Medicine and Health Sciences Commons^™

Partition Decoupling For Multi-Gene Analysis Of Gene Expression Profiling Data, Rosemary Braun, Gregory Leibon, Scott Pauls, Daniel Rockmore

Dartmouth Scholarship

Background:

Multi-gene interactions likely play an important role in the development of complex phenotypes, and relationships between interacting genes pose a challenging statistical problem in microarray analysis, since the genes involved in these interactions may not exhibit marginal differential expression. As a result, it is necessary to develop tools that can identify sets of interacting genes that discriminate phenotypes without requiring that the classification boundary between phenotypes be convex.

Results:

We describe an extension and application of a new unsupervised statistical learning technique, known as the Partition Decoupling Method (PDM), to gene expression microarray data. This method may be used …

Prevalence And Risk Factors Of Major Depressive Disorder In Hiv/Aids As Seen In Semi-Urban Entebbe District, Uganda, Eugene Kinyanda, Susan Hoskins, Juliet Nakku, Saira Nawaz, Vikram Patel

Dartmouth Scholarship

Background:

Not much is known about the risk factors of major depressive disorder (MDD) in HIV/AIDS in the African socio-cultural context. Therefore a study was undertaken to examine the prevalence and risk factors of MDD in HIV/AIDS in semi-urban Uganda.

Methods:

A cross-sectional study was undertaken among 618 respondents attending two HIV clinics in Uganda.

Results:

Prevalence of MDD was 8.1%. Factors associated with MDD at univariate analysis only were female gender, family history of mental illness, negative coping style, alcohol dependency disorder, food insecurity and stress; not associated with MDD were social support, neurocognitive impairment, CD4 counts and BMI. …

Cd2ap Regulates Sumoylation Of Cin85 In Podocytes, Irini Tossidou, Rainer Niedenthal, Malte Klaus, Beina Teng, Kirstin Worthmann, Benjamin King, Kevin Peterson

Dartmouth Scholarship

Podocytes are highly differentiated and polarized epithelial cells located on the visceral side of the glomerulus. They form an indispensable component of the glomerular filter, the slit diaphragm, formed by several transmembrane proteins and adaptor molecules. Disruption of the slit diaphragm can lead to massive proteinuria and nephrotic syndrome in mice and humans. CD2AP is an adaptor protein that is important for the maintenance of the slit diaphragm. Together with its paralogue, CIN85, CD2AP belongs to a family of adaptor proteins that are primarily described as being involved in endocytosis and downregulation of receptor tyrosine kinase activity. We have shown …

A Shared Gene Expression Signature In Mouse Models Of Ebv-Associated And Non-Ebv-Associated Burkitt Lymphoma, Kathryn T. Bieging, Kamonwan Fish, Subbarao Bondada, Richard Longnecker

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The link between EBV infection and Burkitt lymphoma (BL) is strong, but the mechanism underlying that link has been elusive. We have developed a mouse model for EBV-associated BL in which LMP2A, an EBV latency protein, and MYC are expressed in B cells. Our model has demonstrated the ability of LMP2A to accelerate tumor onset, increase spleen size, and bypass p53 inactivation. Here we describe the results of total gene expression analysis of tumor and pretumor B cells from our transgenic mouse model. Although we see many phenotypic differences and changes in gene expression in pretumor B cells, the transcriptional …

Rice Consumption Contributes To Arsenic Exposure In Us Women, Diane Gilbert-Diamond, Kathryn L. Cottingham, Joann F. Gruber, Tracy Punshon, Vicki Sayarath, A. Jay Gandolfi, Emily R. Baker, Brian P. Jackson, Carol L. Folt, Margaret R. Karagas

Dartmouth Scholarship

Emerging data indicate that rice consumption may lead to potentially harmful arsenic exposure. However, few human data are available, and virtually none exist for vulnerable periods such as pregnancy. Here we document a positive association between rice consumption and urinary arsenic excretion, a biomarker of recent arsenic exposure, in 229 pregnant women. At a 6-mo prenatal visit, we collected a urine sample and 3-d dietary record for water, fish/seafood, and rice. We also tested women's home tap water for arsenic, which we combined with tap water consumption to estimate arsenic exposure through water. Women who reported rice intake (n …

Transdisciplinary Assignments In Graduate Health Education As A Model For Future Collaboration, Catherine Christie, A Russell Smith Jr., Michele Bednarzyk

