Medicine and Health Sciences Commons^™

Psychoneuroimmunology-Based Stress Management During Adjuvant Chemotherapy For Early Breast Cancer, Jo Lynne W. Robins, Nancy L. Mccain, R. K. Elswick Jr., Jeanne M. Walter, D. Patricia Gray, Inez Tuck

School of Nursing Publications

Objective. In a randomized trial of women with early stage breast cancer undergoing adjuvant chemotherapy, two stress management interventions, tai chi training and spiritual growth groups, were compared to a usual care control group, to evaluate psychosocial functioning, quality of life (QOL), and biological markers thought to reflect cancer- and treatment-specific mechanisms. Method. The sample consisted of 145 women aged 27–75 years; 75% were Caucasian and 25% African American. A total of 109 participants completed the study, yielding a 75% retention rate. Grounded in a psychoneuroimmunology framework, the overarching hypothesis was that both interventions would reduce perceived stress, enhance QOL …

Control Group Design: Enhancing Rigor In Research Of Mind-Body Therapies For Depression, Patricia Anne Kinser, Jo Lynne W. Robins

School of Nursing Publications

Although a growing body of research suggests that mind-body therapies may be appropriate to integrate into the treatment of depression, studies consistently lack methodological sophistication particularly in the area of control groups. In order to better understand the relationship between control group selection and methodological rigor, we provide a brief review of the literature on control group design in yoga and tai chi studies for depression, and we discuss challenges we have faced in the design of control groups for our recent clinical trials of these mind-body complementary therapies for women with depression. To address the multiple challenges of research …

Epigenetic Alterations And An Increased Frequency Of Micronuclei In Women With Fibromyalgia, Victoria Menzies, Debra E. Lyon, Kellie J. Archer, Kimberly Jones, Guimin Gao, Timothy P. York, Colleen Jackson-Cook

School of Nursing Publications

Fibromyalgia (FM), characterized by chronic widespread pain, fatigue, and cognitive/mood disturbances, leads to reduced workplace productivity and increased healthcare expenses. To determine if acquired epigenetic/genetic changes are associated with FM, we compared the frequency of spontaneously occurring micronuclei (MN) and genome-wide methylation patterns in women with FM () to those seen in comparably aged healthy controls ( (MN); (methylation)). The mean (sd) MN frequency of women with FM (51.4 (21.9)) was significantly higher than that of controls (15.8 (8.5)) (; df = 1; ). Significant differences ( sites) in methylation patterns were observed between cases and controls considering a 5% …

Nosocomial Bloodstream Infections In Brazilian Pediatric Patients: Microbiology, Epidemiology, And Clinical Features, Carlos Albert Pires Pereira, Alexandre R. Marra, Luis Fernando A. Camargo, Antonio Carlos Campos Pignatari, Teresa Sukiennik, Paulo Renato Petersen Behar, Eduardo Alexandrino Servolo Medieros, Julival Ribeiro, Evelyne Girao, Luci Correa, Carla Guerra, Ima Cameiro, Carlos Brites, Marise Reis, Marta Antunes De Souza, Regina Tranchesi, Cristina U. Barata, Michael B. Edmond

Internal Medicine Publications

Background

Nosocomial bloodstream infections (nBSIs) are an important cause of morbidity and mortality and are the most frequent type of nosocomial infection in pediatric patients.

Methods

We identified the predominant pathogens and antimicrobial susceptibilities of nosocomial bloodstream isolates in pediatric patients (≤16 years of age) in the Brazilian Prospective Surveillance for nBSIs at 16 hospitals from 12 June 2007 to 31 March 2010 (Br SCOPE project).

