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Background: Neutrophil gelatinase-associated lipocalin (NGAL), an acute phase protein released by neutrophils, has been described as biomarker of inflammatory states. Type 2 diabetes mellitus (T2DM) is characterized by increased inflammation and an elevated risk for embolization of carotid artery stenosis (CAS). We aimed to explore the role of NGAL systemically and in plaques of diabetics undergoing carotid endarterectomy. Moreover, the potential anti-inflammatory effect of metformin on NGAL was addressed in diabetics. Methods: Serum NGAL and matrix metalloproteinase (MMP)-9/NGAL levels were measured in 136 patients (67 with T2DM vs. 69 non-diabetics) by specific ELISA. Endarterectomy samples were graded histologically according to the American Heart Association's classification. NGAL mRNA expression was detected using RealTime-PCR in carotid endarterectomy specimens. Results: Serum NGAL [median 107.4 ng/ml (quartiles: 75.2-145.0) vs. 64.4 (50.4 -81.3), p < 0.0001] and MMP-9/NGAL [41.5 ng/ml (20.8-63.9) vs. 27.6 (16.0-42.4), p = 0.017] were significantly elevated in diabetics compared to non-diabetics, as were leukocytes, neutrophils, C-reactive protein and fibrinogen (all p < 0.05). In patients with symptomatic and asymptomatic CAS diabetics had higher NGAL levels compared to non-diabetics [128.8 ng/ml (100.8-195.6) vs. 64.8 (48.9-82.2] and [101.6 ng/ml (70.1-125.3) vs. 63.8 (51.0-81.3), respectively, both p < 0.0001]. Presence of T2DM and type VI plaques (with surface defect, hemorrhage or thrombus) had a profound impact on NGAL levels (both p < 0.01) in multiple linear regression analysis. NGAL mRNA was detectable in 95% of analyzed carotid artery lesions of diabetics compared to 5% of non-diabetics (p < 0.0001). Accordingly, cerebral embolization was more frequent in diabetics (52.2% vs. 29%, p = 0.006). Metformin treatment was associated with decreased NGAL [60.7 ng/ml (51.9-69.2) vs. 121.7 (103.7-169.9), p < 0.0001] and MMP-9/NGAL [20.8 ng/ml (12.1-26.5) vs. 53.7 (27.4-73.4), p = 0.007] in diabetics and reduced leukocyte infiltration in carotid lesions of diabetics. Conclusions: Higher NGAL levels in serum and plaques are associated with T2DM in patients with CAS. Metformin significantly reduced the inflammatory burden including NGAL in diabetics. Early treatment of these patients may be recommended, as elevated NGAL levels were linked with vulnerable plaques prone for embolization. [ABSTRACT FROM AUTHOR]

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This study was mainly supported from the British Heart Foundation (BHF) supporting Prof. Manuel Mayr as a Chair Holder (CH/16/3/32406) with BHF programme grant support (RG/16/14/32397) and Dr. Theofilatos with BHF programm grant support (G/20/10387). Background Using proteomics, we strove to reveal novel molecular subtypes of human atherosclerotic lesions, study their associations with histology and imaging and relate them to long-term cardiovascular outcomes. Methods 219 samples were obtained from 120 patients undergoing carotid endarterectomy. Sequential protein extraction was combined with multiplexed, discovery proteomics. Parallel reaction monitoring for 135 proteins was deployed for targeted validation. A combination of statistical, bioinformatics and machine learning methods was used to perform differential expression, network, pathway enrichment analysis and train and evaluate prognostic models. Results Our extensive proteomics analysis from the core and periphery of plaques doubled the coverage of the plaque proteome compared to the largest proteomics study on atherosclerosis thus far. Plaque inflammation and calcification signatures were inversely correlated and validated with targeted proteomics. The inflammation signature was enriched with neutrophil-derived proteins, including calprotectin (S100A8/9) and myeloperoxidase. The calcification signature contained fetuin-A, osteopontin, and gamma-carboxylated proteins. Sex differences in the proteome of atherosclerosis were explained by a higher proportion of calcified plaques in women. Single-cell RNA sequencing data attributed the inflammation signature predominantly to neutrophils and macrophages and the calcification signature to smooth muscle cells, except for certain plasma proteins that were not expressed but retained in the plaque, i.e. fetuin-A. Echogenic lesions reflect the collagen content and calcification of plaque but carotid Duplex ultrasound fails to capture the extent of inflammatory protein changes in symptomatic plaques. Applying dimensionality reduction and machine learning on the proteomics data defined 4 distinct plaque phenotypes and revealed key protein signatures linked to smooth muscle cell content, plaque calcification and structural extracellular matrix, which improved the 9-year prognostic AUC by 25% compared to ultrasound and histology. A biosignature of four proteins (CNN1, PROC, SERPH, and CSPG2) independently predicted the progression of atherosclerosis and cardiovascular mortality with an AUC of 75% Conclusion We combined discovery and targeted proteomics with network reconstruction and clustering techniques to provide molecular insights into protein changes in atherosclerotic plaques. The application of proteomics and machine learning techniques revealed distinct clusters of plaques that inform on disease progression and future adverse cardiovascular events. [ABSTRACT FROM AUTHOR]

