Medicine and Health Sciences Commons^™

Acrolein Induces Endoplasmic Reticulum Stress And Causes Airspace Enlargement, Yoshiaki Kitaguchi, Laimute Taraseviciene-Stewart, Masayuki Hanaoka, Ramesh Natarajan, Donatas Kraskauskas, Norbert F. Voelkel

Internal Medicine Publications

Background

Given the relative abundance and toxic potential of acrolein in inhaled cigarette smoke, it is surprising how little is known about the pulmonary and systemic effects of acrolein. Here we test the hypothesis whether systemic administration of acrolein could cause endoplasmic reticulum (ER) stress, and lung cell apoptosis, leading to the enlargement of the alveolar air spaces in rats.

Methods

Acute and chronic effects of intraperitoneally administered acrolein were tested. Mean alveolar airspace area was measured by using light microscopy and imaging system software. TUNEL staining and immunohistochemistry (IHC) for active caspase 3 and Western blot analysis for active …

Copper Deficiency Induced Emphysema Is Associated With Focal Adhesion Kinase Inactivation, Shiro Mizuno, Masanori Yasuo, Harm J. Bogaard, Donatas Kraskauskas, Aysar A. Alhussini, Jose Gomez-Arroyo, Daniela Farkas, Laszlo Farkas, Norbert F. Voelkel

Internal Medicine Publications

Background

Copper is an important regulator of hypoxia inducible factor 1 alpha (HIF-1α) dependent vascular endothelial growth factor (VEGF) expression, and is also required for the activity of lysyl oxidase (LOX) to effect matrix protein cross-linking. Cell detachment from the extracellular matrix can induce apoptosis (anoikis) via inactivation of focal adhesion kinase (FAK).

Methodology

To examine the molecular mechanisms whereby copper depletion causes the destruction of the normal alveolar architecture via anoikis, Male Sprague-Dawley rats were fed a copper deficient diet for 6 weeks while being treated with the copper chelator, tetrathiomolybdate. Other groups of rats were treated with the …

Bevacizumab Added To Neoadjuvant Chemotherapy For Breast Cancer, Harry D. Bear, Gong Tang, Priya Rastogi, Charles E. Geyer Jr., Andre Robidoux, James N. Atkins, Luis Baez-Diaz, Adam M. Brufsky, Rita S. Mehta, Louis Fehrenbacher, James A. Young, Francis M. Senecal, Rakesh Gaur, Richard G. Margolese, Paul T. Adams, Howard M. Gross, Joseph P. Costantino, Sandra M. Swain, Eleftherios P. Mamounas, Norman Wolmark

Massey Comprehensive Cancer Center Publications

BACKGROUND

Bevacizumab and the antimetabolites capecitabine and gemcitabine have been shown to improve outcomes when added to taxanes in patients with metastatic breast cancer. The primary aims of this trial were to determine whether the addition of capecitabine or gemcitabine to neoadjuvant chemotherapy with docetaxel, followed by doxorubicin plus cyclophosphamide, would increase the rates of pathological complete response in the breast in women with operable, human epidermal growth factor receptor 2 (HER2)–negative breast cancer and whether adding bevacizumab to these chemotherapy regimens would increase the rates of pathological complete response.

METHODS

We randomly assigned 1206 patients to receive neoadjuvant therapy …

Variants Located Upstream Of Chrnb4 On Chromosome 15q25.1 Are Associated With Age At Onset Of Daily Smoking And Habitual Smoking, Manav Kapoor, Jen-Chyong Wang, Sarah Bertelsen, Kathy Bucholz, John P. Budde, Anthony Hinrichs, Arpana Agrawal, Andrew Brooks, David Chorlian, Danielle Dick, Victor Hesselbrock, Tatiana Foroud, John Kramer, Sammuel Kuperman, Niklas Manz, John Numberger Jr, Bernice Porjesz, John Rice, Jay Tischfield, Xiaoling Xuei, Marc Schuckit, Haward J. Edenberg, Laura J. Bierut, Alison M. Goate

Psychiatry Publications

Several genome-wide association and candidate gene studies have linked chromosome 15q24–q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking theCHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week) in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families. Subjects were …

Adenovirus-36 Is Associated With Obesity In Children And Adults In Sweden As Determined By Rapid Elisa, Malin Almgren, Richard Atkinson, Jia He, Agenta Hilding, Emilia Hagman, Alicia Wolk, Anders Thorell, Claude Marcus, Erik Naslund, Claes-Goren Ostenson, Martin Schalling, Catherina Lavebratt

