Cystatin C in the anterior segment of rat and mouse eyes.

Purpose: Cystatin C is a mammalian cysteine protease inhibitor. This study describes the localization of cystatin C in the anterior segment of normal rat and mouse eyes. Cysteine proteases play an important role in protein degradation (e.g. of photoreceptor outer segments in the retinal pigment epithelium) and the balance between these proteases and their specific inhibitors is therefore of great interest. Methods: Cells containing cystatin C were identified by immunohistochemistry and quantified by ELISA. Messenger RNA levels were analysed by quantitative real-time polymerase chain reaction. Results: Cystatin C is present at biologically significant levels in the corneal epithelium, endothelium and stromal keratinocytes, lens epithelium, epithelial cells in the ciliary processes, aqueous humour and iris stromal cells. In the rat anterior segment, the highest cystatin C concentrations were found in the ciliary epithelium. Conclusions: Cystatin C is present in several cell types and is probably locally produced. The inhibitor is likely to be an important regulator of cysteine proteases in the retinal pigment epithelium, ciliary epithelium, aqueous humour, lens epithelium and in the corneal endothelium and epithelium

The relevance of rich club regions for functional outcome post-stroke is enhanced in women

This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and similar to 3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich dub regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.Peer reviewe

Cystatin C in the Eye and in Specific Model Systems

It is a necessity of life to make proteins, and it is an equal necessity to degrade those proteins, to eliminate dysfunctional proteins, and leave room for new ones. The processes of protein synthesis and degradation into peptides - proteolysis - have attracted a great interest during the last decades. The eye contains several highly specialized tissues, in which the protein turnover is of vital interest. Reduced control of proteolysis might, for example, impair the transparency of the lens and the cornea. It may also reduce the capacity to eliminate used photoreceptor elements, a task normally carried out by the specialized retinal pigment epithelial cells, as part of the constant renewal and degradation of our photoreceptors, resulting in accumulation of debris, and leading to visual impairment. We have identified cystatin C, on the mRNA and protein levels, in the mouse, rat and human eye. Furthermore, we have described its precise localization in the ocular tissues, using immunohistochemistry. We show that it is present in the epithelium, endothelium and the stromal cells of the cornea, the epithelial cells lining the ciliary processes, stromal cells of the iris, the lens epithelial cells, the pigment epithelial cells, ganglion cells and occasional other cells in the retina, as well as in the aqueous humor (paper I and II). Our mRNA data suggests that it is locally produced. Cystatin C is the strongest of the few known inhibitors of the lysosomal cysteine protease cathepsin B. We have identified cathepsin B in ocular tissues, both on the protein and mRNA levels (paper III). The immunoreactivity pattern of cathepsin B is strikingly similar to that of cystatin C in all examined ocular tissues apart from the retina, suggesting that cystatin C is a dominating cathepsin B inhibitor in vivo in the cornea, the ciliary body, the iris and the lens. In these cells, cystatin C appears to be localized to the cytoplasm, whereas cathepsin B is localized to the lysosomes. In the retina there are differences in staining pattern, suggesting that another cystatin may be the dominating inhibitor of cathepsin B activity. Since cystatin C is a secreted protein, it is assumed to play its role in the extracellular compartment. There is no previously known specific uptake system for cystatin C. We show that there is an active, high-affinity, and energy-requiring uptake system for cystatin C into macrophages in vitro (paper IV), as well as into several cell types, in the cornea, the ciliary body and the retina, of the eye, in vivo as well as in vitro (paper V). The cell types that take up cystatin C in the eye (paper V) are generally the same types that contain endogenous cystatin C (paper I and II), suggesting that much or all cystatin C seen intracellularly in the normal eye may have been taken up from the surrounding extracellular space. This uptake system may regulate the extracellular levels of cystatin C in the eye, and possibly also in other tissues

Detection of Unilateral Arm Paresis after Stroke by Wearable Accelerometers and Machine Learning

