Assessing visual acuity across five disease types: ETDRS charts are faster with clinical outcome comparable to Landolt Cs.

BACKGROUND: Given the diversity of visual acuity tests being employed across the world, we compared two frequently applied tests: ETDRS charts and an eight-orientation projected Landolt C test in accordance with ISO 8596 and DIN 58220 part 3. The goals of the investigation were to determine (i) test agreement and (ii) test-retest reliability, to assess (iii) test durations, and (iv) the acceptance of the tests by the examinees as well as the subjects' coping with the tests as rated by the examiner. METHODS: Seventy-five adult subjects with a visual acuity of ≥0.2 (4/20) were included in one of the following groups: normal, media opacity, maculopathy, optic neuropathy, (post)chiasmal lesion, or amblyopia. Visual acuity testing was carried out monocularly, in balanced randomized order and in two runs for each test on the same eye, applying forced choice. RESULTS: Agreement: Within each group, all tests were performed similarly, within ±0.048 logMAR. Reliability: Across all subject groups, with a probability of 95 %, test-retest differences were <0.18 logMAR for both ETDRS and Landolt tests. DURATION: The Landolt test lasted, on average, 1.8 times longer than ETDRS charts (p < 0.001). Acceptance: Examinees preferred the ETDRS test (p < 0.001), the examiner on average had no preference. CONCLUSION: The Landolt C test and the ETDRS test yielded comparable results in visual acuity and test-retest reliability in all disease groups. The ETDRS test was usually faster and more accepted by both examiners and examinees than the Landolt test.

Up-regulation of nestin in the infarcted myocardium potentially indicates differentiation of resident cardiac stem cells into various lineages including cardiomyocytes.

To identify proteins involved in cardiac regeneration, a proteomics approach was applied. A total of 26 proteins, which displayed aberrant expression in mouse hearts infarcted through ligation of the left anterior descending coronary artery, were identified. These included the intermediate filament protein nestin, which was up-regulated in the infarct border zone. Corresponding changes were observed for its mRNA. Nestin mRNA was also up-regulated in hearts from 17 of 19 patients with end-stage heart failure, including 4 with acute myocardial infarction in comparison with 8 donor hearts. Immunofluorescence confocal laser scanning microscopy revealed that nestin is expressed, on the one hand, in small proportions of cardiomyocytes, endothelial cells, smooth muscle cells, neuronal cells, and fibroblasts. On the other hand, it was found to be coexpressed with the stem cell markers c-kit, Sca-1, Mdr-1, and Abcg2 in small interstitial cells. In infarcted hearts from chimeric mice transplanted with bone marrow from enhanced green fluorescent protein (EGFP) transgenic mice, less than 1% of nestin-positive cells coexpressed EGFP, although EGFP-positive cells were abundant in these. Consequently, enhanced expression of nestin in the injured myocardium might reflect spontaneous regenerative processes supposedly based on the differentiation of resident cardiac stem cells into diverse cardiac cell types.

Lidocaine medicated plaster, an additional potential treatment option for localized post-surgical neuropathic pain: efficacy and safety results of a randomized, placebo-controlled trial.

OBJECTIVE: To assess the efficacy and safety of lidocaine 700 mg medicated plaster (lidocaine plaster) compared to placebo in patients with moderate to severe chronic post-surgical neuropathic pain (PSNP). METHODS: Patients (n = 363) with a diagnosis of PSNP for a minimum of 3 months to 36 months were randomized (1:1) to lidocaine plaster or placebo for a 12 week double-blind treatment period. Randomization was stratified as "plaster-only" (no concomitant medication for PSNP) or as "add-on" (stable systemic medication for PSNP). The primary efficacy endpoint was the change from baseline in 24 hour average pain intensity at Week 12, assessed by 11 point numerical rating scale (NRS). The trial was registered in ClinicalTrials.gov (NCT01752322) and EudraCT (2012-000347-28). RESULTS: Treatment with lidocaine or placebo plaster led to a clinically relevant reduction in average pain intensity. Pain reduction (least squares mean [LS mean] standard error [SE], [95% confidence interval, CI]) with lidocaine plaster (-1.70 [0.16], [-2.03, -1.38]) was numerically higher than with placebo (-1.47 [0.16], [-1.78, -1.15]) but the difference was not statistically significant (-0.23 [0.23], [-0.69, 0.22]). Pre-specified exploratory subgroup analyses showed the largest differentiation between lidocaine and placebo in patients without concomitant pain medication, and in patients with more than 1 year between surgery and enrollment. Many secondary outcomes showed a numerically larger improvement in favor of lidocaine. The most commonly reported adverse events were administration site reactions linked to topical administration. CONCLUSIONS: A clinically relevant pain reduction was observed with lidocaine plaster in patients with PSNP. The safety and tolerability profile is consistent with current knowledge.

