Therapeutics Commons^™

Tumor Necrosis Factor Α Inhibition For Alzheimer's Disease, Rudy Chang, Kei-Lwun Yee, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Tumor necrosis factor α (TNF-α) plays a central role in the pathophysiology of Alzheimer’s disease (AD). Food and Drug Administration–approved biologic TNF-α inhibitors are thus a potential treatment for AD, but they do not cross the blood-brain barrier. In this short review, we discuss the involvement of TNF-α in AD, challenges associated with the development of existing biologic TNF-α inhibitors for AD, and potential therapeutic strategies for targeting TNF-α for AD therapy.

The Regulation Of Rotavirus–Infected Ht29.F8 And Ma104 Cells Treated With Arachidin 1 Or Arachidin 3, Caleb M. Witcher

Electronic Theses and Dissertations

Rotavirus (RV) infections cause severe life threatening diarrhea in young children and immunocompromised individuals. Several effective vaccines have been developed for young children but are not protective against all strains of RV, and there are no anti-RV therapeutics. Our laboratory has discovered a decrease in the number of infectious simian RV particles (SA114f) in human intestinal cell line, HT29.f8 cells with the addition of either of two stilbenoids, arachidin-1 (A1) or arachidin-3 (A3). This suggests effects on the host cell and RV replication. We examined the cellular effects of human RV strain (Wa) on a human intestinal cell line (HT29.f8) …

Mapping The Interaction Between Lrrc59 And Cip2a Oncoprotein, Tamika C. Reed

Graduate School of Biomedical Sciences Theses and Dissertations

The oncogene cancerous inhibitor of protein phosphatase 2A (CIP2A) has been shown to promote oncogenesis through numerous protein-protein interactions. CIP2A was initially found to be a direct inhibitor of the PP2A tumor suppressor protein; however, new research has demonstrated that CIP2A can act independently of PP2A through protein-protein interactions resulting in deregulation of the cell cycle and the development of therapeutic drug resistance, tumorigenesis, and cell proliferation. It has been shown that leucine rich repeat containing 59 protein (LRRC59) binds to and is required for the nuclear translocation of CIP2A, thereby making this interaction a target for drug therapy. Thus, …

Toward A Research Agenda For Oncology Physical Therapy, Lucinda Pfalzer, Nicole L. Stout, Shana Harrington, Mary Insana Fisher

Physical Therapy Faculty Publications

Research Round-up: Cancer survivors frequently experience cancer treatment–related functional impairments and disability. While a growing body of evidence supports the effectiveness of rehabilitation interventions for these individuals, there are significant gaps in the existing literature and no interdisciplinary agreement on the priorities for cancer rehabilitation research. In 2016, the Oncology Section revised its strategic plan and set an objective to create an oncology rehabilitation research agenda for the physical therapy (PT) profession. To achieve this goal, the scope of the agenda, a development and review process, and dissemination plan need to be developed.

Nephrotoxicity In Patients With Or Without Cystic Fibrosis Treated With Polymyxin B Compared To Colistin, Ryan L. Crass, Wilbur Cliff Rutter, Donna R. Burgess, Craig A. Martin, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Nephrotoxicity is the primary adverse effect of the polymyxins. The relative rates of toxicity of polymyxin B and colistin have not been fully elucidated, especially in patients with cystic fibrosis (CF). A retrospective cohort study of adults treated with polymyxin B or colistin for at least 48 h was conducted. The primary endpoint was the incidence of kidney injury assessed by RIFLE (i.e., risk, injury, failure, loss, end-stage renal disease) criteria. Risk factors for kidney injury were evaluated using multivariate Cox regression. A total of 414 patients were evaluated, 220 of whom had CF. In patients without CF, there was …

Effect Of Exercise Position On Percent Changes In Serratus Anterior Muscle Thickness, Joseph M. Day

Physical Therapy Faculty Publications

Objective: A reliable method for measuring SA thickness with ultrasound imaging has been reported, yet the ability to detect differences in levels of contractility has yet to be established. The purpose of this study was to determine if there are differences in the percent change in thickness of the SA during four different exercise positions performed by healthy individuals.

