Medicine and Health Sciences Commons^™

Acute Toxicity Testing Without Animals: More Scientific And Less Of A Gamble, Gillian R. Langley

Gill Langley, PhD

In this report, we argue specifically that acute toxicity data should not be sought from animal tests. The underlying principle of such tests on rats and mice is that the results can be effectively extrapolated to humans. In fact, after nearly 80 years of use of these tests, the predictivity of rodent data for human acute toxic effects has been disputed but never proven.

Gene Expression Profiling In Salmonella Choleraesuis-Infected Porcine Lung Using A Long Oligonucleotide Microarray, Shu-Hong Zhao, Daniel Kuhar, Joan K. Lunney, Harry Dawson, Catherine Guidry, Jolita J. Uthe, Shawn M. D. Bearson, Justin Recknor, Dan Nettleton, Christopher K. Tuggle

Dan Nettleton

Understanding the transcriptional response to pathogenic bacterial infection within food animals is of fundamental and applied interest. To determine the transcriptional response to Salmonella enterica serovar Choleraesuis (SC) infection, a 13,297-oligonucleotide swine array was used to analyze RNA from control, 24-h postinoculation (hpi), and 48-hpi porcine lung tissue from pigs infected with SC. In total, 57 genes showed differential expression (p < 0.001; false discovery rate = 12%). Quantitative real-time PCR (qRT-PCR) of 61 genes was used to confirm the microarray results and to identify pathways responding to infection. Of the 33 genes identified by microarray analysis as differentially expressed, 23 were confirmed by qRT-PCR results. A novel finding was that two transglutaminase family genes (TGM1 and TGM3) showed dramatic increases in expression postinoculation; combined with several other apoptotic genes, they indicated the induction of apoptotic pathways during SC infection. A predominant T helper 1-type immune response occurred during infection, with interferon …

Analysis Of Porcine Transcriptional Response To Salmonella Enterica Serovar Choleraesuis Suggests Novel Targets Of Nfkappab Are Activated In The Mesenteric Lymph Node, Yanfang Wang, Olivre P. Couture, Long Qu, Jolita J. Uthe, Shawn M. D. Bearson, Daniel Kuhar, Joan K. Lunney, Dan Nettleton, Jack C. M. Dekkers, Christopher K. Tuggle

Dan Nettleton

Background: Specific knowledge of the molecular pathways controlling host-pathogen interactions can increase our understanding of immune response biology as well as provide targets for drug development and genetic improvement of disease resistance. Toward this end, we have characterized the porcine transcriptional response to Salmonella enterica serovar Choleraesuis (S. Choleraesuis), a Salmonella serovar that predominately colonizes swine, yet can cause serious infections in human patients. Affymetrix technology was used to screen for differentially expressed genes in pig mesenteric lymph nodes (MLN) responding to infection with S. Choleraesuis at acute (8 hours (h), 24 h and 48 h post-inoculation (pi)) and chronic …

Distinct Peripheral Blood Rna Responses To Salmonella In Pigs Differing In Salmonella Shedding Levels: Intersection Of Ifng, Tlr And Mirna Pathways, Ting-Hua Huang, Jolita J. Uthe, Shawn M. D. Bearson, Cumhur Yusuf Demirkale, Dan Nettleton, Susan Knetter, Curtis Christian, Amanda E. Ramer-Tait, Michael J. Wannemeuhler, Christopher K. Tuggle

Dan Nettleton

Transcriptomic analysis of the response to bacterial pathogens has been reported for several species, yet few studies have investigated the transcriptional differences in whole blood in subjects that differ in their disease response phenotypes. Salmonella species infect many vertebrate species, and pigs colonized with Salmonella enterica serovar Typhimurium (ST) are usually asymptomatic, making detection of these Salmonella-carrier pigs difficult. The variable fecal shedding of Salmonella is an important cause of foodborne illness and zoonotic disease. To investigate gene pathways and biomarkers associated with the variance in Salmonellashedding following experimental inoculation, we initiated the first analysis of the whole …

Unique Genome-Wide Transcriptome Profiles Of Chicken Macrophages Exposed To Salmonella-Derived Endotoxin, Ceren Ciraci, Christopher K. Tuggle, Michael J. Wannemeuhler, Dan Nettleton, Susan J. Lamont

Dan Nettleton

Background: Macrophages play essential roles in both innate and adaptive immune responses. Bacteria require endotoxin, a complex lipopolysaccharide, for outer membrane permeability and the host interprets endotoxin as a signal to initiate an innate immune response. The focus of this study is kinetic and global transcriptional analysis of the chicken macrophage response to in vitro stimulation with endotoxin from Salmonella typhimurium-798.

