Poverty, hunger, education, and residential status impact survival in HIV.

Despite combination antiretroviral therapy (ART), HIV infected people have higher mortality than non-infected. Lower socioeconomic status (SES) predicts higher mortality in many chronic illnesses but data in people with HIV is limited. We evaluated 878 HIV infected individuals followed from 1995 to 2005.

Inhibition of ABCG2-mediated drug efflux by naphthopyrones from marine crinoids.

Five new naphthopyrones (1-5) along with the known compounds TMC-256A1, 5,8-dihydroxy-6-methoxy-2-propyl-4H-naphtho[2,3-b]pyran-4-one, TMC-256C1, comaparvin, 6-methoxycomaparvin, and 6-methoxycomaparvin 5-methyl ether (6-11) were isolated from crinoids of the family Comasteridae. All compounds were tested for their ability to inhibit the multidrug transporter ABCG2, which plays a role in drug resistance. Six of the seven angular naphthopyrones showed moderate activity with <60% inhibition of ABCG2-mediated transport as compared to the positive control fumitremorgin C.

Isolation, structural elucidation, and absolute stereochemistry of enigmazole A, a cytotoxic phosphomacrolide from the Papua New Guinea marine sponge Cinachyrella enigmatica.

Enigmazole A (1), a novel phosphate-containing macrolide, was isolated from a Papua New Guinea collection of the marine sponge Cinachyrella enigmatica. The structure of 1, including the absolute stereochemistry at all eight chiral centers, was determined by a combination of spectroscopic analyses and a series of microscale chemical derivatization studies. Compound 1 is comprised of an 18-membered phosphomacrolide that contains an embedded exomethylene-substituted tetrahydropyran ring and an acyclic portion that spans an embedded oxazole moiety.

Granulomatous orbital inflammation associated with intraorbital titanium-impregnated acetate fiber.

Herein we report a 52-year-old man with subacute right-sided proptosis and diffuse intraconal enhancing abnormality on MRI. Orbital biopsy revealed granulomatous inflammation consistent with idiopathic orbital inflammatory syndrome (IOIS), or orbital pseudotumor. However, further examination under polarizing light microscopy also revealed acetate fiber fragments within the orbit.

Study on the use of long-term urinary catheters in community-dwelling individuals.

Purpose: The purpose of this study was to determine the incidence and distribution of catheter-related problems in long-term indwelling urinary catheter users. We also sought to assess appropriateness of catheter use and examine relationships among catheter complications and catheter care practices.

Design: This repeated-measures study involved self-reported data collection by recall at intake and by prospective data collection at 2, 4, and 6 months in long-term urinary catheter users.

Mannose-rich glycosylation patterns on HIV-1 subtype C gp120 and sensitivity to the lectins, Griffithsin, Cyanovirin-N and Scytovirin.

Griffithsin (GRFT), Cyanovirin-N (CV-N) and Scytovirin (SVN) are lectins that inhibit HIV-1 infection by binding to multiple mannose-rich glycans on the HIV-1 envelope glycoproteins (Env). Here we show that these lectins neutralize subtype C primary virus isolates in addition to Env-pseudotyped viruses obtained from plasma and cervical vaginal lavages. Among 15 subtype C pseudoviruses, the median IC(50) values were 0.

Impairment of ultrastructure and cytoskeleton during progression of cardiac hypertrophy to heart failure.

Studies at the morphological and molecular level have found that transgenic (Tg) mice that overexpress myotrophin in the heart develop hypertrophy at the early age of 4 weeks; this condition worsens to heart failure (HF) at approximately 36 weeks. However, how the sustained effects of alteration in cytoarchitecture of the contractile machinery lead to malfunction of the normal heart remains unclear. Our data have shown that at 4 weeks, the cytoarchitecture observed in left ventricular (LV) tissue samples of Tg mice is similar to that of wild-type (WT) mice.

A new urinary catheter-related quality of life instrument for adults.

Aims: To develop and assess the measurement properties of a catheter-related quality of life (C-IQoL) instrument designed to support research with persons using long-term urinary catheter users who use indwelling urethral or suprapubic catheters permanently.

