Crural Index and extensive atherosclerosis of crural vessels are associated with long-term cardiovascular mortality in patients with symptomatic peripheral artery disease

Background and aims: Limited data exist on the association of the anatomical distribution of atherosclerotic lesions and the extent of atherosclerosis at defined arterial segments with life expectancy. We recently presented a new classification of the extent of atherosclerosis in crural vessels and showed that Crural Index (CIx) was associated with mid-term survival of symptomatic peripheral artery disease (PAD) patients. This study evaluates the significance of the extent of crural atherosclerosis on long-term cardiovascular mortality. Methods: 887 consecutive patients with PAD, admitted for digital subtraction angiography (DSA) at Turku University Hospital Department of Vascular Surgery (Turku, Finland) between January 1st, 2009 and July 30th, 2011, were retrospectively analysed. Each crural angiographic image was graded according to CIx criteria. Aorto-iliac and femoro-popliteal arterial segments were similarly graded according to modified TASC II criteria. CIx was used as the categorical variable for the extent of atherosclerosis in crural vessels for survival analysis. Survival was also evaluated with respect to which arterial segment was most severely affected. Causes of death were provided by the Cause of Death Registry of Statistics Finland, updated on January 23rd, 2017. Results: Altogether, 408 (46%) patients died during follow-up. The majority of deaths were due to cardiovascular causes (n = 246, 60%). Cardiovascular mortality was strongly associated with a high CIx (CIx III (Hazard ratio (HR) 2.16, Confidence interval (CI) 95% 1.23-3.80, p = 0.007)) and CIx IV (HR 3.513, 95% CI 1.93-4.565, p <0.001), as compared to CIx 0. In patients having the crural segment as the most severely affected arterial segment, cardiovascular mortality was significantly increased (HR 2.321, 95% CI 1.45-3.73, p <0.001), as was overall mortality (HR 2.177, 95% CI 1.53-3.10, p <0.001). Conclusions: High Crural Index and extensive crural vessel atherosclerosis are associated with long-term cardiovascular mortality, and both may serve as useful indicators of survival among patients with symptomatic PAD. (c) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Toe pressure and toe brachial index are predictive of cardiovascular mortality regardless of the most diseased arterial segment in symptomatic lower-extremity artery disease—A retrospective cohort study

Objective Although lower extremity arterial disease (LEAD) is most often multisegmental, the predominant disease location and risk factors differ between patients. Ankle-brachial index (ABI), toe-brachial index (TBI), and toe pressure (TP) are predictive of outcome in LEAD patients. Previously, we reported a classification method defining the most diseased arterial segment (MDAS); crural (CR), femoropopliteal (FP), or aortoiliac (AOI). Current study aimed to analyze the associations between MDAS, peripheral pressure measurements and cardiovascular mortality. Materials and methods We reviewed retrospectively 729 consecutive LEAD patients (Rutherford 2–6) who underwent digital subtraction angiography between January, 2009 to August, 2011 and had standardized peripheral pressure measurements. Results In Cox Regression analyses, cardiovascular mortality was associated with MDAS and noninvasive pressure indices as follows; MDAS AOI, TP 1.30 (HR 6.71, 95% CI 1.89–23.8), and MDAS CR, TP <30 mmHg (HR 4.26, 95% CI 2.19–8.27), TBI <0.25 (HR 7.71, 95% CI 1.86–32.9), and ABI <0.25 (HR 2.59, 95% CI 1.15–5.85). Conclusions Symptomatic LEAD appears to be multisegmental with severe infrapopliteal involvement. Because of this, TP and TBI are strongly predictive of cardiovascular mortality and they should be routinely measured despite the predominant disease location or clinical presentation.Peer reviewe

CERN studies on niobium-coated 1.5 GHz copper cavities

Studies at CERN on niobium-coated 1.5 GHz superconducting cavities are aimed at understanding and possibly curing the causes of the residual resistance increase observed when increasing the accelerating gradient above 15 MV/m. Amongst the possible causes, the surface defects and roughness, the grain size, the hydrogen content and the thermal effects are currently being investigated. The present status of understanding, together with some recent results on high field operation, are presented and discussed

