants, or their caregivers, from AD treatment and prevention CTs were surveyed about research motivators.

Results

The 87 respondents had a mean age of 72.2, were predominantly Caucasian, 55.2% were male, and 56.3% had cognitive impairment. An overwhelming majority rated the potential to help themselves or a loved one and the potential to help others in the future as important motivators. Relatively few respondents were motivated by free …

Word-List Intrusion Errors Predict Progression To Mild Cognitive Impairment, Kelsey R Thomas, Joel Eppig, Emily C Edmonds, Diane M Jacobs, David J Libon, Rhoda Au, David P Salmon, Mark W Bondi, Alzheimer’S Disease Neuroimaging Initiative

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVE: Preclinical Alzheimer's disease (AD) defined by a positive AD biomarker in the presence of normal cognition is presumed to precede mild cognitive impairment (MCI). Subtle cognitive deficits and cognitive inefficiencies in preclinical AD may be detected through process and error scores on neuropsychological tests in those at risk for progression to MCI.

METHOD: Cognitively normal participants (n = 525) from the Alzheimer's Disease Neuroimaging Initiative were followed for up to 5 years and classified as either stable normal (n = 305) or progressed to MCI (n = 220). Cox regressions were used to determine whether baseline process scores on …

Cost-Effectiveness Analysis Of Metformin+Dipeptidyl Peptidase-4 Inhibitors Compared To Metformin+Sulfonylureas For Treatment Of Type 2 Diabetes, Christina S. Kwon, Enrique Seoane-Vazquez, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

Background: Patients with type 2 diabetes (T2D) typically use several drug treatments during their lifetime. There is a debate about the best second-line therapy after metformin monotherapy failure due to the increasing number of available antidiabetic drugs and the lack of comparative clinical trials of secondary treatment regimens. While prior research compared the cost-effectiveness of two alternative drugs, the literature assessing T2D treatment pathways is scarce. The purpose of this study was to evaluate the long-term cost-effectiveness of dipeptidyl peptidase-4 inhibitors (DPP-4i) compared to sulfonylureas (SU) as second-line therapy in combination with metformin in patients with T2D.

Methods: …

Treated Hypothyroidism Is Associated With Cerebrovascular Disease But Not Alzheimer's Disease Pathology In Older Adults, Willa D. Brenowitz, Fang Han, Walter A. Kukull, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

Thyroid hormone (TH) disease is common among older adults and is associated with cognitive impairment. However, pathologic correlates are not well understood. We studied pathologic and clinical factors associated with hypothyroidism, the most common form of TH disease, in research subjects seen annually for clinical evaluations at U.S. Alzheimer’s Disease Centers. Thyroid disease and treatment status were assessed during clinician interviews. Among autopsied subjects, there were 555 participants with treated hypothyroidism and 2,146 with no known thyroid disease; hypothyroidism was associated with severe atherosclerosis (OR=1.35 95% CI: 1.02, 1.79) but not Alzheimer’s disease (AD) pathologies (amyloid plaques or neurofibrillary tangles). …

Incidence Of Dementia In Elderly Latin Americans: Results Of The Maracaibo Aging Study, Gladys E. Maestre, Luis J. Mena, Jesus D. Melgarejo, Daniel C. Aguirre-Acevedo, Gloria Pino-Ramírez, Milady Urribarrí, Inara J. Chacon, Carlos A. Chavez, Luis Falque-Madrid, Ciro A. Gaona

School of Medicine Publications

Introduction—There are few longitudinal studies of dementia in developing countries. We used longitudinal data from the Maracaibo Aging Study (MAS) to accurately determine the age- and sex-specific incidence of dementia in elderly Latin Americans.

Methods—The DSM IV-R was used to diagnose dementia, which was classified as Alzheimer’s disease (AD), vascular dementia (VaD), or other. Age- and sex-specific incidence was estimated as the number of new cases of dementia divided by person-years of follow-up (p-y).

Results—The incidence of all dementia diagnoses was 9.10 per 1000 p-y (95% CI 7.13–11.44; 8026 total p-y), 5.18 for AD (95% CI 3.72–7.03; …

Adropin: An Endocrine Link Between The Biological Clock And Cholesterol Homeostasis, Sarbani Ghoshal, Joseph R. Stevens, Cyrielle Billon, Clemence Girardet, Sadichha Sitaula, Arthur S. Leon, D.C. Rao, James S. Skinner, Tuomo Rankinen, Claude Bouchard, Marinelle V. Nuñez, Kimber L. Stanhope, Deborah A. Howatt, Alan Daugherty, Jinsong Zhang, Matthew Schuelke, Edward P. Weiss, Alisha R. Coffey, Brian J. Bennett, Praveen Sethupathy, Thomas P. Burris, Peter J. Havel, Andrew A. Butler

Physiology Faculty Publications

Objective

Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function.

