Terminal galactose residues on transferrin are increased in mid-life adults compared to young adults

Humans undergo biological ageing at different rates. This associates with functional decline in a number of physiological systems and increasing incidence of age-related pathologies. The discovery of robust biomarkers of ageing could be used to identify early divergence from a path of healthy ageing towards age-related disease. In the present study, we undertook proteomic analysis of plasma from healthy young men (mean age = 21.4 ± 1.5 years) and healthy mid-life men (mean age = 57.0 ±1.6 years). We identified twelve spots including transferrin, complement C3b and transthyretin that differed in abundance between the age groups. Transferrin spots showed an acidic pI shift in older males. Sandwich ELISAs were used to investigate the changes further. C3b levels were below the level of detection by ELISA and plasma concentrations of total transferrin or transthyretin were not different between the age groups studied here. However, analysis of transferrin N-glycan structures showed an increase in terminal galactose residues in older men, suggesting that the loss of terminal N-acetyl neuraminic acid residues contributes to the more acid pI of transferrin spots observed with age. Terminal galactosylation of transferrin may be a biomarker of healthy ageing and is now under investigation in the MARKAGE study.

Sensitivity and reliability of objective image analysis compared to subjective grading of bulbar hyperaemia

Aims: To establish the sensitivity and reliability of objective image analysis in direct comparison with subjective grading of bulbar hyperaemia. Methods: Images of the same eyes were captured with a range of bulbar hyperaemia caused by vasodilation. The progression was recorded and 45 images extracted. The images were objectively analysed on 14 occasions using previously validated edge-detection and colour-extraction techniques. They were also graded by 14 eye-care practitioners (ECPs) and 14 non-clinicians (NCb) using the Efron scale. Six ECPs repeated the grading on three separate occasions Results: Subjective grading was only able to differentiate images with differences in grade of 0.70-1.03 Efron units (sensitivity of 0.30-0.53), compared to 0,02-0.09 Efron units with objective techniques (sensitivity of 0.94-0.99). Significant differences were found between ECPs and individual repeats were also inconsistent (p<0.001). Objective analysis was 16x more reliable than subjective analysis. The NCLs used wider ranges of the scale but were more variable than ECPs, implying that training may have an effect on grading. Conclusions: Objective analysis may offer a new gold standard in anterior ocular examination, and should be developed further as a clinical research tool to allow more highly powered analysis, and to enhance the clinical monitoring of anterior eye disease.

Ocular motor triad with single vision contact lenses compared to spectacle lenses

Aim: Theoretically myopes are required to exert more accommodation and vergence when wearing single vision contact lenses compared to glasses and hypermetropes less. This study aims to quantify the effects clinically. Method: Thirty subjects (21 female, nine male, average age 21.0 ± 2.2 years) with a range of refractive errors (-7.87 D to +3.50 D) viewed in a random order, static targets at 0.1, 0.5, 1.0, 2.0, 3.0, 4.0 and 5.0 D accommodative demand that were matched for angular subtense. The subjects were fully corrected with spectacles and daily disposable contact lenses to their full prescription. Accommodation was monitored objectively with the PowerRefractor and Shin-Nippon SRW5000 and vergence and pupil size with the PowerRefractor. Results: Myopes exerted greater accommodative effort for viewing near targets with contact lenses than glasses and hypermetropes less (r2 = 0.35, p = 0.001 PowerRefractor). Myopes also exerted greater vergence effort for viewing near targets with contact lenses than glasses and hypermetropes less (r2 = 0.22, p < 0.01). Conclusion: Theoretical calculation of the accommodative and vergence requirements with glasses compared to contact lenses reflect clinical findings, although there is reasonable variability between individuals. © 2006 British Contact Lens Association.

Low level of cross-resistance between triclosan and antibiotics in Escherichia coli K-12 and E. coli O55 compared to E-coli O157

Misuse of biocides has encouraged the emergence of resistance and cross-resistance in certain strains. This study investigated resistance of triclosan-adapted Escherichia coli K-12 and E. coli O55 to antimicrobial agents and compared these to E. coli O157:H7. Cross-resistance in E. coli K-12 and E. coli O55 was observed however to a lesser extent than in E. coli O157:H7. Triclosan-adapted E. coli K-12 demonstrated cross-resistance to chloramphenicol, whereas triclosan-adapted E. coli O55 exhibited resistance to trimethoprim. In comparison, E. coli O157:H7 was resistant to chloramphenicol, tetracycline, amoxicillin, amoxicillin/clavulanic acid, trimethoprim, benzalkonium chloride and chlorohexidine suggesting strain specific rather than general resistance mechanisms. © 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

Greater CD8+ TCR heterogeneity and functional flexibility in HIV-2 compared to HIV-1 infection