Methods: Testing was conducted in two small studies for psychometric qualities of reliability (internal consistency and test-retest) and factor analysis. The initial instrument, which was modified after each study, was based on an International Continence Society (ICS) validated generic incontinence quality of life tool.

Broad-spectrum in vitro activity and in vivo efficacy of the antiviral protein griffithsin against emerging viruses of the family Coronaviridae.

Viruses of the family Coronaviridae have recently emerged through zoonotic transmission to become serious human pathogens. The pathogenic agent responsible for severe acute respiratory syndrome (SARS), the SARS coronavirus (SARS-CoV), is a member of this large family of positive-strand RNA viruses that cause a spectrum of disease in humans, other mammals, and birds. Since the publicized outbreaks of SARS in China and Canada in 2002-2003, significant efforts successfully identified the causative agent, host cell receptor(s), and many of the pathogenic mechanisms underlying SARS.

Public versus private: does it matter for water conservation? Insights from California.

This article asks three connected questions: First, does the public view private and public utilities differently, and if so, does this affect attitudes to conservation? Second, do public and private utilities differ in their approaches to conservation? Finally, do differences in the approaches of the utilities, if any, relate to differences in public attitudes? We survey public attitudes in California toward (hypothetical but plausible) voluntary and mandated water conservation, as well as to price increases, during a recent period of shortage. We do this by interviewing households in three pairs of adjacent public and private utilities. We also survey managers of public and private urban water utilities to see if they differ in their approaches to conservation and to their customers.

Development of a high-throughput cell-based reporter assay to identify stabilizers of tumor suppressor Pdcd4.

The novel tumor suppressor Pdcd4 affects tumorigenesis by inhibiting translation. Pdcd4 is phosphorylated and subsequently lost by proteasomal degradation in response to tumor-promoting conditions. Here, the authors describe the development of a reporter cell system to monitor the stability of Pdcd4.

Structural and functional analyses of minimal phosphopeptides targeting the polo-box domain of polo-like kinase 1.

Polo-like kinase-1 (Plk1) has a pivotal role in cell proliferation and is considered a potential target for anticancer therapy. The noncatalytic polo-box domain (PBD) of Plk1 forms a phosphoepitope binding module for protein-protein interaction. Here, we report the identification of minimal phosphopeptides that specifically interact with the PBD of human PLK1, but not those of the closely related PLK2 and PLK3.

Botryllamides: natural product inhibitors of ABCG2.

ABCG2 is a membrane-localized, human transporter protein that has been demonstrated to reduce the intracellular accumulation of substrates through ATP-dependent efflux. Highly expressed in placental syncytiotrophoblasts, brain microvasculature, and the gastrointestinal tract, ABCG2 has been shown to mediate normal tissue protection as well as limit oral bioavailability of substrate compounds. Development of ABCG2 inhibitors for clinical use may allow increased penetration of therapeutic agents into sanctuary sites and increased gastrointestinal absorption.

Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component.

To prevent sexually transmitted HIV, the most desirable active ingredients of microbicides are antiretrovirals (ARVs) that directly target viral entry and avert infection at mucosal surfaces. However, most promising ARV entry inhibitors are biologicals, which are costly to manufacture and deliver to resource-poor areas where effective microbicides are urgently needed. Here, we report a manufacturing breakthrough for griffithsin (GRFT), one of the most potent HIV entry inhibitors.

A selective small-molecule nuclear factor-kappaB inhibitor from a high-throughput cell-based assay for "activator protein-1 hits".

NSC 676914 has been identified as a selective nuclear factor-kappaB (NF-kappaB) inhibitor that does not inhibit cell proliferation. This compound was originally identified in a high-throughput cell-based assay for activator protein-1 (AP-1) inhibitors using synthetic compound libraries and the National Cancer Institute natural product repository. NSC 676914 shows activity against NF-kappaB in luciferase reporter assays at concentrations much less than the IC50 for AP-1.

Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin.