Results: The 38535-probeset Affymetrix GeneChip Chicken Genome array was used to profile transcriptional response to endotoxin 1, 2, 4, and 8 hours post stimulation (hps). Using a maximum FDR (False Discovery Rate) of 0.05 to declare genes as differentially …

Predictors Of Neonatal Abstinence Syndrome In Buprenorphine Exposed Newborn: Can Cord Blood Buprenorphine Metabolite Levels Help?, Darshan Shah, Stacy Brown, Nick Hagemeier, Shimin Zheng, Amy Kyle, Jason Pryor, Nilesh Dankhara, Piyuesh Singh

Stacy D. Brown

Background

Buprenorphine is a semi-synthetic opioid used for the treatment of opioid dependence. Opioid use, including buprenorphine, has been increasing in recent years, in the general population and in pregnant women. Consequently, there has been a rise in frequency of neonatal abstinence syndrome (NAS), associated with buprenorphine use during pregnancy. The purpose of this study was to investigate correlations between buprenorphine and buprenorphine-metabolite concentrations in cord blood and onset of NAS in buprenorphine exposed newborns.

Methods

Nineteen (19) newborns who met inclusion criteria were followed after birth until discharge in a double-blind non-intervention study, after maternal consent. Cord blood and …

Arca Controls Metabolism, Chemotaxis, And Motility Contributing To The Pathogenicity Of Avian Pathogenic Escherichia Coli, Fengwei Jiang, Chunxia An, Yinli Bao, Xuefeng Zhao, Robert L. Jernigan, Andrew Lithio, Dan Nettleton, Ling Li, Eve S. Wurtele, Lisa K. Nolan, Chengping Lu, Ganwu Li

Dan Nettleton

Avian pathogenic Escherichia coli (APEC) strains cause one of the three most significant infectious diseases in the poultry industry and are also potential food-borne pathogens threating human health. In this study, we showed that ArcA (aerobic respiratory control), a global regulator important for E. coli's adaptation from anaerobic to aerobic conditions and control of that bacterium's enzymatic defenses against reactive oxygen species (ROS), is involved in the virulence of APEC. Deletion of arcA significantly attenuates the virulence of APEC in the duck model. Transcriptome sequencing (RNA-Seq) analyses comparing the APEC wild type and the arcA mutant indicate that ArcA regulates …

The Validity Of Online Patient Ratings Of Physicians, Jennifer L. Priestley, Yiyun Zhou, Robert Mcgrath

Jennifer L. Priestley

Background: Information from ratings sites are increasingly informing patient decisions related to health care and the selection of physicians.

Objective: The current study sought to determine the validity of online patient ratings of physicians through comparison with physician peer review.

Methods: We extracted 223,715 reviews of 41,104 physicians from 10 of the largest cities in the United States, including 1142 physicians listed as “America’s Top Doctors” through physician peer review. Differences in mean online patient ratings were tested for physicians who were listed and those who were not.

Results: Overall, no differences were found between the online patient ratings based …

Aggressive Diuresis And Severity-Adjusted Length Of Hospital Stay In Acute Congestive Heart Failure Patients., Muhammad U. Butt M.D.

Muhammad Umer Butt M.D., MSCRD

Data Analysis Basics – Part Ii, Judith A. Savageau

Judith A. Savageau

Blog post to AEA365, a blog sponsored by the American Evaluation Association (AEA) dedicated to highlighting Hot Tips, Cool Tricks, Rad Resources, and Lessons Learned for evaluators. The American Evaluation Association is an international professional association of evaluators devoted to the application and exploration of program evaluation, personnel evaluation, technology, and many other forms of evaluation. Evaluation involves assessing the strengths and weaknesses of programs, policies, personnel, products, and organizations to improve their effectiveness.

Data Analysis Basics – Part I, Judith A. Savageau

Judith A. Savageau

Blog post to AEA365, a blog sponsored by the American Evaluation Association (AEA) dedicated to highlighting Hot Tips, Cool Tricks, Rad Resources, and Lessons Learned for evaluators. The American Evaluation Association is an international professional association of evaluators devoted to the application and exploration of program evaluation, personnel evaluation, technology, and many other forms of evaluation. Evaluation involves assessing the strengths and weaknesses of programs, policies, personnel, products, and organizations to improve their effectiveness.