Recent advances in stroke treatment have provided effective tools to successfully treat ischemic stroke, but still a majority of patients are not treated due to late arrival to hospital. With modern stroke treatment, earlier arrival would greatly improve the overall treatment results. This prospective study was performed to asses the capability of bilateral accelerometers worn in bracelets 24/7 to detect unilateral arm paralysis, a hallmark symptom of stroke, early enough to receive treatment. Classical machine learning algorithms as well as state-of-the-art deep neural networks were evaluated on detection times between 15 min and 120 min. Motion data were collected using triaxial accelerometer bracelets worn on both arms for 24 h. Eighty-four stroke patients with unilateral arm motor impairment and 101 healthy subjects participated in the study. Accelerometer data were divided into data windows of different lengths and analyzed using multiple machine learning algorithms. The results show that all algorithms performed well in separating the two groups early enough to be clinically relevant, based on wrist-worn accelerometers. The two evaluated deep learning models, fully convolutional network and InceptionTime, performed better than the classical machine learning models with an AUC score between 0.947–0.957 on 15 min data windows and up to 0.993–0.994 on 120 min data windows. Window lengths longer than 90 min only marginally improved performance. The difference in performance between the deep learning models and the classical models was statistically significant according to a non-parametric Friedman test followed by a post-hoc Nemenyi test. Introduction of wearable stroke detection devices may dramatically increase the portion of stroke patients eligible for revascularization and shorten the time to treatment. Since the treatment effect is highly time-dependent, early stroke detection may dramatically improve stroke outcomes

Accuracy of uncalibrated 2D digital subtraction angiography measurements on a novel biplane system compared to computed tomography angiography

Background: 2D digital subtraction angiography (DSA) images are the gold standard for neuroradiological vascular assessment and the basis of interventional procedures such as mechanical thrombectomy and cerebral aneurysm coiling. However, length measurements in projected DSA images are affected by the distance between the x-ray source, the object, and the detector. Precise coordination between all integrated parts of a novel biplane system makes it possible to accurately measure DSA distances without manual calibration. The aim of this study was to compare vascular diameter measurements in uncalibrated DSA images with computed tomography angiography (CTA). Methods: Consecutive patients undergoing interventional neuroradiological procedures were retrospectively included. Vascular diameter measurements in the image isocenter and periphery were performed. These measurements were repeated in picture archiving and communication system (PACS) on DSA images and maximum intensity pixel (MIP) CTA images. Results: Forty-two (42) consecutive patients with adequate DSA and CTA images were included in the final analysis. The correlation between vessel diameter measurements in the image isocenter (R2 = 0.81/0.85, p < 0.0001/p < 0.0001 [Reader1/Reader2]), periphery (R2 = 0.85/0.82, p < 0.0001/p < 0.0001 [Reader1/Reader2]), and all measurements combined (R2 = 0.87/0.87, p < 0.0001/p < 0.0001 [Reader1/Reader2]) on DSA and CTA were strong and statistically significant. The interclass correlation coefficient for measurements performed by two independent reviewers was strong (ICC = 0.96, 95% CI 0.92–0.98). Conclusions: The correlations between uncalibrated DSA measurements and CTA for vessel diameter were strong. In addition, there were strong correlations between these image types for repeated measurements in the image isocenter as well as image periphery for vessel diameter. Consequently, endovascular devices can be sized correctly without the need for pre-operative non-invasive imaging

Detection of Perfusion Deficits in Multiphase Computed Tomography Angiography—A Stroke Imaging Technique Based on Iodine Mapping on Spectral Computed Tomography: Initial Findings

Objective: The purpose of this study was to explore a novel method forbrain tissue differentiation using quantitative analysis of multiphase computedtomography (CT) angiography (MP-CTA) on spectral CT, to assesswhether it can distinguish underperfused fromnormal tissue, using CT perfusion(CTP) as reference.Methods: Noncontrast CT and MP-CTA images from 10 patients wereanalyzed in vascular regions through measurements of Hounsfield unit (HU)at 120 kV, HU at 40 keV, and iodine density. Regions were categorizedas normal or ischemic according to CTP. Hounsfield unit and iodinedensity were compared regarding ability to separate normal and ischemictissue, the difference in maximum time derivative of the right overleft hemisphere ratio.Results: Iodine density had the highest maximum time derivatives andgenerated the largest mean separation between normal and ischemic tissue.Conclusions: The method can be used to categorize tissue as normal orunderperfused. Using iodine quantification seems to give a more distinctdifferentiation of perfusion defects compared with conventional HU

sj-docx-1-ine-10.1177_15910199231171656 - Supplemental material for Accuracy of uncalibrated 2D digital subtraction angiography measurements on a novel biplane system compared to computed tomography angiography

Supplemental material, sj-docx-1-ine-10.1177_15910199231171656 for Accuracy of uncalibrated 2D digital subtraction angiography measurements on a novel biplane system compared to computed tomography angiography by Lovisa Landstrom, and Johan A Wasselius in Interventional Neuroradiology</p

Material decomposition in dual-energy computed tomography separates high-Z elements from iodine, identifying potential contrast media tailored for dual contrast medium examinations

The aim of this study was to determine the potential of different high-Z elements to act as contrast media (CMs) alongside iodine (I) in dual-CM, dual-energy (DE) computed tomography examinations