Methods

Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models.

Results

In humans, plasma adropin concentrations are inversely related to atherogenic LDL-cholesterol (LDL-C) levels in men (n = 349), but not in women (n = …

Parp Pet Imaging Agents, Brandon Carney

Dissertations, Theses, and Capstone Projects

The poly (adenosine-diphosphate (ADP) ribose) polymerase (PARP) family of enzymes has been of interest to researchers and clinicians for over fifty years, especially the first member of the family, PARP1. This enzyme has become a target for cancer therapeutics due the reliance of highly proliferating cells on PARP1 for genomic maintenance. In the coming age of individualized medicine, however, highly specific therapeutic agents like PARP inhibitors are in need of similarly highly specific companion diagnostic agents. These kind of agents have been made possible with the quickly progressing field of molecular imaging. Specifically, positron emission tomography (PET) has enabled the …

Microrna 1207-3p In Prostate Cancer, Dibash Das

Dissertations, Theses, and Capstone Projects

Prostate cancer (PCa) is the most commonly diagnosed male cancer and the second leading cause of cancer-related death for men in the United States. Understanding the molecular mechanisms involved in progression from the asymptomatic androgen-dependent PCa to the lethal castration resistant prostate cancer (CRPC) is a major challenge. MicroRNAs (miRNAs), are known to be dysregulated in PCa. MicroRNA-1207-3p (miR-1207-3p) is encoded by the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of miR-1207-3p in PCa is unclear. We have discovered that miR-1207-3p is significantly underexpressed in PCa cell lines …

Novel Scoring System For Prediction Of Cardiac Syndrome X In Women With Typical Angina And A Positive Exercise Tolerance Test, Farzad Masoudkabir, Ali Vasheghani-Farahani, Elham Hakki, Hamidreza Poorhosseini, Saeed Sadeghian, Seyed Hesameddin Abbasi, Shahram Bahmanyar, Seyed Ebrahim Kassaian

The Texas Heart Institute Journal

A major diagnostic challenge for cardiologists is to distinguish cardiac syndrome X (CSX) from obstructive coronary artery disease in women with typical angina and a positive exercise tolerance test (ETT). We performed this study to develop a scoring system that more accurately predicts CSX in this patient population.

Data on 976 women with typical angina and a positive ETT who underwent coronary angiography at our center were randomly divided into derivation and validation datasets. We developed a backward stepwise logistic regression model that predicted the presence of CSX, and a scoring system was derived from it.

The derivation dataset (809 …

A Great Speech From A Great Man, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

Symptomatic Celiomesenteric Trunk: Variable Presentations And Outcomes In 2 Patients, Michael L Kueht, Darrel L Wu, Joseph L Mills, Ramyar Gilani

The Texas Heart Institute Journal

Mesenteric ischemia can be difficult to diagnose without a high degree of suspicion because it presents in a variety of ways. Visceral vascular collaterals between the fore- and midgut often provide protection against ischemia; however, the presence of anatomic variations, such as celiomesenteric trunk, can undermine the expected redundancy. Misdiagnosis can result in prolonged suffering or death, as evidenced in 2 of our patients with celiomesenteric trunk. The first patient with chronic mesenteric ischemia was diagnosed in the clinic and underwent successful surgical correction; the other had overwhelming, acute mesenteric ischemia, which resulted in death. Our cases show that successful …

Cardiac Rehabilitation Improves Cardiometabolic Health In Young Patients With Nonischemic Dilated Cardiomyopathy, Samuel G Wittekind, Yvette Gerdes, Wayne Mays, Clifford Chin, John L Jefferies

The Texas Heart Institute Journal

Nonischemic dilated cardiomyopathy is deadly and costly, and treatment options are limited. Cardiac rehabilitation has proved safe and beneficial for adults with various types of heart failure. Therefore, we retrospectively evaluated the hypothesis that rehabilitation is safe and improves cardiometabolic health in young patients with nonischemic dilated cardiomypathy. From 2011 through 2015, 8 patients (4 males) (mean age, 20.6 ± 6.6 yr; range, 10-31 yr) underwent rehabilitation at our institution. They were in American Heart Association class C or D heart failure and were on maximal medical therapy. Their mean left ventricular ejection fraction at baseline was 0.26 ± 0.15. …

Effects Of Older Donor Age And Cold Ischemic Time On Long-Term Outcomes Of Heart Transplantation, Heidi J Reich, Jon A Kobashigawa, Tamar Aintablian, Danny Ramzy, Michelle M Kittleson, Fardad Esmailian