Catherine Christie

Transdisciplinary health care continues to be at the forefront of patient treatment in the medical arena, in part due to escalating health care costs, an increasing aging population, and the development of multiple chronic diseases. Gaining the knowledge, experience, and principles associated with transdisciplinary teamwork to successfully prepare for modern-day practice is therefore essential for individuals of various health care professions. This report describes an assignment developed and implemented to facilitate professional interaction between graduate physical therapy, nutrition, and nursing students. The objectives of this assignment were to determine through student evaluation the effects of a transdisciplinary experience on students' …

Development Of An Evidence-Based Clinical Practice Guideline On Linear Growth Measurement Of Children, Jan Foote, L. Brady, A. Burke, J. Cook, M. Dutcher, K. Gradoville, J. Groos, K. Kinkade, R. Meeks, P. Mohr, D. Schultheis, B. S. Walker, K. Phillips

Jan M. Foote

Growth is an important indicator of child health; however, measurements are frequently inaccurate and unreliable. This article reviews the literature on linear growth measurement error and describes methods used to develop and evaluate an evidence-based clinical practice guideline on the measurement of recumbent length and stature of infants, children, and adolescents. Systematic methods were used to identify evidence to answer clinical questions about growth measurement. A multidisciplinary team critically appraised and synthesized the evidence to develop clinical practice recommendations using an evidence-based practice rating scheme. The guideline was prospectively evaluated through internal and external reviews and a pilot study to …

Pyloric Channel Stricture Secondary To High-Dose Ibuprofen Therapy In A Patient With Cystic Fibrosis, E. Bell, R. Grothe, V. Zivkovich, Jan Foote, J. Wellendorf

Jan M. Foote

OBJECTIVE: To describe a case of pyloric channel stricture secondary to high-dose ibuprofen therapy in a pediatric patient with cystic fibrosis. CASE SUMMARY: A 12-year-old white girl started taking high-dose ibuprofen to treat the pulmonary manifestations of cystic fibrosis. The peak plasma concentration at dose initiation was within the accepted therapeutic range. Approximately one month later, the patient developed emesis and intolerance of solid foods, which persisted for several months and resulted in a weight loss of seven kilograms. The patient was referred to a pediatric gastroenterologist, who performed an upper endoscopy and subsequently diagnosed a pyloric channel stricture. The …

Getting A Healthy Start. Feeding Issues In The First Year Of Life, Jan Foote

Jan M. Foote

No abstract provided.

Promoting Adherence And Retention To Clinical Trials In Special Populations: A Women's Health Initiative Workshop, Sara Wilcox, Sally Shumaker, Deborah Bowen, Michelle Naughton, Milagros Rosal, Shari Ludlam, Elizabeth Dugan, Julie Hunt, Stephanie Stevens

Elizabeth Dugan

This paper describes a Women's Health Initiative workshop on promoting adherence and retention in randomized clinical trials among ethnic minority women, participants of lower socioeconomic status, and older women. Workshop objectives were: (1) to increase knowledge of demographic and cultural characteristics of diverse groups, (2) to increase awareness of how diversity can affect interactions in clinical research, (3) to explore how research staff behavior can influence adherence and retention, and (4) to increase knowledge of strategies to enhance adherence and retention in special populations. The workshop emphasized the importance of understanding beliefs, values, and experiences that are common in diverse …

Development Of Abbreviated Measures To Assess Patient Trust In A Physician, A Health Insurer, And The Medical Profession, Elizabeth Dugan, Felicia Trachtenberg, Mark Hall

Elizabeth Dugan

BACKGROUND: Despite the recent proliferation in research on patient trust, it is seldom a primary outcome, and is often a peripheral area of interest. The length of our original scales to measure trust may limit their use because of the practical needs to minimize both respondent burden and research cost. The objective of this study was to develop three abbreviated scales to measure trust in: (1) a physician, (2) a health insurer, and (3) the medical profession. METHODS: Data from two samples were used. The first was a telephone survey of English-speaking adults in the United States (N = 1117) …

Patient Education About Anticoagulant Medication: Is Narrative Evidence Or Statistical Evidence More Effective?, Kathleen Mazor, Joann Baril, Elizabeth Dugan, Frederick Spencer, Pamela Burgwinkle, Jerry Gurwitz

Elizabeth Dugan

OBJECTIVE: To determine the relative impact of incorporating narrative evidence, statistical evidence or both into patient education about warfarin, a widely used oral anticoagulant medication.

