Huntington's disease: An immune perspective

Copyright © 2011 Annapurna Nayaketal. This article has been made available through the Brunel Open Access Publishing Fund.Huntington's disease (HD) is a progressive neurodegenerative disorder that is caused by abnormal expansion of CAG trinucleotide repeats. Neuroinflammation is a typical feature of most neurodegenerative diseases that leads to an array of pathological changes within the affected areas in the brain. The neurodegeneration in HD is also caused by aberrant immune response in the presence of aggregated mutant huntingtin protein. The effects of immune activation in HD nervous system are a relatively unexplored area of research. This paper summarises immunological features associated with development and progression of HD.U. Kishore acknowledges funding via BRIEF and Brunel University’s strategic funding for the Centre of Infection, Immunity and Disease Mechanisms

Immune deficiency and autoimmunity in patients with CTLA-4 mutations

Immune deficiency disorders are a heterogeneous group of diseases of variable genetic aetiology. Whilst the hallmark of immunodeficiency is susceptibility to infection, it is increasingly clear that autoimmunity is prevalent suggestive of a more general immune dysregulation in some cases. With the increasing use of genetic technologies the underlying causes of immune dysregulation are beginning to emerge. Here we provide a review of the heterozygous mutations found in the immune checkpoint protein CTLA-4, which was originally identified in cases of Common Variable Immunodeficiency Disorders (CVID) with accompanying autoimmunity. Study of these mutations provides insights into the biology of CTLA-4 as well as suggesting approaches for rational treatment of these patients. This article is protected by copyright. All rights reserved

Robots that can adapt like animals

As robots leave the controlled environments of factories to autonomously function in more complex, natural environments, they will have to respond to the inevitable fact that they will become damaged. However, while animals can quickly adapt to a wide variety of injuries, current robots cannot "think outside the box" to find a compensatory behavior when damaged: they are limited to their pre-specified self-sensing abilities, can diagnose only anticipated failure modes, and require a pre-programmed contingency plan for every type of potential damage, an impracticality for complex robots. Here we introduce an intelligent trial and error algorithm that allows robots to adapt to damage in less than two minutes, without requiring self-diagnosis or pre-specified contingency plans. Before deployment, a robot exploits a novel algorithm to create a detailed map of the space of high-performing behaviors: This map represents the robot's intuitions about what behaviors it can perform and their value. If the robot is damaged, it uses these intuitions to guide a trial-and-error learning algorithm that conducts intelligent experiments to rapidly discover a compensatory behavior that works in spite of the damage. Experiments reveal successful adaptations for a legged robot injured in five different ways, including damaged, broken, and missing legs, and for a robotic arm with joints broken in 14 different ways. This new technique will enable more robust, effective, autonomous robots, and suggests principles that animals may use to adapt to injury

A systematic review of strategies to recruit and retain primary care doctors

Background There is a workforce crisis in primary care. Previous research has looked at the reasons underlying recruitment and retention problems, but little research has looked at what works to improve recruitment and retention. The aim of this systematic review is to evaluate interventions and strategies used to recruit and retain primary care doctors internationally. Methods A systematic review was undertaken. MEDLINE, EMBASE, CENTRAL and grey literature were searched from inception to January 2015.Articles assessing interventions aimed at recruiting or retaining doctors in high income countries, applicable to primary care doctors were included. No restrictions on language or year of publication. The first author screened all titles and abstracts and a second author screened 20%. Data extraction was carried out by one author and checked by a second. Meta-analysis was not possible due to heterogeneity. Results 51 studies assessing 42 interventions were retrieved. Interventions were categorised into thirteen groups: financial incentives (n=11), recruiting rural students (n=6), international recruitment (n=4), rural or primary care focused undergraduate placements (n=3), rural or underserved postgraduate training (n=3), well-being or peer support initiatives (n=3), marketing (n=2), mixed interventions (n=5), support for professional development or research (n=5), retainer schemes (n=4), re-entry schemes (n=1), specialised recruiters or case managers (n=2) and delayed partnerships (n=2). Studies were of low methodological quality with no RCTs and only 15 studies with a comparison group. Weak evidence supported the use of postgraduate placements in underserved areas, undergraduate rural placements and recruiting students to medical school from rural areas. There was mixed evidence about financial incentives. A marketing campaign was associated with lower recruitment. Conclusions This is the first systematic review of interventions to improve recruitment and retention of primary care doctors. Although the evidence base for recruiting and care doctors is weak and more high quality research is needed, this review found evidence to support undergraduate and postgraduate placements in underserved areas, and selective recruitment of medical students. Other initiatives covered may have potential to improve recruitment and retention of primary care practitioners, but their effectiveness has not been established

