Mechanical Thrombectomy in Wake-Up Strokes: A Case Series Using Alberta Stroke Program Early CT Score (ASPECTS) for Patient Selection.

PubMed

Konstas, Angelos Aristeidis; Minaeian, Artin; Ross, Ian B

2017-07-01

There is lack of published studies on mechanical thrombectomy with stent retrievers for wake-up stroke (WUS). To report the outcomes of WUS patients with large vessel occlusions, selected for intervention based on Alberta Stroke Program Early CT Score (ASPECTS) and treated with stent retrievers or primary aspiration thrombectomy. Data were collected retrospectively for each consecutive WUS patient undergoing mechanical thrombectomy with a stent retriever or primary aspiration catheter between February 2015 and September 2016. ASPECTS ≥ 6 was used as the primary imaging criterion for offering thrombectomy in these WUS patients. Main outcomes were the in-hospital improvement in the National Institutes of Health Stroke Scale (NIHSS) and the occurrence of symptomatic hemorrhage. Twelve patients were included in this study; 11 were treated with stent retrievers and 1 was treated with primary aspiration thrombectomy alone. Successful recanalization was achieved in 100% of the patients (33% thrombolysis in cerebral infarction [TICI] 2B and 67% TICI 3). Every patient experienced a reduction in the NIHSS during hospitalization, with a mean NIHSS decrease of 11.1 ± 5.1 points. There was a trend for a larger reduction in the NIHSS in patients with TICI 3 compared to TICI 2B recanalization. There was no symptomatic intracranial hemorrhage in our cohort. For patients with WUS, careful selection of patients using ASPECTS may allow for safe interventions, with low risk of clinical deterioration, and no-periprocedural mortality. All our patients demonstrated a reduction in their NIHSS after the thrombectomy and clinical improvement. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Transjugular Intrahepatic Portosystemic Shunt, Mechanical Aspiration Thrombectomy, and Direct Thrombolysis in the Treatment of Acute Portal and Superior Mesenteric Vein Thrombosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferro, Carlo; Rossi, Umberto G., E-mail: urossi76@hotmail.com; Bovio, Giulio

2007-09-15

A patient was admitted because of severe abdominal pain, anorexia, and intestinal bleeding. Contrast-enhanced multidetector computed tomography demonstrated acute portal and superior mesenteric vein thrombosis (PSMVT). The patient was treated percutaneously with transjugular intrahepatic portosystemic shunt (TIPS), mechanical aspiration thrombectomy, and direct thrombolysis, and 1 week after the procedure, complete patency of the portal and superior mesenteric veins was demonstrated. TIPS, mechanical aspiration thrombectomy, and direct thrombolysis together are promising endovascular techniques for the treatment of symptomatic acute PSMVT.

Revascularization of a thrombosed, previously stented aorto-renal graft using combined directional atherectomy and AngioJet thrombectomy.

PubMed

Seth, A; Mathur, A; Chandra, P; Aggarwal, P; Khanna, N

1999-01-01

We report an interesting case with bilateral PTFE aorto-renal grafts of which one graft underwent balloon angioplasty and stenting for proximal stenosis. Combined debulking by AngioJet thrombectomy and Simpsons directional atherectomy was performed within the stent following reocclusion of the graft 9 months later.

Efficacy and safety of catheter-based rheolytic and aspiration thrombectomy in children.

PubMed

Qureshi, Athar M; Petit, Christopher J; Crystal, Matthew A; Liou, Aimee; Khan, Asra; Justino, Henri

2016-06-01

Vascular thromboses are a significant cause of morbidity and mortality in children. Data in children regarding catheter-based rheolytic and aspiration thrombectomy systems are limited. We sought to review the safety and efficacy of catheter-based rheolytic and aspiration thrombectomy systems in children. Data of all children having undergone thrombectomy using specialized rheolytic or aspiration systems were reviewed. Thrombectomy was performed in 50 vessels in 21 patients, median age 1.9 months (8 days-18 yrs), median weight 4.3 (1.1-67.9) kg. Thrombectomy was performed using AngioJet in 16, Helix Clot Buster in 5, Fetch catheter in 8, Pronto catheter in 1, and a combination of other systems in 20 vessels (with AngioJet in 16). Thrombectomy was successful in 47/50 (94%) vessels in 18/21 (86%) patients with additional balloon/stent therapy or tPA administration performed in 16/18 (89%) of these patients. There were 2 (9.5%) major complications (both with AngioJet) consisting of asystole when thrombectomy was performed using activation times of >5 sec. At a median follow-up of 10 months (2 weeks-7 years), all 47 successfully treated vessels are patent, with 8/18 (44%) patients requiring reintervention with angioplasty/stent placement or repeat thrombectomy. Catheter-based thrombectomy systems are an important adjunctive tool in the treatment of children with thrombotic vessel occlusions. Significant hemodynamic compromise seen when using AngioJet may be minimized by using activation times of ≤5 sec. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Stent-thrombus interaction and the influence of aspiration on mechanical thrombectomy: evaluation of different stent retrievers in a circulation model.

PubMed

Madjidyar, Jawid; Hermes, Julian; Freitag-Wolf, Sandra; Jansen, Olav

2015-08-01

Different devices and techniques are available for endovascular treatment of ischemic stroke. In this in vitro study, we examined the stent-thrombus interaction and the influence of additional aspiration on the efficiency of mechanical thrombectomy with established stent retrievers. Human blood thrombi were made in a Chandler loop. The thrombi were placed into the middle cerebral artery of a vascular silicon phantom. A programmable piston pump was used to acquire physiological flow in the model. Resistances were interposed to gain physiological pressure. The stent retrievers Trevo, Solitaire FR, Separator 3D, and Aperio were used to perform thrombectomy under direct visual control. For the additional aspiration, we used intermediate catheters. Ten attempts per device were made with and without aspiration under standardized conditions, a total of n = 80. For all thrombectomy maneuvers, it was demonstrated that the thrombus was pushed by the stent struts against the vessel wall and was retracted along it. The stent-thrombus interaction was only superficial for all devices. Using additional distal aspiration, the amount of distal embolism and rate of embolism in new territories was significantly lower than without. Moreover, additional aspiration reduced the number of recanalization maneuvers and the recanalization time. Distal aspiration with intermediate catheters increases the efficacy of mechanical thrombectomy with stent retrievers significantly. In contrary to earlier suggestions, the interaction between the thrombus and the stent retriever is only superficial, rather than an integration of the thrombus into the retriever. No significant differences between the proven devices could be shown in our model.

The Basilar Artery on Computed Tomography Angiography Score for Acute Basilar Artery Occlusion Treated with Mechanical Thrombectomy.

PubMed

Yang, Haihua; Ma, Ning; Liu, Lian; Gao, Feng; Mo, Dapeng; Miao, Zhongrong

2018-06-01

Recently, the Basilar Artery on Computed Tomography Angiography (BATMAN) score predicts clinical outcome of acute basilar artery occlusion (BAO), yet there is no extensive external validation. The purpose of this study was to validate the prognostic value of BATMAN scoring system for the prediction of clinical outcome in patients with acute BAO treated with endovascular mechanical thrombectomy by using cerebral digital subtraction angiography (DSA). We analyzed the clinical and angiographic data of consecutive patients with acute BAO from March 2012 to November 2016. The BATMAN scoring system was used to assess the collateral status and thrombus burden. Thrombolysis in Cerebral Infarction (TICI) score 2b-3 was defined as successful recanalization. Receiver operating characteristic (ROC) curve was used to determine the area under the curve (AUC) and the optimum cutoff value. Multivariate regression analysis was used to identify the predictor of clinical outcome. This study included 63 patients with acute BAO who underwent mechanical thrombectomy. Of these patients, 90.5% (57/63) achieved successful recanalization (TICI, 2b-3) and 34.9% (22/63) had a favorable outcome (modified Rankin Scale score 0-2). ROC analysis indicated that the AUC of the BATMAN score was .722 (95% confidence interval [CI], .594-.827), and the optimal cutoff value was 3 (sensitivity = 72.73, specificity = 63.41). In multivariate logistic regression analysis, the BATMAN score higher than 3 was associated with favorable outcome (odds ratio, 5.214; 95% CI, 1.47-18.483; P = .011). The BATMAN score on DSA seems to predict the functional outcome in patients of acute BAO treated with mechanical thrombectomy. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Quantifying the mechanical and histological properties of thrombus analog made from human blood for the creation of synthetic thrombus for thrombectomy device testing.

PubMed

Merritt, William; Holter, Anne Marie; Beahm, Sharna; Gonzalez, Connor; Becker, Timothy A; Tabor, Aaron; Ducruet, Andrew F; Bonsmann, Laura S; Cotter, Trevor R; Frenklakh, Sergey

2018-04-25

Untreated ischemic stroke can lead to severe morbidity and death, and as such, there are numerous endovascular blood-clot removal (thrombectomy) devices approved for human use. Human thrombi types are highly variable and are typically classified in qualitative terms - 'soft/red,' 'hard/white,' or 'aged/calcified.' Quantifying human thrombus properties can accelerate the development of thrombus analogs for the study of thrombectomy outcomes, which are often inconsistent among treated patients. 'Soft'human thrombi were created from blood samples ex vivo (ie, human blood clotted in sample vials) and tested for mechanical properties using a hybrid rheometer material testing system. Synthetic thrombus materials were also mechanically tested and compared with the 'soft' human blood clots. Mechanical testing quantified the shear modulus and dynamic (elastic) modulus of volunteer human thrombus samples. This data was used to formulate a synthetic blood clot made from a composite polymer hydrogel of polyacrylamide and alginate (PAAM-Alg). The PAAM-Alg interpenetrating network of covalently and ionically cross-linked polymers had tunable elastic and shear moduli properties and shape memory characteristics. Due to its adjustable properties, PAAM-Alg can be modified to mimic various thrombi classifications. Future studies will include obtaining and quantitatively classifying patient thrombectomy samples and altering the PAAM-Alg to mimic the results for use with in vitro thrombectomy studies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cell free DNA: A Novel Predictor of Neurological Outcome after Intravenous Thrombolysis and/or Mechanical Thrombectomy in Acute Ischemic Stroke Patients

PubMed Central

Wijatmiko, Teddy; Vajpeyee, Manisha; Taywade, Onjal

2018-01-01

Purpose Several blood markers have been evaluated in stroke patients, but their role remains limited in clinical practice. This study was designed to evaluate the utility of cell free DNA (cf DNA) in stroke patients undergoing therapeutic intervention in the form of mechanical thrombectomy in acute ischemic stroke patients. Materials and Methods Twenty-six patients with ischemic stroke who were managed with interventions like intravenous thrombolysis (IVT) and mechanical thrombectomy were recruited consecutively in this study. The cf DNA was extracted by using circulating nucleic acid kit and measured by real-time quantitative PCR assay for β-globin gene. The neurological outcome was measured by modified Rankin scale (mRS) score at three months after the onset of symptoms. Results Cf DNA levels correlated with severity of stroke at the time of admission (r=0.421, P=0.032) and poor outcome at three months (r=0.606, P=0.001). Therapeutic intervention in the form of mechanical thrombectomy or IVT was associated with improved outcome in patients with cf DNA <10,000 kilogenome-equivalents/L (P=<0.05). Conclusion Cf DNA level correlated well with the 3 month outcome in acute ischemic stroke patients. It can be a potential supplementary marker to predict neurological outcome after therapeutic intervention. PMID:29535894

Mechanical thrombectomy for acute ischemic stroke with occlusion of the M2 segment of the middle cerebral artery: a meta-analysis.

PubMed

Saber, Hamidreza; Narayanan, Sandra; Palla, Mohan; Saver, Jeffrey L; Nogueira, Raul G; Yoo, Albert J; Sheth, Sunil A

2017-11-10

Endovascular thrombectomy has demonstrated benefit for patients with acute ischemic stroke from proximal large vessel occlusion. However, limited evidence is available from recent randomized trials on the role of thrombectomy for M2 segment occlusions of the middle cerebral artery (MCA). We conducted a systematic review and meta-analysis to investigate clinical and radiographic outcomes, rates of hemorrhagic complications, and mortality after M2 occlusion thrombectomy using modern devices, and compared these outcomes against patients with M1 occlusions. Recanalization was defined as Thrombolysis in Cerebral Infarction (TICI) 2b/3 or modified TICI 2b/3. A total of 12 studies with 1080 patients with M2 thrombectomy were included in our analysis. Functional independence (modified Rankin Scale 0-2) rate was 59% (95% CI 54% to 64%). Mortality and symptomatic intracranial hemorrhage rates were 16% (95% CI 11% to 23%) and 10% (95% CI 6% to 16%), respectively. Recanalization rates were 81% (95% CI 79% to 84%), and were equally comparable for stent-retriever versus aspiration (OR 1.05; 95% CI 0.91 to 1.21). Successful M2 recanalization was associated with greater rates of favorable outcome (OR 4.22; 95% CI 1.96 to 9.1) compared with poor M2 recanalization (TICI 0-2a). There was no significant difference in recanalization rates for M2 versus M1 thrombectomy (OR 1.05; 95% CI 0.77 to 1.42). This meta-analysis suggests that mechanical thrombectomy for M2 occlusions that can be safely accessed is associated with high functional independence and recanalization rates, but may be associated with an increased risk of hemorrhage. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Outcomes of early carotid stenting and angioplasty in large-vessel anterior circulation strokes treated with mechanical thrombectomy and intravenous thrombolytics.

PubMed

Mehta, T; Desai, N; Mehta, K; Parikh, R; Male, S; Hussain, M; Ollenschleger, M; Spiegel, G; Grande, A; Ezzeddine, M; Jagadeesan, B; Tummala, R; McCullough, L

2018-01-01

Introduction Proximal cervical internal carotid artery stenosis greater than 50% merits revascularization to mitigate the risk of stroke recurrence among large-vessel anterior circulation strokes undergoing mechanical thrombectomy. Carotid artery stenting necessitates the use of antiplatelets, and there is a theoretical increased risk of hemorrhagic transformation given that such patients may already have received intravenous thrombolytics and have a significant infarct burden. We investigate the outcomes of large-vessel anterior circulation stroke patients treated with intravenous thrombolytics receiving same-day carotid stenting or selective angioplasty compared to no carotid intervention. Materials and methods The study cohort was obtained from the National (Nationwide) Inpatient Sample database between 2006 and 2014, using International Statistical Classification of Diseases, ninth revision discharge diagnosis and procedure codes. A total of 11,825 patients with large-vessel anterior circulation stroke treated with intravenous thrombolytic and mechanical thrombectomy on the same day were identified. The study population was subdivided into three subgroups: no carotid intervention, same-day carotid angioplasty without carotid stenting, and same-day carotid stenting. Outcomes were assessed with respect to mortality, significant disability at discharge, hemorrhagic transformation, and requirement of percutaneous endoscopic gastronomy tube placement, prolonged mechanical ventilation, or craniotomy. Results This study found no statistically significant difference in patient outcomes in those treated with concurrent carotid stenting compared to no carotid intervention in terms of morbidity or mortality. Conclusions If indicated, it is reasonable to consider concurrent carotid stenting and/or angioplasty for large-vessel anterior circulation stroke patients treated with mechanical thrombectomy who also receive intravenous thrombolytics.

Mechanical thrombectomy in acute embolic stroke: preliminary results with the revive device.

PubMed

Rohde, Stefan; Haehnel, Stefan; Herweh, Christian; Pham, Mirko; Stampfl, Sibylle; Ringleb, Peter A; Bendszus, Martin

2011-10-01

The purpose of this study was to evaluate the safety and technical feasibility of a new thrombectomy device (Revive; Micrus Endovascular) in the endovascular treatment of acute ischemic stroke. Ten patients with acute large vessel occlusions were treated with the Revive device between October 2010 and December 2010. Mean National Institutes of Health Stroke Scale on admission was 19.0; mean duration of symptoms was 172 minutes. Recanalization was assessed using the Thrombolysis In Cerebral Infarction score. Clinical outcome (National Institutes of Health Stroke Scale) after thrombectomy was determined on Day 1, at discharge, and at Day 30. Vessel recanalization (Thrombolysis In Cerebral Infarction 2b or 3) was successful in all patients without device-related complications. Mean National Institutes of Health Stroke Scale 24 hours after the intervention, at discharge, and at Day 30 was 14.0, 11.5, and 5.1, respectively. At Day 30, 6 patients had a clinical improvement of >8 points or an National Institutes of Health Stroke Scale of 0 to 1, 1 patient showed minor improvement, and 3 patients had died. Symptomatic intracranial hemorrhage occurred in 2 patients, of which 1 was fatal. Thrombectomy with the Revive device in patients with stroke with acute large vessel occlusions demonstrated to be technically safe and highly effective. Clinical safety and efficacy have to be established in larger clinical trials.

Uric acid therapy improves the outcomes of stroke patients treated with intravenous tissue plasminogen activator and mechanical thrombectomy.

PubMed

Chamorro, Ángel; Amaro, Sergio; Castellanos, Mar; Gomis, Meritxell; Urra, Xabier; Blasco, Jordi; Arenillas, Juan F; Román, Luis S; Muñoz, Roberto; Macho, Juan; Cánovas, David; Marti-Fabregas, Joan; Leira, Enrique C; Planas, Anna M

2017-06-01

Background Numerous neuroprotective drugs have failed to show benefit in the treatment of acute ischemic stroke, making the search for new treatments imperative. Uric acid is an endogenous antioxidant making it a drug candidate to improve stroke outcomes. Aim To report the effects of uric acid therapy in stroke patients receiving intravenous thrombolysis and mechanical thrombectomy. Methods Forty-five patients with proximal vessel occlusions enrolled in the URICO-ICTUS trial received intravenous recombinant tissue plasminogen activator within 4.5 h after stroke onset and randomized to intravenous 1000 mg uric acid or placebo (NCT00860366). These patients also received mechanical thrombectomy because a brain computed tomogaphy angiography confirmed the lack of proximal recanalization at the end of systemic thrombolysis. The primary outcome was good functional outcome at 90 days (modified Rankin Score 0-2). Safety outcomes included mortality, symptomatic intracerebral bleeding, and gout attacks. Results The rate of successful revascularization was >80% in the uric acid and the placebo groups but good functional outcome was observed in 16 out of 24 (67%) patients treated with uric acid and 10 out of 21 (48%) treated with placebo (adjusted Odds Ratio, 6.12 (95% CI 1.08-34.56)). Mortality was observed in two out of 24 (8.3%) patients treated with uric acid and one out of 21 (4.8%) treated with placebo (adjusted Odds Ratio, 3.74 (95% CI 0.06-226.29)). Symptomatic cerebral bleeding and gout attacks were similar in both groups. Conclusions Uric acid therapy was safe and improved stroke outcomes in stroke patients receiving intravenous thrombolysis followed by thrombectomy. Validation of this simple strategy in a larger trial is urgent.

Endovascular Revascularization of Hemodialysis Thrombosed Grafts with the Hydrodynamic Thrombectomy Catheter. Our 7-Year Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bermudez, Patrícia, E-mail: pbermude@clinic.ub.es; Fontseré, Nestor, E-mail: fontsere@clinic.ub.es; Mestres, Gaspar, E-mail: gmestres@clinic.ub.es

2017-02-15

PurposeTo evaluate the efficacy and safety of the hydrodynamic thrombectomy catheter (AngioJet DVX) in the salvage of thrombosed hemodialysis vascular grafts.Materials and MethodsA retrospective study was designed, including all patients with occluded arteriovenous grafts treated with the AngioJet system between 2007 and 2014 in our institution. Outcomes included technical success, clinical success, complications, and primary and secondary patencies. Procedural success was defined as angiographic confirmation of flow restoration, the presence of a pulsatile thrill along the graft, and successful resumption of at least one hemodialysis session. Primary and secondary patencies after first AVG thrombectomy were calculated with Kaplan–Meier curves. Coxmore » regression was used to determine prognostic factors of primary patency after every thrombectomy episode.ResultsA total of 149 thrombectomies were performed in 68 grafts. After thrombectomy, endovascular treatment of one or more stenosis was performed in all cases. Technical success was 93% and clinical success was 86%. Complications occurred in 7 thrombectomies, most of them were minor except for one anastomosis rupture requiring surgery. Primary and secondary patencies were 52, 41, and 23 and 76, 68, and 57% at 3, 6 and 12 months, respectively. Independent prognostic factors of poor patency after every thrombectomy episode were the presence of residual thrombus (OR 1.831, P = 0.008) and time from last thrombosis (less than 1 month; and OR 7.116, P < 0.001).ConclusionPercutaneous mechanical thrombectomy with AngioJet is a safe technique with a high-clinical success rate. The presence of residual thrombus after thrombectomy and early re-occlusions are related to poorer results.« less

Using a new device to prevent pulmonary embolisms during pharmacomechanical thrombectomy.

PubMed

Calleja, E; Ciampi, J J; Puche, J J; Lanciego, C

2018-04-20

We have used a new device to prevent pulmonary embolism during pharmacomechanical thrombectomy in a 25-year-old postpartum woman. The Angel® catheter (BiO2 Medical Inc., Golden, CO, USA) is a temporary device that combines the functions of a vena cava filter (VCF) with those of a triple-lumen central venous catheter. Normally, a VCF is implanted to prevent pulmonary embolism during pharmacomechanical thrombectomy. However, the complications associated with VCFs increase with time, not all of the filter can always be retrieved, and there can be iatrogenic effects both during implantation and retrieval. In our experience, this new device is much simpler to deploy and to retrieve. As is shown in this case, this temporary device can be an interesting alternative to a VCF for preventing pulmonary embolisms during pharmacomechanical thrombectomy. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Thrombectomy for ischemic stroke: meta-analyses of recurrent strokes, vasospasms, and subarachnoid hemorrhages.

PubMed

Emprechtinger, Robert; Piso, Brigitte; Ringleb, Peter A

2017-03-01

Mechanical thrombectomy with stent retrievers is an effective treatment for patients with ischemic stroke. Results of recent meta-analyses report that the treatment is safe. However, the endpoints recurrent stroke, vasospasms, and subarachnoid hemorrhage have not been evaluated sufficiently. Hence, we extracted data on these outcomes from the five recent thrombectomy trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA published in 2015). Subsequently, we conducted meta-analyses for each outcome. We report the results of the fixed, as well as the random effects model. Three studies reported data on recurrent strokes. While the results did not reach statistical significance in the random effects model (despite a three times elevated risk), the fixed effects model revealed a significantly higher rate of recurrent strokes after thrombectomy. Four studies reported data on subarachnoid hemorrhage. The higher pooled rates in the intervention groups were statistically significant in both, the fixed and the random effects model. One study reported on vasospasms. We recorded 14 events in the intervention group and none in the control group. The efficacy of mechanical thrombectomy is not questioned, yet our results indicate an increased risk for recurrent strokes, subarachnoid hemorrhage, and vasospasms post-treatment. Therefore, we strongly recommend a thoroughly surveillance, concerning these adverse events in future clinical trials and routine registries.

Thrombectomy in patients ineligible for iv tPA (THRILL).

PubMed

Bendszus, Martin; Thomalla, Götz; Knauth, Michael; Hacke, Werner; Bonekamp, Susanne; Fiehler, Jens

2015-08-01

A relevant proportion of patients with acute ischemic stroke are ineligible for intravenous thrombolysis with recombinant tissue plasminogen activator. Mechanical thrombectomy offers a treatment alternative for these patients; however, only few data are available on its safety and efficacy. The aim of this study was to compare safety and efficacy of stent retrievers as device class with best medical care alone in acute stroke patients with large intracranial vessel occlusion in the anterior circulation who are not eligible for intravenous thrombolysis with recombinant tissue plasminogen activator up to eight-hours of symptom onset. 'Thrombectomy in patients ineligible for iv tPA' is a prospective, open-label, blinded end-point, binational (Germany and Austria), two-arm, randomized, controlled, post-market study. Primary end-point is the modified Rankin Score shift analysis 90 days (±14) after stroke. Secondary end-points are excellent neurological outcomes (modified Rankin Score ≤ 1), good neurological outcomes (modified Rankin Score ≤ 2 or National Institutes of Health Stroke Scale improvement ≥ 10), difference between predicted infarct volume and actual core infarct volume (computed tomography or magnetic resonance imaging) at 30 (±6) h post-ictus, successful recanalization (thrombolysis in cerebral infarction score 2b or 3), functional health status 90 (±14) days after stroke (European Quality of Life-5 Dimensions) as well as common safety end-points (adverse event, serious adverse event, symptomatic intracranial haemorrhage at 30 (±6) h, death, or dependency). Whether mechanical thrombectomy in patients with acute ischemic stroke who are not eligible for intravenous thrombolysis with recombinant tissue plasminogen activator improves clinical outcomes is unclear. 'Thrombectomy in patients ineligible for iv tPA' may change clinical practice by providing evidence of an effective and safe treatment for such patients. © 2015 World Stroke

[Mechanical thrombectomy in acute ischemic stroke. What is the position after the latest study results?].

PubMed

Hacke, W; Diener, H-C

2015-06-01

Mechanical devices for the recanalization of vessel occlusions in severe acute ischemic stroke have been developed for more than a decade. Several devices have been approved for clinical use on the basis of uncontrolled case series. Many neurologists have asked for randomized clinical trials comparing the new devices with standard treatment, e.g. thrombolytic therapy within a 4.5 h time window. The first 3 investigator initiated randomized trials published in 2013 failed to show superiority of mechanical thrombectomy over standard treatment. In the aftermath of these negative results several new trials with changes in design (e.g. shorter time window and only proximal vessel occlusions) and the use of modern devices with proven higher recanalization rates, so called stent retrievers, have been launched. In October 2014 the first of these new trials was presented and showed a clear superiority of thrombectomy. Based on this result interim analyses of five other studies were performed and most were prematurely terminated because of overwhelming efficacy. Only one trial testing another type of recanalization device failed to reach a statistically significant result. Currently five studies have already been published and two more studies have been presented at scientific conferences. This article provides an overview of the study protocols and the results of the individual studies, their common features and the characteristics of patients who benefit from this treatment. Finally, the consequences that these results may have for the treatment of patients with severe stroke caused by proximal vessel occlusion are discussed.

Prospective, Multi-Centre, Single-Arm Study of Mechanical Thrombectomy using Solitaire FR in Acute Ischemic Stroke-STAR

PubMed Central

Pereira, Vitor M; Gralla, Jan; Davalos, Antoni; Bonafé, Alain; Castaño, Carlos; Chapot, Rene; Liebeskind, David S; Nogueira, Raul G; Arnold, Marcel; Sztajzel, Roman; Liebig, Thomas; Goyal, Mayank; Besselmann, Michael; Moreno, Alfredo; Schroth, Gerhard

2013-01-01

Background and Purpose Mechanical thrombectomy using stent retriever devices have been advocated to increase revascularization in intracranial vessel occlusion. We present the results of a large prospective study on the use of the Solitaire FR in patients with acute ischemic stroke. Methods STAR was an international, multicenter, prospective, single-arm study of Solitaire FR thrombectomy in patients with large vessel anterior circulation strokes treated within 8 hours of symptom onset. Strict criteria for site selection were applied. The primary endpoint was the revascularization rate (3TICI 2b) of the occluded vessel as determined by an independent core lab. The secondary endpoint was the rate of good functional outcome (defined as 90-day modified Rankin scale (mRS) 0–2). Results A total of 202 patients were enrolled across 14 comprehensive stroke centers in Europe, Canada and Australia. The median age was 72 years, 60% were female patients. The median National Institute of Health Stroke Scale (NIHSS) was 17. Most proximal intracranial occlusion was the internal carotid artery in 18%, the middle cerebral artery in 82%. Successful revascularization was achieved in 79.2% of patients. Device and/or procedure related severe adverse events were found in 7.4%. Favorable neurological outcome was found in 57.9%. The mortality rate was 6.9%. Any intracranial hemorrhagic transformation was found in 18.8% of patients, 1.5% were symptomatic. Conclusions In this single arm study, treatment with the Solitaire™ FR device in intracranial anterior circulation occlusions results in high rates of revascularization, low risk of clinically relevant procedural complications, and good clinical outcomes in combination with low mortality at 90 days. Clinical Trial Registration This study is registered with ClinicalTrials.gov, number NCT01327989. PMID:23908066

Outcomes After Direct Thrombectomy or Combined Intravenous and Endovascular Treatment Are Not Different.

PubMed

Abilleira, Sònia; Ribera, Aida; Cardona, Pedro; Rubiera, Marta; López-Cancio, Elena; Amaro, Sergi; Rodríguez-Campello, Ana; Camps-Renom, Pol; Cánovas, David; de Miquel, Maria Angels; Tomasello, Alejandro; Remollo, Sebastian; López-Rueda, Antonio; Vivas, Elio; Perendreu, Joan; Gallofré, Miquel

2017-02-01

Whether intravenous thrombolysis adds a further benefit when given before endovascular thrombectomy (EVT) is unknown. Furthermore, intravenous thrombolysis delays time to groin puncture, mainly among drip and ship patients. Using region-wide registry data, we selected cases that received direct EVT or combined intravenous thrombolysis+EVT for anterior circulation strokes between January 2011 and October 2015. Treatment effect was estimated by stratification on a propensity score. The average odds ratios for the association of treatment with good outcome and death at 3 months and symptomatic bleedings at 24 hours were calculated with the Mantel-Haenszel test statistic. We included 599 direct EVT patients and 567 patients with combined treatment. Stratification through propensity score achieved balance of baseline characteristics across treatment groups. There was no association between treatment modality and good outcome (odds ratio, 0.97; 95% confidence interval, 0.74-1.27), death (odds ratio, 1.07; 95% confidence interval, 0.74-1.54), or symptomatic bleedings (odds ratio, 0.56; 95% confidence interval, 0.25-1.27). This observational study suggests that outcomes after direct EVT or combined intravenous thrombolysis+EVT are not different. If confirmed by a randomized controlled trial, it may have a significant impact on organization of stroke systems of care. © 2017 American Heart Association, Inc.

Successful Reperfusion With Mechanical Thrombectomy Is Associated With Reduced Disability and Mortality in Patients With Pretreatment Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score ≤6.

PubMed

Desilles, Jean-Philippe; Consoli, Arthuro; Redjem, Hocine; Coskun, Oguzhan; Ciccio, Gabriele; Smajda, Stanislas; Labreuche, Julien; Preda, Cristian; Ruiz Guerrero, Clara; Decroix, Jean-Pierre; Rodesch, Georges; Mazighi, Mikael; Blanc, Raphaël; Piotin, Michel; Lapergue, Bertrand

2017-04-01

In acute ischemic stroke patients, diffusion-weighted imaging (DWI)-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is correlated with infarct volume and is an independent factor of functional outcome. Patients with pretreatment DWI-ASPECTS ≤6 were excluded or under-represented in the recent randomized mechanical thrombectomy trials. Our aim was to assess the impact of reperfusion in pretreatment DWI-ASPECTS ≤6 patients treated with mechanical thrombectomy. We analyzed data collected between January 2012 and August 2015 in a bicentric prospective clinical registry of consecutive acute ischemic stroke patients treated with mechanical thrombectomy. Every patient with a documented internal carotid artery or middle cerebral artery occlusion with pretreatment DWI-ASPECTS ≤6 was eligible for this study. The primary end point was a favorable outcome defined by a modified Rankin Scale score ≤2 at 90 days. Two hundred and eighteen patients with a DWI-ASPECTS ≤6 were included. Among them, 145 (66%) patients had successful reperfusion at the end of mechanical thrombectomy. Reperfused patients had an increased rate of favorable outcome (38.7% versus 17.4%; P =0.002) and a decreased rate of mortality at 3 months (22.5% versus 39.1%; P =0.013) compared with nonreperfused patients. The symptomatic intracranial hemorrhage rate was not different between the 2 groups (13.0% versus 14.1%; P =0.83). However, in patients with DWI-ASPECTS <5, favorable outcome was low (13.0% versus 9.5%; P =0.68) with a high mortality rate (45.7% versus 57.1%; P =0.38) with or without successful reperfusion. Successful reperfusion is associated with reduced mortality and disability in patients with a pretreatment DWI-ASPECTS ≤6. Further data from randomized studies are needed, particularly in patients with DWI-ASPECTS <5. © 2017 American Heart Association, Inc.

Percutaneous Venous Thrombectomy Using the Arrow-Trerotola Percutaneous Thrombolytic Device (PTD) with Temporary Caval Filtration: In Vitro Investigations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wildberger, Joachim Ernst, E-mail: wildberg@rad.rwth-aachen.de; Haage, Patrick; Bovelander, Jan

2005-04-15

Purpose. To evaluate the size and quantity of downstream emboli after thrombectomy using the Arrow-Trerotola Percutaneous Thrombolytic Device (PTD) with or without temporary filtration for extensive iliofemoral and iliocaval thrombi in an in vitro flow model. Methods. Iliocaval thrombi were simulated by clotted bovine blood in a flow model (semilucent silicone tubings, diameter 12-16 mm). Five experimental set-ups were performed 10 times each; thrombus particles and distribution were measured in the effluent. First, after retrograde insertion, mechanical thrombectomy was performed using the PTD alone. Then a modified self-expanding tulip-shaped temporary vena cava stent filter was inserted additionally at the beginningmore » of each declotting procedure and removed immediately after the intervention without any manipulation within or at the filter itself. In a third step, the filter was filled with thrombus only. Here, two experiments were performed: Careful closure within the flow circuit without any additional fragmentation procedure and running the PTD within the filter lumen, respectively. In the final set-up, mechanical thrombectomy was performed within the thrombus-filled tubing as well as in the filter lumen. The latter was closed at the end of the procedure and both devices were removed from the flow circuit. Results. Running the PTD in the flow circuit without filter protection led to a fragmentation of 67.9% ({+-}7.14%) of the clot into particles {<=}500 {mu}m; restoration of flow was established in all cases. Additional placement of the filter safely allowed maceration of 82.9% ({+-}5.59%) of the thrombus. Controlled closure of the thrombus-filled filter within the flow circuit without additional mechanical treatment broke up 75.2% ({+-}10.49%), while additional mechanical thrombectomy by running the PTD within the occluded filter led to dissolution of 90.4% ({+-}3.99%) of the initial clot. In the final set-up, an overall fragmentation rate of 99

Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-analysis.

PubMed

Badhiwala, Jetan H; Nassiri, Farshad; Alhazzani, Waleed; Selim, Magdy H; Farrokhyar, Forough; Spears, Julian; Kulkarni, Abhaya V; Singh, Sheila; Alqahtani, Abdulrahman; Rochwerg, Bram; Alshahrani, Mohammad; Murty, Naresh K; Alhazzani, Adel; Yarascavitch, Blake; Reddy, Kesava; Zaidat, Osama O; Almenawer, Saleh A

2015-11-03

Endovascular intervention for acute ischemic stroke improves revascularization. But trials examining endovascular therapy yielded variable functional outcomes, and the effect of endovascular intervention among subgroups needs better definition. To examine the association between endovascular mechanical thrombectomy and clinical outcomes among patients with acute ischemic stroke. We systematically searched MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library without language restriction through August 2015. Eligible studies were randomized clinical trials of endovascular therapy with mechanical thrombectomy vs standard medical care, which includes the use of intravenous tissue plasminogen activator (tPA). Independent reviewers evaluated the quality of studies and abstracted the data. We calculated odds ratios (ORs) and 95% CIs for all outcomes using random-effects meta-analyses and performed subgroup and sensitivity analyses to examine whether certain imaging, patient, treatment, or study characteristics were associated with improved functional outcome. The strength of the evidence was examined for all outcomes using the GRADE method. Ordinal improvement across modified Rankin scale (mRS) scores at 90 days, functional independence (mRS score, 0-2), angiographic revascularization at 24 hours, symptomatic intracranial hemorrhage within 90 days, and all-cause mortality at 90 days. Data were included from 8 trials involving 2423 patients (mean [SD] age, 67.4 [14.4] years; 1131 [46.7%] women), including 1313 who underwent endovascular thrombectomy and 1110 who received standard medical care with tPA. In a meta-analysis of these trials, endovascular therapy was associated with a significant proportional treatment benefit across mRS scores (OR, 1.56; 95% CI, 1.14-2.13; P = .005). Functional independence at 90 days (mRS score, 0-2) occurred among 557 of 1293 patients (44.6%; 95% CI, 36.6%-52.8%) in the endovascular therapy group vs 351 of 1094 patients (31

Thrombus Extraction Catheters vs. Angiojet Rheolytic Thrombectomy in Thrombotic Lesions/SV Grafts

PubMed Central

Alexopoulos, Dimitrios; Davlouros, Periklis A

2012-01-01

Primary percutaneous coronary intervention, (pPCI), of native coronaries and saphenous vein grafts (SVGs), is the recommended reperfusion strategy for STEMI, and an early invasive approach is recommended for high risk patients with UA/NSTEMI. Although PCI effectively restores flow in the infarct related artery/culprit vessel in both situations, myocardial perfusion often remains suboptimal due to microvascular obstruction, partly attributed to distal embolization of thrombus. Hence, thrombectomy (manual or mechanical), prior to stenting may further reduce hard clinical end points in patients with ACS. This article discusses accumulated evidence regarding the safety and effectiveness of thrombectomy in culprit native coronaries and SVGs in such patients, as well as possible strategies for maximizing its benefits relative to the size of the thrombotic burden. PMID:22920486

Randomized trial of primary PCI with or without routine manual thrombectomy.

PubMed

Jolly, Sanjit S; Cairns, John A; Yusuf, Salim; Meeks, Brandi; Pogue, Janice; Rokoss, Michael J; Kedev, Sasko; Thabane, Lehana; Stankovic, Goran; Moreno, Raul; Gershlick, Anthony; Chowdhary, Saqib; Lavi, Shahar; Niemelä, Kari; Steg, Philippe Gabriel; Bernat, Ivo; Xu, Yawei; Cantor, Warren J; Overgaard, Christopher B; Naber, Christoph K; Cheema, Asim N; Welsh, Robert C; Bertrand, Olivier F; Avezum, Alvaro; Bhindi, Ravinay; Pancholy, Samir; Rao, Sunil V; Natarajan, Madhu K; ten Berg, Jurriën M; Shestakovska, Olga; Gao, Peggy; Widimsky, Petr; Džavík, Vladimír

2015-04-09

During primary percutaneous coronary intervention (PCI), manual thrombectomy may reduce distal embolization and thus improve microvascular perfusion. Small trials have suggested that thrombectomy improves surrogate and clinical outcomes, but a larger trial has reported conflicting results. We randomly assigned 10,732 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual thrombectomy versus PCI alone. The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within 180 days. The key safety outcome was stroke within 30 days. The primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomy group versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in the thrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P=0.86). The rates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone; hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P=0.34) and the primary outcome plus stent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio, 1.00; 95% CI, 0.89 to 1.14; P=0.95) were also similar. Stroke within 30 days occurred in 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%) in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P=0.02). In patients with STEMI who were undergoing primary PCI, routine manual thrombectomy, as compared with PCI alone, did not reduce the risk of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heart failure within 180 days but was associated with an increased rate of stroke within 30 days. (Funded by Medtronic and the Canadian Institutes of Health Research; TOTAL ClinicalTrials.gov number, NCT01149044.).

Mechanical thrombectomy in acute ischemic stroke: Consensus statement by ESO-Karolinska Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and EAN.

PubMed

Wahlgren, Nils; Moreira, Tiago; Michel, Patrik; Steiner, Thorsten; Jansen, Olav; Cognard, Christophe; Mattle, Heinrich P; van Zwam, Wim; Holmin, Staffan; Tatlisumak, Turgut; Petersson, Jesper; Caso, Valeria; Hacke, Werner; Mazighi, Mikael; Arnold, Marcel; Fischer, Urs; Szikora, Istvan; Pierot, Laurent; Fiehler, Jens; Gralla, Jan; Fazekas, Franz; Lees, Kennedy R

2016-01-01

The original version of this consensus statement on mechanical thrombectomy was approved at the European Stroke Organisation (ESO)-Karolinska Stroke Update conference in Stockholm, 16-18 November 2014. The statement has later, during 2015, been updated with new clinical trials data in accordance with a decision made at the conference. Revisions have been made at a face-to-face meeting during the ESO Winter School in Berne in February, through email exchanges and the final version has then been approved by each society. The recommendations are identical to the original version with evidence level upgraded by 20 February 2015 and confirmed by 15 May 2015. The purpose of the ESO-Karolinska Stroke Update meetings is to provide updates on recent stroke therapy research and to discuss how the results may be implemented into clinical routine. Selected topics are discussed at consensus sessions, for which a consensus statement is prepared and discussed by the participants at the meeting. The statements are advisory to the ESO guidelines committee. This consensus statement includes recommendations on mechanical thrombectomy after acute stroke. The statement is supported by ESO, European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), and European Academy of Neurology (EAN). © 2016 World Stroke Organization.

TREVO stent-retriever mechanical thrombectomy for acute ischemic stroke secondary to large vessel occlusion registry

PubMed Central

Zaidat, Osama O; Castonguay, Alicia C; Nogueira, Raul G; Haussen, Diogo C; English, Joey D; Satti, Sudhakar R; Chen, Jennifer; Farid, Hamed; Borders, Candace; Veznedaroglu, Erol; Binning, Mandy J; Puri, Ajit; Vora, Nirav A; Budzik, Ron F; Dabus, Guilherme; Linfante, Italo; Janardhan, Vallabh; Alshekhlee, Amer; Abraham, Michael G; Edgell, Randall; Taqi, Muhammad Asif; Khoury, Ramy El; Mokin, Maxim; Majjhoo, Aniel Q; Kabbani, Mouhammed R; Froehler, Michael T; Finch, Ira; Ansari, Sameer A; Novakovic, Roberta; Nguyen, Thanh N

2018-01-01

Background Recent randomized clinical trials (RCTs) demonstrated the efficacy of mechanical thrombectomy using stent-retrievers in patients with acute ischemic stroke (AIS) with large vessel occlusions; however, it remains unclear if these results translate to a real-world setting. The TREVO Stent-Retriever Acute Stroke (TRACK) multicenter Registry aimed to evaluate the use of the Trevo device in everyday clinical practice. Methods Twenty-three centers enrolled consecutive AIS patients treated from March 2013 through August 2015 with the Trevo device. The primary outcome was defined as achieving a Thrombolysis in Cerebral Infarction (TICI) score of ≥2b. Secondary outcomes included 90-day modified Rankin Scale (mRS), mortality, and symptomatic intracranial hemorrhage (sICH). Results A total of 634patients were included. Mean age was 66.1±14.8 years and mean baseline NIH Stroke Scale (NIHSS) score was 17.4±6.7; 86.7% had an anterior circulation occlusion. Mean time from symptom onset to puncture and time to revascularization were 363.1±264.5 min and 78.8±49.6 min, respectively. 80.3% achieved TICI ≥2b. 90-day mRS ≤2 was achieved in 47.9%, compared with 51.4% when restricting the analysis to the anterior circulation and within 6 hours (similar to recent AHA/ASA guidelines), and 54.3% for those who achieved complete revascularization. The 90-day mortality rate was 19.8%. Independent predictors of clinical outcome included age, baseline NIHSS, use of balloon guide catheter, revascularization, and sICH. Conclusion The TRACK Registry results demonstrate the generalizability of the recent thrombectomy RCTs in real-world clinical practice. No differences in clinical and angiographic outcomes were shown between patients treated within the AHA/ASA guidelines and those treated outside the recommendations. PMID:28963367

Value-based procurement of medical devices: Application to devices for mechanical thrombectomy in ischemic stroke.

PubMed

Trippoli, Sabrina; Caccese, Erminia; Marinai, Claudio; Messori, Andrea

2018-03-01

In the acute ischemic stroke, endovascular devices have shown promising clinical results and are also likely to represent value for money, as several modeling studies have shown. Pharmacoeconomic evaluations in this field, however, have little impact on the procurement of these devices. The present study explored how complex pharmacoeconomic models that evaluate effectiveness and cost can be incorporated into the in-hospital procurement of thrombectomy devices. As regards clinical modeling, we extracted outcomes at three months from randomized trials conducted for four thrombectomy devices, and we projected long-term results using standard Markov modeling. In estimating QALYs, the same model was run for the four devices. As regards economic modeling, we firstly estimated for each device the net monetary benefit (NMB) per patient (threshold = $60,000 per QALY); then, we simulated a competitive tender across the four products by determining the tender-based score (on a 0-to-100 scale). Prices of individual devices were obtained from manufacturers. Extensive sensitivity testing was applied to our analyses. For the four devices (Solitaire, Trevo, Penumbra, Solumbra), QALYs were 1.86, 1.52, 1,79, 1.35, NMB was $101,824, $83,546, $101,923, $69,440, and tender-based scores were 99.70, 43.43, 100, 0, respectively. Sensitivity analysis confirmed findings from base-case. Our results indicate that, in the field of thrombectomy devices, incorporating the typical tools of cost-effectiveness into the processes of tenders and procurement is feasible. Bridging the methodology of cost-effectiveness with the every-day practice of in-hospital procurement can contribute to maximizing the health returns that are generated by in-hospital expenditures for medical devices. Copyright © 2018 Elsevier B.V. All rights reserved.

Modified Thrombolysis in Cerebral Infarction 2C/Thrombolysis in Cerebral Infarction 3 Reperfusion Should Be the Aim of Mechanical Thrombectomy: Insights From the ASTER Trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization).

PubMed

Dargazanli, Cyril; Fahed, Robert; Blanc, Raphael; Gory, Benjamin; Labreuche, Julien; Duhamel, Alain; Marnat, Gaultier; Saleme, Suzana; Costalat, Vincent; Bracard, Serge; Desal, Hubert; Mazighi, Mikael; Consoli, Arturo; Piotin, Michel; Lapergue, Bertrand

2018-05-01

Although successful reperfusion is usually defined as a modified Thrombolysis in Cerebral Infarction (mTICI) 2B or 3 at the end of the procedure, studies have shown that mTICI 2B patients had poorer functional outcomes than TICI 3 patients. An mTICI 2C category has been recently introduced for patients with near-complete perfusion except for slow flow in a few distal cortical vessels or presence of small distal cortical emboli after mechanical thrombectomy. The purpose of this study was to evaluate the difference in functional outcome between patients achieving successful reperfusion (ie, mTICI 2B, mTICI 2C, and TICI 3 scores). Ancillary study from the ASTER (Contact Aspiration Versus Stent Retriever for Successful Revascularization) prospective multicenter blinded end point trial. Reperfusion results are reported as the mTICI score, including the mTICI 2C grade. Primary outcome was the percentage of patients with favorable outcome defined as a 90-day modified Rankin Scale score of 0 to 2. Two hundred ninety patients with successful reperfusion (mTICI ≥2B), harboring ischemic stroke secondary to occlusion of the anterior circulation within 6 hours of onset of symptoms, undergoing mechanical thrombectomy by contact aspiration or stent retriever were included. Favorable outcome (pre-specified as primary outcome of this ancillary study) did not differ significantly between the 3 reperfusion grades, with a similar positive effect of 2C (odds ratio, 1.71; 95% confidence interval, 0.98-3.00) and 3 (odds ratio, 1.73; 95% confidence interval, 0.88-3.41) grades compared with 2B grade. After combining grades 2C and 3, patients had a significantly higher rate of favorable outcome than patients with 2B (odds ratio, 1.72; 95% confidence interval, 1.01-2.90; P =0.043). Favorable outcome rate decreased with increasing onset-to-reperfusion time, with no significant interaction between mTICI 2C/3 grade and onset-to-reperfusion time on favorable outcome. Combining mTICI 2C and

Thrombectomy and thrombolysis: the interventional radiology approach.

PubMed

Dunn, Marilyn E

2011-04-01

To present interventional therapeutic options for patients with thrombosis. Thrombosis in small animals results from an unbalance in the normal hemostatic mechanisms leading to vessel occlusion. In veterinary medicine, thrombosis is recognized as a common complication of many acquired diseases, including cardiac, endocrine, immunological, inflammatory, and neoplastic disorders. Clinical signs are variable depending on the location of the thrombus and various laboratory and imaging modalities can aid in its identification and localization. Once identified, a decision must be made to whether or not intervene and which method is most appropriate. A number of minimally invasive approaches for dealing with thrombosis are available and offer veterinarians a choice of therapeutic options when dealing with a thrombotic patient. In the presence of thrombosis, a combined approach of vessel balloon dilatation, catheter-directed thrombolysis and stenting may be most appropriate. Percutaneous mechanical thrombectomy, if available, may also be appropriate. Embolic trapping devices can be used with vena cava thrombosis to help prevent pulmonary embolism. Anticoagulant therapy may be indicated in the postoperative period to prevent further thrombus formation while the patient's fibrinolytic system breaks the clot down. Outcome is variable depending on the site of the thrombus formation. Arterial thrombosis can be life-threatening while venous thrombosis tends to be less life-threatening but may lead to pulmonary embolism. © Veterinary Emergency and Critical Care Society 2011.

Culprit lesion thrombus burden after manual thrombectomy or percutaneous coronary intervention-alone in ST-segment elevation myocardial infarction: the optical coherence tomography sub-study of the TOTAL (ThrOmbecTomy versus PCI ALone) trial.

PubMed

Bhindi, Ravinay; Kajander, Olli A; Jolly, Sanjit S; Kassam, Saleem; Lavi, Shahar; Niemelä, Kari; Fung, Anthony; Cheema, Asim N; Meeks, Brandi; Alexopoulos, Dimitrios; Kočka, Viktor; Cantor, Warren J; Kaivosoja, Timo P; Shestakovska, Olga; Gao, Peggy; Stankovic, Goran; Džavík, Vladimír; Sheth, Tej

2015-08-01

Manual thrombectomy has been proposed as a strategy to reduce thrombus burden during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, the effectiveness of manual thrombectomy in reducing thrombus burden is uncertain. In this substudy of the TOTAL (ThrOmbecTomy versus PCI ALone) trial, we compared the thrombus burden at the culprit lesion using optical coherence tomography (OCT) in patients treated with thrombectomy vs. PCI-alone. The TOTAL trial (N = 10 732) was an international, multicentre, randomized trial of thrombectomy (using the Export catheter, Medtronic Cardiovascular, Santa Rosa, CA, USA) in STEMI patients treated with primary PCI. The OCT substudy prospectively enrolled 214 patients from 13 sites in 5 countries. Optical coherence tomography was performed immediately after thrombectomy or PCI-alone and then repeated after stent deployment. Thrombus quantification was performed by an independent core laboratory blinded to treatment assignment. The primary outcome of pre-stent thrombus burden as a percentage of segment analysed was 2.36% (95% CI: 1.73-3.22) in the thrombectomy group and 2.88% (95% CI: 2.12-3.90) in the PCI-alone group (P = 0.373). Absolute pre-stent thrombus volume was not different (2.99 vs. 3.74 mm(3), P = 0.329). Other secondary outcomes of pre-stent quadrants of thrombus, post-stent atherothrombotic burden, and post-stent atherothrombotic volume were not different between groups. Manual thrombectomy did not reduce pre-stent thrombus burden at the culprit lesion compared with PCI-alone. Both strategies were associated with low thrombus burden at the lesion site after the initial intervention to restore flow. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Pulmonary Hypertension Among End-Stage Renal Failure Patients Following Hemodialysis Access Thrombectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harp, Richard J.; Stavropoulos, S. William; Wasserstein, Alan G.

Purpose: Percutaneous hemodialysis thrombectomy causes subclinical pulmonary emboli without short-term clinical consequence; the long-term effects on the pulmonary arterial vasculature are unknown. We compared the prevalence of pulmonary hypertension between patients who underwent one or more hemodialysis access thrombectomy procedures with controls without prior thrombectomy.Methods: A retrospective case-control study was performed. Cases (n = 88) had undergone one or more hemodialysis graft thrombectomy procedures, with subsequent echocardiography during routine investigation of comorbid cardiovascular disease. Cases were compared with controls without end-stage renal disease (ESRD) (n = 100, group 1), and controls with ESRD but no prior thrombectomy procedures (n =more » 117, group 2). The presence and velocity of tricuspid regurgitation on echocardiography was used to determine the prevalence and grade of pulmonary hypertension; these were compared between cases and controls using the chi-square test and logistic regression.Results: The prevalence of pulmonary hypertension among cases was 52% (46/88), consisting of mild, moderate and severe in 26% (n = 23), 10% (n = 9) and 16% (n = 14), respectively. Prevalence of pulmonary hypertension among group 1 controls was 26% (26/100), consisting of mild, moderate and severe pulmonary hypertension in 14%, 5% and 7%, respectively. Cases had 2.7 times greater odds of having pulmonary hypertension than group 1 controls (p = 0.002). The prevalence of pulmonary hypertension among group 2 controls was 42% (49/117), consisting of mild, moderate and severe pulmonary arterial hypertension in 25% (n = 49), 10% (n = 12) and 4% (n = 5), respectively. Cases were slightly more likely to have pulmonary hypertension than group 2 controls (OR = 1.5), although this failed to reach statistical significance (p = 0.14).Conclusion: Prior hemodialysis access thrombectomy does not appear to be a risk factor for pulmonary arterial

TREVO stent-retriever mechanical thrombectomy for acute ischemic stroke secondary to large vessel occlusion registry.

PubMed

Zaidat, Osama O; Castonguay, Alicia C; Nogueira, Raul G; Haussen, Diogo C; English, Joey D; Satti, Sudhakar R; Chen, Jennifer; Farid, Hamed; Borders, Candace; Veznedaroglu, Erol; Binning, Mandy J; Puri, Ajit; Vora, Nirav A; Budzik, Ron F; Dabus, Guilherme; Linfante, Italo; Janardhan, Vallabh; Alshekhlee, Amer; Abraham, Michael G; Edgell, Randall; Taqi, Muhammad Asif; Khoury, Ramy El; Mokin, Maxim; Majjhoo, Aniel Q; Kabbani, Mouhammed R; Froehler, Michael T; Finch, Ira; Ansari, Sameer A; Novakovic, Roberta; Nguyen, Thanh N

2018-06-01

Recent randomized clinical trials (RCTs) demonstrated the efficacy of mechanical thrombectomy using stent-retrievers in patients with acute ischemic stroke (AIS) with large vessel occlusions; however, it remains unclear if these results translate to a real-world setting. The TREVO Stent-Retriever Acute Stroke (TRACK) multicenter Registry aimed to evaluate the use of the Trevo device in everyday clinical practice. Twenty-three centers enrolled consecutive AIS patients treated from March 2013 through August 2015 with the Trevo device. The primary outcome was defined as achieving a Thrombolysis in Cerebral Infarction (TICI) score of ≥2b. Secondary outcomes included 90-day modified Rankin Scale (mRS), mortality, and symptomatic intracranial hemorrhage (sICH). A total of 634patients were included. Mean age was 66.1±14.8 years and mean baseline NIH Stroke Scale (NIHSS) score was 17.4±6.7; 86.7% had an anterior circulation occlusion. Mean time from symptom onset to puncture and time to revascularization were 363.1±264.5 min and 78.8±49.6 min, respectively. 80.3% achieved TICI ≥2b. 90-day mRS ≤2 was achieved in 47.9%, compared with 51.4% when restricting the analysis to the anterior circulation and within 6 hours (similar to recent AHA/ASA guidelines), and 54.3% for those who achieved complete revascularization. The 90-day mortality rate was 19.8%. Independent predictors of clinical outcome included age, baseline NIHSS, use of balloon guide catheter, revascularization, and sICH. The TRACK Registry results demonstrate the generalizability of the recent thrombectomy RCTs in real-world clinical practice. No differences in clinical and angiographic outcomes were shown between patients treated within the AHA/ASA guidelines and those treated outside the recommendations. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct.

PubMed

Nogueira, Raul G; Jadhav, Ashutosh P; Haussen, Diogo C; Bonafe, Alain; Budzik, Ronald F; Bhuva, Parita; Yavagal, Dileep R; Ribo, Marc; Cognard, Christophe; Hanel, Ricardo A; Sila, Cathy A; Hassan, Ameer E; Millan, Monica; Levy, Elad I; Mitchell, Peter; Chen, Michael; English, Joey D; Shah, Qaisar A; Silver, Frank L; Pereira, Vitor M; Mehta, Brijesh P; Baxter, Blaise W; Abraham, Michael G; Cardona, Pedro; Veznedaroglu, Erol; Hellinger, Frank R; Feng, Lei; Kirmani, Jawad F; Lopes, Demetrius K; Jankowitz, Brian T; Frankel, Michael R; Costalat, Vincent; Vora, Nirav A; Yoo, Albert J; Malik, Amer M; Furlan, Anthony J; Rubiera, Marta; Aghaebrahim, Amin; Olivot, Jean-Marc; Tekle, Wondwossen G; Shields, Ryan; Graves, Todd; Lewis, Roger J; Smith, Wade S; Liebeskind, David S; Saver, Jeffrey L; Jovin, Tudor G

2018-01-04

The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy. We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating more severe disability) at 90 days. A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because of the results of a prespecified interim analysis. The mean score on the utility-weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group (adjusted difference [Bayesian analysis], 2.0 points; 95% credible interval, 1.1 to 3.0; posterior probability of superiority, >0.999), and the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group (adjusted difference, 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the thrombectomy group and 3% in the

Ultrasound guided V3 segment vertebral artery direct percutaneous puncture for basilar artery mechanical thrombectomy in acute stroke: a technical report.

PubMed

Desai, Jamsheed A; Almekhlafi, Mohammed A; Hill, Michael D; Goyal, Mayank; Eesa, Muneer

2014-04-01

A middle aged patient presented with acute ischemic stroke due to basilar artery occlusion. The patient clinically deteriorated despite intravenous thrombolysis and was referred for mechanical thrombectomy. The right vertebral artery was occluded and could not be accessed despite attempting various shaped catheters, even when a radial artery access was used. The left vertebral artery ended in the posterior inferior cerebellar artery. Eventually, ultrasound guided V3 segment vertebral artery direct puncture was successfully done and the procedure was completed. No access related complications were encountered. Direct cervical arterial puncture can be safely used by experienced operators as a last resort in acute stroke cases with difficult access.

Safety and Efficacy of Solitaire Stent Thrombectomy

PubMed Central

Campbell, Bruce C.V.; Hill, Michael D.; Rubiera, Marta; Menon, Bijoy K.; Demchuk, Andrew; Donnan, Geoffrey A.; Roy, Daniel; Thornton, John; Dorado, Laura; Bonafe, Alain; Levy, Elad I.; Diener, Hans-Christoph; Hernández-Pérez, María; Pereira, Vitor Mendes; Blasco, Jordi; Quesada, Helena; Rempel, Jeremy; Jahan, Reza; Davis, Stephen M.; Stouch, Bruce C.; Mitchell, Peter J.; Jovin, Tudor G.; Saver, Jeffrey L.

2016-01-01

Background and Purpose— Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke. Methods— Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration): Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA), and Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses: (1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0–2), symptomatic intracerebral hemorrhage, and mortality. Results— The primary analysis included 787 patients: 401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0–3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent

Clinical outcomes in middle cerebral artery trunk occlusions versus secondary division occlusions after mechanical thrombectomy: pooled analysis of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials.

PubMed

Shi, Zhong-Song; Loh, Yince; Walker, Gary; Duckwiler, Gary R

2010-05-01

The benefit of endovascular revascularization of patients with acute ischemic stroke with middle cerebral artery (MCA) secondary division (M2) occlusions as compared with MCA trunk (M1) occlusions is not known. In this analysis, we compared revascularization status and clinical outcomes in patients with angiographically confirmed MCA M1 versus isolated M2 occlusions treated with mechanical thrombectomy using the Merci Retriever devices. We retrospectively analyzed the pooled data of patients with MCA strokes from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials. Patient data were dichotomized into 2 groups: MCA M1 occlusions and isolated M2 occlusions. Baseline characteristics, revascularization rates, hemorrhage rates, complications, outcomes, and mortality were evaluated for both groups. Of 178 patients with MCA occlusion treated in the MERCI and Multi MERCI trials, 84.3% had M1 lesions and 15.7% had isolated M2 lesions. Patients with isolated M2 occlusions were revascularized at a higher rate, required a lower mean number of passes, and were associated with a trend toward shorter mean procedure time than patients with M1 occlusions. No statistically significant differences were found between M2 and M1 groups for symptomatic hemorrhage, clinically significant procedural adverse events, favorable 90-day outcome, or 90-day mortality, although in all instances, the M2 outcomes were numerically better than those in M1 subjects. In multivariate analysis, final revascularization was the strongest independent predictor of good outcome at 90 days. Patients with both MCA M1 occlusions and isolated M2 occlusions can achieve a relatively high rate of revascularization and favorable clinical outcomes after mechanical thrombectomy. In fact, patients with isolated M2 occlusions had a higher rate of revascularization, required fewer passes, and had no increased complications compared with patients with M1 occlusions.

Increasing Efficacy of Thrombectomy by Using Digital Subtraction Angiography to Confirm Stent Retriever Clot Integration

PubMed Central

Simon, Scott; Cooke, Jonathon

2016-01-01

Physicians performing thrombectomy for acute stroke have had increasing success as thrombectomy-specific devices have continued to evolve. As the devices evolve, so too must the techniques. The current generation of stent retriever thrombectomy devices requires five minutes of dwell time, regardless of the particularities of the case. We have noticed the presence of flow through the stent immediately prior to removal portends a lower chance of successful thrombus retrieval than when no flow is seen, regardless of dwell time. We hypothesize that interventionalists can use the presence or absence of flow to predict adequacy of seating time and decrease the number of deployments per case. This could significantly decrease time to recanalization by avoiding time-consuming, unsuccessful pulls. This is a technical report of a few cases of stent retriever thrombectomy. We propose using post-deployment digital subtraction angiography to confirm thrombus-device integration and increase the chance of thrombus removal. PMID:27182473

Streamlining Workflow for Endovascular Mechanical Thrombectomy: Lessons Learned from a Comprehensive Stroke Center.

PubMed

Wang, Hongjin; Thevathasan, Arthur; Dowling, Richard; Bush, Steven; Mitchell, Peter; Yan, Bernard

2017-08-01

Recently, 5 randomized controlled trials confirmed the superiority of endovascular mechanical thrombectomy (EMT) to intravenous thrombolysis in acute ischemic stroke with large-vessel occlusion. The implication is that our health systems would witness an increasing number of patients treated with EMT. However, in-hospital delays, leading to increased time to reperfusion, are associated with poor clinical outcomes. This review outlines the in-hospital workflow of the treatment of acute ischemic stroke at a comprehensive stroke center and the lessons learned in reduction of in-hospital delays. The in-hospital workflow for acute ischemic stroke was described from prehospital notification to femoral arterial puncture in preparation for EMT. Systematic review of literature was also performed with PubMed. The implementation of workflow streamlining could result in reduction of in-hospital time delays for patients who were eligible for EMT. In particular, time-critical measures, including prehospital notification, the transfer of patients from door to computed tomography (CT) room, initiation of intravenous thrombolysis in the CT room, and the mobilization of neurointervention team in parallel with thrombolysis, all contributed to reduction in time delays. We have identified issues resulting in in-hospital time delays and have reported possible solutions to improve workflow efficiencies. We believe that these measures may help stroke centers initiate an EMT service for eligible patients. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Iodine Extravasation Quantification on Dual-Energy CT of the Brain Performed after Mechanical Thrombectomy for Acute Ischemic Stroke Can Predict Hemorrhagic Complications.