Design: Observational study

Setting: Laboratory

Participants: Twenty-eight healthy participants, mean age 26 (SD 4, 57% female, 100% right handed)

Methods: Volunteers were positioned in a standardized sitting posture and anatomical landmarks were marked for ultrasound probe positioning. Two resting and two …

Vocal Function Exercises For Normal Voice: With And Without Semi-Occlusion, Megan Suzanne Brown

Theses and Dissertations--Communication Sciences and Disorders

The primary purpose of this investigation was to explore the effects of varying degrees of vocal tract semi-occlusion in Vocal Function Exercises (VFEs) on attainment of pre- established maximum phonation time (MPT) goals in individuals between the ages of 18 and 45 with normal voice. Individuals were randomized into three experimental groups: the traditional VFE with a semi-occluded vocal tract (SOVT), modified /o/ with partial occlusion, and modified /a/ without significant occlusion. For six weeks, the participants completed the four exercises two times each, twice daily on corresponding vocal tract postures assigned by group. Results indicated significant change in percent …

Prebiotics And Inflammatory Bowel Disease, Heather Rasmussen, Bruce R. Hamaker

Department of Nutrition and Health Sciences: Faculty Publications

Inflammatory bowel disease risk factors include poor diet, and corresponding low intake of dietary fiber, specifically prebiotics, which is fermented by the gut microbiota. Dietary fibers, many of which are potential prebiotics, have hundreds to thousands of unique chemical structures that may promote bacteria or bacterial groups to provide beneficial health effects. In vitro and in vivo animal models provide some support for the use of prebiotics for inflammatory bowel disease through inflammation reduction. Studies using prebiotics in patients with inflammatory bowel disease are limited and focus on only a select few prebiotic substances.

Keywords: Inflammatory bowel disease, Ulcerative colitis, …

A Murine Model Of Inflammation-Induced Cerebral Microbleeds, Rachita K. Sumbria, Mher Mahoney Grigoryan, Vitaly Vasilevko, Tatiana B. Krasieva, Miriam Scadeng, Alexandra K. Dvornikova, Annlia Paganini-Hill, Ronald Kim, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background: Cerebral microhemorrhages (CMH) are tiny deposits of blood degradation products in the brain and are pathological substrates of cerebral microbleeds. The existing CMH animal models are β-amyloid-, hypoxic brain injury-, or hypertension-induced. Recent evidence shows that CMH develop independently of hypoxic brain injury, hypertension, or amyloid deposition and CMH are associated with normal aging, sepsis, and neurodegenerative conditions. One common factor among the above pathologies is inflammation, and recent clinical studies show a link between systemic inflammation and CMH. Hence, we hypothesize that inflammation induces CMH development and thus, lipopolysaccharide (LPS)-induced CMH may be an appropriate model to …

Synthetic And Biological Exploration Of (+)-Boldine - Identification Of Potential Cns Receptor Ligands, Sujay Joseph

Theses and Dissertations

(+)-Boldine, an aporphine alkaloid, is reported to be biologically active at various Central Nervous System(CNS) receptors. However, only a few Structure Activity Relationship(SAR) studies have been conducted using boldine’s aporphine scaffold. A library of novel analogs was synthesized from boldine to understand the effect of bisbenzylation at C2 and C9 positions on the affinity and selectivity at the serotonin receptors.

Circumventing Cisplatin Resistance In Ovarian Cancers Through Reactivation Of P53 By Non-Cross-Resistant Platinum Analogs, Michelle Martinez-Rivera

Dissertations and Theses (Open Access)

Abstract

CIRCUMVENTING CISPLATIN RESISTANCE IN OVARIAN CANCERS THROUGH REACTIVATION OF P53 BY NON-CROSS-RESISTANT PLATINUM ANALOGS

Michelle Martinez-Rivera, B.S.

