Near-infrared reflectance imaging of neovascular age-related macular degeneration

Contains fulltext : 81007.pdf (publisher's version ) (Closed access)PURPOSE: To evaluate various types of neovascular age-related macular degeneration (AMD) by near-infrared fundus reflectance (NIR) as compared to fundus fluorescein angiography (FFA) and to test NIR for assessment of leakage due to choroidal neovascularization (CNV). PATIENTS AND METHODS: Thirty-three patients with neovascular AMD (cases) and 20 age-matched patients with non-exudative AMD and healthy subjects (controls) were examined with a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2). NIR images of neovascular AMD were qualitatively compared to the corresponding FFA and to age-matched controls. CNV membranes and exudation areas were manually segmented on FFA and NIR and analyzed quantitatively. Results : Of all cases included, five eyes had classic CNV, six had minimal classic lesions, 15 occult CNV's and seven eyes had retinal angiomatous proliferation (RAP). A dark halo on NIR was found in all cases and showed high correspondence to leakage on FFA (r (2) = 0.93; p < 0,0005). In classic CNV and minimal classic CNV, the classic part of the lesion on FFA revealed strong correlation to a dark core surrounded by a bright reflecting ring on NIR (r (2) = 0.88; p < 0.0005). Occult parts on FFA of minimal classic CNV and occult CNV lesions appeared as poorly demarcated, jagged areas of increased NIR. RAP was characterized by speckled NIR located at the intraretinal neovascular complex. CONCLUSIONS: NIR imaging in neovascular AMD revealed characteristic alterations depending on the type of CNV. These changes may reflect histological differences of the lesions. Leakage caused local darkening of NIR, presumably originating from increased light-scattering and absorbance by fluid accumulation and sub-cellular structure alterations

Comparison of printed glycan array, suspension array and ELISA in the detection of human anti-glycan antibodies

Anti-glycan antibodies represent a vast and yet insufficiently investigated subpopulation of naturally occurring and adaptive antibodies in humans. Recently, a variety of glycan-based microarrays emerged, allowing high-throughput profiling of a large repertoire of antibodies. As there are no direct approaches for comparison and evaluation of multi-glycan assays we compared three glycan-based immunoassays, namely printed glycan array (PGA), fluorescent microsphere-based suspension array (SA) and ELISA for their efficacy and selectivity in profiling anti-glycan antibodies in a cohort of 48 patients with and without ovarian cancer. The ABO blood group glycan antigens were selected as well recognized ligands for sensitivity and specificity assessments. As another ligand we selected P1, a member of the P blood group system recently identified by PGA as a potential ovarian cancer biomarker. All three glyco-immunoassays reflected the known ABO blood groups with high performance. In contrast, anti-P1 antibody binding profiles displayed much lower concordance. Whilst anti-P1 antibody levels between benign controls and ovarian cancer patients were significantly discriminated using PGA (p = 0.004), we got only similar results using SA (p = 0.03) but not for ELISA. Our findings demonstrate that whilst assays were largely positively correlated, each presents unique characteristic features and should be validated by an independent patient cohort rather than another array technique. The variety between methods presumably reflects the differences in glycan presentation and the antigen/antibody ratio, assay conditions and detection technique. This indicates that the glycan-antibody interaction of interest has to guide the assay selection

Unemployment and ill health: a connection through inflammation?

<p>Abstract</p> <p>Background</p> <p>Unemployment is a source of acute and long-term psychosocial stress. Acute and chronic psychosocial stress can induce pronounced changes in human immune responses. In this study we tested our hypothesis that stress-induced low-grade tissue inflammation is more prevalent among the unemployed.</p> <p>Methods</p> <p>We determined the inflammatory status of 225 general population subjects below the general retirement age (65 years in Finland). Those who had levels of both interleukin-6 (≥ 0.97 pg/mL) and high-sensitivity C-reactive protein (≥ 1.49 mg/L) above the median were assessed to have an elevated inflammatory status (n = 72).</p> <p>Results</p> <p>An elevated inflammatory status was more common among the unemployed than among other study participants (59% versus 30%, p = 0.011). In the final multivariate model, those who were unemployed had over five-fold greater odds for having an elevated inflammatory status (OR 5.20, 95% CI 1.55-17.43, p = 0.008).</p> <p>Conclusion</p> <p>This preliminary finding suggests that stress-induced low-grade inflammation might be a link between unemployment and ill health.</p

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Brief cognitive assessment in a UK population sample – distributional properties and the relationship between the MMSE and an extended mental state examination

BACKGROUND: Despite the MMSE's known flaws, it is still used extensively as both a screening instrument for dementia and a population measure of cognitive ability. The aim of this paper is to provide data on the distribution of MMSE scores in a representative sample from the UK population and to compare it with an extended cognitive assessment (EMSE) which covers a wider range of cognitive domains and provides a wider range of difficulty levels. METHODS: The MMSE and the EMSE were administered to over 12,000 participants at the screening stage of the MRC Cognitive Function and Ageing Study (MRC CFAS). MRC CFAS is a multi-centre population-based study in England and Wales with respondents aged 65 years and older. RESULTS: Normative values on the MMSE and EMSE are presented by age group, sex and level of education. There are very large differences between age groups, with smaller differences seen between the sexes and by level of education. The EMSE extends the scores at the high end of the ability range, but is no better than the MMSE at differentiating between dementia and non-dementia. CONCLUSION: Population-derived norms are valuable for comparing an individual's score to the score that would be expected among the general population, given the individual's specific demographic characteristics