Evaluation of coronary pressures during angioplasty may functionally quantify collateral circulation. The aim of the study was to evaluate the relation between the amount of collateral circulation and development of myocardial ischemia during balloon occlusion, anatomic degree of collaterals, and functional improvement of myocardium. Study population consisted of 31 pts (mean age 53 +/- 7 years; 25 male) with previous myocardial infarction and significant one-vessel stenosis undergoing angioplasty. Collateral circulation was calculated as the ratio between distal coronary pressure during balloon occlusion (P(w)) and aortic pressure (P(a)). Angiographic appearance of collaterals was evaluated by Rentrop classification. Patients were evaluated by echo for functional improvement of myocardium in the follow-up period. Mean P(w)/P(a) was 0.24 +/- 0.10 (range of 0.07-0.51). Rentrop grade 0 of collaterals was present in 16 patients (52%), grade 1 in11 patients (35%), and grade 2 in 4 patients (13%). A mild correlation between angio and hemodynamic evaluation of collaterals was observed (r = 0.38, P = 0.035). In patients without ECG changes during angioplasty (21 pts, 68%), P(w)/P(a) was significantly higher in comparison to patients with ECG changes (0.28 +/- 0.09 vs. 0.15 +/- 0.06, P < 0.001; area under the curve 0.93). In patients with myocardial functional improvement during follow-up (21 pts, 68%), P(w)/P(a) was significantly higher than in the patients without echo improvement (0.26 +/- 0.10 vs. 0.18 +/- 0.08, P = 0.035). The amount of recruitable collaterals is not negligible even in the patients with no angio visible collaterals. Low values of P(w)/P(a) are associated with ECG changes during balloon occlusion. Higher P(w)/P(a) was associated with better functional improvement of myocardium. [ABSTRACT FROM AUTHOR]

The design of a single-molecule machine consisting of functional components requires a detailed understanding of its mechanical motion. The scanning tunnelling microscope (STM) is the only available tool for driving and imaging such a nanoscale machine on a surface. Both lateral hopping motions and conformational changes of single molecules can be induced using the STM tip. However, no rolling of a wheel has been demonstrated so far at the nanoscale, even though this is a very useful motion at the macroscopic scale. Here we show how the rolling of a single molecule equipped with two wheels (0.8 nm in diameter) can be induced by the STM tip. The characteristics of the rolling are recorded in the STM feedback loop manipulation signal and in real time. We capture unambiguous signatures of the conformational change happening during the rolling. Our approach of controlling the intramolecular mechanics provides a path towards the bottom-up assembly of more complex molecular machines. [ABSTRACT FROM AUTHOR]

Sigmoidoscopy is an essential tool in colorectal clinics in the detection of anorectal lesions including rectosigmoid adenomas and carcinomas. However, rigid sigmoidoscope (RS) is still more widely used than flexible sigmoidoscope (FS) as the primary investigation, despite the fact that the latter is more comfortable to the patient and has greater diagnostic yield. Hence we wanted to compare the two modalities in terms of diagnostic use for picking up significant anorectal lesions.A retrospective review of all patients referred to the colorectal clinic who had undergone both rigid and flexible sigmoidoscopy for investigation of colorectal symptoms in 2001 was done. Findings recorded during rigid and flexible sigmoidoscopy including depth of insertion, site of lesion and complications were analysed.152 patients underwent both rigid and flexible sigmoidoscopy as part of investigation of colorectal symptoms. Of the 115 (75.6%) declared normal by RS, 39 (33.9%) had significant lesions including 7 polyps and 4 malignant lesions within 20 cm of the anal verge during FS. Of the 31 patients (20.4%) in whom RS was not helpful due to faecal loading, 15 (48.4%) had significant lesions including 4 malignancies and 1 polp– all within 20 cm of the anal verge during FS. Only 2 polyps and 1 malignant lesion were picked up by both flexible and rigid sigmoidoscopy. There wre no complications in both procedures.Since flexible sigmoidoscopy is superior to rigid sigmoidoscopy in terms of patient comfort, diagnostic value and ease of doing procedures like biopsy and polypectomy; it can be used as a front line investigation to exclude colorectal pathology in out patient clinics. The utility of rigid sigmoidoscope is in question and in view of obvious shortcomings, may be replaced by flexible sigmoidoscopy, though obvious resource constraints need to be considered. [ABSTRACT FROM AUTHOR]

