Diversity-oriented synthesis probe targets Plasmodium falciparum cytochrome b ubiquinone reduction site and synergizes with oxidation site inhibitors.

Background: The emergence and spread of drug resistance to current antimalarial therapies remains a pressing concern, escalating the need for compounds that demonstrate novel modes of action. Diversity-Oriented Synthesis (DOS) libraries bridge the gap between conventional small molecule and natural product libraries, allowing the interrogation of more diverse chemical space in efforts to identify probes of novel parasite pathways.

Methods: We screened and optimized a probe from a DOS library using whole-cell phenotypic assays.

Longitudinal relationships among visual acuity, daily functional status, and mortality: the Salisbury Eye Evaluation Study.

Importance: Determination of the mechanisms by which visual loss increases mortality risk is important for developing interventional strategies.

Objective: To evaluate the direct and indirect effects of loss of visual acuity (VA) on mortality risk through functional status changes among aging adults.

Design, Setting, And Participants: Prospective longitudinal study of a population-based sample of 2520 noninstitutionalized adults aged 65 to 84 years from September 16, 1993, through July 26, 2003, in the greater Salisbury area of Maryland.

Barriers to employment of African American professionals in hospice: a qualitative study with African American social work students.

A major barrier to African American hospice utilization is the lack of African American hospice professionals. This qualitative study with 10 female African American social work students in a Midwestern university explored whether the participants were interested in hospice employment. Results provided information about reasons for the overall lack of diversity in hospice, reasons for the lack of African American staff in hospice, reasons for the lack of African American patients in hospice, and avenues toward knowledge about hospice by African American professionals.

Catalytic functionalization of methane and light alkanes in supercritical carbon dioxide.

The development of catalytic methods for the effective functionalization of methane yet remains a challenge. The best system known to date is the so-called Catalytica Process based on the use of platinum catalysts to convert methane into methyl bisulfate with a TOF rate of 10(-3) s. In this contribution, we report a series of silver complexes containing perfluorinated tris(indazolyl)borate ligands that catalyze the functionalization of methane into ethyl propionate upon reaction with ethyl diazoacetate (EDA) by using supercritical carbon dioxide (scCO2) as the reaction medium.

Does walking speed mediate the association between visual impairment and self-report of mobility disability? The Salisbury Eye Evaluation Study.

Objectives: To determine whether performance speeds mediate the association between visual impairment and self-reported mobility disability over an 8-year period.

Design: Longitudinal analysis.

Setting: Salisbury, Maryland.

Gender and performance of community treatment assistants in Tanzania.

Objective: To examine the effects of gender and demographics of community treatment assistants (CTAs) on their performance of assigned tasks and quantity of speech during mass drug administration of azithromycin for trachoma in rural Tanzania.

Design: Surveys of CTAs and audio recordings of interactions between CTAs and villagers during drug distribution.

Setting: Mass drug administration program in rural Kongwa district.

Long-term outcomes of boston type 1 keratoprosthesis implantation: a retrospective multicenter cohort.

Purpose: To study the long-term outcomes of Boston type 1 keratoprosthesis (KPro) surgery.

Design: Retrospective, multicenter case series.

Participants: A total of 158 eyes of 150 patients underwent KPro implantation at 5 participating tertiary centers in the United States between January 2003 and December 2006.

Geospatial distribution and clustering of Chlamydia trachomatis in communities undergoing mass azithromycin treatment.

Purpose: We detected spatial clustering of households with Chlamydia trachomatis infection (CI) and active trachoma (AT) in villages undergoing mass treatment with azithromycin (MDA) over time.

Methods: We obtained global positioning system (GPS) coordinates for all households in four villages in Kongwa District, Tanzania. Every 6 months for a period of 42 months, our team examined all children under 10 for AT, and tested for CI with ocular swabbing and Amplicor.

Diversity-oriented synthesis yields a new drug lead for treatment of chagas disease.

A phenotypic high-throughput screen using ∼100,000 compounds prepared using Diversity-Oriented Synthesis yielded stereoisomeric compounds with nanomolar growth-inhibition activity against the parasite Trypanosoma cruzi, the etiological agent of Chagas disease. After evaluating stereochemical dependence on solubility, plasma protein binding and microsomal stability, the SSS analogue (5) was chosen for structure-activity relationship studies. The p-phenoxy benzyl group appended to the secondary amine could be replaced with halobenzyl groups without loss in potency.

Short-term malaria reduction by single-dose azithromycin during mass drug administration for trachoma, Tanzania.

Single-dose mass drug administration of azithromycin (AZT) is underway to eliminate trachoma worldwide. Studies in Ethiopia showed a reduction in all-cause childhood deaths after administration. To examine the effect of single-dose AZ MDA on prevalent malaria infections in a large prospective cohort of children and parents in Dodoma Province, Tanzania, we quantified the temporal prevalence of malaria parasitemia by real-time PCR for 6 months after single-dose AZT.

Longitudinal changes of angle configuration in primary angle-closure suspects: the Zhongshan Angle-Closure Prevention Trial.

Objective: To determine longitudinal changes in angle configuration in the eyes of primary angle-closure suspects (PACS) treated by laser peripheral iridotomy (LPI) and in untreated fellow eyes.

Design: Longitudinal cohort study.

Participants: Primary angle-closure suspects aged 50 to 70 years were enrolled in a randomized, controlled clinical trial.

Identification of inhibitors of PvdQ, an enzyme involved in the synthesis of the siderophore pyoverdine.

Pseudomonas aeruginosa produces the peptide siderophore pyoverdine, which is used to acquire essential Fe(3+) ions from the environment. PvdQ, an Ntn hydrolase, is required for the biosynthesis of pyoverdine. PvdQ knockout strains are not infectious in model systems, suggesting that disruption of siderophore production via PvdQ inhibition could be exploited as a target for novel antibacterial agents, by preventing cells from acquiring iron in the low iron environments of most biological settings.

Altered sedative effects of ethanol in mice with α1 glycine receptor subunits that are insensitive to Gβγ modulation.

Alcohol abuse and alcoholism are major health problems and one of the leading preventable causes of death. Before achieving better treatments for alcoholism, it is necessary to understand the critical actions of alcohol on membrane proteins that regulate fundamental functions in the central nervous system. After generating a genetically modified knock-in (KI) mouse having a glycine receptor (GlyR) with phenotypical silent mutations at KK385/386AA, we studied its cellular and in vivo ethanol sensitivity.