Advisory Professor: Zahid H. Siddik, Ph.D.

Cisplatin (cis-Pt), an anticancer platinum (Pt) drug, is used widely in the treatment of several malignancies, such as ovarian cancer. This Pt compound induces DNA damage, which results in p53 activation through post-translational modifications, mainly phosphorylation, culminating in execution of programmed cell-death. However, despite initial therapeutic response to cis-Pt, clinical resistance to this drug emerges leading to disease progression. Pt-resistance phenotypes have been associated with dysfunction in the p53 signaling pathway. Therefore, an effort to understand …

Oncology Edge Task Force On Prostate Cancer Outcomes: A Systematic Review Of Outcome Measures For Functional Mobility, Claire Davies, Genevieve Colon, Hannah Geyer, Lucinda Pfalzer, Mary Insana Fisher

Physical Therapy Faculty Publications

Background: The medical treatment of prostate cancer results in multiple impairments in body structure and declines functional abilities, resulting in activity limitations and participation restrictions. Measurement of functional mobility is an essential outcome measure in survivorship care.

Purpose: The purpose of this systematic review is to make recommendations of the best measurement tools to assess functional mobility in men treated for prostate cancer based on psychometric properties and clinical utility.

Methods: Multiple electronic databases were searched from February to March 2014. Studies of tools used to assess functional mobility were included if they met the following criteria: reported psychometric properties, …

Characterization Of Bacterial Pathogens Involved In Aerobic Vaginitis: Prevalence, Strain Characterization And Sequelae, Leslie A. Lafferty

Graduate School of Biomedical Sciences Theses and Dissertations

Aerobic vaginitis (AV) is a more recently defined infection that involves aerobic pathogenic bacteria that replace the normal flora of the vaginal tract. It is commonly mistaken for other vaginal infections, such as bacterial vaginosis (BV), because they share many common symptoms. AV leads to complications during pregnancy, such as premature delivery and amnion infection, and is diagnosed by indications that range from vaginal discharge to inflammation. Because this infection is difficult to diagnose differentially from other vaginal infections, it is important to determine what pathogens are involved in AV so that we may have the ability to detect them. …

Stabilization Of Gp120 Outer Domain For Hiv-1-1 Vaccine Immunogen Design, Duoyi Hu

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The sole envelope glycoprotein spike on the surface of Human Immunodeficiency Virus (HIV-1) is composed of two subunits: gp120 and gp41. The gp120 consists of three domains: the inner domain, outer domain and bridging sheet, to which the viral primary receptor CD4 binds and induces a conformational change in gp120 to expose the co-receptor binding site. Previous studies have found that the outer domain of gp120 is relatively more stable than the inner domain and bridging sheet. When superimposed, the co-crystal structures of CD4-gp120 complex and VRC01-gp120 complex revealed that the CD4-binding site (CD4-BS) antibody VRC01 actually mainly bound to …

Extracorporeal Membrane Oxygenation (Ecmo) For Severe Toxicological Exposures: Review Of The Toxicology Investigators Consortium (Toxic)., G S. Wang, R Levitan, T J. Wiegand, Jennifer Lowry, R F. Schult, S Yin, Toxicology Investigators Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Although there have been many developments related to specific strategies for treating patients after poisoning exposures, the mainstay of therapy remains symptomatic and supportive care. One of the most aggressive supportive modalities is extracorporeal membrane oxygenation (ECMO). Our goal was to describe the use of ECMO for toxicological exposures reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC). We performed a retrospective review of the ACMT ToxIC Registry from January 1, 2010 to December 31, 2013. Inclusion criteria included patients aged 0 to 89 years, evaluated between January 2010 through December 2013, and received ECMO for …

Challenges Of Adoptive (T-)Cell Transfer Immunotherapy For Cancer, Aaron Volk

Biology: Student Scholarship & Creative Works

Background and significance: The rebirth of the theory of immunosurveillance in 2001 rejuvenated interest in anticancer immunotherapies. In particular, T-cell-based therapies have garnered substantial interest due to the robustness and tumor antigen-specific cytotoxicity of T-cell anticancer immune responses.

