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The hydrophobic organic contaminants triclosan, triphenyl phosphate (TPhP) and diazinon sorb to dissolved organic matter (DOM) and this may alter their bioavailability and toxicity. 1 H nuclear magnetic resonance (NMR)-based metabolomics was used to investigate how DOM at 1 and 5 mg organic carbon/L may alter the metabolome of Daphnia magna from exposure to equitoxic mixtures of triclosan, TPhP and diazinon. These contaminants have different modes of action toward D. magna. The contaminant concentrations in each mixture were an equal percentage of their lethal concentration to 50% of the population (LC 50 ) values, which equates to 1250 μg/L TPhP, 330 μg/L triclosan and 0.9 μg/L diazinon. The ternary mixture exposure at 1% LC 50 values did not alter the D. magna metabolome. Contaminant mixture exposures at 5%, 10%, and 15% LC 50 values decreased glucose, serine and glycine concentrations and increased asparagine and threonine concentrations, suggesting disruptions in energy metabolism. The contaminant mixture had a unique mode of action in D. magna and DOM at 1 and 5 mg organic carbon/L did not change this mode of action. The estimated sorption of triclosan, TPhP or diazinon to DOM at 1 or 5 mg organic carbon/L in this experimental design was calculated to be <50% for each contaminant. This suggests that the mode of action of the contaminant mixture was not altered by DOM because the two environmentally relevant concentrations of DOM may have not substantially altered contaminant bioavailability. Our results indicate that DOM may not inevitably mitigate or alter the sub-lethal toxicity of a mixture of hydrophobic organic contaminants. This indicates the complexity of predicting the molecular-level toxicity of environmental mixtures. For adequate risk assessment of freshwater ecosystems, it is vital to account for the combined sub-lethal toxicity of an environmental mixture of contaminants., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The pharmaceutical 17α-ethynylestradiol (EE2) and the industrial chemical perfluorooctane sulfonate (PFOS) are organic contaminants frequently detected in freshwater environments. It is hypothesized that hydrophobic organic contaminants can sorb to dissolved organic matter (DOM) and this may reduce the toxicity of these contaminants by reducing the contaminants' bioavailability. To investigate this hypothesis, 1 H nuclear magnetic resonance (NMR)-based metabolomics was used to determine how the metabolome of Daphnia magna changes when a range of DOM concentrations are added during EE2 and PFOS exposure experiments. D. magna were exposed for 48 h to sub-lethal concentrations of 1 mg/L EE2 or 30 mg/L PFOS in the presence of 0, 1, 2, 3 and 4 mg dissolved organic carbon (DOC)/L. EE2 exposure resulted in increased amino acids and decreased glucose in D. magna. All DOM concentrations were able to lessen these metabolite disturbances from EE2 exposure, likely due to reductions in the bioavailability of EE2 through interactions with DOM. Exposure to PFOS resulted in decreased amino acids, and the presence of 1 mg DOC/L did not alter this metabolic response. However, PFOS exposure with the higher DOM concentrations resulted in a different pattern of metabolite changes which may be due to combined impacts of PFOS and DOM on the metabolome or due to an increase in PFOS bioavailability and uptake in D. magna. These results suggest that the concentration of DOM influences the sensitive biochemical changes in organisms that occur during acute sub-lethal exposure to organic contaminants., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Previous studies have shown that contaminant toxicity to target organisms is altered by the presence of dissolved organic matter (DOM). Contaminants can bind to DOM and this may alter the bioavailability and subsequent toxicity of the contaminants. However, molecular-level techniques are needed to more closely evaluate the impact of DOM on the sub-lethal biochemical responses to emerging contaminants. To investigate how DOM may alter the metabolic response to organic contaminant exposure, 1 H nuclear magnetic resonance (NMR)-based metabolomics was used to investigate how the metabolome of Daphnia magna changes when Suwannee River DOM (5 mg organic carbon/L) is included in the acute exposure of four contaminants with varying hydrophobicity. Sub-lethal concentrations of the hydrophobic contaminant 17α-ethynylestradiol (EE2), the relatively more polar compounds carbamazepine and imidacloprid, or the anionic contaminant perfluorooctane sulfonate (PFOS) were used. A 48-h exposure to DOM alone had a minor impact on the metabolome of D. magna. There were significant increases in amino acids from EE2 exposure which were reduced in the presence of DOM, suggesting that DOM may alleviate the sub-lethal metabolic response from EE2 exposure through sorption and a reduction in freely dissolved EE2. The metabolome was relatively unaltered with exposure to carbamazepine and imidacloprid in