Gastrin-releasing peptide receptor-based targeting using bombesin analogues is superior to metabolism-based targeting using choline for in vivo imaging of human prostate cancer xenografts

Purpose: Prostate cancer (PC) is a major health problem. Overexpression of the gastrin-releasing peptide receptor (GRPR) in PC, but not in the hyperplastic prostate, provides a promising target for staging and monitoring of PC. Based on the assumption that cancer cells have increased metabolic activity, metabolism-based tracers are also being used for PC imaging. We compared GRPR-based targeting using the68Ga-labelled bombesin analogue AMBA with metabolism-based tar

Audiologic monitoring of multi-drug resistant tuberculosis patients on aminoglycoside treatment with long term follow-up

<p>Abstract</p> <p>Background</p> <p>Multi-drug resistant tuberculosis has emerged as a significant problem with the resurfacing of tuberculosis and thus the need to use the second line drugs with the resultant increased incidence of adverse effects. We discuss the effect of second line aminoglycoside anti-tubercular drugs on the hearing status of MDR-TB patients.</p> <p>Methods</p> <p>Sixty four patients were put on second line aminoglycoside anti-TB drugs. These were divided into three groups: group I, 34 patients using amikacin, group II, 26 patients using kanamycin and group III, 4 patients using capreomycin.</p> <p>Results</p> <p>Of these, 18.75% of the patients developed sensorineural hearing loss involving higher frequencies while 6.25% had involvement of speech frequencies also. All patients were seen again approximately one year after aminoglycoside discontinuation and all hearing losses were permanent with no threshold improvement.</p> <p>Conclusion</p> <p>Aminoglycosides used in MDR-TB patients may result in irreversible hearing loss involving higher frequencies and can become a hearing handicap as speech frequencies are also involved in some of the patients thus underlining the need for regular audiologic evaluation in patients of MDR-TB during the treatment.</p

Evaluating the effectiveness of a tailored multifaceted performance feedback intervention to improve the quality of care: protocol for a cluster randomized trial in intensive care

Contains fulltext : 95871.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Feedback is potentially effective in improving the quality of care. However, merely sending reports is no guarantee that performance data are used as input for systematic quality improvement (QI). Therefore, we developed a multifaceted intervention tailored to prospectively analyzed barriers to using indicators: the Information Feedback on Quality Indicators (InFoQI) program. This program aims to promote the use of performance indicator data as input for local systematic QI. We will conduct a study to assess the impact of the InFoQI program on patient outcome and organizational process measures of care, and to gain insight into barriers and success factors that affected the program's impact. The study will be executed in the context of intensive care. This paper presents the study's protocol. METHODS/DESIGN: We will conduct a cluster randomized controlled trial with intensive care units (ICUs) in the Netherlands. We will include ICUs that submit indicator data to the Dutch National Intensive Care Evaluation (NICE) quality registry and that agree to allocate at least one intensivist and one ICU nurse for implementation of the intervention. Eligible ICUs (clusters) will be randomized to receive basic NICE registry feedback (control arm) or to participate in the InFoQI program (intervention arm). The InFoQI program consists of comprehensive feedback, establishing a local, multidisciplinary QI team, and educational outreach visits. The primary outcome measures will be length of ICU stay and the proportion of shifts with a bed occupancy rate above 80%. We will also conduct a process evaluation involving ICUs in the intervention arm to investigate their actual exposure to and experiences with the InFoQI program. DISCUSSION: The results of this study will inform those involved in providing ICU care on the feasibility of a tailored multifaceted performance feedback intervention and its ability to accelerate systematic and local quality improvement. Although our study will be conducted within the domain of intensive care, we believe our conclusions will be generalizable to other settings that have a quality registry including an indicator set available. TRIAL REGISTRATION: Current Controlled Trials ISRCTN50542146

Breaking bad habits by improving executive function in individuals with obesity

Background: Two primary factors that contribute to obesity are unhealthy eating and sedentary behavior. These behaviors are particularly difficult to change in the long-term because they are often enacted habitually. Cognitive Remediation Therapy has been modified and applied to the treatment of obesity (CRT-O) with preliminary results of a randomized controlled trial demonstrating significant weight loss and improvements in executive function. The objective of this study was to conduct a secondary data analysis of the CRT-O trial to evaluate whether CRT-O reduces unhealthy habits that contribute to obesity via improvements in executive function. Method: Eighty participants with obesity were randomized to CRT-O or control. Measures of executive function (Wisconsin Card Sort Task and Trail Making Task) and unhealthy eating and sedentary behavior habits were administered at baseline, post-intervention and at 3 month follow-up. Results: Participants receiving CRT-O demonstrated improvements in both measures of executive function and reductions in both unhealthy habit outcomes compared to control. Mediation analyses revealed that change in one element of executive function performance (Wisconsin Card Sort Task perseverance errors) mediated the effect of CRT-O on changes in both habit outcomes. Conclusion: These results suggest that the effectiveness of CRT-O may result from the disruption of unhealthy habits made possible by improvements in executive function. In particular, it appears that cognitive flexibil ity, as measured by the Wisconsin Card Sort task, is a key mechanism in this process. Improving cognitive flexibility may enable individuals to capitalise on interruptions in unhealthy habits by adjusting their behavior in line with their weight loss goals rather than persisting with an unhealthy choice. Trial registration: The RCT was registered with the Australian New Zealand Registry of Clinical Trials (trial id: ACTRN12613000537752)