Medicine and Health Sciences Commons^™

Binding Of An Indenoisoquinoline To The Topoisomerase-Dna Complex Induces Reduction Of Linker Mobility And Strengthening Of Protein-Dna Interaction., Giordano Mancini, Ilda D'Annessa, Andrea Coletta, Giovanni Chillemi, Yves Pommier, Mark S. Cushman, Alessandro Desideri

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Long-duration comparative molecular dynamics simulations of the DNA-topoisomerase binary and DNA-topoisomerase-indenoisoquinoline ternary complexes have been carried out. The analyses demonstrated the role of the drug in conformationally stabilizing the protein-DNA interaction. In detail, the protein lips, clamping the DNA substrate, interact more tightly in the ternary complex than in the binary one. The drug also reduces the conformational space sampled by the protein linker domain through an increased interaction with the helix bundle proximal to the active site. A similar alteration of linker domain dynamics has been observed in a precedent work for topotecan but the molecular mechanisms were different …

Selection Of Trna Charging Quality Control Mechanisms That Increase Mistranslation Of The Genetic Code, Srujana S. Yadavalli, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Mistranslation can follow two events during protein synthesis: production of non-cognate amino acid:transfer RNA (tRNA) pairs by aminoacyl-tRNA synthetases (aaRSs) and inaccurate selection of aminoacyl-tRNAs by the ribosome. Many aaRSs actively edit non-cognate amino acids, but editing mechanisms are not evolutionarily conserved, and their physiological significance remains unclear. To address the connection between aaRSs and mistranslation, the evolutionary divergence of tyrosine editing by phenylalanyl-tRNA synthetase (PheRS) was used as a model. Certain PheRSs are naturally error prone, most notably a Mycoplasma example that displayed a low level of specificity consistent with elevated mistranslation of the proteome. Mycoplasma PheRS was found …

Health & Wellness Page, Ilana A. Mesnard

Blogging the Library

Where is health on your priority list? Good health is crucial for all people, but especially for musicians (or athletes) who need their bodies in top performance shape. Musicians in the conservatory need to be aware of how to stay healthy. The purposes of the Health and Wellness Page are to promote good health, and to create awareness of reliable resources on healthy lifestyle choices as musicians. [excerpt]

December 5, 2012, Communication Disorders & Sciences

Faculty Meeting Minutes & Agendas

Meeting minutes of the December 5, 2012 Faculty Committee meeting.

Prevalence And Predictors Of Giving Birth In Health Facilities In Bugesera District, Rwanda, Shahrzad Joharifard, Stephen Rulisa, Francine Niyonkuru, Andrew Weinhold, Felix Sayinzoga, Jeffrey Wilkinson, Jan Ostermann, Nathan M. Thielman

Faculty Publications

Background The proportion of births attended by skilled health personnel is one of two indicators used to measure progress towards Millennium Development Goal 5, which aims for a 75% reduction in global maternal mortality ratios by 2015. Rwanda has one of the highest maternal mortality ratios in the world, estimated between 249–584 maternal deaths per 100,000 live births. The objectives of this study were to quantify secular trends in health facility delivery and to identify factors that affect the uptake of intrapartum healthcare services among women living in rural villages in Bugesera District, Eastern Province, Rwanda.

Methods Using census data …

The Effect Of A Three Set Tennis Match On Knee Kinematics And Leg Muscle Activation During The Tennis Serve, Brad Fenter

Health and Kinesiology Theses

Tennis matches can be long, physically challenging affairs. Matches are often determined by the serving proficiency of the players. The serve has been extensively studied, but the relationship between the serve and match length regarding knee kinematics and leg muscle activation is not well documented in a real time environment. The purpose of the current study was to determine the effect a three-set tennis match had on knee kinematics and muscle activation of quadriceps and hamstrings during the serve. Ten male collegiate tennis players (age: 19.6±1.7) were recruited from The University of Texas at Tyler. All participants played a three-set …

The Role Of Megalin In The Transport Of Aminoglycosides Across Human Placenta, Amal Akour