PubMed

Bonatti, M; Lombardo, F; Zamboni, G A; Vittadello, F; Currò Dossi, R; Bonetti, B; Pozzi Mucelli, R; Bonatti, G

2018-01-18

Intracerebral hemorrhage represents a potentially severe complication of revascularization of acute ischemic stroke. The aim of our study was to assess the capability of iodine extravasation quantification on dual-energy CT performed immediately after mechanical thrombectomy to predict hemorrhagic complications. Because this was a retrospective study, the need for informed consent was waived. Eighty-five consecutive patients who underwent brain dual-energy CT immediately after mechanical thrombectomy for acute ischemic stroke between August 2013 and January 2017 were included. Two radiologists independently evaluated dual-energy CT images for the presence of parenchymal hyperdensity, iodine extravasation, and hemorrhage. Maximum iodine concentration was measured. Follow-up CT examinations performed until patient discharge were reviewed for intracerebral hemorrhage development. The correlation between dual-energy CT parameters and intracerebral hemorrhage development was analyzed by the Mann-Whitney U test and Fisher exact test. Receiver operating characteristic curves were generated for continuous variables. Thirteen of 85 patients (15.3%) developed hemorrhage. On postoperative dual-energy CT, parenchymal hyperdensities and iodine extravasation were present in 100% of the patients who developed intracerebral hemorrhage and in 56.3% of the patients who did not ( P = .002 for both). Signs of bleeding were present in 35.7% of the patients who developed intracerebral hemorrhage and in none of the patients who did not ( P < .001). Median maximum iodine concentration was 2.63 mg/mL in the patients who developed intracerebral hemorrhage and 1.4 mg/mL in the patients who did not ( P < .001). Maximum iodine concentration showed an area under the curve of 0.89 for identifying patients developing intracerebral hemorrhage. The presence of parenchymal hyperdensity with a maximum iodine concentration of >1.35 mg/mL may identify patients developing intracerebral hemorrhage with

Does Preinterventional Flat-Panel Computer Tomography Pooled Blood Volume Mapping Predict Final Infarct Volume After Mechanical Thrombectomy in Acute Cerebral Artery Occlusion?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagner, Marlies, E-mail: marlies.wagner@kgu.de; Kyriakou, Yiannis, E-mail: yiannis.kyriakou@siemens.com; Mesnil de Rochemont, Richard du, E-mail: mesnil@em.uni-frankfurt.de

2013-08-01

PurposeDecreased cerebral blood volume is known to be a predictor for final infarct volume in acute cerebral artery occlusion. To evaluate the predictability of final infarct volume in patients with acute occlusion of the middle cerebral artery (MCA) or the distal internal carotid artery (ICA) and successful endovascular recanalization, pooled blood volume (PBV) was measured using flat-panel detector computed tomography (FPD CT).Materials and MethodsTwenty patients with acute unilateral occlusion of the MCA or distal ACI without demarcated infarction, as proven by CT at admission, and successful Thrombolysis in cerebral infarction score (TICI 2b or 3) endovascular thrombectomy were included. Cerebralmore » PBV maps were acquired from each patient immediately before endovascular thrombectomy. Twenty-four hours after recanalization, each patient underwent multislice CT to visualize final infarct volume. Extent of the areas of decreased PBV was compared with the final infarct volume proven by follow-up CT the next day.ResultsIn 15 of 20 patients, areas of distinct PBV decrease corresponded to final infarct volume. In 5 patients, areas of decreased PBV overestimated final extension of ischemia probably due to inappropriate timing of data acquisition and misery perfusion.ConclusionPBV mapping using FPD CT is a promising tool to predict areas of irrecoverable brain parenchyma in acute thromboembolic stroke. Further validation is necessary before routine use for decision making for interventional thrombectomy.« less

Endovascular thrombectomy for acute ischemic stroke in failed intravenous tissue plasminogen activator versus non-intravenous tissue plasminogen activator patients: revascularization and outcomes stratified by the site of arterial occlusions.

PubMed

Shi, Zhong-Song; Loh, Yince; Walker, Gary; Duckwiler, Gary R

2010-06-01

Intracranial mechanical thrombectomy is a therapeutic option for acute ischemic stroke patients failing intravenous tissue plasminogen activator (IV tPA). We compared patients treated by mechanical embolus removal in cerebral ischemia (MERCI) thrombectomy after failed IV tPA with those treated with thrombectomy alone. We pooled MERCI and Multi MERCI study patients, grouped them either as failed IV tPA or non-IV tPA, and assessed revascularization rates, procedural complications, symptomatic hemorrhage rates, clinical outcomes, and mortality. We also evaluated outcomes stratified by the occlusion site and final revascularization. Among 305 patients, 48 failed, and 257 were ineligible for IV tPA. Nonresponders to IV tPA trended toward a higher revascularization rate (73% versus 63%) and less mortality (27.7% versus 40.1%) and had similar rates of symptomatic hemorrhage and procedural complications. Favorable 90-day outcomes were similar in failed and non-IV tPA patients (38% versus 31%), with no difference according to occlusion site. Among patients failing IV tPA, good outcomes tended to occur more frequently in revascularized patients (47.1% versus 15.4%), although this relationship was attributable solely to middle cerebral artery and not internal carotid artery occlusions, with no difference in mortality. Among IV tPA-ineligible patients, revascularization correlated with good outcome (47.4% versus 4.4%) and less mortality (28.5% versus 59.6%). The risks of hemorrhage and procedure-related complications after mechanical thrombectomy do not differ with respect to previous IV tPA administration. Thrombectomy after IV tPA achieves similar rates of good outcomes, a tendency toward lower mortality, and similar revascularization rates when stratified by clot location. Good outcomes correlate with successful revascularization except with internal carotid artery occlusions in tPA-nonresponders.

Mechanical Thrombectomy-Ready Comprehensive Stroke Center Requirements and Endovascular Stroke Systems of Care: Recommendations from the Endovascular Stroke Standards Committee of the Society of Vascular and Interventional Neurology (SVIN)

PubMed Central

English, Joey D.; Yavagal, Dileep R.; Gupta, Rishi; Janardhan, Vallabh; Zaidat, Osama O.; Xavier, Andrew R.; Nogueira, Raul G.; Kirmani, Jawad F.; Jovin, Tudor G.

2016-01-01

Five landmark multicenter, prospective, randomized, open-label, blinded end point clinical trials have recently demonstrated significant clinical benefit of endovascular therapy with mechanical thrombectomy in acute ischemic stroke (AIS) patients presenting with proximal intracranial large vessel occlusions. The Society of Vascular and Interventional Neurology (SVIN) appointed an expert writing committee to summarize this new evidence and make recommendations on how these data should guide emergency endovascular therapy for AIS patients. PMID:27051410

Regional Differences in Thrombectomy Rates : Secondary use of Billing Codes in the MIRACUM (Medical Informatics for Research and Care in University Medicine) Consortium.

PubMed

Haverkamp, Christian; Ganslandt, Thomas; Horki, Petar; Boeker, Martin; Dörfler, Arnd; Schwab, Stefan; Berkefeld, Joachim; Pfeilschifter, Waltraud; Niesen, Wolf-Dirk; Egger, Karl; Kaps, Manfred; Brockmann, Marc A; Neumaier-Probst, Eva; Szabo, Kristina; Skalej, Martin; Bien, Siegfried; Best, Christoph; Prokosch, Hans-Ulrich; Urbach, Horst

2018-01-08

Mechanical thrombectomy, in addition to intravenous (i.v.) thrombolysis is recommended for treatment of acute stroke in patients with large vessel occlusions (LVO) in the anterior circulation up to 6 h after symptom onset. We compared thrombectomy rates of eight university hospitals of the MIRACUM consortium to analyze the implementation of this guideline in clinical routine. Anonymized billing data in a standardized format were loaded into a local i2b2 data warehouse by applying already existing extract, transform and load (ETL) routines. A locally executed uniform SQL (structured query language) query delivered aggregated site data for all inpatients with a discharge diagnosis of ischemic stroke (ICD-10 I63) containing counts for type of acute treatment, type of admission and age groups, which were centrally analyzed with R. From 2014 to 2016, the thrombectomy rate almost doubled from a mean of 4.7% to 9.6%, although significant differences between centers exist (range in 2016: 5.8-17%). The number of drip-and-ship procedures increased in 3 out of 8 centers. There was no evidence for a decrease in thrombectomy rates during weekends/holiday or among patients older than 80 years, but this age group is more likely to receive i.v. recombinant tissue plasminogen activator (rtPA). The observed increase of thrombectomy rates and drip-and-ship procedures without a significant difference between weekdays and weekends or patients of different ages is substantiating a rapid implementation of stroke guidelines within the analyzed neurovascular centers. The prototype of the MIRACUM Data Integration Center already contributes to health services research in Germany.

Feasibility of Crosslinked Acrylic Shape Memory Polymer for a Thrombectomy Device

PubMed Central

Muschenborn, Andrea D.; Hearon, Keith; Volk, Brent L.; Conway, Jordan W.; Maitland, Duncan J.

2014-01-01

Purpose To evaluate the feasibility of utilizing a system of SMP acrylates for a thrombectomy device by determining an optimal crosslink density that provides both adequate recovery stress for blood clot removal and sufficient strain capacity to enable catheter delivery. Methods Four thermoset acrylic copolymers containing benzylmethacrylate (BzMA) and bisphenol A ethoxylate diacrylate (Mn~512, BPA) were designed with differing thermomechanical properties. Finite element analysis (FEA) was performed to ensure that the materials were able to undergo the strains imposed by crimping, and fabricated devices were subjected to force-monitored crimping, constrained recovery, and bench-top thrombectomy. Results Devices with 25 and 35 mole% BPA exhibited the highest recovery stress and the highest brittle response as they broke upon constrained recovery. On the contrary, the 15 mole % BPA devices endured all testing and their recovery stress (5 kPa) enabled successful bench-top thrombectomy in 2/3 times, compared to 0/3 for the devices with the lowest BPA content. Conclusion While the 15 mole% BPA devices provided the best trade-off between device integrity and performance, other SMP systems that offer recovery stresses above 5 kPa without increasing brittleness to the point of causing device failure would be more suitable for this application. PMID:25414549

Predictive value of flat-panel CT for haemorrhagic transformations in patients with acute stroke treated with thrombectomy.

PubMed

Rouchaud, Aymeric; Pistocchi, Silvia; Blanc, Raphaël; Engrand, Nicolas; Bartolini, Bruno; Piotin, Michel

2014-03-01

Haemorrhagic transformations are pejorative for patients with acute ischaemic stroke (AIS). We estimated flat-panel CT performances to detect brain parenchymal hyperdense lesions immediately after mechanical thrombectomy directly on the angiography table in patients with AIS, and its ability to predict haemorrhagic transformation. We also evaluated an easy-reading protocol for post-procedure flat-panel CT evaluation by clinicians to enable them to determine the potential risk of haemorrhage. Two neuroradiologists retrospectively reviewed post-procedural flat-panel CT and 24 h follow-up imaging. We evaluated hyperdense lesions on flat-panel CT to predict the occurrence of haemorrhagic transformation within 24 h detected with conventional imaging. Of 63 patients, 60.3% presented post-procedural parenchymal hyperdensity and 54.0% had haemorrhagic transformation. Significantly more patients with hyperdense lesions on post-thrombectomy flat-panel CT presented haemorrhagic transformation (84.2% vs 8.0%; p<0.0001). No significant haemorrhagic transformations were detected for patients without parenchymal hyperdensity. Sensitivity and specificity of hyperdense lesions on flat-panel CT for the prediction of haemorrhagic transformation were 94.1% (80.3-99.3%) and 79.3% (60.3-92.0%), respectively. The positive and negative predictive values for the occurrence of haemorrhage were 84.2% (68.8-94.0%) and 92.0% (74.0-99.0%), respectively. For significant parenchymal haemorrhage type 2, sensitivity and negative predictive values were 100%. We observed good homogeneity between the different readers. Hyperdensity on post-procedural flat-panel CT was associated with a tendency for higher risk of death and lower risk of good clinical outcome. Flat-panel CT appears to be a good tool to detect brain parenchymal hyperdensities after mechanical thrombectomy in patients with AIS and to predict haemorrhagic transformation.

Histological Examination of Trousseau Syndrome-Related Thrombus Retrieved Through Acute Endovascular Thrombectomy: Report of 2 Cases.

PubMed

Matsumoto, Naoki; Fukuda, Hitoshi; Handa, Akira; Kawasaki, Toshinari; Kurosaki, Yoshitaka; Chin, Masaki; Yamagata, Sen

2016-12-01

The mechanism of thrombus formation in Trousseau syndrome remains unclear. The purpose of this study was to investigate specific pathological findings of the thrombi in Trousseau syndrome. The authors report on 2 cases of thrombi in Trousseau syndrome from large cerebral vessels removed by endovascular therapy and compared with thrombi in atherosclerosis or cardiac embolism. The first patient, a 67-year-old man, was transferred to our hospital for sudden onset consciousness disturbance and tetraparesis. He had been diagnosed with stage IV lung cancer. The magnetic resonance (MR) angiography demonstrated basilar artery occlusion. An endovascular thrombectomy was performed. The second patient, an 84-year-old woman, was transferred to our hospital for sudden onset motor aphasia and right-sided motor weakness. She has a history of stage IV pancreatic body cancer. The MR angiography demonstrated left middle cerebral artery occlusion. An endovascular thrombectomy was performed for the floating thrombus. Macroscopic findings of retrieved thrombi were observed immediately after thrombectomy. The thrombi in Trousseau syndrome were white in color and solid against manual compression, whereas thrombi from other causes were red and fragile. In terms of microscopic findings, the thrombi in Trousseau syndrome mainly contained fibrin. On the other hand, thrombi associated with atherosclerosis or cardiac embolism had smaller area of fibrin with a considerable amount of red and white blood cells. The thrombi in Trousseau syndrome, which caused occlusion of large cerebral vessel, almost exclusively consisted of fibrin. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The golden 35 min of stroke intervention with ADAPT: effect of thrombectomy procedural time in acute ischemic stroke on outcome.

PubMed

Alawieh, Ali; Pierce, Alyssa K; Vargas, Jan; Turk, Aquilla S; Turner, Raymond D; Chaudry, M Imran; Spiotta, Alejandro M

2018-03-01

In acute ischemic stroke (AIS), extending mechanical thrombectomy procedural times beyond 60 min has previously been associated with an increased complication rate and poorer outcomes. After improvements in thrombectomy methods, to reassess whether this relationship holds true with a more contemporary thrombectomy approach: a direct aspiration first pass technique (ADAPT). We retrospectively studied a database of patients with AIS who underwent ADAPT thrombectomy for large vessel occlusions. Patients were dichotomized into two groups: 'early recan', in which recanalization (recan) was achieved in ≤35 min, and 'late recan', in which procedures extended beyond 35 min. 197 patients (47.7% women, mean age 66.3 years) were identified. We determined that after 35 min, a poor outcome was more likely than a good (modified Rankin Scale (mRS) score 0-2) outcome. The baseline National Institutes of Health Stroke Scale (NIHSS) score was similar between 'early recan' (n=122) (14.7±6.9) and 'late recan' patients (n=75) (15.9±7.2). Among 'early recan' patients, recanalization was achieved in 17.8±8.8 min compared with 70±39.8 min in 'late recan' patients. The likelihood of achieving a good outcome was higher in the 'early recan' group (65.2%) than in the 'late recan' group (38.2%; p<0.001). Patients in the 'late recan' group had a higher likelihood of postprocedural hemorrhage, specifically parenchymal hematoma type 2, than those in the 'early recan' group. Logistic regression analysis showed that baseline NIHSS, recanalization time, and atrial fibrillation had a significant impact on 90-day outcomes. Our findings suggest that extending ADAPT thrombectomy procedure times beyond 35 min increases the likelihood of complications such as intracerebral hemorrhage while reducing the likelihood of a good outcome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Acute Superior Mesenteric Venous Thrombosis: Transcatheter Thrombolysis and Aspiration Thrombectomy Therapy by Combined Route of Superior Mesenteric Vein and Artery in Eight Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Shuofei, E-mail: yangshuofei@gmail.com; Liu, Baochen, E-mail: 306446264@qq.com; Ding, Weiwei, E-mail: dingwei-nju@hotmail.com

PurposeTo assess the feasibility, effectiveness, and safety of catheter-directed thrombolysis and aspiration thrombectomy therapy by combined route of superior mesenteric vein and artery (SMV+SMA) for acute superior mesenteric venous thrombosis (ASMVT).MethodsThis retrospective study reviewed eight ASMVT patients with transcatheter direct thrombolysis and aspiration thrombectomy therapy via SMV and indirect thrombolysis via SMA during a period of 14 months. The demographics, etiology, risk factors, therapeutic effect, complications, mortality, and follow-up of the study population were assessed. Anatomic and imaging classification of location and extent of thrombus at diagnosis and degree of thrombus lysis were described.ResultsTechnical success was achieved with substantial improvement inmore » symptoms and thrombus resolution after thrombolytic therapy in all patients. The local urokinase infusion by SMA and SMV was performed for 5–7 (6.13 ± 0.83) and 7–15 (12 ± 2.51) days. Anticoagulation was performed catheter-directed and then orally throughout hospitalization and after discharge. Four patients required delayed localized bowel resection after thrombolytic therapy with no death. Thrombolytic therapy was not interrupted despite minor bleeding at the puncture site in two patients and sepsis in another two postoperatively. Nearly complete removal of thrombus was demonstrated by contrast-enhanced CT scan and portography before discharge. Patients were discharged in 10–27 (19.25 ± 4.89) days after admission. No recurrence developed during the follow-up of 10–13 (12.13 ± 0.99) months.ConclusionsCatheter-directed thrombolytic and aspiration therapy via SMV+SMA is beneficial for ASMVT in avoiding patient death, efficient resolving thrombus, rapid improving symptoms, reversing extensive intestinal ischemia, averting bowel resection, or localizing infarcted bowel segment and preventing short bowel syndrome.« less

Racial and socioeconomic disparities in access to mechanical revascularization procedures for acute ischemic stroke.

PubMed

Attenello, Frank J; Adamczyk, Peter; Wen, Ge; He, Shuhan; Zhang, Katie; Russin, Jonathan J; Sanossian, Nerses; Amar, Arun P; Mack, William J

2014-02-01

Mechanical revascularization procedures performed for treatment of acute ischemic stroke have increased in recent years. Data suggest association between operative volume and mortality rates. Understanding procedural allocation and patient access patterns is critical. Few studies have examined these demographics. Data were collected from the 2008 Nationwide Inpatient Sample database. Patients hospitalized with ischemic stroke and the subset of individuals who underwent mechanical thrombectomy were characterized by race, payer source, population density, and median wealth of the patient's zip code. Demographic data among patients undergoing mechanical thrombectomy procedures were examined. Stroke admission demographics were analyzed according to thrombectomy volume at admitting centers and patient demographics assessed according to the thrombectomy volume at treating centers. Significant allocation differences with respect to frequency of mechanical thrombectomy procedures among stroke patients existed according to race, expected payer, population density, and wealth of the patient's zip code (P < .0001). White, Hispanic, and Asian/Pacific Islander patients received endovascular treatment at higher rates than black and Native American patients. Compared with the white stroke patients, black (P < .001), Hispanic (P < .001), Asian/Pacific Islander (P < .001), and Native American stroke patients (P < .001) all demonstrated decreased frequency of admission to hospitals performing mechanical thrombectomy procedures at high volumes. Among treated patients, blacks (P = .0876), Hispanics (P = .0335), and Asian/Pacific Islanders (P < .001) demonstrated decreased frequency in mechanical thrombectomy procedures performed at high-volume centers when compared with whites. While present, socioeconomic disparities were not as consistent or pronounced as racial differences. We demonstrate variances in endovascular acute stroke treatment allocation according to racial and

Mechanical Thrombectomy in Elderly Stroke Patients with Mild-to-Moderate Baseline Disability.

PubMed

Slawski, Diana E; Salahuddin, Hisham; Shawver, Julie; Kenmuir, Cynthia L; Tietjen, Gretchen E; Korsnack, Andrea; Zaidi, Syed F; Jumaa, Mouhammad A

2018-04-01

The number of elderly patients suffering from ischemic stroke is rising. Randomized trials of mechanical thrombectomy (MT) generally exclude patients over the age of 80 years with baseline disability. The aim of this study was to understand the efficacy and safety of MT in elderly patients, many of whom may have baseline impairment. Between January 2015 and April 2017, 96 patients ≥80 years old who underwent MT for stroke were selected for a chart review. The data included baseline characteristics, time to treatment, the rate of revascularization, procedural complications, mortality, and 90-day good outcome defined as a modified Rankin Scale (mRS) score of 0-2 or return to baseline. Of the 96 patients, 50 had mild baseline disability (mRS score 0-1) and 46 had moderate disability (mRS score 2-4). Recanalization was achieved in 84% of the patients, and the rate of symptomatic hemorrhage was 6%. At 90 days, 34% of the patients had a good outcome. There were no significant differences in good outcome between those with mild and those with moderate baseline disability (43 vs. 24%, p = 0.08), between those aged ≤85 and those aged > 85 years (40.8 vs. 26.1%, p = 0.19), and between those treated within and those treated beyond 8 h (39 vs. 20%, p = 0.1). The mortality rate was 38.5% at 90 days. The Alberta Stroke Program Early CT Score (ASPECTS) and the National Institutes of Health Stroke Scale (NIHSS) predicted good outcome regardless of baseline disability ( p < 0.001 and p = 0.009, respectively). Advanced age, baseline disability, and delayed treatment are associated with sub-optimal outcomes after MT. However, redefining good outcome to include return to baseline functioning demonstrates that one-third of this patient population benefits from MT, suggesting the real-life utility of this treatment.

DWI-ASPECTS (Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Scores) and DWI-FLAIR (Diffusion-Weighted Imaging-Fluid Attenuated Inversion Recovery) Mismatch in Thrombectomy Candidates: An Intrarater and Interrater Agreement Study.

PubMed

Fahed, Robert; Lecler, Augustin; Sabben, Candice; Khoury, Naim; Ducroux, Célina; Chalumeau, Vanessa; Botta, Daniele; Kalsoum, Erwah; Boisseau, William; Duron, Loïc; Cabral, Dominique; Koskas, Patricia; Benaïssa, Azzedine; Koulakian, Hasmik; Obadia, Michael; Maïer, Benjamin; Weisenburger-Lile, David; Lapergue, Bertrand; Wang, Adrien; Redjem, Hocine; Ciccio, Gabriele; Smajda, Stanislas; Desilles, Jean-Philippe; Mazighi, Mikaël; Ben Maacha, Malek; Akkari, Inès; Zuber, Kevin; Blanc, Raphaël; Raymond, Jean; Piotin, Michel

2018-01-01

We aimed to study the intrarater and interrater agreement of clinicians attributing DWI-ASPECTS (Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Scores) and DWI-FLAIR (Diffusion-Weighted Imaging-Fluid Attenuated Inversion Recovery) mismatch in patients with acute ischemic stroke referred for mechanical thrombectomy. Eighteen raters independently scored anonymized magnetic resonance imaging scans of 30 participants from a multicentre thrombectomy trial, in 2 different reading sessions. Agreement was measured using Fleiss κ and Cohen κ statistics. Interrater agreement for DWI-ASPECTS was slight (κ=0.17 [0.14-0.21]). Four raters (22.2%) had a substantial (or higher) intrarater agreement. Dichotomization of the DWI-ASPECTS (0-5 versus 6-10 or 0-6 versus 7-10) increased the interrater agreement to a substantial level (κ=0.62 [0.48-0.75] and 0.68 [0.55-0.79], respectively) and more raters reached a substantial (or higher) intrarater agreement (17/18 raters [94.4%]). Interrater agreement for DWI-FLAIR mismatch was moderate (κ=0.43 [0.33-0.57]); 11 raters (61.1%) reached a substantial (or higher) intrarater agreement. Agreement between clinicians assessing DWI-ASPECTS and DWI-FLAIR mismatch may not be sufficient to make repeatable clinical decisions in mechanical thrombectomy. The dichotomization of the DWI-ASPECTS (0-5 versus 0-6 or 0-6 versus 7-10) improved interrater and intrarater agreement, however, its relevance for patients selection for mechanical thrombectomy needs to be validated in a randomized trial. © 2017 American Heart Association, Inc.

Use and impact of thrombectomy in primary percutaneous coronary intervention for acute myocardial infarction with persistent ST-segment elevation: results of the prospective ALKK PCI-registry.

PubMed

Härle, Tobias; Zeymer, Uwe; Hochadel, Matthias; Schmidt, Karin; Zahn, Ralf; Darius, Harald; Behrens, Steffen; Lauer, Bernward; Mudra, Harald; Schächinger, Volker; Elsässer, Albrecht

2015-10-01

Data about the impact of thrombectomy in primary percutaneous coronary intervention (PCI) are inconsistent. The aim of our study was an evaluation of both the real-world use of thrombectomy and the impact of thrombectomy on outcome in unselected patients treated with primary PCI for ST-elevation myocardial infarction (STEMI). We used the data of the prospective ALKK PCI-registry of 35 hospitals from January 2010 to December 2013. A total of 10,755 patients receiving single-vessel primary PCI for acute STEMI were included. In 2176 patients (20.2 %) thrombectomy was performed. There was a wide range of use of thrombectomy in the different ALKK hospitals from 1.1 to 61.7 % (median 18.6 %, quartiles 6.0 and 40.3 %) with a general increase of use over the first years of the study period. In patients with and without thrombectomy there was TIMI 0 flow present before PCI in 6010 patients, TIMI 1 in 1338, TIMI 2 in 2002, and TIMI 3 in 1405. Patients with acute heart failure or cardiogenic shock received significantly more often thrombectomy. Fluoroscopy time (8.1 vs. 7.3 min, p < 0.0001) and dose area product (5373 cGy × cm(2) vs. 4802 cGy × cm(2), p < 0.0001) were significantly higher in patients treated with thrombectomy. The subgroup of patients with TIMI 0 flow before PCI had significantly higher rates of TIMI 3 flow after PCI when treated with thrombectomy (87.1 vs. 84.1 %, p < 0.01), while there was no difference in post-PCI TIMI 3 flow in patients with TIMI 1, 2 or 3 flow before PCI. Rates of major adverse cardiac and cerebrovascular events were similar in both groups in general and in all subgroups of TIMI flow. The use of thrombectomy in patients with STEMI is heterogenous between hospitals. Overall, there was no impact of thrombectomy on TIMI 3 patency or mortality after PCI. In the subgroup of STEMI patients with TIMI 0 flow before PCI individualized thrombectomy had a positive impact on restoration of normal blood flow.

Novel simultaneous combination chemical thrombolysis/rheolytic thrombectomy therapy for acute critical limb ischemia: the power-pulse spray technique.

PubMed

Allie, David E; Hebert, Chris J; Lirtzman, Mitchell D; Wyatt, Charles H; Keller, V Antoine; Khan, Mohamed H; Barker, Esmond A; McElderry, Michael W; Khan, Muhammad A; Fail, Peter S; Stagg, Samuel J; Mitran, Elena V; Chaisson, Gary; Allie, Sonja D; Allie, Adam A; Walker, Craig M

2004-12-01

The novel power-pulse spray (P-PS) technique maximizes and combines the advantages and minimizes the disadvantages of both chemical thrombolysis (CT) and rheolytic thrombectomy (RT). Forty-nine consecutive patients with iliofemoral thrombotic occlusion were treated via P-PS technique. Using a 6 Fr RT catheter, saline prime was exchanged for thrombolytic solution [group 1, 10-20 mg tenecteplase (TNK)/50 cc saline, n = 25; group 2, 1,000,000 urokinase (UK)/50 cc saline, n = 24]. The outflow port was closed, then the catheter was advanced at 1 mm increments while pulsing lytic agent. After 30-min lysis time, RT and definitive treatment of the underlying stenosis were performed. Procedure success was 23/25 (92%) and 22/24 (91.6%) for group 1 and 2, respectively. The mean total procedure time was 72 and 75 min in group 1 and 2, respectively. Thirty-day limb salvage was 91% in both groups. There were no major surgical complications. The P-PS technique is safe and effective using either UK or TNK, offering several potential advantages over monotherapy, including more rapid revascularization, decreases systemic lytic exposure and bleeding complications while facilitating both CT and RT capacity and efficacy. (c) 2004 Wiley-Liss, Inc.

Mechanical Thrombectomy for Minor and Mild Stroke Patients Harboring Large Vessel Occlusion in the Anterior Circulation: A Multicenter Cohort Study.

PubMed

Dargazanli, Cyril; Arquizan, Caroline; Gory, Benjamin; Consoli, Arturo; Labreuche, Julien; Redjem, Hocine; Eker, Omer; Decroix, Jean-Pierre; Corlobé, Astrid; Mourand, Isabelle; Gaillard, Nicolas; Ayrignac, Xavier; Charif, Mahmoud; Duhamel, Alain; Labeyrie, Paul-Emile; Riquelme, Carlos; Ciccio, Gabriele; Smajda, Stanislas; Desilles, Jean-Philippe; Gascou, Grégory; Lefèvre, Pierre-Henri; Mantilla-García, Daniel; Cagnazzo, Federico; Coskun, Oguzhan; Mazighi, Mikael; Riva, Roberto; Bourdain, Frédéric; Labauge, Pierre; Rodesch, Georges; Obadia, Michael; Bonafé, Alain; Turjman, Francis; Costalat, Vincent; Piotin, Michel; Blanc, Raphaël; Lapergue, Bertrand

2017-12-01

Proximal large vessel occlusion (LVO) is present in up to 30% of minor strokes. The effectiveness of mechanical thrombectomy (MT) in the subgroup of minor stroke with LVO in the anterior circulation is still open to debate. Data about MT in this subgroup of patients are sparse, and their optimal management has not yet been defined. The purpose of this multicenter cohort study was to evaluate the effectiveness of MT in patients experiencing acute ischemic stroke (AIS) because of LVO in the anterior circulation, presenting with minor-to-mild stroke symptoms (National Institutes of Health Stroke Scale score of <8). Multicenter cohort study involving 4 comprehensive stroke centers having 2 therapeutic approaches (urgent thrombectomy associated with best medical treatment [BMT] versus BMT first and MT if worsening occurs) about management of patients with minor and mild acute ischemic stroke harboring LVO in the anterior circulation. An intention-to-treat analysis was conducted. The primary end point was the rate of excellent outcome defined as the achievement of a modified Rankin Scale score of 0 to 1 at 3 months. Three hundred one patients were included, 170 with urgent MT associated with BMT, and 131 with BMT alone as first-line treatment. Patients treated with MT were younger, more often received intravenous thrombolysis, and had shorter time to imaging. Twenty-four patients (18.0%) in the medical group had rescue MT because of neurological worsening. Overall, excellent outcome was achieved in 64.5% of patients, with no difference between the 2 groups. Stratified analysis according to key subgroups did not find heterogeneity in the treatment effect size. Minor-to-mild stroke patients with LVO achieved excellent and favorable functional outcomes at 3 months in similar proportions between urgent MT versus delayed MT associated with BMT. There is thus an urgent need for randomized trials to define the effectiveness of MT in this patient subgroup. © 2017 American Heart

Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke.

PubMed

Campbell, Bruce C V; Mitchell, Peter J; Churilov, Leonid; Yassi, Nawaf; Kleinig, Timothy J; Dowling, Richard J; Yan, Bernard; Bush, Steven J; Dewey, Helen M; Thijs, Vincent; Scroop, Rebecca; Simpson, Marion; Brooks, Mark; Asadi, Hamed; Wu, Teddy Y; Shah, Darshan G; Wijeratne, Tissa; Ang, Timothy; Miteff, Ferdinand; Levi, Christopher R; Rodrigues, Edrich; Zhao, Henry; Salvaris, Patrick; Garcia-Esperon, Carlos; Bailey, Peter; Rice, Henry; de Villiers, Laetitia; Brown, Helen; Redmond, Kendal; Leggett, David; Fink, John N; Collecutt, Wayne; Wong, Andrew A; Muller, Claire; Coulthard, Alan; Mitchell, Ken; Clouston, John; Mahady, Kate; Field, Deborah; Ma, Henry; Phan, Thanh G; Chong, Winston; Chandra, Ronil V; Slater, Lee-Anne; Krause, Martin; Harrington, Timothy J; Faulder, Kenneth C; Steinfort, Brendan S; Bladin, Christopher F; Sharma, Gagan; Desmond, Patricia M; Parsons, Mark W; Donnan, Geoffrey A; Davis, Stephen M

2018-04-26

Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion. We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage. Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group. Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health

Outcome and periprocedural time management in referred versus directly admitted stroke patients treated with thrombectomy.

PubMed

Weber, Ralph; Reimann, Gernot; Weimar, Christian; Winkler, Angela; Berger, Klaus; Nordmeyer, Hannes; Hadisurya, Jeffrie; Brassel, Friedhelm; Kitzrow, Martin; Krogias, Christos; Weber, Werner; Busch, Elmar W; Eyding, Jens

2016-03-01

After thrombectomy has shown to be effective in acute stroke patients with large vessel occlusion, the potential benefit of secondary referral for such an intervention needs to be validated. We aimed to compare consecutive stoke patients directly admitted and treated with thrombectomy at a neurointerventional centre with patients secondarily referred for such a procedure from hospitals with a stroke unit. Periprocedure times and mortality in 300 patients primarily treated in eight neurointerventional centres were compared with 343 patients referred from nine other hospitals in a prospective multicentre study of a German neurovascular network. Data on functional outcome at 3 months was available in 430 (76.4%) patients. In-hospital mortality (14.8% versus 11.7%, p = 0.26) and 3 months mortality (21.9% versus 24.1%, p = 0.53) were not statistically different in both patient groups despite a significant shorter symptom to groin puncture time in directly admitted patients, which was mainly caused by a longer interfacility transfer time. We found a nonsignificant trend for better functional outcome at 3 months in directly admitted patients (modified Rankin Scale 0-2, 44.0% versus 35.7%, p = 0.08). Our results show that a drip-and-ship thrombectomy concept can be effectively organized in a metropolitan stroke network. Every effort should be made to speed up the emergency interfacility transfer to a neurointerventional centre in stroke patients eligible for thrombectomy after initial brain imaging.

Endovascular treatment of iliofemoral deep vein thrombosis in pregnancy using US-guided percutaneous aspiration thrombectomy.

PubMed

Gedikoglu, Murat; Oguzkurt, Levent

2017-01-01

We aimed to describe ultrasonography (US)-guided percutaneous aspiration thrombectomy in pregnant women with iliofemoral deep vein thrombosis. This study included nine pregnant women with acute and subacute iliofemoral deep vein thrombosis, who were severe symptomatic cases with massive swelling and pain of the leg. Patients were excluded from the study if they had only femoropopliteal deep vein thrombosis or mild symptoms of deep vein thrombosis. US-guided percutaneous aspiration thrombectomy was applied to achieve thrombus removal and uninterrupted venous flow. The treatment was considered successful if there was adequate venous patency and symptomatic relief. Complete or significant thrombus removal and uninterrupted venous flow from the puncture site up to the iliac veins were achieved in all patients at first intervention. Complete relief of leg pain was achieved immediately in seven patients (77.8%). Two patients (22.2%) had a recurrence of thrombosis in the first week postintervention. One of them underwent a second intervention, where percutaneous aspiration thrombectomy was performed again with successful removal of thrombus and establishment of in line flow. Two patients were lost to follow-up after birth. None of the remaining seven patients had rethrombosis throughout the postpartum period. Symptomatic relief was detected clinically in these patients. Endovascular treatment with US-guided percutaneous aspiration thrombectomy can be considered as a safe and effective way to remove thrombus from the deep veins in pregnant women with acute and subacute iliofemoral deep vein thrombosis.

Endovascular treatment of iliofemoral deep vein thrombosis in pregnancy using US-guided percutaneous aspiration thrombectomy

PubMed Central

Gedikoglu, Murat; Oguzkurt, Levent

2017-01-01

PURPOSE We aimed to describe ultrasonography (US)-guided percutaneous aspiration thrombectomy in pregnant women with iliofemoral deep vein thrombosis. METHODS This study included nine pregnant women with acute and subacute iliofemoral deep vein thrombosis, who were severe symptomatic cases with massive swelling and pain of the leg. Patients were excluded from the study if they had only femoropopliteal deep vein thrombosis or mild symptoms of deep vein thrombosis. US-guided percutaneous aspiration thrombectomy was applied to achieve thrombus removal and uninterrupted venous flow. The treatment was considered successful if there was adequate venous patency and symptomatic relief. RESULTS Complete or significant thrombus removal and uninterrupted venous flow from the puncture site up to the iliac veins were achieved in all patients at first intervention. Complete relief of leg pain was achieved immediately in seven patients (77.8%). Two patients (22.2%) had a recurrence of thrombosis in the first week postintervention. One of them underwent a second intervention, where percutaneous aspiration thrombectomy was performed again with successful removal of thrombus and establishment of in line flow. Two patients were lost to follow-up after birth. None of the remaining seven patients had rethrombosis throughout the postpartum period. Symptomatic relief was detected clinically in these patients. CONCLUSION Endovascular treatment with US-guided percutaneous aspiration thrombectomy can be considered as a safe and effective way to remove thrombus from the deep veins in pregnant women with acute and subacute iliofemoral deep vein thrombosis. PMID:27801353

Massive and submassive pulmonary embolism: experience with an algorithm for catheter-directed mechanical thrombectomy.

PubMed

Nassiri, Naiem; Jain, Amit; McPhee, Diana; Mina, Bushra; Rosen, Robert J; Giangola, Gary; Carroccio, Alfio; Green, Richard M

2012-01-01

The role of catheter-directed mechanical thrombectomy (CDMT) for the treatment of massive pulmonary embolism (MPE) and submassive pulmonary embolism (SMPE) is not clearly defined. We report our experience with an algorithm for CDMT as a primary treatment in patients with MPE and SMPE. We retrospectively reviewed our experience in treating MPE and SMPE in consecutive patients over a 2-year period (2008-2010). Patients with computed tomography angiography evidence of saddle, main branch, or ≥2 lobar pulmonary emboli in the setting of hypoxia, tachycardia, echocardiographic right heart strain, and/or cardiogenic shock underwent AngioJet CDMT, with or without adjunctive thrombolytic power-pulse spray. Outcomes, including angiographic success, clinical improvement, complications, and survival to discharge, were evaluated. Fifteen patients (8 men, 7 women; 14 SMPE, 1 SMPE) with a mean age of 59 years (range: 35-90 years) were treated for heart strain (100%), tachycardia (67%), hypoxia (67%), and cardiogenic shock (7%). Ten patients (67%) also received Alteplase power-pulse spray. Resolution of symptoms and improvement in heart strain were achieved in all patients. There were no in-hospital mortalities. Complications occurred in 3 patients (20%), including 2 patients with acute tubular necrosis and 1 patient with an intraoperative cardiac arrest. Average hospitalization was 9 days (range: 4-26 days). All patients were discharged on full anticoagulation. None required supplemental oxygen at discharge. CDMT as primary treatment of MPE and SMPE has a high rate of technical and clinical success in a high-risk patient population. Experience and strict patient selection criteria may improve therapeutic outcomes. Published by Elsevier Inc.

Safety and efficacy of the Aperio thrombectomy device when compared to the Solitaire AB/FR and the Revive devices in a pulsatile flow system.

PubMed

Saleh, Mahdi; Spence, John Nathan; Nayak, Sanjeev; Pearce, Gillian; Tennuci, Christopher; Roffe, Christine

2012-01-01

There are a limited number of studies comparing the Aperio mechanical thrombectomy device to other stent-based devices. In this paper, we compared the Aperio thrombectomy device to the Solitaire AB, FR and Revive devices in a model of the middle cerebral artery (MCA) within a modified pulsatile flow system. Thrombi made of lamb's blood were placed into a pulsatile flow system perfused with Hartmann's solution at 80 bpm with a mean pressure of 90 mm Hg. 30 experiments were run with each device. Recanalization rates were similar for all three devices (90% with the Solitaire AB, FR, 80% with the Revive, and 90% with the Aperio). The mean number of attempts to retrieve the thrombus was also similar for all three devices (1.7 with the Solitaire AB, FR, 2.1 with the Revive, 1.6 with the Aperio). Clot fragmentation and embolization rates revealed no statistical significance but there was a trend towards lower embolization rates with the Aperio (23% compared to 40% with the Solitaire AB, FR and 47% with the Revive). The Aperio was the fastest to recanalize the MCA (mean of 66 seconds compared to 186 seconds for the Solitaire AB, FR and 169 seconds for the Revive). In this in vitro setting, the Aperio device seems to be an efficacious and safe device when compared to other similar clinically used mechanical thrombectomy devices. Larger clinical trials are warranted.

Safety and efficacy of the Aperio thrombectomy device when compared to the Solitaire AB/FR and the Revive devices in a pulsatile flow system

PubMed Central

Saleh, Mahdi; Spence, John Nathan; Nayak, Sanjeev; Pearce, Gillian; Tennuci, Christopher; Roffe, Christine

2012-01-01

Background and Purpose: There are a limited number of studies comparing the Aperio mechanical thrombectomy device to other stent-based devices. In this paper, we compared the Aperio thrombectomy device to the Solitaire AB, FR and Revive devices in a model of the middle cerebral artery (MCA) within a modified pulsatile flow system. Methods: Thrombi made of lamb’s blood were placed into a pulsatile flow system perfused with Hartmann’s solution at 80 bpm with a mean pressure of 90 mm Hg. 30 experiments were run with each device. Results: Recanalization rates were similar for all three devices (90% with the Solitaire AB, FR, 80% with the Revive, and 90% with the Aperio). The mean number of attempts to retrieve the thrombus was also similar for all three devices (1.7 with the Solitaire AB, FR, 2.1 with the Revive, 1.6 with the Aperio). Clot fragmentation and embolization rates revealed no statistical significance but there was a trend towards lower embolization rates with the Aperio (23% compared to 40% with the Solitaire AB, FR and 47% with the Revive). The Aperio was the fastest to recanalize the MCA (mean of 66 seconds compared to 186 seconds for the Solitaire AB, FR and 169 seconds for the Revive). Conclusions: In this in vitro setting, the Aperio device seems to be an efficacious and safe device when compared to other similar clinically used mechanical thrombectomy devices. Larger clinical trials are warranted. PMID:23173104

Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost.

PubMed

Campbell, Bruce C V; Mitchell, Peter J; Churilov, Leonid; Keshtkaran, Mahsa; Hong, Keun-Sik; Kleinig, Timothy J; Dewey, Helen M; Yassi, Nawaf; Yan, Bernard; Dowling, Richard J; Parsons, Mark W; Wu, Teddy Y; Brooks, Mark; Simpson, Marion A; Miteff, Ferdinand; Levi, Christopher R; Krause, Martin; Harrington, Timothy J; Faulder, Kenneth C; Steinfort, Brendan S; Ang, Timothy; Scroop, Rebecca; Barber, P Alan; McGuinness, Ben; Wijeratne, Tissa; Phan, Thanh G; Chong, Winston; Chandra, Ronil V; Bladin, Christopher F; Rice, Henry; de Villiers, Laetitia; Ma, Henry; Desmond, Patricia M; Meretoja, Atte; Cadilhac, Dominique A; Donnan, Geoffrey A; Davis, Stephen M

2017-01-01

Endovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection. Large vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$ reference year 2014). There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12-19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00-0.91) in the alteplase-only versus 0.91 (0.65-1.00) in the endovascular group ( p  = 0.005). Modeled life expectancy was greater in the endovascular versus alteplase-only group (median 15.6 versus 11.2 years, p  = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2-8.7) versus 8.9 (4.7-13.8), p  = 0.02] and more QALY gained [median (IQR) 9.3 (4.2-13.1) versus 4.9 (0.3-8.5), p  = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3-11) days versus 8 (5-14) days, p  = 0.04] and rehabilitation [median (IQR) 0 (0-28) versus 27 (0-65) days, p  = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p  = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365. Thrombectomy patients with large vessel

Mortality and Disability According to Baseline Blood Pressure in Acute Ischemic Stroke Patients Treated by Thrombectomy: A Collaborative Pooled Analysis.

PubMed

Maïer, Benjamin; Gory, Benjamin; Taylor, Guillaume; Labreuche, Julien; Blanc, Raphaël; Obadia, Michael; Abrivard, Marie; Smajda, Stanislas; Desilles, Jean-Philippe; Redjem, Hocine; Ciccio, Gabriele; Lukaszewicz, Anne Claire; Turjman, Francis; Riva, Roberto; Labeyrie, Paul Emile; Duhamel, Alain; Blacher, Jacques; Piotin, Michel; Lapergue, Bertrand; Mazighi, Mikael

2017-10-10

High blood pressure (BP) is associated with worse clinical outcomes in the setting of acute ischemic stroke, but the optimal blood pressure target is still a matter of debate. We aimed to study the association between baseline BP and mortality in acute ischemic stroke patients treated by mechanical thrombectomy. A total of 1332 acute ischemic stroke patients treated by mechanical thrombectomy were enrolled (from January 2012 to June 2016) in the ETIS (Endovascular Treatment in Ischemic Stroke) registry. Linear and polynomial logistic regression models were used to assess the association between BP and mortality and functional outcome at 90 days. Highest mortality was found at lower and higher baseline systolic blood pressure (SBP) values following a J- or U-shaped relationship, with a nadir at 157 mm Hg (95% confidence interval 143-170). When SBP values were categorized in 10-mm Hg increments, the odds ratio for all-cause mortality was 3.78 (95% confidence interval 1.50-9.55) for SBP<110 mm Hg and 1.81 (95% confidence interval 1.01-3.36) for SBP≥180 mm Hg using SBP≥150 to 160 mm Hg as reference. The rate of favorable outcome was the highest at low SBP values and lowest at high SBP values, with a nonlinear relationship; in unplanned exploratory analysis, an optimal threshold SBP≥177 mm Hg was found to predict unfavorable outcome (adjusted odds ratio 0.47; 95% confidence interval 0.31-0.70). In acute ischemic stroke patients treated by mechanical thrombectomy, baseline SBP is associated with all-cause mortality and favorable outcome. In contrast to mortality, favorable outcome rate was the highest at low SBP values and lowest at high SBP values. Further studies are warranted to confirm these findings. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

A Delphi study and ranking exercise to support commissioning services: future delivery of Thrombectomy services in England.

PubMed

Halvorsrud, Kristoffer; Flynn, Darren; Ford, Gary A; McMeekin, Peter; Bhalla, Ajay; Balami, Joyce; Craig, Dawn; White, Phil

2018-02-22

Intra-arterial thrombectomy is the gold standard treatment for large artery occlusive stroke. However, the evidence of its benefits is almost entirely based on trials delivered by experienced neurointerventionists working in established teams in neuroscience centres. Those responsible for the design and prospective reconfiguration of services need access to a comprehensive and complementary array of information on which to base their decisions. This will help to ensure the demonstrated effects from trials may be realised in practice and account for regional/local variations in resources and skill-sets. One approach to elucidate the implementation preferences and considerations of key experts is a Delphi survey. In order to support commissioning decisions, we aimed using an electronic Delphi survey to establish consensus on the options for future organisation of thrombectomy services among physicians with clinical experience in managing large artery occlusive stroke. A Delphi survey was developed with 12 options for future organisation of thrombectomy services in England. A purposive sampling strategy established an expert panel of stroke physicians from the British Association of Stroke Physicians (BASP) Clinical Standards and/or Executive Membership that deliver 24/7 intravenous thrombolysis. Options with aggregate scores falling within the lowest quartile were removed from the subsequent Delphi round. Options reaching consensus following the two Delphi rounds were then ranked in a final exercise by both the wider BASP membership and the British Society of Neuroradiologists (BSNR). Eleven stroke physicians from BASP completed the initial two Delphi rounds. Three options achieved consensus, with subsequently wider BASP (97%, n = 43) and BSNR members (86%, n = 21) assigning the highest approval rankings in the final exercise for transferring large artery occlusive stroke patients to nearest neuroscience centre for thrombectomy based on local CT

First-in-man experience with the ReVive PV peripheral thrombectomy device for the revascularization of below-the-knee embolic occlusions.

PubMed

Landau, David; Moomey, Charles; Fiorella, David

2014-10-01

To report the initial use of a novel thrombectomy device for revascularization of below-the-knee thromboembolic occlusions encountered during proximal revascularization procedures. The ReVive PV Peripheral Thrombectomy Device is a non-detachable, self-expanding stent-like device recently approved for peripheral thrombectomy. Four patients (3 women; mean age 68.8 years) undergoing proximal revascularization procedures experienced embolic occlusions of all 3 trifurcation vessels in 1 patient, the tibioperoneal trunk alone in 2 cases, and the peroneal artery alone in the last patient. In all cases, the involved arteries represented the primary or sole vessel(s) providing outflow to the lower extremity. In each case, the ReVive PV device was used to successfully extract the thrombus and restore flow to the distal extremity. No complications were encountered during any of the procedures. The ReVive PV peripheral thrombectomy device may facilitate the safe and efficient revascularization of distal arterial embolic occlusions.

Endovascular stent thrombectomy: the new standard of care for large vessel ischaemic stroke.

PubMed

Campbell, Bruce C V; Donnan, Geoffrey A; Lees, Kennedy R; Hacke, Werner; Khatri, Pooja; Hill, Michael D; Goyal, Mayank; Mitchell, Peter J; Saver, Jeffrey L; Diener, Hans-Christoph; Davis, Stephen M

2015-08-01

Results of initial randomised trials of endovascular treatment for ischaemic stroke, published in 2013, were neutral but limited by the selection criteria used, early-generation devices with modest efficacy, non-consecutive enrollment, and treatment delays. In the past year, six positive trials of endovascular thrombectomy for ischaemic stroke have provided level 1 evidence for improved patient outcome compared with standard care. In most patients, thrombectomy was performed in addition to thrombolysis with intravenous alteplase, but benefits were also reported in patients ineligible for alteplase treatment. Despite differences in the details of eligibility requirements, all these trials required proof of major vessel occlusion on non-invasive imaging and most used some imaging technique to exclude patients with a large area of irreversibly injured brain tissue. The results indicate that modern thrombectomy devices achieve faster and more complete reperfusion than do older devices, leading to improved clinical outcomes compared with intravenous alteplase alone. The number needed to treat to achieve one additional patient with independent functional outcome was in the range of 3·2-7·1 and, in most patients, was in addition to the substantial efficacy of intravenous alteplase. No major safety concerns were noted, with low rates of procedural complications and no increase in symptomatic intracerebral haemorrhage. WHERE NEXT?: Thrombectomy benefits patients across a range of ages and levels of clinical severity. A planned meta-analysis of individual patient data might clarify effects in under-represented subgroups, such as those with mild initial stroke severity or elderly patients. Imaging-based selection, used in some of the recent trials to exclude patients with large areas of irreversible brain injury, probably contributed to the proportion of patients with favourable outcomes. The challenge is how best to implement imaging in clinical practice to maximise

Rescue strategy for acute carotid stent thrombosis during carotid stenting with distal filter protection using forced arterial suction thrombectomy with a reperfusion catheter of the Penumbra System: a technical note.

PubMed

Kim, Yong-Won; Kang, Dong-Hun; Hwang, Jeong-Hyun; Park, Jaechan; Hwang, Yang-Ha; Kim, Yong-Sun

2013-08-01

Among the procedural complications related to carotid artery stenting (CAS), internal carotid artery (ICA) flow arrest is one of the most drastic complications, as it can cause major ischemic stroke. Acute carotid stent thrombosis (ACST) is a rare etiology of ICA flow arrest during carotid artery stenting with distal filter protection, but the most devastating. Moreover, no definitive management strategy has been established so far for treating ACST. We introduce a rescue management strategy for differential diagnosis of ICA flow arrest and for recanalization of ACST with a simple endovascular mechanical thrombectomy technique. In three cases of ICA flow arrest caused by ACST, selective angiography with a 1.7 F microcatheter provided confirmative diagnosis. Recanalization was then achieved with a Penumbra System (PS) reperfusion catheter using the forced arterial suction thrombectomy (FAST) technique. Successful recanalization with a Thrombolysis In Cerebral Infarction score of 3 was achieved for all three patients. Recanalization was confirmed with follow-up angiography at least 24 h after the procedure. No complications associated with this technique occurred. Based on our preliminary experiences, selective microangiography can be helpful for rapid diagnosis of ACST, and the present mechanical thrombectomy technique, using a modification of the PS, can play a role in adjuvant management or as a last resort for the treatment of ACST during CAS.

Comparison of Efficacy, Embolism Rate and Safety of Thrombectomy with Stent Retrievers in an Anterior Circulation Stroke Model.

PubMed

Larsen, Naomi; Oberbeck, Katharina; Lima de Miranda, Rodrigo; Trentmann, Jens; Madjidyar, Jawid; Quandt, Eckhard; Jansen, Olav

2018-06-18

 Various stent retrievers differing in stent design and mechanical properties are currently available for the treatment of ischemic stroke. We conducted this in vitro study to compare the efficacy, embolism rate, and safety of commercially available stent retrievers and prototypes.  Whole blood thrombi were produced in a Chandler loop. The thrombi were inserted into the curved M1 segment of a silicone model of the anterior cerebral circulation. Thrombectomy maneuvers were performed with six commercially available stent retrievers and 2 prototypes with different strut thickness. Wall-stent apposition, first pass recanalization rate, retraction force, and embolism rate were compared.  Devices with complete wall-stent apposition had the highest first pass recanalization rate and lowest embolism rate, but showed the highest retraction force. The prototype with thinner struts had a comparable recanalization and embolism rate, while a lower retraction force had to be applied compared to the prototype with thicker struts.  Complete wall-stent apposition facilitates a higher recanalization rate and lower embolism rate but also correlates to a higher necessary retraction force and thus possibly higher risk of endothelium damage. Stent modifications leading to a reduced retraction force do not compromise efficacy and embolism rate.   · Complete wall-stent apposition facilitates an effective thrombectomy. · Complete wall-stent apposition leads to higher retraction force and possibly greater endothelium damage. · Modifications of strut thickness do not compromise recanalization and embolism rate. · Thinner struts correlate with a lower retraction force. · Larsen N, Oberbeck K, Lima de Miranda R et al. Comparison of Efficacy, Embolism Rate and Safety of Thrombectomy with Stent Retrievers in an Anterior Circulation Stroke Model. Fortschr Röntgenstr 2018; DOI: 10.1055/a-0631-4118. © Georg Thieme Verlag KG Stuttgart · New York.

First Pass Effect: A New Measure for Stroke Thrombectomy Devices.

PubMed

Zaidat, Osama O; Castonguay, Alicia C; Linfante, Italo; Gupta, Rishi; Martin, Coleman O; Holloway, William E; Mueller-Kronast, Nils; English, Joey D; Dabus, Guilherme; Malisch, Tim W; Marden, Franklin A; Bozorgchami, Hormozd; Xavier, Andrew; Rai, Ansaar T; Froehler, Michael T; Badruddin, Aamir; Nguyen, Thanh N; Taqi, M Asif; Abraham, Michael G; Yoo, Albert J; Janardhan, Vallabh; Shaltoni, Hashem; Novakovic, Roberta; Abou-Chebl, Alex; Chen, Peng R; Britz, Gavin W; Sun, Chung-Huan J; Bansal, Vibhav; Kaushal, Ritesh; Nanda, Ashish; Nogueira, Raul G

2018-03-01

In acute ischemic stroke, fast and complete recanalization of the occluded vessel is associated with improved outcomes. We describe a novel measure for newer generation devices: the first pass effect (FPE). FPE is defined as achieving a complete recanalization with a single thrombectomy device pass. The North American Solitaire Acute Stroke Registry database was used to identify a FPE subgroup. Their baseline features and clinical outcomes were compared with non-FPE patients. Clinical outcome measures included 90-days modified Rankin Scale score, National Institutes of Health Stroke Scale score, mortality, and symptomatic intracranial hemorrhage. Multivariate analyses were performed to determine whether FPE independently resulted in improved outcomes and to identify predictors of FPE. A total of 354 acute ischemic stroke patients underwent thrombectomy in the North American Solitaire Acute Stroke registry. FPE was achieved in 89 out of 354 (25.1%). More middle cerebral artery occlusions (64% versus 52.5%) and fewer internal carotid artery occlusions (10.1% versus 27.7%) were present in the FPE group. Balloon guide catheters were used more frequently with FPE (64.0% versus 34.7%). Median time to revascularization was significantly faster in the FPE group (median 34 versus 60 minutes; P =0.0003). FPE was an independent predictor of good clinical outcome (modified Rankin Scale score ≤2 was seen in 61.3% in FPE versus 35.3% in non-FPE cohort; P =0.013; odds ratio, 1.7; 95% confidence interval, 1.1-2.7). The independent predictors of achieving FPE were use of balloon guide catheters and non-internal carotid artery terminus occlusion. The achievement of complete revascularization from a single Solitaire thrombectomy device pass (FPE) is associated with significantly higher rates of good clinical outcome. The FPE is more frequently associated with the use of balloon guide catheters and less likely to be achieved with internal carotid artery terminus occlusion. © 2018

Endovascular Treatment of Phlegmasia Cerulea Dolens with Impending Venous Gangrene: Manual Aspiration Thrombectomy as the First-Line Thrombus Removal Method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oguzkurt, Levent, E-mail: loguzkurt@yahoo.com; Ozkan, Ugur; Demirturk, Orhan S.

Purpose: Our purpose was to report the outcome of endovascular treatment with manual aspiration thrombectomy as the first-line thromboablative method for phlegmasia cerulea dolens. Methods: Between October 2006 and May 2010, seven consecutive patients (5 women, 2 men; age range, 31-80 years) with the diagnosis of phlegmasia cerulea dolens secondary to acute iliofemoral deep venous thrombosis had endovascular treatment with manual aspiration thrombectomy. Catheter-directed thrombolysis and stent placement were used as adjunctive procedures. Phlegmasia was left-sided in five and right-sided in two patients. Results: All patients had associated great saphenous vein thrombosis in addition to iliofemoral deep vein thrombosis (DVT).more » Aspiration thrombectomy completely removed the thrombus from the popliteal vein to the inferior vena cava (IVC) in all cases. Three patients with May-Thurner syndrome had stent placement in the left common iliac vein. Two patients had early recurrences. Repeated aspiration thrombectomy was unsuccessful in one patient. There were no complications related to the procedure. One patient who had been successfully treated died of sepsis and another patient who had unsuccessful repeated interventions had below-the-knee amputation. Overall, the clinical success and survival rates of patients in this study were 86%. On follow-up, three patients with successful treatment were asymptomatic with no deep venous insufficiency. One of these patients died during the 4-month follow-up period. Two patients had mild ankle swelling with deep venous insufficiency. Conclusions: Manual aspiration thrombectomy with adjunctive use of catheter-directed thrombolysis and stent placement is an effective endovascular treatment method with high clinical success and survival rates for phlegmasia cerulean dolens.« less

Manual Aspiration Thrombectomy with Stent Placement: Rapid and Effective Treatment for Phlegmasia Cerulea Dolens with Impending Venous Gangrene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oguzkurt, Levent, E-mail: loguzkurt@yahoo.com; Tercan, Fahri; Ozkan, Ugur

2008-01-15

Phlegmasia cerulea dolens is an uncommon but potentially life-threatening complication of acute deep vein thrombosis. It is an emergency and delay in treatment may cause death or loss of the patient's limb. Surgical thrombectomy is the recommended treatment in venous gangrene. Catheter-directed intrathrombus thrombolysis has been reported as successful, but it may require a lengthy infusion. Manual aspiration thrombectomy may clear the entire thrombus with no need for thrombolytic administration and provide rapid and effective treatment for patients with phlegmasia cerulea dolens with impending venous gangrene.

Safety and Efficacy of Solitaire Stent Thrombectomy: Individual Patient Data Meta-Analysis of Randomized Trials.

PubMed

Campbell, Bruce C V; Hill, Michael D; Rubiera, Marta; Menon, Bijoy K; Demchuk, Andrew; Donnan, Geoffrey A; Roy, Daniel; Thornton, John; Dorado, Laura; Bonafe, Alain; Levy, Elad I; Diener, Hans-Christoph; Hernández-Pérez, María; Pereira, Vitor Mendes; Blasco, Jordi; Quesada, Helena; Rempel, Jeremy; Jahan, Reza; Davis, Stephen M; Stouch, Bruce C; Mitchell, Peter J; Jovin, Tudor G; Saver, Jeffrey L; Goyal, Mayank

2016-03-01

Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke. Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration): Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA), and Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses: (1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0-2), symptomatic intracerebral hemorrhage, and mortality. The primary analysis included 787 patients: 401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0-3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent outcome was 4.25 (3.29-5.99). Successful

Safety and efficacy of thrombectomy in acute ischaemic stroke (REVASCAT): 1-year follow-up of a randomised open-label trial.

PubMed

Dávalos, Antoni; Cobo, Erik; Molina, Carlos A; Chamorro, Angel; de Miquel, M Angeles; Román, Luis San; Serena, Joaquín; López-Cancio, Elena; Ribó, Marc; Millán, Mónica; Urra, Xabier; Cardona, Pere; Tomasello, Alejandro; Castaño, Carlos; Blasco, Jordi; Aja, Lucía; Rubiera, Marta; Gomis, Meritxell; Renú, Arturo; Lara, Blanca; Martí-Fàbregas, Joan; Jankowitz, Brian; Cerdà, Neus; Jovin, Tudor G

2017-05-01

The REVASCAT trial and other studies have shown that the neurovascular thrombectomy improves outcomes at 90 days post stroke. However, whether the observed benefit is sustained in the long term remains unknown. We report the results of the prespecified 12-month analysis of the REVASCAT trial. Patients with acute ischaemic stroke who could be treated within 8 h of symptom onset were randomly assigned to medical therapy (including intravenous alteplase when eligible) and neurovascular thrombectomy with Solitaire FR or medical therapy alone. The main secondary outcome measure at 1 year follow-up was disability, measured using the modified Rankin Scale (mRS), ranging from 0 (no symptoms) to 6 (death) with categories 5 (severe disability) and 6 (death) collapsed into one category (severe disability or death), analysed as the distribution of the mRS. Additional prespecified secondary outcome measures included health-related quality of life measured with the EuroQol five dimensions questionnaire (EQ-5D) utility index (ranging from -0·3 to 1, higher values indicate better quality of life), the rate of functional independence (mRS 0-2), and cognitive function measured with the Trail Making Test (reported elsewhere). Treatment allocation was open label but endpoints at 12 months were assessed by masked investigators. The trial was registered at ClinicalTrials.gov, number NCT01692379. From Nov 24, 2012, to Dec 12, 2014, 206 patients were randomly assigned to medical therapy plus endovascular treatment (n=103) or medical treatment alone (n=103), at four centres in Catalonia, Spain. At 12 months post randomisation, based on 205 of 206 outcomes available at 12 months, thrombectomy reduced disability over the range of the mRS (common adjusted odds ratio [aOR] 1·80, 95% CI 1·09-2·99), and improved functional independence (mRS=0-2; 45 [44%] of 103 patients vs 31 [30%] of 103 patients; aOR 1·86, 95% CI 1·01-3·44). Health-related quality of life was superior in the

Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.