the presence of DOM which is likely because these contaminants are water soluble and did not strongly interact with DOM. PFOS exposure resulted in a more significant metabolic response with DOM suggesting that DOM enhanced the uptake and bioavailability of PFOS in D. magna. As such, the presence of DOM should be considered when determining sensitive molecular-level changes in organisms to sub-lethal organic contaminant exposure., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: To date, all published studies analyzing simultaneous treatment of carotid and proximal atherosclerotic lesions are describing retrograde approach and several technical variations. In the presented study, for the first time, antegrade approach is described for simultaneous carotid endarterectomy (CEA) and associated brachiocephalic trunk (BCT) or common carotid artery (CCA) angioplasty in the hybrid operating room., Methods: From January 2012 till January 2016, antegrade hybrid procedures were performed in 18 patients. All patients were admitted to our institute for elective supraaortic arch multidetector computed tomography angiography when significant simultaneous proximal and distal supraaortic arch lesions were revealed. After surgical exposure of carotid arteries, proximal lesions were crossed by antegrade approach. Prior to stent placement, internal carotid artery (ICA) is clamped at its origin with the guidewire placed in the external carotid artery (ECA). After primary stenting and control arteriography, CCA and ECA are clamped and the ICA clamp moved more distally. An arteriotomy is performed in the CCA, with flushing of possible debris and thrombus before performance of the eversion CEA, once again flushing before completion of the anastomosis. Follow-up ranged from 6 to 36 months with average follow-up of 22.15 ± 11.31 months., Results: All procedures went uneventfully. Out of 18 patients, 11 were males and 7 females, mean age 66.6 ± 3.82 years. In 10 patients (55.5%), simultaneous CEA and CCA angioplasty was performed, in 7 patients (38.9%) CEA and BCT angioplasty, and in 1 patient (5.5%) tubular graft interposition between the CCA and the ICA and CCA angioplasty. In 6 patients (33.3%), CCA/BCT balloon angioplasty alone was performed simultaneously with CEA. None of the patient had postoperative transient ischemic attack, stroke, hematoma, dissection, myocardial infarction, or ischemia in the early postoperative period and during the follow-up. There were no lethal outcomes, neither in the early postoperative course nor during the follow-up., Conclusions: Antegrade approach for simultaneous treatment of proximal CCA/BCT and distal carotid lesions with temporary ICA clamping is safe and feasible procedure that should be thought of in the future in addition to already described retrograde approach., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Pharmaceuticals and personal care products are a class of emerging contaminants that are present in wastewater effluents, surface water, and groundwater around the world. There is a need to determine rapid and reliable bioindicators of exposure and the toxic mode of action of these contaminants to aquatic organisms. (1)H nuclear magnetic resonance (NMR)-based metabolomics in combination with multivariate statistical analysis was used to determine the metabolic profile of Daphnia magna after exposure to a range of sub-lethal concentrations of triclosan (6.25-100μg/L), carbamazepine (1.75-14mg/L) and ibuprofen (1.75-14mg/L) for 48h. Sub-lethal triclosan exposure suggested a general oxidative stress condition and the branched-chain amino acids, glutamine, glutamate, and methionine emerged as potential bioindicators. The aromatic amino acids, serine, glycine and alanine are potential bioindicators for sub-lethal carbamazepine exposure that may have altered energy metabolism. The potential bioindicators for sub-lethal ibuprofen exposure are serine, methionine, lysine, arginine and leucine, which showed a concentration-dependent response. The differences in the metabolic changes were related to the dissimilar modes of toxicity of triclosan, carbamazepine and ibuprofen. (1)H NMR-based metabolomics gave an improved understanding of how these emerging contaminants impact the keystone species D. magna., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The cardiac remodelling process in advanced heart failure due to pressure overload has not been clearly defined but likely involves mechanisms of cardiac fibrosis and cardiomyocyte hypertrophy. The aim of this study was to examine pressure overload (PO)-induced cardiac remodelling processes and their reversibility after unloading in both humans with heart failure and a mouse model of PO induced by aortic constriction., Methods & Results: Speckle tracking echocardiography showed PO-induced cardiac dysfunction in mice was reversible after removal of aortic constriction to unload. Masson's Trichrome staining suggested that PO-induced myocardial fibrosis was reversible, however detailed analysis of 3-dimensional collagen