Theses and Dissertations

Background: Intra-amniotic infections (IAIs) are common complications of labor and delivery. If inadequately treated, these infections can lead to significant morbidity and mortality in the mother and the fetus. Intrapartum aminoglycoside (AG) administration is recommended for the management of IAIs. AGs are known to cross the placenta and achieve bactericidal concentrations in fetal serum. However, the highest and most persistent fetal levels are achieved in renal tissue. So, the fetus may be vulnerable to the nephrotoxic effects of AGs. Megalin, a 600 kDaendocytic receptor, is responsible for the uptake of AGs into renal proximal tubular epithelial cells. This receptor is …

Microrna Mir-155 Affects Antiviral Effector And Effector Memory Cd8 T Cell Differentiation, Ching-Yi Tsai, S. Rameeza Allie, Weijun Zhang, Edward J. Usherwood

Dartmouth Scholarship

MicroRNAs are key regulators of the immune response, but their role in CD8 T cell differentiation in vivo is not known. We show that miR-155 is important in both effector and memory antiviral CD8 T cell responses. Without miR-155, there was a weaker effector response and a skewing toward memory precursor cells. At the memory stage, miR-155-deficient CD8 T cells preferentially differentiated into central memory cells and were capable of mounting a potent secondary response.

Myeloid-Derived Suppressor Cells In Murine Retrovirus-Induced Aids Inhibit T- And B-Cell Responses In Vitro That Are Used To Define The Immunodeficiency, Kathy A. Green, W. James Cook, William R. Green

Dartmouth Scholarship

Myeloid-derived suppressor cells (MDSCs) have been characterized in several disease settings, especially in many tumor systems. Compared to their involvement in tumor microenvironments, however, MDSCs have been less well studied in their responses to infectious disease processes, in particular to retroviruses that induce immunodeficiency. Here, we demonstrate for the first time the development of a highly immunosuppressive MDSC population that is dependent on infection by the LP-BM5 retrovirus, which causes murine acquired immunodeficiency. These MDSCs express a cell surface marker signature (CD11b Gr-1 Ly6C ) characteristic of monocyte-type MDSCs. Such MDSCs profoundly inhibit immune responsiveness by a cell dose- and …

2012 December 4 - Medical Student Education Committee Minutes, Medical Student Education Committee, East Tennessee State University

Medical Student Education Committee Minutes

No abstract provided.

Proliferation Of Genetically Modified Human Cells On Electrospun Nanofiber Scaffolds., Mandula Borjigin, Bryan Strouse, Rohina A. Niamat, Pawel Bialk, Chris Eskridge, Jingwei Xie, Eric B. Kmiec

Journal Articles: Pharmaceutical Sciences

Gene editing is a process by which single base mutations can be corrected, in the context of the chromosome, using single-stranded oligodeoxynucleotides (ssODNs). The survival and proliferation of the corrected cells bearing modified genes, however, are impeded by a phenomenon known as reduced proliferation phenotype (RPP); this is a barrier to practical implementation. To overcome the RPP problem, we utilized nanofiber scaffolds as templates on which modified cells were allowed to recover, grow, and expand after gene editing. Here, we present evidence that some HCT116-19, bearing an integrated, mutated enhanced green fluorescent protein (eGFP) gene and corrected by gene editing, …

The Lived Experience Of Fathers Whose Children Are Diagnosed With A Genetic Disorder, Mary T. Rivard

Nursing Theses and Dissertations

Parenting a child with a genetic disorder requires overcoming numerous obstacles. The purpose of this study was to understand the experience of fathers whose children have been diagnosed with a genetic disorder. By gaining insight into a father's reactions and needs, nurses will be better able to provide anticipatory guidance, emotional support, assistance with stressor identification, development of coping mechanisms, and problem solving strategies to assist him in coping with his child's condition.