Results

In our study a total of 2,563 cases of nBSI were reported by hospitals participating in the Br SCOPE project. Among these, 342 clinically significant episodes of BSI were identified in pediatric patients …

Fenretinide Causes Emphysema, Which Is Prevented By Sphingosine 1-Phoshate, Masanori Yasuo, Shiro Mizuno, Jeremy Allegood, Donatas Kraskauskas, Harm J. Bogaard, Sarah Spiegel, Norbert F. Voelkel

Internal Medicine Publications

Sphingolipids play a role in the development of emphysema and ceramide levels are increased in experimental models of emphysema; however, the mechanisms of ceramide-related pulmonary emphysema are not fully understood. Here we examine mechanisms of ceramide-induced pulmonary emphysema. Male Sprague-Dawley rats were treated with fenretinide (20 mg/kg BW), a synthetic derivative of retinoic acid that causes the formation of ceramide, and we postulated that the effects of fenretinide could be offset by administering sphingosine 1-phosphate (S1P) (100 µg/kg BW). Lung tissues were analyzed and mean alveolar airspace area, total length of the alveolar perimeter and the number of caspase-3 positive …

Multi-Snp Analysis Of Gwas Data Identifies Pathways Associated With Nonalcoholic Fatty Liver Disease, Qing-Rong Chen, Rosemary Braun, Ying Hu, Chunhua Yan, Elizabeth M. Brunt, Daoud Meerzaman, Arun J. Sanyal, Kenneth Buetow

Internal Medicine Publications

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease; the histological spectrum of which ranges from steatosis to steatohepatitis. Nonalcoholic steatohepatitis (NASH) often leads to cirrhosis and development of hepatocellular carcinoma. To better understand pathogenesis of NAFLD, we performed the pathway of distinction analysis (PoDA) on a genome-wide association study dataset of 250 non-Hispanic white female adult patients with NAFLD, who were enrolled in the NASH Clinical Research Network (CRN) Database Study, to investigate whether biologic process variation measured through genomic variation of genes within these pathways was related to the development of steatohepatitis or cirrhosis. Pathways such as …

Modulation Of The Metabiome By Rifaximin In Patients With Cirrhosis And Minimal Hepatic Encephalopathy, Jasmohan S. Bajaj, Douglas M. Heuman, Arun J. Sanyal, Phillip B. Hylemon, Richard K. Sterling, R. Todd Stravitz, Michael Fuchs, Jason M. Ridlon, Kalyani Daita, Pamela Monteith, Nicole A. Noble, Melanie B. White, Andmorgan Fisher, Masoumeh Sikaroodi, Huzefa Rangwala, Patrick M. Gillevet

Internal Medicine Publications

Hepatic encephalopathy (HE) represents a dysfunctional gut-liver-brain axis in cirrhosis which can negatively impact outcomes. This altered gut-brain relationship has been treated using gut-selective antibiotics such as rifaximin, that improve cognitive function in HE, especially its subclinical form, minimal HE (MHE). However, the precise mechanism of the action of rifaximin in MHE is unclear. We hypothesized that modulation of gut microbiota and their end-products by rifaximin would affect the gut-brain axis and improve cognitive performance in cirrhosis. Aim To perform a systems biology analysis of the microbiome, metabolome and cognitive change after rifaximin in MHE.

Methods

Twenty cirrhotics with MHE …

Peripheral Blood Mononuclear Cells Of Breast Cancer Patients Can Be Reprogrammed To Enhance Anti-Her-2/Neu Reactivity And Overcome Myeloid-Derived Suppressor Cells [Poster Abstract], Kyle K. Payne, Christine K. Zoon, Wen Wan, Khin Marlar, Rebecca C. Keim, Mehrab Nasirir Kenari, Latif Kazim, Harry D. Bear, Masoud H. Manjili

Massey Comprehensive Cancer Center Publications

Barriers limiting the efficacy of adoptive cellular therapy (ACT) for breast cancer patients include immune suppression mediated by myeloid-derived suppressor cells (MDSC) and a low frequency of tumor-reactive memory T cells (Tm). Recently, we developed an ex vivo protocol to reprogram tumor-reactive murine splenocytes; these cells were found to be resistant to MDSC suppression and protected FVBN202 mice from tumor challenge. Here, we evaluated the clinical applicability of reprogramming tumor-sensitized PBMCs isolated from patients with early stage breast cancer by treatment with bryostatin 1 and ionomycin (B/I) combined with IL-2, IL-7 and IL-15. Our data demonstrate that reprogrammed cells are …

Development, Disease, And Regeneration Of Tissues In The Dental-Craniofacial Complex, Brian L. Foster, Yong-Hee P. Chun, Erica L. Scheller, Zhao Lin, Chad M. Novince, Avina Paranjpe

Periodontics Publications

This article has no abstract.