The Texas Heart Institute Journal

Using older donor hearts in cardiac transplantation may lead to inferior outcomes: older donors have more comorbidities that reduce graft quality, including coronary artery disease, hypertension, diabetes mellitus, and dyslipidemia. Shorter cold ischemic times might overcome the detrimental effect of older donor age. We examined the relationship between donor allograft age and cold ischemic time on the long-term outcomes of heart transplant recipients. rom 1994 through 2010, surgeons at our hospital performed 745 heart transplantations. We retrospectively classified these cases by donor ages of(younger) and ≥50 years (older), then by cold ischemic times of(short), 120 to 240 min (intermediate), and …

Design Of A Framework For The Deployment Of Collaborative Independent Rare Disease-Centric Registries: Gaucher Disease Registry Model, Matthew I. Bellgard, Kathryn R. Napier, Alan Bittles, Jeffrey Szer, Sue Fletcher, Nikolajs Zeps, Adam A. Hunter, Jack Goldblatt

Research outputs 2014 to 2021

Orphan drug clinical trials often are adversely affected by a lack of high quality treatment efficacy data that can be reliably compared across large patient cohorts derived from multiple governmental and country jurisdictions. It is critical that these patient data be captured with limited corporate involvement. For some time, there have been calls to develop collaborative, non-proprietary, patient-centric registries for post-market surveillance of aspects related to orphan drug efficacy. There is an urgent need for the development and sustainable deployment of these ‘independent’ registries that can capture comprehensive clinical, genetic and therapeutic information on patients with rare diseases. We therefore …

Assessment Of Temperature And Ultraviolet Radiation Effects On Sunburn At An Inland U.S. Beach: A Cohort Study, Jason W. Marion, Jiyoung Lee, James Rosenblum, Timothy J. Buckley

EKU Faculty and Staff Scholarship

Background

Increases in outdoor temperature may lead to increases in sunburn, outdoor exposure, and skin cancer in human populations.

Objective

This study aimed to quantify sunburn incidence and risk for Ohio beachgoers exposed to varying outdoor conditions.

Methods

Sunburn incidence data were obtained through a prospective cohort study at East Fork Lake (Cincinnati, Ohio, USA). Recruitment occurred over 26 weekend days. Beach interviews and follow-up telephone interviews obtained exposure and health information. New sunburns were self-reported 8–9 days post-enrollment. Survey data were paired with ultraviolet radiation (UVR) index and temperature data for statistical analysis.

Results

Among 947 beachgoers, new sunburns …

Datasets For Mapping Pastoralist Movement Patterns And Risk Zones Of Rift Valley Fever Occurrence, Gladys Mosomtai, Magnus Evander, Charles Mundia, Per Sandström, Clas Ahlm, Osama Ahmed Hassan, Olivia Wesula Lwande, Moses K. Gachari, Tobias Landmann, Rosemary Sang

All Peer-Reviewed Publications

Rift Valley fever (RVF) is a zoonotic disease affecting humans and animals. It is caused by RVF virus transmitted primarily by Aedes mosquitoes. The data presented in this article propose environmental layers suitable for mapping RVF vector habitat zones and livestock migratory routes. Using species distribution modelling, we used RVF vector occurrence data sampled along livestock migratory routes to identify suitable vector habitats within the study region which is located in the central and the north-eastern part of Kenya. Eleven herds monitored with GPS collars were used to estimate cattle utilization distribution patterns. We used kernel density estimator to produce …

An Aged Canid With Behavioral Deficits Exhibits Blood And Cerebrospinal Fluid Amyloid Beta Oligomers, Clare Rusbridge, Francisco J. Salguero, Monique Antoinette David, Kiterie M. E. Faller, Jose T. Bras, Rita J. Guerreiro, Angela C. Richard-Londt, Duncan Grainger, Elizabeth Head, Sebastian G. P. Brandner, Brian Summers, John Hardy, Mourad Tayebi

Pharmacology and Nutritional Sciences Faculty Publications

Many of the molecular and pathological features associated with human Alzheimer disease (AD) are mirrored in the naturally occurring age-associated neuropathology in the canine species. In aged dogs with declining learned behavior and memory the severity of cognitive dysfunction parallels the progressive build up and location of Aβ in the brain. The main aim of this work was to study the biological behavior of soluble oligomers isolated from an aged dog with cognitive dysfunction through investigating their interaction with a human cell line and synthetic Aβ peptides. We report that soluble oligomers were specifically detected in the dog's blood and …

Review Of Kawasaki Disease, Rani Shah, Hisham Hirzallah, Munes Fares, Ashwini Mallad, Gudjon Karlsson, Mehiar El-Hamdani

Marshall Journal of Medicine

Abstract

Background: Kawasaki disease is one of the leading causes of acquired heart disease in children. It is an acute self-limited vasculitis that predominantly affects infants and children younger than 5 years of age. These patients present with nonspecific symptoms, such as fever and lymphadenopathy, making the diagnosis challenging. This disease can have serious and potentially fatal outcomes, and prompt recognition of this disease is vital to the patient’s outcome. We present a complete review of the disease, including the epidemiology, pathophysiology, diagnosis and management of acute Kawasaki disease, the natural history of this disease, and follow up of …

