Medicine and Health Sciences Commons^™

Abstracts In High Profile Journals Often Fail To Report Harm, Enrique Bernal-Delgado, Elliot S. Fisher

Dartmouth Scholarship

To describe how frequently harm is reported in the abstract of high impact factor medical journals. We carried out a blinded structured review of a random sample of 363 Randomised Controlled Trials (RCTs) carried out on human beings, and published in high impact factor medical journals in 2003. Main endpoint: 1) Proportion of articles reporting harm in the abstract; and 2) Proportion of articles that reported harm in the abstract when harm was reported in the main body of the article. Analysis: Corrected Prevalence Ratio (cPR) and its exact confidence interval were calculated. Non-conditional logistic regression was used.

Genetic Evidence For An Alternative Citrate-Dependent Biofilm Formation Pathway In Staphylococcus Aureus That Is Dependent On Fibronectin Binding Proteins And The Grars Two-Component Regulatory System, Robert M. Q. Shanks, Michael A. Meehl, Kimberly M. Brothers, Raquel M. Martinez, Niles P. Donegan, Martha L. Graber, Ambrose L. Cheung, George A. O'Toole

Dartmouth Scholarship

We reported previously that low concentrations of sodium citrate strongly promote biofilm formation by Staphylococcus aureus laboratory strains and clinical isolates. Here, we show that citrate promotes biofilm formation via stimulating both cell-to-surface and cell-to-cell interactions. Citrate-stimulated biofilm formation is independent of the ica locus, and in fact, citrate represses polysaccharide adhesin production. We show that fibronectin binding proteins FnbA and FnbB and the global regulator SarA, which positively regulates fnbA and fnbB gene expression, are required for citrate's positive effects on biofilm formation, and citrate also stimulates fnbA and fnbB gene expression. Biofilm formation is also stimulated by several …

Basis For Treatment Of Tuberculosis Among Hiv-Infected Patients In Tanzania: The Role Of Chest X-Ray And Sputum Culture, Muhammad Bakari, Robert D. Arbeit, Lillian Mtei, Johnson Lyimo, Richard Waddell, Mecky Matee, Bernard F. Cole, Susan Tvaroha

Dartmouth Scholarship

Active tuberculosis (TB) is common among HIV-infected persons living in tuberculosis endemic countries, and screening for tuberculosis (TB) is recommended routinely. We sought to determine the role of chest x-ray and sputum culture in the decision to treat for presumptive TB using active case finding in a large cohort of HIV-infected patients. Ambulatory HIV-positive subjects with CD4 counts ≥ 200/mm3 entering a Phase III TB vaccine study in Tanzania were screened for TB with a physical examination, standard interview, CD4 count, chest x-ray (CXR), blood culture for TB, and three sputum samples for acid fast bacillus (AFB) smear and culture.

Non-Invasive Raman Tomographic Imaging Of Canine Bone Tissue, Matthew V. Schulmerich, Jacqueline H. Cole, Kathryn A. Dooley, Michael D. Morris, Jaclynn M. Kreider, Steven A. Goldstein, Subhadra Srinivasan, Brian W. Pogue

Dartmouth Scholarship

Raman spectroscopic diffuse tomographic imaging has been demonstrated for the first time. It provides a noninvasive, label-free modality to image the chemical composition of human and animal tissue and other turbid media. This technique has been applied to image the composition of bone tissue within an intact section of a canine limb. Spatially distributed 785-nm laser excitation was employed to prevent thermal damage to the tissue. Diffuse emission tomography reconstruction was used, and the location that was recovered has been confirmed by micro-computed tomography (micro-CT) images.

With recent advances, diffuse tomography shows promise for in vivo clinical imaging.^{1, …}

Using Built Environment Characteristics To Predict Walking For Exercise, Gina S. Lovasi, Anne V. Moudon, Amber L. Pearson, Philip M. Hurvitz, Eric B. Larson, David S. Siscovick, Ethan M. Berke

Dartmouth Scholarship

Environments conducive to walking may help people avoid sedentary lifestyles and associated diseases. Recent studies developed walkability models combining several built environment characteristics to optimally predict walking. Developing and testing such models with the same data could lead to overestimating one's ability to predict walking in an independent sample of the population. More accurate estimates of model fit can be obtained by splitting a single study population into training and validation sets (holdout approach) or through developing and evaluating models in different populations. We used these two approaches to test whether built environment characteristics near the home predict walking for …

Sputum Microscopy For The Diagnosis Of Hiv-Associated Pulmonary Tuberculosis In Tanzania, Mecky Matee, Lillian Mtei, Tarja Lounasvaara, Wendy Wieland-Alter, Richard Waddell, Johnson Lyimo, Muhammed Bakari, Kisali Pallangyo, C Fordham Von Reyn

Dartmouth Scholarship

Background:

In many resource poor settings only sputum microscopy is employed for the diagnosis of HIV-associated pulmonary tuberculosis; sputum culture may not be available.

Methods:

We determined the diagnostic accuracy of sputum microscopy for active case finding of HIV-associated pulmonary tuberculosis using TB culture as the reference standard.