METHODS: 600 patients receiving anticoagulant therapy were randomly assigned to view one of three versions of a video depicting a physician-patient encounter where anticoagulation treatment was discussed, or usual care (no video). The videos differed in whether the physician used narrative evidence (patient anecdotes), statistical evidence, or both to highlight key information. 317 patients completed both the baseline and post-test questionnaires. Questions assessed knowledge, beliefs and adherence to medication and laboratory monitoring regimens.

RESULTS: All …

Project P.A.T.H.S. In Hong Kong: New Curriculum In Response To Adolescent Developmental Issues, Hing Keung Ma, Daniel T. L. Shek, Joav Merrick

Pediatrics Faculty Publications

No abstract.

Histone Deacetylase Inhibitor Valproic Acid Suppresses The Growth And Increases The Androgen Responsiveness Of Prostate Cancer Cells., Yu-Wei Chou, Nagendra K. Chaturvedi, Shougiang Ouyang, Fen-Fen Lin, Dharam Kaushik, Jue Wang, Isaac Kim, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and methylation increased and cyclin proteins decreased. In PAcP shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C-81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments …

Effects Of Prenatal Food And Micronutrient Supplementation On Child Growth From Birth To 54 Months Of Age: A Randomized Trial In Bangladesh, Ashraful Islam Khan, Iqbal Kabir, Eva-Charlotte Ekström, Kajsa Åsling-Monemi, Dewan Shamsul Alam, Edward A. Frongillo Jr., Md Yunus, Shams Arifeen, Lars-Åke Persson

Faculty Publications

Background: There is a lack of information on the optimal timing of food supplementation to malnourished pregnant women and possible combined effects of food and multiple micronutrient supplementations (MMS) on their offspring's growth. We evaluated the effects of prenatal food and micronutrient interventions on postnatal child growth. The hypothesis was that prenatal MMS and early invitation to food supplementation would increase physical growth in the offspring during 0-54 months and a combination of these interventions would further improve these outcomes.

Methods: In the large, randomized MINIMat trial (Maternal and Infant Nutrition Interventions in Matlab), Bangladesh, 4436 pregnant women were enrolled …

Engaging Racial Autoethnography As A Teaching Tool For Womanist Inquiry, Janette Taylor, Melissa Lehan Mackin, A. Oldenburg

Melissa Lehan Mackin

Racial autobiography, self-narratives on how one learned about the idea of race, has been underutilized as a tool to familiarize and orient students in the process of critical inquiry for nursing research. The aims of this article are to explore how racial autoethnography: (1) repositions students to effect an epistemological change, (2) challenges dominant ideology, and (3) functions as a link between the student and critical theories for use in nursing research. Students engage in and share reflective narrative about a variety of instructional materials used in the course. Reflective narratives are presented in a framework that addresses white racial …

Fall Prevention Practices In Adult Medical-Surgical Nursing Units Described By Nurse Managers, L. Shever, M. Titler, Melissa Lehan Mackin, A. Kueny

Melissa Lehan Mackin

The purpose of this article was to describe nursing practices (e.g., assessment, interventions) around fall prevention, as perceived by nurse managers in adult, medical-surgical nursing units. One hundred forty nurse managers from 51 hospitals from across the United States participated. Descriptive frequencies are used to describe nurse manager responses. The most commonly used fall risk assessment tool was the Morse Fall Risk Assessment Tool (40%). The most common fall prevention interventions included bed alarms (90%), rounds (70%), sitters (68%), and relocating the patient closer to the nurses' station (56%). Twenty-nine percent of nurse managers identified physical restraints as an intervention …

The Evolution Of Cauterization: From The Hot Iron To The Bovie., Michelle F. Deleon, Ms, Charles J. Yeo, Md, Pinckney Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

The Bovie electrocautery has become a fundamental tool of modern-day surgery, particularly for its integral role in hemostasis, yet despite this landmark invention and its widespread use, there is very little said about the man behind the machine: William T. Bovie. It would be thousands of years from the inception of cautery in medicine until the birth of Dr. Bovie and his device. However, his work in biophysics and collaboration with Dr. Harvey Cushing would revolutionize surgical practice in the early 20th century and forever ingrain his name into the field of surgery.