Toe Pressure and Toe Brachial Index are Predictive of Cardiovascular Mortality, Overall Mortality, and Amputation Free Survival in Patients with Peripheral Artery Disease

Objective/Background: Peripheral haemodynamic parameters are used to assess the presence and severity of peripheral artery disease (PAD). The prognostic value of ankle brachial index (ABI) has been thoroughly delineated. Nonetheless, the relative usefulness of ankle pressure (AP), ABI, toe pressure (TP), and toe brachial index (TBI) in assessing patient outcome has not been investigated in a concurrent study setting. This study aimed to resolve the association of all four non-invasive haemodynamic parameters in clinically symptomatic patients with PAD with cardiovascular mortality, overall mortality, and amputation free survival (AFS). Methods: In total, 732 symptomatic patients with PAD admitted to the Department of Vascular Surgery for conventional angiography at Turku University Hospital, Turku, Finland, between January 2009 and August 2011 were reviewed retrospectively. Demographic factors, cardiovascular mortality, all-cause mortality, and above foot level amputations were obtained and assessed in relation to AP, ABI, TP, and TBI by means of Kaplan-Meier life tables and a multivariate Cox regression model. Results: The haemodynamic parameter that was associated with poor 36 month general outcome was TP <30 mmHg. Univariate Cox regression analysis of stratified values showed that TP and TBI associated significantly with mortality. In multivariate analysis both TP and TBI were associated with a significant risk of death. For TP <30 mmHg and TBI <0.25 the risk of cardiovascular mortality was hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.75-4.61 [p Conclusion: Among non-invasive haemodynamic measurements and pressure indices both TP and TBI appear to be associated with cardiovascular and overall mortality and AFS for patients with PAD presenting symptoms of the disease. (C) 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Compared to Intermittant Claudication Critical Limb Ischemia Is Associated with Elevated Levels of Cytokines

Critical limb ischemia (CLI) is the advanced stage of peripheral artery disease (PAD) and associated with an extremely poor clinical outcome. In order to understand the possible role of circulating cytokines and poor outcome associated with CLI we compared the circulating cytokine profile of patients with CLI against patients with intermittent claudication (IC). The levels of 48 circulating cytokines were examined in 226 consecutive patients with peripheral artery disease (PAD) admitted for elective, non-urgent, invasive treatment of IC or CLI. The PAD patient cohort was evenly distributed between subjects with IC (46.5%) and CLI (53.5%). As accustomed in PAD, CLI was associated with higher age, chronic kidney disease and diabetes when compared to IC (P < 0.01 for all). In multivariable linear regression modeling taking into account the baseline differences between IC and CLI groups CLI was independently associated with elevated levels of a large number of cytokines: IL-1 beta, IL-1ra, IL-2R alpha, IL-4, IL-6, IL-10, IFN-gamma, GM-CSF, G-CSF (P < 0.01 for all), and IL-2, IL-7, IL-12, IL-13, IL-17, bFGF, VEGF, SCGF-beta (P < 0.05 for all). The current findings indicate that CLI is associated with a circulating cytokine profile, which resembles serious medical conditions such as severe pancreatitis, sepsis, or even cancer. Compared to IC, CLI is a systemic inflammatory condition, which may explain the extremely poor outcome associated with it

Maternal satisfaction with joint and sole child physical placement arrangements following separation in Wisconsin and Finland

Families (and sometimes courts) make important decisions regarding child physical custody arrangements post-separation, and shared parenting arrangements are increasingly common in most developed countries. Shared arrangements may be differentially associated with parental satisfaction, and these associations may vary across countries. Using data from surveys of separated mothers in Wisconsin and Finland, the present study explores this possibility and is guided by three aims: (a) to identify child and family characteristics associated with sole and shared child placements 6 or more years after separation; (b) to estimate associations of children's post-separation placements with maternal satisfaction with placements and expense sharing; (c) to examine whether the relationship between post-separation placement and maternal satisfaction varies by mothers' earnings and the quality of parents' relationships. We find that Finnish mothers with shared placement are more satisfied with their placement than are their counterparts with sole placement, while we find the inverse is true for Wisconsin mothers. Moreover, parental satisfaction with shared placement, overall and relative to sole placement, varies greatly depending on the quality of a mother's relationship with the other parent; and differences in relationship quality in Wisconsin and Finland may help explain the difference in satisfaction with shared placement in the two locations. In both Finland and Wisconsin, we find mothers with shared placement are more satisfied with the way expenses are shared between parents than are mothers with sole placement. Associations between placement and satisfaction are robust to extensive controls for child and maternal characteristics.</p