Virus-specific CD8+ T cells are known to play an important role in the control of HIV infection. In this study we investigated whether there may be qualitative differences in the CD8+ T cell response in HIV-1- and HIV-2-infected individuals that contribute to the relatively efficient control of the latter infection. A molecular comparison of global TCR heterogeneity showed a more oligoclonal pattern of CD8 cells in HIV-1- than HIV-2-infected patients. This was reflected in restricted and conserved TCR usage by CD8+ T cells recognizing individual HLA-A2- and HLA-B57-restricted viral epitopes in HIV-1, with limited plasticity in their response to amino acid substitutions within these epitopes. The more diverse TCR usage observed for HIV-2-specific CD8 T cells was associated with an enhanced potential for CD8+ expansion and IFN- production on cross-recognition of variant epitopes. Our data suggest a mechanism that could account for any possible cross-protection that may be mediated by HIV-2-specific CD8+ T cells against HIV-1 infection. Furthermore, they have implications for HIV vaccine development, demonstrating an association between a polyclonal, virus-specific CD8+ T cell response and an enhanced capacity to tolerate substitutions within T cell epitopes.

Randomised trial of levonorgestrel intrauterine system compared to usual medical treatment for heavy menstrual bleeding:the ECLIPSE Trial

Objective: Heavy menstrual bleeding (menorrhagia) is a common problem, yet evidence is limited to inform therapeutic decisions.We compared the levonorgestrel-releasing intrauterine system(LNG-IUS) to usual medical treatment in a pragmatic randomised trial in primary care. Methods: We randomly assigned 571 women consulting their primary care providers with menorrhagia to LNG-IUS or to usual medical treatment as clinically appropriate (tranexamic acid, mefenamic acid, combined estrogen/progestogen or progestogen only). The primary outcome was a patient-reported measure ofimpact of menorrhagia, the validated Menorrhagia Multi-Attribute Scale (MMAS), assessed over 2 years. Secondary measures included generic quality of life (SF-36), sexual activity and surgical intervention.Results MMAS scores improved from baseline in both the LNG-IUS and usual medical treatment groups by 6 months (mean increases 32.7 points versus 21.4 points, respectively; P < 0.001for both) and were maintained over 2 years, but improvements were significantly greater with LNG-IUS (mean between-group difference 13.4 points, 95%CI, 9.9–16.9; P < 0.001).All domains of MMAS (practical difficulties, social life, family life,work/daily routine, psychological well being and physical health)improved significantly more with LNG-IUS, as were seven of the eight domains of SF-36. More women were still using LNG-IUSthan usual medical treatment at 2 years (64% versus 38%,P < 0.001). There were no significant between-group differences in surgical intervention rates or sexual activity scores. There were no serious adverse events in either group.Conclusions Among women presenting to primary care providers with menorrhagia, LNG-IUS was more effective than usual medical treatment at reducing the impact of this problem on their quality of life. In practice therefore, conventional treatments, such as tranexamic and mefenamic acid, remain helpful choices in women for whom LNG-IUS is considered unsuitable, or due to individual preference. For other women, LNG-IUS can be confidently recommended as an effective initial medical therapy for menorrhagia. Funding: This project was funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme (project number 02/06/02)

Free radical reaction products and antioxidant capacity in beating heart coronary artery surgery compared to conventional bypass

Oxygen-derived free radicals are important agents of tissue injury during ischemia and reperfusion. The aim of this study was to investigate changes in protein and lipid oxidation and antioxidant status in beating heart coronary artery surgery and conventional bypass and to compare oxidative stress parameters between the two bypass methods. Serum lipid hydroperoxide, nitric oxide, protein carbonyl, nitrotyrosine, vitamin E, and β-carotene levels and total antioxidant capacity were measured in blood of 30 patients undergoing beating heart coronary artery surgery (OPCAB, off-pump coronary artery bypass grafting) and 12 patients undergoing conventional bypass (CABG, on-pump coronary artery bypass grafting). In the OPCAB group, nitric oxide and nitrotyrosine levels decreased after reperfusion. Similarly, β-carotene level and total antioxidant capacity also decreased after anesthesia and reperfusion. In the CABG group, nitric oxide and nitrotyrosine levels decreased after ischemia and reperfusion. However, protein carbonyl levels elevated after ischemia and reperfusion. Vitamin E, β-carotene, and total antioxidant capacity decreased after ischemia and reperfusion. Significantly decreased nitration and impaired antioxidant status were seen after reperfusion in both groups. Moreover, elevated protein carbonyls were found in the CABG group. The off-pump procedure is associated with lower degree of oxidative stress than on-pump coronary surgery. © 2011 Pleiades Publishing, Ltd.

Efficacy and safety of infliximab-biosimilar compared to other biological drugs in rheumatoid arthritis: a mixed treatment comparison.