Pathology Publications

Background

Experimental and natural human adenovirus-36 (Adv36) infection of multiple animal species results in obesity through increasing adipogenesis and lipid accumulation in adipocytes. Presence of Adv36 antibodies detected by serum neutralization assay has previously been associated with obesity in children and adults living in the USA, South Korea and Italy, whereas no association with adult obesity was detected in Belgium/the Netherlands nor among USA military personnel. Adv36 infection has also been shown to reduce blood lipid levels, increase glucose uptake by adipose tissue and skeletal muscle biopsies, and to associate with improved glycemic control in non-diabetic individuals.

Principal Findings

Using …

Fracture Detection In Traumatic Pelvic Ct Images, Jie Wu, Pavani Davuluri, Kevin R. Ward, Charles Cockrell, Rosalyn H. Hargraves, Kayvan Najarian

Computer Science Publications

Fracture detection in pelvic bones is vital for patient diagnostic decisions and treatment planning in traumatic pelvic injuries. Manual detection of bone fracture from computed tomography (CT) images is very challenging due to low resolution of the images and the complex pelvic structures. Automated fracture detection from segmented bones can significantly help physicians analyze pelvic CT images and detect the severity of injuries in a very short period. This paper presents an automated hierarchical algorithm for bone fracture detection in pelvic CT scans using adaptive windowing, boundary tracing, and wavelet transform while incorporating anatomical information. Fracture detection is performed on …

An Automated Optimal Engagement And Attention Detection System Using Electrocardiogram, Ashwin Belle, Rosalyn H. Hargraves, Kayvan Najarian

Computer Science Publications

This research proposes to develop a monitoring system which uses Electrocardiograph (ECG) as a fundamental physiological signal, to analyze and predict the presence or lack of cognitive attention in individuals during a task execution. The primary focus of this study is to identify the correlation between fluctuating level of attention and its implications on the cardiac rhythm recorded in the ECG. Furthermore, Electroencephalograph (EEG) signals are also analyzed and classified for use as a benchmark for comparison with ECG analysis. Several advanced signal processing techniques have been implemented and investigated to derive multiple clandestine and informative features from both these …

Antibiotic Prevention Of Acute Exacerbations Of Copd, Richard P. Wenzel, Alpha A. Fowler, Michael B. Edmond

VCU Health Publications

An estimated 24 million persons in the United States have COPD on the basis of lung-function testing.1 Globally, COPD is the fourth leading cause of death,2 and in the United States it is the third most common cause of death and chronic complications.3 The average person with COPD has one to two acute exacerbations each year, with wide variation from patient to patient.4 In 2000 in the United States, 726,000 patients were hospitalized with acute exacerbations of COPD.1 During an acute exacerbation, antibiotics are generally administered for 5 to 10 days,5 creating a national burden of 120 million to 480 …

Cardiorespiratory Fitness, Alcohol Intake, And Metabolic Syndrome Incidence In Men, Kerem Shuval, Carrie E. Finley, Karen G. Chartier, Bijal A. Balasubramanian, Kelley Pettee Gabriel, Carolyn E. Barlow

Social Work Publications

Purpose

To prospectively examine the independent and joint effects of alcohol consumption and cardiorespiratory fitness on the incidence of metabolic syndrome in a cohort of men.

Methods

A prospective examination of 3,411 apparently healthy men at baseline, who came to the Cooper Clinic (Dallas, Texas) for at least 2 preventive visits (1979–2010). Primary exposure variables were cardiorespiratory fitness and alcohol intake; the outcome measure was metabolic syndrome (MetS) and the components thereof. Cox proportional hazard models were computed to assess the relationship between the exposure variables and the incidence of MetS while adjusting for confounders.

