Heat-denatured human immunodeficiency virus type 1 protein 24 antigen: prognostic value in adults with early-stage disease

CD4(+) lymphocyte count and human immunodeficiency virus (HIV) type 1 RNA level are useful for determining when to initiate antiretroviral therapy but are not used widely in developing countries due to the high cost. Heat-denatured protein 24 (p24) antigen is an inexpensive assay that predicts disease progression among persons with advanced disease but has not been assessed among persons with early-stage disease. Plasma levels of heat-denatured p24 antigen were quantified in baseline study-visit specimens obtained from injection drug users enrolled in a longitudinal cohort study of HIV-1 infection. Of the 494 study participants (median initial CD4(+) lymphocyte count, 518 lymphocytes/mm(3)), 90 (18%) progressed to acquired immunodeficiency syndrome within 5 years. p24 antigen level correlated with both CD4(+) lymphocyte count (r=-0.34; P5 pg/mL predicted disease progression, comparable with that of cutoff CD4(+) lymphocyte count 30,000 copies/mL. Heat-denatured p24 antigen level predicted subsequent clinical disease progression in early-stage HIV-1 infection and correlated with both CD4(+) lymphocyte count and HIV-1 RNA leve

Addressing Inequities in Urban Health: Do Decision-Makers Have the Data They Need? Report from the Urban Health Data Special Session at International Conference on Urban Health Dhaka 2015

Rapid and uncontrolled urbanisation across low and middle-income countries is leading to ever expanding numbers of urban poor, defined here as slum dwellers and the homeless. It is estimated that 828 million people are currently living in slum conditions. If governments, donors and NGOs are to respond to these growing inequities they need data that adequately represents the needs of the urban poorest as well as others across the socio-economic spectrum. We report on the findings of a special session held at the International Conference on Urban Health, Dhaka 2015. We present an overview of the need for data on urban health for planning and allocating resources to address urban inequities. Such data needs to provide information on differences between urban and rural areas nationally, between and within urban communities. We discuss the limitations of data most commonly available to national and municipality level government, donor and NGO staff. In particular we assess, with reference to the WHO’s Urban HEART tool, the challenges in the design of household surveys in understanding urban health inequities. We then present two novel approaches aimed at improving the information on the health of the urban poorest. The first uses gridded population sampling techniques within the design and implementation of household surveys and the second adapts Urban HEART into a participatory approach which enables slum residents to assess indicators whilst simultaneously planning the response. We argue that if progress is to be made towards inclusive, safe, resilient and sustainable cities, as articulated in Sustainable Development Goal 11, then understanding urban health inequities is a vital pre-requisite to an effective response by governments, donors, NGOs and communities

Trajectory and Socioeconomic Predictors of Depression in a Prospective Study of Residents of New York City

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63032/1/Beard_depression predictors_2008.pd

Patterns and Predictors of Trajectories of Depression after an Urban Disaster

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64282/1/Nandi_Trajectories of Depression_2009.pd

Treatment of experimental adjuvant arthritis with a novel folate receptor-targeted folic acid-aminopterin conjugate

Introduction Folate receptor (FR)-expressing macrophages have been shown to accumulate at sites of inflammation, where they promote development of inflammatory symptoms. To target such a macrophage population, we designed and evaluated the biologic activity of EC0746, a novel folic acid conjugate of the highly potent antifolate, aminopterin. Methods Using a FR-positive subclone of murine macrophage-derived RAW264.7 cells and rat thioglycollate-elicited macrophages, we studied the effect of EC0746 on dihydrofolate reductase activity, cell proliferation, and cellular response towards bacterial lipopolysaccharide as well as IFNγ activation. The EC0746 anti-inflammatory activity, pharmacokinetics, and toxicity were also evaluated in normal rats or in rats with adjuvant-induced arthritis; that is, a FR-positive macrophage model that closely resembles rheumatoid arthritis in humans. Results EC0746 suppresses the proliferation of RAW264.7 cells and prevents the ability of nonproliferating rat macrophages to respond to inflammatory stimuli. In the macrophage-rich rat arthritis model, brief treatment with subcutaneously administered EC0746 is shown to mediate an FR-specific anti-inflammatory response that is more potent than either orally administered methotrexate or subcutaneously delivered etanercept. More importantly, EC0746 therapy is also shown to be ~40-fold less toxic than unmodified aminopterin, with fewer bone marrow and gastrointestinal problems. Conclusions EC0746 is the first high FR-binding dihydrofolate reductase inhibitor that demonstrates FR-specific anti-inflammatory activities both in vitro and in vivo. Our data reveal that a relatively toxic anti-inflammatory drug, such as aminopterin, can be targeted with folic acid to inflammatory macrophages and thereby relieve inflammatory symptoms with greatly reduced toxicity

Hispanic Ethnicity and Post-traumatic Stress Disorder after a Disaster: Evidence from a General Population Survey after September 11,2001