PubMed

Goyal, Mayank; Menon, Bijoy K; van Zwam, Wim H; Dippel, Diederik W J; Mitchell, Peter J; Demchuk, Andrew M; Dávalos, Antoni; Majoie, Charles B L M; van der Lugt, Aad; de Miquel, Maria A; Donnan, Geoffrey A; Roos, Yvo B W E M; Bonafe, Alain; Jahan, Reza; Diener, Hans-Christoph; van den Berg, Lucie A; Levy, Elad I; Berkhemer, Olvert A; Pereira, Vitor M; Rempel, Jeremy; Millán, Mònica; Davis, Stephen M; Roy, Daniel; Thornton, John; Román, Luis San; Ribó, Marc; Beumer, Debbie; Stouch, Bruce; Brown, Scott; Campbell, Bruce C V; van Oostenbrugge, Robert J; Saver, Jeffrey L; Hill, Michael D; Jovin, Tudor G

2016-04-23

In 2015, five randomised trials showed efficacy of endovascular thrombectomy over standard medical care in patients with acute ischaemic stroke caused by occlusion of arteries of the proximal anterior circulation. In this meta-analysis we, the trial investigators, aimed to pool individual patient data from these trials to address remaining questions about whether the therapy is efficacious across the diverse populations included. We formed the HERMES collaboration to pool patient-level data from five trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA) done between December, 2010, and December, 2014. In these trials, patients with acute ischaemic stroke caused by occlusion of the proximal anterior artery circulation were randomly assigned to receive either endovascular thrombectomy within 12 h of symptom onset or standard care (control), with a primary outcome of reduced disability on the modified Rankin Scale (mRS) at 90 days. By direct access to the study databases, we extracted individual patient data that we used to assess the primary outcome of reduced disability on mRS at 90 days in the pooled population and examine heterogeneity of this treatment effect across prespecified subgroups. To account for between-trial variance we used mixed-effects modelling with random effects for parameters of interest. We then used mixed-effects ordinal logistic regression models to calculate common odds ratios (cOR) for the primary outcome in the whole population (shift analysis) and in subgroups after adjustment for age, sex, baseline stroke severity (National Institutes of Health Stroke Scale score), site of occlusion (internal carotid artery vs M1 segment of middle cerebral artery vs M2 segment of middle cerebral artery), intravenous alteplase (yes vs no), baseline Alberta Stroke Program Early CT score, and time from stroke onset to randomisation. We analysed individual data for 1287 patients (634 assigned to endovascular thrombectomy, 653 assigned to control

Endovascular therapy for acute ischaemic stroke: the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) randomised, controlled trial

PubMed Central

Muir, Keith W; Ford, Gary A; Messow, Claudia-Martina; Ford, Ian; Murray, Alicia; Clifton, Andrew; Brown, Martin M; Madigan, Jeremy; Lenthall, Rob; Robertson, Fergus; Dixit, Anand; Cloud, Geoffrey C; Wardlaw, Joanna; Freeman, Janet; White, Philip

2017-01-01

Objective The Pragmatic Ischaemic Thrombectomy Evaluation (PISTE) trial was a multicentre, randomised, controlled clinical trial comparing intravenous thrombolysis (IVT) alone with IVT and adjunctive intra-arterial mechanical thrombectomy (MT) in patients who had acute ischaemic stroke with large artery occlusive anterior circulation stroke confirmed on CT angiography (CTA). Design Eligible patients had IVT started within 4.5 hours of stroke symptom onset. Those randomised to additional MT underwent thrombectomy using any Conformité Européene (CE)-marked device, with target interval times for IVT start to arterial puncture of <90 min. The primary outcome was the proportion of patients achieving independence defined by a modified Rankin Scale (mRS) score of 0–2 at day 90. Results Ten UK centres enrolled 65 patients between April 2013 and April 2015. Median National Institutes of Health Stroke Scale score was 16 (IQR 13–21). Median stroke onset to IVT start was 120 min. In the intention-to-treat analysis, there was no significant difference in disability-free survival at day 90 with MT (absolute difference 11%, adjusted OR 2.12, 95% CI 0.65 to 6.94, p=0.20). Secondary analyses showed significantly greater likelihood of full neurological recovery (mRS 0–1) at day 90 (OR 7.6, 95% CI 1.6 to 37.2, p=0.010). In the per-protocol population (n=58), the primary and most secondary clinical outcomes significantly favoured MT (absolute difference in mRS 0–2 of 22% and adjusted OR 4.9, 95% CI 1.2 to 19.7, p=0.021). Conclusions The trial did not find a significant difference between treatment groups for the primary end point. However, the effect size was consistent with published data and across primary and secondary end points. Proceeding as fast as possible to MT after CTA confirmation of large artery occlusion on a background of intravenous alteplase is safe, improves excellent clinical outcomes and, in the per-protocol population, improves disability

Trends in mortality following mechanical thrombectomy for the treatment of acute ischemic stroke in the USA.

PubMed

Villwock, Mark R; Padalino, David J; Deshaies, Eric M

2016-05-01

Mechanical thrombectomy (MT) for the treatment of acute ischemic stroke has been growing in popularity while the therapeutic benefit of MT has been increasingly debated. Our objective was to examine national trends in mortality following MT. We analyzed the National Inpatient Sample (2012) and the Nationwide Inpatient Sample (2008-2011) for patients with a primary diagnosis of acute ischemic stroke that received MT. Temporal trends in mortality were examined using Spearman's rank correlation. To account for confounding factors, mortality was further analyzed in binary logistic regression. Hospitals performing MT comprised 8% of all hospitals treating ischemic stroke. The percentage of stroke cases treated with MT increased from 0.6% of cases in 2008 to 1.1% in 2012, totaling 16 307 MT cases in a 5 year period. Inhospital mortality decreased over the study period from 25.4% in 2008 to 16.1% in 2012 (r=-0.081, p<0.001). This finding was supported by regression analysis as each incremental year reduced the odds of mortality by 20% (OR=0.832, p<0.001). Administration of recombinant tissue plasminogen activator was associated with a decrease in the odds of mortality (OR=0.805, p<0.001). Utilization of MT represents a small percentage of stroke cases, although the trend is increasing. Mortality following MT has been showing a steady decline over the past 5 years. This may be a result of a learning curve, improved patient selection, and/or device improvements. Randomized trials remain essential to evaluate the potential benefit of endovascular devices and identify the most appropriate patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Prophylactic Placement of an Inferior Vena Cava Filter During Aspiration Thrombectomy for Acute Deep Venous Thrombosis of the Lower Extremity.

PubMed

Kwon, Se Hwan; Park, So Hyun; Oh, Joo Hyeong; Song, Myung Gyu; Seo, Tae-Seok

2016-05-01

To evaluate the effect of an inferior vena cava (IVC) filter during aspiration thrombectomy for acute deep vein thrombosis (DVT) in the lower extremity. From July 2004 to December 2013, a retrospective analysis of 106 patients with acute DVT was performed. All patients received an IVC filter and were treated initially with aspiration thrombectomy. Among the 106 patients, DVT extension into the IVC was noted in 27 but was not evident in 79. We evaluated the presence of trapped thrombi in the filters after the procedure. The sizes of the trapped thrombi were classified into 2 grades based on the ratio of the maximum transverse length of the trapped thrombus to the diameter of the IVC (Grades I [≤ 50%] and II [> 50%]). A trapped thrombus in the filter was detected in 46 (43%) of 106 patients on final venograms. The sizes of the trapped thrombi were grade I in 12 (26.1%) patients and grade II in 34 (73.9%). Among the 27 patients with DVT extension into the IVC, 20 (74.1%) showed a trapped thrombus in the filter, 75% (15 of 20) of which were grade II. Among the 79 patients without DVT extension into the IVC, 26 (32.9%) showed a trapped thrombus in the IVC filter, 73% (19 of 26) of which were grade II. Thrombus migration occurred frequently during aspiration thrombectomy of patients with acute DVT in the lower extremity. However, further studies are needed to establish a standard protocol for the prophylactic placement of an IVC filter during aspiration thrombectomy. © The Author(s) 2016.

A Stent-Retrieving into an Aspiration Catheter with Proximal Balloon (ASAP) Technique: A Technique of Mechanical Thrombectomy.

PubMed

Goto, Shunsaku; Ohshima, Tomotaka; Ishikawa, Kojiro; Yamamoto, Taiki; Shimato, Shinji; Nishizawa, Toshihisa; Kato, Kyozo

2018-01-01

The best technique for the first attempt at mechanical thrombectomy for acute ischemic stroke is a still matter of debate. In this study, we evaluate the efficacy of a stent-retrieving into an aspiration catheter with proximal balloon (ASAP) technique that uses a series of thrombus extraction by withdrawing the stent retriever into the aspiration catheter and continuous aspiration from the aspiration catheter at the first attempt. We performed a retrospective analysis of 42 consecutive patients with acute ischemic stroke caused by occlusions in the anterior circulation who were treated with the ASAP technique at our institution. Preoperative patient characteristic, including age, thrombus location, Alberta Stroke Program Early CT Score, National Institutions of Health Stroke Scale, and time from onset to puncture; postoperative Thrombolysis in Cerebral Infarction score; modified Rankin Scale score after 3 months; time from puncture to recanalization; the number of passes to achieve recanalization; and procedural complications, including intracranial hemorrhage, embolization to new territory, and distal embolization, were assessed. A Thrombolysis in Cerebral Infarction score of 2B or 3 was achieved in 40/42 patients (95.2%). Average time from puncture to the final recanalization was 21.5 minutes. Recanalization was achieved in a single attempt in 31 patients (77.5%). Embolization to new territory was observed in only 2 patients (4.8%); no patient developed distal embolization or intracranial hemorrhage including asymptomatic subarachnoid hemorrhage. Thirty-two patients (76.2%) achieved modified Rankin Scale scores of 0-2 at 3 months postoperatively. Our ASAP technique showed fast recanalization, minimal complications, and good clinical outcomes in this case series. Copyright © 2017 Elsevier Inc. All rights reserved.

ERic Acute StrokE Recanalization: A study using predictive analytics to assess a new device for mechanical thrombectomy.

PubMed

Siemonsen, Susanne; Forkert, Nils D; Bernhardt, Martina; Thomalla, Götz; Bendszus, Martin; Fiehler, Jens

2017-08-01

Aim and hypothesis Using a new study design, we investigate whether next-generation mechanical thrombectomy devices improve clinical outcomes in ischemic stroke patients. We hypothesize that this new methodology is superior to intravenous tissue plasminogen activator therapy alone. Methods and design ERic Acute StrokE Recanalization is an investigator-initiated prospective single-arm, multicenter, controlled, open label study to compare the safety and effectiveness of a new recanalization device and distal access catheter in acute ischemic stroke patients with symptoms attributable to acute ischemic stroke and vessel occlusion of the internal cerebral artery or middle cerebral artery. Study outcome The primary effectiveness endpoint is the volume of saved tissue. Volume of saved tissue is defined as difference of the actual infarct volume and the brain volume that is predicted to develop infarction by using an optimized high-level machine learning model that is trained on data from a historical cohort treated with IV tissue plasminogen activator. Sample size estimates Based on own preliminary data, 45 patients fulfilling all inclusion criteria need to complete the study to show an efficacy >38% with a power of 80% and a one-sided alpha error risk of 0.05 (based on a one sample t-test). Discussion ERic Acute StrokE Recanalization is the first prospective study in interventional stroke therapy to use predictive analytics as primary and secondary endpoint. Such trial design cannot replace randomized controlled trials with clinical endpoints. However, ERic Acute StrokE Recanalization could serve as an exemplary trial design for evaluating nonpivotal neurovascular interventions.

Does Mechanical Thrombectomy in Acute Embolic Stroke Have Long-term Side Effects on Intracranial Vessels? An Angiographic Follow-up Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurre, Wiebke, E-mail: w.kurre@klinikum-stuttgart.de; Perez, Marta Aguilar; Horvath, Diana

Purpose. Mechanical thrombectomy (mTE) proved to be effective treating acute vessel occlusions with an acceptable rate of procedural complications. Potential long-term side effects of the vessel wall trauma caused by mechanical irritation of the endothelium are unknown up to now. Methods. From a retrospectively established database of 640 acute stroke treatments, we selected 261 patients with 265 embolic vessel occlusions treated successfully by mTE without permanent implantation of a stent. Analysis comprised the type of devices used and the number of passes performed. Digital subtraction angiography immediately after treatment was evaluated for vasospasm, dissection, and extravasation. Control angiographic images weremore » evaluated for any morphological change compared to the immediate posttreatment angiographic run. Results. Recanalization was achieved with a median of one (range 1-10) mTE maneuvers. Vasospasm occurred in 69 territories (26.0 %) and was treated with glyceroltrinitrate in three. Dissection was observed in one vessel (0.4 %). Intraprocedural hemorrhage in two patients (0.8 %) was either wire or device induced. Follow-up digital subtraction angiography was available for 117 territories after a median of 107 days, revealing target vessel occlusion in one segment (0.9 %) and a de novo stenosis of four segments (3.4 %). All findings were clinically asymptomatic. Posttreatment vasospasm was more frequent in patients with de novo stenosis and occlusion (p = 0.038). Conclusion. De novo stenoses and occlusions occur in a small proportion of patients after mTE. Because all lesions were clinically asymptomatic, this finding does not affect the overall benefit of the treatment. Vasospasm may predict late vessel wall changes.« less

Symptomatic iliofemoral deep venous thrombosis treated with hybrid operative thrombectomy.

PubMed

Rodríguez, Limael E; Aponte-Rivera, Francisco; Figueroa-Vicente, Ricardo; Bolanos-Avila, Guillermo E; Martínez-Trabal, Jorge L

2015-10-01

During the past 15 years, strategies that promote immediate and complete thrombus removal have gained popularity for the treatment of acute-onset iliofemoral deep venous thrombosis. In this case report, we describe a novel operative approach to venous thrombus removal known as hybrid operative thrombectomy. The technique employs a direct inguinal approach with concomitant retrograde advancement of a balloon catheter by femoral venotomy. Moreover, it provides effective thrombus removal through a single incision, with or without stent placement, and has the advantage of a completion venogram. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data.

PubMed

Campbell, Bruce C V; van Zwam, Wim H; Goyal, Mayank; Menon, Bijoy K; Dippel, Diederik W J; Demchuk, Andrew M; Bracard, Serge; White, Philip; Dávalos, Antoni; Majoie, Charles B L M; van der Lugt, Aad; Ford, Gary A; de la Ossa, Natalia Pérez; Kelly, Michael; Bourcier, Romain; Donnan, Geoffrey A; Roos, Yvo B W E M; Bang, Oh Young; Nogueira, Raul G; Devlin, Thomas G; van den Berg, Lucie A; Clarençon, Frédéric; Burns, Paul; Carpenter, Jeffrey; Berkhemer, Olvert A; Yavagal, Dileep R; Pereira, Vitor Mendes; Ducrocq, Xavier; Dixit, Anand; Quesada, Helena; Epstein, Jonathan; Davis, Stephen M; Jansen, Olav; Rubiera, Marta; Urra, Xabier; Micard, Emilien; Lingsma, Hester F; Naggara, Olivier; Brown, Scott; Guillemin, Francis; Muir, Keith W; van Oostenbrugge, Robert J; Saver, Jeffrey L; Jovin, Tudor G; Hill, Michael D; Mitchell, Peter J

2018-01-01

General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in

High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy.

PubMed

Shin, Jong Wook; Jeong, Hye Seon; Kwon, Hyon-Jo; Song, Kyu Sang; Kim, Jei

2018-01-01

We evaluated the composition of individual clots retrieved during intra-arterial thrombectomy in relation to recanalization success, stroke subtype, and the presence of clot signs on initial brain images. We analyzed clot and interventional data from 145 retrieval trials performed for 37 patients (69.5±14.0 years, 20 men, large artery atherosclerosis, n = 7; cardioembolism, n = 22; undetermined etiology, n = 8) who had undergone intra-arterial thrombectomy. Rates of clot retrieval and successful recanalization (Arterial Occlusive Lesion score of 2-3) for separate retrieval trials were evaluated. The area occupied by red blood cell (RBC), fibrin/platelets, and white blood cell (WBC) was measured from digitized images of hematoxylin-eosin stained clots. Compositional differences were compared according to recanalization success, stroke subtype, and the presence of hyperdense clot sign on initial computed tomography and/or blooming artifact on magnetic resonance image. Of the 145 total retrieval trials (3.4±2.4 times per patient), clot was retrieved in 93 trials (64%), while recanalization was successful in 73 (50%). Fibrin/platelets (63%) occupied the greatest area in retrieved clots, followed by RBCs (33%) and WBCs (4%). Clots retrieved from successful recanalization exhibited higher RBC composition (37%) than those retrieved from non-recanalization trials (20%, p = 0.001). RBC composition was higher in cardioembolic stroke (38%) rather than large artery atherosclerosis (23%) and undetermined etiology (26%, p = 0.01). Clots exhibiting clot signs (40%) had higher RBC composition than those without clot signs (19%, p = 0.001). RBC-rich clots were associated with successful recanalization of intra-arterial thrombectomy, cardioembolic stroke, and the presence of clot-signs on initial brain images.

High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy

PubMed Central

Shin, Jong Wook; Jeong, Hye Seon; Kwon, Hyon-Jo; Song, Kyu Sang

2018-01-01

We evaluated the composition of individual clots retrieved during intra-arterial thrombectomy in relation to recanalization success, stroke subtype, and the presence of clot signs on initial brain images. We analyzed clot and interventional data from 145 retrieval trials performed for 37 patients (69.5±14.0 years, 20 men, large artery atherosclerosis, n = 7; cardioembolism, n = 22; undetermined etiology, n = 8) who had undergone intra-arterial thrombectomy. Rates of clot retrieval and successful recanalization (Arterial Occlusive Lesion score of 2–3) for separate retrieval trials were evaluated. The area occupied by red blood cell (RBC), fibrin/platelets, and white blood cell (WBC) was measured from digitized images of hematoxylin-eosin stained clots. Compositional differences were compared according to recanalization success, stroke subtype, and the presence of hyperdense clot sign on initial computed tomography and/or blooming artifact on magnetic resonance image. Of the 145 total retrieval trials (3.4±2.4 times per patient), clot was retrieved in 93 trials (64%), while recanalization was successful in 73 (50%). Fibrin/platelets (63%) occupied the greatest area in retrieved clots, followed by RBCs (33%) and WBCs (4%). Clots retrieved from successful recanalization exhibited higher RBC composition (37%) than those retrieved from non-recanalization trials (20%, p = 0.001). RBC composition was higher in cardioembolic stroke (38%) rather than large artery atherosclerosis (23%) and undetermined etiology (26%, p = 0.01). Clots exhibiting clot signs (40%) had higher RBC composition than those without clot signs (19%, p = 0.001). RBC-rich clots were associated with successful recanalization of intra-arterial thrombectomy, cardioembolic stroke, and the presence of clot-signs on initial brain images. PMID:29782513

Radical robot-assisted laparoscopic nephrectomy with thrombectomy in the vena cava.

PubMed

Estébanez Zarranz, J; Belloso Loidi, J; Gutierrez García, M A; Rubio Calaveras, V; Morales Higelmo, G; Melendo Tercilla, P; Busto Leis, L; Sanz Jaka, J P

2018-04-23

Renal cell carcinoma has a natural tendency to extend through the renal vein. When the thrombus reaches the vena cava, thrombectomy and the necessary reconstruction of the vena cava are typically performed by open pathway. Robot-assisted technology provides advantages for performing this complex technique, using a minimally invasive access. We present the technique we employed in the first case performed in our department. After performing renal artery embolisation, we conducted the surgery with the Vinci S robotic system. The main steps of the surgery are as follows: detachment and Kocher manoeuvre; release of the lower renal pole; clamping and sectioning of the renal artery; endocavitary ultrasound to locate the thrombus; placement of tourniquets in the vena cava below and above the renal veins and in the left renal vein; closure of the 3 tourniquets; opening of the vena cava; resection and extraction of the thrombus; suture of the vena cava; opening of the tourniquets; complete release of the kidney; bagging and extraction of the specimen. The surgery was performed without complications. The patient required a transfusion of 2 units of packed red blood cells and was discharged with modest renal failure (creatinine level of 1.60mg/dl). Radical nephrectomy with thrombectomy in the vena cava is a technique susceptible to severe complications and has, to date, been performed in few centres. We believe that the technique is reproducible and has clear advantages for our patients. Copyright © 2018 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Pneumomediastinum and Mediastinal Hematoma Secondary to Right Brachiocephalic Vein Thrombectomy Mimicking STEMI

PubMed Central

Shukla, Prem; Nivera, Noel

2017-01-01

A 50-year-old male with a history of hemodialysis dependent chronic kidney disease presented to our emergency department with acute midsternal crushing chest pain. Patient was diagnosed with acute anterolateral wall Myocardial Infraction due to the presence of corresponding ST segment elevations in EKG and underwent emergent cardiac catheterization which revealed normal patent coronaries without any disease. He continued to have chest pain for which CT of the chest was done which revealed pneumomediastinum with mediastinal hematoma, due to the recent attempted thrombectomy for thrombus in his right brachiocephalic vein. PMID:28804656

Blood Pressure Management after Mechanical Thrombectomy for Acute Ischemic Stroke: A Survey of the StrokeNet Sites.

PubMed

Mistry, Eva A; Mayer, Stephan A; Khatri, Pooja

2018-05-22

It is unclear what factors providers take into account to determine the target blood pressure (BP) after mechanical thrombectomy (MT) in patients who had acute ischemic stroke. We aimed to understand practice patterns of post-MT BP management across institutions in the United States. We surveyed StrokeNet institutions providing MT and post-MT care with an online questionnaire, designed to understand institutional post-MT BP management practices. Of 131 potential institutions, 58 completed the survey. The majority of institutions target systolic BP (SBP, n = 53, 91%) during the first 24 hours post-MT (n = 32, 55%) using nicardipine as a first-line agent (n = 43, 74%). At most institutions, BP management is determined by a team of physicians in a collaborative fashion (n = 30, 52%) and individualized on a case-by-case basis (n = 39, 67%) after taking the reperfusion status into account (n = 42, 72%). In patients with successful reperfusion, 36% (n = 21) of the institutions target SBP in the range of 120-139 mm Hg, 21% (n = 12) target 140-159 mm Hg, and 28% (n = 16) would accept any value less than or equal to 180 mm Hg. In patients with unsuccessful reperfusion, 43% (n = 25) would accept any SBP value less than or equal to 180 mm Hg and 10% (n = 6) would target SBP less than or equal to 220 mm Hg. We found that majority of the institutions do not have a standardized protocol for post-MT BP management. There was interinstitutional heterogeneity in the preferred target of SBP post-MT and most institutions target values of SBP lower than 180 mm Hg in post-MT patients. Prospective data and randomized control trial are needed to identify the optimal target BP. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

In Vitro Evaluation of a Rheolytic Thrombectomy System for Clot Removal from Five Different Temporary Vena Cava Filters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buecker, Arno; Neuerburg, Joerg; Schmitz-Rode, Thomas

1997-11-15

Purpose: To evaluate the feasibility of thrombus removal from temporary vena cava filters using a rheolytic thrombectomy device and to assess the embolization rate of this procedure. Methods: Five temporary vena cava filters together with porcine thrombi were placed in a vena cava flow model (semitranslucent silicone tube of 23 mm diameter, pulsatile flow at a mean flow rate of 4 L/min). A rheolytic thrombectomy system (Hydrolyser) was used with a 9 Fr guiding catheter to remove the clots. The effluent was passed through filters of different size and the amount of embolized particles as well as the remaining thrombusmore » were measured. Results: Thrombus removal rates ranged from 85% to 100%. Embolization rates between 47% and 60% were calculated for the different filters. Conclusion: The Hydrolyser is able to remove sufficiently high amounts of thrombus from temporary vena cava filters. However, the amount of embolized particles makes it impossible to utilize this method without special precautions against embolization.« less

Aspirex Thrombectomy in Occluded Dialysis Access: A Retrospective Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dyer, Jules, E-mail: Jules.Dyer@nhs.net; Rosa, Joao; Chachlani, Menka

PurposeThis study is the first to present the outcomes of the Straub Aspirex device for the salvage of occluded renal dialysis access fistulae.Materials and MethodsThis is a retrospective study, using data from the Renal Unit and Radiology Department database. It included all the patients between 2010 and 2014 who underwent percutaneous mechanical thrombectomy (PMT) treated by JD. Aspirex is an over-the-wire, 6–10 French catheter within which is a rapidly rotating helix which draws thrombus into a window near the tip which it then macerates and removes. Access survival was assessed using the Kaplan–Meier method, and multi-variant analysis was performed usingmore » the Cox proportional hazards model. Significance was considered if p < 0.05.ResultsA total of 27 procedures were performed for 19 patients. 13 had autologous arterio-venous fistulae, and 14 had synthetic (PTFE) arterio-venous grafts. 15 were males, 4 females. 100 % of the patients successfully had a channel of thrombus removed. This resulted in an 81.5 % initial clinical success, with primary patency rates of 53.6, 44.3 and 33 % by days 30, 90 and 480, respectively, without significant difference of any analysed covariates. No major complication (pulmonary embolus, paradoxical cerebral infarction, limb ischaemia or significant haemorrhage) occurred.ConclusionAspirex has rates of patency and complication similar to other PMT devices. No covariant studied affected outcome.« less

Blood pressure levels post mechanical thrombectomy and outcomes in non-recanalized large vessel occlusion patients.

PubMed

Goyal, Nitin; Tsivgoulis, Georgios; Pandhi, Abhi; Dillard, Kira; Alsbrook, Diana; Chang, Jason J; Krishnaiah, Balaji; Nickele, Christopher; Hoit, Daniel; Alsherbini, Khalid; Alexandrov, Andrei V; Arthur, Adam S; Elijovich, Lucas

2018-01-11

Permissive hypertension may benefit patients with non-recanalized large vessel occlusion (nrLVO) post mechanical thrombectomy (MT) by maintaining brain perfusion. Data evaluating the impact of post-MT blood pressure (BP) levels on outcomes in nrLVO patients are scarce. We investigated the association of the post-MT BP course with safety and efficacy outcomes in nrLVO. Hourly systolic BP (SBP) and diastolic BP (DBP) values were prospectively recorded for 24 hours following MT in consecutive nrLVO patients. Maximum, minimum, and mean BP levels were documented. Three-month functional independence (FI) was defined as modified Rankin Scale (mRS) scores of 0-2. A total of 88 nrLVO patients were evaluated post MT. Patients with FI had lower maximum SBP (160±19 mmHg vs 179±23 mmHg; P=0.001) and higher minimum SBP levels (119±12 mmHg vs 108±25 mmHg; P=0.008). Maximum SBP (183±20 mmHg vs 169±23 mmHg; P=0.008) and DBP levels (105±20 mmHg vs 89±18 mmHg; P=0.001) were higher in patients who died at 3 months while minimum SBP values were lower (102±28 mmHg vs 115±16 mmHg; P=0.007). On multivariable analyses, both maximum SBP (OR per 10 mmHg increase: 0.55, 95% CI 0.39 to 0.79; P=0.001) and minimum SBP (OR per 10 mmHg increase: 1.64, 95% CI 1.04 to 2.60; P=0.033) levels were independently associated with the odds of FI. Maximum DBP (OR per 10 mmHg increase: 1.61; 95% CI 1.10 to 2.36; P=0.014) and minimum SBP (OR per 10 mmHg increase: 0.65, 95% CI 0.47 to 0.90; P=0.009) values were independent predictors of 3-month mortality. Our study demonstrates that wide BP excursions from the mean during the first 24 hours post MT are associated with worse outcomes in patients with nrLVO. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

In vitro experiments of cerebral blood flow during aspiration thrombectomy: potential effects on cerebral perfusion pressure and collateral flow.

PubMed

Lally, Frank; Soorani, Mitra; Woo, Timothy; Nayak, Sanjeev; Jadun, Changez; Yang, Ying; McCrudden, John; Naire, Shailesh; Grunwald, Iris; Roffe, Christine

2016-09-01

Mechanical thrombectomy with stent retriever devices is associated with significantly better outcomes than thrombolysis alone in the treatment of acute ischemic stroke. Thrombus aspiration achieves high patency rates, but clinical outcomes are variable. The aim of this study was to examine the effect of different suction conditions on perfusate flow during aspiration thrombectomy. A computational fluid dynamics model of an aspiration device within a patent and occluded blood vessel was used to simulate flow characteristics using fluid flow solver software. A physical particulate flow model of a patent vessel and a vessel occluded by thrombus was then used to visualize flow direction and measure flow rates with the aspiration catheter placed 1-10 mm proximal of the thrombus, and recorded on video. The mathematical model predicted that, in a patent vessel, perfusate is drawn from upstream of the catheter tip while, in an occluded system, perfusate is drawn from the vessel proximal to the device tip with no traction on the occlusion distal of the tip. The in vitro experiments confirmed the predictions of this model. In the occluded vessel aspiration had no effect on the thrombus unless the tip of the catheter was in direct contact with the thrombus. These experiments suggest that aspiration is only effective if the catheter tip is in direct contact with the thrombus. If the catheter tip is not in contact with the thrombus, aspirate is drawn from the vessels proximal of the occlusion. This could affect collateral flow in vivo. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis.

PubMed

Saver, Jeffrey L; Goyal, Mayank; van der Lugt, Aad; Menon, Bijoy K; Majoie, Charles B L M; Dippel, Diederik W; Campbell, Bruce C; Nogueira, Raul G; Demchuk, Andrew M; Tomasello, Alejandro; Cardona, Pere; Devlin, Thomas G; Frei, Donald F; du Mesnil de Rochemont, Richard; Berkhemer, Olvert A; Jovin, Tudor G; Siddiqui, Adnan H; van Zwam, Wim H; Davis, Stephen M; Castaño, Carlos; Sapkota, Biggya L; Fransen, Puck S; Molina, Carlos; van Oostenbrugge, Robert J; Chamorro, Ángel; Lingsma, Hester; Silver, Frank L; Donnan, Geoffrey A; Shuaib, Ashfaq; Brown, Scott; Stouch, Bruce; Mitchell, Peter J; Davalos, Antoni; Roos, Yvo B W E M; Hill, Michael D

2016-09-27

Endovascular thrombectomy with second-generation devices is beneficial for patients with ischemic stroke due to intracranial large-vessel occlusions. Delineation of the association of treatment time with outcomes would help to guide implementation. To characterize the period in which endovascular thrombectomy is associated with benefit, and the extent to which treatment delay is related to functional outcomes, mortality, and symptomatic intracranial hemorrhage. Demographic, clinical, and brain imaging data as well as functional and radiologic outcomes were pooled from randomized phase 3 trials involving stent retrievers or other second-generation devices in a peer-reviewed publication (by July 1, 2016). The identified 5 trials enrolled patients at 89 international sites. Endovascular thrombectomy plus medical therapy vs medical therapy alone; time to treatment. The primary outcome was degree of disability (mRS range, 0-6; lower scores indicating less disability) at 3 months, analyzed with the common odds ratio (cOR) to detect ordinal shift in the distribution of disability over the range of the mRS; secondary outcomes included functional independence at 3 months, mortality by 3 months, and symptomatic hemorrhagic transformation. Among all 1287 patients (endovascular thrombectomy + medical therapy [n = 634]; medical therapy alone [n = 653]) enrolled in the 5 trials (mean age, 66.5 years [SD, 13.1]; women, 47.0%), time from symptom onset to randomization was 196 minutes (IQR, 142 to 267). Among the endovascular group, symptom onset to arterial puncture was 238 minutes (IQR, 180 to 302) and symptom onset to reperfusion was 286 minutes (IQR, 215 to 363). At 90 days, the mean mRS score was 2.9 (95% CI, 2.7 to 3.1) in the endovascular group and 3.6 (95% CI, 3.5 to 3.8) in the medical therapy group. The odds of better disability outcomes at 90 days (mRS scale distribution) with the endovascular group declined with longer time from symptom onset to arterial

Safety and Efficacy of Mechanical Thrombectomy Using Stent Retrievers in the Endovascular Treatment of Acute Ischaemic Stroke: A Systematic Review

PubMed Central

Puñal-Riobóo, Janet; Atienza, Gerardo; Blanco, Miguel

2015-01-01

Background The treatment of choice for acute ischaemic stroke is the intravenous administration of recombinant tissue plasminogen activator within 3-4.5 h of symptom onset. However, the use of a thrombolytic would be limited by its narrow therapeutic window and contraindications. As a result, in recent years, techniques such as mechanical thrombectomy have emerged, which employ thrombus retrieval devices, such as stent retrievers (Solitaire™, Trevo® or Revive™), whose safety and efficacy in the endovascular treatment of acute ischaemic stroke is analysed in this article. Methods A systematic literature search was undertaken until March 2015. The quality of evidence was assessed according to the GRADE methodology. A meta-analysis of the results of randomised controlled trials (RCTs) was performed, and the weighted average for the case series' sample size was calculated (Review Manager v5.2 and SPSS v19). Results Seventeen primary studies (2 RCTs, Solitaire™ and Trevo® vs. Merci®, and 15 case series) were selected. The RCT results show that stent retrievers have a safety profile similar to the Merci® device. However, both Solitaire™ and Trevo® achieved a higher recanalisation success rate (OR, 4.56; 95% CI, 2.63-7.90; p < 0.00001) and appropriate clinical outcome at 90 days (OR, 2.54; 95% CI, 1.52-4.25; p < 0.0004), although the 90-day mortality rate was similar in both groups (OR, 0.75; 95% CI, 0.17-3.37; p = 0.70). Conclusions Stent retrievers appear to be safe and effective devices, achieving high recanalisation rates and good clinical outcomes in the endovascular treatment of patients with acute ischaemic stroke due to the occlusion of intracranial arteries in comparison with the clot retriever Merci®. PMID:26279662

Rheolytic thrombectomy: possibilities and first results.

PubMed

Zatevakhin, I I; Shipovskiĭ, V N; Zolkin, V N; Nechaev, A I; Piliposian, E A

2008-01-01

The present study was undertaken to investigate the possibilities of using the method of rheolytic thrombectomy (hereinafter referred to as RTE) in surgical practice, and to assess its immediate outcomes in treatment of thromboses of arteries and veins of the lower extremities, as well as transjugular intrahepatic portosystemic shunts (hereinafter referred to as TIPS). We have gained experience in carrying out a total of 33 rheolytic thrombectomies with the help of the system JET 9000 (R) using the Xpeedior catheter in a total of thirty-one 43-to-87-year-old patients. Twenty-four interventions were performed for acute thromboses of arteries and shunts of the lower limbs, five - in patients presenting with floating thrombi in the inferior vena cava, and four operations were carried out in patients diagnosed with thrombosis of the segment after TIPS. In the group of the patients with thromboses of the arteries of the lower limbs (n=19), in 16 patients RTE resulted in restoration of >50% of the arterial lumen. In three patients of the same group, we managed to restore the lumen by only 50% and less. In the group of patients with thromboses of the shunts (n=5), RTE with a successful angiographic outcome was performed in three patients. In yet another patient, the lumen was restored only by 50%, and in a further one patient, the lumen of the shunt we failed to restore. Nineteen patients underwent a total of 13 balloon angioplasties (BA), 4 stenting interventions, and 2 regional thrombolytic procedures. Two patients after RTE and V A were subjected to postdilatational endarterectomy. In one patient RTE from the shunt was supplemented with plasty of its proximal anastomosis with a synthetic patch. In two patients, RTE was complicated by embolism of the deep femoral artery. In the group consisting of five patients diagnosed with floating thrombi of the inferior vena cava, a successful outcome was observed only in two. In patients presenting with thromboses of the stems

Exploring the efficacy of cyclic vs static aspiration in a cerebral thrombectomy model: an initial proof of concept study.

PubMed

Simon, Scott; Grey, Casey Paul; Massenzo, Trisha; Simpson, David G; Longest, P Worth

2014-11-01

Current technology for endovascular thrombectomy in ischemic stroke utilizes static loading and is successful in approximately 85% of cases. Existing technology uses either static suction (applied via a continuous pump or syringe) or flow arrest with a proximal balloon. In this paper we evaluate the potential of cyclic loading in aspiration thrombectomy. In order to evaluate the efficacy of cyclic aspiration, a model was created using a Penumbra aspiration system, three-way valve and Penumbra 5Max catheter. Synthetic clots were aspirated at different frequencies and using different aspiration mediums. Success or failure of clot removal and time were recorded. All statistical analyses were based on either a one-way or two-way analysis of variance, Holm-Sidak pairwise multiple comparison procedure (α=0.05). Cyclic aspiration outperformed static aspiration in overall clot removal and removal speed (p<0.001). Within cyclic aspiration, Max Hz frequencies (∼6.3 Hz) cleared clots faster than 1 Hz (p<0.001) and 2 Hz (p=0.024). Loading cycle dynamics (specific pressure waveforms) affected speed and overall clearance (p<0.001). Water as the aspiration medium was more effective at clearing clots than air (p=0.019). Cyclic aspiration significantly outperformed static aspiration in speed and overall clearance of synthetic clots in our experimental model. Within cyclic aspiration, efficacy is improved by increasing cycle frequency, utilizing specific pressure cycle waveforms and using water rather than air as the aspiration medium. These findings provide a starting point for altering existing thrombectomy technology or perhaps the development of new technologies with higher recanalization rates. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Cost-Effectiveness of Solitaire Stent Retriever Thrombectomy for Acute Ischemic Stroke

PubMed Central

Shireman, Theresa I.; Wang, Kaijun; Saver, Jeffrey L.; Goyal, Mayank; Bonafé, Alain; Diener, Hans-Christoph; Levy, Elad I.; Pereira, Vitor M.; Albers, Gregory W.; Cognard, Christophe; Hacke, Werner; Jansen, Olav; Jovin, Tudor G.; Mattle, Heinrich P.; Nogueira, Raul G.; Siddiqui, Adnan H.; Yavagal, Dileep R.; Devlin, Thomas G.; Lopes, Demetrius K.; Reddy, Vivek K.; de Rochemont, Richard du Mesnil; Jahan, Reza; Vilain, Katherine A.; House, John; Lee, Jin-Moo; Cohen, David J.

2017-01-01

Background and Purpose Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator (SST+tPA) compared with tPA. Previous studies suggested that this strategy may be cost-effective, but models were derived from pooled data and older assumptions. Methods In this prospective economic substudy conducted alongside the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), in-trial costs were measured for patients using detailed medical resource utilization and hospital billing data. Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension questionnaire. Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors. Results Index hospitalization costs were $17 183 per patient higher for SST+tPA than for tPA ($45 761 versus $28 578; P<0.001), driven by initial procedure costs. Between discharge and 90 days, costs were $4904 per patient lower for SST+tPA than for tPA ($11 270 versus $16 174; P=0.014); total 90-day costs remained higher with SST+tPA ($57 031 versus $44 752; P<0.001). Higher utility values for SST+tPA led to higher in-trial quality-adjusted life years (0.131 versus 0.105; P=0.005). In lifetime projections, SST+tPA was associated with substantial gains in quality-adjusted life years (6.79 versus 5.05), cost savings of $23 203 per patient and was economically dominant when compared with tPA in 90% of bootstrap replicates. Conclusions Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial, SST increased initial treatment costs, but was projected to improve quality-adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA. PMID:28028150

Implications of limiting mechanical thrombectomy to patients with emergent large vessel occlusion meeting top tier evidence criteria.

PubMed

Bhole, Rohini; Goyal, Nitin; Nearing, Katherine; Belayev, Andrey; Doss, Vinodh T; Elijovich, Lucas; Hoit, Daniel A; Tsivgoulis, Georgios; Alexandrov, Andrei V; Arthur, Adam S; Alexandrov, Anne W

2017-03-01

Recent guidelines for endovascular management of emergent large vessel occlusion (ELVO) award top tier evidence to the same selective criteria in recent trials. We aimed to understand how guideline adherence would have impacted treatment numbers and outcomes in a cohort of patients from a comprehensive stroke center. A retrospective observational study was conducted using consecutive emergent endovascular patients. Mechanical thrombectomy (MT) was performed with stent retrievers or large bore clot aspiration catheters. Procedural outcomes were compared between patients meeting, and those failing to meet, top tier evidence criteria. 126 patients receiving MT from January 2012 to June 2015 were included (age 31-89 years, National Institutes of Health Stroke Scale (NIHSS) score 2-38); 62 (49%) patients would have been excluded if top tier criteria were upheld: pretreatment NIHSS score <6 (10%), Alberta Stroke Program Early CT score <6 (6.5%), premorbid modified Rankin Scale (mRS) score ≥2 (27%), M2 occlusion (10%), posterior circulation (32%), symptom to groin puncture >360 min (58%). 26 (42%) subjects had more than one top tier exclusion. Symptomatic intracerebral hemorrhage (sICH) and systemic hemorrhage rates were similar between the groups. 3 month mortality was 45% in those lacking top tier evidence compared with 26% (p=0.044), and 3 month mRS score 0-2 was 33% versus 46%, respectively (NS). After adjusting for potential confounders, top tier treatment was not associated with neurological improvement during hospitalization (β -8.2; 95% CI -24.6 to -8.2; p=0.321), 3 month mortality (OR=0.38; 95% CI 0.08 to 1.41), or 3 month favorable mRS (OR=0.97; 95% CI 0.28 to 3.35). Our study showed that with strict adherence to top tier evidence criteria, half of patients may not be considered for MT. Our data indicate no increased risk of sICH and a potentially higher mortality that is largely due to treatment of patients with basilar occlusions and those treated at

Comparison of Perfusion CT Software to Predict the Final Infarct Volume After Thrombectomy.

PubMed

Austein, Friederike; Riedel, Christian; Kerby, Tina; Meyne, Johannes; Binder, Andreas; Lindner, Thomas; Huhndorf, Monika; Wodarg, Fritz; Jansen, Olav

2016-09-01

Computed tomographic perfusion represents an interesting physiological imaging modality to select patients for reperfusion therapy in acute ischemic stroke. The purpose of our study was to determine the accuracy of different commercial perfusion CT software packages (Philips (A), Siemens (B), and RAPID (C)) to predict the final infarct volume (FIV) after mechanical thrombectomy. Single-institutional computed tomographic perfusion data from 147 mechanically recanalized acute ischemic stroke patients were postprocessed. Ischemic core and FIV were compared about thrombolysis in cerebral infarction (TICI) score and time interval to reperfusion. FIV was measured at follow-up imaging between days 1 and 8 after stroke. In 118 successfully recanalized patients (TICI 2b/3), a moderately to strongly positive correlation was observed between ischemic core and FIV. The highest accuracy and best correlation are shown in early and fully recanalized patients (Pearson r for A=0.42, B=0.64, and C=0.83; P<0.001). Bland-Altman plots and boxplots demonstrate smaller ranges in package C than in A and B. Significant differences were found between the packages about over- and underestimation of the ischemic core. Package A, compared with B and C, estimated more than twice as many patients with a malignant stroke profile (P<0.001). Package C best predicted hypoperfusion volume in nonsuccessfully recanalized patients. Our study demonstrates best accuracy and approximation between the results of a fully automated software (RAPID) and FIV, especially in early and fully recanalized patients. Furthermore, this software package overestimated the FIV to a significantly lower degree and estimated a malignant mismatch profile less often than other software. © 2016 American Heart Association, Inc.

Hydrodynamic comparison of the Penumbra system and commonly available syringes in forced-suction thrombectomy.

PubMed

Simon, Scott Douglas; Grey, Casey Paul

2014-04-01

The Penumbra system uses a coaxial separator and continuous extracorporeal suction to remove a clot from a cerebral artery. Forced-suction thrombectomy (FST) involves aspirating clots through the same reperfusion catheter using only a syringe, decreasing the procedure time and supplies needed. To evaluate multiple combinations of catheters and syringes to determine the optimal pairing for use in FST. Tests were performed using both the Penumbra system and syringes to aspirate water through Penumbra 0.041 inch (041), 4Max, 0.054 inch (054) and 5Max reperfusion catheters and a shuttle sheath. Dynamic pressure and flow at the catheter tip were calculated from the fill times for each system. Static pressure and force for each aspiration source were determined with a vacuum gauge. All syringes provided significantly higher dynamic pressure at the catheter tip than the Penumbra system (p<0.001). Increasing syringe volume significantly increased static pressure (p<0.001). Both flow and aspiration force significantly increased with catheter size (p<0.001). Cases are presented to demonstrate the clinical value of the laboratory principles. Maximizing static and dynamic pressure when performing FST is achieved by aspirating with a syringe possessing both the largest volume and the largest inlet diameter available. Maximizing aspiration force and flow rate is achieved by using the largest catheter possible.

Aspiration thrombectomy and intracoronary tirofiban via GuideLiner® catheter for a thrombosed aneurysmal vessel.

PubMed

Fry, James; Naqvi, Ali; Bahia, Amit; Seto, Arnold

2017-03-01

A 52-year-old Asian male with no traditional risk factors for coronary artery disease presented with acute coronary syndrome. Coronary angiography showed complete thrombotic occlusion of the left circumflex with a large thrombus burden in the setting of diffuse aneurysmal enlargement of the coronary arteries consistent with antecedent Kawasaki disease. Manual thrombectomy with adjunctive intracoronary tirofiban was performed utilizing the GuideLiner catheter ® (Vascular Solutions, Inc., MN, USA). Stent implantation was deferred. Follow-up imaging 48 h later showed preserved coronary flow and decreased thrombus burden. The GuideLiner catheter, a monorail guiding device, served a novel role in thrombus aspiration and intracoronary medication delivery.

Aspiration Thrombectomy and Drug-Eluting Stent Implantation Decrease the Occurrence of Angina Pectoris One Year After Acute Myocardial Infarction.

PubMed

Lee, Wei-Chieh; Fang, Chih-Yuan; Chen, Huang-Chung; Hsueh, Shu-Kai; Chen, Chien-Jen; Yang, Cheng-Hsu; Yip, Hon-Kan; Hang, Chi-Ling; Wu, Chiung-Jen; Fang, Hsiu-Yu

2016-04-01

Angina pectoris is a treatable symptom that is associated with mortality and decreased quality of life. Angina eradication is a primary care goal of care after an acute myocardial infarction (AMI). Our aim was to evaluate factors influencing angina pectoris 1 year after an AMI.From January 2005 to December 2013, 1547 patient received primary percutaneous intervention in our hospital for an acute ST-segment elevation myocardial infarction (MI). Of these patients, 1336 patients did not experience post-MI angina during a 1-year follow-up, and 211 patients did. Univariate and multivariate logistic regression analyses were performed to identify the factors influencing angina pectoris 1 year after an AMI. Propensity score matched analyses were performed for subgroups analyses.The average age of the patients was 61.08 ± 12.77 years, with a range of 25 to 97 years, and 82.9% of the patients were male. During 1-year follow-up, 13.6% of the patients experienced post-MI angina. There was a longer chest pain-to-reperfusion time in the post-MI angina group (P = 0.01), as well as a higher fasting sugar level, glycohemoglobin (HbA1C), serum creatinine, troponin-I and creatine kinase MB (CK-MB). The post-MI angina group also had a higher prevalence of multiple-vessel disease. Manual thrombectomy, and distal protective device and intracoronary glycoprotein IIb/IIIa inhibitor injection were used frequently in the no post-MI angina group. Antiplatelet agents and post-MI medication usage were similar between the 2 groups. Multivariate logistic regression analyses demonstrated that prior MI was a positive independent predictor of occurrence of post-MI angina. Manual thrombectomy use and drug-eluting stent implantation were negative independent predictors of post-MI angina. Higher troponin-I and longer chest pain-to-reperfusion time exhibited a trend toward predicting post-MI angina.Prior MIs were strong, independent predictors of post-MI angina. Manual thrombectomy and drug

Aspiration Thrombectomy and Drug-Eluting Stent Implantation Decrease the Occurrence of Angina Pectoris One Year After Acute Myocardial Infarction

PubMed Central

Lee, Wei-Chieh; Fang, Chih-Yuan; Chen, Huang-Chung; Hsueh, Shu-Kai; Chen, Chien-Jen; Yang, Cheng-Hsu; Yip, Hon-Kan; Hang, Chi-Ling; Wu, Chiung-Jen; Fang, Hsiu-Yu

2016-01-01

Abstract Angina pectoris is a treatable symptom that is associated with mortality and decreased quality of life. Angina eradication is a primary care goal of care after an acute myocardial infarction (AMI). Our aim was to evaluate factors influencing angina pectoris 1 year after an AMI. From January 2005 to December 2013, 1547 patient received primary percutaneous intervention in our hospital for an acute ST-segment elevation myocardial infarction (MI). Of these patients, 1336 patients did not experience post-MI angina during a 1-year follow-up, and 211 patients did. Univariate and multivariate logistic regression analyses were performed to identify the factors influencing angina pectoris 1 year after an AMI. Propensity score matched analyses were performed for subgroups analyses. The average age of the patients was 61.08 ± 12.77 years, with a range of 25 to 97 years, and 82.9% of the patients were male. During 1-year follow-up, 13.6% of the patients experienced post-MI angina. There was a longer chest pain-to-reperfusion time in the post-MI angina group (P = 0.01), as well as a higher fasting sugar level, glycohemoglobin (HbA1C), serum creatinine, troponin-I and creatine kinase MB (CK-MB). The post-MI angina group also had a higher prevalence of multiple-vessel disease. Manual thrombectomy, and distal protective device and intracoronary glycoprotein IIb/IIIa inhibitor injection were used frequently in the no post-MI angina group. Antiplatelet agents and post-MI medication usage were similar between the 2 groups. Multivariate logistic regression analyses demonstrated that prior MI was a positive independent predictor of occurrence of post-MI angina. Manual thrombectomy use and drug-eluting stent implantation were negative independent predictors of post-MI angina. Higher troponin-I and longer chest pain-to-reperfusion time exhibited a trend toward predicting post-MI angina. Prior MIs were strong, independent predictors of post-MI angina. Manual thrombectomy

Efficacy of Stent-Retriever Thrombectomy in Magnetic Resonance Imaging Versus Computed Tomographic Perfusion-Selected Patients in SWIFT PRIME Trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke).

PubMed

Menjot de Champfleur, Nicolas; Saver, Jeffrey L; Goyal, Mayank; Jahan, Reza; Diener, Hans-Christoph; Bonafe, Alain; Levy, Elad I; Pereira, Vitor M; Cognard, Christophe; Yavagal, Dileep R; Albers, Gregory W

2017-06-01

The majority of patients enrolled in SWIFT PRIME trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke) had computed tomographic perfusion (CTP) imaging before randomization; 34 patients were randomized after magnetic resonance imaging (MRI). Patients with middle cerebral artery and distal carotid occlusions were randomized to treatment with tPA (tissue-type plasminogen activator) alone or tPA+stentriever thrombectomy. The primary outcome was the distribution of the modified Rankin Scale score at 90 days. Patients with the target mismatch profile for enrollment were identified on MRI and CTP. MRI selection was performed in 34 patients; CTP in 139 patients. Baseline National Institutes of Health Stroke Scale score was 17 in both groups. Target mismatch profile was present in 95% (MRI) versus 83% (CTP). A higher percentage of the MRI group was transferred from an outside hospital ( P =0.02), and therefore, the time from stroke onset to randomization was longer in the MRI group ( P =0.003). Time from emergency room arrival to randomization did not differ in CTP versus MRI-selected patients. Baseline ischemic core volumes were similar in both groups. Reperfusion rates (>90%/TICI [Thrombolysis in Cerebral Infarction] score 3) did not differ in the stentriever-treated patients in the MRI versus CTP groups. The primary efficacy analysis (90-day mRS score) demonstrated a statistically significant benefit in both subgroups (MRI, P =0.02; CTP, P =0.01). Infarct growth was reduced in the stentriever-treated group in both MRI and CTP groups. Time to randomization was significantly longer in MRI-selected patients; however, site arrival to randomization times were not prolonged, and the benefits of endovascular therapy were similar. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461. © 2017 American Heart Association, Inc.

Cost-Effectiveness of Solitaire Stent Retriever Thrombectomy for Acute Ischemic Stroke: Results From the SWIFT-PRIME Trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke).

PubMed

Shireman, Theresa I; Wang, Kaijun; Saver, Jeffrey L; Goyal, Mayank; Bonafé, Alain; Diener, Hans-Christoph; Levy, Elad I; Pereira, Vitor M; Albers, Gregory W; Cognard, Christophe; Hacke, Werner; Jansen, Olav; Jovin, Tudor G; Mattle, Heinrich P; Nogueira, Raul G; Siddiqui, Adnan H; Yavagal, Dileep R; Devlin, Thomas G; Lopes, Demetrius K; Reddy, Vivek K; du Mesnil de Rochemont, Richard; Jahan, Reza; Vilain, Katherine A; House, John; Lee, Jin-Moo; Cohen, David J

2017-02-01

Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator (SST+tPA) compared with tPA. Previous studies suggested that this strategy may be cost-effective, but models were derived from pooled data and older assumptions. In this prospective economic substudy conducted alongside the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), in-trial costs were measured for patients using detailed medical resource utilization and hospital billing data. Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension questionnaire. Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors. Index hospitalization costs were $17 183 per patient higher for SST+tPA than for tPA ($45 761 versus $28 578; P<0.001), driven by initial procedure costs. Between discharge and 90 days, costs were $4904 per patient lower for SST+tPA than for tPA ($11 270 versus $16 174; P=0.014); total 90-day costs remained higher with SST+tPA ($57 031 versus $44 752; P<0.001). Higher utility values for SST+tPA led to higher in-trial quality-adjusted life years (0.131 versus 0.105; P=0.005). In lifetime projections, SST+tPA was associated with substantial gains in quality-adjusted life years (6.79 versus 5.05), cost savings of $23 203 per patient and was economically dominant when compared with tPA in 90% of bootstrap replicates. Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial, SST increased initial treatment costs, but was projected to improve quality-adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461. © 2016 American

Clinical Outcome After Mechanical Thrombectomy in Non-elderly Patients with Acute Ischemic Stroke in the Anterior Circulation: Primary Admission Versus Patients Referred from Remote Hospitals.

PubMed

Pfaff, J; Pham, M; Herweh, C; Wolf, M; Ringleb, P A; Schönenberger, S; Bendszus, M; Möhlenbruch, M

2017-06-01

Stroke networks have been installed to increase access to advanced stroke specific treatments like mechanical thrombectomy (MT). This concept often requires patients to be transferred to a comprehensive stroke center (CSC) offering MT. Do patient referral, transportation, and logistic effort translate into clinical outcomes comparable to patients admitted primarily to the CSC? We categorized 112 patients with acute ischemic stroke in the anterior circulation, who received MT at our institution, into primary admissions (A) and referrals from either local (B) or regional (C) hospitals, assessed the clinical outcome, and tested the impact of distance and delay of transportation from the referring remote hospital. The median time from symptom onset to initial CT was similar in all groups (p = 0,939). Patients who were transferred to the CSC had significantly increasing median time between initial CT and MT (in minutes (interquartile range [IQR]); A: 83 [68-120]; B: 174 [159-208]; C: 220 [181-235]; p < 0.001) and median time between onset to MT (in minutes [IQR]; A: 178 [150-210]; B: 274 [238-349]; C: 293 [256-329]; p < 0.001). After 90 days of MT there was no significant difference in clinical outcome (modified Rankin Scale ≤ 2) between primary admitted and referred patients (p = 0.502). Clinical outcome in patients who received MT after transfer from either local or regional remote hospitals was not significantly worse than in patients primarily admitted to the CSC. In the event of an acute ischemic stroke patients living in urban or rural areas should, despite a possible delay, have access to MT.

Treatment of the superior sagittal sinus and transverse sinus thrombosis associated with intracranial hemorrhage with the mechanical thrombectomy and thrombolytics: Case report.

PubMed

Liu, Yuchun; Li, Keqin; Huang, Yi; Sun, Jie; Gao, Xiang

2017-12-01

The superior sagittal sinus (SSS) and transverse sinus are the major dural sinuses that receive a considerable amount of venous drainage. The occlusion of them has been suggested to cause intracranial hypertension, hemorrhage, and lead to potentially fatal consequences. We reported a 35-year-old woman with headache presented to our emergency department with a decreased level of consciousness and epileptic seizures. The examination of speech, higher mental function, and cranial nerve were normal. Computed tomography (CT) demonstrated both subarachnoid and intraparenchymal hemorrhage and brain edema at the right temporal lobe accompanied by high density shadow in the right transverse sinus. Digital subtraction angiography (DSA) revealed extensive thrombosis of the SSS and bilateral transverse sinus. The SSS and transverse sinus thrombosis, accompanied by right temporal lobe hemorrhage, subarachnoid hemorrhage (SAH). An emergent mechanical thrombectomy by placed Solitair AB stent in the SSS, respectively, passed left and right sigmoid sinus-transverse sinus route. We removed the most clots, DSA revealed recanalization of the SSS and left transverse sinus was seen with normalization of the venous outflow, the occlusion of right transverse sinus was still present. There were 4 hours after patient back to neurosurgical intensive care unit (NICU), patient appeared anisocoria (R/L:4.0/2.5 mm), bilateral light reflexes disappeared, then we took a CT reexamination revealed intraparenchymal hemorrhage increased, brain edema was aggravated at the left temporal lobe, and mild midline shift. Subsequently, we performed decompressive hemicraniectomy and puncture the hematoma supplemented by B ultrasonic. Anticoagulation treatment was initiated 24 hours after surgery, and follow-up DSA showed gradually improved patency in the SSS and bilateral transverse sinus. Despite occlusion of the SSS and bilateral transverse sinus, patient's symptoms resolved after the operations and he

Rheolytic thrombectomy with use of the AngioJet-F105 catheter: preclinical evaluation of safety.

PubMed

Sharafuddin, M J; Hicks, M E; Jenson, M L; Morris, J E; Drasler, W J; Wilson, G J

1997-01-01

A preclinical evaluation of the safety of the AngioJet-F105 rheolytic thrombectomy catheter. The AngioJet-F105 catheter uses multiple retrograde high-speed fluid jets impinging on a primary aspiration lumen to create a hydrodynamic recirculation vortex that traps and fragments adjacent thrombus, with simultaneous evacuation of the resulting debris through the aspiration lumen. The effect of the AngioJet on treated vessels was evaluated in 10 canines. Vascular integrity on histopathologic examination and endothelial coverage on scanning electron microscopic study were examined in 15 vessel segments treated with the AngioJet-F105 catheter, compared with four vessel segments subjected to the Fogarty balloon maneuver, and 10 untreated vessel segments. The size distribution of particulate debris, upstream and downstream, after thrombectomy was determined in a flow-circuit model simulating the superficial femoral artery. Aliquots from the downstream effluent were then injected into the renal arteries of two healthy canines. The device caused only minimal focal endothelial denudation and no significant deep injury. No significant difference in endothelial coverage occurred in AngioJet-treated vessel segments compared to untreated control vessels (mean +/- standard deviation: 88.0% +/- 7.9% vs 89.7% +/- 11.6%, P = .77). Vessels treated with the Fogarty balloon pullback maneuver had significantly less residual endothelial coverage (58.0% +/- 8.0%, P < .03). Particulate microemboli in the effluent of the flow model accounted for 12% of the initial thrombus volume (0% > 100 microm, 99.83% < or = 10 microm). Histopathologic evaluation of the four renal beds injected with the resulting debris demonstrated no signs of necrosis. A moderate transient increase in plasma-free hemoglobin occurred, with a mild corresponding decrease in hematocrit. The AngioJet-F105 catheter resulted in only mild and focal injury to the treated vessels. The vast majority of resulting particulate debris

PROTECT: PRoximal balloon Occlusion TogEther with direCt Thrombus aspiration during stent retriever thrombectomy - evaluation of a double embolic protection approach in endovascular stroke treatment.

PubMed

Maegerlein, Christian; Mönch, Sebastian; Boeckh-Behrens, Tobias; Lehm, Manuel; Hedderich, Dennis M; Berndt, Maria Teresa; Wunderlich, Silke; Zimmer, Claus; Kaesmacher, Johannes; Friedrich, Benjamin

2017-12-08

Stent retriever-based mechanical thrombectomy (MT) for emergent large vessel occlusions (ELVO) is often complicated by thrombus fragmentation causing distal embolization and embolization to new vascular territories. Well-established embolic protection approaches include proximal flow arrest and distal aspiration techniques during stent retriever maneuvers. Aiming at the reduction of thrombus fragmentation during MT we evaluated a technical approach combining proximal balloon occlusion together with direct thrombus aspiration during MT: the PROTECT technique. We performed a case-control study comparing the PROTECT technique with sole distal aspiration during MT regarding technical and procedural parameters, n=200 patients with ELVO of either the terminus of the internal carotid artery or the proximal middle artery were included. PROTECT resulted in a shorter procedure time (29 vs 40 min; P=0.002), in a higher rate of successful recanalizations (100% vs 78%; P=0.001) and a higher rate of complete reperfusions (70% vs 39%; P<0.001) compared with sole distal aspiration during MT. The PROTECT technique is a promising new approach to significantly reduce thrombus fragmentation and, hence distal embolization during MT. This safe and efficient technique needs to be validated in larger trials to confirm our results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pharmacomechanical Thrombectomy in Paget–Schroetter Syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kärkkäinen, Jussi M., E-mail: jkarkkai@gmail.com; Nuutinen, Henrik; Riekkinen, Teemu

PurposeThe purpose of the study was to evaluate feasibility of pharmacomechanical thrombectomy (PMT) in the treatment of Paget–Schroetter syndrome (PSS) followed by thoracoscopic or open surgical decompression of the subclavian vein.MethodsTwenty-two out of 27 consecutive patients with PSS received PMT using the Trellis-8 peripheral infusion system (Covidien) between 2010 and 2014. Subsequent surgery was performed in 18 of those patients, 9 patients were treated with thoracoscopic, 7 patients with subclavicular, and 2 patients with transaxillary first rib resection, 4 patients were treated with PMT and anticoagulation alone. Technical success, complications, and patency were registered.ResultsPMT was successful in 21 (95 %) patients;more » 1 patient with unsatisfactory lysis received further catheter-directed thrombolysis, which, however, did not improve the result. The mean endovascular procedure time was 105 ± 33 min (range 70–200 min), and the required median amount of thrombolytic agent was 500,000 international unit (IU; range 250,000–1,000,000 IU). Adjunctive balloon venoplasty and aspiration were used in 18 (82 %) and 7 (32 %) cases, respectively. One patient had an intimal tear of the subclavian vein that was discovered and repaired during surgery. There were no other complications related to the endovascular procedure. At follow-up, 18 of 21 patients (86 %) with follow-up imaging available had patent subclavian vein, and all except 1 of the 22 patients were asymptomatic. The mean follow-up time was 25 ± 17 months.ConclusionsIn experienced hands, PMT is effective for early thrombus removal in PSS. Surgical decompression must be considered after PMT.« less

Rivaroxaban does not influence hemorrhagic transformation in a diabetes ischemic stroke and endovascular thrombectomy model.