Igfbp-3 Inhibits Cytokine-Induced Insulin Resistance And Early Manifestations Of Atherosclerosis, Lathika Mohanraj, Ho-Seong Kim, Wei Li, Qing Cai, Ki E. Kim, Hye-Jung Shin, Yong-Jae Lee, Woo J. Lee, Jung H. Kim, Youngman Oh

Pathology Publications

Metabolic syndrome is associated with visceral obesity, insulin resistance and an increased risk of cardiovascular diseases. Visceral fat tissue primarily consists of adipocytes that secrete cytokines leading to a state of systemic inflammation in obese conditions. One of the IGF-independent functions of IGFBP-3 is its role as an anti-inflammatory molecule. Our study in obese adolescents show a decrease in total IGFBP-3 levels and increase in proteolyzed IGFBP-3 in circulation when compared to their normal counterparts and establishes a positive correlation between IGFBP-3 proteolysis and adiposity parameters as well as insulin resistance. In human adipocytes, we show that IGFBP-3 inhibits TNF-α-induced …

Biomedical Informatics For Computer-Aided Decision Support Systems: A Survey, Ashwin Belle, Mark A. Kon, Kayvan Najarian

Computer Science Publications

The volumes of current patient data as well as their complexity make clinical decision making more challenging than ever for physicians and other care givers. This situation calls for the use of biomedical informatics methods to process data and form recommendations and/or predictions to assist such decision makers. The design, implementation, and use of biomedical informatics systems in the form of computer-aided decision support have become essential and widely used over the last two decades. This paper provides a brief review of such systems, their application protocols and methodologies, and the future challenges and directions they suggest.

An Entropy-Based Automated Cell Nuclei Segmentation And Quantification: Application In Analysis Of Wound Healing Process, Varun Oswal, Ashwin Belle, Robert Diegelmann, Kayvan Najarian

Computer Science Publications

The segmentation and quantification of cell nuclei are two very significant tasks in the analysis of histological images. Accurate results of cell nuclei segmentation are often adapted to a variety of applications such as the detection of cancerous cell nuclei and the observation of overlapping cellular events occurring during wound healing process in the human body. In this paper, an automated entropy-based thresholding system for segmentation and quantification of cell nuclei from histologically stained images has been presented. The proposed translational computation system aims to integrate clinical insight and computational analysis by identifying and segmenting objects of interest within histological …

Comparative Cardiac Toxicity Of Anthracyclines In Vitro And In Vivo In The Mouse, Stefano Toldo, Rachel W. Goehe, Marzia Lotrionte, Eleonora Mezzaroma, Evan T. Sumner, Giuseppe G. L. Biondi-Zoccai, Ignacio M. Seropian, Benjamin W. Van Tassell, Francesco Loperfido, Giovanni Palazzoni, Norbert F. Voelkel, Antonio Abbate, David A. Gewirtz

VCU Health Publications

Purpose

The antineoplastic efficacy of anthracyclines is limited by their cardiac toxicity. In this study, we evaluated the toxicity of doxorubicin, non-pegylated liposomal-delivered doxorubicin, and epirubicin in HL-1 adult cardiomyocytes in culture as well as in the mouse in vivo.

