Age-related differences in the temporal dynamics of prospective memory retrieval: a lifespan approach

The efficiency of prospective memory (PM) typically increases from childhood to young adulthood and then decreases in later adulthood. The current study used event-related brain potentials (ERPs) to examine the development of the neural correlates of processes associated with the detection of a PM cue, switching from the ongoing activity to the prospective task, retrieval of the intention from memory or task set configuration, and strategic monitoring of the environment. The study included 99 participants that were 7.5-83 years of age. Slow wave activity related to strategic monitoring was reliable across the lifespan suggesting that all ages were able to allocate attentional resources to facilitate PM. Additionally, components of the ERPs related to cue detection, switching, and task configuration were reliable across the lifespan, suggesting that similar processes contribute to PM at all ages. In children, PM errors may have resulted from a decoupling of processes supporting cue detection and switching from the ongoing activity to the prospective element of the task. In younger and older adults, PM errors appeared to result from the failure to detect PM cues in the environment. These findings lead to the conclusion that different processes may contribute to variation in PM across the lifespan.     

Intra-articular fate of degradable poly(ethyleneglycol)-hydrogel microspheres as carriers for sustained drug delivery

A novel degradable microsphere (MS) for intra-articular drug delivery, composed of a polyethylene glycol (PEG) core containing degradable regions made of short poly-(lactic-co-glycolic acid) (PLGA) sequences – named PEG-hydrogel MS – was injected into the cavity of sheep shoulder joint, and compared to non-degradable MS devoid of hydrolysable crosslinker in terms of location, degradation and inflammation. One week after intra-articular injection both groups of MS were localized beneath the synovial lining of the synovial fringes located at bottom of the shoulder joint, while a fraction of particles remained in synovial fluid. Histological analyses made one and 4 weeks after intra-articular injection showed cell proliferation around the non-degradable MS entrapped within the synovium. By contrast, degradable PEG-hydrogel MS were surrounded by few cells. The degradation of degradable PEG-hydrogel MS within the synovium was slow and was not fully complete after four weeks. Our findings indicate that the tissue entrapment of MS below the synovial lining was independent of the material degradability, while degradable PEG-hydrogel MS are less inflammatory than the non-degradable one. Degradable PEG-hydrogel MS offer several advantages over the non-degradable MS as carriers for a sustained drug delivery in synovial tissue according to the low intensity of inflammatory reaction triggered in synovium.     

Phase I dose-escalation study of a monovalent heat shock protein 70-herpes simplex virus type 2 (HSV-2) peptide-based vaccine designed to prime or boost CD8 T-cell responses in HSV-naïve and HSV-2-infected subjects

This was a phase I study to assess the safety, tolerability, and immunogenicity of escalating doses of AG-702, a noncovalent complex of an HLA A*0201-restricted epitope in the glycoprotein B protein of herpes simplex virus type 2 (gB2) and truncated human constitutive heat shock protein 70. Similar vaccines have been immunogenic in animals. Three injections of 10 to 250 mug were administered intradermally to HLA A*0201-bearing subjects who were either herpes simplex virus type 2 (HSV-2)-infected or HSV uninfected. Sixty-two participants received the vaccine, 60 completed the protocol, and T-cell data were accrued for 56 subjects. The vaccine was safe and well tolerated. New or boosted responses to the HSV-2 CD8 epitope were not detected. Baseline responses to an epitope in virion proteins 13/14 were higher than responses to the gB2 epitope. A heat shock protein vaccine with an HSV-2 peptide appears to be safe at the doses studied in healthy adults with or without HSV infection. Modifications of the dose, adjuvant, route, schedule, or HSV antigen may be required to improve responses.     

IL28B polymorphism -- predictive factor of HCV infected genotype 1 individuals to treatment response and management of therapy

It is estimated that approximately 3% of the world population are chronically infected with HCV, as the annual incidence of HCV infection is approximately 3-4 million people. Despite all efforts made to eradicate the HCV infection, after the standard therapy (PegIFN and ribavirin for 48 weeks) only 40-50% of the HCV infected individuals with genotype 1 achieve sustained virological response (SVR). Since our goal today is the eradication of HCV infection, our prior concern has become the identification of predictor factors concerning treatment response. Recent studies such as GWAS have been concerned with the genetic factors and the response to treatment. Recently all interest has been turned towards the demonstration of the host polymorphism located upstream of the IL-28B gene and which is associated with sustained virological response to treatment with pegylated interferon Alfa in combination with ribavirin. Although 2011 comes with the FDA approval of the new triple therapy associating telaprevir/ boceprevir to the standard therapy, a new ethical concern regarding the high costs of this treatment rises the problem of who is the first in line? This is just the beginning of a new quest to further investigate the relationship between the host's polymorphism of the IL-28 gene and the standard and triple therapy in HCV infected individuals in achieving SVR as well as who should receive standard or triple therapy. Determination of the IL-28 polymorphisms may be used together with clinical assessment in order to evaluate patients and to personalize their treatment. The purpose of this paper is to underline the main concerns regarding the goal and endpoints of the HCV therapy, and the relationship of IL-28 in achieving sustained virological response, as well as in pointing out the importance to determine prior to initiating treatment the polymorphism of IL-28 since it is a strong predictor. This is important because it will increase the chances to achieve SVR, it will be cost-effective and reduces adverse effects.     

Assessment of liver steatosis in chicken by using acoustic radiation force impulse imaging: preliminary results

Objective

To evaluate acoustic radiation force impulse (ARFI) imaging as a non-invasive tool for quantification of the grades of liver steatosis in chickens.

Methods

We used two different diets: a standard diet (SD group) and a hyperlipidaemic diet (HD group). The ARFI technique was performed in all the animals in the right hepatic lobe and shear wave velocity (SWV) was measured and expressed in metres per second (m/s). Plasma lipid levels were analysed. Steatosis was quantified by using semiquantitative analysis. Statistical analysis was used and Pearson’s correlation coefficient was calculated.

Results

Mean SWV was 0.94?±?0.16 m/s (range 0.8–1.3 m/s) in the SD group and 1.91?±?0.25 m/s (range 1.3–2.2 m/s) in the HD group (p?<?0.001). The lowest SWVs (≤1.3 m/s) corresponded to the chickens in the SD group, with 100% of the animals returning a score of 0, whereas the range of SWV in the HD group chickens was between 1.6 and 2.2 m/s. A substantial correlation was observed between SWVs with histological semiquantitative analysis of steatosis (r?=?0.85, p?<?0.001).

Conclusion

ARFI imaging is a non-invasive diagnostic tool that allows discrimination between the grades of liver steatosis in chickens.     

Effect of pH on the catalytic electrooxidation of NADH using different two-electron mediators immobilised on zirconium phosphate

A detailed study is reported on the electrocatalytic oxidation of β-nicotinamide adenine dinucleotide at three different carbon paste electrodes modified with redox mediators commonly used in bioelectrochemistry, viz. Meldola blue, methylene green and riboflavin, adsorbed on zirconium phosphate. Cyclic voltammetric investigations of these chemically modified electrodes performed in aqueous tris buffer solutions at different pHs allowed us to conclude that the immobilised redox species presented very stable redox properties, with midpoint potentials (E_m, ?125, ?40, and ?140 mV versus SCE for Meldola blue, methylene green and riboflavin, respectively) virtually independent of the pH of the contacting solution. The second-order rate constant for electrocatalytic oxidation of NADH as well as its pH dependence (from 6 to 8) were evaluated from rotating disk electrode (RDE) experiments, using the Koutecky–Levich approach.