Results

Over a mean follow-up …

Lipid Environment Modulates The Development Of Acute Tolerance To Ethanol In Caenorhabditis Elegans, Jill C. Bettinger, Kapo Leung, Mia H. Bolling, Andrew D. Goldsmith, Andrew G. Davies

Pharmacology and Toxicology Publications

The development of tolerance to a drug at the level of the neuron reflects a homeostatic mechanism by which neurons respond to perturbations of their function by external stimuli. Acute functional tolerance (AFT) to ethanol is a fast compensatory response that develops within a single drug session and normalizes neuronal function despite the continued presence of the drug. We performed a genetic screen to identify genes required for the development of acute functional tolerance to ethanol in the nematode C. elegans. We identified mutations affecting multiple genes in a genetic pathway known to regulate levels of triacylglycerols (TAGs) via …

Morphine Decreases Enteric Neuron Excitability Via Inhibition Of Sodium Channels, Tricia H. Smith, John R. Grider, William L. Dewey, Hamid I. Akbarali

Pharmacology and Toxicology Publications

Gastrointestinal peristalsis is significantly dependent on the enteric nervous system. Constipation due to reduced peristalsis is a major side-effect of morphine, which limits the chronic usefulness of this excellent pain reliever in man. The ionic basis for the inhibition of enteric neuron excitability by morphine is not well characterized as previous studies have mainly utilized microelectrode recordings from whole mount myenteric plexus preparations in guinea pigs. Here we have developed a Swiss-Webster mouse myenteric neuron culture and examined their electrophysiological properties by patch-clamp techniques and determined the mechanism for morphine-induced decrease in neuronal excitability. Isolated neurons in culture were confirmed …

Is Aging A Disability?, Edward F. Ansello

Director's Editorials from Age in Action

Growing older is not predictable decline, and the overwhelming majority age without acquiring disabilities. Because age does not equal disability, the Virginia Commission on Government Reform and Restructuring should not fold the Virginia Department of the Aging, the Department of Rehabilitative Services, and the Department for the Deaf and Hard of Hearing into one agency.

All The World's A Stage, Edward F. Ansello

Director's Editorials from Age in Action

Population aging is occurring worldwide because of success in attacking causes of infant mortality, improved public hygiene, and falling fertility rates; health care in later life itself has had only marginal impact in the numbers. Societies should appreciate the differences associated with being older but also deem to later life the value and protections given to other ages.

Walkability, Edward F. Ansello

Director's Editorials from Age in Action

A starting point for assessing how friendly or livable a community is, is to consider its walkability. Walkability has different dimensions, for it implies not only that there be amenities in the community to which one would want to go, but also that one can move about safely; that the person motivated would have the health status or needed support to move about; that there would be means of transportation within and outside of the community, such as public transportation and taxis.

We Are Family: When Elder Abuse, Neglect, And Financial Exploitation Hit Home, Jeannie J. Beidler

Case Studies from Age in Action

Educational Objectives

1. To describe a case, from discovery to prosecution, of familial abuse, neglect, and financial exploitation.

2. To demonstrate gaps in elder care policy.

3. To share my experience in order to help protect the vulnerable older adults.

The Fairfax County Hoarding Task Force, Michael Congleton

Case Studies from Age in Action

Educational Objectives

1. Describe the reasons for forming the Fairfax County Hoarding Task Force.

2. Explain the organizational makeup of the Hoarding Task Force.

3. Understand the risk factors in hoarding and what is being done to address them.

Hoarding Behavior In The Elderly, Henriette Kellum

Case Studies from Age in Action

Educational Objectives

1. Identify the medical and mental health factors that contribute to hoarding behavior.

2. Describe the unique aspects of hoarding in the elderly.

3. Examine intervention and treatment strategies.

Arthritis And Physical Activity In Mid- And Later-Life, Nicholas Turkas

Case Studies from Age in Action

Educational Objectives

1. Describe some of the more common types of arthritic conditions.

2. Discuss co-morbidities or coexisting conditions often occurring with arthritis.

3. Describe the Arthritis Foundation as a relevant resource when dealing with arthritic conditions.

Otx But Not Mitf Transcription Factors Are Required For Zebrafish Retinal Pigment Epithelium Development, Brandon M. Lane, James A. Lister

Human and Molecular Genetics Publications

Otx and Mitf transcription factors have been implicated in the development of the retinal pigmented epithelium (RPE), but the relationship between these factors and their specific roles in the development of the RPE have not been fully defined. The role of the three Otx transcription factors (Otx1a, Otx1b, and Otx2) and two Mitf transcription factors (Mitfa and Mitfb) in the development of the zebrafish RPE was explored in these experiments. The loss of Otx activity through morpholino knockdown produced variable eye defects, ranging from delayed RPE pigmentation to severe coloboma, depending on the combination of Otx factors that were targeted. …