Methods

The cardiomyocytes were incubated with the three anthracyclines (1 µM) to assess reactive oxygen generation, DNA damage and apoptotic cell death. CF-1 mice (10/group) received doxorubicin, epirubicin or non-pegylated liposomal-doxorubicin (10 mg/kg) and cardiac function was monitored by Doppler echocardiography to measure left ventricular ejection fraction (LVEF), heart rate (HR) and cardiac output (CO) both prior to and …

Intracellular Function Of Interleukin-1 Receptor Antagonist In Ischemic Cardiomyocytes, Elena Vecile, Aldo Dobrina, Fadi N. Salloum, Benjamin W. Van Tassell, Antonella Falcione, Edorado Gustini, Samuele Secchiero, Sergio Crovella, Gianfranco Sinagra, Nicoletta Finato, Martin J. Nicklin, Antonio Abbate

VCU Health Publications

Background

Loss of cardiac myocytes due to apoptosis is a relevant feature of ischemic heart disease. It has been described in infarct and peri-infarct regions of the myocardium in coronary syndromes and in ischemia-linked heart remodeling. Previous studies have provided protection against ischemia-induced cardiomyocyte apoptosis by the anti-inflammatory cytokine interleukin-1 receptor-antagonist (IL-1Ra). Mitochondria triggering of caspases plays a central role in ischemia-induced apoptosis. We examined the production of IL-1Ra in the ischemic heart and, based on dual intra/extracellular function of some other interleukins, we hypothesized that IL-1Ra may also directly inhibit mitochondria-activated caspases and cardiomyocyte apoptosis.

Methodology/Principal Findings

Synthesis of …

Effect Of Daily Chlorhexidine Bathing On Hospital-Acquired Infection, Michael W. Climo, Edward S. Wong, Kakotan Sanogo, Deborah S. Yokoe, David K. Warren, Trish M. Perl, Maureen Bolon, Robert A. Weinstein, Loreen A. Herwaldt, Kent A. Sepkowitz, John A. Jernigan

VCU Health Publications

BACKGROUND

Results of previous single-center, observational studies suggest that daily bathing of patients with chlorhexidine may prevent hospital-acquired bloodstream infections and the acquisition of multidrug-resistant organisms (MDROs).

METHODS

We conducted a multicenter, cluster-randomized, nonblinded crossover trial to evaluate the effect of daily bathing with chlorhexidine-impregnated washcloths on the acquisition of MDROs and the incidence of hospital-acquired bloodstream infections. Nine intensive care and bone marrow transplantation units in six hospitals were randomly assigned to bathe patients either with no-rinse 2% chlorhexidine– impregnated washcloths or with nonantimicrobial washcloths for a 6-month period, exchanged for the alternate product during the subsequent 6 months. …

Dreams And Wonder, Edward F. Ansello

Director's Editorials from Age in Action

Many centenarians have dreams and a sense of wonder. Many of the very old possess dreams that push or pull them; these seem to act as goals still ahead. Perhaps this orientation to a future impels their continuation.

Being In The Moment, Edward F. Ansello

Director's Editorials from Age in Action

There seems to be a disconnect between the moment in time and really experiencing it. In the past, if one were privileged to reach late life, one would take time to be in that moment, rather than trying to avoid it. This returns us to the observations of being in the moment and having the full experience of it. Reflection is a gift to be opened in late life.

Partnering, Edward F. Ansello

Director's Editorials from Age in Action

Collaborative partnering has been a core value of Virginia Center on Aging. Several members are partnering with institutions of higher education, public schools, community businesses, and talented instructors.

Lessons From A Sequoia Grove, Edward F. Ansello

Director's Editorials from Age in Action

Studies have identified loneliness as a predictor of declines in health and accelerated death. We are assisted by others to become autonomous. Autonomy is a product of an interdependent process. Assisting others to maintain or regain dignity is assisted autonomy in practice. It is community.

Medications As A Risk Factor In Falls By Older Adults With And Without Intellectual Disabilities, Patricia Slattum, Edward F. Ansello

Case Studies from Age in Action

Educational Objectives

1. Review common intrinsic and extrinsic risk factors for falls by older adults.

2. Compare risk factors for older adults with and without intellectual disabilities.

3. Focus on medications as a risk factor among a complexity of risk factors.

4. Suggest steps to improve appropriateness of medication regimens, as a step to help reduce risk for falls.

Virginia Post: Improving Patient- Physician Communication About End Of Life Care, Chris Pile, Laura Pole

Case Studies from Age in Action

Educational Objectives

1. Examine the complexities of medical decision-making at the end of life and the inadequacy of advance directives alone to affect care at the end of life.