PubMed

Liu, Feng-Di; Zhao, Rong; Feng, Xiao-Yan; Shi, Yan-Hui; Wu, Yi-Lan; Shen, Xiao-Lei; Li, Ge-Fei; Liu, Yi-Sheng; Zhao, Ying; He, Xin-Wei; Yin, Jia-Wen; Zhuang, Mei-Ting; Zhao, Bing-Qiao; Liu, Jian-Ren

2018-05-09

Managing endovascular thrombectomy (ET) in diabetic ischemic stroke (IS) with novel anticoagulants is challenging due to putative risk of intracerebral hemorrhage. The study evaluates increased hemorrhagic transformation (HT) risk in Rivaroxaban-treated diabetic rats post ET. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 60 mg/kg streptozotocin. After 4-weeks, rats were pretreated orally with 30 mg/kg Rivaroxaban/saline; prothrombin time was monitored. IS and ET was induced after 1 h, by thread-induced transient middle cerebral artery occlusion (tMCAO) that mimicked mechanical ET for proximal MCA occlusion at 60 min. After 24 h reperfusion, infarct volumes, HT, blood-brain barrier (BBB) permeability, tight junction at peri-ischemic lesion and matrix metalloproteinase-9 (MMP-9) activity was measured. Diabetic rats seemed to exhibit increased infarct volume and HT at 24 h after ET than normal rats. Infarct volumes and functional outcomes did not differ between Rivaroxaban and diabetic control groups. A significant increase in HT volumes and BBB permeability under Rivaroxaban treatment was not detected. Compared to diabetic control group, neither the occludin expression was remarkably lower in the Rivaroxaban group nor the MMP-9 activity was higher. Together, Rivaroxaban does not increase HT after ET in diabetic rats with proximal MCA occlusion, since Rivaroxaban has fewer effects on post-ischemic BBB permeability.

Low Cerebral Blood Volume Identifies Poor Outcome in Stent Retriever Thrombectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Protto, Sara, E-mail: sara.protto@pshp.fi; Pienimäki, Juha-Pekka; Seppänen, Janne

BackgroundMechanical thrombectomy (MT) is an efficient treatment of acute stroke caused by large-vessel occlusion. We evaluated the factors predicting poor clinical outcome (3-month modified Rankin Scale, mRS >2) although MT performed with modern stent retrievers.MethodsWe prospectively collected the clinical and imaging data of 105 consecutive anterior circulation stroke patients who underwent MT after multimodal CT imaging. Patients with occlusion of the internal carotid artery and/or middle cerebral artery up to the M2 segment were included. We recorded baseline clinical, procedural and imaging variables, technical outcome, 24-h imaging outcome and the clinical outcome. Differences between the groups were studied with appropriatemore » statistical tests and binary logistic regression analysis.ResultsLow cerebral blood volume Alberta stroke program early CT score (CBV-ASPECTS) was associated with poor clinical outcome (median 7 vs. 9, p = 0.01). Lower collateral score (CS) significantly predicted poor outcome in regression modelling with CS = 0 increasing the odds of poor outcome 4.4-fold compared to CS = 3 (95% CI 1.27–15.5, p = 0.02). Lower CBV-ASPECTS significantly predicted poor clinical outcome among those with moderate or severe stroke (OR 0.82, 95% CI 0.68–1, p = 0.05) or poor collateral circulation (CS 0–1, OR 0.66, 95% CI 0.48–0.90, p = 0.009) but not among those with mild strokes or good collaterals.ConclusionsCBV-ASPECTS estimating infarct core is a significant predictor of poor clinical outcome among anterior circulation stroke patients treated with MT, especially in the setting of poor collateral circulation and/or moderate or severe stroke.« less

Stent Retriever Thrombectomy in Different Thrombus Locations of Anterior Cerebral Circulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Protto, Sara; Sillanpää, Niko, E-mail: niko.sillanpaa@pshp.fi; Pienimäki, Juha-Pekka

BackgroundMechanical thrombectomy (MT) is a safe and efficient treatment for acute ischemic stroke in patients with proximal anterior occlusion and large penumbra. We evaluated the technical and clinical success of MT in relation to the location of the occlusion (internal carotid artery, M1 and M2 segments of the middle cerebral artery).MethodsWe prospectively reviewed 130 patients of whom 105 met the inclusion criteria. Baseline clinical, procedural and imaging variables, technical outcome (TICI, thrombolysis in cerebral infarction), 24 h imaging outcome and three-month clinical outcome (mRS, modified Rankin Scale) were recorded. Differences between the groups were studied with statistical tests according to themore » type of the variable.ResultsThere were 37, 46 and 22 patients in the internal carotid artery (ICA), M1 and M2 groups, respectively. TICI 2b or 3 was achieved in 92 cases (88 %) with a non-significant trend towards a better recanalization outcome in the ICA and M1 groups. Overall, 57 of the 105 patients (55 %) experienced favorable clinical outcome (mRS ≤ 2) with no significant differences between the groups. Excellent outcome (mRS ≤ 1) was seen in 40 patients (39 %) and there proportionally more patients with excellent outcome in the ICA and M1 groups (ICA: 44 %, M1: 41 %, M2: 23 % of patients, p = 0.22).ConclusionsThere were no statistically significant differences in the technical or clinical outcomes between the different sites of occlusion (ICA, M1 or M2). There was a non-significant trend towards achieving excellent clinical outcome (3-month mRS ≤ 1) more often and better recanalization results in the two more proximal locations.« less

Combined hydrophobicity and mechanical durability through surface nanoengineering

DOE PAGES

Elliott, Paul R.; Stagon, Stephen P.; Huang, Hanchen; ...

2015-04-08

This paper reports combined hydrophobicity and mechanical durability through the nanoscale engineering of surfaces in the form of nanorod-polymer composites. Specifically, the hydrophobicity derives from nanoscale features of mechanically hard ZnO nanorods and the mechanical durability derives from the composite structure of a hard ZnO nanorod core and soft polymer shell. Experimental characterization correlates the morphology of the nanoengineered surfaces with the combined hydrophobicity and mechanical durability, and reveals the responsible mechanisms. Such surfaces may find use in applications, such as boat hulls, that benefit from hydrophobicity and require mechanical durability.

A multicenter study of the safety and effectiveness of mechanical thrombectomy for patients with acute ischemic stroke not meeting top-tier evidence criteria.

PubMed

Goyal, Nitin; Tsivgoulis, Georgios; Frei, Donald; Turk, Aquilla; Baxter, Blaise; Froehler, Michael T; Mocco, J; Vachhani, Jay; Hoit, Daniel; Elijovich, Lucas; Loy, David; Turner, Raymond D; Mascitelli, Justin; Espaillat, Kiersten; Alexandrov, Andrei V; Alexandrov, Anne W; Arthur, Adam S

2018-01-01

While mechanical thrombectomy (MT) has become the standard of care for patients with acute ischemic stroke (AIS) with emergent large-vessel occlusions (ELVO), recently published guidelines appropriately award top-tier evidence to the same selective criteria that were employed in completed clinical trials. We sought to evaluate the safety and effectiveness of MT in patients with AIS with ELVO who do not meet top-tier evidence criteria (TTEC). We conducted an observational study on consecutive patients with AIS with ELVO who underwent MT at six high-volume endovascular centers. Standard safety outcomes (3-month mortality, symptomatic intracranial hemorrhage) and effectiveness outcomes (3-month functional independence: modified Rankin Scale scores of 0-2) were compared between patients meeting and failing TTEC. The sample consisted of 349 (60%) controls fulfilling TTEC and 234 (40%) non-TTEC patients. Control patients meeting TTEC for MT tended to have higher functional independence rates at 3 months (47% vs 39%; p=0.055), while the rates of symptomatic intracerebral hemorrhage (sICH) were similar (9%) in both groups (p=0.983). In multivariable logistic regression models, adherence to TTEC for MT was not independently related to any safety outcome (sICH: OR 0.71, 95% CI 0.30 to 1.68, p=0.434; 3-month mortality: OR 1.27, 95% CI 0.69 to 2.33, p=0.448) or effectiveness outcome (3-month functional independence: OR 0.81, 95% CI 0.48 to 1.37, p=0.434; 3-month functional improvement: OR 0.73, 95% CI 0.48 to 1.11, p=0.138) after adjusting for potential confounders. Approximately 40% of patients with AIS with ELVO offered MT do not fulfill TTEC for MT. Patients who did not meet TTEC had high rates of good clinical outcome and low complication rates. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The Use of the 'Preclosure' Technique for Antegrade Aspiration Thrombectomy with Large Catheters in Acute Limb Ischemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Funke, C., E-mail: claas_funke@hotmail.com; Pfiffner, R.; Husmann, M.

2013-04-15

This study was designed to assess retrospectively short- and mid-term outcomes of the use of a suture-mediated closure device to close the antegrade access in patients undergoing percutaneous aspiration thrombectomy with large catheters for acute leg ischemia. Between November 2005 and February 2010, a suture-mediated active closure system (ProGlide{sup Registered-Sign} 6F, Abbott) was placed before arterial sheath (mean 9 F, range 6-12 F) introduction in 101 patients (74 men, 73 %, mean age 70.1 {+-} 12.6 years standard deviation). Data regarding mortality, complications, and factors contributing to vascular complications at the access site was collected for 6 month after themore » intervention to detect device-related problems. As a coincidence, 77 patients had follow-up visits for a duplex ultrasound. There were a total of 19 vascular complications (19 %) at the puncture site, all of which were of hemorrhagic nature and none of which consisted of vessel occlusion. Two major outcome complications (2 %) occurred. A retroperitoneal hematoma and a serious inguinal bleeding required additive treatment and did not result in permanent sequelae. Nine cases involved death of which eight were not attributable to the closure and one remained unclear. Successful closure was achieved in 95 patients (94 %); additional manual compression was sufficient in the majority of the remaining patients. Numerous factors contributing to vascular complications were encountered. With acceptable short- and mid-term outcomes, the 'preclose' technique can be a reliable option for the closure of a large antegrade femoral access even for patients at a high risk of vascular complications, such as those undergoing aspiration thrombectomy.« less

Dump the pump: manual aspiration thrombectomy (MAT) with a syringe is technically effective, expeditious, and cost-efficient.

PubMed

Gross, Bradley A; Jadhav, Ashutosh P; Jovin, Tudor G; Jankowitz, Brian Thomas

2018-04-01

Syringe aspiration for manual aspiration thrombectomy (MAT) is a cost- and time-efficient alternative to an aspiration pump with likely similar efficacy. It is counterintuitive to expect the pump to perform better than direct vacuum with a syringe, as the pump must deliver vacuum additionally through a canister and meters of tubing. To present in vitro and clinical results of MAT with a syringe. An in vitro analysis was performed comparing vacuum pressures generated by syringe aspiration and with pump aspiration. This was then complemented with prospective clinical data providing details of angiographic and clinical outcomes for syringe MAT. The in vitro analysis demonstrated that equal to slightly greater vacuum pressures were generated by a 60 cc syringe as compared with the pump in both static and partial flow conditions. In our clinical series, 106/113 acute stroke thrombectomies over a 6-month period were performed with syringe MAT on the first pass. Syringe usage instead of pump tubing and a canister led to a total savings of $58 300. The rate of Thrombolysis in Cerebral Infarction 2b/3 recanalization was 93%. Adjunctive stentriever usage was performed in 23% of cases. Median puncture to reperfusion time was 25 min; mean change in National Institute of Health Stroke Scale score at 24 hours was an improvement of 5.1 (median 6). The in-hospital mortality rate was 10%. Seventy percent of patients were discharged to home (modified Rankin Scale (mRS) score 0-2) or a rehabilitation facility (mRS score 2-4). MAT using a syringe is a safe, fast, and more cost-effective approach than using an aspiration pump. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Urologic Oncologic SurveyRobotic level III inferior vena cava tumor thrombectomy: Initial series. Gill IS, Metcalfe C, Abreu A, Duddalwar V, Chopra S, Cunningham M, Thangathurai D, Ukimura O, Satkunasivam R, Hung A, Papalia R, Aron M, Desai M, Gallucci M. J Urol. 2015 Oct;194(4):929-938. [Epub 2015 Apr 6]. doi: 10.1016/j.juro.2015.03.119.

PubMed

Meng, Max

2017-05-01

Level III inferior vena cava tumor thrombectomy for renal cancer is one of the most challenging open urologic surgeries. We present the initial series of completely intracorporeal robotic level III inferior vena cava tumor thrombectomy. Nine patients underwent robotic level III inferior vena cava thrombectomy and 7 patients underwent level II thrombectomy. The entire operation (high intrahepatic inferior vena cava control, caval exclusion, tumor thrombectomy, inferior vena cava repair, radical nephrectomy, and retroperitoneal lymphadenectomy) was performed exclusively robotically. To minimize the chances of intraoperative inferior vena cava thrombus embolization, an "inferior vena cava-first, kidney-last" robotic technique was developed. Data were accrued prospectively. All 16 robotic procedures were successful, without open conversion or mortality. For level III cases (9), median primary kidney (right 6, left 3) cancer size was 8.5cm (range: 5.3-10.8) and inferior vena cava thrombus length was 5.7cm (range: 4-7). Median operative time was 4.9 hours (range: 4.5-6.3), estimated blood loss was 375ml (range: 200-7,000), and hospital stay was 4.5 days. All surgical margins were negative. There were no intraoperative complications and 1 postoperative complication (Clavien 3b). At a median 7 months of follow-up (range: 1-18) all patients are alive. Compared to level II thrombi the level III cohort trended toward greater inferior vena cava thrombus length (3.3 vs 5.7cm), operative time (4.5 vs 4.9h) and blood loss (290 vs 375ml). With appropriate patient selection, surgical planning and robotic experience, completely intracorporeal robotic level III inferior vena cava thrombectomy is feasible and can be performed efficiently. Larger experience, longer follow-up and comparison with open surgery are needed to confirm these initial outcomes. Copyright © 2017. Published by Elsevier Inc.

Clinical and Angiographic Outcomes with the Combined Local Aspiration and Retriever in the North American Solitaire Stent-Retriever Acute Stroke (NASA) Registry.

PubMed

Malisch, Tim W; Zaidat, Osama O; Castonguay, Alicia C; Marden, Franklin A; Gupta, Rishi; Sun, Chung-Huan J; Martin, Coleman O; Holloway, William E; Mueller-Kronast, Nils; English, Joey; Linfante, Italo; Dabus, Guilherme; Bozorgchami, Hormozd; Xavier, Andrew; Rai, Ansaar T; Froehler, Michael; Badruddin, Aamir; Nguyen, Thanh N; Taqi, M Asif; Abraham, Michael G; Janardhan, Vallabh; Shaltoni, Hashem; Novakovic, Robin; Yoo, Albert J; Abou-Chebl, Alex; Chen, Peng Roc; Britz, Gavin W; Kaushal, Ritesh; Nanda, Ashish; Nogueira, Raul G

2018-02-01

Various techniques are used to enhance the results of mechanical thrombectomy with stent-retrievers, including proximal arrest with balloon guide catheter (BGC), conventional large bore proximal catheter (CGC), or in combination with local aspiration through a large-bore catheter positioned at the clot interface (Aspiration-Retriever Technique for Stroke [ARTS]). We evaluated the impact of ARTS in the North American Solitaire Acute Stroke (NASA) registry. Data on the use of the aspiration technique were available for 285 anterior circulation patients, of which 29 underwent ARTS technique, 131 CGC, and 125 BGC. Baseline demographics were comparable, except that ARTS patients are less likely to have hypertension or atrial fibrillation. The ARTS group had more ICA occlusions (41.4 vs. 22% in the BGC, p = 0.04 and 26% in CGC, p = 0.1) and less MCA/M1 occlusions (44.8 vs. 68% in BGC and 62% in CGC). Time from arterial puncture to reperfusion or end of procedure with ARTS was shorter than with CGC (54 vs. 91 min, p = 0.001) and was comparable to the BGC time (54 vs. 67, p = 0.11). Final degree of reperfusion was comparable among the groups (TICI [modified Thrombolysis in Cerebral Infarction] score 2b or higher was 72 vs. 70% for CGC vs. 78% for BGC). Procedural complications, mortality, and good clinical outcome at 90 days were similar between the groups. The ARTS mechanical thrombectomy in acute ischemic stroke patients appears to yield better results as compared to the use of CGCs with no significant difference when compared to BGC. This early ARTS technique NASA registry data are limited by the earlier generation distal large bore catheters and small sample size. Future studies should focus on the comparison of ARTS and BGC techniques.

Outcome After Reperfusion Therapies in Patients With Large Baseline Diffusion-Weighted Imaging Stroke Lesions: A THRACE Trial (Mechanical Thrombectomy After Intravenous Alteplase Versus Alteplase Alone After Stroke) Subgroup Analysis.

PubMed

Gautheron, Vincent; Xie, Yu; Tisserand, Marie; Raoult, Hélène; Soize, Sébastien; Naggara, Olivier; Bourcier, Romain; Richard, Sébastien; Guillemin, Francis; Bracard, Serge; Oppenheim, Catherine

2018-03-01

Stroke patients with large diffusion-weighted imaging (DWI) volumes are often excluded from reperfusion because of reckoned futility. In those with DWI volume >70 mL, included in the THRACE trial (Mechanical Thrombectomy After Intravenous Alteplase Versus Alteplase Alone After Stroke), we report the associations between baseline parameters and outcome. We examined 304 patients with anterior circulation stroke and pretreatment magnetic resonance imaging. Variables were extracted from the THRACE database, and DWI volumes were measured semiautomatically. Among 53 patients with DWI volume >70 mL, 12 had favorable outcome (modified Rankin Scale score, ≤2) at 3 months; they had less coronary disease (0/12 versus 12/38; P =0.046) and less history of smoking (1/10 versus 12/31; P =0.013) than patients with modified Rankin Scale score >2. None of the 8 patients >75 years of age reached modified Rankin Scale score ≤2. Favorable outcome occurred in 12 of 37 M1-occluded patients but in 0 of 16 internal carotid-T/L-occluded patients ( P =0.010). Favorable outcome was more frequent (6/13) when DWI lesion was limited to the superficial middle cerebral artery territory than when it extended to the deep middle cerebral artery territory (6/40; P =0.050). Stroke patients with DWI lesion >70 mL may benefit from reperfusion therapy, especially those with isolated M1 occlusion or ischemia restricted to the superficial middle cerebral artery territory. The benefit of treatment seems questionable for patients with carotid occlusion or lesion extending to the deep middle cerebral artery territory. © 2018 American Heart Association, Inc.

Endovascular thrombectomy with or without systemic thrombolysis?

PubMed

Tsivgoulis, Georgios; Katsanos, Aristeidis H; Mavridis, Dimitris; Alexandrov, Anne W; Magoufis, Georgios; Arthur, Adam; Caso, Valeria; Schellinger, Peter D; Alexandrov, Andrei V

2017-03-01

Current recommendations advocate that pretreatment with intravenous thrombolysis (IVT) should first be offered to all eligible patients with emergent large vessel occlusion (ELVO) before an endovascular thrombectomy (ET) procedure. However, there are observational data that question the safety and efficacy of IVT pretreatment in patients with ELVO. We performed a meta-analysis of the included subgroups from ET randomized controlled trials (RCTs) to evaluate the comparative efficacy between direct ET without IVT pretreatment and bridging therapy (IVT and ET) in patients with ELVO. We included a total of seven RCTs, including 1764 patients with ELVO (52.8% men). Patients receiving bridging therapy (IVT followed by ET) had lower rates ( p = 0.041) of 90-day death/severe dependency (modified Rankin Scale-score of 5-6; 19.0%, 95% CI: 14.1-25.1%) compared with patients receiving only ET (31.0%, 95% CI: 21.2-42.9%). Moreover, patients receiving IVT and ET had a nonsignificant ( p = 0.389) trend towards higher 90-day functional independence rates (51.4%, 95% CI: 42.5-60.1%) compared with patients undergoing only ET (41.7%, 95% CI: 24.1-61.7%). Finally, shift-analysis uncovered a nonsignificant trend towards functional improvement at 90 days for bridging therapy over ET (cOR = 1.28, 95% CI: 0.91-1.89; p = 0.155). It should be noted that patients included in the present meta-analysis were not randomized to receive IVT, and thus the two groups (bridging therapy versus ET monotherapy) may differ in terms of baseline characteristics and, in particular, in terms of onset to groin puncture time and thus the risk of confounding bias cannot be ruled out. Despite the limitations and the risk of confounding bias, our findings contradict the recent notion regarding potential equality between ET and bridging therapy in ELVO patients and suggest that IVT and ET are complementary therapies that should be pursued in a parallel and noncompeting fashion.

Technology of combined chemical-mechanical fabrication of durable coatings

NASA Astrophysics Data System (ADS)

Smolentsev, V. P.; Ivanov, V. V.; Portnykh, A. I.

2018-03-01

The article presents the scientific fundamentals of methodology for calculating the modes and structuring the technological processes of combined chemical-mechanical fabrication of durable coatings. It is shown that they are based on classical patterns, describing the processes of simultaneous chemical and mechanical impact. The paper demonstrates the possibility of structuring a technological process, taking into account the systematic approach to impact management and strengthening the reciprocal positive influence of each impact upon the combined process. The combined processes have been planned for fabricating the model types of chemical-mechanical coatings of durable products in machine construction. The planning methodology is underpinned by a scientific hypothesis of a single source of impact management through energy potential of process components themselves, or by means of external energy supply through mechanical impact. The control of it is fairly thoroughly studied in the case of pulsed external strikes of hard pellets, similar to processes of vibroimpact hardening, thoroughly studied and mastered in many scientific schools of Russia.

Mechanical removal of a refluxed Onyx piece from the middle cerebral artery using the Solitaire Stent: Technical report.

PubMed

Gungor, Dilara; Oğuz, Şükrü; Dinc, Hasan

2017-06-01

Onyx reflux into the parent artery is a rare and sometimes significant complication in the treatment of cerebral arteriovenous malformations (AVMs). We report a patient who presented with Onyx reflux into the M1 segment of the middle cerebral artery (MCA) during embolization of a right temporal AVM. The refluxed Onyx cast was successfully removed by a mechanical thrombectomy device using a self-expandable and fully retrievable Solitaire AB stent.

General Anesthesia Versus Conscious Sedation in Acute Stroke Treatment: The Importance of Head Immobilization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Janssen, H., E-mail: hendrik.janssen@med.uni-muenchen.de; Buchholz, G.; Killer, M.

PurposeWhile today mechanical thrombectomy is an established treatment option for main branch occlusions in anterior circulation stroke, there is still an ongoing debate on the kind of anesthesia to be preferred. Introducing a simple method for head stabilization, we analyzed safety and duration of endovascular recanalization procedures under general anesthesia (GA) and conscious sedation (CS).MethodsWe retrospectively identified 84 consecutive patients who underwent mechanical thrombectomy owing to acute anterior circulation stroke. Fifty-three were treated under GA and 31 under CS equipped with a standard cervical collar to reduce head movement. We evaluated recanalization results, in-house time to start recanalization, procedure times,more » technical and clinical complication rates, and conversion rates from CS to GA.ResultsRecanalization of mTICI ≥2b was achieved in 80 % under CS and in 81 % under GA. Median in-house time to start recanalization for CS was 60 min (IQR 28; 44–72) and 77 min (IQR 23; 68–91) for GA (P = 0.001). Median procedure time under CS was 35 min (IQR 43; 69–25) and 41 min (IQR 43; 66–23) for GA (P = 0.9). No major complications such as ICH occurred in either group, and no conversions from CS to GA were necessary.ConclusionMechanical thrombectomy can be performed faster and safely under CS in combination with simple head immobilization using a standard cervical collar.« less

Stenting of the cervical internal carotid artery in acute stroke management: The Karolinska experience.

PubMed

Mpotsaris, Anastasios; Kabbasch, Christoph; Borggrefe, Jan; Gontu, Vamsi; Soderman, Michael

2017-04-01

Background Emergency stent placement in the extracranial internal carotid artery in combination with anterior circulation thrombectomy is a routine procedure. Yet, precise indications and clinical safety in this setting remains controversial. Present data for mechanical thrombectomy include few studies with acute stenting of tandem occlusions. We evaluated the feasibility, safety and clinical outcome of this endovascular treatment in a retrospective analysis of all consecutive cases at a comprehensive stroke centre. Methods This was a retrospective analysis of all consecutive patients with acute extracranial carotid artery occlusion including acute dissection or high-grade stenosis and concomitant intracranial large-vessel occlusion treated with emergency carotid stenting and intracranial mechanical thrombectomy between November 2007 and May 2015. Results A total of 63 patients with a median age of 67 years (range 33-84 years) were treated. Of these, 33 (52%) patients had concomitant intravenous thrombolysis with recombinant tissue-type plasminogen activator initially. Median admission National Institutes of Health Stroke Scale was 14 (range 1-29). Median time from stroke onset to recanalization was 408 minutes (range 165-1846 minutes). Procedure time was significantly shorter after intravenous thrombolysis (110 minutes [range 15-202 minutes] vs. 130 minutes [range 60-280 minutes]; p = 0.02). Three (5%) patients experienced post-procedural symptomatic intracerebral haemorrhage. In 55/63 (87%) patients, a score of ≥2b on the Thrombolysis in Cerebral Infarction scale could be achieved. Eight (13%) patients died, five (8%) during the acute phase. A total of 29/63 (46%) patients showed a favourable outcome (modified Rankin Scale score of 0-2) after three months. Conclusions Our single-centre retrospective analysis of emergency stent placement in the extracranial internal carotid artery in combination with anterior circulation thrombectomy demonstrated high

Tuning Cell and Tissue Development by Combining Multiple Mechanical Signals.

PubMed

Sinha, Ravi; Verdonschot, Nico; Koopman, Bart; Rouwkema, Jeroen

2017-10-01

Mechanical signals offer a promising way to control cell and tissue development. It has been established that cells constantly probe their mechanical microenvironment and employ force feedback mechanisms to modify themselves and when possible, their environment, to reach a homeostatic state. Thus, a correct mechanical microenvironment (external forces and mechanical properties and shapes of cellular surroundings) is necessary for the proper functioning of cells. In vitro or in the case of nonbiological implants in vivo, where cells are in an artificial environment, addition of the adequate mechanical signals can, therefore, enable the cells to function normally as in vivo. Hence, a wide variety of approaches have been developed to apply mechanical stimuli (such as substrate stretch, flow-induced shear stress, substrate stiffness, topography, and modulation of attachment area) to cells in vitro. These approaches have not just revealed the effects of the mechanical signals on cells but also provided ways for probing cellular molecules and structures that can provide a mechanistic understanding of the effects. However, they remain lower in complexity compared with the in vivo conditions, where the cellular mechanical microenvironment is the result of a combination of multiple mechanical signals. Therefore, combinations of mechanical stimuli have also been applied to cells in vitro. These studies have had varying focus-developing novel platforms to apply complex combinations of mechanical stimuli, observing the co-operation/competition between stimuli, combining benefits of multiple stimuli toward an application, or uncovering the underlying mechanisms of their action. In general, they provided new insights that could not have been predicted from previous knowledge. We present here a review of several such studies and the insights gained from them, thereby making a case for such studies to be continued and further developed.

Mechanical removal of a refluxed Onyx piece from the middle cerebral artery using the Solitaire Stent: Technical report

PubMed Central

Oğuz, Şükrü; Dinc, Hasan

2017-01-01

Onyx reflux into the parent artery is a rare and sometimes significant complication in the treatment of cerebral arteriovenous malformations (AVMs). We report a patient who presented with Onyx reflux into the M1 segment of the middle cerebral artery (MCA) during embolization of a right temporal AVM. The refluxed Onyx cast was successfully removed by a mechanical thrombectomy device using a self-expandable and fully retrievable Solitaire AB stent. PMID:28604186

Combined mechanical loading of composite tubes

NASA Technical Reports Server (NTRS)

Derstine, Mark S.; Pindera, Marek-Jerzy; Bowles, David E.

1988-01-01

An analytical/experimental investigation was performed to study the effect of material nonlinearities on the response of composite tubes subjected to combined axial and torsional loading. The effect of residual stresses on subsequent mechanical response was included in the investigation. Experiments were performed on P75/934 graphite-epoxy tubes with a stacking sequence of (15/0/ + or - 10/0/ -15), using pure torsion and combined axial/torsional loading. In the presence of residual stresses, the analytical model predicted a reduction in the initial shear modulus. Experimentally, coupling between axial loading and shear strain was observed in laminated tubes under combined loading. The phenomenon was predicted by the nonlinear analytical model. The experimentally observed linear limit of the global shear response was found to correspond to the analytically predicted first ply failure. Further, the failure of the tubes was found to be path dependent above a critical load level.

Intervention radiology for venous thrombosis: early thrombus removal using invasive methods.

PubMed

Casanegra, Ana I; McBane, Robert D; Bjarnason, Haraldur

2017-04-01

The post thrombotic syndrome is one of the most dreaded complications of proximal deep vein thrombosis. This syndrome leads to pain and suffering with leg swelling, recalcitrant ulceration and venous claudication which greatly impairs mobility and quality of life. The prevalence can be high in patients with iliofemoral venous involvement particularly in the setting of a proximal venous stenosis, such as occurs in May Thurner syndrome. Anticoagulation alone does not reduce the likelihood of this outcome. Compression therapy may be effective but garment discomfort limits its implementation. Pharmacomechanical thrombectomy, which combines catheter-directed thrombolysis with mechanical thrombus dissolution, provides an attractive treatment strategy for such patients. The rationale and delivery of pharmacomechanical thrombectomy, including patient selection and adjunctive antithrombotic therapy, will be reviewed in addition to tips and tricks for managing difficult patient scenarios. © 2017 John Wiley & Sons Ltd.

Predictors of Functional Dependence Despite Successful Revascularization in Large-Vessel Occlusion Strokes

PubMed Central

Shi, Zhong-Song; Liebeskind, David S.; Xiang, Bin; Ge, Sijian Grace; Feng, Lei; Albers, Gregory W.; Budzik, Ronald; Devlin, Thomas; Gupta, Rishi; Jansen, Olav; Jovin, Tudor G.; Killer-Oberpfalzer, Monika; Lutsep, Helmi L.; Macho, Juan; Nogueira, Raul G.; Rymer, Marilyn; Smith, Wade S.; Wahlgren, Nils; Duckwiler, Gary R.

2014-01-01

Background and Purpose High revascularization rates in large-vessel occlusion strokes treated by mechanical thrombectomy are not always associated with good clinical outcomes. We evaluated predictors of functional dependence despite successful revascularization among patients with acute ischemic stroke treated with thrombectomy. Methods We analyzed the pooled data from the Multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI), Thrombectomy Revascularization of Large Vessel Occlusions in Acute Ischemic Stroke (TREVO), and TREVO 2 trials. Successful revascularization was defined as thrombolysis in cerebral infarction score 2b or 3. Functional dependence was defined as a score of 3 to 6 on the modified Rankin Scale at 3 months. We assessed relationship of demographic, clinical, angiographic characteristics, and hemorrhage with functional dependence despite successful revascularization. Results Two hundred and twenty-eight patients with successful revascularization had clinical outcome follow-up. The rates of functional dependence with endovascular success were 48.6% for Trevo thrombectomy and 58.0% for Merci thrombectomy. Age (odds ratio, 1.04; 95% confidence interval, 1.02–1.06 per 1-year increase), National Institutes of Health Stroke Scale score (odds ratio, 1.08; 95% confidence interval, 1.02–1.15 per 1-point increase), and symptom onset to endovascular treatment time (odds ratio, 1.11; 95% confidence interval, 1.01–1.22 per 30-minute delay) were predictors of functional dependence despite successful revascularization. Symptom onset to reperfusion time beyond 5 hours was associated with functional dependence. All subjects with symptomatic intracranial hemorrhage had functional dependence. Conclusions One half of patients with successful mechanical thrombectomy do not have good outcomes. Age, severe neurological deficits, and delayed endovascular treatment were associated with functional dependence despite successful revascularization. Our data

Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients - a position paper endorsed by ESMINT and ESNR : part II: methodology of future trials.

PubMed

Fiehler, Jens; Söderman, Michael; Turjman, Francis; White, Philip M; Bakke, Søren Jacob; Mangiafico, Salvatore; von Kummer, Rüdiger; Muto, Mario; Cognard, Christophe; Gralla, Jan

2012-12-01

Based on current data and experience, the joint working group of the European Society of Minimally Invasive Neurological Therapy (ESMINT) and the European Society of Neuroradiology (ESNR) make suggestions on trial design and conduct aimed to investigate therapeutic effects of mechanical thrombectomy (MT). We anticipate that this roadmap will facilitate the setting up and conduct of successful trials in close collaboration with our neighbouring disciplines.

Combination of biochemical and mechanical cues for tendon tissue engineering.

PubMed

Testa, Stefano; Costantini, Marco; Fornetti, Ersilia; Bernardini, Sergio; Trombetta, Marcella; Seliktar, Dror; Cannata, Stefano; Rainer, Alberto; Gargioli, Cesare

2017-11-01

Tendinopathies negatively affect the life quality of millions of people in occupational and athletic settings, as well as the general population. Tendon healing is a slow process, often with insufficient results to restore complete endurance and functionality of the tissue. Tissue engineering, using tendon progenitors, artificial matrices and bioreactors for mechanical stimulation, could be an important approach for treating rips, fraying and tissue rupture. In our work, C3H10T1/2 murine fibroblast cell line was exposed to a combination of stimuli: a biochemical stimulus provided by Transforming Growth Factor Beta (TGF-β) and Ascorbic Acid (AA); a three-dimensional environment represented by PEGylated-Fibrinogen (PEG-Fibrinogen) biomimetic matrix; and a mechanical induction exploiting a custom bioreactor applying uniaxial stretching. In vitro analyses by immunofluorescence and mechanical testing revealed that the proposed combined approach favours the organization of a three-dimensional tissue-like structure promoting a remarkable arrangement of the cells and the neo-extracellular matrix, reflecting into enhanced mechanical strength. The proposed method represents a novel approach for tendon tissue engineering, demonstrating how the combined effect of biochemical and mechanical stimuli ameliorates biological and mechanical properties of the artificial tissue compared to those obtained with single inducement. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Multiconfiguration Molecular Mechanics Based on Combined Quantum Mechanical and Molecular Mechanical Calculations.

PubMed

Lin, Hai; Zhao, Yan; Tishchenko, Oksana; Truhlar, Donald G

2006-09-01

The multiconfiguration molecular mechanics (MCMM) method is a general algorithm for generating potential energy surfaces for chemical reactions by fitting high-level electronic structure data with the help of molecular mechanical (MM) potentials. It was previously developed as an extension of standard MM to reactive systems by inclusion of multidimensional resonance interactions between MM configurations corresponding to specific valence bonding patterns, with the resonance matrix element obtained from quantum mechanical (QM) electronic structure calculations. In particular, the resonance matrix element is obtained by multidimensional interpolation employing a finite number of geometries at which electronic-structure calculations of the energy, gradient, and Hessian are carried out. In this paper, we present a strategy for combining MCMM with hybrid quantum mechanical molecular mechanical (QM/MM) methods. In the new scheme, electronic-structure information for obtaining the resonance integral is obtained by means of hybrid QM/MM calculations instead of fully QM calculations. As such, the new strategy can be applied to the studies of very large reactive systems. The new MCMM scheme is tested for two hydrogen-transfer reactions. Very encouraging convergence is obtained for rate constants including tunneling, suggesting that the new MCMM method, called QM/MM-MCMM, is a very general, stable, and efficient procedure for generating potential energy surfaces for large reactive systems. The results are found to converge well with respect to the number of Hessians. The results are also compared to calculations in which the resonance integral data are obtained by pure QM, and this illustrates the sensitivity of reaction rate calculations to the treatment of the QM-MM border. For the smaller of the two systems, comparison is also made to direct dynamics calculations in which the potential energies are computed quantum mechanically on the fly.

Endovascular Treatment of Ischemic Stroke: An Updated Meta-Analysis of Efficacy and Safety.

PubMed

Vidale, Simone; Agostoni, Elio

2017-05-01

Recent randomized trials demonstrated the superiority of the mechanical thrombectomy over the best medical treatment in patients with acute ischemic stroke due to an occlusion of arteries of proximal anterior circulation. In this updated meta-analysis, we aimed to summarize the total clinical effects of the treatment, including the last trials. We performed literature search of Randomized Crontrolled Trials (RCTs) published between 2010 and October 2016, comparing endovenous thrombolysis plus mechanical thrombectomy (intervention group) with best medical care alone (control group). We identified 8 trials. Primary outcomes were reduced disability at 90 days from the event and symptomatic intracranial hemorrhage. Statistical analysis was performed pooling data into the 2 groups, evaluating outcome heterogeneity. The Mantel-Haenszel method was used to calculate odds ratios (ORs). We analyzed data for 1845 patients (interventional group: 911; control group: 934). Mechanical thrombectomy contributed to a significant reduction in disability rate compared to the best medical treatment alone (OR: 2.087; 95% confidence interval [CI]: 1.718-2.535; P < .001). We calculated that for every 100 treated patients, 16 more participants have a good outcome as a result of mechanical treatment. No significant differences between groups were observed concerning the occurrence of symptomatic hemorrhage (OR: 1.021; 95% CI: 0.641-1.629; P = .739). Mechanical thrombectomy contributes to significantly increase the functional benefit of endovenous thrombolysis in patients with acute ischemic stroke caused by arterial occlusion of proximal anterior circulation, without reduction in safety. These findings are relevant for the optimization of the acute stroke management, including the implementation of networks between stroke centers.

Diagnosing Early Ischemic Changes with the Latest-Generation Flat Detector CT: A Comparative Study with Multidetector CT.

PubMed

Maier, I L; Leyhe, J R; Tsogkas, I; Behme, D; Schregel, K; Knauth, M; Schnieder, M; Liman, J; Psychogios, M-N

2018-05-01

One-stop management of mechanical thrombectomy-eligible patients with large-vessel occlusion represents an innovative approach in acute stroke treatment. This approach reduces door-to-reperfusion times by omitting multidetector CT, using flat detector CT as pre-mechanical thrombectomy imaging. The purpose of this study was to compare the diagnostic performance of the latest-generation flat detector CT with multidetector CT. Prospectively derived data from patients with ischemic stroke with large-vessel occlusion and mechanical thrombectomy were analyzed in this monocentric study. All included patients underwent multidetector CT before referral to our comprehensive stroke center and flat detector CT in the angiography suite before mechanical thrombectomy. Diagnosis of early ischemic signs, quantified by the ASPECTS, was compared between modalities using cross tables, the Pearson correlation, and Bland-Altman plots. The predictive value of multidetector CT- and flat detector CT-derived ASPECTS for functional outcome was investigated using area under the receiver operating characteristic curve analysis. Of 25 patients, 24 (96%) had flat detector CT with sufficient diagnostic quality. Median multidetector CT and flat detector CT ASPECTSs were 7 (interquartile range, 5.5-9 and 4.25-8, respectively) with a mean period of 143.6 ± 49.5 minutes between both modalities. The overall sensitivity was 85.1% and specificity was 83.1% for flat detector CT ASPECTS compared with multidetector CT ASPECTS as the reference technique. Multidetector CT and flat detector CT ASPECTS were strongly correlated ( r = 0.849, P < .001) and moderately predicted functional outcome (area under the receiver operating characteristic curve, 0.738; P = .007 and .715; P = .069, respectively). Determination of ASPECTS on flat detector CT is feasible, showing no significant difference compared with multidetector CT ASPECTS and a similar predictive value for functional outcome. Our findings support the

Treatment protocol based on assessment of clot quality during endovascular thrombectomy for acute ischemic stroke using the Trevo stent retriever

PubMed Central

Ishikawa, Kojiro; Ohshima, Tomotaka; Nishihori, Masahiro; Imai, Tasuku; Goto, Shunsaku; Yamamoto, Taiki; Nishizawa, Toshihisa; Shimato, Shinji; Kato, Kyozo

2016-01-01

ABSTRACT The optional endovascular approach for acute ischemic stroke is unclear. The Trevo stent retriever can be used as first-line treatment for fast mechanical recanalization. The authors developed a treatment protocol for acute ischemic stroke based on the assessment of clot quality during clot removal with the Trevo. This prospective single-center study included all patients admitted for acute ischemic stroke between July 2014 and February 2015, who underwent emergency endovascular treatment. According to the protocol, the Trevo was used for first-line treatment. Immediately after the Trevo was deployed, the stent delivery wire was pushed to open the stent by force (ACAPT technique). Clot quality was assessed on the basis of the perfusion status after deployment of the Trevo; continued occlusion or immediate reopening either reoccluded or maintained after the stent retriever had been in place for 5 min. If there was no obvious clot removal after the first pass with the Trevo, according to the quality of the clot, either a second pass was performed or another endovascular device was selected. Twelve consecutive patients with acute major cerebral artery occlusion were analyzed. Thrombolysis in cerebral infarction score 2b and 3 was achieved in 11 patients (91.7%) and 9 (75%) had a good clinical outcome after 90 days based on a modified Rankin scale score ≤ 2. Symptomatic intracranial hemorrhage occurred in 1 patient (8.3%). The overall mortality rate was 8.3%. Endovascular thrombectomy using the Trevo stent retriever for first-line treatment is feasible and effective. PMID:27578909

Atomistic insight into the catalytic mechanism of glycosyltransferases by combined quantum mechanics/molecular mechanics (QM/MM) methods.

PubMed

Tvaroška, Igor

2015-02-11

Glycosyltransferases catalyze the formation of glycosidic bonds by assisting the transfer of a sugar residue from donors to specific acceptor molecules. Although structural and kinetic data have provided insight into mechanistic strategies employed by these enzymes, molecular modeling studies are essential for the understanding of glycosyltransferase catalyzed reactions at the atomistic level. For such modeling, combined quantum mechanics/molecular mechanics (QM/MM) methods have emerged as crucial. These methods allow the modeling of enzymatic reactions by using quantum mechanical methods for the calculation of the electronic structure of the active site models and treating the remaining enzyme environment by faster molecular mechanics methods. Herein, the application of QM/MM methods to glycosyltransferase catalyzed reactions is reviewed, and the insight from modeling of glycosyl transfer into the mechanisms and transition states structures of both inverting and retaining glycosyltransferases are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

View Combination: A Generalization Mechanism for Visual Recognition

ERIC Educational Resources Information Center

Friedman, Alinda; Waller, David; Thrash, Tyler; Greenauer, Nathan; Hodgson, Eric

2011-01-01

We examined whether view combination mechanisms shown to underlie object and scene recognition can integrate visual information across views that have little or no three-dimensional information at either the object or scene level. In three experiments, people learned four "views" of a two dimensional visual array derived from a three-dimensional…

Unexpected Rupture of a Giant Lobulated Thrombotic Middle Cerebral Artery Aneurysm and Emergency Surgical Treatment With Thrombectomy: A Case Report and Review of the Literature

PubMed Central

Koksal, Vaner; Kayaci, Selim

2016-01-01

Introduction The treatment of giant intracranial aneurysms is one of the most challenging cerebrovascular problems of neurosurgery. We report the rupture of a giant, lobulated, and almost completely thrombosed middle cerebral artery (MCA) aneurysm that is the ninth such report in the literature. We also investigated additional solutions used in the treatment of this patient. Case Presentation A 58-year-old man had been admitted with headache 8 years previously (in 2005), and a giant MCA aneurysm was detected. Two separate endovascular interventions were performed, and both failed. The patient began to live with the giant aneurysm. As there was a large thrombosis filling the aneurysm lumen during the previous endovascular procedures, the aneurysm was not expected to rupture. However, a rupture eventually occurred, in 2013. Even if an aneurysm is very large, lobulated, old, and almost completely thrombosed, it can suddenly bleed. During surgery on this patient, we observed severe cerebral vasospasm caused by a giant thrombosed aneurysmal rupture. Despite the complications, surgery is a life-saving treatment for this emergency when other strategies are not possible. Thrombectomy and clipping are approaches that require a great deal of courage for the neurosurgeon, in terms of entering the risky area within the aneurysm. Conclusions We believe that it would be more appropriate to plan for combined treatment with surgical and endovascular approaches before the emergency condition could occur. PMID:27781115

Thrombus Aspiration in ST-Segment-Elevation Myocardial Infarction: An Individual Patient Meta-Analysis: Thrombectomy Trialists Collaboration.

PubMed

Jolly, Sanjit S; James, Stefan; Džavík, Vladimír; Cairns, John A; Mahmoud, Karim D; Zijlstra, Felix; Yusuf, Salim; Olivecrona, Goran K; Renlund, Henrik; Gao, Peggy; Lagerqvist, Bo; Alazzoni, Ashraf; Kedev, Sasko; Stankovic, Goran; Meeks, Brandi; Frøbert, Ole

2017-01-10

Thrombus aspiration during percutaneous coronary intervention (PCI) for the treatment of ST-segment-elevation myocardial infarction (STEMI) has been widely used; however, recent trials have questioned its value and safety. In this meta-analysis, we, the trial investigators, aimed to pool the individual patient data from these trials to determine the benefits and risks of thrombus aspiration during PCI in patients with ST-segment-elevation myocardial infarction. Included were large (n≥1000), randomized, controlled trials comparing manual thrombectomy and PCI alone in patients with ST-segment-elevation myocardial infarction. Individual patient data were provided by the leadership of each trial. The prespecified primary efficacy outcome was cardiovascular mortality within 30 days, and the primary safety outcome was stroke or transient ischemic attack within 30 days. The 3 eligible randomized trials (TAPAS [Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction], TASTE [Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia], and TOTAL [Trial of Routine Aspiration Thrombectomy With PCI Versus PCI Alone in Patients With STEMI]) enrolled 19 047 patients, of whom 18 306 underwent PCI and were included in the primary analysis. Cardiovascular death at 30 days occurred in 221 of 9155 patients (2.4%) randomized to thrombus aspiration and 262 of 9151 (2.9%) randomized to PCI alone (hazard ratio, 0.84; 95% confidence interval, 0.70-1.01; P=0.06). Stroke or transient ischemic attack occurred in 66 (0.8%) randomized to thrombus aspiration and 46 (0.5%) randomized to PCI alone (odds ratio, 1.43; 95% confidence interval, 0.98-2.10; P=0.06). There were no significant differences in recurrent myocardial infarction, stent thrombosis, heart failure, or target vessel revascularization. In the subgroup with high thrombus burden (TIMI [Thrombolysis in Myocardial Infarction] thrombus grade ≥3), thrombus aspiration was

Combined Pharmacomechanical Thrombolysis of Complete Portomesenteric Thrombosis in a Liver Transplant Recipient

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lorenz, Jonathan M., E-mail: jlorenz@radiology.bsd.uchicago.edu; Bennett, Shelby; Patel, Jay

2013-01-30

Treatment options for portomesenteric venous thrombosis range from anticoagulation to surgery, depending on chronicity, severity of symptoms, extent of thrombosis, and the availability of local expertise. For acute and subacute cases, a variety of endovascular options have been described in limited published series and case reports, including thrombolysis and mechanical thrombectomy. We report what is to our knowledge the first case in which the Trellis pharmacomechanical thrombolysis device was used successfully to treat complete acute thrombosis of the entire superior mesenteric vein and the entire portal vein with extension into all segmental intrahepatic portal branches in a young adult aftermore » liver transplantation. This device, coupled with adjunctive techniques using balloon catheters, facilitated complete restoration of flow, resulting in graft salvage and long-term patency.« less

Resizing procedure for optimum design of structures under combined mechanical and thermal loading

NASA Technical Reports Server (NTRS)

Adelman, H. M.; Narayanaswami, R.

1976-01-01

An algorithm is reported for resizing structures subjected to combined thermal and mechanical loading. The algorithm is applicable to uniaxial stress elements (rods) and membrane biaxial stress members. Thermal Fully Stressed Design (TFSD) is based on the basic difference between mechanical and thermal stresses in their response to resizing. The TFSD technique is found to converge in fewer iterations than ordinary fully stressed design for problems where thermal stresses are comparable to the mechanical stresses. The improved convergence is demonstrated by example with a study of a simplified wing structure, built-up with rods and membranes and subjected to a combination of mechanical loads and a three dimensional temperature distribution.

COMBINE*: An integrated opto-mechanical tool for laser performance modeling

NASA Astrophysics Data System (ADS)

Rehak, M.; Di Nicola, J. M.

2015-02-01

Accurate modeling of thermal, mechanical and optical processes is important for achieving reliable, high-performance high energy lasers such as those at the National Ignition Facility [1] (NIF). The need for this capability is even more critical for high average power, high repetition rate applications. Modeling the effects of stresses and temperature fields on optical properties allows for optimal design of optical components and more generally of the architecture of the laser system itself. Stresses change the indices of refractions and induce inhomogeneities and anisotropy. We present a modern, integrated analysis tool that efficiently produces reliable results that are used in our laser propagation tools such as VBL [5]. COMBINE is built on and supplants the existing legacy tools developed for the previous generations of lasers at LLNL but also uses commercially available mechanical finite element codes ANSYS or COMSOL (including computational fluid dynamics). The COMBINE code computes birefringence and wave front distortions due to mechanical stresses on lenses and slabs of arbitrary geometry. The stresses calculated typically originate from mounting support, vacuum load, gravity, heat absorption and/or attending cooling. Of particular importance are the depolarization and detuning effects of nonlinear crystals due to thermal loading. Results are given in the form of Jones matrices, depolarization maps and wave front distributions. An incremental evaluation of Jones matrices and ray propagation in a 3D mesh with a stress and temperature field is performed. Wavefront and depolarization maps are available at the optical aperture and at slices within the optical element. The suite is validated, user friendly, supported, documented and amenable to collaborative development. * COMBINE stands for Code for Opto-Mechanical Birefringence Integrated Numerical Evaluations.

Percutaneous Aspiration Thrombectomy for the Treatment of Arterial Thromboembolic Occlusions Following Percutaneous Transluminal Angioplasty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schleder, Stephan, E-mail: stephan.schleder@ukr.de; Diekmann, Matthias; Manke, Christoph

2015-02-15

PurposeThis study was designed to evaluate the technical success and the early clinical outcome of patients undergoing percutaneous aspiration thrombectomy (PAT) for the treatment of arterial thromboembolism following percutaneous infrainguinal transluminal angioplasty (PTA).MethodsIn this single-center study, during a period of 7 years retrospectively, 47 patients (22 male, 47 %) with a mean age of 73 (range 53–96) years were identified in whom PAT was performed for the treatment of thromboembolic complications of infrainguinal PTA. Primary technical success was defined as residual stenosis of <50 % in diameter after sole PAT, whereas secondary technical success was defined as residual stenosis of <50 % in diametermore » after PAT and additional PTA and/or stenting. Clinical outcome parameters (e.g., need for further intervention, minor/major amputation) were evaluated for the 30-day postinterventional period.ResultsPrimary technical success was achieved in 64 % of patients (30/47); secondary technical success was obtained in 96 % of patients (45/47). Clinical outcome data were available in 38 patients. In 87 % of patients (33/38), there was no need for further intervention within the 30-day postinterventional period. In three patients, minor amputations were conducted due to preexisting ulcerations (Rutherford Category 5 respectively).ConclusionsPAT enables endovascular treatment of iatrogenic thromboembolic complications after PTA with good technical and early clinical results and minimal morbidity.« less

Mechanical Removal of Migrated Onyx Due to Microcatheter Rupture During AVM Embolization: A Technical Case Report.

PubMed

Senturk, Cagin

2015-12-01

We report a case where migrated Onyx could be removed safely with a mechanical thrombectomy device after withdrawal of the damaged microcatheter. A microcatheter was retained in the superior cerebellar artery with attached Onyx fragments on its tip during embolization of a bled cerebellar AVM. During retrieval maneuvers microcatheter shaft was ruptured and Onyx fragments were released into the vertebrobasilar system causing occlusion. Finally, Onyx fragment on tip of the microcatheter could be detached with dimethyl sulfoxide injection and the microcatheter could be withdrawn. A Merci retriever device (Concentric Medical, Mountain View, CA, USA) was successfully used to retrieve most of the dislodged Onyx material and recanalize the vertebrobasilar circulation.

Combination of Universal Mechanical Testing Machine with Atomic Force Microscope for Materials Research

PubMed Central

Zhong, Jian; He, Dannong

2015-01-01

Surface deformation and fracture processes of materials under external force are important for understanding and developing materials. Here, a combined horizontal universal mechanical testing machine (HUMTM)-atomic force microscope (AFM) system is developed by modifying UMTM to combine with AFM and designing a height-adjustable stabilizing apparatus. Then the combined HUMTM-AFM system is evaluated. Finally, as initial demonstrations, it is applied to analyze the relationship among macroscopic mechanical properties, surface nanomorphological changes under external force, and fracture processes of two kinds of representative large scale thin film materials: polymer material with high strain rate (Parafilm) and metal material with low strain rate (aluminum foil). All the results demonstrate the combined HUMTM-AFM system overcomes several disadvantages of current AFM-combined tensile/compression devices including small load force, incapability for large scale specimens, disability for materials with high strain rate, and etc. Therefore, the combined HUMTM-AFM system is a promising tool for materials research in the future. PMID:26265357

Combination of Universal Mechanical Testing Machine with Atomic Force Microscope for Materials Research.

PubMed

Zhong, Jian; He, Dannong

2015-08-12

Surface deformation and fracture processes of materials under external force are important for understanding and developing materials. Here, a combined horizontal universal mechanical testing machine (HUMTM)-atomic force microscope (AFM) system is developed by modifying UMTM to combine with AFM and designing a height-adjustable stabilizing apparatus. Then the combined HUMTM-AFM system is evaluated. Finally, as initial demonstrations, it is applied to analyze the relationship among macroscopic mechanical properties, surface nanomorphological changes under external force, and fracture processes of two kinds of representative large scale thin film materials: polymer material with high strain rate (Parafilm) and metal material with low strain rate (aluminum foil). All the results demonstrate the combined HUMTM-AFM system overcomes several disadvantages of current AFM-combined tensile/compression devices including small load force, incapability for large scale specimens, disability for materials with high strain rate, and etc. Therefore, the combined HUMTM-AFM system is a promising tool for materials research in the future.

The effect of combined mechanism ankle support on postural control of patients with chronic ankle instability.

PubMed

Hadadi, Mohammad; Ebrahimi, Ismaeil; Mousavi, Mohammad Ebrahim; Aminian, Gholamreza; Esteki, Ali; Rahgozar, Mehdi

2017-02-01

Chronic ankle instability is associated with neuromechanical changes and poor postural stability. Despite variety of mechanisms of foot and ankle orthoses, almost none apply comprehensive mechanisms to improve postural control in all subgroups of chronic ankle instability patients. The purpose of this study was to investigate the effect of an ankle support implementing combined mechanisms to improve postural control in chronic ankle instability patients. Cross-sectional study. An ankle support with combined mechanism was designed based on most effective action mechanisms of foot and ankle orthoses. The effect of this orthosis on postural control was evaluated in 20 participants with chronic ankle instability and 20 matched healthy participants. The single-limb stance balance test was measured in both groups with and without the new orthosis using a force platform. The results showed that application of combined mechanism ankle support significantly improved all postural sway parameters in chronic ankle instability patients. There were no differences in means of investigated parameters with and without the orthosis in the healthy group. No statistically significant differences were found in postural sway between chronic ankle instability patients and healthy participants after applying the combined mechanism ankle support. The combined mechanism ankle support is effective in improving static postural control of chronic ankle instability patients to close to the postural sway of healthy individual. the orthosis had no adverse effects on balance performance of healthy individuals. Clinical relevance Application of the combined mechanism ankle support for patients with chronic ankle instability is effective in improving static balance. This may be helpful in reduction of recurrence of ankle sprain although further research about dynamic conditions is needed.

Effects of combined mechanical stimulation on the proliferation and differentiation of pre-osteoblasts

PubMed Central

Kang, Kyung Shin; Lee, Seung-Jae; Lee, Haksue; Moon, Wonkyu

2011-01-01

We observed how combined mechanical stimuli affect the proliferation and differentiation of pre-osteoblasts. For this research, a bioreactor system was developed that can simultaneously stimulate cells with cyclic strain and ultrasound, each of which is known to effectively stimulate bone tissue regeneration. MC3T3-E1 pre-osteoblasts were chosen for bone tissue engineering due to their osteoblast-like characteristics. 3-D scaffolds were fabricated with polycaprolactone and poly-L-lactic acid using the salt leaching method. The cells were stimulated by the bioreactor with cyclic strain and ultrasound. The bioreactor was set at a frequency of 1.0 Hz and 10% strain for cyclic strain and 1.0 MHz and 30 mW/cm2 for ultrasound. Three experimental groups (ultrasound, cyclic strain, and combined stimulation) and a control group were examined. Each group was stimulated for 20 min/day. Mechanical stimuli did not affect MC3T3-E1 cell proliferation significantly up to 10 days when measured with the cell counting kit-8. However, gene expression analysis of collagen type-I, osteocalcin, RUNX2, and osterix revealed that the combined mechanical stimulation accelerated the matrix maturation of MC3T3-E1 cells. These results indicate that the combined mechanical stimulation can enhance the differentiation of pre-osteoblasts more efficiently than simple stimuli, in spite of no effect on cell proliferation. PMID:21532314

Rheolytic thrombectomy in the management of limb ischemia: 30-day results from a multicenter registry.

PubMed

Ansel, Gary M; George, Barry S; Botti, Charles F; McNamara, Thomas O; Jenkins, J Stephen; Ramee, Steven R; Rosenfield, Kenneth; Noethen, Alice A; Mehta, Tejas

2002-08-01

To evaluate the use of rheolytic thrombectomy (RT) with the AngioJet catheter for treatment of lower extremity ischemia due to arterial/graft thrombotic occlusion. A retrospective multicenter review was performed of 99 consecutive patients (52 men; mean age 67 +/- 13 years, range 30-90) who underwent RT for thrombotic occlusions in native arteries (n=80) or bypass grafts (n=19). Pre- and postprocedural limb ischemia and in-hospital events were evaluated. Amputation and mortality rates at 30 days were determined. The majority of patients (78.8%) presented within 14 days of symptom onset. RT resulted in substantial to complete thrombus removal in 70 (70.7%) patients and partial in 22 (22.2%); there was no angiographic change in 7 (7.1%). Adjunctive post RT thrombolysis was used in 37 patients. Underlying stenoses found in 81 limbs were treated with one or more of the following procedures: balloon angioplasty (n=62), stenting (n=35), or nonemergent surgical revision (n=5). In-hospital complications included 2 major amputations, 5 cases of minor tissue loss, 7 rethromboses, and 3 cases of transient renal insufficiency. Four (4.0% patients died in-hospital; the 95 surviving patients all had viable limbs at discharge. Mortality and amputation rates at 30 days were 7.1% and 4.0%, respectively. Percutaneous treatment of thrombotic occlusions with RT, followed by definitive treatment of the underlying stenosis, is a promising therapeutic option for patients with limb-threatening ischemia.

Multiple Coaxial Catheter System for Reliable Access in Interventional Stroke Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kulcsar, Zsolt, E-mail: kulcsarzsolt22@gmail.com; Yilmaz, Hasan; Bonvin, Christophe

2010-12-15

In some patients with acute cerebral vessel occlusion, navigating mechanical thrombectomy systems is difficult due to tortuous anatomy of the aortic arch, carotid arteries, or vertebral arteries. Our purpose was to describe a multiple coaxial catheter system used for mechanical revascularization that helps navigation and manipulations in tortuous vessels. A triple or quadruple coaxial catheter system was built in 28 consecutive cases presenting with acute ischemic stroke. All cases were treated by mechanical thrombectomy with the Penumbra System. In cases of unsuccessful thrombo-aspiration, additional thrombolysis or angioplasty with stent placement was used for improving recanalization. The catheter system consisted ofmore » an outermost 8-Fr and an intermediate 6-Fr guiding catheter, containing the inner Penumbra reperfusion catheters. The largest, 4.1-Fr, reperfusion catheter was navigated over a Prowler Select Plus microcatheter. The catheter system provided access to reach the cerebral lesions and provided stability for the mechanically demanding manipulations of thromboaspiration and stent navigation in all cases. Apart from their mechanical role, the specific parts of the system could also provide access to different types of interventions, like carotid stenting through the 8-Fr guiding catheter and intracranial stenting and thrombolysis through the Prowler Select Plus microcatheter. In this series, there were no complications related to the catheter system. In conclusion, building up a triple or quadruple coaxial system proved to be safe and efficient in our experience for the mechanical thrombectomy treatment of acute ischemic stroke.« less

Quantitative Evaluation of Performance in Interventional Neuroradiology: An Integrated Curriculum Featuring Theoretical and Practical Challenges.

PubMed

Ernst, Marielle; Kriston, Levente; Romero, Javier M; Frölich, Andreas M; Jansen, Olav; Fiehler, Jens; Buhk, Jan-Hendrik

2016-01-01

We sought to develop a standardized curriculum capable of assessing key competencies in Interventional Neuroradiology by the use of models and simulators in an objective, quantitative, and efficient way. In this evaluation we analyzed the associations between the practical experience, theoretical knowledge, and the skills lab performance of interventionalists. We evaluated the endovascular skills of 26 participants of the Advanced Course in Endovascular Interventional Neuroradiology of the European Society of Neuroradiology with a set of three tasks (aneurysm coiling and thrombectomy in a virtual simulator and placement of an intra-aneurysmal flow disruptor in a flow model). Practical experience was assessed by a survey. Participants completed a written and oral examination to evaluate theoretical knowledge. Bivariate and multivariate analyses were performed. In multivariate analysis knowledge of materials and techniques in Interventional Neuroradiology was moderately associated with skills in aneurysm coiling and thrombectomy. Experience in mechanical thrombectomy was moderately associated with thrombectomy skills, while age was negatively associated with thrombectomy skills. We found no significant association between age, sex, or work experience and skills in aneurysm coiling. Our study gives an example of how an integrated curriculum for reasonable and cost-effective assessment of key competences of an interventional neuroradiologist could look. In addition to traditional assessment of theoretical knowledge practical skills are measured by the use of endovascular simulators yielding objective, quantitative, and constructive data for the evaluation of the current performance status of participants as well as the evolution of their technical competency over time.

