This study assesses lateral tipping motion-induced interruptions (MIIs) in a simulated motion environment. The objective is to revisit MII occurrence and sway motion relationship by focusing on the frequency and acceleration of the lateral motion stimulus. Results verify that MIIs increase with increasing peak sway acceleration, but the effect of sway frequency is not as clear as that of acceleration.
View Article and Find Full Text PDFBackground: Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%.
View Article and Find Full Text PDFThe human APOBEC3 proteins are a family of DNA-editing enzymes that play an important role in the innate immune response against retroviruses and retrotransposons. APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism.
View Article and Find Full Text PDFBackground: Throughout history, people have soothed their fear of disease outbreaks by searching for someone to blame. Such was the case with the April 2009 H1N1 flu outbreak. Mexicans and other Latinos living in the US were quickly stigmatized by non-Latinos as carriers of the virus, partly because of news reports on the outbreak's alleged origin in Mexican pig farms.
View Article and Find Full Text PDFThe human immunodeficiency virus type 1 (HIV-1) nucleocapsid (NC) protein contains 15 basic residues located throughout its 55-amino acid sequence, as well as one aromatic residue in each of its two CCHC-type zinc finger motifs. NC facilitates nucleic acid (NA) rearrangements via its chaperone activity, but the structural basis for this activity and its consequences in vivo are not completely understood. Here, we investigate the role played by basic residues in the N-terminal domain, the N-terminal zinc finger and the linker region between the two zinc fingers.
View Article and Find Full Text PDFBackground: The cost-effectiveness of early antiretroviral therapy (ART) in persons infected with human immunodeficiency virus (HIV) in serodiscordant couples is not known. Using a computer simulation of the progression of HIV infection and data from the HIV Prevention Trials Network 052 study, we projected the cost-effectiveness of early ART for such persons.
Methods: For HIV-infected partners in serodiscordant couples in South Africa and India, we compared the early initiation of ART with delayed ART.
The HIV Prevention Trials Network 052 study enrolled serodiscordant couples. Index participants infected with human immunodeficiency virus reported no prior antiretroviral (ARV) treatment at enrollment. ARV drug testing was performed retrospectively using enrollment samples from a subset of index participants.
View Article and Find Full Text PDFIn the United States, diabetes is common and costly. Programs to prevent new cases of diabetes are often carried out at the level of the county, a unit of local government. Thus, efficient targeting of such programs requires county-level estimates of diabetes incidence-the fraction of the non-diabetic population who received their diagnosis of diabetes during the past 12 months.
View Article and Find Full Text PDFEukaryotic High-Mobility Group B (HMGB) proteins alter DNA elasticity while facilitating transcription, replication and DNA repair. We developed a new single-molecule method to probe non-specific DNA interactions for two HMGB homologs: the human HMGB2 box A domain and yeast Nhp6Ap, along with chimeric mutants replacing neutral N-terminal residues of the HMGB2 protein with cationic sequences from Nhp6Ap. Surprisingly, HMGB proteins constrain DNA winding, and this torsional constraint is released over short timescales.
View Article and Find Full Text PDFCancer Epidemiol Biomarkers Prev
October 2012
The radical and transformative developments in information and communication technologies (ICT) offer unprecedented opportunities to promote cancer control and enhance population and individual health. However, the current context in which these technologies are being deployed--where cancer incidence and mortality and communication are characterized by inequalities among different racial/ethnic and socioeconomic status groups--raises important questions for cancer communication research, policy, and practice. Drawing on illustrative data, this essay characterizes the communications revolution and elucidates its implications for cancer control, with a particular focus on communication inequalities and cancer disparities.
View Article and Find Full Text PDFObjective: The purpose of this study was to assess respondents' self-reported choices for vaccinating their young children; knowledge, attitudes, and beliefs (KABs) about vaccination; and communication with their child's vaccination provider.
Methods: A national telephone survey of 1500 parents of children aged 6 to 23 months was conducted in 2010. We calculated proportions of parents who had chosen-or planned-to refuse or delay 1 or more recommended vaccines, and proportions for responses to KABs and communication questions, stratified by vaccination choice (ie, refuse or delay).
The news media play a vital role in disseminating health information, yet little is known about the social characteristics of health journalists or the impact they have on the newsmaking process. This study examines how the social group influences of US health journalists impact two important aspects of news production--'media agenda-setting' and 'framing'. Using data from a national survey of health and medical science journalists, the authors conducted multivariable logistic regression analyses to study the links between the gender, age and race/ethnicity of respondents, and the ways in which they utilized news sources, other resources, news priorities and story angles.
View Article and Find Full Text PDFThe human immunodeficiency virus type 1 (HIV-1) nucleocapsid (NC) protein plays an essential role in several stages of HIV-1 replication. One important function of HIV-1 NC is to act as a nucleic acid chaperone, in which the protein facilitates nucleic acid rearrangements important for reverse transcription and recombination. NC contains only 55 amino acids, with 15 basic residues and two zinc fingers, each having a single aromatic residue (Phe16 and Trp37).