2. Demonstrate how effective communication can facilitate medical decision-making and improve congruency between care received and patient goals, priorities, and values.

3. Discuss the National POLST Paradigm and the current status of POST in Virginia.

Falling Down: Assessing The Risk Of Falls In Older Adults, Steven Morrison

Case Studies from Age in Action

Educational Objectives

1. To provide an overview of the problems associated with falling in older adults.

2. To outline the strengths and weaknesses of the various screening tools used for effective evaluation of an individual’s fall risk.

3. To highlight the benefits of assessing physiological function when screening for falls risk.

Timeslips: Creativity For People With Dementia, Anne Davis Basting

Case Studies from Age in Action

Educational Objectives

1. Recognize the value of creative storytelling for people with dementia, with its shift in emphasis from memory to imagination.

2. Understand the impact of creative storytelling upon facilitators, storytellers, audiences, and readers.

3. Explore the potential mechanisms at work in creative storytelling.

Genetic, Maternal And Placental Factors In The Association Between Birth Weight And Physical Fitness: A Longitudinal Twin Study, Robert N. H. Touwaslagar, Marji Gielen, Grans E. S. Tan, Antonius L. M. Mulder, Williem J. M. Gerver, Luc J. Zimmermann, Alfons J. H. M. Houben, Maurice P. Zeegers, Catherine Derom, Robert Vlietinck, Hermine Maes, Coen D. A. Stehouwer, Martine Thomis

Human and Molecular Genetics Publications

Background

Adult cardiorespiratory fitness and muscle strength are related to all-cause and cardiovascular mortality. Both are possibly related to birth weight, but it is unclear what the importance is of genetic, maternal and placental factors in these associations.

Design

Peak oxygen uptake and measures of strength, flexibility and balance were obtained yearly during adolescence (10–18 years) in 114 twin pairs in the Leuven Longitudinal Twin Study. Their birth weights had been collected prospectively within the East Flanders Prospective Twin Survey.

Results

We identified linear associations between birth weight and adolescent vertical jump (b = 1.96 cm per kg birth weight, …

Increased Frequency Of Micronuclei In Adults With A History Of Childhood Sexual Abuse: A Discordant Monozygotic Twin Study, Timothy P. York, Jenni Brumelle, Jane Juusola, Kenneth S. Kendler, Lindon J. Eaves, Ananda B. Amstadler, Steven H. Aggen, Kimberly H. Jones, Andrea Ferreira-Gonzalez, Colleen Jackson-Cook

Human and Molecular Genetics Publications

Background

Childhood sexual abuse (CSA) is a traumatic life event associated with an increased lifetime risk for psychopathology/morbidity. The long-term biological consequences of CSA-elicited stress on chromosomal stability in adults are unknown. The primary aim of this study was to determine if the rate of acquired chromosomal changes, measured using the cytokinesis-block micronucleus assay on stimulated peripheral blood lymphocytes, differs in adult female monozygotic twins discordant for CSA.

Methods

Monozygotic twin pairs discordant for CSA were identified from a larger population-based sample of female adult twins for whom the experience of CSA was assessed by self-report (51 individuals including a …

The Role Of Tumor-Associated Macrophages In Tumor Vascularization, Chunqing Guo, Annicole Buranych, Devanand Sarkar, Paul B. Fisher, Xiang-Yang Wang

Human and Molecular Genetics Publications

Tumor vascularization is a highly complex process that involves the interaction between tumors and their surrounding stroma, as well as many distinct angiogenesis-regulating factors. Tumor associated macrophages (TAMs) represent one of the most abundant cell components in the tumor environment and key contributors to cancer-related inflammation. A large body of evidence supports the notion that TAMs play a critical role in promoting the formation of an abnormal tumor vascular network and subsequent tumor progression and invasion. Clinical and experimental evidence has shown that high levels of infiltrating TAMs are associated with poor patient prognosis and tumor resistance to therapies. In …