Objective To determine the degree of inter-observer variability between two reporters of dynamic evacuation proctography (DEP). Patients and methods The videotapes of 136 patients who had undergone the investigation of DEP in a 1-year period were retrospectively and independently reported by two of the authors. The authors recorded the presence or absence of an anterior rectocoele (as well as size—small, medium or large), an intussusception, a rectal prolapse and any degree of non-relaxing puborectalis syndrome (NRPS). Results The results were analysed using the κ statistic. I.W.I. reported 18% of the proctograms as normal. S.G.S. reported 26% of the proctograms as normal. κ scores for agreement on the presence or absence of rectal prolapses, NRPS, intussusception and anterior rectocoeles between the two reporters were 0.79, 0.70, 0.54 and 0.82, respectively. Conclusion Usefulness of an investigation is dependent upon its reproducibility and hence on the degree of inter-observer variability in its reporting. Our study shows that DEP is a useful investigation for delineating the mechanics of the pelvic floor and that consistency of reporting in our Department is good. [ABSTRACT FROM AUTHOR]

Presents results of a study in correctional crowding which identified variables for an index of the severity of jail crowding. Descriptions of the comprehensive model of jail crowding in which severity is a function of population factors, facilities, and management practices; The limited usefulness for research and management; Intake fluctuations; Composition of inmates in population; Relationships with outside agencies and organizations; More.

Stress echocardiography has become an accepted and cost-effective method for diagnosing coronary artery disease. However, as exercise stress echocardiography is a demanding technique, difficult to reproduce, pharmacological stress echocardiography has become very popular in recent years. The two most popular tests from the pharmacological stress echocardiography arena are dipyridamole and dobutamine. They have enabled the technical limitations inherent in exercise echocardiography to be overcome, and have provided the opportunity to obtain, during stress, images of unchanged quality in comparison to baseline. However, the sensitivity of both pharmacological stresses applied separately is less than ideal in patients with milder forms of coronary artery disease and in patients under therapy. To overcome this, a new generation of pharmacological stress tests, the combined dipyridamole-dobutamine tests were introduced. A combined dipyridamole-dobutamine echocardiography stress test should suggest that the agents are natural allies rather than competitors but in some instances they are applicable only in selected patients, and each pharmacological agent may be clinically contraindicated for administration. This is the message from a large scale study of recent years. [ABSTRACT FROM PUBLISHER]

Aim The aim of this study was to evaluate simultaneously echocardiographic, haemodynamic and angiographic changes that occur during adenosine and dipyridamole infusion, in patients with one-vessel coronary artery stenosis. This would assess whether deterioration in left ventricular haemodynamics during vasodilator agent infusion is influenced by vasodilation per se, or the development of myocardial ischaemia. Methods and results We performed adenosine (140 μg.kg−1.min−1 over 4 min) and dipyridamole (up to 0·84 mg.kg−1 over 10 min) stress echocardiography tests, together with angiographic and haemodynamic assessment, in 26 patients undergoing elective coronary angioplasty. In 12 of 26 patients, adenosine and dipyridamole tests were repeated 24 h after angioplasty. The criterion for echocardiography test positivity was the appearance of a new transient regional wall motion abnormality. Coronary angiograms were analysed with quantitative coronary arteriography. Adenosine and dipyridamole induced regional dysfunction in 18/26 (69%) and 14/26 (54%) patients before angioplasty, respectively (P=ns). In the echocardiography-positive patients, the percent diameter stenosis was significantly (P<0·05) tighter stenosis than in the echocardiography-negative patients (adenosine, 66·6±8·3% vs 58·0±8·9%; dipyridamole, 69·2±7·1% vs 57·±7·6%). During both tests, left ventricular end-diastolic pressure significantly increased (P<0·05) in echocardiography-positive patients (adenosine, 9·8±2·7 mmHg to 13·5±4·1 mmHg; dipyridamole, 10·1±2·8 mmHg to 14·1±4·3 mmHg), but not in echocardiography-negative patients. In the patients who had undergone successful angioplasty (reduction to <50% diameter stenosis), both adenosine and dipyridamole confirmed the arteriographic success of the procedure (echocardiography negative in all patients). In this group of patients, no significant change was observed in left ventricular end-diastolic pressure during adenosine or dipyridamole infusion. Conclusions Intravenous infusion of either adenosine or dipyridamole was accompanied by an obvious increase in left ventricular end-diastolic pressure only in patients with induced wall motion abnormalities. Coronary vasodilation per se has no significant effect on left ventricular end-diastolic pressure when no ischaemia is induced, disproving any clinically significant ‘erectile’ and adverse effects of coronary vasodilation per se. [ABSTRACT FROM PUBLISHER]

