The pro-inflammatory and regulatory roles of T lymphocytes in atherosclerosis are well established but less is known about natural killer (NK) cells and natural killer T (NKT)-like cells. The effects of cardiovascular risk management on the phenotypes of these cells are unknown. To assess changes in NK cell and lymphocyte phenotypes and circulating inflammatory proteins in response to cardiovascular risk management in patients with carotid atherosclerosis. Fifty patients were included in a prospective clinical study. Measurements were at baseline and after 12 months of cardiovascular risk management. Circulating NK, NKT-like and T lymphocyte subpopulations were phenotyped by multi-colour flow cytometry. Proximity extension assay was performed for 176 plasma proteins associated with inflammation and cardiovascular disease. At 12 months there were significant reductions in LDL (P=0.001) and blood pressure (P=0.028). NK cells responded with a reduction in pro-inflammatory (NKG2C(+)) cells (P=0.0003), an increase in anti-inflammatory (NKG2A(+)) cells (P=0.032), and a reduction in terminally differentiated (CD57(+)) NK cells. NKT-like cells showed a similar decrease in terminally differentiated subpopulations (P=0.000002). Subpopulations of T helper cells exhibited a significant reduction in central memory (P=1.09x10(-8)) and a significant increase in CD4(+) naive- (P=0.0008) and effector memory T cells (P=0.006). The protein analysis indicated that cardiovascular risk management affects proteins involved in the inflammatory NF-kappa B pathway. The consistent decrease in senescent phenotypes of NK, NKT-like and CD4(+) cells with a concomitant increase in more naive, phenotypes suggests a change towards a less pro-inflammatory lymphocyte profile in response to cardiovascular risk management.Trial registry name: CARotid MRI of Atherosclerosis (CARMA). ClinicalTrials.gov identifier NCT04835571 (08/04/2021). https://www.clinicaltrials.gov/study/NCT04835571.

Background MRI can be used to generate fat fraction (FF) and R2* data, which have been previously shown to characterize the plaque compositional features lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in the carotid arteries (CAs). Previously, these data were extracted from CA plaques using time-consuming manual analyses. Purpose To design and demonstrate a method for segmenting the CA and extracting data describing the composition of the vessel wall. Study Type Prospective. Subjects 31 subjects from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Field Strength/Sequences T-1-weighted (T1W) quadruple inversion recovery, contrast-enhanced MR angiography (CE-MRA), and 4-point Dixon data were acquired at 3T. Assessment The vessel lumen of the CA was automatically segmented using support vector machines (SVM) with CE-MRA data, and the vessel wall region was subsequently delineated. Automatically generated segmentations were quantitatively measured and three observers visually compared the segmentations to manual segmentations performed on T(1)w images. Dixon data were used to generate FF and R2* maps. Both manually and automatically generated segmentations of the CA and vessel wall were used to extract compositional data. Statistical Tests Two-tailedt-tests were used to examine differences between results generated using manual and automated analyses, and among different configurations of the automated method. Interobserver agreement was assessed with Fleiss kappa. Results Automated segmentation of the CA using SVM had a Dice score of 0.89 +/- 0.02 and true-positive ratio 0.93 +/- 0.03 when compared against ground truth, and median qualitative score of 4/5 when assessed visually by multiple observers. Vessel wall regions of 0.5 and 1 mm yielded compositional information similar to that gained from manual analyses. Using the 0.5 mm vessel wall region, the mean difference was 0.1 +/- 2.5% considering FF and 1.1 +/- 5.7[1/s] for R2*. Level of Evidence 1. Technical Efficacy Stage 1. J. Magn. Reson. Imaging 2020;52:710-719.

Cardiovascular diseases, including myocardial infarction, are the cause of significant morbidity and mortality globally. Tissue engineering is a key emerging treatment method for supporting and repairing the cardiac scar tissue caused by myocardial infarction. Creating cell supportive scaffolds that can be directly implanted on a myocardial infarct is an attractive solution. Hydrogels made of collagen are highly biocompatible materials that can be molded into a range of shapes suitable for cardiac patch applications. The addition of mechanically reinforcing materials, carbon nanotubes, at subtoxic levels allows for the collagen hydrogels to be strengthened, up to a toughness of 30 J m^-1 and a two to threefold improvement in Youngs' modulus, thus improving their viability as cardiac patch materials. The addition of carbon nanotubes is shown to be both nontoxic to stem cells, and when using single-walled carbon nanotubes, supportive of live, beating cardiac cells, providing a pathway for the further development of a cardiac patch.