The Burden Of Moderate-To-Heavy Soil-Transmitted Helminth Infections Among Rural Malaysian Aborigines: An Urgent Need For An Integrated Control Programme, Init Ithoi

Init Ithoi

Background: Soil-transmitted helminth (STH) infections, among the most common neglected tropical diseases, continue to be a major threat to the health and socioeconomic wellbeing of infected people especially children in developing countries. Methods: A cross-sectional study among 254 aboriginal schoolchildren was conducted in order to determine the current prevalence and intensity of infections and to investigate the potential risk factors associated with moderate-to-heavy burden of STH infections among these children. Results: Overall, 93.7% of children were found to be infected with one or more STH species. The prevalence of trichuriasis, ascariasis and hookworm infections were 84.6%, 47.6% and 3.9%, respectively. …

Widespread Regulation Of Mirna Biogenesis At The Dicer Step By The Cold-Inducible Rna-Binding Protein, Rbm3, Julie Pilotte, Esther E. Dupont-Versteegden, Peter W. Vanderklish

Physical Therapy Faculty Publications

MicroRNAs (miRNAs) play critical roles in diverse cellular events through their effects on translation. Emerging data suggest that modulation of miRNA biogenesis at post-transcriptional steps by RNA-binding proteins is a key point of regulatory control over the expression of some miRNAs and the cellular processes they influence. However, the extent and conditions under which the miRNA pathway is amenable to regulation at posttranscriptional steps are poorly understood. Here we show that RBM3, a cold-inducible, developmentally regulated RNA-binding protein and putative protooncogene, is an essential regulator of miRNA biogenesis. Utilizing miRNA array, Northern blot, and PCR methods, we observed that over …

Switches, Excitable Responses And Oscillations In The Ring1b/Bmi1 Ubiquitination System., Lan K Nguyen, Javier Muñoz-García, Helene Maccario, Aaron Ciechanover, Walter Kolch, Boris N Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches, overshoot transitions and self-perpetuating oscillations between its distinct ubiquitination and activity states. These different Ring1B states display canonical or multiply branched, atypical polyubiquitin chains and involve association with the Polycomb-group protein Bmi1. Bistable switches and oscillations may lead to all-or-none histone H2A monoubiquitination rates and result in discrete periods of gene (in)activity. Switches, overshoots …

Factors Affecting Growth In Infants With Single Ventricle Physiology: A Report From The Pediatric Heart Network Infant Single Ventricle Trial., Richard V. Williams, Victor Zak, Chitra Ravishankar, Karen Altmann, Jeffrey Anderson, Andrew M. Atz, Carolyn Dunbar-Masterson, Nancy Ghanayem, Linda Lambert, Karen Lurito, Barbara Medoff-Cooper, Renee Margossian, Victoria L. Pemberton, Jennifer Russell, Mario Stylianou, Daphne Hsu, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To describe growth patterns in infants with single ventricle physiology and determine factors influencing growth.

STUDY DESIGN: Data from 230 subjects enrolled in the Pediatric Heart Network Infant Single Ventricle Enalapril Trial were used to assess factors influencing change in weight-for-age z-score (z) from study enrollment (0.7 ± 0.4 months) to pre-superior cavopulmonary connection (SCPC; 5.1 ± 1.8 months, period 1) and pre-SCPC to final study visit (14.1 ± 0.9 months, period 2). Predictor variables included patient characteristics, feeding regimen, clinical center, and medical factors during neonatal (period 1) and SCPC hospitalizations (period 2). Univariate regression analysis was performed, …

B1b Lymphocyte-Derived Antibodies Control Borrelia Hermsii Independent Of Fcα/Μ Receptor And In The Absence Of Host Cell Contact., Matthew J. Colombo, David Abraham, Akira Shibuya, Kishore R. Alugupalli

Department of Microbiology and Immunology Faculty Papers

The critical role of IgM in controlling pathogen burden has been demonstrated in a variety of infection models. In the murine model of Borrelia hermsii infection, IgM is necessary and sufficient for the rapid clearance of bacteremia. Convalescent, but not naïve, B1b cells generate a specific IgM response against B. hermsii, but the mechanism of IgM-mediated protection is unknown. Here, we show that neither Fcα/μR, a high-affinity receptor for IgM, nor IgM-dependent complement activation is required for controlling B. hermsii. Bacteria in diffusion chambers with a pore size impermeable to cells were killed when diffusion chambers were implanted into either …