A First-Generation Multi-Functional Cytokine For Simultaneous Optical Tracking And Tumor Therapy, Shawn Hingtgen, Randa Kasmieh, Elizabeth Elbayly, Irina Nesterenko, Jose-Luiz Figueiredo, Rupesh Dash, Devanand Sarkar, David Hall, Dima Kozakov, Sandor Vajda, Paul B. Fisher, Khalid Shah

Human and Molecular Genetics Publications

Creating new molecules that simultaneously enhance tumor cell killing and permit diagnostic tracking is vital to overcoming the limitations rendering current therapeutic regimens for terminal cancers ineffective. Accordingly, we investigated the efficacy of an innovative new multi-functional targeted anti-cancer molecule, SM7L, using models of the lethal brain tumor Glioblastoma multiforme (GBM). Designed using predictive computer modeling, SM7L incorporates the therapeutic activity of the promising anti-tumor cytokine MDA-7/IL-24, an enhanced secretory domain, and diagnostic domain for non-invasive tracking. In vitro assays revealed the diagnostic domain of SM7L produced robust photon emission, while the therapeutic domain showed marked anti-tumor efficacy and significant …

Genetic Dissection Of Acute Ethanol Responsive Gene Networks In Prefrontal Cortex: Functional And Mechanistic Implications, Aaron R. Wolen, Charles A. Phillips, Michael A. Langston, Alex H. Putman, Paul J. Vorster, Nathan A. Bruce, Timothy P. York, Robert W. Williams, Michael F. Miles

Human and Molecular Genetics Publications

Background

Individual differences in initial sensitivity to ethanol are strongly related to the heritable risk of alcoholism in humans. To elucidate key molecular networks that modulate ethanol sensitivity we performed the first systems genetics analysis of ethanol-responsive gene expression in brain regions of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens, and ventral midbrain) across a highly diverse family of 27 isogenic mouse strains (BXD panel) before and after treatment with ethanol.

Results

Acute ethanol altered the expression of ~2,750 genes in one or more regions and 400 transcripts were jointly modulated in all three. Ethanol-responsive gene networks were extracted …

A Duplication Cnv That Conveys Traits Reciprocal To Metabolic Syndrome And Protects Against Diet-Induced Obesity In Mice And Men, Melanie Lacaria, Pradip Saha, Lorraine Potocki, Weimin Bi, Jiong Yan, Santhosh Girirajan, Brooke Burns, Sarah H. Elsea, Katherina Walz, Lawrence Chan, James R. Lupski, Wenli Gu

Human and Molecular Genetics Publications

The functional contribution of CNV to human biology and disease pathophysiology has undergone limited exploration. Recent observations in humans indicate a tentative link between CNV and weight regulation. Smith-Magenis syndrome (SMS), manifesting obesity and hypercholesterolemia, results from a deletion CNV at 17p11.2, but is sometimes due to haploinsufficiency of a single gene, RAI1. The reciprocal duplication in 17p11.2 causes Potocki-Lupski syndrome (PTLS). We previously constructed mouse strains with a deletion,Df(11)17, or duplication, Dp(11)17, of the mouse genomic interval syntenic to the SMS/PTLS region. We demonstrate that Dp(11)17 is obesity-opposing; it conveys a highly penetrant, strain-independent phenotype …

An Automated Method For Analysis Of Microcirculation Videos For Accurate Assessment Of Tissue Perfusion, Kayvan Najarian

Electrical and Computer Engineering Publications

Background

Imaging of the human microcirculation in real-time has the potential to detect injuries and illnesses that disturb the microcirculation at earlier stages and may improve the efficacy of resuscitation. Despite advanced imaging techniques to monitor the microcirculation, there are currently no tools for the near real-time analysis of the videos produced by these imaging systems. An automated system tool that can extract microvasculature information and monitor changes in tissue perfusion quantitatively might be invaluable as a diagnostic and therapeutic endpoint for resuscitation.

Methods

The experimental algorithm automatically extracts microvascular network and quantitatively measures changes in the microcirculation. There are …

Racial Differences In Symptom Management Approaches Among Persons With Radiographic Knee Osteoarthritis, Shibing Yang, Rachel Jawahar, Timothy Mcalindon, Charles B. Eaton, Kate L. Lapane

Family Medicine and Population Health Publications

Background

The extent to which racial differences exist in use of treatments for osteoarthritis (OA) is debatable. The purpose of this study was to describe the differences between African Americans (AA) and Caucasian Americans (CA) in using treatment approaches to manage symptoms among individuals with radiographic-confirmed knee OA.