Hypothesis: The efficacy of adoptive cell transfer (ACT) T-cell immunotherapy could significantly improve and gain widespread approval if future innovations in ACT-based approaches account for the pro- and antitumoral properties of non-CD8⁺ lineages of effector T-cells, evasion of T-cell antitumor immunity, and tumor-induced suppression of antitumor immunity.

Problem Analysis: Despite numerous reports of highly successful ACT-based clinical trials, no such therapy …

Task-Oriented Ankle And Foot Training For Improving Gait, Balance, And Strength In Individuals With Multiple Sclerosis: A Pilot Study, Cizelle Rodriques, Kurt Jackson, Joaquin Alberto Barrios, Lloyd L. Laubach, Kimberly Edginton Bigelow

Physical Therapy Faculty Publications

The purpose of this pilot study was to investigate the effects and feasibility of a task-oriented ankle and foot exercise program on gait, balance, and strength in 6 adults with mild to moderate disability from multiple sclerosis (MS). The subjects participated in an 8-wk task-specific home-based ankle and foot exercise program. Outcome measures included stance phase ankle joint torque and power, limits of stability, isometric and isokinetic ankle strength, gait speed, and the 12-item Multiple Sclerosis Walking Scale (MSWS-12). Five subjects completed the 8- wk intervention. Following training, there were significant increases in ankle power during early (38.1%) and late …

Breast Cancer Rehabilitation: Clinical Examination And Outcomes Assessment, Nicole L. Stout, Shana Harrington, Lucinda Pfalzer, Mary Insana Fisher

Physical Therapy Faculty Publications

Breast cancer is the most commonly diagnosed cancer in women in the United States. The treatment for breast cancer occurs along a protracted time period and includes many different disease treatment modalities. These treatments carry with them a large number of adverse effects that negatively impact function in both the short term and long term. It is necessary for rehabilitation providers to interface with patients being treated for breast cancer throughout the continuum of care so that interval assessments can be conducted to identify emerging impairments and alleviate disability. To achieve this, the rehabilitation provider must have an understanding of …

Home Exercise Adherence In An Underserved Ecuadorian Community, Joseph M. Day, Jean Irion, Meridith Anile, Jared Henson, Ben Roussel, Christina Shepherd, Huybrechts Bindele

Physical Therapy Faculty Publications

Purpose: Physical therapy service learning projects and volunteer experiences in foreign countries are becoming more commonplace. Patients in underserved regions are not likely to receive therapy services regularly; therefore, adherence to a home exercise program (HEP) is critical. The primary purpose of this study was to observe home exercise adherence rates between the 1st and 2nd visits in an underserved population. The secondary purpose of this study was to determine specific factors that affect HEP adherence in this population.

Methods: Consecutive patients seen in Santo Domingo, Ecuador were considered for participation in this observational study. All patients were recruited from …

A Comparison Of The Upper Limb Lift Test Between Women With Breast Cancer And Healthy Control Subjects, Mary Insana Fisher, Lucinda Pfalzer, Ellen W. Levy, Shana Harrington, Lynn H. Gerber, Nicole L. Stout

Physical Therapy Faculty Publications

Presentation at the World Confederation for Physical Therapy Congress, held May 1-4, 2015, in Singapore.

Background: Objective measures of upper limb (UL) function specific to breast cancer survivors (BC) are limited. Motion, strength, and muscular endurance are measurable components of UL function. A clinical test that quantifies these components is needed.

