Tracking the source of the hepatitis B virus-specific CD8 T cells during lamivudine treatment

Lamivudine treatment in chronic hepatitis B leads to the reconstitution of virus-specific T cells in the circulation, but it is not clear whether this is the preferential result of T cell efflux from the liver or lymph nodes. To address this question, the frequency and function of liver-, lymph node-, and blood-derived hepatitis B virus (HBV)-specific CD8 T cells were analyzed in patients treated with lamivudine and undergoing liver transplantation. HBV-specific CD8 T cells, identified in portal lymph nodes, were able to expand in vitro after antigen-specific stimulation and displayed a heterogeneous profile of cytokine production. These findings suggest that the peripherally reconstituted HBV-specific CD8 T cells can originate from precursor cells within lymph nodes

Genotoxic effect induced by hydrogen peroxide in human hepatoma cells using comet assay

Background: Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) is a common reactive oxygen intermediate generated by various forms of oxidative stress. Aim: The aim of this study was to investigate the DNA damage capacity of H<sub>2</sub>O<sub>2</sub> in HepG2 cells. Methods: Cells were treated with H<sub>2</sub>O<sub>2</sub> at concentrations of 25 mM or 50 mM for 5 min, 30 min, 40 min, 1 h, or 24 h in parallel. The extent of DNA damage was assessed by the comet assay. Results: Compared to the control, DNA damage by 25 and 50 mM H<sub>2</sub>O<sub>2</sub> increased significantly with increasing incubation time up to 1 h, but it was not increased at 24 h. Conclusions: Our findings confirm that H<sub>2</sub>O<sub>2</sub> is a typical DNA damage-inducing agent and thus is a good model system to study the effects of oxidative stress. DNA damage in HepG2 cells increased significantly with H<sub>2</sub>O<sub>2</sub> concentration and time of incubation but later decreased likely due to DNA repair mechanisms and antioxidant enzymes.Keywords: DNA damage; hydrogen peroxide; HepG2 cells; comet assa

Beyond theory:an examination of lean new product introduction practices in the UK

Interest is growing around the application of lean techniques to new product introduction (NPI). Although a relatively emergent topic compared with the application of ‘lean’ within the factory, since 2000 there has been an exponential rise in the literature on this subject. However, much of this work focuses on describing and extolling the virtues of the ‘Toyota approach’ to design. Therefore, by way of a stock take for the UK, the present authors' research has set out to understand how well lean product design practices have been adopted by leading manufacturers. This has been achieved by carrying out in-depth case studies with three carefully selected manufacturers of complex engineered products. This paper describes these studies, the detailed results and subsequent findings, and concludes that both the awareness and adoption of practices is generally embryonic and far removed from the theory advocated in the literature

Oscillatory, Computational, and Behavioral Evidence for Impaired GABAergic Inhibition in Schizophrenia

The dysconnection hypothesis of schizophrenia (SZ) proposes that psychosis is best understood in terms of aberrant connectivity. Specifically, it suggests that dysconnectivity arises through aberrant synaptic modulation associated with deficits in GABAergic inhibition, excitation-inhibition balance and disturbances of high-frequency oscillations. Using a computational model combined with a graded-difficulty visual orientation discrimination paradigm, we demonstrate that, in SZ, perceptual performance is determined by the balance of excitation-inhibition in superficial cortical layers. Twenty-eight individuals with a DSM-IV diagnosis of SZ, and 30 age- and gender-matched healthy controls participated in a psychophysics orientation discrimination task, a visual grating magnetoencephalography (MEG) recording, and a magnetic resonance spectroscopy (MRS) scan for GABA. Using a neurophysiologically informed model, we quantified group differences in GABA, gamma measures, and the predictive validity of model parameters for orientation discrimination in the SZ group. MEG visual gamma frequency was reduced in SZ, with lower peak frequency associated with more severe negative symptoms. Orientation discrimination performance was impaired in SZ. Dynamic causal modeling of the MEG data showed that local synaptic connections were reduced in SZ and local inhibition correlated negatively with the severity of negative symptoms. The effective connectivity between inhibitory interneurons and superficial pyramidal cells predicted orientation discrimination performance within the SZ group; consistent with graded, behaviorally relevant, disease-related changes in local GABAergic connections. Occipital GABA levels were significantly reduced in SZ but did not predict behavioral performance or oscillatory measures. These findings endorse the importance, and behavioral relevance, of GABAergic synaptic disconnection in schizophrenia that underwrites excitation-inhibition balance

A preliminary audit of medical and aid provision in English Rugby union clubs:compliance with Regulation 9