Purpose: Despite the fact that techniques for recanalization of chronic total occlusions (CTO) are improved, the benefit of successful recanalization of the artery remains unclear. The aim of our study is to determine the success rate of percutaneous procedures and to evaluate the event free long-term survival in patients with CTO who underwent percutaneous coronary intervention (PCI).Methods: Our study included 283 consecutive patients with chronic total occlusions who underwent percutaneous coronary intervention on CTO at Clinic for Cardiology, between Jan 1st 2009 and Dec 31st 2010. Data were obtained retrospectively from Cath lab database at Clinic for Cardiology. Follow up data were obtained by direct phone contact.Results: Overall procedural success was achieved in 62.3% interventions. Independent predictors for procedural failure were presence of vessel tortuosity (P=0.007), vessel wall calcifications (P=0.000), blunt stump (P=0.000) and unstable angina pectoris as negative predictor (P=0.009). Overall MACE rates were similar in the procedural success and procedural failure groups (10% vs. 12.8%, p=0.455). There was no significant difference in the event free survival rate between success and failure group (89.8% vs. 87.2%, Log-Rank =0.468, p=0.494).Conclusions: Our study demonstrated that success rate of PCI in patients with CTO is acceptable and safe. Nevertheless, successful recanalization of CTO was not associated with an improved event free survival. [ABSTRACT FROM AUTHOR]

Background: Interleukin (IL)-33 is a member of the IL-1 cytokine family. IL-33 was previously shown to induce angiogenesis and the expression of inflammatory cytokines and adhesion molecules in endothelial cells. Tissue factor (TF) is a primary trigger of coagulation. Elevated levels of TF are found in atherosclerotic plaques, and TF leads to thrombus formation, when released upon plaque rupture.Aim: Here we investigated the impact of IL-33 on TF expression in human endothelial cells, as a new possible mechanism for IL-33 to regulate their thrombotic potential.Methods and Results: Human umbilical vein endothelial cells (HUVEC) and human coronary artery endothelial cells (HCAEC) were treated with 100, 10 and 1ng/ml recombinant human IL-33. Expression of mRNA specific for TF was determined by RT-PCR. TF protein levels were measured by specific enzyme-linked immunosorbent assays (ELISAs). We found that IL-33 significantly induced TF mRNA up to 200-fold and protein expression up to 145-fold in a time- and concentration-dependent manner in HUVEC and HCAEC. ST2-siRNA-mediated gene knockdown inhibited IL-33-induced TF expression, suggesting that this effect of IL-33 is facilitated through its receptor ST2. Preincubation of HUVEC with 100μM of the NFkB-inhibitor dimethyl-fumarate abrogated IL-33-induced TF protein synthesis. IL-1 receptor antagonist had no effect on IL-33-induced increase of TF expression. In human carotid atherosclerotic plaques (n=16), TF mRNA positively correlated with IL-33 mRNA expression (r=0.86, p<0.001).Conclusion: Our results showed that IL-33 increases TF expression in human endothelial cells, and that this effect is ST2/NFkB-dependent, but IL-1-independent. Furthermore, we supported our in vitro data in human atherosclerotic tissue where we found a strong positive correlation of IL-33 and TF expression. Thus, IL-33-induced changes in TF expression could affect the thrombotic potential of endothelial cells, as well as potentiate thrombotic events in the setting of ruptured human atherosclerotic plaques. [ABSTRACT FROM PUBLISHER]

An abstract of the article "The Interactive Effects of UV Radiation and Enhanced Co2 Concentrations on Aquatic Photoautotrophs," by S. Stojkovic, J. Beardall and R. Matear is presented.

An abstract of the article "Noninvasive assessment of coronary flow reserve after elective stenting in patients with previous myocardial infarction: Relation to left ventricular recovery," by B. Beleslin and colleagues is presented.

An abstract of the article "Can we predict acute coronary events by myocardial jeopardy score in patients with natural progression of coronary artery disease,' by I. Nedeljkovic and colleagues is presented.

An abstract of the study "Myocardial Jeopardy Score as a New Predictor of Acute Coronary Events in Patients with Natural Progression of Coronary Artery Disease," by M. Ostojic and colleagues is presented.

An abstract of the study "Does Athens QRS Score Contain More Prognostic Information About Functional Significance of Coronary Stenosis Than Stress-induced ST Depression? Correlation With Stress Echocardiography," by J. Stepanovic and V. Giga, is presented.

An abstract of the article "Assessment of Myocardial Viability in Patients With Myocardial Infarction: Comparison of Low Dose Dipyridamole Radionuclide Ventriculography With Dipyridamole Stress Echocardiography" by Z. Petrasinovic and colleagues is presented.

An abstract of the article "Cultural Evolution of Digital Description of Coronary Artery Disease Severity Potential of Inducing Myocardial Ischemia During Exercise Stress Echocardiography" by I.P. Nedeljkovic and colleagues is presented.