Quantitative HBsAg and HBeAg Predict Hepatitis B Seroconversion after Initiation of HAART in HIV-HBV Coinfected Individuals

Objective

Anti-HBe seroconversion and HBsAg loss are important therapeutic endpoints in patients with hepatitis B virus (HBV) infection. Quantitative measures of hepatitis B surface antigen (qHBsAg) and e antigen (qHBeAg) have been identified as potentially useful indicators of therapeutic response in HBV monoinfection. The aim of this study was to examine serological change including quantitative biomarkers in HIV-HBV coinfected patients initiating HBV active antiretroviral therapy (ART).

Methods

HIV-HBV coinfected individuals from Thailand were followed for up to 168 weeks post ART. Rates and associations of qualitative serological change were determined. Longitudinal changes in qHBsAg and qHBeAg were measured and their utility as predictors of response examined.

Results

Forty seven patients were included of whom 27 (57%) were HBeAg positive at baseline. Median CD4 count was 48 cells/mm³. Over a median follow-up of 108 weeks 48% (13/27) lost HBeAg, 12/27 (44%) achieved anti-HBe seroconversion and 13% (6/47) HBsAg loss. Anti-HBe seroconversion was associated with higher baseline ALT (p = 0.034), lower qHBsAg (p = 0.015), lower qHBeAg (p = 0.031) and greater HBV DNA decline to week 24 (p = 0.045). Sensitivity and specificity for qHBsAg and qHBeAg decline of >0.5 log at week 12 and >1.0 log at week 24 were high for both anti-HBe seroconversion and HBsAg loss.

Conclusions

Rates of serological change in these HIV-HBV coinfected individuals with advanced immunodeficiency initiating HBV-active ART were high. Baseline and on treatment factors were identified that were associated with a greater likelihood of subsequent anti-HBe seroconversion, including both quantitative HBsAg and HBeAg, suggesting these biomarkers may have utility in this clinical setting.     

Plastic male mating behavior evolves in response to the competitive environment*

Male reproductive phenotypes can evolve in response to the social and sexual environment. The expression of many such phenotypes may also be plastic within an individual's lifetime. For example, male Drosophila melanogaster show significantly extended mating duration following a period of exposure to conspecific male rivals. The costs and benefits of reproductive investment, and plasticity itself, can be shaped by the prevailing sociosexual environment and by resource availability. We investigated these ideas using experimental evolution lines of D. melanogaster evolving under three fixed sex ratios (high, medium, and low male‐male competition) on either rich or poor adult diets. We found that males evolving in high‐competition environments evolved longer mating durations overall. In addition, these males expressed a novel type of plastic behavioral response following exposure to rival males: they both significantly reduced and showed altered courtship delivery, and exhibited significantly longer mating latencies. Plasticity in male mating duration in response to rivals was maintained in all of the lines, suggesting that the costs of plasticity were minimal. None of the evolutionary responses tested were consistently affected by dietary resource regimes. Collectively, the results show that fixed behavioral changes and new augmentations to the repertoire of reproductive behaviors can evolve rapidly.     

Sequential bottlenecks drive viral evolution in early acute hepatitis C virus infection

Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection.     

Recovery of ponderosa pine ecosystem carbon and water fluxes from thinning and stand‐replacing fire

Carbon uptake by forests is a major sink in the global carbon cycle, helping buffer the rising concentration of CO₂ in the atmosphere, yet the potential for future carbon uptake by forests is uncertain. Climate warming and drought can reduce forest carbon uptake by reducing photosynthesis, increasing respiration, and by increasing the frequency and intensity of wildfires, leading to large releases of stored carbon. Five years of eddy covariance measurements in a ponderosa pine (Pinus ponderosa)‐dominated ecosystem in northern Arizona showed that an intense wildfire that converted forest into sparse grassland shifted site carbon balance from sink to source for at least 15 years after burning. In contrast, recovery of carbon sink strength after thinning, a management practice used to reduce the likelihood of intense wildfires, was rapid. Comparisons between an undisturbed‐control site and an experimentally thinned site showed that thinning reduced carbon sink strength only for the first two posttreatment years. In the third and fourth posttreatment years, annual carbon sink strength of the thinned site was higher than the undisturbed site because thinning reduced aridity and drought limitation to carbon uptake. As a result, annual maximum gross primary production occurred when temperature was 3 °C higher at the thinned site compared with the undisturbed site. The severe fire consistently reduced annual evapotranspiration (range of 12–30%), whereas effects of thinning were smaller and transient, and could not be detected in the fourth year after thinning. Our results show large and persistent effects of intense fire and minor and short‐lived effects of thinning on southwestern ponderosa pine ecosystem carbon and water exchanges.     