BackgroundGoverning bodies are largely responsible for the monitoring and management of risks associated with a safe playing environment, yet adherence to regulations is currently unknown. The aim of this study was to investigate and evaluate the current status of medical personnel, facilities, and equipment in Rugby Union clubs at regional level in England.MethodsA nationwide cross-sectional survey of 242 registered clubs was undertaken, where clubs were surveyed online on their current medical personnel, facilities, and equipment provision, according to regulation 9 of the Rugby Football Union (RFU).ResultsOverall, 91 (45. 04%) surveys were returned from the successfully contacted recipients. Of the completed responses, only 23.61% (n = 17) were found to be compliant with regulations. Furthermore, 30.56% (n = 22) of clubs were unsure if their medical personnel had required qualifications; thus, compliance could not be determined. There was a significant correlation (p = −0.029, r = 0.295) between club level and numbers of practitioners. There was no significant correlation indicated between the number of practitioners/number of teams and number of practitioners/number of players. There were significant correlations found between club level and equipment score (p = 0.003, r = −0.410), club level and automated external defibrillator (AED) access (p = 0.002, r = −0.352) and practitioner level and AED access (p = 0.0001, r = 0.404). Follow-up, thematic analysis highlighted widespread club concern around funding/cost, awareness, availability of practitioners and AED training.ConclusionThe proportion of clubs not adhering overall compliance with Regulation 9 of the RFU is concerning for player welfare, and an overhaul, nationally, is required

Reflections of physiotherapy students in the United Arab Emirates during their clinical placements: A qualitative study

BACKGROUND: Although Western models of education are being used to establish health professional programs in non-Western countries, little is known about how students in these countries perceive their learning experiences. The purpose of this qualitative study was to describe the reflections of physiotherapy students from a Middle East culture during their clinical placements and to compare them to reflections of physiotherapy students from a Western culture. METHODS: Subjects were six senior students (3 females, 3 males, mean age 22.6 years) and 15 junior, female students (mean age 20.1 years) in the baccalaureate physiotherapy program at a university in the United Arab Emirates (UAE). They wrote weekly entries in a journal while in their clinical placements. They described an event, their reaction to it, and how it might affect their future behavior. Two evaluators independently read and coded the content of all the journals, and then worked together to categorize the data and develop themes. A third evaluator, an UAE national, independently read the journals to validate the content analysis. A feedback session with students was used to further validate the data interpretation. The themes were compared to those derived from a similar study of Canadian physiotherapy students. RESULTS: The content of the students' reflections were grouped into 4 themes: professional behavior, awareness of learning, self-development and shift to a patient orientation, and identification and analysis of ethical issues. Although the events were different, students from the UAE considered many of the same issues reflected on by Canadian students. CONCLUSION: Physiotherapy students from a Middle East culture consider many of the same issues as students from a Western culture when asked to reflect on their clinical experience. They reflect on their personal growth, on how they learn in a clinical setting, and on the ethical and professional behaviors of themselves and others

Defining critical factors in multi-country studies of assisted reproductive technologies (ART): data from the US and UK health systems

As the worldwide use of assisted reproductive technologies (ART) continues to grow, there is a critical need to assess the safety of these treatment parameters and the potential adverse health effects of their use in adults and their offspring. While key elements remain similar across nations, geographic variations both in treatments and populations make generalizability challenging. We describe and compare the demographic factors between the USA and the UK related to ART use and discuss implications for research. The USA and the UK share some common elements of ART practice and in how data are collected regarding long-term outcomes. However, the monitoring of ART in these two countries each brings strengths that complement each other’s limitations

CD80 on Human T Cells Is Associated With FoxP3 Expression and Supports Treg Homeostasis

CD80 and CD86 are expressed on antigen presenting cells (APCs) and their role in providing costimulation to T cells is well established. However, it has been shown that these molecules can also be expressed by T cells, but the significance of this observation remains unknown. We have investigated stimuli that control CD80 and CD86 expression on T cells and show that in APC-free conditions around 40% of activated, proliferating CD4+ T cells express either CD80, CD86 or both. Expression of CD80 and CD86 was strongly dependent upon provision of CD28 costimulation as ligands were not expressed following TCR stimulation alone. Furthermore, we observed that CD80+ T cells possessed the hallmarks of induced regulatory T cells (iTreg), expressing Foxp3 and high levels of CTLA-4 whilst proliferating less extensively. In contrast, CD86 was preferentially expressed on INF-γ producing cells, which proliferated more extensively and had characteristics of effector T cells. Finally, we demonstrated that CD80 expressed on T cells inhibits CTLA-4 function and facilitates the growth of iTreg. Together these data establish endogenous expression of CD80 and CD86 by activated T cells is not due to ligand capture by transendocytosis and highlight clear differences in their expression patterns and associated functions