Methods

A cross-sectional study was conducted. Using data from the Osteoarthritis Initiative, we identified 508 AA and 2,075 CA with radiographic tibiofemoral OA in at least one knee. Trained interviewers asked questions relating to current OA treatments including seven CAM therapy categories—alternative medical systems, mind-body interventions, manipulation and body-based methods, energy therapies, …

Developing Clinical Practice Guidelines: Reviewing, Reporting, And Publishing Guidelines; Updating Guidelines; And The Emerging Issues Of Enhancing Guideline Implementability And Accounting For Comorbid Conditions In Guideline Development, Paul Shekelle, Steven H. Woolf, Jeremy M. Grimshaw, Holger J. Schünemann, Martin P. Eccles

Family Medicine and Population Health Publications

Clinical practice guidelines are one of the foundations of efforts to improve health care. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearing houses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this third paper we discuss the …

Developing Clinical Practice Guidelines: Target Audiences, Identifying Topics For Guidelines, Guideline Group Composition And Functioning And Conflicts Of Interest, Martin P. Eccles, Jeremy M. Grimshaw, Paul Shekelle, Holger J. Schünemann, Steven H. Woolf

Family Medicine and Population Health Publications

Clinical practice guidelines are one of the foundations of efforts to improve health care. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearing houses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this first paper we discuss: the …

Developing Clinical Practice Guidelines: Types Of Evidence And Outcomes; Values And Economics, Synthesis, Grading, And Presentation And Deriving Recommendations, Steven H. Woolf, Holger J. Schünemann, Martin P. Eccles, Jeremy M. Grimshaw, Paul Shekelle

Family Medicine and Population Health Publications

Clinical practice guidelines are one of the foundations of efforts to improve healthcare. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearinghouses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this second paper, we discuss issues of identifying …

Treatment For Schistosoma Japonicum, Reduction Of Intestinal Parasite Load, And Cognitive Test Score Improvements In School-Aged Children, Amara E. Ezeamama, Stephen T. Mcgarvey, Joseph Hogan, Kate L. Lapane, David C. Bellinger, Luz P. Acosta, Tjalling Leenstra, Remigio M. Olveda, Jonathan D. Kurtis, Jennifer F. Friedman

Family Medicine and Population Health Publications

Background

To determine whether treatment of intestinal parasitic infections improves cognitive function in school-aged children, we examined changes in cognitive testscores over 18 months in relation to: (i) treatment-related Schistosoma japonicum intensity decline, (ii) spontaneous reduction of single soil-transmitted helminth (STH) species, and (iii) ≥2 STH infections among 253 S. japonicum-infected children.

Methodology

Helminth infections were assessed at baseline and quarterly by the Kato-Katz method. S. japonicum infection was treated at baseline using praziquantel. An intensity-based indicator of lower vs. no change/higher infection was defined separately for each helminth species and joint intensity declines of ≥2 STH species. In …

Consumers’ Choice Of Dentists: How And Why People Choose Dental School Faculty Members As Their Oral Health Care Providers, M. Julie Kim, Peter C. Damiano, Jed Hand, Gerald E. Denehy, Deborah S. Cobb, Fang Qian

General Practice Publications

This study aimed to better understand how and why people choose dental school faculty members as their oral health care providers. Increasing financial constraints in U.S. dental schools have led their administrators to seek alternative funding sources, one of which can be revenues from dental school faculty practice. To effectively promote faculty practice, it is necessary to understand how and why one chooses a dental school faculty member as his or her oral health care provider. A survey of 1,150 dental school faculty practice patients who recently chose their dentist was conducted, and 221 responded. The information sources these respondents …

Immunotherapy Of Cancer: Reprogramming Tumor-Immune Crosstalk, Kyle K. Payne, Amir A. Toor, Xiang-Yang Wang, Masoud H. Manjili

Microbiology and Immunology Publications

The advancement of cancer immunotherapy faces barriers which limit its efficacy. These include weak immunogenicity of the tumor, as well as immunosuppressive mechanisms which prevent effective antitumor immune responses. Recent studies suggest that aberrant expression of cancer testis antigens (CTAs) can generate robust antitumor immune responses, which implicates CTAs as potential targets for immunotherapy. However, the heterogeneity of tumor cells in the presence and quantity of CTA expression results in tumor escape from CTA-specific immune responses. Thus, the ability to modulate the tumor cell epigenome to homogenously induce expression of such antigens will likely render the tumor more immunogenic. Additionally, …