Cyanovirin-N (CV-N) is a cyanobacterial lectin that binds to specific oligomannoses on the surface of gp120, resulting in nanomolar antiviral activity against HIV. In its monomeric form, CV-N contains two functional carbohydrate-binding domains, A and B. When refolded at high concentration, the protein can form a domain-swapped dimer.

Quassinoid inhibition of AP-1 function does not correlate with cytotoxicity or protein synthesis inhibition.

Several quassinoids were identified in a high-throughput screening assay as inhibitors of the transcription factor AP-1. Further biological characterization revealed that while their effect was not specific to AP-1, protein synthesis inhibition and cell growth assays were inconsistent with a mechanism of simple protein synthesis inhibition. Numerous plant extracts from the plant family Simaroubaceae were also identified in the same screen; bioassay-guided fractionation of one extract (Ailanthus triphylla) yielded two known quassinoids, ailanthinone (3) and glaucarubinone (4), which were also identified in the pure compound screening procedure.

Craniofacial architectural constraints and their importance for reconstructing the early Homo skull KNM-ER 1470.

Objective: Our objective is to exploit architectural constraint for the analysis and interpretation of craniofacial form, which we apply here to the reconstruction of the early Homo cranium KNM-ER 1470. We are motivated to perform this study because in the absence of biological criteria our preconceptions are likely to govern our concept of craniofacial form.

Study Design: We reassembled the fragmented parts--left and right halves of the calvaria and the face--according to mammalian craniofacial architectural constraints described by Donald H.

A cell-based high-throughput screen to identify synergistic TRAIL sensitizers.

We have developed a high-throughput screen (HTS) to search for novel molecules that can synergize with TRAIL, thus promoting apoptosis of ACHN renal tumor cells in a combinatorial fashion. The HTS detects synthetic compounds and pure natural products that can pre-sensitize the cancer cells to TRAIL-mediated apoptosis, yet have limited toxicity on their own. We have taken into account the individual effects of the single agents, versus the combination, and have identified hits that are synergistic, synergistic-toxic, or additive when combined with TRAIL in promoting tumor cell death.

Fast food hamburgers: what are we really eating?

Americans consume about 5 billion hamburgers a year. It is presumed that most hamburgers are composed primarily of meat. The purpose of this study is to assess the content of 8 fast food hamburger brands using histologic methods.

Discovery of new pyridoacridine alkaloids from Lissoclinum cf. badium that inhibit the ubiquitin ligase activity of Hdm2 and stabilize p53.

Compounds that stabilize p53 could suppress tumors providing a additional tool to fight cancer. Mdm2, and the human ortholog, Hdm2 serve as ubiquitin E3 ligases and target p53 for ubiquitylation and degradation. Inhibition of Hdm2 stabilizes p53, inhibits cell proliferation and induces apoptosis.

Ultrastructural abnormalities of respiratory cilia: a 25-year experience.

Context: Ciliary dyskinesia is a rare, but significant, cause of chronic respiratory infections, and transmission electron microscopy is a critical adjunct to making the diagnosis.

Objective: To investigate a single institution's experience with patients demonstrating abnormal ciliary ultrastructure.

Design: Retrospective clinicopathologic review of 278 bronchial or nasal turbinate brushings or biopsies from 1983 through 2007.

Surgical treatment of subaortic stenosis and noncompaction of the left ventricle.

Late presentation of noncompaction of the left ventricle is rare, especially in the adult congenital population. We describe successful surgical management of severe pulmonary hypertension related to severe left ventricular outflow tract narrowing in the context of noncompaction of the ventricle in a 46-year-old female.

Intranasal transmission of hepatitis C virus: virological and clinical evidence.

Intranasal transmission of hepatitis C virus (HCV) via contaminated drug-sniffing implements is a potential but unconfirmed source of viral infection. We demonstrate the virological plausibility of intranasal transmission by confirming that blood and HCV RNA are present in the nasal secretions and drug-sniffing implements of HCV-infected intranasal drug users recruited from a community health clinic in New York City.