OBJECTIVE: The aim of this meta-analysis was to compare the efficacy and safety of infliximab-biosimilar and other available biologicals for the treatment of rheumatoid arthritis (RA), namely abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab and tocilizumab. METHODS: A systematic literature review of MEDLINE database until August 2013 was carried out to identify relevant randomized controlled trials (RCTs). Bayesian mixed treatment comparison method was applied for the pairwise comparison of treatments. Improvement rates by the American College of Rheumatology criteria (ACR20 and ACR50) at week 24 were used as efficacy endpoints, and the occurrence of serious adverse events was considered to assess the safety of the biologicals. RESULTS: Thirty-six RCTs were included in the meta-analysis. All the biological agents proved to be superior to placebo. For ACR20 response, certolizumab pegol showed the highest odds ratio (OR) compared to placebo, OR 7.69 [95 % CI 3.69-14.26], followed by abatacept OR 3.7 [95 % CI 2.17-6.06], tocilizumab OR 3.69 [95 % CI 1.87-6.62] and infliximab-biosimilar OR 3.47 [95 % CI 0.85-9.7]. For ACR50 response, certolizumab pegol showed the highest OR compared to placebo OR 8.46 [3.74-16.82], followed by tocilizumab OR 5.57 [95 % CI 2.77-10.09], and infliximab-biosimilar OR 4.06 [95 % CI 1.01-11.54]. Regarding the occurrence of serious adverse events, the results show no statistically significant difference between infliximab-biosimilar and placebo, OR 1.87 [95 % CI 0.74-3.84]. No significant difference regarding efficacy and safety was found between infliximab-biosimilar and the other biological treatments. CONCLUSION: This is the first indirect meta-analysis in RA that compares the efficacy and safety of biosimilar-infliximab to the other biologicals indicated in RA. We found no significant difference between infliximab-biosimilar and other biological agents in terms of clinical efficacy and safety.

Initial placement methods for Haitian adult ESOL students : the NYS place test plus profile data compared to subjective assessment

Few valid and reliable placement procedures are available to assess the English language proficiency of adults who enroll in English for Speakers of Other Languages (ESOL) programs. Whereas placement material exists for children and university ESOL students, the needs of students in adult community education programs have not been adequately addressed. Furthermore, the research suggests that a number of variables, such as, native language, age, prior schooling, length of residence, and employment are related to second language acquisition. Numerous studies contribute to our understanding of the relationship of these factors to second language acquisition of Spanish-speaking students. Again, there is a void in the research investigating the factors affecting second language acquisition and consequently, appropriate placement of Haitian Creole-speaking students. This study compared a standardized instrument, the NYS Place Test, used alone and in combination with a writing sample in English, to subjective judgement of a department coordinator for initial placement of Haitian adult ESOL students in a community education program. The study also investigated whether or not consideration of student profile data improved the accuracy of the test. Finally, the study sought to determine if a relationship existed between student profile data and those who withdrew from the program or did not enter a class after registering. Analysis of the data by crosstabulation and chi-square revealed that the standardized NYS Place Test was at least as accurate as subjective department coordinator placement and that one procedure could be substituted for li other. Although the writing sample in English improved accuracy of placement by the NYS test, the results were not significant. Of the profile variables, only length of residence was found to be significantly related to accuracy of placement using the NYS Place Test. The number of incorrect placements was higher for those students who lived in the host country from twenty-five to one hundred ten months. A post hoc analysis of NYS test scores according to level showed that those learners who placed in level three also had a significantly higher incidence of incorrect placements. No significant relationship was observed between the profile variables and those who withdrew from the program or registered but did not enter a class.

The feasibility of determining the effectiveness and cost-effectiveness of medication organisation devices compared with usual care for older people in a community setting : systematic review, stakeholder focus groups and feasibility randomised controlled trial

This project was funded by National Institute for Health Research (NIHR) Health Technology Assessment Programme and will be published in full in Health Technology Assessment; Vol. 20, No. 50. See the NIHR Journals Library website for further project information.

A systematic review of economic evaluations of the use of robotic assisted laparoscopy in surgery compared with open or laparoscopic surgery

Peer reviewed

A systematic review of economic evaluations of the use of robotic assisted laparoscopy in surgery compared with open or laparoscopic surgery

Peer reviewed

Incidentally Raised Cardiac Troponin I Has a Worse Prognosis in Older Patients Compared to Those with Normal Cardiac Troponin I and Patients with Acute Coronary Syndrome : A Cohort Study

Acknowledgement J.H.B.-S. was supported by the Norfolk and Norwich University Hospital (NNUH) Research and Development (R&D) research capability funds between July 2013 and December 2014.

Medium-term prognosis of an incident cohort of parkinsonian patients compared to controls

Funding This work was supported by Parkinson's UK (grant numbers G0502, G0914), BMA Doris Hillier Award, the BUPA Foundation, NHS Grampian Endowments, RS MacDonald Trust.