Rapid And Inexpensive Screening Of Genomic Copy Number Variations Using A Novel Quantitative Fluorescent Pcr Method, Martin Stofanko, Joan C. Han, Sarah H. Elsea, Heloísa B. Pena, Higgor Gonçalves-Dornelas, Sérgio Danilo Junho Pena

Human and Molecular Genetics Publications

Detection of human microdeletion and microduplication syndromes poses significant burden on public healthcare systems in developing countries. With genome-wide diagnostic assays frequently inaccessible, targeted low-cost PCR-based approaches are preferred. However, their reproducibility depends on equally efficient amplification using a number of target and control primers. To address this, the recently described technique called Microdeletion/Microduplication Quantitative Fluorescent PCR (MQF-PCR) was shown to reliably detect four human syndromes by quantifying DNA amplification in an internally controlled PCR reaction. Here, we confirm its utility in the detection of eight human microdeletion syndromes, including the more common WAGR, Smith-Magenis, and Potocki-Lupski syndromes with 100% …

Identification Of Genes Potentially Regulated By Human Polynucleotide Phosphorylase (Hpnpaseold-35) Using Melanoma As A Model, Upneet K. Sokhi, Manny D. Bacolod, Santanu Dasgupta, Luni Emdad, Swadesh K. Das

Human and Molecular Genetics Publications

Human Polynucleotide Phosphorylase (hPNPaseold-35 or PNPT1) is an evolutionarily conserved 3′→5′ exoribonuclease implicated in the regulation of numerous physiological processes including maintenance of mitochondrial homeostasis, mtRNA import and aging-associated inflammation. From an RNase perspective, little is known about the RNA or miRNA species it targets for degradation or whose expression it regulates; except for c-myc and miR-221. To further elucidate the functional implications of hPNPaseold-35 in cellular physiology, we knocked-down and overexpressed hPNPaseold-35 in human melanoma cells and performed gene expression analyses to identify differentially expressed transcripts. Ingenuity Pathway Analysis indicated that knockdown of hPNPaseold-35 resulted in significant …

The Krüppel-Like Factor 2 And Krüppel-Like Factor 4 Genes Interact To Maintain Endothelial Integrity In Mouse Embryonic Vasculogenesis, Aditi R. Chiplunkar, Benjamin C. Curtis, Gabriel L. Eades, Megan S. Kane, Sean J. Fox, Jack L. Haar, Joyce A. Lloyd

Human and Molecular Genetics Publications

Background Krüppel-like Factor 2 (KLF2) plays an important role in vessel maturation during embryonic development. In adult mice, KLF2 regulates expression of the tight junction protein occludin, which may allow KLF2 to maintain vascular integrity. Adult tamoxifen-inducible Krüppel-like Factor 4 (KLF4) knockout mice have thickened arterial intima following vascular injury. The role of KLF4, and the possible overlapping functions of KLF2 and KLF4, in the developing vasculature are not well-studied.

Results Endothelial breaks are observed in a major vessel, the primary head vein (PHV), in KLF2-/-KLF4-/- embryos at E9.5. KLF2-/-KLF4-/- embryos die by E10.5, which is earlier than either single …

Krüppel-Like Factor 2 Is Required For Normal Mouse Cardiac Development, Aditi R. Chiplunkar, Tina K. Lung, Yousef Alhashem, Benjamin A. Koppenhaver, Fadi N. Salloum, Rakesh C. Kukreja, Jack L. Haar, Joyce A. Lloyd

Human and Molecular Genetics Publications

Krüppel-like factor 2 (KLF2) is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV) canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure and death by mouse embryonic day 14.5 (E14.5) in a mixed genetic background. This work identifies an earlier and more fundamental role for KLF2 in mouse cardiac development in FVB/N mice. FVB/N KLF2−/− embryos die earlier, by E11.5. E9.5 FVB/N KLF2−/− hearts have multiple, disorganized cell layers lining the AV cushions, the primordia of the AV valves, rather than the normal single layer. By …