Etiology Of Community Acquired Clostridium Difficile-Associated Disease, Shannan Sherman, Dr. Pamela Ark

The Pegasus Review: UCF Undergraduate Research Journal

A review of literature related to community acquired Clostridium difficile -associated disease (CA-CDAD) was conducted. Nine relevant studies were identified using the Cumulative Index to Nursing and Allied Health (CINAHL) and MEDLINE-EBSCOhost databases. Clinical practice recommendations were obtained from the Centers for Disease Control and Prevention. The studies provided information about epidemiology of infection due to C. difficile in the community and interventions to reduce transmission. Multiple studies found underlying gastrointestinal disorders and use of cephalosporin antibiotics to be a risk factor. Another risk factor was administration of gastric acid suppressive drugs. No particular C. difficile strain was more likely …

Factors Associated With Eating Disorders In Women, Christina Knowles

The Pegasus Review: UCF Undergraduate Research Journal

Although various factors associated with eating disorders have been studied, no comprehensive source of research findings was identified in this review. The purpose of this study was to identify and synthesize research findings of factors associated with eating disorders in women published from 1992-2008. These findings may be useful to nurses, other professionals, families, and the public to facilitate the prevention, recognition, treatment, and rehabilitation of women with eating disorders.

The factors most closely associated with eating disorders identified through this review were depression, sexual abuse, substance abuse, anxiety disorders, early pubertal onset and the personality traits of perfectionism and …

Amyloid-Beta Solubility In The Treatment Of Alzheimer's Disease, Michael Paul Murphy

Molecular and Cellular Biochemistry Faculty Publications

No abstract provided.

Treatment And Outcomes Of Non-Small-Cell Lung Cancer Patients With High Comorbidity, Jorge Rios, Rahul Gosain, Bernardo H. L. Goulart, Bin Huang, Margaret N. Oechsli, Jaclyn K. Mcdowell, Quan Chen, Thomas Tucker, Goetz H. Kloecker

Biostatistics Faculty Publications

Background: The life expectancy of untreated non-small-cell lung cancer (NSCLC) is dismal, while treatment for NSCLC improves survival. The presence of comorbidities is thought to play a significant role in the decision to treat or not treat a given patient. We aim to evaluate the association of comorbidities with the survival of patients treated for NSCLC.

Methods: We performed a retrospective study of patients aged ≥66 years with invasive NSCLC between the years 2007 and 2011 in the Surveillance, Epidemiology, and End Results Kentucky Cancer Registry. Comorbidity was measured using the Klabunde Comorbidity Index (KCI), and univariate and multivariate logistic …

Fk506-Binding Protein 12.6/1b, A Negative Regulator Of [Ca2+], Rescues Memory And Restores Genomic Regulation In The Hippocampus Of Aging Rats, John C. Gant, Eric M. Blalock, Kuey-Chu Chen, Inga Kadish, Olivier Thibault, Nada M. Porter, Philip W. Landfield

Pharmacology and Nutritional Sciences Faculty Publications

Hippocampal overexpression of FK506-binding protein 12.6/1b (FKBP1b), a negative regulator of ryanodine receptor Ca²⁺ release, reverses aging-induced memory impairment and neuronal Ca²⁺ dysregulation. Here, we tested the hypothesis that FKBP1b also can protect downstream transcriptional networks from aging-induced dysregulation. We gave hippocampal microinjections of FKBP1b-expressing viral vector to male rats at either 13 months of age (long-term, LT) or 19 months of age (short-term, ST) and tested memory performance in the Morris water maze at 21 months of age. Aged rats treated ST or LT with FKBP1b substantially outperformed age-matched vector controls and performed similarly …

Sertraline, Paroxetine, And Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable Of Clinical Repurposing., Janis C Weeks, William M Roberts, Caitlyn Leasure, Brian M Suzuki, Kristin J Robinson, John M Hawdon, +Several Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Parasitic helminths infect over 1 billion people worldwide, while current treatments rely on a limited arsenal of drugs. To expedite drug discovery, we screened a small-molecule library of compounds with histories of use in human clinical trials for anthelmintic activity against the soil nematode Caenorhabditis elegans. From this screen, we found that the neuromodulatory drugs sertraline, paroxetine, and chlorpromazine kill C. elegans at multiple life stages including embryos, developing larvae and gravid adults. These drugs act rapidly to inhibit C. elegans feeding within minutes of exposure. Sertraline, paroxetine, and chlorpromazine also decrease motility of adult Trichuris muris whipworms, prevent hatching …