Purpose: This study compares the Upper Limb Lift Test (ULLT) between women with BC and healthy control subjects (HC) at baseline, 1-3 months, and 12+ months post-operatively enrolled in a prospective surveillance trial with early intervention. A secondary purpose was to validate the ULLT by comparing findings to self-reported …

A Qualitative Examination Of Optimal Professional Traits Of Physical Therapists. – An Exploratory Investigation, Nicholas G. Wood

Honors College Theses

Physical therapists are constantly searching for aspects of their professional practice to improve, in order to enhance interactions with patients, eventually leading to a more successful practice (Resnek & Jensen, 2003). Although this is the case, limited research has been found which has examined optimal qualities of physical therapists from neither a qualitative perspective, nor based upon their location. Thus, the purpose of this study is to use a qualitative approach to describe optimal qualities necessary for a successful physical therapy practice. In addition, this study aims to determine if therapists practicing in a rural community describe different qualities than …

The Association Between Critical Thinking And Scholastic Aptitude On First-Time Pass Rate Of The National Physical Therapy Examination, Daniel W. Suckow, C. Jayne Brahler, Betsy Donahoe-Fillmore, Mary Insana Fisher, Philip A. Anloague

Physical Therapy Faculty Publications

Objectives: 1) To investigate the relationships among critical thinking (CT) abilities, overall academic performance in the Doctorate of Physical Therapy (DPT) program as measured by cumulative grade point average (GPA), and National Physical Therapy Examination (NPTE) licensure scores, and 2) To determine if NPTE scores were significantly different between groups of students who were classified as having low, moderate or high CT abilities.

Background: It is well-established that physical therapy practice requires good clinical reasoning skills. Passage of the NPTE is required for licensure. Research to date has been mixed as to whether CT abilities or GPA can predict success …

Oncology Section Edge Task Force On Prostate Cancer Outcomes: A Systematic Review Of Clinical Measures Of Strength And Muscular Endurance, Mary Insana Fisher, Claire Davies, Genevieve Colon, Hannah Geyer, Lucinda Pfalzer

Physical Therapy Faculty Publications

Background: Strength deficits are a common morbidity following treatment for prostate cancer. Accurate assessment of strength and muscular endurance following prostate cancer treatments is essential to identify deficits and plan rehabilitation.

Purpose: To identify strength and muscular endurance outcome measures that possess strong psychometric properties and are clinically useful for examination of men treated for prostate cancer.

Methods: Multiple electronic databases were searched for articles published after 1995. Studies of tools used to assess strength and muscular endurance were included if they reported psychometric properties, were clinically feasible methods, performed on adults, and published in the English language. Each outcome …

Research Roundup From The Research Committee, Mary Insana Fisher, Shana Harrington

Physical Therapy Faculty Publications

With the expectations of accountability by consumers and third party payors for the efficacy of physical therapy practice, there has been a significant increase in the push to develop outcome measures in rehabilitation. One type of these measures, patient-reported outcome measures (PROs), are becoming increasingly more common in clinical practice. The American Physical Therapy Association’s Guide to Physical Therapist Practice 3rd edition includes outcomes assessment as an integral part of the Patient and Client Management model, and delineates that appropriate tests and measures depend upon established psychometric properties of the measurement.1 The Section on Research formed the Evidence Database to …

Research Round-Up: Manual Muscle Testing, Mary Insana Fisher, Shana Harrington

Physical Therapy Faculty Publications

Manual muscle testing was developed in response to the need to assess muscle strength losses during the polio outbreak in early part of the 20th century. The development of this original method is credited to Wilhelmine Wright and Robert W. Lovett, MD. Wright presented this method in 1912 in the Boston Medical Surgical Journal, and Lovett expanded the description of the testing method in 1916 in the Journal of the American Medical Association. The development of quantifying muscle strength by rating force generated against external resistance was an important development in objectifying assessment methods of the time.