Exploring The Differences Between Adult Cancer Survivors And Their Caregivers' Social Support, Self-Efficacy For Physical Activity, Physical Activity Behavior, And Quality Of Life, Fedricker Diane Barber

Nursing Theses and Dissertations

Less than 20% of cancer survivors meet recommended physical activity (PA) guidelines. Research reporting positive impact of social support on PA in cancer survivors has not included their caregivers' PA. A review of the literature examining social support and PA in cancer survivors supported including caregivers in developing strategies to increase PA in cancer survivors. The purposes of this study were: (1) to explore the differences and relationships between adult cancer survivors' and caregivers' social support, self-efficacy for physical activity (SEPA), PA, and quality of life (QOL), and (2) understand cancer survivors and caregivers' perception of social support in PA …

Vulnerability And Adaptation For Traumatic Brain Injury Survivors, Amy Johnson

Nursing Theses and Dissertations

Many of the over 5 million survivors of traumatic brain injury (TBI) with related disabilities living in the community do not have support for their unmet needs. Adapting to life after TBI is difficult because of cognitive, emotional, and behavioral complications. Nurses and other healthcare professionals have the opportunity to promote positive outcomes for persons with TBI. However, to increase the depth and breadth of that support, nurses need a base of knowledge that includes an understanding of the TBI survivors' needs, vulnerabilities, and obstacles to adaptation. TBIs result in physical, psychological, developmental, and emotional losses. The needs that ensue …

Effect Of Telephone Counseling On Physical Activity Among Older Adult Cancer Survivors, Ellen C. Mullen

Nursing Theses and Dissertations

The elderly population, especially those with cancer coupled with low health literacy, is at high risk for poor health outcomes. Telephone counseling has been shown to be effective in improving health behaviors among other populations, but it has not been studied for older adult cancer survivors. The purpose of this mixed methods study was to examine the effectiveness of telephone counseling on physical activity among older adult cancer survivors (n=50). The relationship between health literacy level and perceived changes in physical activity was assessed. Based on existing literature and Orem's Theory of Self-care, the following hypotheses were tested: H1: Telephone …

Fluoroquinolone And Macrolide Co-Resistance In Clinical Isolates Of Campylobacter Species: A 15-Year Study In Karachi, Pakistan, Seema Irfan, A Ahmad, D Guhar, E Khan, Fasial Malik, Syed Mahmood, Afia Zafar

Department of Pathology and Laboratory Medicine

Fluoroquinolone and macrolide antibiotics are generally considered as first-line drugs for the treatment of severe campylobacteriosis. This study was conducted to analyse the trend of erythromycin and ofloxacin resistance among Campylobacter spp. isolated from stool specimens over a period of 15 years (1992-2007) at The Aga Khan University clinical laboratory in Karachi, Pakistan. A total of 83 396 stool specimens were processed, with a 14% isolation rate for enteric pathogens. The isolation rate of Campylobacter spp. was low during 1992-93 (6%-13%), peaked in 1996 (46%), then ranged from 20% to 40%. We report a rising trend in ofloxacin resistance, re-emergence …

Diffuse Traumatic Axonal Injury Within The Visual System: Implications For Visual Pathway Reorganization, Jiaqiong Wang

Theses and Dissertations

Traumatic brain injury is a major health problem with much of its morbidity associated with traumatic axonal injury (TAI). To date, significant insight has been gained into the initiating pathogenesis of TAI. However, the specific anterograde and retrograde sequelae of TAI are poorly understood because the diffuse nature of TAI complicates data analysis. To overcome this limitation, we subjected transgenic mice expressing yellow fluorescent protein (YFP) within the visual system to central fluid percussion injury, and consistently generated diffuse TAI within the optic nerve that could easily be followed in the organized YFP positive fibers. We demonstrated progressive axonal swelling, …

Pediatric Spasticity, Kavita Parikh, Olga Morozova, Melanie Anspacher, Neha Shah

Pediatrics Posters and Presentations

No abstract provided.

Pediatric Spasticity, Kavita Parikh, Olga Morozova, Melanie Anspacher, Neha Shah

E-Learning Modules

Children with special health care needs (CSHCN) are increasingly prevalent in US hospitals. The pediatric hospitalist is often the primary provider of inpatient care for these patients. However, exposure to this patient population during training varies from provider to provider. No published educational curricula are specific to the inpatient care of this population. The purpose of this project is to build a multi-modal educational curriculum for providers with the overall goal of improving inpatient care for this at-risk population.

This curriculum is primarily composed of a series of topic-specific learning modules. Asynchronous learning modules, utilized appropriately, can augment learning by …

Heart Failure Transition Of Care Program: The Pharmacist’S Role In Reducing Readmissions, Joseph Favatella, Pharmd Candidate 2013, Joanne Heil, Pharmd, Bcps

College of Pharmacy Faculty Papers

Presented at: ASHP Mid-Year Clinical Meeting in Las Vegas.