Relationship Between Vancomycin Trough Concentrations And Nephrotoxicity: A Prospective Multicenter Trial, John A. Bosso, Jean Nappi, Celeste Rudisill, Marlea Wellein, P Brandon Bookstaver, Jenna Swindler, Patrick D. Mauldin

Faculty Publications

Several single-center studies have suggested that higher doses of vancomycin, aimed at producing trough concentrations of >15 mg/liter, are associated with increased risk of nephrotoxicity. We prospectively assessed the relative incidence of nephrotoxicity in relation to trough concentration in patients with documented methicillin-resistant Staphylococcus aureus (MRSA) infections at seven hospitals throughout South Carolina. Adult patients receiving vancomycin for at least 72 h with at least one vancomycin trough concentration determined under steady-state conditions were prospectively studied. The relationship between vancomycin trough concentrations of >15 mg/ml and the occurrence of nephrotoxicity was assessed using univariate and multivariate analyses, controlling for age, …

Becoming A Registered Nurse: The Nurse Extern Experience, K. Starr, Virginia Conley

Virginia M. Conley

Little is known about the perceptions of nursing students externing in newly developed hospital-based programs that focus on socialization and transition to the registered nurse (RN) role rather than on institutional recruitment and retention goals. This qualitative study explored student nurse externs' expectations, experiences, and benefits of participation in a student-focused externship program. Externs wanted to gain experience with skills and learn what it was like to be an RN. Goals were met or exceeded by becoming comfortable in the externship role, growing in skill performance and confidence, and becoming members of the healthcare team. The experience fostered growth from …

Integrating Massage Into Rural Caregiving At End-Of-Life, Virginia Conley, D. Kempson

Virginia M. Conley

No abstract provided.

Informational Needs Of Caregivers Of Terminal Patients In A Rural State, Virginia Conley, M. Burman

Virginia M. Conley

Home care of a terminally ill family member is stressful, especially in rural areas. This qualitative study sought to determine informational needs of rural caregivers and how that information is obtained. Although most caregivers stated satisfaction with available information, mostly obtained from physicians and nurses, their behavior belied their satisfaction. Assertive and self-reliant, they used informal communications rather than written information to meet most of their needs. Approaches home care nurses can use to help caregivers obtain important information are presented.

National Health Policy Influence On Medicare Home Health, Virginia Conley, M. Walker

Virginia M. Conley

National health policy regulates the delivery of Medicare home health services. These services have grown exponentially over the past several years. Current challenges to service delivery revolve around attempts to contain costs while ensuring quality of and access to care. To meet these challenges, providers must be aware of the societal and ideological influences on national health policies that impact service delivery. This article uses Wong's model of the progression of health care reform to address past health policy influences on Medicare home health delivery, investigate recent sociological trends for relevance to health policy, and propose changes based on current …

Patient And Parent/Guardian Perspectives On The Health Care Of Adults With Mental Retardation, Sarah Voss Horrell, William Maclean, Virginia Conley

Virginia M. Conley

Individuals with mental retardation and their parents/guardians have long been neglected in health care research. In this study we used a qualitative methodology to describe the experiences adults with mental retardation and their parents/guardians have with the delivery of primary care services. Semi-structured in-depth interviews were conducted with 12 adults who had mental retardation and 9 parents/guardians. The grounded theory approach was utilized to guide data collection and analysis. Findings suggest an overall positive experience with primary care services. Unique themes were identified that distinguished parent/guardian experiences from those of adults with mental retardation, who focused on immediate, concrete issues …

Reconceptualizing The Core Of Nurse Practitioner Education And Practice, M. Burman, A. Hart, Virginia Conley, J. Brown, P. Sherard, P. Clarke

Virginia M. Conley

PURPOSE: The movement to the doctor of nursing practice (DNP) is progressing rapidly with new programs emerging and curricular documents being developed. We argue that the implementation of the DNP is a good move for nursing, provided that we use the opportunity to reconceptualize the core of advanced practice nursing, especially nurse practitioner (NP) practice. DATA SOURCES: Theory and research articles from nursing focused on advanced practice nursing, NPs, and doctoral education. CONCLUSIONS: The foundation of NP education is currently based essentially on borrowed or shared content in assessment, pharmacology, and pathophysiology. We argue that the heart and soul of …