Salvage therapy after two or more prior Helicobacter pylori treatment failures: the super salvage regimen

Background. Although effective therapies are available for curing Helicobacter pylori infection, the problem persists about what to do for patients who fail two or more treatment courses despite a good compliance. Aim. To test a twice a day midday quadruple therapy as salvage therapy. Methods. Dyspeptic H. pylori‐infected patients who failed two or more courses of anti‐H. pylori therapy received omeprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate caplets 240 mg twice a day (with the midday and evening meals) for 14 days. H. pylori status was evaluated by ¹³C‐urea breath test and histology 4–6 weeks after therapy. Eradication was defined as no positive test. Results. Seventy‐one patients were enrolled and 68 completed the full 14 days of therapy (mean age 46 years; 28 men). Thirty‐three patients had failed prior treatment twice, 19 had failed three times, and 16 had failed four or more times. The cure rates were: intention to treat = 93% (66/71); (95% CI = 84% to 98%), per protocol = 97% (66/68); (95% CI = 89%– 100%). Success was excellent irrespective of diagnosis, age, prior treatment protocols, or smoking status. Moderate side‐effects were experienced by only two patients. Conclusion. Midday bismuth subcitrate based twice a day quadruple therapy was an excellent salvage therapy. BID midday quadruple regimen should be considered as the therapy of choice.     

Imaging dynamic redox changes in mammalian cells with green fluorescent protein indicators

Changes in the redox equilibrium of cells influence a host of cell functions. Alterations in the redox equilibrium are precipitated by changing either the glutathione/glutathione-disulfide ratio (GSH/GSSG) and/or the reduced/oxidized thioredoxin ratio. Redox-sensitive green fluorescent proteins (GFP) allow real time visualization of the oxidation state of the indicator. Ratios of fluorescence from excitation at 400 and 490 nm indicate the extent of oxidation and thus the redox potential while canceling out the amount of indicator and the absolute optical sensitivity. Because the indicator is genetically encoded, it can be targeted to specific proteins or organelles of interest and expressed in a wide variety of cells and organisms. We evaluated roGFP1 (GFP with mutations C48S, S147C, and Q204C) and roGFP2 (the same plus S65T) with physiologically or toxicologically relevant oxidants both in vitro and in living mammalian cells. Furthermore, we investigated the response of the redox probes under physiological redox changes during superoxide bursts in macrophage cells, hyperoxic and hypoxic conditions, and in responses to H(2)O(2)-stimulating agents, e.g. epidermal growth factor and lysophosphatidic acid.     

Treatments with gras compounds to keep fig fruit (Ficus carica L.) quality during cold storage

The trade of fresh fig fruit is restricted by its high perishability and numerous attempts have been done to extend the postharvest life. The main difficulties can be found in the fast ripening and the easiness of pathogen spread. Although the ripening can be slowed by low storage temperatures (close to 0 degrees C) the control of pathogens remains still unsolved since no pesticide treatments are allowed. Generally Recognized As Save Compounds (G.R.A.S.) are possible candidates to fulfil this void. Sodium carbonate (SC) solutions (0.5, 1, 2 and 3%) and acetic acid (AAC) vapours (25, 50 and 100 ppm) have been used as postharvest treatments to control Botrytis cinerea on black (Craxiou de Porcu) and white (Rampelina) fig varieties. Fruit was subsequently stored at 2 or 8 degrees C and 90% relative humidity for two weeks. At the end of the experiment decay, weight loss, pH, acidity, total soluble solids and visual assessment were performed. SC treatment at 1% reduced significantly the decay while, lower and higher concentrations did not. Between the two studied varieties the lowest decay percentage (9.8%) was found for the Craxiou de Porcu. Using AAC a good efficacy was achieved only with 100 ppm, this treatment decrease to 2.4% the incidence of decay irrespective to storage temperature. Lower concentrations were lesser effective and the efficacy was strictly dependent on the storage temperature, being higher at 2 degrees C. No treatment damages were observed following SC or AAC applications. Regarding fruit weight loss all treatments did not affect this parameter that was 10.1% and 16.9% at 2 and 8 degrees C, respectively. Chemical analyses performed at the end of the storage period did not evidenced differences among the treatments and slight ones if compared to initial values. Visual score of the fruit at the end of storage evidenced a better keeping quality for Craxiou de Porcu especially when stored at 2 degrees C. Both G.R.A.S. compounds are promising, but in the reported experiments AAC was the most effective.