Therapeutic challenges in hepatitis C-infected injection drug using patients

Hepatitis C Viral (HCV) infection in the injection drug user (IDU) population is a major medical concern. Concurrent substance abuse, co-morbid mental health conditions, poor socioeconomic status and a complex treatment protocol that is often incompatible with the life styles of IDUs combine to account for poor uptake and completion of HCV treatment. This article discusses HCV antiviral treatment issues relevant to IDUs chronically infected with this virus. The effect of non-injected substances of abuse on treatment outcome is considered. Priority issues requiring research are discussed

Duplications and functional divergence of ADP-glucose pyrophosphorylase genes in plants

<p>Abstract</p> <p>Background</p> <p>ADP-glucose pyrophosphorylase (AGPase), which catalyses a rate limiting step in starch synthesis, is a heterotetramer comprised of two identical large and two identical small subunits in plants. Although the large and small subunits are equally sensitive to activity-altering amino acid changes when expressed in a bacterial system, the overall rate of non-synonymous evolution is ~2.7-fold greater for the large subunit than for the small subunit. Herein, we examine the basis for their different rates of evolution, the number of duplications in both large and small subunit genes and document changes in the patterns of AGPase evolution over time.</p> <p>Results</p> <p>We found that the first duplication in the AGPase large subunit family occurred early in the history of land plants, while the earliest small subunit duplication occurred after the divergence of monocots and eudicots. The large subunit also had a larger number of gene duplications than did the small subunit. The ancient duplications in the large subunit family raise concern about the saturation of synonymous substitutions, but estimates of the absolute rate of AGPase evolution were highly correlated with estimates of ω (the non-synonymous to synonymous rate ratio). Both subunits showed evidence for positive selection and relaxation of purifying selection after duplication, but these phenomena could not explain the different evolutionary rates of the two subunits. Instead, evolutionary constraints appear to be permanently relaxed for the large subunit relative to the small subunit. Both subunits exhibit branch-specific patterns of rate variation among sites.</p> <p>Conclusion</p> <p>These analyses indicate that the higher evolutionary rate of the plant AGPase large subunit reflects permanent relaxation of constraints relative to the small subunit and they show that the large subunit genes have undergone more gene duplications than small subunit genes. Candidate sites potentially responsible for functional divergence within each of the AGPase subunits were investigated by examining branch-specific patterns of rate variation. We discuss the phenotypes of mutants that alter some candidate sites and strategies for examining candidate sites of presently unknown function.</p

Equitable access to HCV care in HIV-HCV co-infection can be achieved despite barriers to health care provision

Language barrier, race, immigration status, mental health illness, substance abuse and socioeconomic status are often not considered when evaluating hepatitis C virus (HCV) sustained virological response (SVR) in human immunodeficiency virus (HIV) infection. The influence of these factors on HCV work-up, treatment initiation and SVR were assessed in an HIV–HCV coinfected population and compared to patients with HCV mono-infection. The setting was a publicly funded, urban-based, multidisciplinary viral hepatitis clinic. A clinical database was utilized to identify HIV and HCV consults between June 2000 and June 2007. Measures of access to HCV care (ie, liver biopsy and HCV antiviral initiation) and SVR as a function of the above variables were evaluated and compared between patients with HIV–HCV and HCV. HIV–HCV co-infected (n = 106) and HCV mono-infected (n = 802) patients were evaluated. HIV–HCV patients were more often white (94% versus 84%) and male (87% versus 69%). Bridging fibrosis or cirrhosis on biopsy was more frequent in HIV–HCV (37% versus 22%; P = 0.03). HIV infection itself did not influence access to biopsy (50% versus 52%) or treatment initiation (39% versus 38%). Race, language barrier, immigration status, injection drug history and socioeconomic status did not influence access to biopsy or treatment. SVR was 54% in HCV and 30% in HIV–HCV (P = 0.003). Genotype and HIV were the only evaluated variables to predict SVR. Within the context of a socialized, multidisciplinary clinic, HIV–HCV co-infected patients received similar access to HCV work-up and care as HCV mono-infected patients. SVR is diminished in HIV–HCV co-infection independent of language barrier, race, immigration status, or socioeconomic status

Life expectancy of persons receiving combination antiretroviral therapy in low-income countries: a cohort analysis from Uganda

Little is known about the effect of combination antiretroviral therapy (cART) on life expectancy in sub-Saharan Africa

Long-term use of antibiotics and risk of colorectal adenoma

Objective—Recent evidence suggests that antibiotic use, which alters the gut microbiome, is associated with an increased risk of colorectal cancer. However, the association between antibiotic use and risk of colorectal adenoma, the precursor for the majority of colorectal cancers, has not been investigated. Design—We prospectively evaluated the association between antibiotic use at age 20–39 and 40–59 (assessed in 2004) and recent antibiotic use (assessed in 2008) with risk of subsequent colorectal adenoma among 16,642 women aged ≥60 enrolled in the Nurses’ Health Study who underwent at least one colonoscopy through 2010. We used multivariate logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results—We documented 1,195 cases of adenoma. Increasing duration of antibiotic use at age 20–39 (Ptrend=0.002) and 40–59 (Ptrend=0.001) was significantly associated with an increased risk of colorectal adenoma. Compared to non-users, women who used antibiotics for ≥2 months between age 20–39 had a multivariable OR of 1.36 (95% CI: 1.03–1.79). Women who used ≥2 months of antibiotics between age 40–59 had a multivariable OR of 1.69 (95% CI: 1.24–2.31). The associations were similar for low-risk vs. high-risk adenomas (size ≥1 cm, or with tubulovillous/villous histology, or ≥3 detected lesions), but appeared modestly stronger for proximal compared with distal adenomas. In contrast, recent antibiotic use within the past 4 years was not associated with risk of adenoma (Ptrend=0.44). Conclusions—Long-term antibiotic use in early to middle adulthood was associated with increased risk of colorectal adenoma

Atomic oxygen durability evaluation of the flexible batten for the photovoltaic array mast on Space Station

A test program was conducted at the National Aeronautics and Space Administration's Lewis Research Center (LeRC) to evaluate the long term low Earth orbital (LEO) atomic oxygen (AO) durability of a flexible (fiberglass-epoxy composite) batten. The flexible batten is a component used to provide structural rigidity in the photovoltaic array mast on Space Station. The mast is used to support and articulate the photovoltaic array, therefore, the flexible batten must be preloaded for the 15 year lifetime of an array blanket. Development hardware and composite materials were evaluated in ground testing facilities for AO durability and dynamic retraction-deployment cyclic loading representative of expected full life in-space application. The CV1144 silicone (AO protective) coating was determined to provide adequate protection against AO degradation of the composite material and provided fiber containment, thus the structural integrity of the flexible batten was maintained. Both silicone coated and uncoated flexible battens maintained load carrying capabilities. Results of the testing did indicate that the CV1144 silicone protective coating was oxidized by AO reactions to form a brittle glassy (SiO2) skin that formed cracking patterns on all sides of the coated samples. The cracking was observed in samples that were mechanically stressed as well as samples in non-stressed conditions. The oxidized silicon was observed to randomly spall in small localized areas, on the flexible battens that underwent retraction-deployment cycling. Some darkening of the silicon, attributed to vacuum ultraviolet (VUV) radiation, was observed