Results:

2216 potential subjects screened for a TB vaccine trial submitted 9454 expectorated sputum specimens: 212 (2.2%) were sputum culture positive for Mycobacterium tuberculosis (MTB), 31 (0.3%) for non-tuberculous mycobacteria, and 79 (0.8%) were contaminated. The overall sensitivity of sputum microscopy was 61.8% (131/212) and specificity 99.7% (9108/9132). Sputum microscopy sensitivity varied …

Arsenic As An Endocrine Disruptor: Arsenic Disrupts Retinoic Acid Receptor–And Thyroid Hormone Receptor–Mediated Gene Regulation And Thyroid Hormone–Mediated Amphibian Tail Metamorphosis, Jennifer C. Davey, Athena P. Nomikos, Manida Wungjiranirun, Jenna R. Sherman, Liam Ingram, Cavus Batki, Jean P. Lariviere, Joshua W. Hamilton

Dartmouth Scholarship

Background:

Chronic exposure to excess arsenic in drinking water has been strongly associated with increased risks of multiple cancers, diabetes, heart disease, and reproductive and developmental problems in humans. We previously demonstrated that As, a potent endocrine disruptor at low, environmentally relevant levels, alters steroid signaling at the level of receptor-mediated gene regulation for all five steroid receptors.

Objectives:

The goal of this study was to determine whether As can also disrupt gene regulation via the retinoic acid (RA) receptor (RAR) and/or the thyroid hormone (TH) receptor (TR) and whether these effects are similar to previously observed effects on steroid …

Adenomatous Polyposis Coli Is Present Near The Minimal Level Required For Accurate Graded Responses To The Wingless Morphogen, Hassina Benchabane, Edward G. Hughes, Carter M. Takacs, Jason R. Baird, Yashi Ahmed

Dartmouth Scholarship

The mechanisms by which the Wingless (Wg) morphogen modulates the activity of the transcriptional activator Armadillo (Arm) to elicit precise, concentration-dependent cellular responses remain uncertain. Arm is targeted for proteolysis by the Axin/Adenomatous polyposis coli (Apc1 and Apc2)/Zeste-white 3 destruction complex, and Wg-dependent inactivation of destruction complex activity is crucial to trigger Arm signaling. In the prevailing model for Wg transduction, only Axin levels limit destruction complex activity, whereas Apc is present in vast excess. To test this model, we reduced Apc activity to different degrees, and analyzed the effects on three concentration-dependent responses to Arm signaling that specify distinct …

In Vitro Analysis Of Tobramycin-Treated Pseudomonas Aeruginosa Biofilms On Cystic Fibrosis-Derived Airway Epithelial Cells, Gregory G. Anderson, Sophie Moreau-Marquis, Bruce A. Stanton, George A. O'Toole

Dartmouth Scholarship

P. aeruginosa forms biofilms in the lungs of individuals with cystic fibrosis (CF); however, there have been no effective model systems for studying biofilm formation in the CF lung. We have developed a tissue culture system for growth of P. aeruginosa biofilms on CF-derived human airway cells that promotes the formation of highly antibiotic-resistant microcolonies, which produce an extracellular polysaccharide matrix and require the known abiotic biofilm formation genes flgK and pilB. Treatment of P. aeruginosa biofilms with tobramycin reduced the virulence of the biofilms both by reducing bacterial numbers and by altering virulence gene expression. We performed microarray analysis …

Inhibition Of Signal Transducer And Activator Of Transcription 3 Expression By Rna Interference Suppresses Invasion Through Inducing Anoikis In Human Colon Cancer Cells, Yu Fan, You-Li Zhang, Ying Wu, Wei Zhang, Yin-Huan Wang, Zhao-Ming Cheng, Hua Li

Dartmouth Scholarship

AIM: To investigate the roles and mechanism of signal transducer and activator of transcription 3 (STAT3) in invasion of human colon cancer cells by RNA interference.

Amp-Activated Protein Kinase Regulates Co2-Induced Alveolar Epithelial Dysfunction In Rats And Human Cells By Promoting Na,K-Atpase Endocytosis, István Vadász, Laura A. Dada, Arturo Briva, Humberto E. Trejo, Lynn C. Welch, Jiwang Chen, Peter T. Toth, Emilia Lecuona, Lee A. Witters, Paul T. Schumacker, Navdeep S. Chandel, Werner Seeger, Jacob I. Sznajder

Dartmouth Scholarship

Hypercapnia (elevated CO₂ levels) occurs as a consequence of poor alveolar ventilation and impairs alveolar fluid reabsorption (AFR) by promoting Na,K-ATPase endocytosis. We studied the mechanisms regulating CO₂-induced Na,K-ATPase endocytosis in alveolar epithelial cells (AECs) and alveolar epithelial dysfunction in rats. Elevated CO₂ levels caused a rapid activation of AMP-activated protein kinase (AMPK) in AECs, a key regulator of metabolic homeostasis. Activation of AMPK was mediated by a CO₂-triggered increase in intracellular Ca²⁺ concentration and Ca²⁺/calmodulin-dependent kinase kinase-β (CaMKK-β). Chelating intracellular Ca²⁺ or abrogating CaMKK-β function by gene silencing or …

Repression Of Hla By Rot Is Dependent On Sae In Staphylococcus Aureus, Dongmei Li, Ambrose Cheung

Dartmouth Scholarship

The regulatory locus sae is a two-component system in Staphylococcus aureus that regulates many important virulence factors, including alpha-toxin (encoded by hla) at the transcriptional level. The SarA homologs Rot and SarT were previously shown to be repressors of hla in selected S. aureus backgrounds. To delineate the interaction of rot and sae and the contribution of sarT to hla expression, an assortment of rot and sae isogenic single mutants, a rot sae double mutant, and a rot sae sarT markerless triple mutant were constructed from wild-type strain COL. Using Northern blot analysis and transcriptional reporter gene green fluorescent protein, …