Differential optical densities of intraretinal spaces

PURPOSE: To test the hypothesis that hyporeflective spaces in the neuroretina found on optical coherence tomography (OCT) examination have different optical reflectivities according to whether they are associated with exudation or degeneration. METHODS: Retrospective analysis of eyes with idiopathic perifoveal telangiectasia (IPT), diabetic macular edema (DME), idiopathic central serous chorioretinopathy (CSC), retinitis pigmentosa (RP), or cone dystrophy (CD) and eyes of healthy control subjects. OCT scans were performed. Raw scan data were exported and used to calculate light reflectivity profiles. Reflectivity data were acquired by projecting three rectangular boxes, each 50 pixels long and 5 pixels wide, into the intraretinal cystoid spaces, centrally onto unaffected peripheral RPE, and onto the prefoveolar vitreous. Light reflectivity in the retinal pigment epithelium (RPE), vitreous, and intraretinal spaces for the different retinal conditions and control subjects were compared. RESULTS: Reflectivities of the vitreous and the RPE were similar among the groups. Hyporeflective spaces in eyes with exudation (DME, RP, and CSC) had higher reflectivity compared with the mean reflectivity of the vitreous, whereas the cystoid spaces in the maculae of the eyes without exudation (CD and IPT) had a lower reflectivity than did the normal vitreous. CONCLUSIONS: Analysis of the light reflectivity profiles may be a tool to determine whether the density of hyporeflective spaces in the macula is greater or less than that of the vitreous, and may be a way to differentiate degenerative from exudative macular disease.

A new method to monitor visual field defects caused by photoreceptor degeneration by quantitative optical coherence tomography

PURPOSE: To correlate the dimension of the visual field (VF) tested by Goldman kinetic perimetry with the extent of visibility of the highly reflective layer between inner and outer segments of photoreceptors (IOS) seen in optical coherence tomography (OCT) images in patients with retinitis pigmentosa (RP). METHODS: In a retrospectively designed cross-sectional study, 18 eyes of 18 patients with RP were examined with OCT and Goldmann perimetry using test target I4e and compared with 18 eyes of 18 control subjects. A-scans of raw scan data of Stratus OCT images (Carl Zeiss Meditec, AG, Oberkochen, Germany) were quantitatively analyzed for the presence of the signal generated by the highly reflective layer between the IOS in OCT images. Starting in the fovea, the distance to which this signal was detectable was measured. Visual fields were analyzed by measuring the distance from the center point to isopter I4e. OCT and visual field data were analyzed in a clockwise fashion every 30 degrees , and corresponding measures were correlated. RESULTS: In corresponding alignments, the distance from the center point to isopter I4e and the distance to which the highly reflective signal from the IOS can be detected correlate significantly (r = 0.75, P < 0.0001). The greater the distance in VF, the greater the distance measured in OCT. CONCLUSIONS: The authors hypothesize that the retinal structure from which the highly reflective layer between the IOS emanates is of critical importance for visual and photoreceptor function. Further research is warranted to determine whether this may be useful as an objective marker of progression of retinal degeneration in patients with RP.

Serine residues 994 and 1023/25 are important for insulin receptor kinase inhibition by protein kinase C isoforms beta2 and theta

AIMS/HYPOTHESIS: Inhibition of the signalling function of the human insulin receptor (HIR) is one of the principle mechanisms which induce cellular insulin resistance. It is speculated that serine residues in the insulin receptor beta-subunit are involved in receptor inhibition either as inhibitory phosphorylation sites or as part of receptor domains which bind inhibitory proteins or tyrosine phosphatases. As reported earlier we prepared 16 serine to alanine point mutations of the HIR and found that serine to alanine mutants HIR-994 and HIR-1023/25 showed increased tyrosine autophosphorylation when expressed in human embryonic kidney (HEK) 293 cells. In this study we examined whether these mutant receptors have a different susceptibility to inhibition by serine kinases or an altered tyrosine kinase activity. METHODS: Tyrosine kinase assay and transfection studies. RESULTS: In an in vitro kinase assay using IRS-1 as a substrate we could detect a higher intrinsic tyrosine kinase activity of both receptor constructs. Additionally, a higher capacity to phosphorylate the adapter protein Shc in intact cells was seen. To test the inhibition by serine kinases, the receptor constructs were expressed in HEK 293 cells together with IRS-1 and protein kinase C isoforms beta2 and theta. Phorbol ester stimulation of these cells reduced wild-type receptor autophosphorylation to 58 % or 55 % of the insulin simulated state, respectively. This inhibitory effect was not observed with HIR-994 and HIR-1023/25, although all other tested HIR mutants showed similar inhibition induced by protein kinase C. CONCLUSION/INTERPRETATION: The data suggest that the HIR-domain which contains the serine residues 994 and 1023/25 is important for the inhibitory effect of protein kinase C isoforms beta2 and theta on insulin receptor autophosphorylation.