Relationship between Different Combinations of Personality Traits and Motivation Mechanism: Change Leadership as Mediator

ERIC Educational Resources Information Center

Chen, Kun-Dang

2017-01-01

The aim of this study is to identify combinations of different personality traits among teaching faculty and explore for which combinations college managers should use change leadership to mediate their cognition in a motivation mechanism and for which combinations doing so is not necessary. In this study, two-stage cluster analysis and partial…

Agreement between core laboratory and study investigators for imaging scores in a thrombectomy trial.

PubMed

Fahed, Robert; Ben Maacha, Malek; Ducroux, Célina; Khoury, Naim; Blanc, Raphaël; Piotin, Michel; Lapergue, Bertrand

2018-05-14

We aimed to assess the agreement between study investigators and the core laboratory (core lab) of a thrombectomy trial for imaging scores. The Alberta Stroke Program Early CT Score (ASPECTS), the European Collaborative Acute Stroke Study (ECASS) hemorrhagic transformation (HT) classification, and the Thrombolysis In Cerebral Infarction (TICI) scores as recorded by study investigators were compared with the core lab scores in order to assess interrater agreement, using Cohen's unweighted and weighted kappa statistics. There were frequent discrepancies between study sites and core lab for all the scores. Agreement for ASPECTS and ECASS HT classification was less than substantial, with disagreement occurring in more than one-third of cases. Agreement was higher on MRI-based scores than on CT, and was improved after dichotomization on both CT and MRI. Agreement for TICI scores was moderate (with disagreement occurring in more than 25% of patients), and went above the substantial level (less than 10% disagreement) after dichotomization (TICI 0/1/2a vs 2b/3). Discrepancies between scores assessed by the imaging core lab and those reported by study sites occurred in a significant proportion of patients. Disagreement in the assessment of ASPECTS and day 1 HT scores was more frequent on CT than on MRI. The agreement for the dichotomized TICI score (the trial's primary outcome) was substantial, with less than 10% of disagreement between study sites and core lab. NCT02523261, Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparison of the efficacy and safety of thrombectomy devices in acute stroke : a network meta-analysis of randomized trials.

PubMed

Saber, Hamidreza; Rajah, Gary B; Kherallah, Riyad Y; Jadhav, Ashutosh P; Narayanan, Sandra

2017-12-15

Mechanical thrombectomy (MT) is increasingly used for large-vessel occlusions (LVO), but randomized clinical trial (RCT) level data with regard to differences in clinical outcomes of MT devices are limited. We conducted a network meta-analysis (NMA) that enables comparison of modern MT devices (Trevo, Solitaire, Aspiration) and strategies (stent retriever vs aspiration) across trials. Relevant RCTs were identified by a systematic review. The efficacy outcome was 90-day functional independence (modified Rankin Scale (mRS) score 0-2). Safety outcomes were 90-day catastrophic outcome (mRS 5-6) and symptomatic intracranial hemorrhage (sICH). Fixed-effect Bayesian NMA was performed to calculate risk estimates and the rank probabilities. In a NMA of six relevant RCTs (SWIFT, TREVO2, EXTEND-IA, SWIFT-PRIME, REVASCAT, THERAPY; total of 871 patients, 472 Solitaire vs medical-only, 108 Aspiration vs medical-only, 178 Trevo vs Merci, and 113 Solitaire vs Merci) with medical-only arm as the reference, Trevo had the greatest functional independence (OR 4.14, 95% credible interval (CrI) 1.41-11.80; top rank probability 92%) followed by Solitaire (OR 2.55, 95% CrI 1.75-3.74; top rank probability 72%). Solitaire and Aspiration devices had the greatest top rank probability with respect to low sICH and catastrophic outcomes (76% and 91%, respectively), but without significant differences between each other. In a separate network of seven RCTs (MR-CLEAN, ESCAPE, EXTEND-IA, SWIFT-PRIME, REVASCAT, THERAPY, ASTER; 1737 patients), first-line stent retriever was associated with a higher top rank probability of functional independence than aspiration (95% vs 54%), with comparable safety outcomes. These findings suggest that Trevo and Solitaire devices are associated with a greater likelihood of functional independence whereas Solitaire and Aspiration devices appear to be safer. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights

A numerical study of combined use of two biocontrol agents with different biocontrol mechanisms in controlling foliar pathogens.

PubMed

Xu, X-M; Jeffries, P; Pautasso, M; Jeger, M J

2011-09-01

Effective use of biocontrol agents is an important component of sustainable agriculture. A previous numerical study of a generic model showed that biocontrol efficacy was greatest for a single biocontrol agent (BCA) combining competition with mycoparasitism or antibiosis. This study uses the same mathematical model to investigate whether the biocontrol efficacy of combined use of two BCAs with different biocontrol mechanisms is greater than that of a single BCA with either or both of the two mechanisms, assuming that two BCAs occupy the same host tissue as the pathogen. Within the parameter values considered, a BCA with two biocontrol mechanisms always outperformed the combined use of two BCAs with a single but different biocontrol mechanism. Similarly, combined use of two BCAs with a single but different biocontrol mechanism is shown to be far less effective than that of a single BCA with both mechanisms. Disease suppression from combined use of two BCAs was very similar to that achieved by the more efficacious one. As expected, a higher BCA introduction rate led to increased disease suppression. Incorporation of interactions between two BCAs did not greatly affect the disease dynamics except when a mycoparasitic and, to a lesser extent, an antibiotic-producing BCA was involved. Increasing the competitiveness of a mycoparasitic BCA over a BCA whose biocontrol mechanism is either competition or antibiosis may lead to improved biocontrol initially and reduced fluctuations in disease dynamics. The present study suggests that, under the model assumptions, combined use of two BCAs with different biocontrol mechanisms in most cases only results in control efficacies similar to using the more efficacious one alone. These predictions are consistent with published experimental results, suggesting that combined use of BCAs should not be recommended without clear understanding of their main biocontrol mechanisms and relative competitiveness, and experimental evaluation.

A Hybrid Approach to Composite Damage and Failure Analysis Combining Synergistic Damage Mechanics and Peridynamics

DTIC Science & Technology

2017-03-30

Composite Damage and Failure Analysis Combining Synergistic Damage Mechanics and Peridynamics 5b. GRANT NUMBER NOOO 14-16-1-21 73 5c. PROGRAM...ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Texas A&M Engineering Experiment Station (TEES) 400 Harvey Mitchell Parkway, Suite 300 M160 1473 I...Failure Analysis Combining Synergistic Damage Mechanics and Peridynamics Award Number N00014-16-1-2173 DOD-NAVY- Office of Naval Research PI: Ramesh

Synaptic Scaling in Combination with Many Generic Plasticity Mechanisms Stabilizes Circuit Connectivity

PubMed Central

Tetzlaff, Christian; Kolodziejski, Christoph; Timme, Marc; Wörgötter, Florentin

2011-01-01

Synaptic scaling is a slow process that modifies synapses, keeping the firing rate of neural circuits in specific regimes. Together with other processes, such as conventional synaptic plasticity in the form of long term depression and potentiation, synaptic scaling changes the synaptic patterns in a network, ensuring diverse, functionally relevant, stable, and input-dependent connectivity. How synaptic patterns are generated and stabilized, however, is largely unknown. Here we formally describe and analyze synaptic scaling based on results from experimental studies and demonstrate that the combination of different conventional plasticity mechanisms and synaptic scaling provides a powerful general framework for regulating network connectivity. In addition, we design several simple models that reproduce experimentally observed synaptic distributions as well as the observed synaptic modifications during sustained activity changes. These models predict that the combination of plasticity with scaling generates globally stable, input-controlled synaptic patterns, also in recurrent networks. Thus, in combination with other forms of plasticity, synaptic scaling can robustly yield neuronal circuits with high synaptic diversity, which potentially enables robust dynamic storage of complex activation patterns. This mechanism is even more pronounced when considering networks with a realistic degree of inhibition. Synaptic scaling combined with plasticity could thus be the basis for learning structured behavior even in initially random networks. PMID:22203799

Quantitative Evaluation of Performance in Interventional Neuroradiology: An Integrated Curriculum Featuring Theoretical and Practical Challenges

PubMed Central

Ernst, Marielle; Kriston, Levente; Romero, Javier M.; Frölich, Andreas M.; Jansen, Olav; Fiehler, Jens; Buhk, Jan-Hendrik

2016-01-01

Purpose We sought to develop a standardized curriculum capable of assessing key competencies in Interventional Neuroradiology by the use of models and simulators in an objective, quantitative, and efficient way. In this evaluation we analyzed the associations between the practical experience, theoretical knowledge, and the skills lab performance of interventionalists. Materials and Methods We evaluated the endovascular skills of 26 participants of the Advanced Course in Endovascular Interventional Neuroradiology of the European Society of Neuroradiology with a set of three tasks (aneurysm coiling and thrombectomy in a virtual simulator and placement of an intra-aneurysmal flow disruptor in a flow model). Practical experience was assessed by a survey. Participants completed a written and oral examination to evaluate theoretical knowledge. Bivariate and multivariate analyses were performed. Results In multivariate analysis knowledge of materials and techniques in Interventional Neuroradiology was moderately associated with skills in aneurysm coiling and thrombectomy. Experience in mechanical thrombectomy was moderately associated with thrombectomy skills, while age was negatively associated with thrombectomy skills. We found no significant association between age, sex, or work experience and skills in aneurysm coiling. Conclusion Our study gives an example of how an integrated curriculum for reasonable and cost-effective assessment of key competences of an interventional neuroradiologist could look. In addition to traditional assessment of theoretical knowledge practical skills are measured by the use of endovascular simulators yielding objective, quantitative, and constructive data for the evaluation of the current performance status of participants as well as the evolution of their technical competency over time. PMID:26848840

Combination therapy including serratiopeptidase improves outcomes of mechanical-antibiotic treatment of periimplantitis.

PubMed

Sannino, G; Gigola, P; Puttini, M; Pera, F; Passariello, C

2013-01-01

This study was designed as a retrospective analysis of clinical outcomes of cases of periimplantitis treated by mechanical debridement and the administration of antibiotics combined or not with the administration of either the proteolytic enzyme serratiopeptidase (SPEP) or non-steroidal anti-inflammatory drugs (NSAIDs). Clinical charts of 544 partially edentulous patients treated for periimplantitis between June 1996 and December 2010 were analyzed to obtain clinical data of the affected implants just before the beginning of treatment and 12 months later to evaluate the outcomes of combined mechanical antibiotic treatment alone or in combination with the co-administration of the anti-inflammatory SPEP or NSAIDs. The comparative analysis revealed that therapeutic outcomes were significantly different in the three groups. Failure rate in the group that received SPEP (6 percent) was significantly lower compared to the group that received NSAIDS (16.9 percent; P less than 0.01) and to the group that received no anti-inflammatory therapy (18.9 percent; P less than 0.01). Treatment including SPEP was associated with significantly better healing also when successful treatments alone were considered. The data reported in this paper strongly support the hypothesis that SPEP is a valid addition to protocols for the combined therapy of peri-implantitis. In fact, it allows to enhance success rates significantly and also favors better tissue repair around successfully treated implants as compared to other regimens.

Quantum Mechanics/Molecular Mechanics Method Combined with Hybrid All-Atom and Coarse-Grained Model: Theory and Application on Redox Potential Calculations.

PubMed

Shen, Lin; Yang, Weitao

2016-04-12

We developed a new multiresolution method that spans three levels of resolution with quantum mechanical, atomistic molecular mechanical, and coarse-grained models. The resolution-adapted all-atom and coarse-grained water model, in which an all-atom structural description of the entire system is maintained during the simulations, is combined with the ab initio quantum mechanics and molecular mechanics method. We apply this model to calculate the redox potentials of the aqueous ruthenium and iron complexes by using the fractional number of electrons approach and thermodynamic integration simulations. The redox potentials are recovered in excellent accordance with the experimental data. The speed-up of the hybrid all-atom and coarse-grained water model renders it computationally more attractive. The accuracy depends on the hybrid all-atom and coarse-grained water model used in the combined quantum mechanical and molecular mechanical method. We have used another multiresolution model, in which an atomic-level layer of water molecules around redox center is solvated in supramolecular coarse-grained waters for the redox potential calculations. Compared with the experimental data, this alternative multilayer model leads to less accurate results when used with the coarse-grained polarizable MARTINI water or big multipole water model for the coarse-grained layer.

Efficacy and Safety of REVIVE SE Thrombectomy Device for Acute Ischemic Stroke: River JAPAN (Reperfuse Ischemic Vessels with Endovascular Recanalization Device in Japan).

PubMed

Sakai, Nobuyuki; Ota, Shinzo; Matsumoto, Yasushi; Kondo, Rei; Satow, Tetsu; Kubo, Michiya; Tsumoto, Tomoyuki; Enomoto, Yukiko; Kataoka, Taketo; Imamura, Hirotoshi; Todo, Kenichi; Hayakawa, Mikito; Yamagami, Hiroshi; Toyoda, Kazunori; Ito, Yasushi; Sugiu, Kenji; Matsumaru, Yuji; Yoshimura, Shinichi

2018-04-15

REVIVE SE (REVIVE) is a closed-ended, self-expanding stent retriever used in the RIVER JAPAN study. We present our early experience with REVIVE for revascularization of acute ischemic stroke (AIS) in patients who have failed or are ineligible for intravenous recombinant tissue plasminogen activator treatment. This prospective, single-arm, non-randomized, multicenter registry study followed up patients undergoing mechanical thrombectomy with REVIVE for 90 days. The primary endpoint was a post-procedure Thrombolysis in Cerebral Infarction (TICI) score ≥2a. Secondary endpoints were clot migration/embolization; recanalization without symptomatic intracranial hemorrhage (ICH) at 24 h; symptomatic ICH; good neurological outcome (modified Rankin Scale score ≤2 National Institute of Health Stroke Scale (NIHSS) score decrease ≥10) at day 90; device- or procedure-related serious adverse events (SAEs) and mortality at day 90. To confirm non-inferiority of REVIVE, results were compared with historical data of the Merci Retriever. About 49 patients were enrolled (median age 73 years; males 46.9%; middle cerebral artery (MCA) occlusion 83.7%; median NIHSS score 17). A post-procedure TICI score ≥2a was observed in 73.5% (36/49, 95% confidence interval [CI] 58.9-85.1) of patients. No post-procedural clot migration/embolization events occurred. Successful recanalization without symptomatic ICH was observed in 62.5% (30/48, 95% CI 47.4-76.0). The good neurological outcome was achieved in 66.7% (32/48) patients. Symptomatic ICH and device- or procedure-related SAEs were reported in 6.3% and 12.2% of patients, respectively. Two deaths were reported. REVIVE demonstrated equivalent efficacy and safety as the Merci Retriever. Results suggest that REVIVE is effective and safe in recanalizing occluded intracranial arteries in AIS.

Efficacy and Safety of REVIVE SE Thrombectomy Device for Acute Ischemic Stroke: River JAPAN (Reperfuse Ischemic Vessels with Endovascular Recanalization Device in Japan)

PubMed Central

SAKAI, Nobuyuki; OTA, Shinzo; MATSUMOTO, Yasushi; KONDO, Rei; SATOW, Tetsu; KUBO, Michiya; TSUMOTO, Tomoyuki; ENOMOTO, Yukiko; KATAOKA, Taketo; IMAMURA, Hirotoshi; TODO, Kenichi; HAYAKAWA, Mikito; YAMAGAMI, Hiroshi; TOYODA, Kazunori; ITO, Yasushi; SUGIU, Kenji; MATSUMARU, Yuji; YOSHIMURA, Shinichi

2018-01-01

REVIVE SE (REVIVE) is a closed-ended, self-expanding stent retriever used in the RIVER JAPAN study. We present our early experience with REVIVE for revascularization of acute ischemic stroke (AIS) in patients who have failed or are ineligible for intravenous recombinant tissue plasminogen activator treatment. This prospective, single-arm, non-randomized, multicenter registry study followed up patients undergoing mechanical thrombectomy with REVIVE for 90 days. The primary endpoint was a post-procedure Thrombolysis in Cerebral Infarction (TICI) score ≥2a. Secondary endpoints were clot migration/embolization; recanalization without symptomatic intracranial hemorrhage (ICH) at 24 h; symptomatic ICH; good neurological outcome (modified Rankin Scale score ≤2 National Institute of Health Stroke Scale (NIHSS) score decrease ≥10) at day 90; device- or procedure-related serious adverse events (SAEs) and mortality at day 90. To confirm non-inferiority of REVIVE, results were compared with historical data of the Merci Retriever. About 49 patients were enrolled (median age 73 years; males 46.9%; middle cerebral artery (MCA) occlusion 83.7%; median NIHSS score 17). A post-procedure TICI score ≥2a was observed in 73.5% (36/49, 95% confidence interval [CI] 58.9–85.1) of patients. No post-procedural clot migration/embolization events occurred. Successful recanalization without symptomatic ICH was observed in 62.5% (30/48, 95% CI 47.4–76.0). The good neurological outcome was achieved in 66.7% (32/48) patients. Symptomatic ICH and device- or procedure-related SAEs were reported in 6.3% and 12.2% of patients, respectively. Two deaths were reported. REVIVE demonstrated equivalent efficacy and safety as the Merci Retriever. Results suggest that REVIVE is effective and safe in recanalizing occluded intracranial arteries in AIS. PMID:29526881

Fibrinolysis and Beyond: Bridging the Gap between Local and Systemic Clot Removal

PubMed Central

Knauer, K.; Huber, Roman

2011-01-01

Recanalization methods in ischemic stroke have been progressively expanded over the past years. In addition the continuous development of specialized mechanical devices for thrombectomy a broad spectrum of new drugs has been tested: Both options, novel drugs as well as new devices, can be employed independently of each other, but in most cases a combination of the two with the standard treatment of intravenous fibrinolysis is applied. Until recently, a large number of case series have been performed to investigate the effects of various drugs and interventions, but only a few trials have been conducted to determine the optimal conditions for combining both procedures. This review surveys the different systemic and endovascular vessel reopening practices and their major bridging techniques. PMID:21373206

An ischemic stroke patient with free floating thrombus in carotid artery, successfully treated by open carotid thrombectomy: a first case report in Nepal.

PubMed

Shrestha, Prabin; Adhikari, Rupendra; Tamrakar, Samantha; Pant, Basanta; Koirala, Bhagwan; Yamaguchi, Satoshi; Kurisu, Kaoru

2012-12-01

Free floating thrombus in the carotid artery is a well-known phenomenon, though relatively rare. We present a case in which we performed open surgery and achieved successful retrieval of the thrombus. A 40 year-old male patient presented with ischemic stroke and mild left hemiparesis. Computerized tomography and magnetic resonance imaging showed infarction in the right parieto-occipital area. Carotid Doppler study showed carotid stenosis on the right side. Further investigation with CT angiography of the neck vessels confirmed significant carotid artery occlusion with a free-floating thrombus in the internal carotid artery. Carotid endarterectomy was planned under EEG monitoring. The right carotid artery was exposed with a vertical incision along the medial margin of the sternocleido-mastoid muscle. The carotid artery was opened and, as expected, showed a soft, mobile thrombus. Thus thrombectomy was planned. A 2 Fr fogarty catheter was introduced distal to the thrombus, the balloon was inflated and pulled back gently, which removed the thrombus completely. There was no postoperative complication and the patient is fine at 1 year follow-up.

A novel route of revascularization in basilar artery occlusion and review of the literature

PubMed Central

Morales, Alejandro; Parry, Phillip Vaughan; Jadhav, Ashutosh; Jovin, Tudor

2015-01-01

Ischemia of the basilar artery is one of the most devastating types of arterial occlusive disease. Despite treatment of basilar artery occlusions (BAO) with intravenous tissue plasminogen activator, antiplatelet agents, intra-arterial therapy or a combination, fatality rates remain high. Aggressive recanalization with mechanical thrombectomy is therefore often necessary to preserve life. When direct access to the basilar trunk is not possible, exploration of chronically occluded vessels through collaterals with angioplasty and stenting creates access for manual aspiration. We describe the first report of retrograde vertebral artery (VA) revascularization using thyrocervical collaterals for anterograde mechanical aspiration of a BAO followed by stenting of the chronically occluded VA origin. Our novel retrograde–anterograde approach resulted in resolution of the patient's clinical stroke syndrome. PMID:26055597

Recanalization of Acute and Subacute Venous and Synthetic Bypass-Graft Occlusions With a Mechanical Rotational Catheter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wissgott, Christian, E-mail: cwissgott@wkk-hei.de; Kamusella, Peter; Andresen, Reimer

2013-08-01

PurposePercutaneous mechanical thrombectomy (PMT) is now established as an alternative treatment of acute arterial occlusions in addition to fibrinolysis and surgical thrombectomy. The objective of this retrospective study was the investigation of a rotational atherothrombectomy catheter in terms of safety and efficacy in the treatment of acute and subacute femoropopliteal bypass occlusions.Materials and MethodsForty-two patients (average age 65.8 {+-} 9.1 years) with acute (<14 days [n = 31]) and subacute (14-42 days [n = 11]) femoropopliteal bypass occlusions were treated consecutively with a rotational debulking and removal catheter (Straub Rotarex). The average occlusion length was 28.4 {+-} 2.9 (24-34) cm.more » Thirty-four (81 %) patients underwent venous bypass, and 8 (19 %) patients underwent polytetrafluoroethylene bypass.ResultsThe technical success rate was 97.6 % (41 of 42). In 1 patient, blood flow could not be restored despite the use of the atherothrombectomy system. The average catheter intervention time was 6.9 {+-} 2.1 (4-9) min. Ankle-brachial index increased from 0.39 {+-} 0.13 to 0.83 {+-} 0.11 at discharge and to 0.82 {+-} 0.17 after 1 month (p < 0.05). There were a total of 2 (4.8 %) peri-interventional complications: One patient developed a distal embolism, which was successfully treated with local lysis, and another patient had a small perforation at the distal anastomosis, which was successfully treated with a stent.ConclusionPMT with the Rotarex atherothrombectomy catheter represents a safe and effective option in the treatment of acute and subacute femoropopliteal bypass occlusions because it can quickly restore blood flow.« less

Deficient Binocular Combination Reveals Mechanisms of Anisometropic Amblyopia: Signal Attenuation and Interocular Inhibition

PubMed Central

Huang, Chang-Bing; Zhou, Jiawei; Lu, Zhong-Lin; Zhou, Yifeng

2012-01-01

Amblyopia is a developmental disorder that results in deficits of monocular and binocular vision. It's presently unclear whether these deficits result from attenuation of signals in the amblyopic eye, inhibition by signals in the fellow eye, or both. In this study, we characterize the mechanisms underlying anisometropic amblyopia using a binocular phase and contrast combination paradigm and a contrast-gain control model. Subjects dichoptically viewed two slightly different images and reported the perceived contrast and phase of the resulting cyclopean percept. We found that the properties of binocular combination were abnormal in many aspects, which is explained by a combination of (1) attenuated monocular signal in the amblyopic eye, (2) stronger interocular contrast-gain control from the fellow eye to the signal in amblyopic eye (direct interocular inhibition), and (3) stronger interocular contrast-gain control from the fellow eye to the contrast gain control signal from the amblyopic eye (indirect interocular inhibition). We conclude that anisometropic amblyopia led to both monocular and interocular deficits. A complete understanding of the mechanisms underlying amblyopia requires studies of both monocular deficits and binocular interactions. PMID:21546609

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minko, P., E-mail: peterminko@yahoo.com; Bücker, A.; Laschke, M.

PurposeTo investigate the efficacy and safety of mechanical thrombectomy for iliac vein thrombosis using Rotarex and Aspirex catheters in a pig model.Materials and MethodsIliac vein thrombosis was induced in six pigs by means of an occlusion-balloon catheter and thrombin injection. The presence of thrombi was verified by digital subtraction angiography (DSA) and computed tomography (CT). Thrombectomy was performed using 6F and 8F Rotarex and 6F, 8F, and 10F Aspirex catheters (Straub Medical AG, Wangs, Switzerland). After intervention, DSA and CT were repeated to evaluate the efficacy of mechanical thrombectomy and to exclude local complications. In addition, pulmonary CT was performedmore » to rule out pulmonary embolism. Finally, all pigs were killed, and iliac veins were dissected to perform macroscopic and histological examination.ResultsThrombus induction was successfully achieved in all animals as verified by DSA and CT. Subsequent thrombectomy lead to incomplete recanalization of the iliac veins with residual thrombi in all cases. However, the use of the 6F and 8F Rotarex catheters caused vessel perforation and retroperitoneal hemorrhage in all cases. Application of the Aspirex device caused one small transmural perforation in a vessel treated with a 10F Aspirex catheter, and this was only seen microscopically. Pulmonary embolism was detected in one animal treated with the Rotarex catheters, whereas no pulmonary emboli were seen in animals treated with the Aspirex catheters.ConclusionThe Aspirex catheter allowed subtotal and safe recanalization of iliac vein thrombosis. In contrast, the use of the Rotarex catheter caused macroscopically obvious vessel perforations in all cases.« less

Isobolographic analysis of the mechanisms of action of anticonvulsants from a combination effect.

PubMed

Matsumura, Nobuko; Nakaki, Toshio

2014-10-15

The nature of the pharmacodynamic interactions of drugs is influenced by the drugs׳ mechanisms of action. It has been hypothesized that drugs with different mechanisms are likely to interact synergistically, whereas those with similar mechanisms seem to produce additive interactions. In this review, we describe an extensive investigation of the published literature on drug combinations of anticonvulsants, the nature of the interaction of which has been evaluated by type I and II isobolographic analyses and the subthreshold method. The molecular targets of antiepileptic drugs (AEDs) include Na(+) and Ca(2+) channels, GABA type-A receptor, and glutamate receptors such as NMDA and AMPA/kainate receptors. The results of this review indicate that the nature of interactions evaluated by type I isobolographic analyses but not by the two other methods seems to be consistent with the above hypothesis. Type I isobolographic analyses may be used not only for evaluating drug combinations but also for predicting the targets of new drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popovic, Peter, E-mail: peter.popovic@kclj.s; Bunc, Matjaz

Massive pulmonary embolism (PE) is a life-threatening condition with a high early mortality rate caused by acute right ventricular failure and cardiogenic shock. A 51-year-old woman with a massive PE and contraindication for thrombolytic therapy was treated with percutaneous mechanical thrombectomy using an Aspirex 11F catheter (Straub Medical AG, Wangs, Switzerland). The procedure was successfully performed and showed a good immediate angiographic result. The patient made a full recovery from the acute episode and was discharged on heparin treatment. Our case report indicates that in patients with contraindications to systemic thrombolysis, catheter thrombectomy may constitute a life-saving intervention for massivemore » PE.« less

Determining the Number of Ischemic Strokes Potentially Eligible for Endovascular Thrombectomy: A Population-Based Study.

PubMed

Chia, Nicholas H; Leyden, James M; Newbury, Jonathan; Jannes, Jim; Kleinig, Timothy J

2016-05-01

Endovascular thrombectomy (ET) is standard-of-care for ischemic stroke patients with large vessel occlusion, but estimates of potentially eligible patients from population-based studies have not been published. Such data are urgently needed to rationally plan hyperacute services. Retrospective analysis determined the incidence of ET-eligible ischemic strokes in a comprehensive population-based stroke study (Adelaide, Australia 2009-2010). Stroke patients were stratified via a prespecified eligibility algorithm derived from recent ET trials comprising stroke subtype, pathogenesis, severity, premorbid modified Rankin Score, presentation delay, large vessel occlusion, and target mismatch penumbra. Recognizing centers may interpret recent ET trials either loosely or rigidly; 2 eligibility algorithms were applied: restrictive (key criteria modified Rankin Scale score 0-1, presentation delay <3.5 hours, and target mismatch penumbra) and permissive (modified Rankin Scale score 0-3 and presentation delay <5 hours). In a population of 148 027 people, 318 strokes occurred in the 1-year study period (crude attack rate 215 [192-240] per 100 000 person-years). The number of ischemic strokes eligible by restrictive criteria was 17/258 (7%; 95% confidence intervals 4%-10%) and by permissive criteria, an additional 16 were identified, total 33/258 (13%; 95% confidence intervals 9%-18%). Two of 17 patients (and 6/33 permissive patients) had thrombolysis contraindications. Using the restrictive algorithm, there were 11 (95% confidence intervals 4-18) potential ET cases per 100 000 person-years or 22 (95% confidence intervals 13-31) using the permissive algorithm. In this cohort, ≈7% of ischemic strokes were potentially eligible for ET (13% with permissive criteria). In similar populations, the permissive criteria predict that ≤22 strokes per 100 000 person-years may be eligible for ET. © 2016 American Heart Association, Inc.

Transverse crack initiation under combined thermal and mechanical loading of Fibre Metal Laminates and Glass Fibre Reinforced Polymers

NASA Astrophysics Data System (ADS)

van de Camp, W.; Dhallé, M. M. J.; Warnet, L.; Wessel, W. A. J.; Vos, G. S.; Akkerman, R.; ter Brake, H. J. M.

2017-02-01

The paper describes a temperature-dependent extension of the classical laminate theory (CLT) that may be used to predict the mechanical behaviour of Fibre Metal Laminates (FML) at cryogenic conditions, including crack initiation. FML are considered as a possible alternative class of structural materials for the transport and storage of liquified gasses such as LNG. Combining different constituents in a laminate opens up the possibility to enhance its functionality, e.g. offering lower specific weight and increased damage tolerance. To explore this possibility, a test programme is underway at the University of Twente to study transverse crack initiation in different material combinations under combined thermal and mechanical loading. Specifically, the samples are tested in a three-point bending experiment at temperatures ranging from 77 to 293 K. These tests will serve as a validation of the model presented in this paper which, by incorporating temperature-dependent mechanical properties and differential thermal expansion, will allow to select optimal material combinations and laminate layouts. By combining the temperature-dependent mechanical properties and the differential thermal contraction explicitly, the model allows for a more accurate estimate of the resulting thermal stresses which can then be compared to the strength of the constituent materials.

Parametrization of Combined Quantum Mechanical and Molecular Mechanical Methods: Bond-Tuned Link Atoms.

PubMed

Wu, Xin-Ping; Gagliardi, Laura; Truhlar, Donald G

2018-05-30

Combined quantum mechanical and molecular mechanical (QM/MM) methods are the most powerful available methods for high-level treatments of subsystems of very large systems. The treatment of the QM-MM boundary strongly affects the accuracy of QM/MM calculations. For QM/MM calculations having covalent bonds cut by the QM-MM boundary, it has been proposed previously to use a scheme with system-specific tuned fluorine link atoms. Here, we propose a broadly parametrized scheme where the parameters of the tuned F link atoms depend only on the type of bond being cut. In the proposed new scheme, the F link atom is tuned for systems with a certain type of cut bond at the QM-MM boundary instead of for a specific target system, and the resulting link atoms are call bond-tuned link atoms. In principle, the bond-tuned link atoms can be as convenient as the popular H link atoms, and they are especially well adapted for high-throughput and accurate QM/MM calculations. Here, we present the parameters for several kinds of cut bonds along with a set of validation calculations that confirm that the proposed bond-tuned link-atom scheme can be as accurate as the system-specific tuned F link-atom scheme.

Examination of turbulent entrainment-mixing mechanisms using a combined approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, C.; Liu, Y.; Niu, S.

2011-10-01

Turbulent entrainment-mixing mechanisms are investigated by applying a combined approach to the aircraft measurements of three drizzling and two nondrizzling stratocumulus clouds collected over the U.S. Department of Energy's Atmospheric Radiation Measurement Southern Great Plains site during the March 2000 cloud Intensive Observation Period. Microphysical analysis shows that the inhomogeneous entrainment-mixing process occurs much more frequently than the homogeneous counterpart, and most cases of the inhomogeneous entrainment-mixing process are close to the extreme scenario, having drastically varying cloud droplet concentration but roughly constant volume-mean radius. It is also found that the inhomogeneous entrainment-mixing process can occur both near the cloudmore » top and in the middle level of a cloud, and in both the nondrizzling clouds and nondrizzling legs in the drizzling clouds. A new dimensionless number, the scale number, is introduced as a dynamical measure for different entrainment-mixing processes, with a larger scale number corresponding to a higher degree of homogeneous entrainment mixing. Further empirical analysis shows that the scale number that separates the homogeneous from the inhomogeneous entrainment-mixing process is around 50, and most legs have smaller scale numbers. Thermodynamic analysis shows that sampling average of filament structures finer than the instrumental spatial resolution also contributes to the dominance of inhomogeneous entrainment-mixing mechanism. The combined microphysical-dynamical-thermodynamic analysis sheds new light on developing parameterization of entrainment-mixing processes and their microphysical and radiative effects in large-scale models.« less

Aging of XLPE cable insulation under combined electrical and mechanical stresses

DOE Office of Scientific and Technical Information (OSTI.GOV)

David, E.; Parpal, J.L.; Crine, J.P.

1996-12-31

Extruded crosslinked polyethylene (XLPE) insulation is widely used in high-voltage cables since it presents such attractive features as excellent dielectric properties and good thermomechanical behavior. However, its performance is affected by long-term degradation when it is subjected to the various thermal, mechanical and environmental stresses occurring in service in combination with electrical stress. The synergetic effect of superposed electrical and other stresses remains to be fully clarified. In particular, a fairly high level of mechanical stresses can be present in the insulation volume, originating from residual internal stresses created during the cooling process in the fabrication, external forces when cablesmore » are bent sharply, or thermomechanical stresses caused by differential thermal expansion between the conductor and the insulating material. In order to investigate the influence of the superposition of mechanical and electrical stresses, various measurements were conducted on XLPE and LDPE specimens in tip-plane and plane-plane geometries. Experimental data of time-to-breakdown, breakdown field and tree length are presented as a function of the magnitude of the stresses. In all cases, superposition of the mechanical stress was found to reduce the dielectric strength of the material.« less

Single-Center Experience Using the 3MAX Reperfusion Catheter for the Treatment of Acute Ischemic Stroke with Distal Arterial Occlusions.

PubMed

Premat, Kévin; Bartolini, Bruno; Baronnet-Chauvet, Flore; Shotar, Eimad; Degos, Vincent; Muresan, Paul; Di Maria, Federico; Gabrieli, Joseph; Rosso, Charlotte; Pistocchi, Silvia; Chiras, Jacques; Sourour, Nader; Alamowitch, Sonia; Samson, Yves; Clarençon, Frédéric

2017-05-15

Most recent guidelines recommend the use of stent retriever devices in endovascular treatment of acute ischemic stroke with large vessel occlusion (LVO). Recently published data reported convincing results with thromboaspiration devices such as the Penumbra System (Penumbra, Alameda, CA, USA) combined with supple reperfusion catheters by using the ADAPT (A Direct Aspiration First-Pass Thrombectomy) technique. The aim of this study was to report our initial experience with the 3MAX (3.8 F) reperfusion catheter for the recanalization of distal intracranial arteries. From August 2015 to December 2016, 32 consecutive patients (16 females, 50%; mean age = 67.4 ± 18.7 years, range: 22-91) for 38 distal occlusions underwent mechanical thrombectomy (MT) by thromboaspiration using the 3MAX. Median NIHSS score at admission was 14 (IQR: 9-19). Distal occlusions were distributed as follows: M2 (n: 23), M3 (n: 6), P1 (n: 3), P2 (n: 2), P3 (n: 2), A3 segment (n: 1) and superior cerebellar artery (n: 1). In 1/38 (2.6%) target artery, the 3MAX could not be navigated. Of the 37 (59.5%) remaining arteries, 22 were successfully reperfused (TICI 2b/3) after ADAPT with the 3MAX alone. Additional stent retriever thrombectomy allowed a 76.3% final reperfusion rate. Good functional outcome (mRS ≤2) was obtained in 45.5% of patients at 3 months. Three (9.4%) 3MAX-related complications occurred: 2 emboli to new territory (ENT) and one vascular perforation. The 3MAX is well-navigable in distal arteries making it useful as a frontline technique. However, the reperfusion rate with the 3MAX catheter alone seems lower than the ones reported with stent retrievers for such distal occlusions.

Similar Outcomes for Contact Aspiration and Stent Retriever Use According to the Admission Clot Burden Score in ASTER.

PubMed

Zhu, François; Lapergue, Bertrand; Kyheng, Maéva; Blanc, Raphael; Labreuche, Julien; Ben Machaa, Malek; Duhamel, Alain; Marnat, Gautier; Saleme, Suzana; Costalat, Vincent; Bracard, Serge; Richard, Sébastien; Desal, Hubert; Mazighi, Mikael; Consoli, Arturo; Piotin, Michel; Gory, Benjamin

2018-07-01

The clot burden score (CBS) at admission reliably evaluates the thrombus burden in acute ischemic stroke patients with anterior circulation large vessel occlusion. Mechanical thrombectomy has been diversified, especially with contact aspiration technique, and its efficiency with respect to the thrombus burden is not known. We compared reperfusion, adverse events, neurological recovery, and 90-day functional outcome of stent retriever use versus contact aspiration according to the admission CBS. This is a post hoc analysis of the ASTER (Contact Aspiration Versus Stent Retriever for Successful Revascularization) randomized trial. The primary outcome was successful reperfusion after all procedures, defined as modified Thrombolysis in Cerebral Infarction scores 2b/3. Secondary outcomes were 90-day functional outcome, assessed with the modified Rankin Scale. Safety outcomes included 90-day mortality and any intracerebral hemorrhage. A total of 231 randomized patients were included in this study: 114 patients had a CBS of 0 to 6 and 117 a CBS ≥7 at admission. Successful reperfusion at procedure end was achieved more frequently in patients with CBS ≥7 (88.9%) than patients with a CBS 0 to 6 (81.6%; fully adjusted risk ratio, 1.09; 95% confidence interval, 1.01-1.28). Favorable outcome (modified Rankin Scale score, 0-2) at 90 days was achieved in significantly more patients with CBS ≥7 (61.9%) than in patients with CBS 0 to 6 (41.8%; fully adjusted risk ratio, 1.19; 95% confidence interval, 1.02-1.40). No outcome differences of first-line mechanical thrombectomy strategy (aspiration versus stent) on any angiographic or clinical outcomes were observed between the 2 groups. We also found no evidence of interaction between first-line mechanical thrombectomy strategy and CBS groups regarding safety. First-line mechanical thrombectomy with contact aspiration compared with stent retriever did not result in an increased successful reperfusion rate in acute ischemic stroke

A procedure for combining acoustically induced and mechanically induced loads (first passage failure design criterion)

NASA Technical Reports Server (NTRS)

Crowe, D. R.; Henricks, W.

1983-01-01

The combined load statistics are developed by taking the acoustically induced load to be a random population, assumed to be stationary. Each element of this ensemble of acoustically induced loads is assumed to have the same power spectral density (PSD), obtained previously from a random response analysis employing the given acoustic field in the STS cargo bay as a stationary random excitation. The mechanically induced load is treated as either (1) a known deterministic transient, or (2) a nonstationary random variable of known first and second statistical moments which vary with time. A method is then shown for determining the probability that the combined load would, at any time, have a value equal to or less than a certain level. Having obtained a statistical representation of how the acoustic and mechanical loads are expected to combine, an analytical approximation for defining design levels for these loads is presented using the First Passage failure criterion.

Probabilistic Simulation of Combined Thermo-Mechanical Cyclic Fatigue in Composites

NASA Technical Reports Server (NTRS)

Chamis, Christos C.

2011-01-01

A methodology to compute probabilistically-combined thermo-mechanical fatigue life of polymer matrix laminated composites has been developed and is demonstrated. Matrix degradation effects caused by long-term environmental exposure and mechanical/thermal cyclic loads are accounted for in the simulation process. A unified time-temperature-stress-dependent multifactor-interaction relationship developed at NASA Glenn Research Center has been used to model the degradation/aging of material properties due to cyclic loads. The fast probability-integration method is used to compute probabilistic distribution of response. Sensitivities of fatigue life reliability to uncertainties in the primitive random variables (e.g., constituent properties, fiber volume ratio, void volume ratio, ply thickness, etc.) computed and their significance in the reliability-based design for maximum life is discussed. The effect of variation in the thermal cyclic loads on the fatigue reliability for a (0/+/-45/90)s graphite/epoxy laminate with a ply thickness of 0.127 mm, with respect to impending failure modes has been studied. The results show that, at low mechanical-cyclic loads and low thermal-cyclic amplitudes, fatigue life for 0.999 reliability is most sensitive to matrix compressive strength, matrix modulus, thermal expansion coefficient, and ply thickness. Whereas at high mechanical-cyclic loads and high thermal-cyclic amplitudes, fatigue life at 0.999 reliability is more sensitive to the shear strength of matrix, longitudinal fiber modulus, matrix modulus, and ply thickness.

Probabilistic Simulation of Combined Thermo-Mechanical Cyclic Fatigue in Composites

NASA Technical Reports Server (NTRS)

Chamis, Christos C.

2010-01-01

A methodology to compute probabilistically-combined thermo-mechanical fatigue life of polymer matrix laminated composites has been developed and is demonstrated. Matrix degradation effects caused by long-term environmental exposure and mechanical/thermal cyclic loads are accounted for in the simulation process. A unified time-temperature-stress-dependent multifactor-interaction relationship developed at NASA Glenn Research Center has been used to model the degradation/aging of material properties due to cyclic loads. The fast probability-integration method is used to compute probabilistic distribution of response. Sensitivities of fatigue life reliability to uncertainties in the primitive random variables (e.g., constituent properties, fiber volume ratio, void volume ratio, ply thickness, etc.) computed and their significance in the reliability-based design for maximum life is discussed. The effect of variation in the thermal cyclic loads on the fatigue reliability for a (0/+/-45/90)s graphite/epoxy laminate with a ply thickness of 0.127 mm, with respect to impending failure modes has been studied. The results show that, at low mechanical-cyclic loads and low thermal-cyclic amplitudes, fatigue life for 0.999 reliability is most sensitive to matrix compressive strength, matrix modulus, thermal expansion coefficient, and ply thickness. Whereas at high mechanical-cyclic loads and high thermal-cyclic amplitudes, fatigue life at 0.999 reliability is more sensitive to the shear strength of matrix, longitudinal fiber modulus, matrix modulus, and ply thickness.

Treatment with Uric Acid Reduces Infarct and Improves Neurologic Function in Female Mice After Transient Cerebral Ischemia.

PubMed

Dhanesha, Nirav; Vázquez-Rosa, Edwin; Cintrón-Pérez, Coral J; Thedens, Daniel; Kort, Alexa J; Chuong, Vicky; Rivera-Dompenciel, Adriana M; Chauhan, Anil K; Leira, Enrique C; Pieper, Andrew A

2018-05-01

Exogenous administration of uric acid, a naturally occurring antioxidant that scavenges reactive oxygen species in vasculature, has shown protective efficacy in both rodent models of stroke and human stroke patients in Spain as an adjuvant treatment to mechanical thrombectomy. Before clinical trials can be initiated in the United States, however, confirmation of efficacy in alternative preclinical models is required in accordance with stroke therapy academic industry roundtable-RIGOR criteria. To date, preclinical efficacy has only been established in the acute setting in male rodents. To address this need, we subjected 7- to 9-week old ovariectomized female mice to filament-induced right middle cerebral artery ischemia and reperfusion, an established preclinical model of mechanical thrombectomy. Fidelity of the procedure was monitored by laser Doppler flowmetry. A separate lab randomly assigned animals to vehicle versus uric acid infusion, which was initiated immediately after 45 minutes of reperfusion. Poststroke analysis of infarction size and neurologic function were conducted by investigators blind to treatment group, with a 7-day primary endpoint and a 3-day intermediary analysis at 1and. Infarct size and neurologic function at 7 days poststroke were significantly improved in uric acid-treated animals, relative to vehicle. Efficacy of uric acid in preclinical models of stroke is now expanded to include female mice analyzed at a later time point than has been investigated previously. These results support stroke therapy academic industry roundtable-RIGOR driven determination of the suitability of acute administration of uric acid as an adjuvant to mechanical thrombectomy in clinical trials for patients with stroke. Published by Elsevier Inc.

Anti-Inflammatory Targets for the Treatment of Reperfusion Injury in Stroke

PubMed Central

Mizuma, Atsushi; Yenari, Midori A.

2017-01-01

While the mainstay of acute stroke treatment includes revascularization via recombinant tissue plasminogen activator or mechanical thrombectomy, only a minority of stroke patients are eligible for treatment, as delayed treatment can lead to worsened outcome. This worsened outcome at the experimental level has been attributed to an entity known as reperfusion injury (R/I). R/I is occurred when revascularization is delayed after critical brain and vascular injury has occurred, so that when oxygenated blood is restored, ischemic damage is increased, rather than decreased. R/I can increase lesion size and also worsen blood barrier breakdown and lead to brain edema and hemorrhage. A major mechanism underlying R/I is that of poststroke inflammation. The poststroke immune response consists of the aberrant activation of glial cell, infiltration of peripheral leukocytes, and the release of damage-associated molecular pattern (DAMP) molecules elaborated by ischemic cells of the brain. Inflammatory mediators involved in this response include cytokines, chemokines, adhesion molecules, and several immune molecule effectors such as matrix metalloproteinases-9, inducible nitric oxide synthase, nitric oxide, and reactive oxygen species. Several experimental studies over the years have characterized these molecules and have shown that their inhibition improves neurological outcome. Yet, numerous clinical studies failed to demonstrate any positive outcomes in stroke patients. However, many of these clinical trials were carried out before the routine use of revascularization therapies. In this review, we cover mechanisms of inflammation involved in R/I, therapeutic targets, and relevant experimental and clinical studies, which might stimulate renewed interest in designing clinical trials to specifically target R/I. We propose that by targeting anti-inflammatory targets in R/I as a combined therapy, it may be possible to further improve outcomes from pharmacological thrombolysis or

Fabrication of microfibrillated cellulose gel from waste pulp sludge via mild maceration combined with mechanical shearing

Treesearch

Nusheng Chen; Junyong Zhu; Zhaohui Tong

2016-01-01

This article describes a facile route, which combines mild maceration of waste pulp sludge and a mechanical shearing process, to prepare microfibrillated cellulose (MFC) with a high storage modulus. In the maceration, the mixture of glacial acetic acid and hydrogen peroxide was used to extract cellulose from never-dried waste pulp sludge. Then, two different mechanical...

Apparent-Strain Correction for Combined Thermal and Mechanical Testing

NASA Technical Reports Server (NTRS)

Johnson, Theodore F.; O'Neil, Teresa L.

2007-01-01

Combined thermal and mechanical testing requires that the total strain be corrected for the coefficient of thermal expansion mismatch between the strain gage and the specimen or apparent strain when the temperature varies while a mechanical load is being applied. Collecting data for an apparent strain test becomes problematic as the specimen size increases. If the test specimen cannot be placed in a variable temperature test chamber to generate apparent strain data with no mechanical loads, coupons can be used to generate the required data. The coupons, however, must have the same strain gage type, coefficient of thermal expansion, and constraints as the specimen to be useful. Obtaining apparent-strain data at temperatures lower than -320 F is challenging due to the difficulty to maintain steady-state and uniform temperatures on a given specimen. Equations to correct for apparent strain in a real-time fashion and data from apparent-strain tests for composite and metallic specimens over a temperature range from -450 F to +250 F are presented in this paper. Three approaches to extrapolate apparent-strain data from -320 F to -430 F are presented and compared to the measured apparent-strain data. The first two approaches use a subset of the apparent-strain curves between -320 F and 100 F to extrapolate to -430 F, while the third approach extrapolates the apparent-strain curve over the temperature range of -320 F to +250 F to -430 F. The first two approaches are superior to the third approach but the use of either of the first two approaches is contingent upon the degree of non-linearity of the apparent-strain curve.

[Construction of research system for processing mechanism of traditional Chinese medicine based on chemical composition transformation combined with intestinal absorption barrier].

PubMed

Sun, E; Xu, Feng-Juan; Zhang, Zhen-Hai; Wei, Ying-Jie; Tan, Xiao-Bin; Cheng, Xu-Dong; Jia, Xiao-Bin

2014-02-01

Based on practice of Epimedium processing mechanism for many years and integrated multidisciplinary theory and technology, this paper initially constructs the research system for processing mechanism of traditional Chinese medicine based on chemical composition transformation combined with intestinal absorption barrier, which to form an innovative research mode of the " chemical composition changes-biological transformation-metabolism in vitro and in vivo-intestinal absorption-pharmacokinetic combined pharmacodynamic-pharmacodynamic mechanism". Combined with specific examples of Epimedium and other Chinese herbal medicine processing mechanism, this paper also discusses the academic thoughts, research methods and key technologies of this research system, which will be conducive to systematically reveal the modem scientific connotation of traditional Chinese medicine processing, and enrich the theory of Chinese herbal medicine processing.

The Strange Case of CDK4/6 Inhibitors: Mechanisms, Resistance, and Combination Strategies

PubMed Central

Knudsen, Erik S.; Witkiewicz, Agnieszka K.

2016-01-01

CDK4/6 inhibitors have emerged as a powerful class of agents with clinical activity in a number of malignancies. Targeting the cell cycle represents a core attack on a defining feature of cancer. However, the mechanisms through which selective CDK4/6 targeted agents act has few parallels in the current pharmaceutical armamentarium against cancer. Notably, CDK4/6 inhibitors act downstream of most mitogenic signaling cascades, which have implications both related to clinical efficacy and resistance. Core knowledge of cell cycle processes has provided insights into mechanisms of intrinsic resistance to CDK4/6 inhibitors; however, the basis of acquired resistance versus durable response is only beginning to emerge. This review focuses on the mechanism of action and biomarkers to direct the precision use of CDK4/6 inhibitors and rationally-developed combination therapies. PMID:28303264

Endovascular Mechanical Recanalisation of Acute Carotid-T Occlusions: A Single-Center Retrospective Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fesl, Gunther, E-mail: gunther.fesl@med.uni-muenchen.de; Wiesmann, Martin; Patzig, Maximilian

2011-04-15

Purpose: Acute carotid-T occlusion generally responds poorly to thrombolysis. Endovascular mechanical thrombectomy (EMT) seems to be a promising alternative. However, there are few data on EMT in carotid-T occlusions. Materials and Methods: We reviewed data of 14 consecutive patients with acute carotid-T occlusions treated with mechanical recanalisation devices. A clot separation/aspiration system was used in 11 patients; different other mechanical retriever devices were used in seven patients; and stents were used in four patients. Modified Rankin Scale scores at 90 days were recorded to assess functional outcome. Results: Six women and eight men were included in the study. Mean patientmore » age was 59.2 years; median National Institute of Health Stroke Scale score on admission was 19; and mean time to treatment was 4.2 h. Successful recanalisation (Thrombolysis in Myocardial Infarction [TIMI] score II and III) was achieved in 11 patients (78.6%). Seven patients (50.0%) were treated with more than one device, leading to successful recanalisation in six of these patients (85.7%). Subarachnoid haemorrhage and large space-occupying bleedings occurred in one (7.1%) and three (21.4%) patients, respectively. At follow-up, three patients (21.4%) were functionally independent, and six (42.9%) had died. Conclusion: When applying different mechanical devices, we found a high recanalisation rate. However, discrepancy between recanalisation and clinical outcome remained. More data are needed to assess the effect of the different methods on the prognoses of stroke patients.« less

An Opportunistic Routing Mechanism Combined with Long-Term and Short-Term Metrics for WMN

PubMed Central

Piao, Xianglan; Qiu, Tie

2014-01-01

WMN (wireless mesh network) is a useful wireless multihop network with tremendous research value. The routing strategy decides the performance of network and the quality of transmission. A good routing algorithm will use the whole bandwidth of network and assure the quality of service of traffic. Since the routing metric ETX (expected transmission count) does not assure good quality of wireless links, to improve the routing performance, an opportunistic routing mechanism combined with long-term and short-term metrics for WMN based on OLSR (optimized link state routing) and ETX is proposed in this paper. This mechanism always chooses the highest throughput links to improve the performance of routing over WMN and then reduces the energy consumption of mesh routers. The simulations and analyses show that the opportunistic routing mechanism is better than the mechanism with the metric of ETX. PMID:25250379

An opportunistic routing mechanism combined with long-term and short-term metrics for WMN.

PubMed

Sun, Weifeng; Wang, Haotian; Piao, Xianglan; Qiu, Tie

2014-01-01

WMN (wireless mesh network) is a useful wireless multihop network with tremendous research value. The routing strategy decides the performance of network and the quality of transmission. A good routing algorithm will use the whole bandwidth of network and assure the quality of service of traffic. Since the routing metric ETX (expected transmission count) does not assure good quality of wireless links, to improve the routing performance, an opportunistic routing mechanism combined with long-term and short-term metrics for WMN based on OLSR (optimized link state routing) and ETX is proposed in this paper. This mechanism always chooses the highest throughput links to improve the performance of routing over WMN and then reduces the energy consumption of mesh routers. The simulations and analyses show that the opportunistic routing mechanism is better than the mechanism with the metric of ETX.

Combination of experimental and numerical methods for mechanical characterization of Al-Si alloys

NASA Astrophysics Data System (ADS)

Kruglova, A.; Roland, M.; Diebels, S.; Mücklich, F.

2017-10-01

In general, mechanical properties of Al-Si alloys strongly depend on the morphology and arrangement of microconstituents, such as primary aluminium dendrites, silicon particles, etc. Therefore, a detailed characterization of morphological and mechanical properties of the alloys is necessary to better understand the relations between the underlined properties and to tailor the material’s microstructure to the specific application needs. The mechanical characterization usually implies numerical simulations and mechanical tests, which allow to investigate the influence of different microstructural aspects on different scales. In this study, the uniaxial tension and compression tests have been carried out on Al-Si alloys having different microstructures. The mechanical behavior of the alloys has been interpreted with respect to the morphology of the microconstituents and has been correlated with the results of numerical simulations. The advantages and limitations of the experimental and numerical methods have been disclosed and the importance of combining both techniques for the interpretation of the mechanical behavior of Al-Si alloys has been shown. Thereby, it has been suggested that the density of Si particles and the size of Al dendrites are more important for the strengthening of the alloys than the size-shape features of the eutectic Si induced by the modification.

Combination of Heel-strike like Mechanical Loading with Deproteinized Cancellous Bone Scaffold Implantation to Repair Segmental Bone Defects in Rabbits.

PubMed

Huang, Guofeng; Liu, Guojun; Zhang, Feng; Gao, Jianting; Wang, Jiangze; Chen, Qi; Wu, Benwen; Ding, Zhenqi; Cai, Taoyi

2017-01-01

Under physiological conditions bone defects often occur at mechanical load bearing sites and bone substitutes used for regeneration should be similarly subjected to mechanical loading stress. In this study, we investigated whether a novel heel-strike like mechanical loading method can be used as a complementary therapy to promote bone regeneration following bone substitute grafting. To test this, three groups of rabbits with segmental bone defects in the tibia were implanted with bovine deproteinized cancellous bone scaffold (DCBS), with one group also receiving heel-strike like mechanical loading generated by a rap stress stimulator. From weeks 4-12 post-operation X-ray and micro-CT scanning showed that rabbits receiving combination therapy had significantly more callus at the bone defect. Moreover, bone defects in the combination group were completely replaced with new bone at week 12, while the DCBS implantation alone group healed only partially and rabbits receiving neither DCBS nor mechanical loading developed only small calluses throughout the observation period. Analysis of micro-CT scanning results demonstrated that new bone density in the combination group was significantly higher than the DCBS only group at weeks 4 and 12 ( p <0.05). H&E staining results also indicated a significantly higher percentage of new bone in the bone defect area and a lower percentage of residual scaffold in the combination group compared to the DCBS only group ( p <0.05). Thus, this heel-strike like mechanical loading method appears to accelerate bone regeneration following substitute implantation by restoring a local mechanical loading environment in segmental bone defects.

Action Reflected and Project Based Combined Methodology for the Appropriate Comprehension of Mechanisms in Industrial Design Education

ERIC Educational Resources Information Center

Yavuzcan, H. Güçlü; Sahin, Damla

2017-01-01

In industrial design (ID) education, mechanics-based courses are mainly based on a traditional lecture approach and they are highly abstract for ID students to comprehend. The existing studies highlight the requirement of a new approach for mechanics-based courses in ID departments. This study presents a combined teaching model for mechanisms…

Combined quantum mechanical and molecular mechanical method for metal-organic frameworks: proton topologies of NU-1000.

PubMed

Wu, Xin-Ping; Gagliardi, Laura; Truhlar, Donald G

2018-01-17

Metal-organic frameworks (MOFs) are materials with applications in catalysis, gas separations, and storage. Quantum mechanical (QM) calculations can provide valuable guidance to understand and predict their properties. In order to make the calculations faster, rather than modeling these materials as periodic (infinite) systems, it is useful to construct finite models (called cluster models) and use subsystem methods such as fragment methods or combined quantum mechanical and molecular mechanical (QM/MM) methods. Here we employ a QM/MM methodology to study one particular MOF that has been of widespread interest because of its wide pores and good solvent and thermal stability, namely NU-1000, which contains hexanuclear zirconium nodes and 1,3,6,8-tetrakis(p-benzoic acid)pyrene (TBAPy 4- ) linkers. A modified version of the Bristow-Tiana-Walsh transferable force field has been developed to allow QM/MM calculations on NU-1000; we call the new parametrization the NU1T force field. We consider isomeric structures corresponding to various proton topologies of the [Zr 6 (μ 3 -O) 8 O 8 H 16 ] 8+ node of NU-1000, and we compute their relative energies using a QM/MM scheme designed for the present kind of problem. We compared the results to full quantum mechanical (QM) energy calculations and found that the QM/MM models can reproduce the full QM relative energetics (which span a range of 334 kJ mol -1 ) with a mean unsigned deviation (MUD) of only 2 kJ mol -1 . Furthermore, we found that the structures optimized by QM/MM are nearly identical to their full QM optimized counterparts.

Multi-functional polyelectrolyte multilayer films: combining mechanical resistance, biodegradability and bioactivity

PubMed Central

Schneider, Aurore; Vodouhê, Constant; Richert, Ludovic; Francius, Gregory; Le Guen, Erell; Schaaf, Pierre; Voegel, Jean-Claude; Frisch, Benoît; Picart, Catherine

2008-01-01

Cross-linked polyelectrolyte multilayer films (CL PEM) have an increased rigidity and are mechanically more resistant than native (e.g. uncrosslinked) films. However, they are still biodegradable, which make them interesting candidates for biomedical applications. In this study, CL PEM films have been explored for their multifunctional properties as i) mechanically resistant ii) biodegradable and iii) bioactive films. Toward this end, we investigated drug loading into CL chitosan/hyaluronan (CHI/HA) and poly(L-lysine)/hyaluronan (PLL/HA) films by simple diffusion of the drugs. Sodium diclofenac and paclitaxel were chosen as model drugs and were successfully loaded into the films. The effect of varying the number of layers in the (CHI/HA) films as well as the cross-linker concentration on diclofenac loading were studied. Diclofenac was released from the film in about ten hours. Paclitaxel was also found to diffuse within CL films. Its activity was maintained after loading in the CL films and cellular viability could be reduced by about 55% over three days. Such simple approach may be applied to other types of cross-linked films and to other drugs. These results prove that it is possible to design multifunctional multilayer films that combine mechanical resistance, biodegradability and bioactivity properties into a single PEM architecture. PMID:17206799

Long-term outcomes of acute ischemic stroke patients treated with endovascular thrombectomy: A real-world experience.

PubMed

Zhao, Wenbo; Shang, Shuyi; Li, Chuanhui; Wu, Longfei; Wu, Chuanjie; Chen, Jian; Song, Haiqing; Zhang, Hongqi; Zhang, Yunzhou; Duan, Jiangang; Feng, Wuwei; Ji, Xunming

2018-07-15

Long-term follow-up of large trials have confirmed the superiority of endovascular thrombectomy (ET) for treating acute ischemic stroke (AIS). However, it is still unknown whether these results can be generalized to clinical practice. In this study, we aimed to determine the long-term outcomes of AIS post-ET in the real-world clinical practice. This observational study is based on a single-center prospective registry study. AIS patients were treated with second-generation stent retrievers from December 2012 to April 2016. The primary outcome was modified Ranks scale (mRS) at the time of the latest assessment. Favorable outcome was defined as mRS scores 0-2, and the unfavorable outcome was defined as mRS scores 3-6. Eighty-nine AIS subjects with large artery occlusion in anterior circulation undergoing ET were eligible for analysis. Median follow-up duration was 20 months (interquartile range 6-32), and 47 subjects (53%) achieved favorable outcome whereas 17 subjects (19%) were functional dependence and 25 subjects (28%) died. Independent predicators for long-term unfavorable outcome were higher baseline National Institutes of Health Stroke Scale (NIHSS) score (odd ratio:1.21;95% confidence interval 1.09-1.35; p < 0.001) and symptomatic intracerebral hemorrhage (sICH) (odd ratio:16.45;95% confidence interval 1.34-193.44; p = 0.026). More subjects of large-artery-atherosclerosis underwent permanent intracranial stenting (22%vs.10%) as compared with those of cardioembolism, while subjects of cardioembolism were more likely to experience sICH (13%vs.8%) and died (32%vs.16%). Over half of AIS patients can achieve favorable long-term outcomes post-ET. Higher baseline NIHSS scores and sICH are independently associated with unfavorable outcome. Overall, clinical practice in this single canter can replicate the long-term outcomes from the published endovascular clinical trials. Copyright © 2018 Elsevier B.V. All rights reserved.

SOLITAIRE™ with the intention for thrombectomy (SWIFT) trial: design of a randomized, controlled, multicenter study comparing the SOLITAIRE™ Flow Restoration device and the MERCI Retriever in acute ischaemic stroke.

PubMed

Saver, J L; Jahan, R; Levy, E I; Jovin, T G; Baxter, B; Nogueira, R; Clark, W; Budzik, R; Zaidat, O O

2014-07-01

Self-expanding stent retrievers are a promising new device class designed for rapid flow restoration in acute cerebral ischaemia. The SOLITAIRE™ Flow Restoration device (SOLITAIRE) has shown high rates of recanalization in preclinical models and in uncontrolled clinical series. (1) To demonstrate non-inferiority of SOLITAIRE compared with a legally marketed device, the MERCI Retrieval System®; (2) To demonstrate safety, feasibility, and efficacy of SOLITAIRE in subjects requiring mechanical thrombectomy diagnosed with acute ischaemic stroke. DESIGN : Multicenter, randomized, prospective, controlled trial with blinded primary end-point ascertainment. Key entry criteria include: age 22-85; National Institute of Health Stroke Scale (NIHSS) ≥8 and <30; clinical and imaging findings consistent with acute ischaemic stroke; patient ineligible or failed intravenous tissue plasminogen activator; accessible occlusion in M1 or M2 middle cerebral artery, internal carotid artery, basilar artery, or vertebral artery; and patient able to be treated within 8 h of onset. Sites first participate in a roll-in phase, treating two patients with the SOLITAIRE device, before proceeding to the randomized phase. In patients unresponsive to the initially assigned therapy, after the angiographic component of the primary end-point is ascertained (reperfusion with the initial assigned device), rescue therapy with other reperfusion techniques is permitted. The primary efficacy end-point is successful recanalization with the assigned study device (no use of rescue therapy) and with no symptomatic intracranial haemorrhage. Successful recanalization is defined as achieving Thrombolysis In Myocardial Ischemia 2 or 3 flow in all treatable vessels. The primary safety end-point is the incidence of device-related and procedure-related serious adverse events. A major secondary efficacy end-point is time to achieve initial recanalization. Additional secondary end-points include clinical outcomes

Maize water status and physiological traits as affected by root endophytic fungus Piriformospora indica under combined drought and mechanical stresses.