Today, manual muscle …

Oncology Section Edge Task Force On Breast Cancer Outcomes: A Systematic Review Of Outcome Measures For Functional Mobility, Mary Insana Fisher, Jeannette Lee, Claire Davies, Hannah Geyer, Genevieve Colon, Lucinda Pfalzer

Physical Therapy Faculty Publications

Background: Breast cancer treatments in women with breast cancer often result in physical impairments that lead to activity limitations and participation restrictions. These limitations and restrictions manifest in impaired functional mobility skills that may impact survivorship. Thus, evaluation of functional mobility is an important part of survivorship care.

Purpose: To identify functional mobility outcome measures that possess strong psychometric properties and are clinically useful for examination of women treated for breast cancer.

Methods: Multiple electronic databases were searched for articles published after 1995. Studies were included if they reported psychometric properties, used clinically feasible methods, were performed on adults, and …

The Effects Of Home-Based Pilates In Healthy College-Age Females, Betsy Donahoe-Fillmore, Mary Insana Fisher, C. Jayne Brahler

Physical Therapy Faculty Publications

Objectives: To quantify and determine the effects of Pilates on core endurance, hamstring flexibility, balance, body composition/mass and perceived stress level in healthy college age females.

Study Design: Randomized controlled trial design.

Background: Emerging research on the Pilates technique is inconclusive regarding benefits to core endurance, flexibility, balance, body mass, and perceived stress.

Methods and Measures: Female college students (n=57; 18-35 years old) were randomly assigned to a Pilates group, who exercised at home with a DVD, or a control group who did not engage in Pilates practice. Core endurance, hamstring flexibility, balance, body composition and stress measurements were taken …

Dysregulation Of Micrornas In Blood As Biomarkers For Diagnosing Prostate Cancer, Rhonda W. Daniel

Theses and Dissertations

Prostate cancer is the most common noncutaneous cancer among men, yet current diagnostic methods are insufficient and more reliable diagnostic markers need to be developed. The answer that can bridge this gap and enable more efficient diagnoses may lie in microRNAs. These small, single stranded RNA molecules impact protein expression at the translational level and regulate important cellular pathways. Dysregulation of these small RNA molecules can have tumorigenic effects on cells and lead to many types of cancers.

Currently the Prostate-Stimulating Antigen (PSA) is used as a diagnostic marker for prostate cancer. However, many factors can elevate PSA levels such …

Effects Of Yoga On Arm Volume Among Women With Breast Cancer Related Lymphedema: A Pilot Study, Mary Insana Fisher, Betsy Donahoe-Fillmore, Laura Leach, Colleen O'Malley, Cheryl Paeplow, Tess Prescott, Harold L. Merriman

Physical Therapy Faculty Publications

Lymphedema affects 3–58% of survivors of breast cancer and can result in upper extremity impairments. Exercise can be beneficial in managing lymphedema. Yoga practice has been minimally studied for its effects on breast cancer related lymphedema (BCRL). The purpose of this study was to determine the effect of yoga on arm volume, quality of life (QOL), self-reported arm function, and hand grip strength in women with BCRL. Six women with BCRL participated in modified Hatha yoga 3×/week for 8 weeks. Compression sleeves were worn during yoga sessions. Arm volume, QOL, self-reported arm function, and hand grip strength were measured at …

Effects Of Pde4 Pathway Inhibition In Rat Experimental Stroke, Fan Yang, Rachita K. Sumbria, Dong Xue, Chuanhui Yu, Dan He, Shuo Liu, Annlia Paganini-Hill, Mark J. Fisher

Pharmacy Faculty Articles and Research

PURPOSE: The first genomewide association study indicated that variations in the phosphodiesterase 4D (PDE4D) gene confer risk for ischemic stroke. However, inconsistencies among the studies designed to replicate the findings indicated the need for further investigation to elucidate the role of the PDE4 pathway in stroke pathogenesis. Hence, we studied the effect of global inhibition of the PDE4 pathway in two rat experimental stroke models, using the PDE4 inhibitor rolipram. Further, the specific role of the PDE4D isoform in ischemic stroke pathogenesis was studied using PDE4D knockout rats in experimental stroke. METHODS: Rats were subjected to either the …