Data on consistency among different methods to assess atherosclerotic plaque echogenicity on standard ultrasound and intraplaque neovascularization on contrast-enhanced ultrasound imaging in human carotid artery

AbstractHere we provide the correlation among different carotid ultrasound (US) variables to assess echogenicity n standard carotid US and to assess intraplaque neovascularization on contrast enhanced US. We recruited 45 consecutive subjects with an asymptomatic≥50% carotid artery stenosis. Carotid plaque echogenicity at standard US was visually graded according to Gray–Weale classification (GW) and measured by the greyscale median (GSM), a semi-automated computerized measurement performed by Adobe Photoshop®. On CEUS imaging IPNV was graded according to the visual appearance of contrast within the plaque according to three different methods: CEUS_A (1=absent; 2=present); CEUS_B a three-point scale (increasing IPNV from 1 to 3); CEUS_C a four-point scale (increasing IPNV from 0 to 3). We have also implemented a new simple quantification method derived from region of interest (ROI) signal intensity ratio as assessed by QLAB software. Further information is available in “Contrast-enhanced ultrasound imaging of intraplaque neovascularization and its correlation to plaque echogenicity in human carotid arteries atherosclerosis (M. Cattaneo, D. Staub, A.P. Porretta, J.M. Gallino, P. Santini, C. Limoni et al., 2016) [1]

Progression of human carotid and femoral atherosclerosis: a prospective follow-up study by magnetic resonance vessel wall imaging

Aims The time course of atherosclerosis burden in distinct vascular territories remains poorly understood. We longitudinally evaluated the natural history of atherosclerotic progression in two different arterial territories using high spatial resolution magnetic resonance imaging (HR-MRI), a powerful, safe, and non-invasive tool. Methods and results We prospectively studied a cohort of 30 patients (mean age 68.3, n = 9 females) with high Framingham general cardiovascular disease 10-year risk score (29.5%) and standard medical therapy with mild-to-moderate atherosclerosis intra-individually at the level of both carotid and femoral arteries. A total of 178 HR-MRI studies of carotid and femoral arteries performed at baseline and at 1- and 2-year follow-up were evaluated in consensus reading by two experienced readers for lumen area (LA), total vessel area (TVA), vessel wall area (VWA = TVA − LA), and normalized wall area index (NWI = VWA/TVA). At the carotid level, LA decreased (−3.19%/year, P = 0.018), VWA increased (+3.83%/year, P = 0.019), and TVA remained unchanged. At the femoral level, LA remained unchanged, VWA and TVA increased (+5.23%/year and +3.11%/year, both P < 0.01), and NWI increased for both carotid and femoral arteries (+2.28%/year, P = 0.01, and +1.8%/year, P = 0.033). Conclusion The atherosclerotic burden increased significantly in both carotid and femoral arteries. However, carotid plaque progression was associated with negative remodelling, whereas the increase in femoral plaque burden was compensated by positive remodelling. This finding could be related to anatomic and flow differences and/or to the distinct degree of obstruction in the two arterial territorie

Intractable coronary fibromuscular dysplasia leading to end‐stage heart failure and fatal heart transplantation

Coronary fibromuscular dysplasia is uncommon, and even rarer its unstable and recurrent course. We present the unique case of a 52-year-old woman who underwent in total 12 coronary angiographies and three percutaneous coronary intervention within 24 months because of repetitive acute coronary syndromes due to refractory spasm, dissection, restenosis all leading to end-stage heart failure, and heart transplantation. The patient died 12 days after the heart transplantation complicated by intraoperative acute thrombotic occlusion of left anterior descending artery of the graft despite normal pretransplant coronary angiography. Autopsy of the recipient heart confirmed coronary fibromuscular dysplasia with massive intimal hyperplasia and restenosis

VIP induces the decidualization program and conditions the immunoregulation of the implantation process