Monitoring thrombin generation by electrochemistry: development of an amperometric biosensor screening test for plasma and whole blood

BACKGROUND: Complete investigation of thrombophilic or hemorrhagic clinical presentations is a time-, apparatus-, and cost-intensive process. Sensitive screening tests for characterizing the overall function of the hemostatic system, or defined parts of it, would be very useful. For this purpose, we are developing an electrochemical biosensor system that allows measurement of thrombin generation in whole blood as well as in plasma. METHODS: The measuring system consists of a single-use electrochemical sensor in the shape of a strip and a measuring unit connected to a personal computer, recording the electrical signal. Blood is added to a specific reagent mixture immobilized in dry form on the strip, including a coagulation activator (e.g., tissue factor or silica) and an electrogenic substrate specific to thrombin. RESULTS: Increasing thrombin concentrations gave standard curves with progressively increasing maximal current and decreasing time to reach the peak. Because the measurement was unaffected by color or turbidity, any type of blood sample could be analyzed: platelet-poor plasma, platelet-rich plasma, and whole blood. The test strips with the predried reagents were stable when stored for several months before testing. Analysis of the combined results obtained with different activators allowed discrimination between defects of the extrinsic, intrinsic, and common coagulation pathways. Activated protein C (APC) predried on the strips allowed identification of APC-resistance in plasma and whole blood samples. CONCLUSIONS: The biosensor system provides a new method for assessing thrombin generation in plasma or whole blood samples as small as 10 microL. The assay is easy to use, thus allowing it to be performed in a point-of-care setting.

Organic vs. Conventional Grassland Management: Do N-15 and C-13 Isotopic Signatures of Hay and Soil Samples Differ?

Distinguishing organic and conventional products is a major issue of food security and authenticity. Previous studies successfully used stable isotopes to separate organic and conventional products, but up to now, this approach was not tested for organic grassland hay and soil. Moreover, isotopic abundances could be a powerful tool to elucidate differences in ecosystem functioning and driving mechanisms of element cycling in organic and conventional management systems. Here, we studied the delta N-15 and delta C-13 isotopic composition of soil and hay samples of 21 organic and 34 conventional grasslands in two German regions. We also used Delta delta N-15 (delta N-15 plant - delta N-15 soil) to characterize nitrogen dynamics. In order to detect temporal trends, isotopic abundances in organic grasslands were related to the time since certification. Furthermore, discriminant analysis was used to test whether the respective management type can be deduced from observed isotopic abundances. Isotopic analyses revealed no significant differences in delta C-13 in hay and delta C-13 in both soil and hay between management types, but showed that delta C-13 abundances were significantly lower in soil of organic compared to conventional grasslands. delta C-15 values implied that management types did not substantially differ in nitrogen cycling. Only delta C-13 in soil and hay showed significant negative relationships with the time since certification. Thus, our result suggest that organic grasslands suffered less from drought stress compared to conventional grasslands most likely due to a benefit of higher plant species richness, as previously shown by manipulative biodiversity experiments. Finally, it was possible to correctly classify about two third of the samples according to their management using isotopic abundances in soil and hay. However, as more than half of the organic samples were incorrectly classified, we infer that more research is needed to improve this approach before it can be efficiently used in practice.

How do indirect measures of evaluation work? Evaluating the inference of prejudice in the Implicit Association Test

There has been significant interest in indirect measures of attitudes like the Implicit Association Test (IAT), presumably because of the possibility of uncovering implicit prejudices. The authors derived a set of qualitative predictions for people's performance in the IAT on the basis of random walk models. These were supported in 3 experiments comparing clearly positive or negative categories to nonwords. They also provided evidence that participants shift their response criterion when doing the IAT. Because of these criterion shifts, a response pattern in the IAT can have multiple causes. Thus, it is not possible to infer a single cause (such as prejudice) from IAT results. A surprising additional result was that nonwords were treated as though they were evaluated more negatively than obviously negative items like insects, suggesting that low familiarity items may generate the pattern of data previously interpreted as evidence for implicit prejudice.

Complex visual hallucinations and attentional performance in eye disease and dementia: a test of the Perception and Attention Deficit model

OBJECTIVE This study aimed to test the prediction from the Perception and Attention Deficit model of complex visual hallucinations (CVH) that impairments in visual attention and perception are key risk factors for complex hallucinations in eye disease and dementia. METHODS Two studies ran concurrently to investigate the relationship between CVH and impairments in perception (picture naming using the Graded Naming Test) and attention (Stroop task plus a novel Imagery task). The studies were in two populations-older patients with dementia (n = 28) and older people with eye disease (n = 50) with a shared control group (n = 37). The same methodology was used in both studies, and the North East Visual Hallucinations Inventory was used to identify CVH. RESULTS A reliable relationship was found for older patients with dementia between impaired perceptual and attentional performance and CVH. A reliable relationship was not found in the population of people with eye disease. CONCLUSIONS The results add to previous research that object perception and attentional deficits are associated with CVH in dementia, but that risk factors for CVH in eye disease are inconsistent, suggesting that dynamic rather than static impairments in attentional processes may be key in this population.