Introduction & Background

Current Trends¹

•Approximately 19.6% of Medicare patients are readmitted to the hospital within 30 days

•These readmissions accounted for $15 billion of Medicare spending in 2009

Changes Coming

•As part of the Affordable Care Act, Medicare will not be reimbursing hospitals for patients readmitted within 30 days of discharge

•Hospitals have already begun improving discharge protocols to provide a greater continuity of care and minimize the financial loss of future readmissions

A Model²

•Boston University Medical Center's Re-Engineered Discharge (RED) was the first program to improve …

The Use Of Glucarpidase In An Open-Label Treatment Protocol As Adjunctive Treatment For A Patient With Delayed Methotrexate Elimination, Cheryl A. Abbas, Pharmd, Anne Marie Valorie-Oberle, Bs, Pharmd, Bcop

College of Pharmacy Faculty Papers

Presented at: ASHP Clinical MidYear Meeting in Las Vegas.

Background

Methotrexate (MTX)

• Cytotoxic agent that competitively inhibits dihydrofolate reductase (DHFR), the intracellular enzyme responsible for converting folic acid to reduced folate inhibitors, necessary for DNA synthesis
• Used since 1948 in the treatment of various malignancies and as a disease-modifying agent in rheumatoid arthritis and psoriasis
• High-dose mexthotrexate (HDMTX) began in 1960s solely or in combination with other chemotherapeutic agents

Methotrexate Toxicity

• Almost exclusively cleared through the kidneys
  • Precipitation of drug occurs in the renal tubules
  • Prolonged elevations of systemic MTX concentrations results in potential serious toxicity
• Increased use of HDMTX …

Medical School Watercooler Newsletter - December 2, 2012, Lindsey Lyle

Watercooler Newsletter

This is the December 2, 2012 edition of the Frederick P. Whiddon College of Medicine's newsletter - Watercooler.

Contents Include:

• USA Hospitals Host Tree Lighting Ceremonies
• Med School Café - Expert Advice for the Community
• USA Awarded NIH Grant To Address Health Disparities
• This Week's DSS - Dr. David Lefer

Using Systematic And Engaging Early Literacy Instruction And Digital Books To Teach At-Risk Kindergarteners To Read Target Words, Audra Marie Hales

Theses and Dissertations

The purpose of this study was to examine the effects of using Systematic and Engaging Early Literacy (SEEL) intervention activities that incorporate digital books to teach kindergarteners to read. The study used a single-subject-multiple-baseline-across-behaviors design to compare kindergarten students' reading of comparable CVC words before and after intervention. Four students at-risk for reading difficulties were chosen for the study based on their performance on assessments and their teachers' recommendations. Students were divided into two dyads and received intervention three times a week for 25 minutes for approximately six weeks, or 18 total sessions. Baseline assessment data was collected prior to …

An Opportunity For Diagonal Development In Global Surgery: Cleft Lip And Palate Care In Resource-Limited Settings, Christopher D. Hughes

Articles - Patient Care

Global cleft surgery missions have provided much-needed care to millions of poor patients worldwide. Still, surgical capacity in low- and middle-income countries is generally inadequate. Through surgical missions, global cleft care has largely ascribed to a vertical model of healthcare delivery, which is disease specific, and tends to deliver services parallel to, but not necessarily within, the local healthcare system. The vertical model has been used to address infectious diseases as well as humanitarian emergencies. By contrast, a horizontal model for healthcare delivery tends to focus on long-term investments in public health infrastructure and human capital and has less often …

Lc-Ms/Ms Identification Of A Bromelain Peptide Biomarker From Ananas Comosus Merr, Eric R. Secor, Steven M. Szczepanek, Linda Guernsey, Prabitha Natarajan, Karim Rezaul, David K. Han, Roger S. Thrall, Lawrence K. Silbart