Comparative evaluation of diode laser versus argon laser photocoagulation in patients with central serous retinopathy: A pilot, randomized controlled trial [ISRCTN84128484]

BACKGROUND: To evaluate the efficacy of diode laser photocoagulation in patients with central serous retinopathy (CSR) and to compare it with the effects of argon green laser. METHODS: Thirty patients with type 1 unilateral CSR were enrolled and evaluated on parameters like best corrected visual acuity (BCVA), direct and indirect ophthalmoscopy, amsler grid for recording scotoma and metamorphopsia, contrast sensitivity using Cambridge low contrast gratings and fluorescein angiography to determine the site of leakage. Patients were randomly assigned into 2 groups according to the statistical random table using sequence generation. In Group 1 (n = 15), diode laser (810 nm) photocoagulation was performed at the site of leakage while in Group 2 (n = 15), eyes were treated with argon green laser (514 nm) using the same laser parameters. Patients were followed up at 4, 8 and 12 weeks after laser. RESULTS: The mean BCVA in group 1 improved from a pre-laser decimal value of 0.29 ± 0.14 to 0.84 ± 0.23 at 4 weeks and 1.06 ± 0.09 at 12 weeks following laser. In group 2, the same improved from 0.32 ± 0.16 to 0.67 ± 0.18 at 4 weeks and 0.98 ± 0.14 at 12 weeks following laser. The improvement in BCVA was significantly better in group 1 (p < 0.0001) at 4 weeks. At 4 weeks following laser, all the patients in group1 were free of scotoma while 6 patients in group 2 had residual scotoma (p < 0.05). The mean contrast sensitivity in group 1 improved from pre-laser value of 98.4 ± 24.77 to 231.33 ± 48.97 at 4 weeks and 306.00 ± 46.57 at 12 weeks following laser. In group 2, the same improved from 130.66 ± 31.95 to 190.66 ± 23.44 at 4 weeks and 215.33 ± 23.25 at 12 weeks. On comparative evaluation, a significantly better (p < 0.001) improvement was noted in group 1. CONCLUSION: Diode laser may be a better alternative to argon green laser whenever laser treatment becomes indicated in patients with central serous retinopathy in terms of faster visual rehabilitation and better contrast sensitivity. In addition, diode laser also has the well-recognized ergonomic and economic advantages

Tensile strength assay comparing the resistance between two different autologous platelet concentrates (leucocyte-platelet rich fibrin versus advanced-platelet rich fibrin): a pilot study

Background: Since the leucocyte-platelet rich fibrin (L-PRF) was published in 2001, many studies have been developed, analyzing its properties, and also verifying new possibilities to improve it. Thereby, it emerges the advanced-platelet rich fibrin (A-PRF) with a protocol that optimizes the properties obtained by the L-PRF. Nonetheless, there is a gap in the literature to landmark the evolutive process concerning the mechanical properties in specific the resistance to tensile strength which consequently may influence the time for membrane degradation. Thus, this study had the goal to compare the resistance to the traction of membranes produced with the original L-PRF and A-PRF protocols, being the first to this direct comparison. Findings: The harvest of blood from a healthy single person, with no history of anticoagulant usage. We performed the protocols described in the literature, within a total of 13 membranes produced for each protocol (n = 26). Afterward, the membranes were prepared and submitted to a traction test assessing the maximal and the average traction achieved for each membrane. The data were analyzed statistically using the unpaired t test. Regarding average traction, A-PRF obtained a value of 0.0288 N mm−2 and L-PRF 0.0192 N mm−2 (p < 0.05 using unpaired t test). For maximal traction, A-PRF obtained 0.0752 N mm−2 and L-PRF 0.0425 N mm−2 (p < 0.05 using unpaired t test). Conclusion: With this study, it was possible to conclude that indeed A-PRF has a significative higher maximal traction score and higher average traction compared to L-PRF, indicating that it had a higher resistance when two opposing forces are applied.info:eu-repo/semantics/publishedVersio

Enriching Peptide Libraries for Binding Affinity and Specificity Through Computationally Directed Library Design

Peptide reagents with high affinity or specificity for their target protein interaction partner are of utility for many important applications. Optimization of peptide binding by screening large libraries is a proven and powerful approach. Libraries designed to be enriched in peptide sequences that are predicted to have desired affinity or specificity characteristics are more likely to yield success than random mutagenesis. We present a library optimization method in which the choice of amino acids to encode at each peptide position can be guided by available experimental data or structure-based predictions. We discuss how to use analysis of predicted library performance to inform rounds of library design. Finally, we include protocols for more complex library design procedures that consider the chemical diversity of the amino acids at each peptide position and optimize a library score based on a user-specified input model.National Institute of General Medical Sciences (U.S.) (Award R01 GM110048