The combination of stem cell therapy with a supportive scaffold is a promising approach to improving cardiac tissue engineering. Stem cell therapy can be used to repair nonfunctioning heart tissue and achieve myocardial regeneration, and scaffold materials can be utilized in order to successfully deliver and support stem cells in vivo. Current research describes passive scaffold materials; here an electroactive scaffold that provides electrical, mechanical, and topographical cues to induced human pluripotent stem cells (iPS) is presented. The poly(lactic-co-glycolic acid) fiber scaffold coated with conductive polymer polypyrrole (PPy) is capable of delivering direct electrical and mechanical stimulation to the iPS. The electroactive scaffolds demonstrate no cytotoxic effects on the iPS as well as an increased expression of cardiac markers for both stimulated and unstimulated protocols. This study demonstrates the first application of PPy as a supportive electroactive material for iPS and the first development of a fiber scaffold capable of dynamic mechanical actuation.

BACKGROUND: Patients with high-grade (≥70%) carotid artery stenosis (CAS) rank in the highest risk category for future cardiovascular (CV) events, but the quality of cardiovascular risk management in this patient group is unknown.

DESIGN: Cross-sectional retrospective study.

METHODS: Data were collected for all patients diagnosed with high-grade CAS in Östergötland county, Sweden between 1 January 2009 and 31 July 2012 regarding the quality of cardiovascular risk management, co-morbidity and outcomes during the 2-year follow-up period after a diagnosis of CAS with a carotid ultrasound scan. Patients were included regardless of whether they underwent carotid endarterectomy (CEA).

RESULTS: A total of 393 patients with CAS were included in the study; 133 (33.8%) underwent CEA and 260 (66.2%) were assigned to a conservative management (CM) group. In both groups of patients the prescription of platelet inhibitors, statins and antihypertensive drugs increased significantly (p < 0.001) after diagnosis. However treatment targets were not met in the majority of patients and the low-density lipoprotein level was on target in only 13.5% of patients. During follow-up, low-density lipoprotein levels were not measured in 19.8% of patients who underwent CEA and 44.2% of patients in the CM group (p < 0.001); HbA1c was not measured in 24.4% of patients with diabetes in the CEA group and in 18.8% of patients in the CM group (p = 0.560). There was no documentation of counselling on diet, exercise, smoking cessation or adherence to medication. The combined clinical event rate (all-cause mortality, cardiovascular mortality and non-fatal cardiovascular events) was high in both groups (CEA 36.8% and CM 36.9%; p = 1.00) with no difference in the occurrence of ipsilateral ischaemic stroke.

CONCLUSIONS: The clinical event rate was high in patients with high-grade CAS and the management of cardiovascular risk was deficient in all aspects.

PURPOSE: The purpose of this study was to develop an X-Band electron paramagnetic resonance imaging protocol for visualization of oxidative stress in biopsies.

METHODS: The developed electron paramagnetic resonance imaging protocol was based on spin trapping with the cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. Computer software was developed for deconvolution and back-projection of the EPR image. A phantom containing radicals of known spatial characteristic was used for evaluation of the developed protocol. As a demonstration of the technique electron paramagnetic resonance imaging of oxidative stress was performed in six sections of atherosclerotic plaques. Histopathological analyses were performed on adjoining sections.

RESULTS: The developed computer software for deconvolution and back-projection of the EPR images could accurately reproduce the shape of a phantom of known spatial distribution of radicals. The developed protocol could successfully be used to image oxidative stress in six sections of the three ex vivo atherosclerotic plaques.

CONCLUSIONS: We have shown that oxidative stress can be imaged using a combination of spin trapping with the cyclic hydroxylamine spin probe cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. A thorough and systematic evaluation on different types of biopsies must be performed in the future to validate the proposed technique. Magn Reson Med, 2014.