Thermal acclimation to 4 or 10 degrees C imparts minimal benefit on swimming performance in Atlantic cod (Gadus morhua L.).

Thermal acclimation is frequently cited as a means by which ectothermic animals improve their Darwinian fitness, i.e. the beneficial acclimation hypothesis. As the critical swimming speed (U (crit)) test is often used as a proxy measure of fitness, we acclimated Atlantic cod (Gadus morhua) to 4 and 10 degrees C and then assessed their U (crit) swimming performance at their respective acclimation temperatures and during acute temperature reversal. Because phenotypic differences exist between different populations of cod, we undertook these experiments in two different populations, North Sea cod and North East Arctic cod. Acclimation to 4 or 10 degrees C had a minimal effect on swimming performance or U (crit), however test temperature did, with all groups having a 10-17% higher U (crit) at 10 degrees C. The swimming efficiency was significantly lower in all groups at 4 degrees C arguably due to the compression of the muscle fibre recruitment order. This also led to a reduction in the duration of "kick and glide" swimming at 4 degrees C. No significant differences were seen between the two populations in any of the measured parameters, due possibly to the extended acclimation period. Our data indicate that acclimation imparts little benefit on U (crit) swimming test in Atlantic cod. Further efforts need to identify the functional consequences of the long-term thermal acclimation process.

Can a novel computerized cognitive screening test provide additional information for early detection of Alzheimer's disease?

BACKGROUND: Virtual reality testing of everyday activities is a novel type of computerized assessment that measures cognitive, executive, and motor performance as a screening tool for early dementia. This study used a virtual reality day-out task (VR-DOT) environment to evaluate its predictive value in patients with mild cognitive impairment (MCI). METHODS: One hundred thirty-four patients with MCI were selected and compared with 75 healthy control subjects. Participants received an initial assessment that included VR-DOT, a neuropsychological evaluation, magnetic resonance imaging (MRI) scan, and event-related potentials (ERPs). After 12 months, participants were assessed again with MRI, ERP, VR-DOT, and neuropsychological tests. RESULTS: At the end of the study, we differentiated two subgroups of patients with MCI according to their clinical evolution from baseline to follow-up: 56 MCI progressors and 78 MCI nonprogressors. VR-DOT performance profiles correlated strongly with existing predictive biomarkers, especially the ERP and MRI biomarkers of cortical thickness. CONCLUSIONS: Compared with ERP, MRI, or neuropsychological tests alone, the VR-DOT could provide additional predictive information in a low-cost, computerized, and noninvasive way.

Elderly age is not a negative predictive factor for virological response to therapy with pegylated interferon-α and ribavirin in chronic hepatitis C virus patients

BACKGROUND & AIMS: Age is frequently discussed as negative host factor to achieve a sustained virological response (SVR) to antiviral therapy of chronic hepatitis C. However, elderly patients often show advanced fibrosis/cirrhosis as known negative predictive factor. The aim of this study was to assess age as an independent predictive factor during antiviral therapy. METHODS: Overall, 516 hepatitis C patients were treated with pegylated interferon-α and ribavirin, thereof 66 patients ≥60 years. We analysed the impact of host factors (age, gender, fibrosis, haemoglobin, previous hepatitis C treatment) and viral factors (genotype, viral load) on SVR per therapy course by performing a generalized estimating equations (GEE) regression modelling, a matched pair analysis and a classification tree analysis. RESULTS: Overall, SVR per therapy course was 42.9 and 26.1%, respectively, in young and elderly patients with hepatitis C virus (HCV) genotypes 1/4/6. The corresponding figures for HCV genotypes 2/3 were 74.4 and 84%. In the GEE model, age had no significant influence on achieving SVR. In matched pair analysis, SVR was not different in young and elderly patients (54.2 and 55.9% respectively; P = 0.795 in binominal test). In classification tree analysis, age was not a relevant splitting variable. CONCLUSIONS: Age is not a significant predictive factor for achieving SVR, when relevant confounders are taken into account. As life expectancy in Western Europe at age 60 is more than 20 years, it is reasonable to treat chronic hepatitis C in selected elderly patients with relevant fibrosis or cirrhosis but without major concomitant diseases, as SVR improves survival and reduces carcinogenesis.