The decidualization process involves phenotype and functional changes on endometrial cells and the modulation of mediators with immunoregulatory properties as the vasoactive intestinal peptide (VIP). We investigate VIP contribution to the decidualization program and to immunoregulation throughout the human embryo implantation process. The decidualization of Human endometrial stromal cell line (HESC) with Medroxyprogesterone-dibutyryl-cAMP increased VIP/VPAC-receptors system. In fact, VIP could induce decidualization increasing differentiation markers (IGFBP1, PRL, KLF13/KLF9 ratio, CXCL12, CXCL8 and CCL2) and allowing Blastocyst-like spheroids (BLS) invasion in an in vitro model of embryo implantation. Focus on the tolerogenic effects, decidualized cells induced a semi-mature profile on maternal dendritic cells; restrained CD4+ cells recruitment while increased regulatory T-cells recruitment. Interestingly, the human blastocyst conditioned media from developmentally impaired embryos diminished the invasion and T-regulatory cells recruitment in these settings. These evidences suggest that VIP contributes to the implantation process inducing decidualization, allowing BLS invasion and favoring a tolerogenic micro-environment.Fil: Grasso, Esteban Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Gori, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Paparini, Daniel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Soczewski, Elizabeth Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Fernández, Laura del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Gallino, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Salamone, Gabriela Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Martinez, Gustavo. Instituto de Fertilidad; ArgentinaFil: Irigoyen, Marcela. Instituto de Fertilidad; ArgentinaFil: Ruhlmann, Claudio. Instituto de Fertilidad; ArgentinaFil: Perez Leiros, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Ramhorst, Rosanna Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentin

Stress-inducible phosphoprotein 1 (HOP/STI1/STIP1) regulates the accumulation and toxicity of α-synuclein in vivo

The predominantly pre-synaptic intrinsically disordered protein α-synuclein is prone to misfolding and aggregation in synucleinopathies, such as Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB). Molecular chaperones play important roles in protein misfolding diseases and members of the chaperone machinery are often deposited in Lewy bodies. Here, we show that the Hsp90 co-chaperone STI1 co-immunoprecipitated α-synuclein, and co-deposited with Hsp90 and Hsp70 in insoluble protein fractions in two mouse models of α-synuclein misfolding. STI1 and Hsp90 also co-localized extensively with filamentous S129 phosphorylated α-synuclein in ubiquitin-positive inclusions. In PD human brains, STI1 transcripts were increased, and in neurologically healthy brains, STI1 and α-synuclein transcripts correlated. Nuclear Magnetic Resonance (NMR) analyses revealed direct interaction of α-synuclein with STI1 and indicated that the STI1 TPR2A, but not TPR1 or TPR2B domains, interacted with the C-terminal domain of α-synuclein. In vitro, the STI1 TPR2A domain facilitated S129 phosphorylation by Polo-like kinase 3. Moreover, mice over-expressing STI1 and Hsp90ß presented elevated α-synuclein S129 phosphorylation accompanied by inclusions when injected with α-synuclein pre-formed fibrils. In contrast, reduced STI1 function decreased protein inclusion formation, S129 α-synuclein phosphorylation, while mitigating motor and cognitive deficits as well as mesoscopic brain atrophy in α-synuclein-over-expressing mice. Our findings reveal a vicious cycle in which STI1 facilitates the generation and accumulation of toxic α-synuclein conformers, while α-synuclein-induced proteostatic stress increased insoluble STI1 and Hsp90

Binary systems and their nuclear explosions

Peer ReviewedPreprin

The Growing Field of Imaging of Atherosclerosis in Peripheral Arteries.

In the past decades, peripheral arteries have represented a model for the comprehension of atherosclerosis as well as for the development of new diagnostic imaging modalities and therapeutic strategies. Peripheral arteries may represent a window to study atherosclerosis. Pathology has prominently contributed to move the clinical and research attention from the arterial lumen stenosis and angiography to morphological and functional imaging techniques. Evidence from large and prospective cohort or randomized controlled studies is still modest. Nevertheless, several emerging imaging investigations represent a potential tool for a comprehensive "in vivo" evaluation of the entire natural history of peripheral atherosclerosis. This constitutes a demanding assignment, as it would be desirable to obtain both single-lesion focused and extensive arterial system views to achieve the most accurate prognostic information. Our narrative review rests upon the fundamental pathological evidence, summarizing the rapidly growing field of imaging of atherosclerosis in peripheral arteries and presenting a selection of both currently available and emerging imaging techniques