PURPOSE: To assess ethnic differences in the risk of post-traumatic stress disorder (PTSD) after a disaster, and to assess the factors that may explain these differences. METHODS: We used data from a representative survey of the New York City metropolitan area (n = 2616) conducted 6 months after September 11, 2001. Linear models were fit to assess differences in the prevalence of PTSD between different groups of Hispanics and non-Hispanics and to evaluate potential explanatory variables. RESULTS: Hispanics of Dominican or Puerto Rican origin (14.3% and 13.2%, respectively) were more likely than other Hispanics (6.1%) and non-Hispanics (5.2%) to report symptoms consistent with probable PTSD after the September 11 terrorist attacks. Dominicans and Puerto Ricans were more likely than persons of other races/ethnicities to have lower incomes, be younger, have lower social support, have had greater exposure to the September 11 attacks, and to have experienced a peri-event panic attack upon hearing of the September 11 attacks; these variables accounted for 60% to 74% of the observed higher prevalence of probable PTSD in these groups. CONCLUSION: Socio-economic position, event exposures, social support, and peri-event emotional reactions may help explain differences in PTSD risk after disaster between Hispanic subgroups and non-HispanicsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/40349/2/Galea_Hispanic Ethnicity and Post-Traumatic Stress Disorder_2004.PD

Alcohol Drinking Problems Among New York City Residents after the September 11 Terrorist Attacks

Recent studies have shown an increase in alcohol use in New York City in the months after the September 11 terrorist attacks; thus far there have been no studies documenting changes in drinking problems. In 2002, a random digit dial phone survey was conducted of residents of New York City. This study provided us with estimates of the prevalence of alcohol drinking problems among residents of New York City 6 months after September 11 compared with the 6 months before September 11. Among 1,570 adults, the prevalence of drinking problems was 3.7% in the 6 months before September 11 and 4.2% in the 6 months after September 11. The incidence of drinking problems among those without drinking problems before September 11 was 2.2%. Persons with incident drinking problems were more likely than those without to report symptoms consistent with posttraumatic stress disorder (17.4% vs. 0.4% in those without drinking problems and 1.4% in nondrinkers), and depression (23.5% vs 5.6% vs. 4.9%, respectively) after September 11. After a disaster, a link between drinking problems and posttraumatic stress disorder or depression should be assessed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/40250/2/vlahov_alcohol drinking problems among NYC residents_2006.pd

Control of translation elongation in health and disease.

Regulation of protein synthesis makes a major contribution to post-transcriptional control pathways. During disease, or under stress, cells initiate processes to reprogramme protein synthesis and thus orchestrate the appropriate cellular response. Recent data show that the elongation stage of protein synthesis is a key regulatory node for translational control in health and disease. There is a complex set of factors that individually affect the overall rate of elongation and, for the most part, these influence either transfer RNA (tRNA)- and eukaryotic elongation factor 1A (eEF1A)-dependent codon decoding, and/or elongation factor 2 (eEF2)-dependent ribosome translocation along the mRNA. Decoding speeds depend on the relative abundance of each tRNA, the cognate:near-cognate tRNA ratios and the degree of tRNA modification, whereas eEF2-dependent ribosome translocation is negatively regulated by phosphorylation on threonine-56 by eEF2 kinase. Additional factors that contribute to the control of the elongation rate include epigenetic modification of the mRNA, coding sequence variation and the expression of eIF5A, which stimulates peptide bond formation between proline residues. Importantly, dysregulation of elongation control is central to disease mechanisms in both tumorigenesis and neurodegeneration, making the individual key steps in this process attractive therapeutic targets. Here, we discuss the relative contribution of individual components of the translational apparatus (e.g. tRNAs, elongation factors and their modifiers) to the overall control of translation elongation and how their dysregulation contributes towards disease processes

Job Loss, Unemployment, Work Stress, Job Satisfaction, and the Persistence of Posttraumatic Stress Disorder One Year After the September 11 Attacks

The influence of unemployment and adverse work conditions on the course of psychopathology after a mass disaster is unclear. We recruited a representative sample of adults living in the New York City metropolitan area six months after the September 11 attacks and completed follow-up interviews on 71% of the baseline sample six months later (N = 1939). At follow-up, posttraumatic stress disorder (PTSD) persisted in 42.7% of the 149 cases with PTSD at baseline. In multivariable models, unemployment at any time since baseline predicted PTSD persistence in the entire cohort (P = 0.02) and among persons employed at follow-up (P = 0.02). High levels of perceived work stress predicted PTSD persistence among persons employed at follow-up (P = 0.02). Persons unemployed in the aftermath of a disaster may be at risk for poor mental health in the long-term.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/40294/2/Nandi_Job Loss, Unemploymet, Work Stress, Job Satisfation_2004.pd