PubMed

Hosseini, Fatemeh; Mosaddeghi, Mohammad Reza; Dexter, Anthony Roger; Sepehri, Mozhgan

2018-05-01

Under combined drought and mechanical stresses, mechanical stress primarily controlled physiological responses of maize. Piriformospora indica mitigated the adverse effects of stresses, and inoculated maize experienced less oxidative damage and had better adaptation to stressful conditions. The objective of this study was to investigate the effect of maize root colonization by an endophytic fungus P. indica on plant water status, physiological traits and root morphology under combined drought and mechanical stresses. Seedlings of inoculated and non-inoculated maize (Zea mays L., cv. single cross 704) were cultivated in growth chambers filled with moistened siliceous sand at a matric suction of 20 hPa. Drought stress was induced using PEG 6000 solution with osmotic potentials of 0, - 0.3 and - 0.5 MPa. Mechanical stress (i.e., penetration resistances of 1.05, 4.23 and 6.34 MPa) was exerted by placing weights on the surface of the sand medium. After 30 days, leaf water potential (LWP) and relative water content (RWC), root and shoot fresh weights, root volume (RV) and diameter (RD), leaf proline content, leaf area (LA) and catalase (CAT) and ascorbate peroxidase (APX) activities were measured. The results show that exposure to individual drought and mechanical stresses led to higher RD and proline content and lower plant biomass, RV and LA. Moreover, increasing drought and mechanical stress severity increased APX activity by about 1.9- and 3.1-fold compared with the control. When plants were exposed to combined stresses, mechanical stress played the dominant role in controlling plant responses. P. indica-inoculated plants are better adapted to individual and combined stresses. The inoculated plants had greater RV, LA, RWC, LWP and proline content under stressful conditions. In comparison with non-inoculated plants, inoculated plants showed lower CAT and APX activities which means that they experienced less oxidative stress induced by stressful conditions.

Mechanisms Mediating Enhanced Neutralization Efficacy of Staphylococcal Enterotoxin B by Combinations of Monoclonal Antibodies*

PubMed Central

Dutta, Kaushik; Varshney, Avanish K.; Franklin, Matthew C.; Goger, Michael; Wang, Xiaobo; Fries, Bettina C.

2015-01-01

Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major histocompatibility complex class II and specific V-β chains of the T-cell receptor, thus forming a ternary complex. Developing neutralizing mAb to disrupt the ternary complex and abrogate the resulting toxicity is a major therapeutic challenge because SEB is effective at very low concentrations. We show that combining two SEB-specific mAbs enhances their efficacy, even though one of the two mAbs by itself has no effect on neutralization. Crystallography was employed for fine-mapping conformational epitopes in binary and ternary complexes between SEB and Fab fragments. NMR spectroscopy was used to validate and identify subtle allosteric changes induced by mAbs binding to SEB. The mapping of epitopes established that a combination of different mAbs can enhance efficacy of mAb-mediated protection from SEB induced lethal shock by two different mechanisms: one mAb mixture promoted clearance of the toxin both in vitro and in vivo by FcR-mediated cross-linking and clearance, whereas the other mAb mixture induced subtle allosteric conformational changes in SEB that perturbed formation of the SEB·T-cell receptor·major histocompatibility complex class II trimer. Finally structural information accurately predicted mAb binding to other superantigens that share conformational epitopes with SEB. Fine mapping of conformational epitopes is a powerful tool to establish the mechanism and optimize the action of synergistic mAb combinations. PMID:25572397

Mechanisms mediating enhanced neutralization efficacy of Staphylococcal enterotoxin B by combinations of monoclonal antibodies

DOE PAGES

Dutta, Kaushik; Varshney, Avanish K.; Franklin, Matthew C.; ...

2015-01-08

Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major histocompatibility complex class II and specific V-β chains of the T-cell receptor, thus forming a ternary complex. Developing neutralizing mAb to disrupt the ternary complex and abrogate the resulting toxicity is a major therapeutic challenge because SEB is effective at very low concentrations. We show that combining two SEB-specific mAbs enhances their efficacy, even though one of the two mAbs by itself has no effect on neutralization. Crystallography was employed for fine-mapping conformational epitopes in binary and ternary complexes between SEB and Fab fragments. NMR spectroscopy was used tomore » validate and identify subtle allosteric changes induced by mAbs binding to SEB. The mapping of epitopes established that a combination of different mAbs can enhance efficacy of mAb-mediated protection from SEB induced lethal shock by two different mechanisms: one mAb mixture promoted clearance of the toxin both in vitro and in vivo by FcR-mediated cross-linking and clearance, whereas the other mAb mixture induced subtle allosteric conformational changes in SEB that perturbed formation of the SEB·T-cell receptor·major histocompatibility complex class II trimer. Lastly structural information accurately predicted mAb binding to other superantigens that share conformational epitopes with SEB. Fine mapping of conformational epitopes is a powerful tool to establish the mechanism and optimize the action of synergistic mAb combinations.« less

Liraglutide, leptin, and their combined effects on feeding: additive intake reduction through common intracellular signaling mechanisms

PubMed Central

Kanoski, Scott E.; Ong, Zhi Yi; Fortin, Samantha M.; Schlessinger, Elizabeth S.; Grill, Harvey J.

2014-01-01

Aims Glucagon like peptide-1 receptor (GLP-1R) agonists and leptin each exert anorexigenic effects. In combination, the intake inhibitory and weight loss effects are greater than either treatment alone, however the mechanisms unclear. Materials and methods Effects of liraglutide (a long-acting GLP-1 analogue) and leptin co-treatment, delivered in low or moderate doses subcutaneously (SC) or to the 3rd ventricle respectively, on cumulative intake, meal patterns, and hypothalamic expression of intracellular signaling proteins [phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein tyrosine phosphatase-1B (PTP1B)] were examined in lean rats. Results A low-dose combination of liraglutide (25μg/kg) and leptin (0.75μg) additively reduced cumulative food intake and body weight, a result mediated predominantly through a significant reduction in meal frequency that was not present with either drug alone. Liraglutide treatment alone also reduced meal size; an effect not enhanced with leptin co-administration. Moderate doses of liraglutide (75μg/kg) and leptin (4μg) examined separately each reduced meal frequency, cumulative food intake, and body weight; only liraglutide reduced meal size. In combination these doses did not further enhance the anorexigenic effects of either treatment alone. Ex vivo immunoblot showed elevated pSTAT3 in hypothalamic tissue following liraglutide-leptin co-treatment, an effect greater than leptin treatment alone. In addition, SC liraglutide reduced expression of PTP1B (a negative regulator of leptin receptor signaling), revealing a potential mechanism for the enhanced pSTAT3 response following liraglutide-leptin co-administration. Conclusions Collectively, these results provide novel behavioral and molecular mechanisms underlying the additive reduction in food intake and body weight following liraglutide-leptin combination treatment. PMID:25475828

Insight into the Phosphodiesterase Mechanism from Combined QM/MM Free Energy Simulations

PubMed Central

Wong, Kin-Yiu; Gao, Jiali

2011-01-01

Summary Molecular dynamics simulations employing a combined quantum mechanical and molecular mechanical potential have been carried out to elucidate the reaction mechanism of the hydrolysis of a cyclic nucleotide cAMP substrate by phosphodiesterase 4B (PDE4B). PDE4B is a member of the PDE superfamily of enzymes that play crucial roles in cellular signal transduction. We have determined a two-dimensional potential of mean force for the coupled phosphoryl bond cleavage and proton transfer through a general acid catalysis mechanism in PDE4B. The results indicate that the ring-opening process takes place through an SN2 reaction mechanism, followed by a proton transfer to stabilize the leaving group. The computed free energy of activation for the PDE4B-catalyzed cAMP hydrolysis is about 13 kcal/mol and an overall reaction free energy is about −17 kcal/mol, both in accord with experimental results. In comparison with the uncatalyzed reaction in water, the enzyme PDE4B provides a strong stabilization of the transition state, lowering the free energy barrier by 14 kcal/mol. We found that the proton transfer from the general acid residue His234 to the O3' oxyanion of the ribosyl leaving group lags behind the nucleophilic attack, resulting in a shallow minimum on the free energy surface. A key contributing factor to transition state stabilization is the elongation of the distance between the divalent metal ions Zn2+ and Mg2+ in the active site as the reaction proceeds from the Michaelis complex to the transition state. PMID:21595828

Theoretical Modeling of Hydrogen Bonding in omolecular Solutions: The Combination of Quantum Mechanics and Molecular Mechanics

NASA Astrophysics Data System (ADS)

Ma, Jing; Jiang, Nan; Li, Hui

Hydrogen bonding interaction takes an important position in solutions. The non-classic nature of hydrogen bonding requires the resource-demanding quantum mechanical (QM) calculations. The molecular mechanics (MM) method, with much lower computational load, is applicable to the large-sized system. The combination of QM and MM is an efficient way in the treatment of solution. Taking advantage of the low-cost energy-based fragmentation QM approach (in which the o-molecule is divided into several subsystems, and QM calculation is carried out on each subsystem that is embedded in the environment of background charges of distant parts), the fragmentation-based QM/MM and polarization models have been implemented for the modeling of o-molecule in aqueous solutions, respectively. Within the framework of the fragmentation-based QM/MM hybrid model, the solute is treated by the fragmentation QM calculation while the numerous solvent molecules are described by MM. In the polarization model, the polarizability is considered by allowing the partial charges and fragment-centered dipole moments to be variables, with values coming from the energy-based fragmentation QM calculations. Applications of these two methods to the solvated long oligomers and cyclic peptides have demonstrated that the hydrogen bonding interaction affects the dynamic change in chain conformations of backbone.

Design and fabrication of miniaturized PEM fuel cell combined microreactor with self-regulated hydrogen mechanism

NASA Astrophysics Data System (ADS)

Balakrishnan, A.; Frei, M.; Kerzenmacher, S.; Reinecke, H.; Mueller, C.

2015-12-01

In this work we present the design and fabrication of the miniaturized PEM fuel cell combined microreactor system with hydrogen regulation mechanism and testing of prototype microreactor. The system consists of two components (i) fuel cell component and (ii) microreactor component. The fuel cell component represents the miniaturized PEM fuel cell system (combination of screen printed fuel cell assembly and an on-board hydrogen storage medium). Hydrogen production based on catalytic hydrolysis of chemical hydride takes place in the microreactor component. The self-regulated hydrogen mechanism based on the gaseous hydrogen produced from the catalytic hydrolysis of sodium borohydride (NaBH4) gets accumulated as bubbles at the vicinity of the hydrophobic coated hydrogen exhaust holes. When the built up hydrogen bubbles pressure exceeds the burst pressure at the hydrogen exhaust holes the bubble collapses. This collapse causes a surge of fresh NaBH4 solution onto the catalyst surface leading to the removal of the reaction by-products formed at the active sites of the catalyst. The catalyst used in the system is platinum deposited on a base substrate. Nickel foam, carbon porous medium (CPM) and ceramic plate were selected as candidates for base substrate for developing a robust catalyst surface. For the first time the platinum layer fabricated by pulsed electrodeposition and dealloying (EPDD) technique is used for hydrolysis of NaBH4. The major advantages of such platinum catalyst layers are its high surface area and their mechanical stability. Prototype microreactor system with self-regulated hydrogen mechanism is demonstrated.

Multi-Drug Resistance Transporters and a Mechanism-Based Strategy for Assessing Risks of Pesticide Combinations to Honey Bees

PubMed Central

Guseman, Alex J.; Miller, Kaliah; Kunkle, Grace; Dively, Galen P.; Pettis, Jeffrey S.; Evans, Jay D.; vanEngelsdorp, Dennis; Hawthorne, David J.

2016-01-01

Annual losses of honey bee colonies remain high and pesticide exposure is one possible cause. Dangerous combinations of pesticides, plant-produced compounds and antibiotics added to hives may cause or contribute to losses, but it is very difficult to test the many combinations of those compounds that bees encounter. We propose a mechanism-based strategy for simplifying the assessment of combinations of compounds, focusing here on compounds that interact with xenobiotic handling ABC transporters. We evaluate the use of ivermectin as a model substrate for these transporters. Compounds that increase sensitivity of bees to ivermectin may be inhibiting key transporters. We show that several compounds commonly encountered by honey bees (fumagillin, Pristine, quercetin) significantly increased honey bee mortality due to ivermectin and significantly reduced the LC50 of ivermectin suggesting that they may interfere with transporter function. These inhibitors also significantly increased honey bees sensitivity to the neonicotinoid insecticide acetamiprid. This mechanism-based strategy may dramatically reduce the number of tests needed to assess the possibility of adverse combinations among pesticides. We also demonstrate an in vivo transporter assay that provides physical evidence of transporter inhibition by tracking the dynamics of a fluorescent substrate of these transporters (Rhodamine B) in bee tissues. Significantly more Rhodamine B remains in the head and hemolymph of bees pretreated with higher concentrations of the transporter inhibitor verapamil. Mechanism-based strategies for simplifying the assessment of adverse chemical interactions such as described here could improve our ability to identify those combinations that pose significantly greater risk to bees and perhaps improve the risk assessment protocols for honey bees and similar sensitive species. PMID:26840460

Multi-Drug Resistance Transporters and a Mechanism-Based Strategy for Assessing Risks of Pesticide Combinations to Honey Bees.

PubMed

Guseman, Alex J; Miller, Kaliah; Kunkle, Grace; Dively, Galen P; Pettis, Jeffrey S; Evans, Jay D; vanEngelsdorp, Dennis; Hawthorne, David J

2016-01-01

Annual losses of honey bee colonies remain high and pesticide exposure is one possible cause. Dangerous combinations of pesticides, plant-produced compounds and antibiotics added to hives may cause or contribute to losses, but it is very difficult to test the many combinations of those compounds that bees encounter. We propose a mechanism-based strategy for simplifying the assessment of combinations of compounds, focusing here on compounds that interact with xenobiotic handling ABC transporters. We evaluate the use of ivermectin as a model substrate for these transporters. Compounds that increase sensitivity of bees to ivermectin may be inhibiting key transporters. We show that several compounds commonly encountered by honey bees (fumagillin, Pristine, quercetin) significantly increased honey bee mortality due to ivermectin and significantly reduced the LC50 of ivermectin suggesting that they may interfere with transporter function. These inhibitors also significantly increased honey bees sensitivity to the neonicotinoid insecticide acetamiprid. This mechanism-based strategy may dramatically reduce the number of tests needed to assess the possibility of adverse combinations among pesticides. We also demonstrate an in vivo transporter assay that provides physical evidence of transporter inhibition by tracking the dynamics of a fluorescent substrate of these transporters (Rhodamine B) in bee tissues. Significantly more Rhodamine B remains in the head and hemolymph of bees pretreated with higher concentrations of the transporter inhibitor verapamil. Mechanism-based strategies for simplifying the assessment of adverse chemical interactions such as described here could improve our ability to identify those combinations that pose significantly greater risk to bees and perhaps improve the risk assessment protocols for honey bees and similar sensitive species.

Shared and unique responses of plants to multiple individual stresses and stress combinations: physiological and molecular mechanisms

PubMed Central

Pandey, Prachi; Ramegowda, Venkategowda; Senthil-Kumar, Muthappa

2015-01-01

In field conditions, plants are often simultaneously exposed to multiple biotic and abiotic stresses resulting in substantial yield loss. Plants have evolved various physiological and molecular adaptations to protect themselves under stress combinations. Emerging evidences suggest that plant responses to a combination of stresses are unique from individual stress responses. In addition, plants exhibit shared responses which are common to individual stresses and stress combination. In this review, we provide an update on the current understanding of both unique and shared responses. Specific focus of this review is on heat–drought stress as a major abiotic stress combination and, drought–pathogen and heat–pathogen as examples of abiotic–biotic stress combinations. We also comprehend the current understanding of molecular mechanisms of cross talk in relation to shared and unique molecular responses for plant survival under stress combinations. Thus, the knowledge of shared responses of plants from individual stress studies and stress combinations can be utilized to develop varieties with broad spectrum stress tolerance. PMID:26442037

Insight into the phosphodiesterase mechanism from combined QM/MM free energy simulations.

PubMed

Wong, Kin-Yiu; Gao, Jiali

2011-07-01

Molecular dynamics simulations employing a combined quantum mechanical and molecular mechanical potential have been carried out to elucidate the reaction mechanism of the hydrolysis of a cyclic nucleotide cAMP substrate by phosphodiesterase 4B (PDE4B). PDE4B is a member of the PDE superfamily of enzymes that play crucial roles in cellular signal transduction. We have determined a two-dimensional potential of mean force (PMF) for the coupled phosphoryl bond cleavage and proton transfer through a general acid catalysis mechanism in PDE4B. The results indicate that the ring-opening process takes place through an S(N)2 reaction mechanism, followed by a proton transfer to stabilize the leaving group. The computed free energy of activation for the PDE4B-catalyzed cAMP hydrolysis is about 13 kcal·mol(-1) and an overall reaction free energy is about -17 kcal·mol(-1), both in accord with experimental results. In comparison with the uncatalyzed reaction in water, the enzyme PDE4B provides a strong stabilization of the transition state, lowering the free energy barrier by 14 kcal·mol(-1). We found that the proton transfer from the general acid residue His234 to the O3' oxyanion of the ribosyl leaving group lags behind the nucleophilic attack, resulting in a shallow minimum on the free energy surface. A key contributing factor to transition state stabilization is the elongation of the distance between the divalent metal ions Zn(2+) and Mg(2+) in the active site as the reaction proceeds from the Michaelis complex to the transition state. © 2011 The Authors Journal compilation © 2011 FEBS.

Mechanically fastened composite laminates subjected to combined bearing-bypass and shear loading

NASA Technical Reports Server (NTRS)

Madenci, Erdogan

1993-01-01

Bolts and rivets provide a means of load transfer in the construction of aircraft. However, they give rise to stress concentrations and are often the source and location of static and fatigue failures. Furthermore, fastener holes are prone to cracks during take-off and landing. These cracks present the most common origin of structural failures in aircraft. Therefore, accurate determination of the contact stresses associated with such loaded holes in mechanically fastened joints is essential to reliable strength evaluation and failure prediction. As the laminate is subjected to loading, the contact region, whose extent is not known, develops between the fastener and the hole boundary through this contact region, which consists of slip and no-slip zones due to friction. The presence of the unknown contact stress distribution over the contact region between the pin and the composite laminate, material anisotropy, friction between the pin and the laminate, pin-hole clearance, combined bearing-bypass and shear loading, and finite geometry of the laminate result in a complex non-linear problem. In the case of bearing-bypass loading in compression, this non-linear problem is further complicated by the presence of dual contact regions. Previous research concerning the analysis of mechanical joints subjected to combined bearing-bypass and shear loading is non-existent. In the case of bearing-bypass loading only, except for the study conducted by Naik and Crews (1991), others employed the concept of superposition which is not valid for this non-linear problem. Naik and Crews applied a linear finite element analysis with conditions along the pin-hole contact region specified as displacement constraint equations. The major shortcoming of this method is that the variation of the contract region as a function of the applied load should be known a priori. Also, their analysis is limited to symmetric geometry and material systems, and frictionless boundary conditions. Since the

Synergistic Antiproliferative Effects of Combined γ-Tocotrienol and PPARγ Antagonist Treatment Are Mediated through PPARγ-Independent Mechanisms in Breast Cancer Cells

PubMed Central

Sylvester, Paul W.

2014-01-01

Previous findings showed that the anticancer effects of combined γ-tocotrienol and peroxisome proliferator activated receptor γ (PPARγ) antagonist treatment caused a large reduction in PPARγ expression. However, other studies suggest that the antiproliferative effects of γ-tocotrienol and/or PPARγ antagonists are mediated, at least in part, through PPARγ-independent mechanism(s). Studies were conducted to characterize the role of PPARγ in mediating the effects of combined treatment of γ-tocotrienol with PPARγ agonists or antagonists on the growth of PPARγ negative +SA mammary cells and PPARγ-positive and PPARγ-silenced MCF-7 and MDA-MB-231 breast cancer cells. Combined treatment of γ-tocotrienol with PPARγ antagonist decreased, while combined treatment of γ-tocotrienol with PPARγ agonist increased, growth of all cancer cells. However, treatment with high doses of 15d-PGJ2, an endogenous natural ligand for PPARγ, had no effect on cancer cell growth. Western blot and qRT-PCR studies showed that the growth inhibitory effects of combined γ-tocotrienol and PPARγ antagonist treatment decreased cyclooxygenase (COX-2), prostaglandin synthase (PGDS), and prostaglandin D2 (PGD2) synthesis. In conclusion, the anticancer effects of combined γ-tocotrienol and PPARγ antagonists treatment in PPARγ negative/silenced breast cancer cells are mediated through PPARγ-independent mechanisms that are associated with a downregulation in COX-2, PGDS, and PGD2 synthesis. PMID:24729783

Economic Evaluation of the Combined Use of Warfarin and Low-dose Aspirin Versus Warfarin Alone in Mechanical Valve Prostheses.

PubMed

El-Hamamsy, Manal H; Elsisi, Gihan H; Eldessouki, Randa; Elmazar, Mohamed M; Taha, Ahmed S; Awad, Basma F; Elmansy, Hossam

2016-08-01

The use of combined therapy of antiplatelet and anticoagulant versus anticoagulant alone to reduce instances of thromboembolic events in patients with heart valve prostheses is an established standard of care in many countries but not in Egypt. A previous Markov model cost-effectiveness study on Egyptian patients aged 50-60 years demonstrated that the combined therapy reduces the overall treatment cost. However, due to the lack of actual real-world data on cost-effectiveness and the limitation of the Markov model study to 50- to 60-year-old patients, the Egyptian medical community is still questioning whether the added benefit is worth the cost. To assess, from the perspective of the Egyptian health sector, the cost-effectiveness of the combined use of warfarin and low-dose aspirin (75 mg) versus that of warfarin alone in patients with mechanical heart valve prostheses who began therapy between the age of 15 and 50 years. An economic evaluation was conducted alongside a randomized, controlled trial to assess the cost-effectiveness of the combined therapy in patients with mechanical valve prostheses. A total of 316 patients aged between 15 and 50 years were included in the study and randomly assigned to a group treated with both warfarin and aspirin or a group treated with warfarin alone. The patients in the combined therapy group exhibited a significantly longer duration of protection against the first event. Fewer primary events were observed in the patients treated with warfarin plus aspirin than in those treated with warfarin alone (1.4 %/year, vs. 4.8 %/year), and a higher mean quality-adjusted life-years (QALYs) value over 4 years was obtained for the group treated with warfarin plus aspirin (difference 0.058; 95 % CI 0.013-0.118), although this difference did not reach a conventional level of statistical significance. The total costs over a 4-year period were lower with the combined therapy (difference -US$244; 95 % CI -US$483.1 to -US$3.8), which

Mechanism of Sporicidal Activity for the Synergistic Combination of Peracetic Acid and Hydrogen Peroxide.

PubMed

Leggett, Mark J; Schwarz, J Spencer; Burke, Peter A; McDonnell, Gerald; Denyer, Stephen P; Maillard, Jean-Yves

2016-02-15

There is still great interest in controlling bacterial endospores. The use of chemical disinfectants and, notably, oxidizing agents to sterilize medical devices is increasing. With this in mind, hydrogen peroxide (H2O2) and peracetic acid (PAA) have been used in combination, but until now there has been no explanation for the observed increase in sporicidal activity. This study provides information on the mechanism of synergistic interaction of PAA and H2O2 against bacterial spores. We performed investigations of the efficacies of different combinations, including pretreatments with the two oxidizers, against wild-type spores and a range of spore mutants deficient in the spore coat or small acid-soluble spore proteins. The concentrations of the two biocides were also measured in the reaction vessels, enabling the assessment of any shift from H2O2 to PAA formation. This study confirmed the synergistic activity of the combination of H2O2 and PAA. However, we observed that the sporicidal activity of the combination is largely due to PAA and not H2O2. Furthermore, we observed that the synergistic combination was based on H2O2 compromising the spore coat, which was the main spore resistance factor, likely allowing better penetration of PAA and resulting in the increased sporicidal activity. Copyright © 2016 Leggett et al.

Mechanism of Sporicidal Activity for the Synergistic Combination of Peracetic Acid and Hydrogen Peroxide

PubMed Central

Leggett, Mark J.; Schwarz, J. Spencer; Burke, Peter A.; McDonnell, Gerald; Denyer, Stephen P.

2015-01-01

There is still great interest in controlling bacterial endospores. The use of chemical disinfectants and, notably, oxidizing agents to sterilize medical devices is increasing. With this in mind, hydrogen peroxide (H2O2) and peracetic acid (PAA) have been used in combination, but until now there has been no explanation for the observed increase in sporicidal activity. This study provides information on the mechanism of synergistic interaction of PAA and H2O2 against bacterial spores. We performed investigations of the efficacies of different combinations, including pretreatments with the two oxidizers, against wild-type spores and a range of spore mutants deficient in the spore coat or small acid-soluble spore proteins. The concentrations of the two biocides were also measured in the reaction vessels, enabling the assessment of any shift from H2O2 to PAA formation. This study confirmed the synergistic activity of the combination of H2O2 and PAA. However, we observed that the sporicidal activity of the combination is largely due to PAA and not H2O2. Furthermore, we observed that the synergistic combination was based on H2O2 compromising the spore coat, which was the main spore resistance factor, likely allowing better penetration of PAA and resulting in the increased sporicidal activity. PMID:26637595

Clinical and Procedural Predictors of Outcomes From the Endovascular Treatment of Posterior Circulation Strokes.

PubMed

Mokin, Maxim; Sonig, Ashish; Sivakanthan, Sananthan; Ren, Zeguang; Elijovich, Lucas; Arthur, Adam; Goyal, Nitin; Kan, Peter; Duckworth, Edward; Veznedaroglu, Erol; Binning, Mandy J; Liebman, Kenneth M; Rao, Vikas; Turner, Raymond D; Turk, Aquilla S; Baxter, Blaise W; Dabus, Guilherme; Linfante, Italo; Snyder, Kenneth V; Levy, Elad I; Siddiqui, Adnan H

2016-03-01

Patients with posterior circulation strokes have been excluded from recent randomized endovascular stroke trials. We reviewed the recent multicenter experience with endovascular treatment of posterior circulation strokes to identify the clinical, radiographic, and procedural predictors of successful recanalization and good neurological outcomes. We performed a multicenter retrospective analysis of consecutive patients with posterior circulation strokes, who underwent thrombectomy with stent retrievers or primary aspiration thrombectomy (including A Direct Aspiration First Pass Technique [ADAPT] approach). We correlated clinical and radiographic outcomes with demographic, clinical, and technical characteristics. A total of 100 patients were included in the final analysis (mean age, 63.5±14.2 years; mean admission National Institutes of Health Stroke Scale score, 19.2±8.2). Favorable clinical outcome at 3 months (modified Rankin Scale score ≤2) was achieved in 35% of patients. Successful recanalization and shorter time from stroke onset to the start of the procedure were significant predictors of favorable clinical outcome at 90 days. Stent retriever and aspiration thrombectomy as primary treatment approaches showed comparable procedural and clinical outcomes. None of the baseline advanced imaging modalities (magnetic resonance imaging, computed tomographic perfusion, or computed tomography angiography assessment of collaterals) showed superiority in selecting patients for thrombectomy. Time to the start of the procedure is an important predictor of clinical success after thrombectomy in patients with posterior circulation strokes. Both stent retriever and aspiration thrombectomy as primary treatment approaches are effective in achieving successful recanalization. © 2016 American Heart Association, Inc.

Simulation of Semi-Solid Material Mechanical Behavior Using a Combined Discrete/Finite Element Method

NASA Astrophysics Data System (ADS)

Sistaninia, M.; Phillion, A. B.; Drezet, J.-M.; Rappaz, M.

2011-01-01

As a necessary step toward the quantitative prediction of hot tearing defects, a three-dimensional stress-strain simulation based on a combined finite element (FE)/discrete element method (DEM) has been developed that is capable of predicting the mechanical behavior of semisolid metallic alloys during solidification. The solidification model used for generating the initial solid-liquid structure is based on a Voronoi tessellation of randomly distributed nucleation centers and a solute diffusion model for each element of this tessellation. At a given fraction of solid, the deformation is then simulated with the solid grains being modeled using an elastoviscoplastic constitutive law, whereas the remaining liquid layers at grain boundaries are approximated by flexible connectors, each consisting of a spring element and a damper element acting in parallel. The model predictions have been validated against Al-Cu alloy experimental data from the literature. The results show that a combined FE/DEM approach is able to express the overall mechanical behavior of semisolid alloys at the macroscale based on the morphology of the grain structure. For the first time, the localization of strain in the intergranular regions is taken into account. Thus, this approach constitutes an indispensible step towards the development of a comprehensive model of hot tearing.

Vena cava thrombectomy and primary repair after radical nephrectomy for renal cell carcinoma: single-center experience.

PubMed

Helfand, Brian T; Smith, Norm D; Kozlowski, James M; Eskandari, Mark K

2011-01-01

Inferior vena cava (IVC) reconstruction for locally advanced renal cell carcinoma (RCC) includes resection with and without interposition grafting, patch graft, or primary repair. The proposed benefits of lateral venorrhaphy and primary repair are avoidance of foreign material, a more expeditious repair, and preservation of lower extremity venous outflow. A single-center retrospective review of 22 patients with RCC and IVC tumor thrombus treated with radical nephrectomy, lateral venorrhaphy, thrombectomy, and primary vena cava repair between July 2002 and June 2009 was carried out. Demographic data, diagnostic information, radiographic cross-sectional imaging, and procedural outcomes were examined. Among the 13 men and nine women, the mean age was 62.1 years (42-83); mean tumor size was 9.8 cm (3-17 cm), and 90% (n = 18) of the cases with RCC were identified pathologically as clear cell adenocarcinoma; on the basis of the classification system adopted by Neves, level I was for 50% (n = 11), level II for 32% (n = 7), level III for 9% (n = 2), and level IV for 9% (n = 2) of the patients. All patients underwent en bloc radical nephrectomy with tumor thrombus removal and primary IVC repair. Mean total operative time was 547.9 ± 138.5 minutes, whereas mean IVC cross-clamp time was 10.8 minutes (6-29 minutes). There were no intraoperative deaths or pulmonary embolism and all IVC margins were found to be pathologically negative. Postoperative complications included one pulmonary embolism, one exacerbation of chronic lymphedema, and two cases of new onset erectile dysfunction. Mean follow-up was 36.4 ± 23.2 months (6-92 months). There were no radiographic or clinically significant changes in mean IVC diameter during follow-up. Five late deaths (23%) occurred as a result of metastatic RCC over a mean period of 24 months (range, 12-48), but without any local recurrences. For advanced RCC with tumor thrombus extension into the IVC, lateral venorrhaphy and primary IVC repair

Mechanism of red mud combined with Fenton's reagent in sewage sludge conditioning.

PubMed

Zhang, Hao; Yang, Jiakuan; Yu, Wenbo; Luo, Sen; Peng, Li; Shen, Xingxing; Shi, Yafei; Zhang, Shinan; Song, Jian; Ye, Nan; Li, Ye; Yang, Changzhu; Liang, Sha

2014-08-01

Red mud was evaluated as an alternative skeleton builder combined with Fenton's reagent in sewage sludge conditioning. The results show that red mud combined with Fenton's reagent showed good conditioning capability with the pH of the filtrate close to neutrality, indicating that red mud acted as a neutralizer as well as a skeleton builder when jointly used with Fenton's reagent. Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. Thus, sludge dewatering performance was effectively improved. The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Combined use of leptin and mechanical stress has osteogenic effects on ossification of the posterior longitudinal ligament.

PubMed

Chen, Shuai; Zhu, Haifeng; Wang, Gangliang; Xie, Ziang; Wang, Jiying; Chen, Jian

2018-06-16

To evaluate the effects of leptin/leptin receptor (LepR) combined with mechanical stress on the development of ossification of the posterior longitudinal ligament (OPLL), which is a disease characterized by ectopic bone formation of the posterior longitudinal ligament (PLL) and can lead to radiculopathy and myelopathy. Six human samples of the PLL were analyzed for the expression of leptin and LepR by RT-PCR and western blotting. PLL cells were stimulated with leptin and mechanical stress delivered via a Flexcell tension system, and osteogenic differentiation was evaluated by RT-PCR and western blotting analysis of osteogenic marker expression as well as by alkaline phosphatase (ALP) staining and alizarin red S staining. Activation of mitogen-activated protein kinase (MAPK), Janus kinase (JAK) 2-signal transducer, activator of transcription (STAT) 3 and phosphatidylinositol 3-kinase (PI3K)-Akt was evaluated by western blotting. Samples from the OPLL group had higher LepR mRNA and protein levels and lower leptin levels than those from healthy controls. Exposure to leptin and Flexcell increased the number of ALP-positive cells and calcium nodules in a dose-dependent manner; this effect was accompanied by upregulation of the osteogenic markers osteocalcin, runt-related transcription factor 2 (RUNX2) and osteopontin. Extracellular signal-regulated kinase, P38 MAPK, JAK2, STAT3, PI3K and Akt signaling, was also activated by the combined effects of leptin and mechanical stress. Leptin and LepR are differentially expressed in OPLL tissues, and the combined use of leptin/LepR and mechanical stress promotes osteogenic differentiation of PLL cells via MAPK, JAK2-STAT3 and PI3K/Akt signaling. These slides can be retrieved under Electronic Supplementary Material.

Treating electrostatics with Wolf summation in combined quantum mechanical and molecular mechanical simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ojeda-May, Pedro; Pu, Jingzhi, E-mail: jpu@iupui.edu

The Wolf summation approach [D. Wolf et al., J. Chem. Phys. 110, 8254 (1999)], in the damped shifted force (DSF) formalism [C. J. Fennell and J. D. Gezelter, J. Chem. Phys. 124, 234104 (2006)], is extended for treating electrostatics in combined quantum mechanical and molecular mechanical (QM/MM) molecular dynamics simulations. In this development, we split the QM/MM electrostatic potential energy function into the conventional Coulomb r{sup −1} term and a term that contains the DSF contribution. The former is handled by the standard machinery of cutoff-based QM/MM simulations whereas the latter is incorporated into the QM/MM interaction Hamiltonian as amore » Fock matrix correction. We tested the resulting QM/MM-DSF method for two solution-phase reactions, i.e., the association of ammonium and chloride ions and a symmetric SN{sub 2} reaction in which a methyl group is exchanged between two chloride ions. The performance of the QM/MM-DSF method was assessed by comparing the potential of mean force (PMF) profiles with those from the QM/MM-Ewald and QM/MM-isotropic periodic sum (IPS) methods, both of which include long-range electrostatics explicitly. For ion association, the QM/MM-DSF method successfully eliminates the artificial free energy drift observed in the QM/MM-Cutoff simulations, in a remarkable agreement with the two long-range-containing methods. For the SN{sub 2} reaction, the free energy of activation obtained by the QM/MM-DSF method agrees well with both the QM/MM-Ewald and QM/MM-IPS results. The latter, however, requires a greater cutoff distance than QM/MM-DSF for a proper convergence of the PMF. Avoiding time-consuming lattice summation, the QM/MM-DSF method yields a 55% reduction in computational cost compared with the QM/MM-Ewald method. These results suggest that, in addition to QM/MM-IPS, the QM/MM-DSF method may serve as another efficient and accurate alternative to QM/MM-Ewald for treating electrostatics in condensed-phase simulations of

Treating electrostatics with Wolf summation in combined quantum mechanical and molecular mechanical simulations.

PubMed

Ojeda-May, Pedro; Pu, Jingzhi

2015-11-07

The Wolf summation approach [D. Wolf et al., J. Chem. Phys. 110, 8254 (1999)], in the damped shifted force (DSF) formalism [C. J. Fennell and J. D. Gezelter, J. Chem. Phys. 124, 234104 (2006)], is extended for treating electrostatics in combined quantum mechanical and molecular mechanical (QM/MM) molecular dynamics simulations. In this development, we split the QM/MM electrostatic potential energy function into the conventional Coulomb r(-1) term and a term that contains the DSF contribution. The former is handled by the standard machinery of cutoff-based QM/MM simulations whereas the latter is incorporated into the QM/MM interaction Hamiltonian as a Fock matrix correction. We tested the resulting QM/MM-DSF method for two solution-phase reactions, i.e., the association of ammonium and chloride ions and a symmetric SN2 reaction in which a methyl group is exchanged between two chloride ions. The performance of the QM/MM-DSF method was assessed by comparing the potential of mean force (PMF) profiles with those from the QM/MM-Ewald and QM/MM-isotropic periodic sum (IPS) methods, both of which include long-range electrostatics explicitly. For ion association, the QM/MM-DSF method successfully eliminates the artificial free energy drift observed in the QM/MM-Cutoff simulations, in a remarkable agreement with the two long-range-containing methods. For the SN2 reaction, the free energy of activation obtained by the QM/MM-DSF method agrees well with both the QM/MM-Ewald and QM/MM-IPS results. The latter, however, requires a greater cutoff distance than QM/MM-DSF for a proper convergence of the PMF. Avoiding time-consuming lattice summation, the QM/MM-DSF method yields a 55% reduction in computational cost compared with the QM/MM-Ewald method. These results suggest that, in addition to QM/MM-IPS, the QM/MM-DSF method may serve as another efficient and accurate alternative to QM/MM-Ewald for treating electrostatics in condensed-phase simulations of chemical reactions.

Treating electrostatics with Wolf summation in combined quantum mechanical and molecular mechanical simulations

NASA Astrophysics Data System (ADS)

Ojeda-May, Pedro; Pu, Jingzhi

2015-11-01

The Wolf summation approach [D. Wolf et al., J. Chem. Phys. 110, 8254 (1999)], in the damped shifted force (DSF) formalism [C. J. Fennell and J. D. Gezelter, J. Chem. Phys. 124, 234104 (2006)], is extended for treating electrostatics in combined quantum mechanical and molecular mechanical (QM/MM) molecular dynamics simulations. In this development, we split the QM/MM electrostatic potential energy function into the conventional Coulomb r-1 term and a term that contains the DSF contribution. The former is handled by the standard machinery of cutoff-based QM/MM simulations whereas the latter is incorporated into the QM/MM interaction Hamiltonian as a Fock matrix correction. We tested the resulting QM/MM-DSF method for two solution-phase reactions, i.e., the association of ammonium and chloride ions and a symmetric SN2 reaction in which a methyl group is exchanged between two chloride ions. The performance of the QM/MM-DSF method was assessed by comparing the potential of mean force (PMF) profiles with those from the QM/MM-Ewald and QM/MM-isotropic periodic sum (IPS) methods, both of which include long-range electrostatics explicitly. For ion association, the QM/MM-DSF method successfully eliminates the artificial free energy drift observed in the QM/MM-Cutoff simulations, in a remarkable agreement with the two long-range-containing methods. For the SN2 reaction, the free energy of activation obtained by the QM/MM-DSF method agrees well with both the QM/MM-Ewald and QM/MM-IPS results. The latter, however, requires a greater cutoff distance than QM/MM-DSF for a proper convergence of the PMF. Avoiding time-consuming lattice summation, the QM/MM-DSF method yields a 55% reduction in computational cost compared with the QM/MM-Ewald method. These results suggest that, in addition to QM/MM-IPS, the QM/MM-DSF method may serve as another efficient and accurate alternative to QM/MM-Ewald for treating electrostatics in condensed-phase simulations of chemical reactions.

Mechanisms of tramadol-related neurotoxicity in the rat: Does diazepam/tramadol combination play a worsening role in overdose?

PubMed

Lagard, Camille; Chevillard, Lucie; Malissin, Isabelle; Risède, Patricia; Callebert, Jacques; Labat, Laurence; Launay, Jean-Marie; Laplanche, Jean-Louis; Mégarbane, Bruno

2016-11-01

Poisoning with opioid analgesics including tramadol represents a challenge. Tramadol may induce respiratory depression, seizures and serotonin syndrome, possibly worsened when in combination to benzodiazepines. Our objectives were to investigate tramadol-related neurotoxicity, consequences of diazepam/tramadol combination, and mechanisms of drug-drug interactions in rats. Median lethal-doses were determined using Dixon-Bruce's up-and-down method. Sedation, seizures, electroencephalography and plethysmography parameters were studied. Concentrations of tramadol and its metabolites were measured using liquid-chromatography-high-resolution-mass-spectrometry. Plasma, platelet and brain monoamines were measured using liquid-chromatography coupled to fluorimetry. Median lethal-doses of tramadol and diazepam/tramadol combination did not significantly differ, although time-to-death was longer with combination (P=0.04). Tramadol induced dose-dependent sedation (P<0.05), early-onset seizures (P<0.001) and increase in inspiratory (P<0.01) and expiratory times (P<0.05). The diazepam/tramadol combination abolished seizures but significantly enhanced sedation (P<0.01) and respiratory depression (P<0.05) by reducing tidal volume (P<0.05) in addition to tramadol-related increase in respiratory times, suggesting a pharmacodynamic mechanism of interaction. Plasma M1 and M5 metabolites were mildly increased, contributing additionally to tramadol-related respiratory depression. Tramadol-induced early-onset increase in brain concentrations of serotonin and norepinephrine was not significantly altered by the diazepam/tramadol combination. Interestingly neither pretreatment with cyproheptadine (a serotonin-receptor antagonist) nor a benserazide/5-hydroxytryptophane combination (enhancing brain serotonin) reduced tramadol-induced seizures. Our study shows that diazepam/tramadol combination does not worsen tramadol-induced fatality risk but alters its toxicity pattern with enhanced

Combined quantum-mechanics/molecular-mechanics dynamics simulation of A-DNA double strands irradiated by ultra-low-energy carbon ions

NASA Astrophysics Data System (ADS)

Ngaojampa, C.; Nimmanpipug, P.; Yu, L. D.; Anuntalabhochai, S.; Lee, V. S.

2011-02-01

In order to promote understanding of the fundamentals of ultra-low-energy ion interaction with DNA, molecular dynamics simulations using combined quantum-mechanics/molecular-mechanics of poly-AT and poly-GC A-DNA double strands irradiated by <200 eV carbon ions were performed to investigate the molecular implications of mutation bias. The simulations were focused on the responses of the DNA backbones and nitrogenous bases to irradiation. Analyses of the root mean square displacements of the backbones and non-hydrogen atoms of base rings of the simulated DNA structure after irradiation revealed a potential preference of DNA double strand separation, dependent on the irradiating energy. The results show that for the backbones, the large difference in the displacement between poly-GC and poly-AT in the initial time period could be the reason for the backbone breakage; for the nitrogenous base pairs, A-T is 30% more sensitive or vulnerable to ion irradiation than G-C, demonstrating a preferential, instead of random, effect of irradiation-induced mutation.

Measuring the mechanical properties of plant cells by combining micro-indentation with osmotic treatments.

PubMed

Weber, Alain; Braybrook, Siobhan; Huflejt, Michal; Mosca, Gabriella; Routier-Kierzkowska, Anne-Lise; Smith, Richard S

2015-06-01

Growth in plants results from the interaction between genetic and signalling networks and the mechanical properties of cells and tissues. There has been a recent resurgence in research directed at understanding the mechanical aspects of growth, and their feedback on genetic regulation. This has been driven in part by the development of new micro-indentation techniques to measure the mechanical properties of plant cells in vivo. However, the interpretation of indentation experiments remains a challenge, since the force measures results from a combination of turgor pressure, cell wall stiffness, and cell and indenter geometry. In order to interpret the measurements, an accurate mechanical model of the experiment is required. Here, we used a plant cell system with a simple geometry, Nicotiana tabacum Bright Yellow-2 (BY-2) cells, to examine the sensitivity of micro-indentation to a variety of mechanical and experimental parameters. Using a finite-element mechanical model, we found that, for indentations of a few microns on turgid cells, the measurements were mostly sensitive to turgor pressure and the radius of the cell, and not to the exact indenter shape or elastic properties of the cell wall. By complementing indentation experiments with osmotic experiments to measure the elastic strain in turgid cells, we could fit the model to both turgor pressure and cell wall elasticity. This allowed us to interpret apparent stiffness values in terms of meaningful physical parameters that are relevant for morphogenesis. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Elastomers in Combined Rolling-Sliding Contact; Wear and its Underlying Mechanisms

NASA Astrophysics Data System (ADS)

Rowe, Kyle Gene

Elastomeric materials, specifically rubbers, being both of a practical and scientific importance, have been the subjects of vast amounts of research spanning well over two centuries. There is currently a large effort by tire manufacturers to design new rubber compounds with lower rolling resistance, higher sliding friction, and reduced or predictable wear. At present, these efforts are primarily based on a few empirical rules and very costly trial and error testing; only a basic understanding of the mechanisms involved in the wear of elastomeric materials exists despite rigorous study. In general, the only well controlled experiments have been for simple loading and sliding schemes. The aim of this work is to characterize the tribological properties of a carbon black filled natural rubber sample. This work explores (1) its behavior in unidirectional sliding, (2) contact mechanics, (3) traction properties in combined rolling and sliding, (4) frictional heating response, and (5) wear. It was found that the friction coefficient of this material was dependent upon sliding velocity, contact pressure, and surface roughness. The high friction coefficients also lead to a bifurcation of the contact area into two different pressure regimes at sliding velocities greater than 10 mm/s . The traction response of this material in combined rolling and sliding exhibited similar behavior, being a function of the contact pressure, but not rolling velocity. The wear of this material was found to be linearly dependent upon the global slip condition and occurred preferentially on the sample. Investigations of the worn surface revealed that the most likely mechanism of wear is the degradation of surface material in a confined layer a few micrometers thick. A simple spring-mass model was developed to offer an explanation of localized wear. It was found that the coupling of system elements in the normal direction helped to shift the load from wearing elements to non-wearing ones. The

Antifungal mechanism of the combination of Cinnamomum verum and Pelargonium graveolens essential oils with fluconazole against pathogenic Candida strains.

PubMed

Essid, Rym; Hammami, Majdi; Gharbi, Dorra; Karkouch, Ines; Hamouda, Thouraya Ben; Elkahoui, Salem; Limam, Ferid; Tabbene, Olfa

2017-09-01

The present study aimed to investigate the anti-Candida activity of ten essential oils (EOs) and to evaluate their potential synergism with conventional drugs. The effect on secreted aspartic protease (SAP) activity and the mechanism of action were also explored. The antifungal properties of essential oils were investigated using standard micro-broth dilution assay. Only Cinnamomum verum, Thymus capitatus, Syzygium aromaticum, and Pelargonium graveolens exhibited a broad spectrum of activity against a variety of pathogenic Candida strains. Chemical composition of active essential oils was performed by gas chromatography-mass spectrometry (GC-MS). Synergistic effect was observed with the combinations C. verum/fluconazole and P. graveolens/fluconazole, with FIC value 0.37. Investigation of the mechanism of action revealed that C. verum EO reduced the quantity of ergosterol to 83%. A total inhibition was observed for the combination C. verum/fluconazole. However, P. graveolens EO may disturb the permeability barrier of the fungal cell wall. An increase of MIC values of P. graveolens EO and the combination with fluconazole was observed with osmoprotectants (sorbitol and PEG6000). Furthermore, the combination with fluconazole may affect ergosterol biosynthesis and disturb fatty acid homeostasis in C. albicans cells as the quantity of ergosterol and oleic acid was reduced to 52.33 and 72%, respectively. The combination of P. graveolens and C. verum EOs with fluconazole inhibited 78.31 and 64.72% SAP activity, respectively. To our knowledge, this is the first report underlying the mechanism of action and the inhibitory effect of SAP activity of essential oils in synergy with fluconazole. Naturally occurring phytochemicals C. verum and P. graveolens could be effective candidate to enhance the efficacy of fluconazole-based therapy of C. albicans infections.

Combination of dynamic transformation and dynamic recrystallization for realizing ultrafine-grained steels with superior mechanical properties

PubMed Central

Zhao, Lijia; Park, Nokeun; Tian, Yanzhong; Shibata, Akinobu; Tsuji, Nobuhiro

2016-01-01

Dynamic recrystallization (DRX) is an important grain refinement mechanism to fabricate steels with high strength and high ductility (toughness). The conventional DRX mechanism has reached the limitation of refining grains to several microns even though employing high-strain deformation. Here we show a DRX phenomenon occurring in the dynamically transformed (DT) ferrite, by which the required strain for the operation of DRX and the formation of ultrafine grains is significantly reduced. The DRX of DT ferrite shows an unconventional temperature dependence, which suggests an optimal condition for grain refinement. We further show that new strategies for ultra grain refinement can be evoked by combining DT and DRX mechanisms, based on which fully ultrafine microstructures having a mean grain size down to 0.35 microns can be obtained without high-strain deformation and exhibit superior mechanical properties. This study will open the door to achieving optimal grain refinement to nanoscale in a variety of steels requiring no high-strain deformation in practical industrial application. PMID:27966603

Effect of combined extrusion parameters on mechanical properties of basalt fiber-reinforced plastics based on polypropylene

NASA Astrophysics Data System (ADS)

Bashtannik, P. I.; Ovcharenko, V. G.; Boot, Yu. A.

1997-11-01

Basalt fibers are efficient reinforcing fillers for polypropylene because they increase both the mechanical and the tribotechnical properties of composites. Basalt fibers can compete with traditional fillers (glass and asbestos fibers) of polypropylene with respect to technological, economic, and toxic properties. The effect of technological parameters of producing polypropylene-based basalt fiber-reinforced plastics (BFRPs) by combined extrusion on their mechanical properties has been investigated. The extrusion temperature was found to be the main parameter determining the mechanical properties of the BFRPs. With temperature growth from 180 to 240°C, the residual length of the basalt fibers in the composite, as well as the adhesive strength of the polymer-fiber system, increased, while the composite defectiveness decreased. The tensile strength and elastic modulus increased from 35 to 42 MPa and 3.2 to 4.2 GPa, respectively. At the same time, the growth in composite solidity led to its higher brittleness. Thus, a higher temperature of extrusion allows us to produce materials which can be subjected to tensile and bending loads, while the materials produced at a lower temperature of extrusion are impact stable. The effect of the gap size between the extruder body and moving disks on the mechanical properties of the BFRPs is less significant than that of temperature. An increase of the gap size from 2 to 8 mm improves the impregnation quality of the fibers, but the extruder productivity diminishes. The possibility of controling the properties of reinforced polypropylene by varying the technological parameters of combined extrusion is shown. The polypropylene-based BFRPs produced by the proposed method surpass the properties of glass and asbestos fiber-reinforced plastics.

Synergistic Effects and Mechanisms of Budesonide in Combination with Fluconazole against Resistant Candida albicans.

PubMed

Li, Xiuyun; Yu, Cuixiang; Huang, Xin; Sun, Shujuan

2016-01-01

Candida albicans is an important opportunistic pathogen, causing both superficial mucosal infections and life-threatening systemic diseases in the clinic. The emergence of drug resistance in Candida albicans has become a noteworthy phenomenon due to the extensive use of antifungal agents and the development of biofilms. This study showed that budesonide potentiates the antifungal effect of fluconazole against fluconazole-resistant Candida albicans strains both in vitro and in vivo. In addition, our results demonstrated, for the first time, that the combination of fluconazole and budesonide can reverse the resistance of Candida albicans by inhibiting the function of drug transporters, reducing the formation of biofilms, promoting apoptosis and inhibiting the activity of extracellular phospholipases. This is the first study implicating the effects and mechanisms of budesonide against Candida albicans alone or in combination with fluconazole, which may ultimately lead to the identification of new potential antifungal targets.

Mechanical energy profiles of the combined ankle-foot system in normal gait: insights for prosthetic designs.

PubMed

Takahashi, Kota Z; Stanhope, Steven J

2013-09-01

Over the last half-century, the field of prosthetic engineering has continuously evolved with much attention being dedicated to restoring the mechanical energy properties of ankle joint musculatures during gait. However, the contributions of 'distal foot structures' (e.g., foot muscles, plantar soft tissue) have been overlooked. Therefore, the purpose of this study was to quantify the total mechanical energy profiles (e.g., power, work, and work-ratio) of the natural ankle-foot system (NAFS) by combining the contributions of the ankle joint and all distal foot structures during stance in level-ground steady state walking across various speeds (0.4, 0.6, 0.8 and 1.0 statures/s). The results from eleven healthy subjects walking barefoot indicated ankle joint and distal foot structures generally performed opposing roles: the ankle joint performed net positive work that systematically increased its energy generation with faster walking speeds, while the distal foot performed net negative work that systematically increased its energy absorption with faster walking speeds. Accounting for these simultaneous effects, the combined ankle-foot system exhibited increased work-ratios with faster walking. Most notably, the work-ratio was not significantly greater than 1.0 during the normal walking speed of 0.8 statures/s. Therefore, a prosthetic design that strategically exploits passive-dynamic properties (e.g., elastic energy storage and return) has the potential to replicate the mechanical energy profiles of the NAFS during level-ground steady-state walking. Copyright © 2013 Elsevier B.V. All rights reserved.

Dynamic Response and Failure Mechanism of Brittle Rocks Under Combined Compression-Shear Loading Experiments

NASA Astrophysics Data System (ADS)

Xu, Yuan; Dai, Feng

2018-03-01

A novel method is developed for characterizing the mechanical response and failure mechanism of brittle rocks under dynamic compression-shear loading: an inclined cylinder specimen using a modified split Hopkinson pressure bar (SHPB) system. With the specimen axis inclining to the loading direction of SHPB, a shear component can be introduced into the specimen. Both static and dynamic experiments are conducted on sandstone specimens. Given carefully pulse shaping, the dynamic equilibrium of the inclined specimens can be satisfied, and thus the quasi-static data reduction is employed. The normal and shear stress-strain relationships of specimens are subsequently established. The progressive failure process of the specimen illustrated via high-speed photographs manifests a mixed failure mode accommodating both the shear-dominated failure and the localized tensile damage. The elastic and shear moduli exhibit certain loading-path dependence under quasi-static loading but loading-path insensitivity under high loading rates. Loading rate dependence is evidently demonstrated through the failure characteristics involving fragmentation, compression and shear strength and failure surfaces based on Drucker-Prager criterion. Our proposed method is convenient and reliable to study the dynamic response and failure mechanism of rocks under combined compression-shear loading.

Recolonization of the oral cavity by Streptococcus mutans after a combined mechanical/chemical antisepsis protocol.

PubMed

Farina, R; Squarzoni, M A; Calura, G; Trombelli, L

2009-06-01

The bacterial colonization of teeth by Streptococcus mutans (StrepM) represents a major risk factor for the development of dental caries. At present, no clinical studies have explored the effect of a combined mechanical-chemical antisepsis protocol in a periodontally-healthy population and the pattern of recolonization of StrepM in subjects whose StrepM infection was successfully eradicated. The present study was designed in order to 1) determine the salivary and plaque changes in StrepM content after a combined mechanical/chemical antisepsis protocol; and 2) evaluate the pattern of recolonization when StrepM was successfully eradicated from saliva and plaque. Thirty-five periodontally-healthy and caries-susceptible subjects successfully entered and concluded the study. At baseline, non-surgical periodontal therapy was performed according to the principles of full mouth disinfection. Adjunctive home-based rinsing with a 0.2% chlorhexidine mouthrinse was requested for the following week. StrepM concentration was assessed in saliva and plaque at the initial contact appointment, at baseline, and 1-week, 1-month, 3-month and 6-month follow-up. A significant effect of ''time'' on StrepM concentration in saliva and plaque was observed (P<0.000). In subjects with successful eradication of StrepM at 1 week (N=17 plaque samples), StrepM infection recurrence occurred within 3-6 months. The results of the present study demonstrated that 1) the application of the investigated mechanical/chemical antisepsis protocol can effectively reduce StrepM colonies in saliva and plaque of periodontally healthy subjects; and 2) in plaque samples, StrepM infection recurrence tends to occur within 3-6 months.

Intra-aortic balloon pump combined with mechanical ventilation for treating patients aged > 60 years in cardiogenic shock: Retrospective analysis

PubMed Central

Liu, Hongwei; Wu, Xueping; Zhao, Xiaoning; Zhu, Ping

2016-01-01

Objective To examine if mechanical ventilation with positive end-expiratory pressure (PEEP) combined with intra-aortic balloon pump (IABP) provided a better outcome than IABP alone for the treatment of cardiogenic shock after acute myocardial infarction in patients aged > 60 years. Methods This was a retrospective analysis of data from patients in cardiogenic shock, refractory to pharmacological therapy and treated at a geriatric coronary care unit. Results Sixty-two patients were eligible for study inclusion: 33 received IABP alone; 29 received IABP combined with mechanical ventilation. Patients in the IABP + mechanical ventilation group had lower mean arterial blood pressure (BP), systolic BP and partial pressure of oxygen compared with the IABP group, indicating worse cardiac and pulmonary function. In addition, higher rates of pulmonary infection and renal insufficiency were observed in the IABP + mechanical ventilation group than in the IABP group. A statistically significant improvement of left ventricular function before and after treatment was observed in the IABP + mechanical ventilation group, but not in the IABP group. Pulmonary infection and renal insufficiency were risk factors for all-cause in-hospital mortality; successful revascularization was a negative risk factor. There was no between-group difference in survival. Conclusion Mechanical ventilation with an appropriate level of PEEP appears to enhance the beneficial effects of IABP on left ventricular function for patients in cardiogenic shock. PMID:27020597

Mechanisms of tramadol-related neurotoxicity in the rat: Does diazepam/tramadol combination play a worsening role in overdose?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lagard, Camille, E-mail: camille.lagard@gmail.com

Poisoning with opioid analgesics including tramadol represents a challenge. Tramadol may induce respiratory depression, seizures and serotonin syndrome, possibly worsened when in combination to benzodiazepines. Our objectives were to investigate tramadol-related neurotoxicity, consequences of diazepam/tramadol combination, and mechanisms of drug-drug interactions in rats. Median lethal-doses were determined using Dixon–Bruce's up-and-down method. Sedation, seizures, electroencephalography and plethysmography parameters were studied. Concentrations of tramadol and its metabolites were measured using liquid-chromatography-high-resolution-mass-spectrometry. Plasma, platelet and brain monoamines were measured using liquid-chromatography coupled to fluorimetry. Median lethal-doses of tramadol and diazepam/tramadol combination did not significantly differ, although time-to-death was longer with combination (P =more » 0.04). Tramadol induced dose-dependent sedation (P < 0.05), early-onset seizures (P < 0.001) and increase in inspiratory (P < 0.01) and expiratory times (P < 0.05). The diazepam/tramadol combination abolished seizures but significantly enhanced sedation (P < 0.01) and respiratory depression (P < 0.05) by reducing tidal volume (P < 0.05) in addition to tramadol-related increase in respiratory times, suggesting a pharmacodynamic mechanism of interaction. Plasma M1 and M5 metabolites were mildly increased, contributing additionally to tramadol-related respiratory depression. Tramadol-induced early-onset increase in brain concentrations of serotonin and norepinephrine was not significantly altered by the diazepam/tramadol combination. Interestingly neither pretreatment with cyproheptadine (a serotonin-receptor antagonist) nor a benserazide/5-hydroxytryptophane combination (enhancing brain serotonin) reduced tramadol-induced seizures. Our study shows that diazepam/tramadol combination does not worsen tramadol-induced fatality risk but alters its toxicity

Combined quantum and molecular mechanics (QM/MM).

PubMed

Friesner, Richard A

2004-12-01

We describe the current state of the art of mixed quantum mechanics/molecular mechanics (QM/MM) methodology, with a particular focus on modeling of enzymatic reactions. Over the past decade, the effectiveness of these methods has increased dramatically, based on improved quantum chemical methods, advances in the description of the QM/MM interface, and reductions in the cost/performance of computing hardware. Two examples of pharmaceutically relevant applications, cytochrome P450 and class C β-lactamase, are presented.: © 2004 Elsevier Ltd . All rights reserved.

Additively manufactured metallic porous biomaterials based on minimal surfaces: A unique combination of topological, mechanical, and mass transport properties.

PubMed

Bobbert, F S L; Lietaert, K; Eftekhari, A A; Pouran, B; Ahmadi, S M; Weinans, H; Zadpoor, A A

2017-04-15

Porous biomaterials that simultaneously mimic the topological, mechanical, and mass transport properties of bone are in great demand but are rarely found in the literature. In this study, we rationally designed and additively manufactured (AM) porous metallic biomaterials based on four different types of triply periodic minimal surfaces (TPMS) that mimic the properties of bone to an unprecedented level of multi-physics detail. Sixteen different types of porous biomaterials were rationally designed and fabricated using selective laser melting (SLM) from a titanium alloy (Ti-6Al-4V). The topology, quasi-static mechanical properties, fatigue resistance, and permeability of the developed biomaterials were then characterized. In terms of topology, the biomaterials resembled the morphological properties of trabecular bone including mean surface curvatures close to zero. The biomaterials showed a favorable but rare combination of relatively low elastic properties in the range of those observed for trabecular bone and high yield strengths exceeding those reported for cortical bone. This combination allows for simultaneously avoiding stress shielding, while providing ample mechanical support for bone tissue regeneration and osseointegration. Furthermore, as opposed to other AM porous biomaterials developed to date for which the fatigue endurance limit has been found to be ≈20% of their yield (or plateau) stress, some of the biomaterials developed in the current study show extremely high fatigue resistance with endurance limits up to 60% of their yield stress. It was also found that the permeability values measured for the developed biomaterials were in the range of values reported for trabecular bone. In summary, the developed porous metallic biomaterials based on TPMS mimic the topological, mechanical, and physical properties of trabecular bone to a great degree. These properties make them potential candidates to be applied as parts of orthopedic implants and/or as bone

The synergistic effects of combining the high energy mechanical milling and wet milling on Si negative electrode materials for lithium ion battery

NASA Astrophysics Data System (ADS)

Hou, Shang-Chieh; Su, Yuh-Fan; Chang, Chia-Chin; Hu, Chih-Wei; Chen, Tsan-Yao; Yang, Shun-Min; Huang, Jow-Lay

2017-05-01

The submicro-sized and nanostructured Si aggregated powder is prepared by combinational routes of high energy mechanical milling (HEMM) and wet milling. Milled Si powder is investigated by particle size analyzer, SEM, TEM, XPS and XRD as well as the control ones. Its electrode is also investigated by in situ XRD and electrochemical performance. Morphology reveals that combining the high energy mechanical milling and wet milling not only fracture primary Si particles but also form submicro-sized Si aggregates constructed by amorphous and nanocrystalline phases. Moreover, XPS shows that wet milling in ethanol trigger Sisbnd Osbnd CH2CH3 bonding on Si surface might enhance the SEI formation. In situ XRD analysis shows negative electrode made of submicro-sized Si aggregated powder can effectively suppress formation of crystalline Li15Si4 during lithiation and delithiation due to amorphous and nanocrystalline construction. Thus, the submicro-sized Si powder with synergistic effects combining the high energy mechanical milling and wet milling in ethanol as negative electrode performs better capacity retention.