View Article and Find Full Text PDFThe HIV Prevention Trial Network (HPTN) 052 Study is a Phase III, two-arm, controlled, open-labeled, randomized clinical trial designed to determine whether early antiretroviral therapy (ART) can prevent the sexual transmission of human immunodeficiency virus type 1 (HIV-1). A total of 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative were enrolled in four continents, nine countries and thirteen study sites. The HIV-1-positive partner was randomly assigned to either of the two arms: "immediate" (early) therapy with ART initiated upon enrollment plus HIV primary care, or "delayed" therapy with HIV primary care but ART initiated when the index case would have two consecutive measurements of a CD4+ cell count within or below the range of 200-250 cells/mm(3), or develop an AIDS-defining illness.
View Article and Find Full Text PDFBackground: Obtaining the definitive data necessary to determine the safety and efficacy of using antiretroviral treatment (ART) to reduce the sexual transmission of HIV in heterosexual couples encountered an array of ethical challenges that threatened to compromise HIV Prevention Trials Network (HPTN) 052, the multinational clinical trial addressing this issue that has profound public health implications.
Purpose: To describe and analyze the major ethical challenges faced in HPTN 052.
Methods: The ethical issues and modifications of HPTN 052 in response to these issues were cataloged by the principal investigator, the lead coordinator, and the ethicist working on the trial.
Background: About a fourth of acute decompensated heart failure (ADHF) patients develop renal dysfunction during their admission. To date, the association of ADHF treatment with the development of worsening renal function (WRF) remains contentious. Thus, we examined the association of WRF with changes in BNP levels and with mortality.
View Article and Find Full Text PDFObjectives: Nationwide among nursing home residents, receipt of the influenza vaccine is 8 to 9 percentage points lower among blacks than among whites. The objective of this study was to determine if the national inequity in vaccination is because of the characteristics of facilities and/or residents.
Design: Cross-sectional study with multilevel modeling.
Sudden cardiac death exhibits diurnal variation in both acquired and hereditary forms of heart disease, but the molecular basis of this variation is unknown. A common mechanism that underlies susceptibility to ventricular arrhythmias is abnormalities in the duration (for example, short or long QT syndromes and heart failure) or pattern (for example, Brugada's syndrome) of myocardial repolarization. Here we provide molecular evidence that links circadian rhythms to vulnerability in ventricular arrhythmias in mice.
View Article and Find Full Text PDFActinomycin D (ActD) is a small molecule with strong antibiotic and anticancer activity. However, its biologically relevant DNA-binding mechanism has never been resolved, with some studies suggesting that the primary binding mode is intercalation, and others suggesting that single-stranded DNA binding is most important. To resolve this controversy, we develop a method to quantify ActD's equilibrium and kinetic DNA-binding properties as a function of stretching force applied to a single DNA molecule.
View Article and Find Full Text PDFPurpose Of Review: This review summarizes the development and implementation of a large clinical trial, HIV Prevention Trials Network (HPTN) 052, whose initial results were recently presented and published.
Recent Findings: A randomized, clinical trial demonstrated that antiretroviral therapy reduces the sexual transmission of HIV in HIV-serodiscordant couples by more than 96%. The logistical challenges in preparing for and conducting such a trial were considerable.
HMGB (high-mobility group box) proteins are members of a class of small proteins that are ubiquitous in eukaryotic cells and nonspecifically bind to DNA, inducing large-angle DNA bends, enhancing the flexibility of DNA, and likely facilitating numerous important biological interactions. To determine the nature of this behavior for different HMGB proteins, we used atomic force microscopy to quantitatively characterize the bend angle distributions of DNA complexes with human HMGB2(Box A), yeast Nhp6A, and two chimeric mutants of these proteins. While all of the HMGB proteins bend DNA to preferred angles, Nhp6A promoted the formation of higher-order oligomer structures and induced a significantly broader distribution of angles, suggesting that the mechanism of Nhp6A is like a flexible hinge more than that of HMGB2(Box A).
View Article and Find Full Text PDFRett syndrome is a neurodevelopmental disorder typically caused by mutations in methyl-CpG-binding protein 2 (MECP2) in which 26% of deaths are sudden and of unknown cause. To explore the hypothesis that these deaths may be due to cardiac dysfunction, we characterized the electrocardiograms in 379 people with Rett syndrome and found that 18.5% show prolongation of the corrected QT interval (QTc), an indication of a repolarization abnormality that can predispose to the development of an unstable fatal cardiac rhythm.
View Article and Find Full Text PDFBackground: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early initiation of antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) transmission from HIV-infected adults (index participants) to their HIV-uninfected sexual partners. We analyzed HIV from 38 index-partner pairs and 80 unrelated index participants (controls) to assess the linkage of seroconversion events.
Methods: Linkage was assessed using phylogenetic analysis of HIV pol sequences and Bayesian analysis of genetic distances between pol sequences from index-partner pairs and controls.