architecture by scanning electron microscopy demonstrated that matrix remodelling was not completely normalised as a disorganised network of thin collagen fibres was evident. Analysis of human left ventricular biopsy samples from HF patients revealed increased presence of large collagen fibres which were greatly reduced in paired samples from the same individuals after unloading by left ventricular assist device implantation. Again, an extensive network of small collagen fibres was still clearly seen to closely surround cardiomyocytes after unloading. Other features of PO-induced remodelling including increased myofibroblast content, cardiomyocyte disarray and hypertrophy were largely reversed upon unloading in both humans and mouse model. Previous work in humans demonstrated that receptors for adiponectin, an important mediator of cardiac fibrosis and hypertrophy, decreased in heart failure patients and returned to normal after unloading. Here we provide novel data showing a similar trend for adiponectin receptor adaptor protein APPL1, but not APPL2 isoform., Conclusions: LV unloading diminishes PO-induced cardiac remodelling and improves function. These findings add new insights into the cardiac remodelling process, and provide novel targets for future pharmacologic therapies., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The purpose of this study was to evaluate the initial and long-term results of endovascular treatment (EVT) in patients with symptomatic high-grade extracranial vertebral artery (VA) origin stenosis., Methods: From February 2001 to March 2013, 73 consecutive patients (33 men with a mean age of 61.7 ± 8.8 years) underwent EVT for symptomatic high-grade VA stenosis. Preoperative evaluation included Duplex ultrasonography and arteriography. After successful treatment, all patients were followed up at 1, 3, 6, and 12 months after the procedure and every 6 months thereafter., Results: Successful EVT of the VA stenosis was achieved in 68 patients (93.2%). All procedures were performed without use of cerebral protection. The early complication rate was 5.5%, which included one periprocedural transient ischemic attack, two hematomas at the puncture site, and one allergic reaction to the contrast agent. No in-hospital deaths occurred. During follow-up (mean, 44.3 ± 31.2 months; range, 2-144 months), the primary patency rates at 1, 3, 5, and 7 years were 98.4%, 87.3%, 87.3%, and 87.3%, respectively. Ultrasound Doppler controls during follow-up detected seven VA restenoses (10.3%). Univariate analysis failed to identify any variable predictive of long-term patency of successfully treated VA stenosis., Conclusions: EVT of symptomatic VA origin stenosis is a safe and effective procedure associated with low risk and good long-term results, even without use of cerebral protection devices., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

We present a rare case of anterior nutcracker syndrome caused by an abdominal aorta aneurysm (AAA). A 61-year-old woman was admitted to our institution for computed tomography angiography. It revealed an AAA 51 mm in diameter that was lifting off of the left renal vein toward the superior mesenteric artery, causing anterior nutcracker syndrome with consequent left renal vein compression and left ovarian vein congestion. Aneurysm resection was performed, followed by left ovarian vein ligation and left adnexectomy to prevent vein conglomerate rupture. This is the first case that describes anterior nutcracker syndrome caused by AAA, which was successfully treated by aneurysm resection., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: To study the initial and long-term results of endovascular treatment in patients aged <50 years with trans-Atlantic inter-society consensus-II type B unilateral iliac lesions and chronic limb ischemia., Methods: From January 2000 to February 2010, 60 consecutive endovascular interventions were performed on 23 women and 37 men aged ≤50 years. After successful treatment, all patients were followed up at 1, 3, 6, and 12 months after the procedure and every 6 months thereafter., Results: Successful percutaneous revascularization of the iliac artery was achieved in 56 patients (93.3%). The early vascular-related complication rate was 6.7%. The primary patency rates at 1, 3, and 5 years were 88%, 59%, and 49%, respectively. Cox univariate analysis revealed that an age range of 45 to 50 years (hazard ratio [HR]: 0.290; 95% confidence interval [CI]: 0.152-0.553; P = 0.0001), lower preprocedural ankle-brachial index (HR: 2.438; 95% CI: 1.04-5.715; P = 0.047), lesion length >5 cm (HR: 0.838; 95% CI: 0.746-0.943; P = 0.003), and diabetes (HR: 2.005; 95% CI: 1.010-3.980; P = 0.047) had significant influence on decreasing primary patency., Conclusions: Endovascular treatment of TASC-II type B iliac lesions in patients aged <50 years is a safe procedure with low procedural risk. Primary patency rates at 1, 3, and 5 years were 88%, 59%, and 49%, respectively., (Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)