Global Stability For A 2n+1 Dimensional Hiv Aids Epidemic Model With Treatments, Olusegun M. Otunuga

Olusegun Michael Otunuga

Integrated Bioinformatics, Environmental Epidemiologic And Genomic Approaches To Identify Environmental And Molecular Links Between Endometriosis And Breast Cancer, Deodutta Roy, Marisa L. Morgan, Changwon Yoo, Alok Deoraj, Sandhya Roy, Vijay Kumar Yadav, Mohannad Garoub, Hamza Assaggaf, Mayur Doke

Alok Deoraj

We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC) and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs), bisphenols (BPs), and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA) and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by …

Predictors Of Neonatal Abstinence Syndrome In Buprenorphine Exposed Newborn: Can Cord Blood Buprenorphine Metabolite Levels Help?, Darshan Shah, Stacy Brown, Nick Hagemeier, Shimin Zheng, Amy Kyle, Jason Pryor, Nilesh Dankhara, Piyuesh Singh

Nicholas E. Hagemeier

Background

Buprenorphine is a semi-synthetic opioid used for the treatment of opioid dependence. Opioid use, including buprenorphine, has been increasing in recent years, in the general population and in pregnant women. Consequently, there has been a rise in frequency of neonatal abstinence syndrome (NAS), associated with buprenorphine use during pregnancy. The purpose of this study was to investigate correlations between buprenorphine and buprenorphine-metabolite concentrations in cord blood and onset of NAS in buprenorphine exposed newborns.

Methods

Nineteen (19) newborns who met inclusion criteria were followed after birth until discharge in a double-blind non-intervention study, after maternal consent. Cord blood and …

Characterization Of Plasmodium Falciparum And Plasmodium Vivax Recent Exposure In An Area Of Significantly Decreased Transmission Intensity In Central Vietnam, Johanna Helena Kattenberg, Annette Erhart, Minh Hieu Truong, Eduard Rovira-Vallbona, Khac Anh Dung Vu, Thi Hong Ngoc Nguyen, Van Hong Nguyen, Van Van Nguyen, Melanie Bannister-Tyrrell, Michael Theisen, Adam Bennet, Andrew A. Lover, Thanh Duong Tran, Xuan Xa Nguyen, Anna Rosanas-Urgell

Andrew Lover

Malaria Elimination: Time To Target All Species, Andrew A. Lover, J. Kevin Baird, Roly Gosling, Ric N. Price

Andrew Lover

Vitamin D Status And Demographic And Lifestyle Determinants Among Adults In The United States (Nhanes 2001-2006), Yan Cao, Katie L. Callahan, Sreenivas P. Veeranki, Yang Chen, Ying Liu, Shimin Zheng

Shimin Zheng

This study looked at risk factors associated with vitamin D levels in the body among a representative sample of adults in the U.S., NHANES III (2001-2006) data were used to assess the relationship between several demographic and health risk factors and vitamin D levels in the body. The Baseline-Category Logit Model was used to test the association between vitamin D level and the potential risk factors age, education, ethnicity, poverty status, physical activity, smoking, alcohol, obesity, diabetes and total cholesterol with both genders. Vitamin D insufficiency and deficiency were significantly associated with age, race, education, physical activity, obesity, diabetes and …

The Use Of Vital Statistics Data For Research Of Consequence: Birth Outcomes And Population Health In A Rural Region, Claudia Kozinetz, Shimin Zheng, Eunice Mogusu

Shimin Zheng

Objective: The Affordable Care Act (ACA) has influenced increasing interests in population health and population health outcomes. The purpose of this study was to exemplify the importance of using existing vital statistics data for understanding and monitoring health outcomes and consequentially health disparities at the population level. Data from birth records for two geographic regions from 2009-2014 were compared; low birth weight (LBW) and preterm delivery (PD) were used as surrogates for population health outcomes. Methods: A population-based, multi-year, cross-sectional study design using a pooled dataset of birth records from Tennessee (TN) was the framework for the analyses. A sub-population …

Trends And Determinants Of Up-To-Date Status With Colorectal Cancer Screening In Tennessee, 2002-2008, Sreenivas P. Veeranki, Shimin Zheng

Shimin Zheng

BACKGROUND: Screening rates for colorectal cancer (CRC) are increasing nationwide including Tennessee (TN); however, their up-to-date status is unknown. The objective of this study is to determine the trends and characteristics of TN adults who are up-to-date status with CRC screening during 2002-2008. METHODS: We examined data from the TN Behavioral Risk Factor Surveillance System for 2002, 2004, 2006 and 2008 to estimate the proportion of respondents aged 50 years and above who were up-to-date status with CRC screening, defined as an annual home fecal occult blood test and/or sigmoidoscopy or colonoscopy in the past 5 years. We identified trends …

