Objective To examine whether slowed rod-mediated dark adaptation in adults in normal macular health at baseline is associated with the incidence of age-related macular degeneration (AMD) three years later. Design Prospective cohort Participants Adults ≥ 60 years old were recruited from primary care ophthalmology clinics. Both eyes were required to be step 1 (normal) on the AREDS 9-step AMD classification system based on color fundus photographs graded by experienced and masked evaluators. Methods Rod-mediated dark adaptation was assessed at baseline in one eye following a photobleach using a computerized dark adaptometer with targets centered at 5° on the inferior vertical meridian. Speed of dark adaptation was characterized by the rod-intercept value, with abnormal dark adaptation defined as rod-intercept ≥ 12.3 minutes. Demographic characteristics, best-corrected visual acuity, and smoking status were also assessed. Log-binomial regression was used to calculate unadjusted and adjusted risk ratios (RRs) and associated 95% confidence intervals (CIs) for the association between baseline dark adaptation and incident AMD. Main Outcome Measure AMD presence at the three-year follow-up visit for the eye tested for dark adaptation at baseline. Results Both baseline and follow-up visits were completed by 325 persons (mean age 67.8 years). At baseline 263 participants had normal dark adaptation with mean rod intercept of 9.1 (SD 1.5), and 62 had abnormal dark adaptation with mean rod intercept of 15.1 (SD 4.0). After adjustment for age and smoking, those with abnormal dark adaptation in the tested eye at baseline were almost 2 times more likely to have AMD in that eye (RR 1.92, 95% CI 1.03-3.62) by the time of the follow-up visit, as compared to those who had normal dark adaptation at baseline. Conclusions Delayed rod-mediated dark adaptation in older adults in normal macular health is associated with incident early AMD three years later, and thus is a functional biomarker for early disease. The biological relevance of this test is high, because it assesses translocation of vitamin A derivatives across the retinal pigment epithelium and Bruch's membrane, two tissues with prominent age- and AMD-related pathology.

Cumulative risk refers to the combined threats from exposure via all relevant routes to multiple stressors including biological, chemical, physical, and psychosocial entities. Cumulative risk assessment is a tool for organizing and analyzing information to examine, characterize, and possibly quantify the combined adverse effects on human health or ecologic resources from multiple environmental stressors. The U.S. Environmental Protection Agency (EPA) has initiated a long-term effort to develop future guidelines for cumulative risk assessment, including publication in 2003 of a framework that describes important features of the process and discusses theoretical issues, technical matters, and key definitions. The framework divides the process of cumulative risk assessment into three interrelated phases: a) planning, scoping, and problem formulation; b) analysis; and c) interpretation and risk characterization. It also discusses the additional complexities introduced by attempts to analyze cumulative risks from multiple stressors and describes some of the theoretical approaches that can be used. The development of guidelines for cumulative risk assessment is an essential element in the transition of the U.S. EPA risk assessment methodology from a narrow focus on a single stressor, end point, source, pathway, and exposure route to a broader, more holistic approach involving analysis of combined effects of cumulative exposure to multiple stressors via all relevant sources, pathways, and routes.

Despite having normal macular health according to accepted definitions of AMD presence, approximately one-quarter of older adults recruited from primary eye care clinics had abnormal DA, which was associated with known risk factors for AMD, including elevated CRP.

Environmental health information resources lack exposure data required to translate molecular insights, elucidate environmental contributions to diseases, and assess human health and ecological risks. We report development of an Exposure Ontology, ExO, designed to address this information gap by facilitating centralization and integration of exposure data. Major concepts were defined and the ontology drafted and evaluated by a working group of exposure scientists and other ontology and database experts. The resulting major concepts forming the basis for the ontology are “exposure stressor”, “exposure receptor”, “exposure event”, and “exposure outcome”. Although design of the first version of ExO focused on human exposure to chemicals, we anticipate expansion by the scientific community to address exposures of human and ecological receptors to the full suite of environmental stressors. Like other widely used ontologies, ExO is intended to link exposure science and diverse environmental health disciplines including toxicology, epidemiology, disease surveillance, and epigenetics.

Viral protein U (Vpu) is a protein encoded by human immunodeficiency virus type 1 (HIV-1) that promotes the degradation of the virus receptor, CD4, and enhances the release of virus particles from cells. We isolated a cDNA that encodes a novel cellular protein that interacts with Vpu in vitro, in vivo, and in yeast cells. This Vpu-binding protein (UBP) has a molecular mass of 41 kDa and is expressed ubiquitously in human tissues at the RNA level. UBP is a novel member of the tetratricopeptide repeat (TPR) protein family containing four copies of the 34-amino-acid TPR motif. Other proteins that contain TPR motifs include members of the immunophilin superfamily, organelle-targeting proteins, and a protein phosphatase. UBP also interacts directly with HIV-1 Gag protein, the principal structural component of the viral capsid. However, when Vpu and Gag are coexpressed, stable interaction between UBP and Gag is diminished. Furthermore, overexpression of UBP in virus-producing cells resulted in a significant reduction in HIV-1 virion release. Taken together, these data indicate that UBP plays a role in Vpu-mediated enhancement of particle release.