Pancreas Transplant Venous Thrombosis: Role of Endovascular Interventions for Graft Salvage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stockland, Andrew H.; Willingham, Darrin L.; Paz-Fumagalli, Ricardo

2009-03-15

Venous thrombosis of pancreas transplant allografts often leads to graft loss. We evaluated the efficacy of emergent endovascular techniques to salvage thrombosed pancreatic allografts in a series of six patients. Of the 76 pancreas transplants performed between 2002 and 2006, six patients were diagnosed with venous thrombosis on MRI between 2 and 28 days posttransplant (mean, 9 days). Five patients were systemic-enteric (donor portal vein anastomosis to recipient iliac vein) and one patient was portal-enteric (donor portal vein anastomosis to recipient superior mesenteric vein). Conventional venography confirmed the diagnosis of venous thrombosis in all patients. One patient was treated withmore » catheter-directed venous thrombolysis and balloon thrombectomy. Another patient was treated with rheolytic thrombectomy alone. The remaining four patients were treated with a combination of these mechanical and thrombolytic techniques. Completion venography revealed >50% clot reduction and resumption of venous drainage in all patients. One patient required additional intervention 16 days later for recurrent thrombosis. Two patients required metal stent placement for anastomotic stenoses or kinks. One patient required pancreatectomy 36 h after attempted salvage secondary to a major hemorrhage and graft necrosis. Two patients recovered pancreatic function initially but lost graft function at 8 and 14 months, respectively, from severe chronic rejection. Patient survival was 100%, long-term graft survival was 50%, rethrombosis rate was 16.6%, and graft loss from rejection was 33%. In conclusion, early recognition and treatment of venous thrombosis after pancreas transplantation has acceptable morbidity and no mortality using short-term endovascular pharmacomechanical therapy.« less

High-throughput profiling of signaling networks identifies mechanism-based combination therapy to eliminate microenvironmental resistance in acute myeloid leukemia.

PubMed

Zeng, Zhihong; Liu, Wenbin; Tsao, Twee; Qiu, YiHua; Zhao, Yang; Samudio, Ismael; Sarbassov, Dos D; Kornblau, Steven M; Baggerly, Keith A; Kantarjian, Hagop M; Konopleva, Marina; Andreeff, Michael

2017-09-01

The bone marrow microenvironment is known to provide a survival advantage to residual acute myeloid leukemia cells, possibly contributing to disease recurrence. The mechanisms by which stroma in the microenvironment regulates leukemia survival remain largely unknown. Using reverse-phase protein array technology, we profiled 53 key protein molecules in 11 signaling pathways in 20 primary acute myeloid leukemia samples and two cell lines, aiming to understand stroma-mediated signaling modulation in response to the targeted agents temsirolimus (MTOR), ABT737 (BCL2/BCL-XL), and Nutlin-3a (MDM2), and to identify the effective combination therapy targeting acute myeloid leukemia in the context of the leukemia microenvironment. Stroma reprogrammed signaling networks and modified the sensitivity of acute myeloid leukemia samples to all three targeted inhibitors. Stroma activated AKT at Ser473 in the majority of samples treated with single-agent ABT737 or Nutlin-3a. This survival mechanism was partially abrogated by concomitant treatment with temsirolimus plus ABT737 or Nutlin-3a. Mapping the signaling networks revealed that combinations of two inhibitors increased the number of affected proteins in the targeted pathways and in multiple parallel signaling, translating into facilitated cell death. These results demonstrated that a mechanism-based selection of combined inhibitors can be used to guide clinical drug selection and tailor treatment regimens to eliminate microenvironment-mediated resistance in acute myeloid leukemia. Copyright© 2017 Ferrata Storti Foundation.

Enhancement of mechanical properties of 3D printed hydroxyapatite by combined low and high molecular weight polycaprolactone sequential infiltration.

PubMed

Suwanprateeb, Jintamai; Thammarakcharoen, Faungchat; Hobang, Nattapat

2016-11-01

A new infiltration technique using a combination of low and high molecular weight polycaprolactone (PCL) in sequence was developed as a mean to improve the mechanical properties of three dimensional printed hydroxyapatite (HA). It was observed that using either high (M n ~80,000) or low (M n ~10,000) molecular weight infiltration could only increase the flexural modulus compared to non-infiltrated HA, but did not affect strength, strain at break and energy at break. In contrast, a combination of low and high molecular infiltration in sequence increased the flexural modulus, strength and energy at break compared to those of non-infiltrated HA or infiltrated by high or low molecular weight PCL alone. This overall enhancement was found to be attributed to the densification of low molecular weight PCL and the reinforcement of high molecular PCL concurrently. The combined low and high molecular weight infiltration in sequence also maintained high osteoblast proliferation and differentiation of the composites at the similar level of the HA. Densification was a dominant mechanism for the change in modulus with porosity and density of the infiltrated HA/PCL composites. However, both densification and the reinforcing performance of the infiltration phase were crucial for strength and toughening enhancement of the composites possibly by the defect healing and stress shielding mechanisms. The sequence of using low molecular weight infiltration and followed by high molecular infiltration was seen to provide the greatest flexural properties and highest cells proliferation and differentiation capabilities.

Thromboembolic Risk of Endovascular Intervention for Lower Extremity Deep Venous Thrombosis.

PubMed

Lindsey, Philip; Echeverria, Angela; Poi, Mun J; Matos, Jesus; Bechara, Carlos F; Cheung, Mathew; Lin, Peter H

2018-05-01

This study evaluated the risk of thromboembolism during endovascular interventions in patients with symptomatic lower extremity deep vein thrombosis (DVT) METHODS: Clinical records of all patients who underwent endovascular interventions for symptomatic lower extremity DVT from 2001 to 2017 were retrospectively analyzed using a prospectively maintained database. Only patients who received an inferior vena cava (IVC) filter were included in the analysis. Trapped intrafilter thrombus was assessed for procedure-related thromboembolism. Clinical outcomes of thrombus management and thromboembolism risk were analyzed. A total 172 patients (mean age 57.4 years, 98 females) who underwent 174 endovascular DVT interventions were included in the analysis. Treatment strategies included thrombolytic therapy (64%), mechanical thrombectomy (n = 86%), pharmacomechanical thrombolysis (51%), balloon angioplasty (98%), and stent placement (28%). Thrombectomy device used included AngioJet (56%), Trellis (19%), and Aspire (11%). Trapped IVC filter thrombus was identified in 58 patients (38%) based on the IVC venogram. No patient developed clinically evident pulmonary embolism (PE). IVC filter retrieval was performed in 98 patients (56%, mean 11.8 months after implantation). Multivariate analysis showed that iliac vein occlusion (P = 0.04) was predictive for procedure-related thromboembolism. Iliac vein thrombotic occlusion is associated with an increased thromboembolic risk in DVT intervention. Retrievable IVC filter should be considered when performing percutaneous thrombectomy in patients with iliac venous occlusion to prevent PE. Copyright © 2017 Elsevier Inc. All rights reserved.

[Mechanism and Prospect of Radiotherapy Combined with Apotatinib
in the Treatment of Non-small Cell Lung Cancer].

PubMed

Liu, Guohui; Wang, Chunbo; E, Mingyan

2017-12-20

Non-small cell lung cancer is one of the most commom malignant tumor being harmful to people's life and health. Most of the patients have developed to the last stage which not suitable for surgical indications, so radiation and chemotherapy is the main treatment strategy. In recent years, with the theory of anti-angiogenesis therapy for malignant tumors, apatinib as a promising novel medicine to treat malignant tumors, represents synergistic antitumor effects in combination with radiotherapy. The underlying mechanisms may include make blood vessel normalization, alleviating inner hypoxia, and angiogenic factors regulation. Apatinib in combination with radiotherapy may become a new and effective treatment strategy of non-small cell lung cancer.

40 CFR 280.94 - Allowable mechanisms and combinations of mechanisms.

Code of Federal Regulations, 2010 CFR

2010-07-01

... requirements of the financial test under this rule, the financial statements of the owner or operator are not consolidated with the financial statements of the guarantor. [53 FR 43370, Oct. 26, 1988, as amended at 58 FR... OPERATORS OF UNDERGROUND STORAGE TANKS (UST) Financial Responsibility § 280.94 Allowable mechanisms and...

Mechanism of Bacterial Inactivation by (+)-Limonene and Its Potential Use in Food Preservation Combined Processes

PubMed Central

Espina, Laura; Gelaw, Tilahun K.; de Lamo-Castellví, Sílvia; Pagán, Rafael; García-Gonzalo, Diego

2013-01-01

This work explores the bactericidal effect of (+)-limonene, the major constituent of citrus fruits' essential oils, against E. coli. The degree of E. coli BJ4 inactivation achieved by (+)-limonene was influenced by the pH of the treatment medium, being more bactericidal at pH 4.0 than at pH 7.0. Deletion of rpoS and exposure to a sub-lethal heat or an acid shock did not modify E. coli BJ4 resistance to (+)-limonene. However, exposure to a sub-lethal cold shock decreased its resistance to (+)-limonene. Although no sub-lethal injury was detected in the cell envelopes after exposure to (+)-limonene by the selective-plating technique, the uptake of propidium iodide by inactivated E. coli BJ4 cells pointed out these structures as important targets in the mechanism of action. Attenuated Total Reflectance Infrared Microspectroscopy (ATR-IRMS) allowed identification of altered E. coli BJ4 structures after (+)-limonene treatments as a function of the treatment pH: β-sheet proteins at pH 4.0 and phosphodiester bonds at pH 7.0. The increased sensitivity to (+)-limonene observed at pH 4.0 in an E. coli MC4100 lptD4213 mutant with an increased outer membrane permeability along with the identification of altered β-sheet proteins by ATR-IRMS indicated the importance of this structure in the mechanism of action of (+)-limonene. The study of mechanism of inactivation by (+)-limonene led to the design of a synergistic combined process with heat for the inactivation of the pathogen E. coli O157:H7 in fruit juices. These results show the potential of (+)-limonene in food preservation, either acting alone or in combination with lethal heat treatments. PMID:23424676

Mechanism of bacterial inactivation by (+)-limonene and its potential use in food preservation combined processes.

PubMed

Espina, Laura; Gelaw, Tilahun K; de Lamo-Castellví, Sílvia; Pagán, Rafael; García-Gonzalo, Diego

2013-01-01

This work explores the bactericidal effect of (+)-limonene, the major constituent of citrus fruits' essential oils, against E. coli. The degree of E. coli BJ4 inactivation achieved by (+)-limonene was influenced by the pH of the treatment medium, being more bactericidal at pH 4.0 than at pH 7.0. Deletion of rpoS and exposure to a sub-lethal heat or an acid shock did not modify E. coli BJ4 resistance to (+)-limonene. However, exposure to a sub-lethal cold shock decreased its resistance to (+)-limonene. Although no sub-lethal injury was detected in the cell envelopes after exposure to (+)-limonene by the selective-plating technique, the uptake of propidium iodide by inactivated E. coli BJ4 cells pointed out these structures as important targets in the mechanism of action. Attenuated Total Reflectance Infrared Microspectroscopy (ATR-IRMS) allowed identification of altered E. coli BJ4 structures after (+)-limonene treatments as a function of the treatment pH: β-sheet proteins at pH 4.0 and phosphodiester bonds at pH 7.0. The increased sensitivity to (+)-limonene observed at pH 4.0 in an E. coli MC4100 lptD4213 mutant with an increased outer membrane permeability along with the identification of altered β-sheet proteins by ATR-IRMS indicated the importance of this structure in the mechanism of action of (+)-limonene. The study of mechanism of inactivation by (+)-limonene led to the design of a synergistic combined process with heat for the inactivation of the pathogen E. coli O157:H7 in fruit juices. These results show the potential of (+)-limonene in food preservation, either acting alone or in combination with lethal heat treatments.

Combined low-dose aspirin and warfarin anticoagulant therapy of postoperative atrial fibrillation following mechanical heart valve replacement.

PubMed

Wang, Jian-tang; Dong, Ming-feng; Song, Guang-min; Ma, Zeng-shan; Ma, Sheng-jun

2014-12-01

The safety and efficacy of combined low dose aspirin and warfarin therapy in patients with atrial fibrillation after mechanical heart valve replacement were evaluated. A total of 1016 patients (620 females, mean age of 36.8±7.7 years) admitted for cardiac valve replacement and complicated with atrial fibrillation after surgery were randomly divided into study (warfarin plus 75-100 mg aspirin) or control (warfarin only) groups. International normalized ratio (INR) and prothrombin time were maintained at 1.8-2.5 and 1.5-2.0 times the normal values, respectively. Thromboembolic events and major bleedings were registered during the follow-up period. Patients were followed up for 24±9 months. The average dose of warfarin in the study and control groups was 2.91±0.83 mg and 2.88±0.76 mg, respectively (P>0.05). The incidence of overall thromboembolic events in study group was lower than that in control group (2.16% vs. 4.35%, P=0.049). No statistically significant differences were found in hemorrhage events (3.53% vs. 3.95%, P=0.722) or mortality (0.20% vs. 0.40%, P=0.559) between the two groups. Combined low dose aspirin and warfarin therapy in the patients with atrial fibrillation following mechanical heart valve replacement significantly decreased thromboembolic events as compared with warfarin therapy alone. This combined treatment was not associated with an increase in the risk of major bleeding or mortality.

Cellular graphene aerogel combines ultralow weight and high mechanical strength: A highly efficient reactor for catalytic hydrogenation

PubMed Central

Zhang, Bingxing; Zhang, Jianling; Sang, Xinxin; Liu, Chengcheng; Luo, Tian; Peng, Li; Han, Buxing; Tan, Xiuniang; Ma, Xue; Wang, Dong; Zhao, Ning

2016-01-01

The construction of three-dimensional graphene aerogels (GAs) is of great importance owing to their outstanding properties for various applications. Up to now, the combination of ultralow weight and super mechanical strength for GA remains a great challenge. Here we demonstrate the fabrication of cellular GAs by a facile, easily controlled and versatile route, i.e. the chemical reduction of graphene oxide assemblies at oil-water interface under a mild condition (70 °C). The GA is ultralight (with density <3 mg cm−3) yet mechanically resilient because the walls of the cell closely pack in a highly ordered manner to maximize mechanical strength. The GA has been utilized as an appealing reactor for catalytic hydrogenation, which exhibited great advantages such as large oil absorption capability, exceptional catalytic activity, ease of product separation and high stability. PMID:27174450

Cellular graphene aerogel combines ultralow weight and high mechanical strength: A highly efficient reactor for catalytic hydrogenation

NASA Astrophysics Data System (ADS)

Zhang, Bingxing; Zhang, Jianling; Sang, Xinxin; Liu, Chengcheng; Luo, Tian; Peng, Li; Han, Buxing; Tan, Xiuniang; Ma, Xue; Wang, Dong; Zhao, Ning

2016-05-01

The construction of three-dimensional graphene aerogels (GAs) is of great importance owing to their outstanding properties for various applications. Up to now, the combination of ultralow weight and super mechanical strength for GA remains a great challenge. Here we demonstrate the fabrication of cellular GAs by a facile, easily controlled and versatile route, i.e. the chemical reduction of graphene oxide assemblies at oil-water interface under a mild condition (70 °C). The GA is ultralight (with density <3 mg cm-3) yet mechanically resilient because the walls of the cell closely pack in a highly ordered manner to maximize mechanical strength. The GA has been utilized as an appealing reactor for catalytic hydrogenation, which exhibited great advantages such as large oil absorption capability, exceptional catalytic activity, ease of product separation and high stability.

Effects and mechanisms of the combined pollution of lanthanum and acid rain on the root phenotype of soybean seedlings.

PubMed

Sun, Zhaoguo; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

2013-09-01

Rare earth pollution and acid rain pollution are both important environmental issues worldwide. In regions which simultaneously occur, the combined pollution of rare earth and acid rain becomes a new environmental issue, and the relevant research is rarely reported. Accordingly, we investigated the combined effects and mechanisms of lanthanum ion (La(3+)) and acid rain on the root phenotype of soybean seedlings. The combined pollution of low-concentration La(3+) and acid rain exerted deleterious effects on the phenotype and growth of roots, which were aggravated by the combined pollution of high-concentration La(3+) and acid rain. The deleterious effects of the combined pollution were stronger than those of single La(3+) or acid rain pollution. These stronger deleterious effects on the root phenotype and growth of roots were due to the increased disturbance of absorption and utilization of mineral nutrients in roots. Copyright © 2013 Elsevier Ltd. All rights reserved.

Motion mechanics of non-adherent giant liposomes with a combined optical and atomic force microscope

NASA Astrophysics Data System (ADS)

Moreno-Flores, Susana; Ortíz, Rocío

2017-11-01

Herein we present an investigation of the motional dynamics of single mesoscopic bodies of biological relevance with an AFM-based macromanipulation tool and an optical microscope. Giant liposomes are prominent case examples as minimal cell models; studying their mechanics provides a means to address the influence of structural components in the mechanical behaviour of living cells. However, they also pose an experimental challenge due to their lightness, fragility, and high mobility. Their entrapment in wells in a fluid of lower density allows their study under conditions of constrained motion, which enables the synchronous measurement of nanoforces with motion tracking. The procedure enables to estimate sliding friction coefficients and masses of vesicles, and sheds light upon the region between the vesicle and the underlying substrate. The present study paves the way for the investigation of motion and deformation mechanics with one combined technique and a single type of experiment traditionally vetoed to objects that can move as well as deform. Such an approach can be directly applied to cells in suspension, adherent cells or cellular 3D-assemblies so as to assess substrate biocompatibility, monitor adhesion, detachment, motility as well as deformability.

Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality.

PubMed

Díaz-Martín, Ana; Martínez-González, María Luisa; Ferrer, Ricard; Ortiz-Leyba, Carlos; Piacentini, Enrique; Lopez-Pueyo, Maria Jesus; Martín-Loeches, Ignacio; Levy, Mitchell M; Artigas, Antoni; Garnacho-Montero, José

2012-11-18

Although early institution of adequate antimicrobial therapy is lifesaving in sepsis patients, optimal antimicrobial strategy has not been established. Moreover, the benefit of combination therapy over monotherapy remains to be determined. Our aims are to describe patterns of empiric antimicrobial therapy in severe sepsis, assessing the impact of combination therapy, including antimicrobials with different mechanisms of action, on mortality. This is a Spanish national multicenter study, analyzing all patients admitted to ICUs who received antibiotics within the first 6 hours of diagnosis of severe sepsis or septic shock. Antibiotic-prescription patterns in community-acquired infections and nosocomial infections were analyzed separately and compared. We compared the impact on mortality of empiric antibiotic treatment, including antibiotics with different mechanisms of action, termed different-class combination therapy (DCCT), with that of monotherapy and any other combination therapy possibilities (non-DCCT). We included 1,372 patients, 1,022 (74.5%) of whom had community-acquired sepsis and 350 (25.5%) of whom had nosocomial sepsis. The most frequently prescribed antibiotic agents were β-lactams (902, 65.7%) and carbapenems (345, 25.1%). DCCT was administered to 388 patients (28.3%), whereas non-DCCT was administered to 984 (71.7%). The mortality rate was significantly lower in patients administered DCCTs than in those who were administered non-DCCTs (34% versus 40%; P = 0.042). The variables independently associated with mortality were age, male sex, APACHE II score, and community origin of the infection. DCCT was a protective factor against in-hospital mortality (odds ratio (OR), 0.699; 95% confidence interval (CI), 0.522 to 0.936; P = 0.016), as was urologic focus of infection (OR, 0.241; 95% CI, 0.102 to 0.569; P = 0.001). β-Lactams, including carbapenems, are the most frequently prescribed antibiotics in empiric therapy in patients with severe sepsis and

Low- and high-spin iron (II) complexes studied by effective crystal field method combined with molecular mechanics.

PubMed

Darkhovskii, M B; Pletnev, I V; Tchougréeff, A L

2003-11-15

A computational method targeted to Werner-type complexes is developed on the basis of quantum mechanical effective Hamiltonian crystal field (EHCF) methodology (previously proposed for describing electronic structure of transition metal complexes) combined with the Gillespie-Kepert version of molecular mechanics (MM). It is a special version of the hybrid quantum/MM approach. The MM part is responsible for representing the whole molecule, including ligand atoms and metal ion coordination sphere, but leaving out the effects of the d-shell. The quantum mechanical EHCF part is limited to the metal ion d-shell. The method reproduces with reasonable accuracy geometry and spin states of the Fe(II) complexes with monodentate and polydentate aromatic ligands with nitrogen donor atoms. In this setting a single set of MM parameters set is shown to be sufficient for handling all spin states of the complexes under consideration. Copyright 2003 Wiley Periodicals, Inc.

Restrained Proton Indicator in Combined Quantum-Mechanics/Molecular-Mechanics Dynamics Simulations of Proton Transfer through a Carbon Nanotube.

PubMed

Duster, Adam W; Lin, Hai

2017-09-14

Recently, a collective variable "proton indicator" was purposed for tracking an excess proton solvated in bulk water in molecular dynamics simulations. In this work, we demonstrate the feasibility of utilizing the position of this proton indicator as a reaction coordinate to model an excess proton migrating through a hydrophobic carbon nanotube in combined quantum-mechanics/molecular-mechanics simulations. Our results indicate that applying a harmonic restraint to the proton indicator in the bulk solvent near the nanotube pore entrance leads to the recruitment of water molecules into the pore. This is consistent with an earlier study that employed a multistate empirical valence bond potential and a different representation (center of excess charge) of the proton. We attribute this water recruitment to the delocalized nature of the solvated proton, which prefers to be in high-dielectric bulk solvent. While water recruitment into the pore is considered an artifact in the present simulations (because of the artificially imposed restraint on the proton), if the proton were naturally restrained, it could assist in building water wires prior to proton transfer through the pore. The potential of mean force for a proton translocation through the water-filled pore was computed by umbrella sampling, where the bias potentials were applied to the proton indicator. The free energy curve and barrier heights agree reasonably with those in the literature. The results suggest that the proton indicator can be used as a reaction coordinate in simulations of proton transport in confined environments.

Free Radical Damage in Ischemia-Reperfusion Injury: An Obstacle in Acute Ischemic Stroke after Revascularization Therapy

PubMed Central

Jin, Hang; Sun, Xin; Huang, Shuo; Zhang, Fu-Liang; Guo, Zhen-Ni

2018-01-01

Acute ischemic stroke is a common cause of morbidity and mortality worldwide. Thrombolysis with recombinant tissue plasminogen activator and endovascular thrombectomy are the main revascularization therapies for acute ischemic stroke. However, ischemia-reperfusion injury after revascularization therapy can result in worsening outcomes. Among all possible pathological mechanisms of ischemia-reperfusion injury, free radical damage (mainly oxidative/nitrosative stress injury) has been found to play a key role in the process. Free radicals lead to protein dysfunction, DNA damage, and lipid peroxidation, resulting in cell death. Additionally, free radical damage has a strong connection with inducing hemorrhagic transformation and cerebral edema, which are the major complications of revascularization therapy, and mainly influencing neurological outcomes due to the disruption of the blood-brain barrier. In order to get a better clinical prognosis, more and more studies focus on the pharmaceutical and nonpharmaceutical neuroprotective therapies against free radical damage. This review discusses the pathological mechanisms of free radicals in ischemia-reperfusion injury and adjunctive neuroprotective therapies combined with revascularization therapy against free radical damage. PMID:29770166

Damage Detection Based on Power Dissipation Measured with PZT Sensors through the Combination of Electro-Mechanical Impedances and Guided Waves

PubMed Central

Sevillano, Enrique; Sun, Rui; Perera, Ricardo

2016-01-01

The use of piezoelectric ceramic transducers (such as Lead-Zirconate-Titanate—PZT) has become more and more widespread for Structural Health Monitoring (SHM) applications. Among all the techniques that are based on this smart sensing solution, guided waves and electro-mechanical impedance techniques have found wider acceptance, and so more studies and experimental works can be found containing these applications. However, even though these two techniques can be considered as complementary to each other, little work can be found focused on the combination of them in order to define a new and integrated damage detection procedure. In this work, this combination of techniques has been studied by proposing a new integrated damage indicator based on Electro-Mechanical Power Dissipation (EMPD). The applicability of this proposed technique has been tested through different experimental tests, with both lab-scale and real-scale structures. PMID:27164104

Damage Detection Based on Power Dissipation Measured with PZT Sensors through the Combination of Electro-Mechanical Impedances and Guided Waves.

PubMed

Sevillano, Enrique; Sun, Rui; Perera, Ricardo

2016-05-05

The use of piezoelectric ceramic transducers (such as Lead-Zirconate-Titanate-PZT) has become more and more widespread for Structural Health Monitoring (SHM) applications. Among all the techniques that are based on this smart sensing solution, guided waves and electro-mechanical impedance techniques have found wider acceptance, and so more studies and experimental works can be found containing these applications. However, even though these two techniques can be considered as complementary to each other, little work can be found focused on the combination of them in order to define a new and integrated damage detection procedure. In this work, this combination of techniques has been studied by proposing a new integrated damage indicator based on Electro-Mechanical Power Dissipation (EMPD). The applicability of this proposed technique has been tested through different experimental tests, with both lab-scale and real-scale structures.

[Synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells and its related mechanism].

PubMed

Zhang, Shao-nan; Yong, Qun; Wu, Xin-li; Liu, Xiao-ping

2014-11-01

To investigate the synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells and the down-regulating effect of curcumin on the Keapl-Nrf2 pathway, a well recognized anti-drug pathway in almost drugged tumor cells. T24 cells were cultured and treated with increasing concentrations of curcumin(5 ,10 and 20 µmol/mL) combined with cisplatin(30 µg/mL) for 24 hours. The inhibitory effects on T24 cells were tested with MTI colorimetric assay. Nuclear Nrf2 and Keapl , cytoplasmic Keapl and two typical phase II enzymes (GSTP1 and NQOl) were checked with Western blotting. The proliferation of T24 cells was significantly inhibited by different concentrations of curcumin combined with cisplatin. After the treatment with different concentrations of curcumin, Nuclear Nrf2 was decreased but Keapl was increased, and GSTP1 and NQO1 were decreased. Synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells is observed in this research. The Keapl-Nrf2 pathway in T24 cells is down-regulated by curcumin. The expression of typical phase I enzymes (GSTP1 and NQO1) mediated by Nrf2 are decreased by curcumin. The sensitivity of tumor cells to chemotherapeutic drugs is then enhanced. These may be the mechanism of synergism effect of curcumin combined with cisplatin.

Physiological mechanisms contributing to the QTL-combination effects on improved performance of IR64 rice NILs under drought

PubMed Central

Henry, Amelia; Swamy, B. P. Mallikarjuna; Dixit, Shalabh; Torres, Rolando D.; Batoto, Tristram C.; Manalili, Mervin; Anantha, M. S.; Mandal, N. P.; Kumar, Arvind

2015-01-01

Characterizing the physiological mechanisms behind major-effect drought-yield quantitative trait loci (QTLs) can provide an understanding of the function of the QTLs—as well as plant responses to drought in general. In this study, we characterized rice (Oryza sativa L.) genotypes with QTLs derived from drought-tolerant traditional variety AdaySel that were introgressed into drought-susceptible high-yielding variety IR64, one of the most popular megavarieties in South Asian rainfed lowland systems. Of the different combinations of the four QTLs evaluated, genotypes with two QTLs (qDTY 2.2 + qDTY 4.1) showed the greatest degree of improvement under drought compared with IR64 in terms of yield, canopy temperature, and normalized difference vegetation index (NDVI). Furthermore, qDTY 2.2 and qDTY 4.1 showed a potential for complementarity in that they were each most effective under different severities of drought stress. Multiple drought-response mechanisms were observed to be conferred in the genotypes with the two-QTL combination: higher root hydraulic conductivity and in some cases greater root growth at depth. As evidenced by multiple leaf water status and plant growth indicators, these traits affected transpiration but not transpiration efficiency or harvest index. The results from this study highlight the complex interactions among major-effect drought-yield QTLs and the drought-response traits they confer, and the need to evaluate the optimal combinations of QTLs that complement each other when present in a common genetic background. PMID:25680791

Combined Effects of Ventilation Mode and Positive End-Expiratory Pressure on Mechanics, Gas Exchange and the Epithelium in Mice with Acute Lung Injury

PubMed Central

Thammanomai, Apiradee; Hamakawa, Hiroshi; Bartolák-Suki, Erzsébet; Suki, Béla

2013-01-01

The accepted protocol to ventilate patients with acute lung injury is to use low tidal volume (VT) in combination with recruitment maneuvers or positive end-expiratory pressure (PEEP). However, an important aspect of mechanical ventilation has not been considered: the combined effects of PEEP and ventilation modes on the integrity of the epithelium. Additionally, it is implicitly assumed that the best PEEP-VT combination also protects the epithelium. We aimed to investigate the effects of ventilation mode and PEEP on respiratory mechanics, peak airway pressures and gas exchange as well as on lung surfactant and epithelial cell integrity in mice with acute lung injury. HCl-injured mice were ventilated at PEEPs of 3 and 6 cmH2O with conventional ventilation (CV), CV with intermittent large breaths (CVLB) to promote recruitment, and a new mode, variable ventilation, optimized for mice (VVN). Mechanics and gas exchange were measured during ventilation and surfactant protein (SP)-B, proSP-B and E-cadherin levels were determined from lavage and lung homogenate. PEEP had a significant effect on mechanics, gas exchange and the epithelium. The higher PEEP reduced lung collapse and improved mechanics and gas exchange but it also down regulated surfactant release and production and increased epithelial cell injury. While CVLB was better than CV, VVN outperformed CVLB in recruitment, reduced epithelial injury and, via a dynamic mechanotransduction, it also triggered increased release and production of surfactant. For long-term outcome, selection of optimal PEEP and ventilation mode may be based on balancing lung physiology with epithelial injury. PMID:23326543

Biomechanical aspects of segmented arch mechanics combined with power arm for controlled anterior tooth movement: A three-dimensional finite element study.

PubMed

Ozaki, Hiroya; Tominaga, Jun-Ya; Hamanaka, Ryo; Sumi, Mayumi; Chiang, Pao-Chang; Tanaka, Motohiro; Koga, Yoshiyuki; Yoshida, Noriaki

2015-01-01

The porpose of this study was to determine the optimal length of power arms for achieving controlled anterior tooth movement in segmented arch mechanics combined with power arm. A three-dimensional finite element method was applied for the simulation of en masse anterior tooth retraction in segmented power arm mechanics. The type of tooth movement, namely, the location of center of rotation of the maxillary central incisor in association with power arm length, was calculated after the retraction force was applied. When a 0.017 × 0.022-in archwire was inserted into the 0.018-in slot bracket, bodily movement was obtained at 9.1 mm length of power arm, namely, at the level of 1.8 mm above the center of resistance. In case a 0.018 × 0.025-in full-size archwire was used, bodily movement of the tooth was produced at the power arm length of 7.0 mm, namely, at the level of 0.3 mm below the center of resistance. Segmented arch mechanics required shorter length of power arms for achieving any type of controlled anterior tooth movement as compared to sliding mechanics. Therefore, this space closing mechanics could be widely applied even for the patients whose gingivobuccal fold is shallow. The segmented arch mechanics combined with power arm could provide higher amount of moment-to-force ratio sufficient for controlled anterior tooth movement without generating friction, and vertical forces when applying retraction force parallel to the occlusal plane. It is, therefore, considered that the segmented power arm mechanics has a simple appliance design and allows more efficient and controllable tooth movement.

SGLT2 inhibitor/DPP-4 inhibitor combination therapy - complementary mechanisms of action for management of type 2 diabetes mellitus.

PubMed

Dey, Jayant

2017-05-01

Type 2 diabetes mellitus is a progressive disease with multiple underlying pathophysiologic defects. Monotherapy alone cannot maintain glycemic control and leads to treatment failure. Ideally, a combination of glucose-lowering agents should have complementary mechanisms of action that address multiple pathophysiologic pathways, can be used at all stages of the disease, and be generally well tolerated with no increased risk of hypoglycemia, cardiovascular events, or weight gain. The combination should also provide conveniences for patients, such as oral dosing, single-pill formulations, and once-daily administration, potentially translating to improved adherence. Two classes of glucose-lowering agents that meet these criteria are the sodium glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. This article reviews the rationale for combination therapy with these agents, and evidence from clinical trials with empagliflozin and linagliptin or dapagliflozin and saxagliptin in the management of type 2 diabetes mellitus. Both combinations have been approved as single-pill formulations.

Combining 3D printed forms with textile structures - mechanical and geometrical properties of multi-material systems

NASA Astrophysics Data System (ADS)

Sabantina, L.; Kinzel, F.; Ehrmann, A.; Finsterbusch, K.

2015-07-01

The 3D printing belongs to the rapidly emerging technologies which have the chance to revolutionize the way products are created. In the textile industry, several designers have already presented creations of shoes, dresses or other garments which could not be produced with common techniques. 3D printing, however, is still far away from being a usual process in textile and clothing production. The main challenge results from the insufficient mechanical properties, especially the low tensile strength, of pure 3D printed products, prohibiting them from replacing common technologies such as weaving or knitting. Thus, one way to the application of 3D printed forms in garments is combining them with textile fabrics, the latter ensuring the necessary tensile strength. This article reports about different approaches to combine 3D printed polymers with different textile materials and fabrics, showing chances and limits of this technique.

Combined comparative and chemical proteomics on the mechanisms of levo-tetrahydropalmatine-induced antinociception in the formalin test.

PubMed

Wang, Chen; Zhou, Jiangrui; Wang, Shuowen; Ye, Mingliang; Jiang, Chunlei; Fan, Guorong; Zou, Hanfa

2010-06-04

This study investigated the mechanisms involved in the antinociceptive action induced by levo-tetrahydropalmatine (l-THP) in the formalin test by combined comparative and chemical proteomics. Rats were pretreated with l-THP by the oral route (40 mg/kg) 1 h before formalin injection. The antinociceptive effect of l-THP was shown in the first and second phases of the formalin test. To address the mechanisms by which l-THP inhibits formalin-induced nociception in rats, the combined comparative and chemical proteomics were applied. A novel high-throughput comparative proteomic approach based on 2D-nano-LC-MS/MS was applied to simultaneously evaluate the deregulated proteins involved in the response of l-THP treatment in formalin-induced pain rats. Thousands of proteins were identified, among which 17 proteins survived the stringent filter criteria and were further included for functional discussion. Two proteins (Neurabin-1 and Calcium-dependent secretion activator 1) were randomly selected, and their expression levels were further confirmed by Western Blots. The results matched well with those of proteomics. In the present study, we also described the development and application of l-THP immobilized beads to bind the targets. Following incubation with cellular lysates, the proteome interacting with the fixed l-THP was identified. The results of comparative and chemical proteomics were quite complementary. Although the precise roles of these identified moleculars in l-THP-induced antinociception need further study, the combined results indicated that proteins associated with signal transduction, vesicular trafficking and neurotransmitter release, energy metabolism, and ion transport play important roles in l-THP-induced antinociception in the formalin test.

Synergistic activity and mechanism of action of ceftazidime and apigenin combination against ceftazidime-resistant Enterobacter cloacae.

PubMed

Eumkeb, Griangsak; Chukrathok, Somnuk

2013-02-15

compared to control or single treatment of these agents. Both o-nitrophenyl-β-D-galactoside (ONPG) uptake and release of UV-absorbing material concentrations results exhibited that ceftazidime and apigenin combination damaged CREC cytoplasmic membrane (CM) and caused subsequent leakage of intracellular constituents. From the results, it can be concluded that apigenin and naringenin have the synergistic effect with ceftazidime to reverse bacterial resistance to this cephalosporin against CREC. This activity may be involved three mechanisms of action by apigenin. The first is on the peptidoglycan synthesis inhibition. The second mechanism is inhibition the activity of certain β-lactamase enzymes. The third mode of action is alteration of OM and CM permeabilization. Apigenin and naringenin have a sufficient margin of safety for therapeutic use. For this reason, apigenin and naringenin offer for the development of a valuable adjunct to ceftazidime against CREC, which currently almost cephalosporins resistance. Copyright © 2012 Elsevier GmbH. All rights reserved.

Late-onset renal vein thrombosis: A case report and review of the literature

PubMed Central

Hogan, Jessica L.; Rosenthal, Stanton J.; Yarlagadda, Sri G.; Jones, Jill A.; Schmitt, Timothy M.; Kumer, Sean C.; Kaplan, Bruce; Deas, Shenequa L.; Nawabi, Atta M.

2014-01-01

INTRODUCTION Renal vein thrombosis, a rare complication of renal transplantation, often causes graft loss. Diagnosis includes ultrasound with Doppler, and it is often treated with anticoagulation or mechanical thrombectomy. Success is improved with early diagnosis and institution of treatment. PRESENTATION OF CASE We report here the case of a 29 year-old female with sudden development of very late-onset renal vein thrombosis after simultaneous kidney pancreas transplant. This resolved initially with thrombectomy, stenting and anticoagulation, but thrombosis recurred, necessitating operative intervention. Intraoperatively the renal vein was discovered to be compressed by a large ovarian cyst. DISCUSSION Compression of the renal vein by a lymphocele or hematoma is a known cause of thrombosis, but this is the first documented case of compression and thrombosis due to an ovarian cyst. CONCLUSION Early detection and treatment of renal vein thrombosis is paramount to restoring renal allograft function. Any woman of childbearing age may have thrombosis due to compression by an ovarian cyst, and screening for this possibility may improve long-term graft function in this population. PMID:25528029

Late-onset renal vein thrombosis: A case report and review of the literature.

PubMed

Hogan, Jessica L; Rosenthal, Stanton J; Yarlagadda, Sri G; Jones, Jill A; Schmitt, Timothy M; Kumer, Sean C; Kaplan, Bruce; Deas, Shenequa L; Nawabi, Atta M

2015-01-01

Renal vein thrombosis, a rare complication of renal transplantation, often causes graft loss. Diagnosis includes ultrasound with Doppler, and it is often treated with anticoagulation or mechanical thrombectomy. Success is improved with early diagnosis and institution of treatment. We report here the case of a 29 year-old female with sudden development of very late-onset renal vein thrombosis after simultaneous kidney pancreas transplant. This resolved initially with thrombectomy, stenting and anticoagulation, but thrombosis recurred, necessitating operative intervention. Intraoperatively the renal vein was discovered to be compressed by a large ovarian cyst. Compression of the renal vein by a lymphocele or hematoma is a known cause of thrombosis, but this is the first documented case of compression and thrombosis due to an ovarian cyst. Early detection and treatment of renal vein thrombosis is paramount to restoring renal allograft function. Any woman of childbearing age may have thrombosis due to compression by an ovarian cyst, and screening for this possibility may improve long-term graft function in this population. Published by Elsevier Ltd.

Possible Peroxo State of the Dicopper Site of Particulate Methane Monooxygenase from Combined Quantum Mechanics and Molecular Mechanics Calculations.

PubMed

Itoyama, Shuhei; Doitomi, Kazuki; Kamachi, Takashi; Shiota, Yoshihito; Yoshizawa, Kazunari

2016-03-21

Enzymatic methane hydroxylation is proposed to efficiently occur at the dinuclear copper site of particulate methane monooxygenase (pMMO), which is an integral membrane metalloenzyme in methanotrophic bacteria. The resting state and a possible peroxo state of the dicopper active site of pMMO are discussed by using combined quantum mechanics and molecular mechanics calculations on the basis of reported X-ray crystal structures of the resting state of pMMO by Rosenzweig and co-workers. The dicopper site has a unique structure, in which one copper is coordinated by two histidine imidazoles and another is chelated by a histidine imidazole and primary amine of an N-terminal histidine. The resting state of the dicopper site is assignable to the mixed-valent Cu(I)Cu(II) state from a computed Cu-Cu distance of 2.62 Å from calculations at the B3LYP-D/TZVP level of theory. A μ-η(2):η(2)-peroxo-Cu(II)2 structure similar to those of hemocyanin and tyrosinase is reasonably obtained by using the resting state structure and dioxygen. Computed Cu-Cu and O-O distances are 3.63 and 1.46 Å, respectively, in the open-shell singlet state. Structural features of the dicopper peroxo species of pMMO are compared with those of hemocyanin and tyrosinase and synthetic dicopper model compounds. Optical features of the μ-η(2):η(2)-peroxo-Cu(II)2 state are calculated and analyzed with TD-DFT calculations.

[Apoptosis mechanism of taxol combined with resveratrol on human laryngeal carcinoma Hep-2 cells].

PubMed

Lu, Chen-Xin; Sun, Jing-Hui; Wu, Chun-Lian

2016-02-01

Laryngeal cancer is one of the most common malignant tumors in the respiratory tumors, and its incidence ranks second highest in the respiratory tumors. Resveratrol (Res) is a kind of polyphenols, which can inhibit nucleotides can inhibit the growth of liver cancer cells, gastric cancer cells, pancreatic cells and other tumor cells by inhibiting ribonucleotide reductase in the cells. Taxol (Tax) is a kind of secondary metabolites of Taxus chinensis, which has anti-tumor activity for breast cancer, cervical cancer, ovarian cancer and other tumors by inhibiting cellular microtubule depolymerization. But at present the effects of resveratrol combined with taxol on human laryngeal carcinoma cell strain Hep-2 and their underlying molecular mechanisms are rarely reported. After human laryngeal cancer cell Hep-2 cells were processed with resveratrol (Res) and taxol (Tax), CCK-8 assay was used to evaluate the effect of these two herbs on the proliferation of cancer cells; AO/PI staining and JC-1 were used to detect Hep-1 cells apoptosis; the expression of Bax, Bcl-2, PARP, TRIB3, and XIAP genes was detected by real time quantitative PCR; the activity of caspase-3 and caspase-8 was determined with quantitative fluorescence method. The experimental results showed that compared with Tax, Res medication alone, joint group significantly enhanced inhibition of Hep-2 cells activity, decreased the dosage of Tax, increased the expression of Bax and PARP, TRIB3, reduced the expression of the Bcl-2 and XIAP, and promoted the activity of caspase-3 and caspase-8. The test results showed that compared with the single medication, combined group could significantly increase the inhibitory effect on Hep-2 cells, significantly reduce Tax dosage, increase expressions of Bax, PARP, TRIB3, reduce expressions of Bcl-2, XIAP, and promote activity of caspase-3, caspase-8. This indicated apoptosis of human laryngeal carcinoma cell strain Hep-2 may be induced with Res, Tax, and the combination of

Mechanisms of CCl4-induced liver fibrosis with combined transcriptomic and proteomic analysis.

PubMed

Dong, Shu; Chen, Qi-Long; Song, Ya-Nan; Sun, Yang; Wei, Bin; Li, Xiao-Yan; Hu, Yi-Yang; Liu, Ping; Su, Shi-Bing

2016-01-01

The classic toxicity of carbon tetrachloride (CCl4) is to induce liver lesion and liver fibrosis. Liver fibrosis is a consequence of chronic liver lesion, which can progress into liver cirrhosis even hepatocarcinoma. However, the toxicological mechanisms of CCl4-induced liver fibrosis remain not fully understood. We combined transcriptomic and proteomic analysis and biological network technology, predicted toxicological targets and regulatory networks of CCl4 in liver fibrosis. Wistar rats were treated with CCl4 for 9 weeks. Histopathological changes, hydroxyproline (Hyp) contents, serum ALT and AST in the CCl4-treated group were significantly higher than that of CCl4-untreated group. CCl4-treated and -untreated liver tissues were examined by microarray and iTRAQ. The results showed that 3535 genes (fold change ≥ 1.5, P < 0.05) and 1412 proteins (fold change ≥ 1.2, P < 0.05) were differentially expressed. Moreover, the integrative analysis of transcriptomics and proteomics data showed 523 overlapped proteins, enriched in 182 GO terms including oxidation reduction, response to oxidative stress, inflammatory response, extracellular matrix organization, etc. Furthermore, KEGG pathway analysis showed that 36 pathways including retinol metabolism, PPAR signaling pathway, glycolysis/gluconeogenesis, arachidonic acid metabolism, metabolism of xenobiotics by cytochrome P450 and drug metabolism. Network of protein-protein interaction (PPI) and key function with their related targets were performed and the degree of network was calculated with Cytoscape. The expression of key targets such as CYP4A3, ALDH2 and ALDH7A1 decreased after CCl4 treatment. Therefore, the toxicological mechanisms of CCl4-induced liver fibrosis may be related with multi biological process, pathway and targets which may provide potential protection reaction mechanism for CCl4 detoxication in the liver.

Contact Aspiration Versus Stent Retriever in Patients With Acute Ischemic Stroke With M2 Occlusion in the ASTER Randomized Trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization).

PubMed

Gory, Benjamin; Lapergue, Bertrand; Blanc, Raphael; Labreuche, Julien; Ben Machaa, Malek; Duhamel, Alain; Marnat, Gautier; Saleme, Suzana; Costalat, Vincent; Bracard, Serge; Desal, Hubert; Mazighi, Mikael; Consoli, Arturo; Piotin, Michel

2018-02-01

Middle cerebral artery M2-segment occlusions represent an important subgroup of patients with acute stroke with large-vessel occlusion. The safety of mechanical thrombectomy, especially contact aspiration (CA), in such distal intracranial occlusions is still under debate. We compared reperfusion, adverse events, neurological recovery, and functional outcome of patients with isolated M2 occlusions according to the first-line strategy mechanical thrombectomy devices (CA versus stent retriever [SR]). This is a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization). The primary outcome was successful reperfusion at the end of all endovascular procedures, defined as modified Thrombolysis in Cerebral Infarction (mTICI) scores 2b/3. Secondary outcomes were mTICI 2c/3 and mTICI 3, 90-day functional outcome, assessed with the modified Rankin Scale score. Safety outcomes included 90-day mortality and any symptomatic intracerebral hemorrhage. Seventy-nine patients were included: 48 were allocated to the CA group and 31 to the SR group. There were no significant differences between CA and SR groups in reperfusion after all endovascular procedures regarding mTICI 2b/3 (89.6% versus 83.9%; P =0.36), mTICI 2c/3 (54.2% versus 54.8%; P =0.90), and mTICI 3 (35.4% versus 41.9%; P =0.36) rates. There were no significant differences between CA and SR groups in 90-day modified Rankin Scale ≤2 rate (54.4% versus 50.0%; P =0.84), 24-hour change in National Institutes of Health Stroke Scale (mean difference, -3.9; 95% confidence interval, -7.9 to 0.01), and Alberta Stroke Program Early Computed Tomography score (mean difference, 0.9; 95% confidence interval, -0.1 to 2.0) scores. Safety parameters were well balanced between the 2 groups except for a higher 90-day mortality rate in the CA group (19.6% versus 3.3%; P =0.078). First-line mechanical thrombectomy with CA compared with SR did not result in an increased successful

Energy neutral: the human foot and ankle subsections combine to produce near zero net mechanical work during walking.

PubMed

Takahashi, Kota Z; Worster, Kate; Bruening, Dustin A

2017-11-13

The human foot and ankle system is equipped with structures that can produce mechanical work through elastic (e.g., Achilles tendon, plantar fascia) or viscoelastic (e.g., heel pad) mechanisms, or by active muscle contractions. Yet, quantifying the work distribution among various subsections of the foot and ankle can be difficult, in large part due to a lack of objective methods for partitioning the forces acting underneath the stance foot. In this study, we deconstructed the mechanical work production during barefoot walking in a segment-by-segment manner (hallux, forefoot, hindfoot, and shank). This was accomplished by isolating the forces acting within each foot segment through controlling the placement of the participants' foot as it contacted a ground-mounted force platform. Combined with an analysis that incorporated non-rigid mechanics, we quantified the total work production distal to each of the four isolated segments. We found that various subsections within the foot and ankle showed disparate work distribution, particularly within structures distal to the hindfoot. When accounting for all sources of positive and negative work distal to the shank (i.e., ankle joint and all foot structures), these structures resembled an energy-neutral system that produced net mechanical work close to zero (-0.012 ± 0.054 J/kg).

Bridging Therapy with i. v. rtPA in MCA Occlusion Prior to Endovascular Thrombectomy: a Double-Edged Sword?

PubMed

Kaesmacher, Johannes; Kleine, Justus F

2018-03-01

Recent studies suggested that preinterventional intravenous (i. v.) recombinant tissue plasminogen activator (rtPA) as bridging therapy facilitates successful and fast vessel recanalization in endovascular stroke treatment (EST); however, data on this effect and the associated clinical value are discrepant. This study examined if this discrepancy could be related to an effect-modifying variable, specifically to the exact occlusion site. Retrospective analysis of 239 patients with acute occlusion of the middle cerebral artery (MCA) treated with up to date endovascular techniques. Effects of i. v.-rtPA bridging on clinical outcomes and safety/efficacy of EST, defined as the respective rates of successful, first pass and thrombolysis in cerebral infarction (TICI) scale 3 recanalization, were evaluated and stratified according to distal versus proximal occlusion sites. Overall, i. v.-rtPA bridging was associated with a significantly higher rate of successful recanalization (86.9 % vs. 75.7 %, p = 0.028). i. v.-rtPA bridging-related effects, however, were observable only in distal, but not in proximal MCA-occlusions. In distal occlusions, i. v.-rtPA clearly favored successful recanalization (adj. OR 4.6, 95 %-CI 1.5-13.6, p = 0.006) and first-pass successes (adj. OR 2.8, 95 %-CI 1.0-7.6, p = 0.042), but tended to be associated with lower rates of complete (TICI-3) reperfusion (adj. OR 0.4, 95 %-CI 0.2-1.1, p = 0.068). The net effect was a small clinical benefit, reflected in higher rates of strong neurological improvement (adj. OR: 2.8, 95 %-CI: 1.1-6.9, p = 0.03). i. v.-rtPA-bridging-related effects are occlusion site-dependent, paralleling similar effects of systemic i. v.-rtPA when applied without subsequent endovascular therapy. In distal occlusions, i. v.-rtPA facilitates thrombectomy, but may also promote distal embolization, with a small clinical benefit as overall net effect. Randomized trials assessing i.v-rtPA bridging need

Non-invasive diagnostic system and its opto-mechanical probe for combining confocal Raman spectroscopy and optical coherence tomography.

PubMed

Klemes, Jan; Kotzianova, Adela; Pokorny, Marek; Mojzes, Peter; Novak, Jindrich; Sukova, Lada; Demuth, Jaroslav; Vesely, Jaroslav; Sasek, Ladislav; Velebny, Vladimir

2017-11-01

Non-invasive optical diagnostic methods allow important information about studied systems to be obtained in a non-destructive way. Complete diagnosis requires information about the chemical composition as well as the morphological structure of a sample. We report on the development of an opto-mechanical probe that combines Raman spectroscopy (RS) and optical coherence tomography (OCT), two methods that provide all the crucial information needed for a non-invasive diagnosis. The aim of this paper is to introduce the technical design, construction and optimization of a dual opto-mechanical probe combining two in-house developed devices for confocal RS and OCT. The unique benefit of the probe is a gradual acquisition of OCT and RS data, which allows to use the acquired OCT images to pinpoint locations of interest for RS measurements. The parameters and the correct functioning of the probe were verified by RS scanning of various samples (silicon wafer and ex vivo tissue) based on their OCT images - lateral as well as depth scanning was performed. Both the OCT and RS systems were developed, optimized and tested with the ultimate aim of verifying the functionality of the probe. Picture: Schematic illustration and visualization of the developed RS-OCT probe. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bioremediation mechanisms of combined pollution of PAHs and heavy metals by bacteria and fungi: A mini review.

PubMed

Liu, Shao-Heng; Zeng, Guang-Ming; Niu, Qiu-Ya; Liu, Yang; Zhou, Lu; Jiang, Lu-Hua; Tan, Xiao-Fei; Xu, Piao; Zhang, Chen; Cheng, Min

2017-01-01

In recent years, knowledge in regard to bioremediation of combined pollution of polycyclic aromatic hydrocarbons (PAHs) and heavy metals by bacteria and fungi has been widely developed. This paper reviews the species of bacteria and fungi which can tackle with various types of PAHs and heavy metals entering into environment simultaneously or successively. Microbial activity, pollutants bioavailability and environmental factors (e.g. pH, temperature, low molecular weight organic acids and humic acids) can all affect the bioremediation of PAHs and heavy metals. Moreover, this paper summarizes the remediation mechanisms of PAHs and heavy metals by microbes via elucidating the interaction mechanisms of heavy metals with heavy metals, PAHs/PAHs metabolites with PAHs and PAHs with heavy metals. Based on the above reviews, this paper also discusses the potential research needs for this field. Copyright © 2016 Elsevier Ltd. All rights reserved.

Emergency liver resection for combined biliary and vascular injury following laparoscopic cholecystectomy: case report and review of the literature.

PubMed

Felekouras, Evangelos; Megas, Thomas; Michail, Othon P; Papaconstantinou, Ioannis; Nikiteas, Nikolaos; Dimitroulis, Dimitrios; Griniatsos, John; Tsechpenakis, Anastasios; Kouraklis, Gregorios

2007-03-01

A 75-year-old woman suffering from symptomatic cholelithiasis was admitted to our hospital for elective laparoscopic cholecystectomy (LC). Intraoperatively, because of severe inflammation and dense adhesions in the region of the Calot triangle and bleeding arising from the porta hepatis which obscured the operating field, the method was converted to a conventional open approach. Copious hemostasis was achieved using sutures, clips and diathermy, and no bile duct or vascular injuries were recognized intraoperatively. Because of severe right upper quadrant abdominal pain and significant deterioration of the liver function tests (LFTs) on the first postoperative day, the patient underwent a Doppler ultrasound scan which showed absence of blood flow at the level of porta hepatis. Urgent relaparotomy revealed an ischemic liver on the right, a transected common bile duct at the level of its confluence, a divided and ligated right hepatic artery and thrombosed portal vein down to its confluence. Thrombectomy and reconstruction of the portal vein were performed to salvage the left hemiliver, and after restoration of blood flow to the left hemiliver, a right hemihepatectomy and a Roux-en-Y hepaticojejunostomy on the left were performed. Liver resection serves an important role in the case of parenchymal necrosis due to combined biliary, hepatic artery and portal vein injury following laparoscopic cholecystectomy and moreover, the operation can be safely performed in the acute setting.

Creation of fibrinogen-enhanced experimental blood clots to evaluate mechanical thrombectomy devices for treatment of acute stroke: an in vitro study.

PubMed

Luo, Zhong Hua; Chung, Alex; Choi, Gibok; Lin, Yih Huie; Uchida, Barry T; Pavcnik, Dusan; Loriaux, Marc M; Nesbit, Gary M; Keller, Frederick S; Rösch, Josef

2012-08-01

To explore if addition of fibrinogen to the most commonly used experimental blood clot (EBC) model would improve its mechanical properties and histologic structure. Fresh blood from three swine was used to create four EBC types. The Gralla model of thrombin-induced barium-opaque EBC served as the control. In three other EBC types, 50 mg, 100 mg, and 200 mg of bovine fibrinogen were added. Evaluation of EBCs was done with three tests: manual elongation, injection through an 8-F catheter, and an opacity test. Thirty EBCs of each type were evaluated with each test. Histologic evaluation followed. The control EBCs had low tensile strength and broke at 165% elongation. However, they were elastic and returned to their original length after catheter injection. The EBCs with fibrinogen exhibited increased tensile strength with increasing fibrinogen doses and withstood elongation to 213% (P < .01). Their elasticity decreased with increased tensile strength, and they remained elongated after catheter injection (P < .01 for EBC with 100 mg and 200 mg fibrinogen). Histologic examination showed more thorough mixing of blood with barium and a significantly increased amount of fibrin after addition of fibrinogen. Addition of fibrinogen to a Gralla EBC model changes its mechanical properties proportionately to the fibrinogen dose. Fibrinogen increases EBC tensile strength but decreases its elasticity. Fibrinogen also significantly increases the binding of blood cells with fibrin on histologic slides. Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.

Harvesting Mechanical and Thermal Energy by Combining ZnO Nanowires and NiTi Shape Memory Alloy

DOE PAGES

Radousky, Harry; Qian, Fang; An, Yonghao; ...

2017-02-19

In the expanding world of small scale energy harvesting, the ability to combine thermal and mechanical harvesting is growing ever more important. Here, we demonstrate the feasibility of using ZnO nanowires to harvest both mechanical and low-quality thermal energy in simple, scalable devices. These devices were fabricated on kapton films and used ZnO nanowires with the same growth direction to assure alignment of the piezoelectric potentials of all of the wires. Mechanical harvesting from these devices was demonstrated using a periodic application of force, modeling the motion of the human body. Tapping the device from the top of the devicemore » with a wood stick, for example yielded an Open Circuit Voltage (OCV) of 0.2 - 4 V, which is in an ideal range for device applications. In order to demonstrate thermal harvesting from low quality heat sources, a commercially available Nitinol (Ni-Ti alloy) foil was attached to the nanowire piezoelectric device to create a compound thermoelectric. When bent at room temperature and then heated to 50°C, the Nitinol foil was restored to its original flat shape, which yielded an output voltage of nearly 1 V from the ZnO nanowire device.« less

Harvesting Mechanical and Thermal Energy by Combining ZnO Nanowires and NiTi Shape Memory Alloy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radousky, Harry; Qian, Fang; An, Yonghao

In the expanding world of small scale energy harvesting, the ability to combine thermal and mechanical harvesting is growing ever more important. Here, we demonstrate the feasibility of using ZnO nanowires to harvest both mechanical and low-quality thermal energy in simple, scalable devices. These devices were fabricated on kapton films and used ZnO nanowires with the same growth direction to assure alignment of the piezoelectric potentials of all of the wires. Mechanical harvesting from these devices was demonstrated using a periodic application of force, modeling the motion of the human body. Tapping the device from the top of the devicemore » with a wood stick, for example yielded an Open Circuit Voltage (OCV) of 0.2 - 4 V, which is in an ideal range for device applications. In order to demonstrate thermal harvesting from low quality heat sources, a commercially available Nitinol (Ni-Ti alloy) foil was attached to the nanowire piezoelectric device to create a compound thermoelectric. When bent at room temperature and then heated to 50°C, the Nitinol foil was restored to its original flat shape, which yielded an output voltage of nearly 1 V from the ZnO nanowire device.« less

Structural Stability of a Stiffened Aluminum Fuselage Panel Subjected to Combined Mechanical and Internal Pressure Loads

NASA Technical Reports Server (NTRS)

Rouse, Marshall; Young, Richard D.; Gehrki, Ralph R.

2003-01-01

Results from an experimental and analytical study of a curved stiffened aluminum panel subjected to combined mechanical and internal pressure loads are presented. The panel loading conditions were simulated using a D-box test fixture. Analytical buckling load results calculated from a finite element analysis are presented and compared to experimental results. Buckling results presented indicate that the buckling load of the fuselage panel is significantly influenced by internal pressure loading. The experimental results suggest that the stress distribution is uniform in the panel prior to buckling. Nonlinear finite element analysis results correlates well with experimental results up to buckling.

Structure of Low-Lying Excited States of Guanine in DNA and Solution: Combined Molecular Mechanics and High-Level Coupled Cluster Studies

DOE PAGES

Kowalski, Karol; Valiev, Marat

2007-01-01

High-level ab-initio equation-of-motion coupled-cluster methods with singles, doubles, and noniterative triples are used, in conjunction with the combined quantum mechanical molecular mechanics approach, to investigate the structure of low-lying excited states of the guanine base in DNA and solvated environments. Our results indicate that while the excitation energy of the first excited state is barely changed compared to its gas-phase counterpart, the excitation energy of the second excited state is blue-shifted by 0.24 eV.

Design and Testing of a Minimally Invasive Blood Clot Removal Device ConstructedWith Elements of Superelastic Nitinol

NASA Astrophysics Data System (ADS)

Puffer, Andrew J.

Many vascular system problems stem from insufficient blood return flow to the heart. One of the main causes is a blockage within veins or arteries known as a blood clot, or thrombus. This can occur after trauma, surgery, or other phenomenological reasons. Each year in the U.S. more than 175,000 bypass procedures and more than 160,000 amputations resulting from peripheral vessel disease are performed. Clinical data indicates that clot removal devices and procedures can reduce the need for an amputation by 80 percent. Percutaneous thrombectomy refers to the removal of thrombus using catheter based non-surgical methods. The ultimate goal of any modality to treat these conditions of the arterial or venous system is to restore patency, quickly, safely, and cost effectively. Catheter directed thrombectomy and thrombolysis is less traumatic and avoids the morbidity and mortality associated with conventional surgical technique. As a result, there has been a push recently for the use of percutaneous mechanical thrombectomy (PMT) devices. However, all devices have their own set of drawbacks: distal embolization, vessel wall trauma, hemolysis, to name a few. Ongoing efforts have been made to create a prototype thrombectomy device that uses elements of superelastic nitinol (a type of shape memory alloy), that seeks to address some of the drawbacks of current devices. The prototype was designed and tested in a simulated human circulatory system along side a commercially available device (The DiverCE Clot Extraction Catheter). The test evaluated how well the devices minimized distal embolization of a human blood clot created in vitro.. Results of the testing showed that the prototype device created significantly less embolization when compared to the DiverCE particles greater than 102mum (p = 0.0332). Means were statistically not different for particles between 25mum and 102mum (p = 0.2454), and particles between 5mum and 25mum (p = 0.6524). In addition the prototype was shown

Soluble collagen approach to a combination tannage mechanism

USDA-ARS?s Scientific Manuscript database

Although complex salts of Cr(III) sulfate are currently the most effective tanning agents, salts of other metals, including aluminum, have been used either alone or in combination with vegetable tannins or other organic chemicals. In the present study, the interactions of aluminum sulfate, and quebr...

Soluble collagen approach to a combination tannage mechanism

USDA-ARS?s Scientific Manuscript database

Although complex salts of Cr(III) sulfate are currently the most effective tanning agents, salts of other metals, including aluminum, have been used either alone or in combination with vegetable tannins or other organic chemicals. In the present study, the interactions of metallic sulfates, and cond...