Homologous housekeeping proteins in Nocardia--the NoDaMS proteomic database.

Nocardiosis is on the rise but hard to diagnose and the application of advanced subtyping technologies is called for. While the genomic sequence for the most virulent strain, Nocardia farcinica is available, proteome data are essentially non-existent. Nevertheless, they are necessary for functional studies on virulence and disease prevention. Here, comparative gel electrophoresis (PAGE)-based analyses of the five Nocardia strains SD1828, N. africana SD910, SD 925, N. sp. 1086, and N. asteroides N317 are discussed. The two-dimensional gel images of all strains are similar and dominated by housekeeping proteins such as chaperones and metabolic enzymes. The sequences of many proteins are highly homologous among strains and in some cases Mycobacterium sequences are closer matches to the unknown than those of N. farcinica. All mass spectrometry data are made available in the NoDaMS database at URL http://ifg.uni-muenster.de/ (Proteomics-Projects-NoDaMS) for re-evaluation with fresh sequencing information. Assignments, homology analyses, and peptide matches are presented. This data review comprises the first comprehensive summary of proteomic data of Nocardia.

Mass spectrometric analyses of CL(39), CL(41) and H(1), H(2), H(3) confirm identity with fetidin and lysenin produced by earthworm leukocytes.

Antibacterial proteins realize effective immunological mechanisms against invading pathogens. Some of them exert hemolytic and agglutinating properties. Here, we analyzed two hemolysins isolated from cell lysate (CL(39) and CL(41)) and three hemolytic proteins isolated from coelomic fluid (H(1), H(2) and H(3)) of the annelid Eisenia fetida using mass spectrometry and bioinformatics. We demonstrated the identity of CL(39,41) with fetidin and lysenin; these have been described earlier. H(1-3) share sequence components with fetidin but they seem to be glycosylated as shown for H(1). The results help to resolve a long debate concerning nomenclature and identity of these hemolytic proteins. They support: (1). the concept that the hemolytic proteins originate from chloragocytes; (2). their origin to some extent from large coelomocytes; and (3). the view that they are secreted into CF.

Regeneration of retinal ganglion cell axons in organ culture is increased in rats with hereditary buphthalmos.

This study used organ cultures to examine whether retinal ganglion cells (RGCs) retain their ability to regenerate axons in buphthalmos. A rat mutant with hereditary buphthalmos was used to (1) determine whether the extent of RGC loss corresponds to the severity and duration of elevated intraocular pressure (IOP), (2) examine whether RGCs exposed to an elevated IOP are able to regenerate their axons in a retina culture model, and (3) analyze the proteome of the regenerating retina in order to identify putative regeneration-associated proteins. Retrograde labeling of RGCs revealed a decrease in their numbers in the retinas of buphthalmic eyes that increased with age. Quantification of axons growing out of retinal explants taken at different stages of the disease demonstrated that buphthalmic RGCs possess a remarkable potential to regrow axons. As expected, immunohistochemistry and immunoblotting revealed that elevated IOP was associated with upregulation of certain known proteins, such as growth-associated protein 43, glial fibrillary acidic protein, and endothelin-1. In addition, two-dimensional polyacrylamide gel electrophoresis and mass spectrometry revealed several spots corresponding to proteins that were specifically regulated when buphthalmic RGCs were permitted to regrow their axons. Out of the proteins identified, heat-shock protein (HSP)-60 was constantly expressed during axonal growth at all stages of the disease. Antibodies against HSP-60 reduced axonal growth, indicating the involvement of this protein in regenerative axonal growth. These data are the first to show that diseased retinal neurons can grow their axons, and that HSP-60 supports neuritogenesis. This model may help to elucidate the fundamental mechanisms of optic neuropathy at stages preceding death caused by chronic injury, and aid in the development of neuroprotective strategies.

Surface plasmon resonance/mass spectrometry interface.

A strategy for combining surface plasmon resonance (SPR) biomolecular interaction analysis, and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is reported. Both techniques are highly complementary but need separate optimization to improve their individual specificity and sensitivity. Sensor surfaces that are optimal for kinetic analysis are not well suited for MALDI-MS and vice versa. In addition, the transfer of analyte from SPR to MS is crucial and often accompanied by sample loss. To address both of these points, a bifunctional SPR fluid cell was constructed where optimized surfaces can be used for binding studies and MS simultaneously with regard to the special need of each technique. The setup guarantees that the SPR and the loading experiment for MS are performed at identical conditions. A removable pin carries the affinity-surface-bound analyte to the mass spectrometer so that handling is minimized, avoiding analyte elution. Functionalized transfer pins can also be used independently of SPR for microaffinity capture-MS.