BAKGRUND: Magnetkamera (MR) kan identifiera aterosklerotiska plack som löper risk att brista och därmed orsaka stroke eller hjärtinfarkt. Metoden är dock bristfälligt validerad på grund av den osäkerhet som uppstår då 2D histologiska snitt ska registreras med 3D MR-bilder.

SYFTE: Att optimera validering av MR-bildtagning av aterosklerotiska plack genom användning av multi-modal MR och 3D histologi.

MATERIAL och METOD: Patienter som skulle opereras för att avlägsna aterosklerotiska plack från arteria karotis genomgick dedikerad plack-MR där följande parametrar undersöktes: plackets fettinnehåll, blödning inuti placket och maximal intensitet av turbulent blodflöde. Undersökningarna gjordes med en Philips 3T MR-kamera: (a) 4-punkt Dixon 3D gradient-eko, (b) T1-viktad spin-eko, (c) 4D fas-kontrast. Upplösningen var 0.6x0.6x0.7mm, 0.35x0.35x3mm respektive 1.14x1.25x1.14mm x 25ms. Vatten-, fett- and R2*-bilder (blödning) beräknades utifrån Dixon-sekvensen.Efter operation bäddades placken in i paraffin och enface-bilder togs varje 50µm i Z-riktning. Bilderna registrerades i ImageJ/Fiji och användes för att bygga en 3D-volym av placket. Vid varje 200µm togs snitt för biologiska markörer och histologiska färgningar. De färgade snitten registrerades med motsvarande enface-bilder. Detta resulterade i 3D-volymer med en upplösning på 1.02x1.02x200µm. Den histologiska 3D-volymen registrerades manuellt med uppsamplade och co-registrerade MR-bilder.

RESULTAT: T1-viktade bilder var bäst för registrering av plack inom varje snitt. Registrering av kärlets lumen optimerades genom en kombination av 4D fas-kontrast, det första Dixon-ekot och vatten-bilder. Registrering av fett och R2* från MR-bilder med fett och blödning från 3D histologi uppvisade god överensstämmelse.

SLUTSATS: Optimal validering av MR-bilder av aterosklerotiska plack kan åstadkommas genom att kombinera olika anatomiska landmärken från multimodala MR-bilder av plack och 3D-histologi. Genom att använda 3D-histologi korrigerar man för registreringsproblem som är relaterade till ”out-of-plane” vinklingar av vävnadssnitt och krympning och deformering till följd av histologiskt bearbetning av placket. Den detaljerade biologiska informationen från 3D-histologi kan förväntas förstärka fynden från in vivo MR-bilder.

This paper proposes a new methodology for computing Hausdorff distances between sets of points in a robust way. In a first step, robust nearest neighbor distance distributions between the two sets of points are obtained by considering reliability measures in the computations through a Monte Carlo scheme. In a second step, the computed distributions are operated using random variables algebra in order to obtain probability distributions of the average, minimum or maximum distances. In the last step, different statistics are computed from these distributions. A statistical test of significance, the nearest neighbor index, in addition to the newly proposed divergence and clustering indices are used to compare the computed measurements with respect to values obtained by chance. Results on synthetic and real data show that the proposed method is more robust than the standard Hausdorff distance. In addition, unlike previously proposed methods based on thresholding, it is appropriate for problems that can be modeled through point processes.

Human beings suffer from a myriad of disorders caused by biochemical or biophysical alteration of physiological systems leading to organ failure. For a number of these conditions, stem cells and their enormous reparative potential may be the last hope for restoring function to these failing organ or tissue systems. To harness the potential of stem cells for biotherapeutic applications, we need to work at the size scale of molecules and processes that govern stem cells fate. Nanotechnology provides us with such capacity. Therefore, effective amalgamation of nanotechnology and stem cells - medical nanoscience or nanomedicine - offers immense benefits to the human race. The aim of this paper is to discuss the role and importance of nanotechnology in stem cell research by focusing on several important areas such as stem cell visualization and imaging, genetic modifications and reprogramming by gene delivery systems, creating stem cell niche, and similar therapeutic applications.