The Association Of Calcium Intake And Other Risk Factors With Cardiovascular Disease Among Obese Adults In Usa, Yang Chen, Sheryl Strasser, Katie Callahan, David Blackley, Yan Cao, Liang Wang, Shimin Zheng

Shimin Zheng

In this study, we used a cross-sectional study design to examine the relationship between the calcium intake and risk factors for CVD among obese adults by using continuous waves of National Health and Nutrition Examination Survey (NHANES) data 1999-2010. The association between calcium intake and risk factors of CVD (hypertension, total cholesterol, HDL, glycohemoglobin), CRP, albuminuria) is assessed among obese adults in USA. The incidence of Cardiovascular Disease (CVD) is high among obese people. The potential effects of inadequate calcium intake on CVD are receiving increased epidemiologic attention. Understanding the association between risk factors for CVD and calcium intake among …

Screening For Elder Mistreatment Among Older Adults Seeking Legal Assistance Services, Sheryl M. Strasser, Megan Smith, Scott Weaver, Shimin Zheng, Yan Cao

Shimin Zheng

Introduction: The aging population is a rapidly growing demographic in the United States. Isolation, limited autonomy, and declining physical and mental health render many older adults vulnerable to elder mistreatment (EM). The purpose of this study was to assess the prevalence and correlates of EM among a sample of older adults using legal assistance services in Atlanta, Georgia. Methods: Researchers administered surveys to consenting older adults (aged 60þ) in 5 metro Atlanta community centers that hosted legal assistance information sessions as part of the Elderly Legal Assistance Program. The surveys screened for risk factors and prevalence of EM risk using …

Predictors Of Neonatal Abstinence Syndrome In Buprenorphine Exposed Newborn: Can Cord Blood Buprenorphine Metabolite Levels Help?, Darshan Shah, Stacy Brown, Nick Hagemeier, Shimin Zheng, Amy Kyle, Jason Pryor, Nilesh Dankhara, Piyuesh Singh

Shimin Zheng

Background

Buprenorphine is a semi-synthetic opioid used for the treatment of opioid dependence. Opioid use, including buprenorphine, has been increasing in recent years, in the general population and in pregnant women. Consequently, there has been a rise in frequency of neonatal abstinence syndrome (NAS), associated with buprenorphine use during pregnancy. The purpose of this study was to investigate correlations between buprenorphine and buprenorphine-metabolite concentrations in cord blood and onset of NAS in buprenorphine exposed newborns.

Methods

Nineteen (19) newborns who met inclusion criteria were followed after birth until discharge in a double-blind non-intervention study, after maternal consent. Cord blood and …

Prevalence Of And Risk Factors For Adolescent Obesity In Tennessee Using The 2010 Youth Risk Behavior Survey (Yrbs) Data: An Analysis Using Weighted Hierarchical Logistic Regression, Shimin Zheng, Nicole Holt, Jodi L. Southerland, Yan Cao, Trevor Taylor, Deborah L. Slawson, Mark Bloodworth

Shimin Zheng

Background: The rate of adolescent overweight and obesity has more than quadrupled over the past few decades, and has become a major public health problem [1]. In 2011, 55% of 12-19 year olds in the United States (U.S.) were overweight or obese [2]. Adolescence is a pivotal time in which many health risk behaviors such as tobacco, alcohol, and drug use are initiated. Such health risk behaviors have been significantly associated with overweight and obesity among adolescents. Objective: The purpose of this study is to evaluate the relationship between obesity and the health risk behaviors most commonly associated with premature …

Predictors Of Treatments Acceptable To Patients For Late-Life Depression, Gerald J. Jogerst, Shimin Zheng, Erik Vanderlip

Shimin Zheng

Objectives. Describe older patients’ perceptions about depression and characteristics associated with acceptance of treatments. Design. Cross-sectional study. Setting. Three primary care clinics in Iowa. Participants. Consecutive sample of 529 primary care patients. Measurements. Depression screening tool (a 9-item patient health questionnaire [PHQ-9]) and questionnaire including sociodemographic data, patient attitudes about depression, and acceptability of different treatments. Results. Mean age was 71.9 years (range 60–93 years), 314 (59%) female. Among the 529 participants, 93 (17.5%) had history of depression and 60 (11.3%) had PHQ-9 scores of 10 or greater. Participants believed depression is a disease for which they would use medication …

Associations Of Smoking Status And Serious Psychological Distress With Chronic Obstructive Pulmonary Disease, Ke-Sheng Wang, Liang Wang, Shimin Zheng, Long-Yang Wu