Leukocyte trafficking-associated vascular adhesion protein 1 is expressed and functionally active in atherosclerotic plaques

Given the important role of inflammation and the potential association of the leukocyte trafficking-associated adhesion molecule vascular adhesion protein 1 (VAP-1) with atherosclerosis, this study examined whether functional VAP-1 is expressed in atherosclerotic lesions and, if so, whether it could be targeted by positron emission tomography (PET). First, immunohistochemistry revealed that VAP-1 localized to endothelial cells of intra-plaque neovessels in human carotid endarterectomy samples from patients with recent ischemic symptoms. In low-density lipoprotein receptor-deficient mice expressing only apolipoprotein B100 (LDLR-/- ApoB(100/100)), VAP-1 was expressed on endothelial cells lining inflamed atherosclerotic lesions; normal vessel walls in aortas of C57BL/6N control mice were VAP-1-negative. Second, we discovered that the focal uptake of VAP-1 targeting sialic acid-binding immunoglobulin-like lectin 9 based PET tracer [Ga-68]DOTA-Siglec-9 in atherosclerotic plaques was associated with the density of activated macrophages (r = 0.58, P = 0.022). As a final point, we found that the inhibition of VAP-1 activity with small molecule LJP1586 decreased the density of macrophages in inflamed atherosclerotic plaques in mice. Our results suggest for the first time VAP-1 as a potential imaging target for inflamed atherosclerotic plaques, and corroborate VAP-1 inhibition as a therapeutic approach in the treatment of atherosclerosis

18-kDa translocator protein ligand 18F-FEMPA: Biodistribution and uptake into atherosclerotic plaques in mice

18F-FEMPA shows rapid blood clearance and uptake in the mouse aorta. Uptake in atherosclerotic plaques correlated with the amount of macrophages, but did not exceed that in the normal vessel wall.</p

Cytostatic Factor Proteins Are Present in Male Meiotic Cells and β-Nerve Growth Factor Increases Mos Levels in Rat Late Spermatocytes

Background: In co-cultures of pachytene spermatocytes with Sertoli cells, beta-NGF regulates the second meiotic division by blocking secondary spermatocytes in metaphase (metaphase II), and thereby lowers round spermatid formation. In vertebrates, mature oocytes are arrested at metaphase II until fertilization, because of the presence of cytostatic factor (CSF) in their cytoplasm. By analogy, we hypothesized the presence of CSF in male germ cells. Methodology/Principal Findings: We show here, that Mos, Emi2, cyclin E and Cdk2, the four proteins of CSF, and their respective mRNAs, are present in male rat meiotic cells; this was assessed by using Western blotting, immunocytochemistry and reverse transcriptase PCR. We measured the relative cellular levels of Mos, Emi2, Cyclin E and Cdk2 in the meiotic cells by flow cytometry and found that the four proteins increased throughout the first meiotic prophase, reaching their highest levels in middle to late pachytene spermatocytes, then decreased following the meiotic divisions. In co-cultures of pachytene spermatocytes with Sertoli cells, beta-NGF increased the number of metaphases II, while enhancing Mos and Emi2 levels in middle to late pachytene spermatocytes, pachytene spermatocytes in division and secondary spermatocytes. Conclusion/Significance: Our results suggest that CSF is not restricted to the oocyte. In addition, they reinforce the view that NGF, by enhancing Mos in late spermatocytes, is one of the intra-testicular factors which adjusts the number of round spermatids that can be supported by Sertoli cells