UCHC Articles - Research

Bromelain (Br) is a cysteine peptidase (GenBank AEH26024.1) from pineapple, with over 40 years of clinical use. The constituents mediating its anti-inflammatory activity are not thoroughly characterized and no peptide biomarker exists. Our objective is to characterize Br raw material and identify peptides in the plasma of Br treated mice. After SDS-PAGE in-gel digestion, Br (VN#3507; Middletown, CT, USA) peptides were analyzed via LC/MS/MS using 95% protein probability, 95% peptide probability, and a minimum peptide number = 5. Br spiked mouse plasma (1 ug/ul) and plasma from i.p. treated mice (12 mg/kg) were assessed using SRM. In Br raw material, …

Bone-Specific Overexpression Of Npy Modulates Osteogenesis, I Matic, B G. Matthews, T Kizivat, J C. Igwe, D J. Adams, Ivo Kalajzic

UCHC Articles - Research

Objectives

Neuropeptide Y (NPY) is a peptide involved in the regulation of appetite and energy homeostasis. Genetic data indicates that NPY decreases bone formation via central and peripheral activities. NPY is produced by various cell types including osteocytes and osteoblasts and there is evidence suggesting that peripheral NPY is important for regulation of bone formation. We sought to investigate the role of bone-derived NPY in bone metabolism.

Methods

We generated a mouse where NPY was over-expressed specifically in mature osteoblasts and osteocytes (Col2.3NPY) and characterized the bone phenotype of these mice in vivo and in vitro.

Results

Trabecular and cortical …

Distinct Mechanisms Mediate Naïve And Memory Cd8 T-Cell Tolerance, Evan R. Jellison, Elizabeth G. Lingenheld, Li Zu, Lynn Puddington, Leo Lefrancois

UCHC Articles - Research

Peripheral tolerance to developmentally regulated antigens is necessary to sustain tissue homeostasis. We have now devised an inducible and reversible system that allows interrogation of T-cell tolerance induction in endogenous naïve and memory CD8 T cells. Our data show that peripheral CD8 T-cell tolerance can be preserved through two distinct mechanisms, antigen addiction leading to anergy for naïve T cells and ignorance for memory T cells. Induction of antigen in dendritic cells resulted in substantial expansion and maintenance of endogenous antigen-specific CD8 T cells. The self-reactive cells initially exhibited effector activity but eventually became unresponsive. Upon antigen removal, the antigen-specific …

Moving Toward Leadership: A Case Study Of Latina Adolescents And Effective Communication, Isela Estrada

Creative Arts Therapies Theses

The problem addressed in this study is the need for Latina adolescents to develop effective communication and leadership skills that will support their success in U.S. culture and society. This thesis is a case study of two Mexican-American adolescents who participated in a twelve-session leadership program at a dance studio. The goal of the study was to test the effectiveness of Rena Kornblum’s (2002) Disarming the Playground curriculum as a social skills program to improve leadership, effective communication skills, and group cohesion. This study included video footage of the adolescents engaging in movement-based role-play scenarios, which was examined using qualitative …

Mindful Bodies: The Use Of Guided Meditation With Dance/Movement Therapy In Addiction Treatment, Melissa A. Sanchez

Creative Arts Therapies Theses

Body-based approaches, such as dance/movement therapy (DMT), in addiction treatment can be anxiety provoking for those seeking sobriety. Strengthening the relationship between therapist and client using compassionate methods, such as guided meditation, prior to DMT sessions has, in the experience of this researcher, helped establish a safe environment in which to experience DMT. Using guided meditation as a method of creating comfort within the body aided in achieving the goal of enhancing one’s awareness of emotions, thoughts and sensations through the use of body-based methods.

Increasing self-awareness of emotions and physical sensations is an important step on the road to …

Doing It Alone: Supporting A Single Mother Through Authentic Movement (An Artistic Inquiry), Lucrecia Platt

Creative Arts Therapies Theses

The purpose of this study was to take an in-depth look at the human experience of single motherhood and how authentic movement, a body based movement practice used in dance/movement therapy, can play a role in supporting one single mother cope and navigate through mental, emotional, and physical struggles. This study documented my experience, illuminating the relationship between single motherhood and authentic movement. Heuristic methodology was used to collect data and took the form of personal journals. This data documented my authentic movement experience.

The creative process method of artistic inquiry was then used to help further analyze my experience …