Shimin Zheng

Background: Chronic obstructive pulmonary disease (COPD) has been a major public health problem due to its high prevalence, morbidity, and mortality. Smoking is a major risk factor for COPD, while serious psychological distress (SPD) is prevalent among COPD patients. However, no study focusing on the effect of SPD on COPD has been so far conducted, while few studies have focused on the associations of SPD and behavioral factors with COPD by smoking status. Objectives: This study aimed to examine the associations of SPD and behavioral factors (such as smoking and physical activity) with COPD. Materials and Methods: Weighted logistic regression …

Evaluation Of Progress Towards The Unaids 90-90-90 Hiv Care Cascade: A Description Of Statistical Methods Used In An Interim Analysis Of The Intervention Communities In The Search Study, Laura Balzer, Joshua Schwab, Mark J. Van Der Laan, Maya L. Petersen

Laura B. Balzer

WHO guidelines call for universal antiretroviral treatment, and UNAIDS has set a global target to virally suppress most HIV-positive individuals. Accurate estimates of population-level coverage at each step of the HIV care cascade (testing, treatment, and viral suppression) are needed to assess the effectiveness of "test and treat" strategies implemented to achieve this goal. The data available to inform such estimates, however, are susceptible to informative missingness: the number of HIV-positive individuals in a population is unknown; individuals tested for HIV may not be representative of those whom a testing intervention fails to reach, and HIV-positive individuals with a viral …

Regional Initiatives For Malaria Elimination: Building And Maintaining Partnerships, Andrew A. Lover, Kelly E. Harvard, Alistair E. Lindawson, Cara Smith Gueye, Rima Shretta, Roly Gosling, Richard Feachem

Andrew Lover

• Country programs and international donors are increasingly focused on regional approaches to malaria elimination; regional initiatives have been established in southern Africa, the Arabian Peninsula, Asia Pacific, Eastern Europe, and Latin America. Despite this growing attention, there is limited information and guidance on both key activities and organizational components of regional initiatives.
• In a review conducted for this policy forum, common characteristics across existing regional initiatives emerged: building a region-specific evidence base, leveraging expertise and resources, shifting commodities or pooling procurement, developing data-sharing systems, mobilizing resources, promoting high-level accountability, and strengthening advocacy.
• Regional initiatives share key structural elements: a strategic …

Malaria Risk Factors And Care-Seeking Behaviour Within The Private Sector Among High-Risk Populations In Vietnam: A Qualitative Study, Ingrid Chen, Huong Ngo Thi Thanh, Andrew A. Lover, Phung Thi Thao, Tang Viet Luu, Hoang Nghia Thang, Ngo Duc Thang, Josselyn Neukom, Adam Bennett

Andrew Lover

Correlates Of Hiv Acquisition In A Cohort Of Black Men Who Have Sex With Men In The United States: Hiv Prevention Trials Network (Hptn) 061, Beryl A. Koblin, Kenneth H. Mayer, Susan H. Eshleman, Lei Wang, Sharon B. Mannheimer, Carlos Del Rio, Steve Shoptaw, Manya Magnus, Susan Buchbinder, Leo Wilton, Ting-Yuan Liu, Vanessa Cummings, Estelle Piwowar-Manning, Sheldon D. Fields, Sam Griffith, Vanessa Elharrar, Darrell Wheeler

Leo Wilton

Background

Black men who have sex with men (MSM) in the United States (US) are affected by HIV at disproportionate rates compared to MSM of other race/ethnicities. Current HIV incidence estimates in this group are needed to appropriately target prevention efforts.

Methods

From July 2009 to October 2010, Black MSM reporting unprotected anal intercourse with a man in the past six months were enrolled and followed for one year in six US cities for a feasibility study of a multi-component intervention to reduce HIV infection. HIV incidence based on HIV seroconversion was calculated as number of events/100 person-years. Multivariate proportional …

Non-Human Primates In Neuroscience Research: The Case Against Its Scientific Necessity, Jarrod Bailey, Katy Taylor

Jarrod Bailey, PhD

Public opposition to non-human primate (NHP) experiments is significant, yet those who defend them cite minimal harm to NHPs and substantial human benefit. Here we review these claims of benefit, specifically in neuroscience, and show that: a) there is a default assumption of their human relevance and benefit, rather than robust evidence; b) their human relevance and essential contribution and necessity are wholly overstated; c) the contribution and capacity of non-animal investigative methods are greatly understated; and d) confounding issues, such as species differences and the effects of stress and anaesthesia, are usually overlooked. This is the case in NHP …