Metabolic features of clear-cell renal cell carcinoma: mechanisms and clinical implications

Central to the malignant behaviour that endows cancer cells with growth advantage is their unique metabolism. Cancer cells can process nutrient molecules differently from normal cells and use it to overcome stress imposed on them by various therapies. This metabolic conversion is controlled by specific genetic mutations that are associated with activation of oncogenes and loss of tumour suppressor proteins. Understanding these processes is important as it can lead to the discovery of biomarkers that can predict the aggressiveness of the disease and its response to therapy, and even more importantly, to the development of novel therapeutics. A classic tumour in this respect is clear-cell renal cell carcinoma (RCC). In this review, we will begin with a brief summary of normal cellular bioenergetic pathways, which will be followed by a description of the characteristic metabolism of glucose and lipids in clear-cell RCC cells and its clinical implications. Data relating to the potential effect of dietary nutrients on RCC will also be reviewed along with potential therapies targeted at interrupting specific metabolic pathways in clear-cell RCC

Imaging of Carotid Plaque Neovascularization by Contrast-Enhanced Ultrasound and Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

BACKGROUND Carotid plaque neovascularization (vasa vasorum [VV]) may be useful for detecting high-risk atherosclerotic plaques. Contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are 2 commonly used techniques for imaging VV of the carotid plaque, yet the relationship between their measurements remains unknown. OBJECTIVES We aimed to blindly evaluate the correlation between CEUS and DCE-MRI in measuring carotid plaque VV. METHODS We recruited subjects with asymptomatic carotid stenosis (≥50%). VV was graded by CEUS, based on richness of contrast signal, according to 3 different methods named CEUS_A, CEUS_B and CEUS_C on different point scales (the higher the values, the higher the estimated VV). A 3.0 T MRI scanner was used for VV quantification by DCE-MRI using gadolinium contrast kinetic modelling for computing the fractional plasma volume (vp) and transfer constant (Ktrans). RESULTS The analysis included 30 patients. A significant correlation between CEUS and DCE-MRI findings was observed when CEUS_C was used for neovessel grading and DCE-MRI was used to determine adventitial (r = 0.460, p = 0.010) and plaque (r = 0.374, p = 0.042) Ktrans values. CEUS_B (r = 0.416, p = 0.022) and CEUS_C (r = 0.443, p = 0.014) grading showed a significant correlation with regard to the maximal Ktrans. CONCLUSIONS We found a positive but weak correlation and a moderate diagnostic agreement between neovessels as visually graded by CEUS and adventitial neovessels assessed by DCE-MRI Ktrans in carotid atherosclerosis. These findings may help in understanding how VV density, flow, and permeability influence in vivo measurements by CEUS and DCE-MRI as well as in selecting the most appropriate variables and imaging method in future research and potentially in clinical settings. Further confirmative studies are necessary to confirm our results

The Growing Field of Imaging of Atherosclerosis in Peripheral Arteries

In the past decades, peripheral arteries have represented a model for the comprehension of atherosclerosis as well as for the development of new diagnostic imaging modalities and therapeutic strategies. Peripheral arteries may represent a window to study atherosclerosis. Pathology has prominently contributed to move the clinical and research attention from the arterial lumen stenosis and angiography to morphological and functional imaging techniques. Evidence from large and prospective cohort or randomized controlled studies is still modest. Nevertheless, several emerging imaging investigations represent a potential tool for a comprehensive "in vivo" evaluation of the entire natural history of peripheral atherosclerosis. This constitutes a demanding assignment, as it would be desirable to obtain both single-lesion focused and extensive arterial system views to achieve the most accurate prognostic information. Our narrative review rests upon the fundamental pathological evidence, summarizing the rapidly growing field of imaging of atherosclerosis in peripheral arteries and presenting a selection of both currently available and emerging imaging techniques