ELECTROSPUN MESOFIBERS, A NOVEL BIODEGRADABLE PHEROMONE DISPENSER TECHNOLOGY, ARE COMBINED WITH MECHANICAL DEPLOYMENT FOR EFFICIENT IPM OF LOBESIA BOTRANA IN VINEYARDS.

PubMed

Hummel, Hans E; Langner, S S; Breuer, M

2015-01-01

Behaviour modifying pheromones are well known agents for disrupting mating communication of pest insects. For optimal activity, they must be dispensed in time and space at a quantitatively measurable, predetermined release rate covering the flight period of the target species. Pheromones appeal to environmentally conscientious entomologists for their biodegradability, non-toxicity and ecological compatibility. In attempts of combining the virtues of pheromones, suitable slow release dispensers, and their mechanical deployment, an ecologically sensible, reasonably priced and patented procedure was developed and tested with the vineyard pest Lobesia botrana (Lep.: Tortricidae). It is characterized by (1) Electrospun mesofibers with diameters ranging from 0.6 to 3.5 micrometres, containing disruptants and dispensing it by slow release diffusion into the crop, (2) simultaneous application of the fully biodegradable combination of pheromone with Ecoflex polyester mesofiber, (3) combination of mechanical deployment by multi-purpose cultivators of the prefabricated pheromone dispensers with other simultaneous cultivation measures, and thus further reducing labour time and treatment costs. The dispensers are biodegradable within half a year without leaving any objectionable residues. In the standard eco-toxicology tests pheromone dispensers are harmless to non-target organisms. The disruptive effect of one treatment lasts for seven weeks which covers well one of several flight periods of L. botrana.

Atom Probe Tomography Unveils Formation Mechanisms of Wear-Protective Tribofilms by ZDDP, Ionic Liquid, and Their Combination

DOE PAGES

Guo, Wei; Zhou, Yan; Sang, Xiahan; ...

2017-06-20

The development of advanced lubricant additives has been a critical component in paving the way for increasing energy efficiency and durability for numerous industry applications. However, the formation mechanisms of additive-induced protective tribofilms are not yet fully understood because of the complex chemomechanical interactions at the contact interface and the limited spatial resolution of many characterizing techniques currently used. In this paper, the tribofilms on a gray cast iron surface formed by three antiwear additives are systematically studied; a phosphonium-phosphate ionic liquid (IL), a zinc dialkyldithiophosphate (ZDDP), and an IL+ZDDP combination. All three additives provide excellent wear protection, with themore » IL+ZDDP combination exhibiting a synergetic effect, resulting in further reduced friction and wear. Atom probe tomography (APT) and scanning transmission electron microscopy (STEM) imaging and electron energy loss spectroscopy (EELS) were used to interrogate the subnm chemistry and bonding states for each of the tribofilms of interest. The IL tribofilm appeared amorphous and was Fe, P, and O rich. Wear debris particles having an Fe-rich core and an oxide shell were present in this tribofilm and a transitional oxide (Fe 2O 3)-containing layer was identified at the interface between the tribofilm and the cast iron substrate. The ZDDP+IL tribofilm shared some of the characteristics found in the IL and ZDDP tribofilms. Finally, tribofilm formation mechanisms are proposed on the basis of the observations made at the atomic level.« less

Atom Probe Tomography Unveils Formation Mechanisms of Wear-Protective Tribofilms by ZDDP, Ionic Liquid, and Their Combination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Wei; Zhou, Yan; Sang, Xiahan

The development of advanced lubricant additives has been a critical component in paving the way for increasing energy efficiency and durability for numerous industry applications. However, the formation mechanisms of additive-induced protective tribofilms are not yet fully understood because of the complex chemomechanical interactions at the contact interface and the limited spatial resolution of many characterizing techniques currently used. In this paper, the tribofilms on a gray cast iron surface formed by three antiwear additives are systematically studied; a phosphonium-phosphate ionic liquid (IL), a zinc dialkyldithiophosphate (ZDDP), and an IL+ZDDP combination. All three additives provide excellent wear protection, with themore » IL+ZDDP combination exhibiting a synergetic effect, resulting in further reduced friction and wear. Atom probe tomography (APT) and scanning transmission electron microscopy (STEM) imaging and electron energy loss spectroscopy (EELS) were used to interrogate the subnm chemistry and bonding states for each of the tribofilms of interest. The IL tribofilm appeared amorphous and was Fe, P, and O rich. Wear debris particles having an Fe-rich core and an oxide shell were present in this tribofilm and a transitional oxide (Fe 2O 3)-containing layer was identified at the interface between the tribofilm and the cast iron substrate. The ZDDP+IL tribofilm shared some of the characteristics found in the IL and ZDDP tribofilms. Finally, tribofilm formation mechanisms are proposed on the basis of the observations made at the atomic level.« less

Characterization of the mechanical properties of skin by inverse analysis combined with the indentation test.

PubMed

Delalleau, Alexandre; Josse, Gwendal; Lagarde, Jean-Michel; Zahouani, Hassan; Bergheau, Jean-Michel

2006-01-01

This study proposes a new method to determine the mechanical properties of human skin by the use of the indentation test [Pailler-Mattei, 2004. Caractérisation mécanique et tribologique de la peau humaine in vivo, Ph.D. Thesis, ECL-no. 2004-31; Pailler-Mattei, Zahouani, 2004. Journal of Adhesion Science and Technology 18, 1739-1758]. The principle of the measurements consists in applying an in vivo compressive stress [Zhang et al., 1994. Proceedings of the Institution of Mechanical Engineers 208, 217-222; Bosboom et al., 2001. Journal of Biomechanics 34, 1365-1368; Oomens et al., 1984. Selected Proceedings of Meetings of European Society of Biomechanics, pp. 227-232; Oomens et al., 1987. Journal of Biomechanics 20(9), 877-885] on the skin tissue of an individual's forearm. These measurements show an increase in the normal contact force as a function of the indentation depth. The interpretation of such results usually requires a long and tedious phenomenological study. We propose a new method to determine the mechanical parameters which control the response of skin tissue. This method is threefold: experimental, numerical, and comparative. It consists combining experimental results with a numerical finite elements model in order to find out the required parameters. This process uses a scheme of extended Kalman filters (EKF) [Gu et al., 2003. Materials Science and Engineering A345, 223-233; Nakamura et al., 2000. Acta Mater 48, 4293-4306; Leustean and Rosu, 2003. Certifying Kalman filters. RIACS Technical Report 03.02, 27pp. http://gureni.cs.uiuc.edu/~grosu/download/luta + leo.pdf; Welch and Bishop, An introduction to Kalman filter, University of North Carolina at Chapel Hill, 16p. http://www.cs.unc.edu/~welch/kalman/]. The first results presented in this study correspond to a simplified numerical modeling of the global system. The skin is assumed to be a semi-infinite layer with an isotropic linear elastic mechanical behavior [Zhang et al., 1994. Proceedings of

Bacterial radiosensitization by using radiation processing in combination with essential oil: Mechanism of action

NASA Astrophysics Data System (ADS)

Lacroix, Monique; Caillet, Stéphane; Shareck, Francois

2009-07-01

Spice extracts under the form of essential oils were tested for their efficiency to increase the relative radiosensitivity of Listeria monocytogenes and Escherichia coli O157H7 in culture media. The two pathogens were treated by gamma-irradiation alone or in combination with oregano essential oil to evaluate their mechanism of action. The membrane murein composition, and the intracellular and extracellular concentration of ATP was determined. The bacterial strains were treated with two irradiation doses: 1.2 kGy to induce cell damage and 3.5 kGy to cause cell death for L. monocytogenes. A dose of 0.4 kGy to induce cell damages, 1.1 kGy to obtain viable but nonculturable (VBNC) state and 1.3 kGy to obtain a lethal dose was also applied on E. coli O157H7. Oregano essential oil was used at 0.020% and 0.025% (w/v), which is the minimum inhibitory concentration (MIC) for L. monocytogenes. For E. coli O157H7, a concentration of 0.006% and 0.025% (w/v) which is the minimum inhibitory concentration was applied. The use of essential oils in combination with irradiation has permitted an increase of the bacterial radiosensitization by more than 3.1 times. All treatments had also a significant effect ( p⩽0.05) on the murein composition, although some muropeptides did not seem to be affected by the treatment. Each treatment influenced differently the relative percentage and number of muropeptides. There was a significant ( p⩽0.05) correlation between the reduction of intracellular ATP and increase in extracellular ATP following treatment of the cells with oregano oil. The reduction of intracellular ATP was even more important when essential oil was combined with irradiation, but irradiation of L. monocytogenes alone induced a significant decrease ( p⩽0.05) of the internal ATP without affecting the external ATP.

Drink refusal training as part of a combined behavioral intervention: Effectiveness and mechanisms of change

PubMed Central

Witkiewitz, Katie; Donovan, Dennis M.; Hartzler, Bryan

2012-01-01

Objective Many trials have demonstrated the effectiveness of cognitive behavioral interventions for alcohol dependence, yet few studies have examined why particular treatments are effective. This study was designed to evaluate whether drink refusal training was an effective component of a combined behavioral intervention (CBI) and whether change in self-efficacy was a mechanism of change following drink refusal training for individuals with alcohol dependence. Method The current study is a secondary analysis of data from the COMBINE study, a randomized clinical trial that combined pharmacotherapy with behavioral intervention in the treatment of alcohol dependence. The goal of the current study was to examine whether a drink refusal skills training module, administered as part of a 16-week CBI (n=776; 31% female, 23% non-White, average age=44) predicted changes in drinking frequency and self-efficacy during and following the CBI, and whether changes in self-efficacy following drink refusal training predicted changes in drinking frequency up to one year following treatment. Results Participants (n=302) who received drink refusal skills training had significantly fewer drinking days during treatment (d=0.50) and up to one year following treatment (d=0.23). In addition the effect of the drink refusal skills training module on drinking outcomes following treatment was significantly mediated by changes in self-efficacy, even after controlling for changes in drinking outcomes during treatment (proportion mediated = 0.47). Conclusions Drink refusal training is an effective component of CBI and some of the effectiveness may be attributed to changes in client self-efficacy. PMID:22289131

Combination of Oral Antibiotics and Mechanical Bowel Preparation Reduces Surgical Site Infection in Colorectal Surgery.

PubMed

Ohman, Kerri A; Wan, Leping; Guthrie, Tracey; Johnston, Bonnie; Leinicke, Jennifer A; Glasgow, Sean C; Hunt, Steven R; Mutch, Matthew G; Wise, Paul E; Silviera, Matthew L

2017-10-01

Surgical site infections (SSI) are a common complication after colorectal surgery. An infection prevention bundle (IPB) was implemented to improve outcomes. A standardized IPB that included the administration of oral antibiotics with a mechanical bowel preparation, preoperative shower with chlorhexidine, hair removal and skin preparation in holding, antibiotic wound irrigation, and a "clean-closure" protocol was implemented in January 2013. Data from the American College of Surgeons NSQIP were analyzed at a single academic institution to compare pre-IPB and post-IPB SSI rates. In January 2014, a prospective database was implemented to determine compliance with individual IPB elements and their effect on outcomes. For the 24 months pre-IPB, the overall SSI rate was 19.7%. During the 30 months after IPB implementation, the SSI rate decreased to 8.2% (p < 0.0001). A subset of 307 patients was identified in both NSQIP and our prospective compliance databases. Elements of IPB associated with decreased SSI rates included preoperative shower with chlorhexidine (4.6% vs 16.2%; p = 0.005), oral antibiotics (3.4% vs 15.4%; p < 0.001), and mechanical bowel preparation (4.4% vs 14.3%; p = 0.008). Patients who received a full bowel preparation of both oral antibiotics and a mechanical bowel preparation had a 2.7% SSI rate compared with 15.8% for all others (p < 0.001). On multivariate analysis, full bowel preparation was independently associated with significantly fewer SSI (adjusted odds ratio 0.2; 95% CI 0.1 to 0.9; p = 0.006). Implementation of an IPB was successful in decreasing SSI rates in colorectal surgery patients. The combination of oral antibiotics with a mechanical bowel preparation was the strongest predictor of decreased SSI. Copyright © 2017 American College of Surgeons. All rights reserved.

Development and Testing of a ``Backlash-Free'' Gas-Tight High Precision Sample Handling Mechanism for Combined Science on the ExoMars 2018 Rover

NASA Astrophysics Data System (ADS)

Paul, R.; Redlich, D.; Richter, L.; Zuknik, K.-H.; Muhlbauer, Q.; Thiel, M.; Fowler, L.; Tattusch, T.; Weisz, H.; Musso, F.; Durrant, S.

2015-09-01

This paper presents the development and testing by the OHB System AG of the Powdered Sample Handling Mechanism (PSHS) that is part of the rover of the European Space Agency 2018 ExoMars Mission, a cooperative mission with Roscosmos including a scientific instrument contribution from NASA. The task of this mechanism is to flatten and position powdered Martian soil samples allowing subsequent investigation of selected grains by different optical instruments thus providing combined science in an ultra-clean environment.The exceptional sensitivity of these instruments causes extremely challenging requirements with respect to positioning performance as well as cleanliness and contamination control. The impact of these design drivers is highlighted focusing on specific mechanism features such as the pre-torque device to minimize the backlash and the dynamic feed-through, allowing a gas-tight encapsulation of an ultra-clean zone free of drive-train components.Subsequently the results of the test campaign of an elegant breadboard under Mars-like conditions, as well as first QM test results are described. Furthermore the outcomes of combined tests with an optical instrument are reported.

Combined quantum mechanics/molecular mechanics (QM/MM) simulations for protein-ligand complexes: free energies of binding of water molecules in influenza neuraminidase.

PubMed

Woods, Christopher J; Shaw, Katherine E; Mulholland, Adrian J

2015-01-22

The applicability of combined quantum mechanics/molecular mechanics (QM/MM) methods for the calculation of absolute binding free energies of conserved water molecules in protein/ligand complexes is demonstrated. Here, we apply QM/MM Monte Carlo simulations to investigate binding of water molecules to influenza neuraminidase. We investigate five different complexes, including those with the drugs oseltamivir and peramivir. We investigate water molecules in two different environments, one more hydrophobic and one hydrophilic. We calculate the free-energy change for perturbation of a QM to MM representation of the bound water molecule. The calculations are performed at the BLYP/aVDZ (QM) and TIP4P (MM) levels of theory, which we have previously demonstrated to be consistent with one another for QM/MM modeling. The results show that the QM to MM perturbation is significant in both environments (greater than 1 kcal mol(-1)) and larger in the more hydrophilic site. Comparison with the same perturbation in bulk water shows that this makes a contribution to binding. The results quantify how electronic polarization differences in different environments affect binding affinity and also demonstrate that extensive, converged QM/MM free-energy simulations, with good levels of QM theory, are now practical for protein/ligand complexes.

Uncovering stability mechanisms in microbial ecosystems - combining microcosm experiments, computational modelling and ecological theory in a multidisciplinary approach

NASA Astrophysics Data System (ADS)

Worrich, Anja; König, Sara; Banitz, Thomas; Centler, Florian; Frank, Karin; Kästner, Matthias; Miltner, Anja; Thullner, Martin; Wick, Lukas

2015-04-01

Although bacterial degraders in soil are commonly exposed to fluctuating environmental conditions, the functional performance of the biodegradation processes can often be maintained by resistance and resilience mechanisms. However, there is still a gap in the mechanistic understanding of key factors contributing to the stability of such an ecosystem service. Therefore we developed an integrated approach combining microcosm experiments, simulation models and ecological theory to directly make use of the strengths of these disciplines. In a continuous interplay process, data, hypotheses, and central questions are exchanged between disciplines to initiate new experiments and models to ultimately identify buffer mechanisms and factors providing functional stability. We focus on drying and rewetting-cycles in soil ecosystems, which are a major abiotic driver for bacterial activity. Functional recovery of the system was found to depend on different spatial processes in the computational model. In particular, bacterial motility is a prerequisite for biodegradation if either bacteria or substrate are heterogeneously distributed. Hence, laboratory experiments focussing on bacterial dispersal processes were conducted and confirmed this finding also for functional resistance. Obtained results will be incorporated into the model in the next step. Overall, the combination of computational modelling and laboratory experiments identified spatial processes as the main driving force for functional stability in the considered system, and has proved a powerful methodological approach.

Mechanical competence of ovariectomy-induced compromised bone after single or combined treatment with high-frequency loading and bisphosphonates

PubMed Central

Camargos G. V.; Bhattacharya P.; van Lenthe G. H.; Del Bel Cury A. A.; Naert I.; Duyck J.; Vandamme K.

2015-01-01

Osteoporosis leads to increased bone fragility, thus effective approaches enhancing bone strength are needed. Hence, this study investigated the effect of single or combined application of high-frequency (HF) loading through whole body vibration (WBV) and alendronate (ALN) on the mechanical competence of ovariectomy-induced osteoporotic bone. Thirty-four female Wistar rats were ovariectomized (OVX) or sham-operated (shOVX) and divided into five groups: shOVX, OVX-shWBV, OVX-WBV, ALN-shWBV and ALN-WBV. (Sham)WBV loading was applied for 10 min/day (130 to 150 Hz at 0.3g) for 14 days and ALN at 2 mg/kg/dose was administered 3x/week. Finite element analysis based on micro-CT was employed to assess bone biomechanical properties, relative to bone micro-structural parameters. HF loading application to OVX resulted in an enlarged cortex, but it was not able to improve the biomechanical properties. ALN prevented trabecular bone deterioration and increased bone stiffness and bone strength of OVX bone. Finally, the combination of ALN with HF resulted in an increased cortical thickness in OVX rats when compared to single treatments. Compared to HF loading, ALN treatment is preferred for improving the compromised mechanical competence of OVX bone. In addition, the association of ALN with HF loading results in an additive effect on the cortical thickness. PMID:26027958

Mechanism-based corrector combination restores ΔF508-CFTR folding and function

PubMed Central

Okiyoneda, Tsukasa; Veit, Guido; Dekkers, Johanna F.; Bagdany, Miklos; Soya, Naoto; Xu, Haijin; Roldan, Ariel; Verkman, Alan S.; Kurth, Mark; Simon, Agnes; Hegedus, Tamas; Beekman, Jeffrey M.; Lukacs, Gergely L.

2013-01-01

The most common cystic fibrosis (CF) mutation, ΔF508 in the nucleotide binding domain-1 (NBD1), impairs CFTR coupled-domain folding, plasma membrane (PM) expression, function and stability. VX-809, a promising investigational corrector of ΔF508-CFTR misprocessing, has limited clinical benefit and incompletely understood mechanism, hampering drug development. Based on the effect of second site suppressor mutations, robust ΔF508-CFTR correction likely requires stabilization of NBD1 and the membrane spanning domains (MSDs)-NBD1 interface, both established primary conformational defects. Here, we elucidated the molecular targets of available correctors; class-I stabilizes the NBD1-MSD1/2 interface, class-II targets NBD2, and only chemical chaperones, surrogates of class-III correctors, stabilize the human ΔF508-NBD1. While VX-809 can correct missense mutations primarily destabilizing the NBD1-MSD1/2 interface, functional PM expression of ΔF508-CFTR also requires compounds that counteract the NBD1 and NBD2 stability defects in CF bronchial epithelial cells and intestinal organoids. Thus, structure-guided corrector combination represents an effective approach for CF therapy. PMID:23666117

A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest

NASA Astrophysics Data System (ADS)

Arenz, Stefan; Bock, Lars V.; Graf, Michael; Innis, C. Axel; Beckmann, Roland; Grubmüller, Helmut; Vaiana, Andrea C.; Wilson, Daniel N.

2016-07-01

Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-Å-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation.

Combined effects of cerium and cooling rate on microstructure and mechanical properties of AZ91 magnesium alloy

NASA Astrophysics Data System (ADS)

Cai, Huisheng; Guo, Feng; Su, Juan

2018-01-01

The specimens of AZ91-xCe(x = 0, 0.3, 0.6, 0.9, 1.2, mass fraction wt%) with different thicknesses were prepared by die casting process, their as-cast microstructure and room temperature mechanical properties were investigated to analyze the change rule of microstructure and mechanical properties of AZ91 magnesium alloy under combined effects of cooling rate and cerium content. The results show that, the microstructure and mechanical properties of AZ91 magnesium alloy were twofold influenced by cooling rate and cerium content. With the increase of cooling rate and Ce content, the average as-cast grain size is evidently refined; the amount of β-Mg17Al12 decreases and distribution becomes discrete. While decreasing cooling rate or increasing Ce content, Al4Ce phase is more and the morphology tends to strip and needle from granular and short rod-like. The tensile strength and elongation of AZ91-xCe magnesium alloy are improved with increasing cooling rate. With the increase of Ce content, the tensile strength and elongation of AZ91-xCe magnesium alloy increased first and decreased afterwards, besides the action of Ce to improve tensile strength and elongation is more evident under faster cooling rate. Mechanical properties of samples are optimal in this work, when Ce content is 0.96% and cooling rate is 39.6 K s-1, tensile strength (259.7 MPa) and elongation (5.5%) are reached maximum, respectively.

Thrombus aspiration in non-ST-elevation myocardial infarction - 12-month clinical outcome of the randomised TATORT-NSTEMI trial.

PubMed

Meyer-Saraei, Roza; de Waha, Suzanne; Eitel, Ingo; Desch, Steffen; Scheller, Bruno; Böhm, Michael; Lauer, Bernward; Gawaz, Meinrad; Geisler, Tobias; Gunkel, Oliver; Bruch, Leonhard; Klein, Norbert; Pfeiffer, Dietrich; Schuler, Gerhard; Zeymer, Uwe; Thiele, Holger

2017-02-01

In the randomised TATORT-NSTEMI trial routine thrombus aspiration in comparison with standard percutaneous coronary intervention (PCI) did not reduce the primary endpoint of microvascular obstruction assessed by cardiac magnetic resonance imaging in patients with non-ST-elevation myocardial infarction (NSTEMI). So far, no data on long-term outcome of head-to-head comparisons between both treatment strategies in NSTEMI patients have been reported. The prospective, controlled, multicentre, randomised, open-label TATORT-NSTEMI trial assigned patients with NSTEMI and thrombus-containing lesions to aspiration thrombectomy plus PCI ( n=221) or standard PCI only ( n=219). The primary endpoint of the current analysis was the occurrence of major adverse cardiac events defined as the composite of death, myocardial reinfarction, target vessel revascularisation, and new congestive heart failure at 12-month follow-up. In addition, functional outcome and quality of life were assessed. At one year, major adverse cardiac events occurred in 19 patients in the thrombectomy arm and 29 patients in the standard PCI group (8.7% vs. 13.4%, relative risk 0.63, 95% confidence interval 0.35-1.12, p=0.11). The individual components of the combined endpoint such as death ( p=0.20), myocardial reinfarction ( p=0.73), target vessel revascularisation ( p=0.42), and congestive heart failure ( p=0.18) were similar in both groups. Functional outcome and quality of life did not differ significantly between both groups (Canadian Cardiovascular Society class: p=0.68, New York Heart Association class: p=0.70 and EuroQol5D score: p=0.96). Post-hoc analyses revealed consistent results with regard to the occurrence of major adverse cardiac events across a wide range of subgroups (all p>0.05). In this first randomised trial on thrombectomy in NSTEMI patients, routine thrombus aspiration before PCI did not improve clinical outcome at 12-month follow-up.

A bifurcation study to guide the design of a landing gear with a combined uplock/downlock mechanism.

PubMed

Knowles, James A C; Lowenberg, Mark H; Neild, Simon A; Krauskopf, Bernd

2014-12-08

This paper discusses the insights that a bifurcation analysis can provide when designing mechanisms. A model, in the form of a set of coupled steady-state equations, can be derived to describe the mechanism. Solutions to this model can be traced through the mechanism's state versus parameter space via numerical continuation, under the simultaneous variation of one or more parameters. With this approach, crucial features in the response surface, such as bifurcation points, can be identified. By numerically continuing these points in the appropriate parameter space, the resulting bifurcation diagram can be used to guide parameter selection and optimization. In this paper, we demonstrate the potential of this technique by considering an aircraft nose landing gear, with a novel locking strategy that uses a combined uplock/downlock mechanism. The landing gear is locked when in the retracted or deployed states. Transitions between these locked states and the unlocked state (where the landing gear is a mechanism) are shown to depend upon the positions of two fold point bifurcations. By performing a two-parameter continuation, the critical points are traced to identify operational boundaries. Following the variation of the fold points through parameter space, a minimum spring stiffness is identified that enables the landing gear to be locked in the retracted state. The bifurcation analysis also shows that the unlocking of a retracted landing gear should use an unlock force measure, rather than a position indicator, to de-couple the effects of the retraction and locking actuators. Overall, the study demonstrates that bifurcation analysis can enhance the understanding of the influence of design choices over a wide operating range where nonlinearity is significant.

A bifurcation study to guide the design of a landing gear with a combined uplock/downlock mechanism

PubMed Central

Knowles, James A. C.; Lowenberg, Mark H.; Neild, Simon A.; Krauskopf, Bernd

2014-01-01

This paper discusses the insights that a bifurcation analysis can provide when designing mechanisms. A model, in the form of a set of coupled steady-state equations, can be derived to describe the mechanism. Solutions to this model can be traced through the mechanism's state versus parameter space via numerical continuation, under the simultaneous variation of one or more parameters. With this approach, crucial features in the response surface, such as bifurcation points, can be identified. By numerically continuing these points in the appropriate parameter space, the resulting bifurcation diagram can be used to guide parameter selection and optimization. In this paper, we demonstrate the potential of this technique by considering an aircraft nose landing gear, with a novel locking strategy that uses a combined uplock/downlock mechanism. The landing gear is locked when in the retracted or deployed states. Transitions between these locked states and the unlocked state (where the landing gear is a mechanism) are shown to depend upon the positions of two fold point bifurcations. By performing a two-parameter continuation, the critical points are traced to identify operational boundaries. Following the variation of the fold points through parameter space, a minimum spring stiffness is identified that enables the landing gear to be locked in the retracted state. The bifurcation analysis also shows that the unlocking of a retracted landing gear should use an unlock force measure, rather than a position indicator, to de-couple the effects of the retraction and locking actuators. Overall, the study demonstrates that bifurcation analysis can enhance the understanding of the influence of design choices over a wide operating range where nonlinearity is significant. PMID:25484601

Toward innovative combinational immunotherapy: A systems biology perspective.

PubMed

Li, Xue-Tao; Yang, Jin-Ji; Wu, Yi-Long; Hou, Jun

2018-05-08

The treatment of non-small-cell lung cancer (NSCLC) has advanced significantly in the last decades. Especially immune checkpoint inhibitors have shown inconceivable effect on enhancing host anti-tumor activity in NSCLC. However, the limitation of checkpoint blockade monotherapy seems unavoidable in most of the NSCLC patients and only ∼20% of them achieved response to monotherapy with immune checkpoint inhibitors. Thus combining immune checkpoint inhibitors with other agents with different action mechanisms holds a promise to revitalize NSCLC treatment, such as the combination of checkpoint inhibitors with angiogenesis inhibitors, or with chemotherapy, as well as the combination of two checkpoint inhibitors. Recently, various combinational strategies have been explored to setup promising combination regimens and to understand the action mechanisms. In this review, we summarize the suspected synergistic mechanisms of several combinational approaches by reviewing the available preclinical and clinical data. Then we discuss in light of the current knowledge of cancer biology and systems biology the important facets to be examined when setting up a framework for developing immunotherapy-based combination strategies. Copyright © 2018. Published by Elsevier Ltd.

Combined therapeutic effect and molecular mechanisms of metformin and cisplatin in human lung cancer xenografts in nude mice.

PubMed

Chen, Yu-Qin; Chen, Gang

2015-01-01

This work was aimed at studying the inhibitory activity of metformin combined with the commonly used chemotherapy drug cisplatin in human lung cancer xenografts in nude mice. We also examined the combined effects of these drugs on the molecular expression of survivin, matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor-C (VEGF-C), and vascular endothelial growth factor receptor-3 (VEGFR-3) to determine the mechanism of action and to explore the potential applications of the new effective drug therapy in lung cancer. The nude mice model of lung cancer xenografts was established, and mice were randomly divided into the metformin group, the cisplatin group, the metformin + cisplatin group, and the control group. The animals were killed 42 days after drug administration, and the tumor tissues were then sampled to detect the messenger ribonucleic acid (mRNA) and protein expression levels of survivin, MMP-2, VEGF-C, and VEGFR-3 by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). The protein and mRNA expression levels of survivin, MMP-2, VEGF-C, and VEGFR-3 in the cisplatin group and the combined treatment group were lower than that in the control group (P < 0.05). In the metformin group, the expression of MMP-2 protein and mRNA was lower than that in the control group (P < 0.05). The protein and mRNA expression levels of survivin, MMP-2, VEGF-C, and VEGFR-3 in the combined treatment group were lower than that in the cisplatin group and the metformin group (P < 0.05). Metformin inhibited the expression of MMP-2, cisplatin and the combined treatment inhibited the expression of survivin, MMP-2, VEGF-C, and VEGFR-3, and the combined treatment of metformin with cisplatin resulted in enhanced anti-tumor efficacy.

Theoretical Characterization of the Spectral Density of the Water-Soluble Chlorophyll-Binding Protein from Combined Quantum Mechanics/Molecular Mechanics Molecular Dynamics Simulations.

PubMed

Rosnik, Andreana M; Curutchet, Carles

2015-12-08

Over the past decade, both experimentalists and theorists have worked to develop methods to describe pigment-protein coupling in photosynthetic light-harvesting complexes in order to understand the molecular basis of quantum coherence effects observed in photosynthesis. Here we present an improved strategy based on the combination of quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations and excited-state calculations to predict the spectral density of electronic-vibrational coupling. We study the water-soluble chlorophyll-binding protein (WSCP) reconstituted with Chl a or Chl b pigments as the system of interest and compare our work with data obtained by Pieper and co-workers from differential fluorescence line-narrowing spectra (Pieper et al. J. Phys. Chem. B 2011, 115 (14), 4042-4052). Our results demonstrate that the use of QM/MM MD simulations where the nuclear positions are still propagated at the classical level leads to a striking improvement of the predicted spectral densities in the middle- and high-frequency regions, where they nearly reach quantitative accuracy. This demonstrates that the so-called "geometry mismatch" problem related to the use of low-quality structures in QM calculations, not the quantum features of pigments high-frequency motions, causes the failure of previous studies relying on similar protocols. Thus, this work paves the way toward quantitative predictions of pigment-protein coupling and the comprehension of quantum coherence effects in photosynthesis.

Mechanism of Fructus Aurantii Flavonoids Promoting Gastrointestinal Motility: From Organic and Inorganic Endogenous Substances Combination Point of View.

PubMed

Wang, Shuai; Bao, Yong-Rui; Li, Tian-Jiao; Yu, Ting; Chang, Xin; Yang, Guan-Lin; Meng, Xian-Sheng

2017-01-01

Fructus Aurantii (FA) derived from the dried, and unripe fruit of Citrus aurantium L. is one of the commonly used traditional Chinese medicines to treat gastrointestinal motility dysfunction diseases. According to the literature research, FA flavonoids (FAF) are important active ingredients of FA promoting gastrointestinal motility, but the exact material basis and mechanism of action are still not very clear. This experiment was designed to illustrate the material basis of FAF promoting gastrointestinal motility and explore the mechanism of action from an organic and inorganic combination point of view. In this experiment, high-performance liquid chromatography (HPLC) method was used to analyze the composition and content of FAF. Based on the prominent prokinetic effect of FAF on mice, the mechanism of action was speculated through a combination of HPLC coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) and inductively coupled plasma mass spectrometry (ICP-MS). With the method of HPLC, ten dominating components of FAF including neoeriocitrin, narirutin, rhoifolin, naringin, hesperidin, neohesperidin, neoponcirin, naringenin, hesperetin, and nobiletin accounting for more than 86% of FAF were identified. Combined HPLC-QTOF-MS with ICP-MS, the endogenous substances with difference in the blood of mice were analyzed, in which 4-dimethylallyltryptophan, corticosterone, phytosphingosine, sphinganine, LysoPC (20:4(5Z, 8Z, 11Z, 14Z)), LysoPC(18:2 (9Z, 12Z)), and Ca 2+ , Mg 2+ , Zn 2+ metal ions had significant changes, involving tryptophan metabolism, corticosterone metabolism, sphingolipid metabolism, and other pathways. The results preliminarily elaborated the mechanism of FAF promoting gastrointestinal motility from an organic and inorganic point of view, which provide valuable information for researching and developing new multi-component Chinese medicine curing gastrointestinal underpower associated diseases. Fructus Aurantii flavonoids are one

The mechanical properties of stored red blood cells measured by a convenient microfluidic approach combining with mathematic model.

PubMed

Wang, Ying; You, Guoxing; Chen, Peipei; Li, Jianjun; Chen, Gan; Wang, Bo; Li, Penglong; Han, Dong; Zhou, Hong; Zhao, Lian

2016-03-01

The mechanical properties of red blood cells (RBCs) are critical to the rheological and hemodynamic behavior of blood. Although measurements of the mechanical properties of RBCs have been studied for many years, the existing methods, such as ektacytometry, micropipette aspiration, and microfluidic approaches, still have limitations. Mechanical changes to RBCs during storage play an important role in transfusions, and so need to be evaluated pre-transfusion, which demands a convenient and rapid detection method. We present a microfluidic approach that focuses on the mechanical properties of single cell under physiological shear flow and does not require any high-end equipment, like a high-speed camera. Using this method, the images of stretched RBCs under physical shear can be obtained. The subsequent analysis, combined with mathematic models, gives the deformability distribution, the morphology distribution, the normalized curvature, and the Young's modulus (E) of the stored RBCs. The deformability index and the morphology distribution show that the deformability of RBCs decreases significantly with storage time. The normalized curvature, which is defined as the curvature of the cell tail during stretching in flow, suggests that the surface charge of the stored RBCs decreases significantly. According to the mathematic model, which derives from the relation between shear stress and the adherent cells' extension ratio, the Young's moduli of the stored RBCs are also calculated and show significant increase with storage. Therefore, the present method is capable of representing the mechanical properties and can distinguish the mechanical changes of the RBCs during storage. The advantages of this method are the small sample needed, high-throughput, and easy-use, which make it promising for the quality monitoring of RBCs.

Comprehensive mechanical characterization of PLA fabric combined with PCL to form a composite structure vascular graft.

PubMed

Li, Chaojing; Wang, Fujun; Douglas, Graeham; Zhang, Ze; Guidoin, Robert; Wang, Lu

2017-05-01

Vascular grafts made by tissue engineering processes are prone to buckling and twisting, which can impede blood flow and lead to collapse of the vessel. These vascular conduits may suffer not only from insufficient tensile strength, but also from vulnerabilities related to compression, torsion, and pulsatile pressurization. Aiming to develop a tissue engineering-inspired blood conduit, composite vascular graft (cVG) prototypes were created by combining a flexible polylactic acid (PLA) knitted fabric with a soft polycaprolactone (PCL) matrix. The graft is to be populated in-situ with cellular migration and proliferation into the device. Comprehensive characterizations probed the relationship between structure and mechanical properties of the different cVG prototypes. The composite grafts exhibited major improvements in mechanical characteristics compared to single-material devices, with particular improvement in compression and torsional resistance. A commercial expanded polytetrafluoroethylene (ePTFE) vascular graft was used as a control against the proposed composite vascular grafts. CVG devices showed high tensile strength, high bursting strength, and improved suture retention. Compression, elastic recovery, and compliance were similar to those for the ePTFE graft. Copyright © 2016 Elsevier Ltd. All rights reserved.

Suitability of a PLCL fibrous scaffold for soft tissue engineering applications: A combined biological and mechanical characterisation.

PubMed

Laurent, Cédric P; Vaquette, Cédryck; Liu, Xing; Schmitt, Jean-François; Rahouadj, Rachid

2018-04-01

Poly(lactide-co-ε-caprolactone) (PLCL) has been reported to be a good candidate for tissue engineering because of its good biocompatibility. Particularly, a braided PLCL scaffold (PLL/PCL ratio = 85/15) has been recently designed and partially validated for ligament tissue engineering. In the present study, we assessed the in vivo biocompatibility of acellular and cellularised scaffolds in a rat model. We then determined its in vitro biocompatibility using stem cells issued from both bone marrow and Wharton Jelly. From a biological point of view, the scaffold was shown to be suitable for tissue engineering in all these cases. Secondly, while the initial mechanical properties of this scaffold have been previously reported to be adapted to load-bearing applications, we studied the evolution in time of the mechanical properties of PLCL fibres due to hydrolytic degradation. Results for isolated PLCL fibres were extrapolated to the fibrous scaffold using a previously developed numerical model. It was shown that no accumulation of plastic strain was to be expected for a load-bearing application such as anterior cruciate ligament tissue engineering. However, PLCL fibres exhibited a non-expected brittle behaviour after two months. This may involve a potential risk of premature failure of the scaffold, unless tissue growth compensates this change in mechanical properties. This combined study emphasises the need to characterise the properties of biomaterials in a pluridisciplinary approach, since biological and mechanical characterisations led in this case to different conclusions concerning the suitability of this scaffold for load-bearing applications.

Mechanisms of colitis-accelerated colon carcinogenesis and its prevention with the combination of aspirin and curcumin: Transcriptomic analysis using RNA-seq.

PubMed

Guo, Yue; Su, Zheng-Yuan; Zhang, Chengyue; Gaspar, John M; Wang, Rui; Hart, Ronald P; Verzi, Michael P; Kong, Ah-Ng Tony

2017-07-01

Colorectal cancer (CRC) remains the leading cause of cancer-related death in the world. Aspirin (ASA) and curcumin (CUR) are widely investigated chemopreventive candidates for CRC. However, the precise mechanisms of their action and their combinatorial effects have not been evaluated. The purpose of the present study was to determine the effect of ASA, CUR, and their combination in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-accelerated colorectal cancer (CAC). We also aimed to characterize the differential gene expression profiles in AOM/DSS-induced tumors as well as in tumors modulated by ASA and CUR using RNA-seq. Diets supplemented with 0.02% ASA, 2% CUR or 0.01% ASA+1% CUR were given to mice from 1week prior to the AOM injection until the experiment was terminated 22weeks after AOM initiation. Our results showed that CUR had a superior inhibitory effect in colon tumorigenesis compared to that of ASA. The combination of ASA and CUR at a lower dose exhibited similar efficacy to that of a higher dose of CUR at 2%. RNA isolated from colonic tissue from the control group and from tumor samples from the experimental groups was subjected to RNA-seq. Transcriptomic analysis suggested that the low-dose combination of ASA and CUR modulated larger gene sets than the single treatment. These differentially expressed genes were situated in several canonical pathways important in the inflammatory network and liver metastasis in CAC. We identified a small subset of genes as potential molecular targets involved in the preventive action of the combination of ASA and CUR. Taken together, the current results provide the first evidence in support of the chemopreventive effect of a low-dose combination of ASA and CUR in CAC. Moreover, the transcriptional profile obtained in our study may provide a framework for identifying the mechanisms underlying the carcinogenesis process from normal colonic tissue to tumor development as well as the cancer inhibitory effects

Network Bursting Dynamics in Excitatory Cortical Neuron Cultures Results from the Combination of Different Adaptive Mechanism

PubMed Central

Masquelier, Timothée; Deco, Gustavo

2013-01-01

In the brain, synchronization among cells of an assembly is a common phenomenon, and thought to be functionally relevant. Here we used an in vitro experimental model of cell assemblies, cortical cultures, combined with numerical simulations of a spiking neural network (SNN) to investigate how and why spontaneous synchronization occurs. In order to deal with excitation only, we pharmacologically blocked GABAAergic transmission using bicuculline. Synchronous events in cortical cultures tend to involve almost every cell and to display relatively constant durations. We have thus named these “network spikes” (NS). The inter-NS-intervals (INSIs) proved to be a more interesting phenomenon. In most cortical cultures NSs typically come in series or bursts (“bursts of NSs”, BNS), with short (∼1 s) INSIs and separated by long silent intervals (tens of s), which leads to bimodal INSI distributions. This suggests that a facilitating mechanism is at work, presumably short-term synaptic facilitation, as well as two fatigue mechanisms: one with a short timescale, presumably short-term synaptic depression, and another one with a longer timescale, presumably cellular adaptation. We thus incorporated these three mechanisms into the SNN, which, indeed, produced realistic BNSs. Next, we systematically varied the recurrent excitation for various adaptation timescales. Strong excitability led to frequent, quasi-periodic BNSs (CV∼0), and weak excitability led to rare BNSs, approaching a Poisson process (CV∼1). Experimental cultures appear to operate within an intermediate weakly-synchronized regime (CV∼0.5), with an adaptation timescale in the 2–8 s range, and well described by a Poisson-with-refractory-period model. Taken together, our results demonstrate that the INSI statistics are indeed informative: they allowed us to infer the mechanisms at work, and many parameters that we cannot access experimentally. PMID:24146781

Responses to combined abiotic and biotic stress in tomato are governed by stress intensity and resistance mechanism

PubMed Central

Kissoudis, Christos; Sunarti, Sri; van de Wiel, Clemens; Visser, Richard G.F.; van der Linden, C. Gerard; Bai, Yuling

2016-01-01

Stress conditions in agricultural ecosystems can occur at variable intensities. Different resistance mechanisms against abiotic stress and pathogens are deployed by plants. Thus, it is important to examine plant responses to stress combinations under different scenarios. Here, we evaluated the effect of different levels of salt stress ranging from mild to severe (50, 100, and 150mM NaCl) on powdery mildew resistance and overall performance of tomato introgression lines with contrasting levels of partial resistance, as well as near-isogenic lines (NILs) carrying the resistance gene Ol-1 (associated with a slow hypersensitivity response; HR), ol-2 (an mlo mutant associated with papilla formation), and Ol-4 (an R gene associated with a fast HR). Powdery mildew resistance was affected by salt stress in a genotype- and stress intensity-dependent manner. In susceptible and partial resistant lines, increased susceptibility was observed under mild salt stress (50mM) which was accompanied by accelerated cell death-like senescence. In contrast, severe salt stress (150mM) reduced disease symptoms. Na+ and Cl− accumulation in the leaves was linearly related to the decreased pathogen symptoms under severe stress. In contrast, complete resistance mediated by ol-2 and Ol-4 was unaffected under all treatment combinations, and was associated with a decreased growth penalty. Increased susceptibility and senescence under combined stress in NIL-Ol-1 was associated with the induction of ethylene and jasmonic acid pathway genes and the cell wall invertase gene LIN6. These results highlight the significance of stress severity and resistance type on the plant’s performance under the combination of abiotic and biotic stress. PMID:27436279

Serial assessment of the index of microcirculatory resistance during primary percutaneous coronary intervention comparing manual aspiration catheter thrombectomy with balloon angioplasty (IMPACT study): a randomised controlled pilot study.

PubMed

Hoole, Stephen P; Jaworski, Catherine; Brown, Adam J; McCormick, Liam M; Agrawal, Bobby; Clarke, Sarah C; West, Nick E J

2015-01-01

Utilising a novel study design, we evaluated serial measurements of the index of microcirculatory resistance (IMR) in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) to assess the impact of device therapy on microvascular function, and determine what proportion of microvascular injury is related to the PPCI procedure, and what is an inevitable consequence of STEMI. 41 patients undergoing PPCI for STEMI were randomised to balloon angioplasty (BA, n=20) or manual thrombectomy (MT, n=21) prior to stenting. Serial IMR measurements, corrected for collaterals, were recorded at baseline and at each stage of the procedure. Microvascular obstruction (MVO) and infarct size at 24 h and 3 months were measured by troponin and cardiac MRI (CMR). IMR did not change significantly following PPCI, but patients with lower IMR values (<32, n=30) at baseline had a significant increase in IMR following PPCI (baseline: 21.2±7.9 vs post-stent: 33.0±23.7, p=0.01) attributable to prestent IRA instrumentation (baseline: 21.7±8.0 vs post-BA or MT: 36.9±25.9, p=0.006). Post-stent IMR correlated with early MVO on CMR (p=0.01). There was no significant difference in post-stent IMR, presence of early MVO or final infarct size between patients with BA and patients treated with MT. Patients with STEMI and less microcirculatory dysfunction may be susceptible to acute iatrogenic microcirculatory injury from prestent coronary devices. MT did not appear to be superior to BA in maintaining microcirculatory integrity when the guide wire partially restores IRA flow during PPCI. ISRCTN31767278.

Epigallocatechin-3-gallate(EGCG) : mechanisms and the combined applications.

PubMed

Song, Xuekun; Du, Juan; Zhao, Wenyuan; Guo, Zheng

2017-12-17

EGCG is the most important pharmacological component in tea. Researches have confirmed its effects, including anti-tumor, anti-inflammation, anti-aging, anti-obesity, anti-diabetic, cardiovascular disease prevention and protection, immunoregulation and neuroprotection. Paradoxically, the clinical application of EGCG is very rare. One of the most important reasons is its poor stability and low bioavailability. Excepting for altering the dosage form or synthesizing the analogues to overcome the loss during absorption, an increasing number of studies indicate that EGCG can exert certain auxiliary effect and enhance chemosensitivity in combined medication. The pharmacological action, the pharmacology network including mutation of signaling receptor and modulation of intracellular signaling pathway, and the combination treatment strategy of EGCG are clarified and sorted out, both the possible targets and combinatorial applications based on the characteristics of EGCG are systematically summarized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Spline-Screw Multiple-Rotation Mechanism

NASA Technical Reports Server (NTRS)

Vranish, John M.

1994-01-01

Mechanism functions like combined robotic gripper and nut runner. Spline-screw multiple-rotation mechanism related to spline-screw payload-fastening system described in (GSC-13454). Incorporated as subsystem in alternative version of system. Mechanism functions like combination of robotic gripper and nut runner; provides both secure grip and rotary actuation of other parts of system. Used in system in which no need to make or break electrical connections to payload during robotic installation or removal of payload. More complicated version needed to make and break electrical connections. Mechanism mounted in payload.

Molecular mechanism of Poria cocos combined with oxaliplatin on the inhibition of epithelial-mesenchymal transition in gastric cancer cells.

PubMed

Wang, Na; Liu, Dengxiang; Guo, Jun; Sun, Yawei; Guo, Ting; Zhu, Xiaoyan

2018-06-01

Natural product Poria cocos possesses antitumor effect. This study will explore the molecular mechanism of Poria cocos combined with chemotherapy in the inhibition of gastric cancer cell EMT process. The experiment was divided into blank control group, Poria cocos group, oxaliplatin group and Poria cocos combined with oxaliplatin group. Scratch and Transwell assay were used to detect cell migration and invasion respectively. RT-qPCR and Western Blot analyses were used to detect mRNA and protein expression of the epithelial-mesenchymal transition (EMT) related factors including Snail, Twist, Vimentin, E-cadherin and N-cadherin respectively. Morphologic assessment was performed with HPIAS-1000 automated image analysis system. The migration and invasion abilities of gastric cancer cells in the Poria cocos combined with oxaliplatin group were significantly decreased (P < 0.01). The mRNA and protein expression of Snail, Twist, Vimentin and N-cadherin were significantly decreased while the mRNA and protein expression of E-cadherin were significantly increased (P < 0.01) compared with blank control group. Nude mice model of gastric cancer was successfully established. Poria cocos combined with oxaliplatin could significantly inhibit gastric tumor progression. The expression of EMT related factors were consistent with in vitro study. Morphologic assessment showed that the nucleus area, perimeter, mean diameter, volume, long diameter and shape factor in the Poria cocos combined with oxaliplatin group were significantly different compared with the blank control group (P < 0.01) but not significantly different compared with the normal control. Poria cocos combined with oxaliplatin could significantly inhibit the migration and invasion of gastric cancer cells. Through both in vitro and in vivo studies, it is confirmed that Poria cocos combined with oxaliplatin could significantly inhibit the EMT process of gastric cancer. Poria cocos combined with oxaliplatin could

Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke)

PubMed Central

Saver, Jeffrey L.; Zaidat, Osama O.; Jahan, Reza; Aziz-Sultan, Mohammad Ali; Klucznik, Richard P.; Haussen, Diogo C.; Hellinger, Frank R.; Yavagal, Dileep R.; Yao, Tom L.; Liebeskind, David S.; Jadhav, Ashutosh P.; Gupta, Rishi; Hassan, Ameer E.; Martin, Coleman O.; Bozorgchami, Hormozd; Kaushal, Ritesh; Nogueira, Raul G.; Gandhi, Ravi H.; Peterson, Eric C.; Dashti, Shervin R.; Given, Curtis A.; Mehta, Brijesh P.; Deshmukh, Vivek; Starkman, Sidney; Linfante, Italo; McPherson, Scott H.; Kvamme, Peter; Grobelny, Thomas J.; Hussain, Muhammad S.; Thacker, Ike; Vora, Nirav; Chen, Peng Roc; Monteith, Stephen J.; Ecker, Robert D.; Schirmer, Clemens M.; Sauvageau, Eric; Abou-Chebl, Alex; Derdeyn, Colin P.; Maidan, Lucian; Badruddin, Aamir; Siddiqui, Adnan H.; Dumont, Travis M.; Alhajeri, Abdulnasser; Taqi, M. Asif; Asi, Khaled; Carpenter, Jeffrey; Boulos, Alan; Jindal, Gaurav; Puri, Ajit S.; Chitale, Rohan; Deshaies, Eric M.; Robinson, David H.; Kallmes, David F.; Baxter, Blaise W.; Jumaa, Mouhammad A.; Sunenshine, Peter; Majjhoo, Aniel; English, Joey D.; Suzuki, Shuichi; Fessler, Richard D.; Delgado Almandoz, Josser E.; Martin, Jerry C.; Mueller-Kronast, Nils H.

2017-01-01

Background: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. Methods: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0–2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. Results: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients (P<0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06–1.79; P=0.02). Likewise, excellent outcome (modified Rankin Score 0–1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13–1.92; P=0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P=0.55). Intravenous tissue plasminogen activator did not impact

Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).

PubMed

Froehler, Michael T; Saver, Jeffrey L; Zaidat, Osama O; Jahan, Reza; Aziz-Sultan, Mohammad Ali; Klucznik, Richard P; Haussen, Diogo C; Hellinger, Frank R; Yavagal, Dileep R; Yao, Tom L; Liebeskind, David S; Jadhav, Ashutosh P; Gupta, Rishi; Hassan, Ameer E; Martin, Coleman O; Bozorgchami, Hormozd; Kaushal, Ritesh; Nogueira, Raul G; Gandhi, Ravi H; Peterson, Eric C; Dashti, Shervin R; Given, Curtis A; Mehta, Brijesh P; Deshmukh, Vivek; Starkman, Sidney; Linfante, Italo; McPherson, Scott H; Kvamme, Peter; Grobelny, Thomas J; Hussain, Muhammad S; Thacker, Ike; Vora, Nirav; Chen, Peng Roc; Monteith, Stephen J; Ecker, Robert D; Schirmer, Clemens M; Sauvageau, Eric; Abou-Chebl, Alex; Derdeyn, Colin P; Maidan, Lucian; Badruddin, Aamir; Siddiqui, Adnan H; Dumont, Travis M; Alhajeri, Abdulnasser; Taqi, M Asif; Asi, Khaled; Carpenter, Jeffrey; Boulos, Alan; Jindal, Gaurav; Puri, Ajit S; Chitale, Rohan; Deshaies, Eric M; Robinson, David H; Kallmes, David F; Baxter, Blaise W; Jumaa, Mouhammad A; Sunenshine, Peter; Majjhoo, Aniel; English, Joey D; Suzuki, Shuichi; Fessler, Richard D; Delgado Almandoz, Josser E; Martin, Jerry C; Mueller-Kronast, Nils H

2017-12-12

Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( P <0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06-1.79; P =0.02). Likewise, excellent outcome (modified Rankin Score 0-1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13-1.92; P =0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P =0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass

The use of Rheology Combined with Differential Scanning Calorimetry to Elucidate the Granulation Mechanism of an Immiscible Formulation During Continuous Twin-Screw Melt Granulation.

PubMed

Monteyne, Tinne; Heeze, Liza; Mortier, Severine Therese F C; Oldörp, Klaus; Cardinaels, Ruth; Nopens, Ingmar; Vervaet, Chris; Remon, Jean-Paul; De Beer, Thomas

2016-10-01

Twin screw hot melt granulation (TS HMG) is a valuable, but still unexplored alternative to continuous granulation of moisture sensitive drugs. However, knowledge of the material behavior during TS HMG is crucial to optimize the formulation, process and resulting granule properties. The aim of this study was to evaluate the agglomeration mechanism during TS HMG using a rheometer in combination with differential scanning calorimetry (DSC). An immiscible drug-binder formulation (caffeine-Soluplus(®)) was granulated via TS HMG in combination with thermal and rheological analysis (conventional and Rheoscope), granule characterization and Near Infrared chemical imaging (NIR-CI). A thin binder layer with restricted mobility was formed on the surface of the drug particles during granulation and is covered by a second layer with improved mobility when the Soluplus(®) concentration exceeded 15% (w/w). The formation of this second layer was facilitated at elevated granulation temperatures and resulted in smaller and more spherical granules. The combination of thermal and rheological analysis and NIR-CI images was advantageous to develop in-depth understanding of the agglomeration mechanism during continuous TS HMG and provided insight in the granule properties as function of process temperature and binder concentration.

Animal models of ischaemic stroke and characterisation of the ischaemic penumbra.

PubMed

McCabe, Christopher; Arroja, Mariana M; Reid, Emma; Macrae, I Mhairi

2018-05-15

Over the past forty years, animal models of focal cerebral ischaemia have allowed us to identify the critical cerebral blood flow thresholds responsible for irreversible cell death, electrical failure, inhibition of protein synthesis, energy depletion and thereby the lifespan of the potentially salvageable penumbra. They have allowed us to understand the intricate biochemical and molecular mechanisms within the 'ischaemic cascade' that initiate cell death in the first minutes, hours and days following stroke. Models of permanent, transient middle cerebral artery occlusion and embolic stroke have been developed each with advantages and limitations when trying to model the complex heterogeneous nature of stroke in humans. Yet despite these advances in understanding the pathophysiological mechanisms of stroke-induced cell death with numerous targets identified and drugs tested, a lack of translation to the clinic has hampered pre-clinical stroke research. With recent positive clinical trials of endovascular thrombectomy in acute ischaemic stroke the stroke community has been reinvigorated, opening up the potential for future translation of adjunctive treatments that can be given alongside thrombectomy/thrombolysis. This review discusses the major animal models of focal cerebral ischaemia highlighting their advantages and limitations. Acute imaging is crucial in longitudinal pre-clinical stroke studies in order to identify the influence of acute therapies on tissue salvage over time. Therefore, the methods of identifying potentially salvageable ischaemic penumbra are discussed. This article is part of the Special Issue entitled 'Cerebral Ischemia'. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Combined effects of zooplankton grazing and dispersal on the diversity and assembly mechanisms of bacterial metacommunities.

PubMed

Berga, Mercè; Östman, Örjan; Lindström, Eva S; Langenheder, Silke

2015-07-01

Effects of dispersal and the presence of predators on diversity, assembly and functioning of bacterial communities are well studied in isolation. In reality, however, dispersal and trophic interactions act simultaneously and can therefore have combined effects, which are poorly investigated. We performed an experiment with aquatic metacommunities consisting of three environmentally different patches and manipulated dispersal rates among them as well as the presence or absence of the keystone species Daphnia magna. Daphnia magna reduced both local and regional diversity, whereas dispersal increased local diversity but decreased beta-diversity having no net effect on regional diversity. Dispersal modified the assembly mechanisms of bacterial communities by increasing the degree of determinism. Additionally, the combination of the D. magna and dispersal increased the importance of deterministic processes, presumably because predator-tolerant taxa were spread in the metacommunity via dispersal. Moreover, the presence of D. magna affected community composition, increased community respiration rates but did not affect bacterial production or abundance, whereas dispersal slightly increased bacterial production. In conclusion, our study suggests that predation by a keystone species such as D. magna and dispersal additively influence bacterial diversity, assembly processes and ecosystem functioning. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

Neural mechanisms of attention become more specialised during infancy: Insights from combined eye tracking and EEG.

PubMed

Kulke, Louisa; Atkinson, Janette; Braddick, Oliver

2017-03-01

The Fixation Shift Paradigm (FSP) measures infants' ability to shift gaze from a central fixation stimulus to a peripheral target (e.g. Hood & Atkinson, 1993: Infant Behavior and Development, 16(4), 405-422). Cortical maturation has been suggested as crucial for the developing ability to shift attention. This study investigated the development of neural mechanisms by combining EEG with simultaneous eye tracking during FSP testing, in typically developing infants aged between 1 and 8 months. The most prominent neural response was a frontal positivity which occurred only in the hemisphere contralateral to the target in the youngest infants but became more ipsilateral with age. This changing lateralisation was associated with improving ability to shift attention (decreasing saccade latencies and fewer 'sticky fixations'-failures to disengage attention from the central target). These findings suggest that the lateralisation of neural responses develops during infancy, possibly due to developing intracortical connections, allowing infants to shift attention more efficiently. Successful use of combined simultaneous remote eye tracking and EEG to measure infant attention shifts. Neural responses involved in attention shifts change in the first year of life. The lateralisation of EEG responses changes with age in the first year of life. Frontal cortex is involved in attention shifts from around 2 months of age. © 2016 Wiley Periodicals, Inc.

Influence of extremely low frequency, low energy electromagnetic fields and combined mechanical stimulation on chondrocytes in 3-D constructs for cartilage tissue engineering.

PubMed

Hilz, Florian M; Ahrens, Philipp; Grad, Sibylle; Stoddart, Martin J; Dahmani, Chiheb; Wilken, Frauke L; Sauerschnig, Martin; Niemeyer, Philipp; Zwingmann, Jörn; Burgkart, Rainer; von Eisenhart-Rothe, Rüdiger; Südkamp, Norbert P; Weyh, Thomas; Imhoff, Andreas B; Alini, Mauro; Salzmann, Gian M

2014-02-01

Articular cartilage, once damaged, has very low regenerative potential. Various experimental approaches have been conducted to enhance chondrogenesis and cartilage maturation. Among those, non-invasive electromagnetic fields have shown their beneficial influence for cartilage regeneration and are widely used for the treatment of non-unions, fractures, avascular necrosis and osteoarthritis. One very well accepted way to promote cartilage maturation is physical stimulation through bioreactors. The aim of this study was the investigation of combined mechanical and electromagnetic stress affecting cartilage cells in vitro. Primary articular chondrocytes from bovine fetlock joints were seeded into three-dimensional (3-D) polyurethane scaffolds and distributed into seven stimulated experimental groups. They either underwent mechanical or electromagnetic stimulation (sinusoidal electromagnetic field of 1 mT, 2 mT, or 3 mT; 60 Hz) or both within a joint-specific bioreactor and a coil system. The scaffold-cell constructs were analyzed for glycosaminoglycan (GAG) and DNA content, histology, and gene expression of collagen-1, collagen-2, aggrecan, cartilage oligomeric matrix protein (COMP), Sox9, proteoglycan-4 (PRG-4), and matrix metalloproteinases (MMP-3 and -13). There were statistically significant differences in GAG/DNA content between the stimulated versus the control group with highest levels in the combined stimulation group. Gene expression was significantly higher for combined stimulation groups versus static control for collagen 2/collagen 1 ratio and lower for MMP-13. Amongst other genes, a more chondrogenic phenotype was noticed in expression patterns for the stimulated groups. To conclude, there is an effect of electromagnetic and mechanical stimulation on chondrocytes seeded in a 3-D scaffold, resulting in improved extracellular matrix production. © 2013 Wiley Periodicals, Inc.

Incidence and etiological mechanism of stroke in cardiac surgery.

PubMed

Arribas, J M; Garcia, E; Jara, R; Gutierrez, F; Albert, L; Bixquert, D; García-Puente, J; Albacete, C; Canovas, S; Morales, A

2017-12-14

We studied patients who had experienced a stroke in the postoperative period of cardiac surgery, aiming to analyse their progression and determine the factors that may influence prognosis and treatment. We established a protocol for early detection of stroke after cardiac surgery and collected data on stroke onset and a number of clinical, surgical, and prognostic variables in order to perform a descriptive analysis. Over the 15-month study period we recorded 16 strokes, which represent 2.5% of the patients who underwent cardiac surgery. Mean age in our sample was 69 ± 8 years; 63% of patients were men. The incidence of stroke in patients aged 80 and older was 5.1%. Five patients (31%) underwent emergency surgery. By type of cardiac surgery, 7% of patients underwent mitral valve surgery, 6.5% combined surgery, 3% aortic valve surgery, and 2.24% coronary surgery. Most cases of stroke (44%) were due to embolism, followed by hypoperfusion (25%). Stroke occurred within 2 days of surgery in 69% of cases. The mean NIHSS score in our sample of stroke patients was 9; code stroke was activated in 10 cases (62%); one patient (14%) underwent thrombectomy. Most patients progressed favourably: 13 (80%) scored≤2 on the modified Rankin Scale at 3 months. None of the patients died during the postoperative hospital stay. In our setting, strokes occurring after cardiac surgery are usually small and have a good long-term prognosis. Most of them occur within 2 days, and they are mostly embolic in origin. The incidence of stroke in patients aged 80 and older and undergoing cardiac surgery is twice as high as that of the general population. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Mechanisms of Zn(II) binded to collagen and its effect on the capacity of eco-friendly Zn-Cr combination tanning system.

PubMed

Cao, Shan; Liu, Bing; Cheng, Baozhen; Lu, Fuping; Wang, Yanping; Li, Yu

2017-01-05

The eco-friendly combination tanning process has been developed to reduce chromium in existing researches, which is based on zinc tanning agents. This can be considered as a less-chrome substitute for current tanning process. To gain deeper understanding of the binding mechanisms of zinc-collagen interaction, which are affected by tanning pH, experiments have been carried out. Analysis in this paper reveals how chemical bonds from the collagen's main function groups combine with zinc. XPS and NIR data was analyzed for further understanding of where the zinc binding sites lie on collagen fibers at different pH. The results indicate that high pH is helpful to amino-binding sites while low pH promotes carboxyl-binding sites on collagen fibers. Furthermore, from the effect of Zinc-chrome combination tanning, we can see that the new method reduces the chromium dosage in tanning process compared to the conventional chrome tanning method. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of the fungus Piriformospora indica on physiological characteristics and root morphology of wheat under combined drought and mechanical stresses.

PubMed

Hosseini, Fatemeh; Mosaddeghi, Mohammad Reza; Dexter, Anthony Roger

2017-09-01

This study was done to evaluate the effects of the root-colonizing endophytic fungus Piriformospora indica on wheat growth under combined drought and mechanical stresses. Inoculated (colonized) and non-inoculated (uncolonized) wheat (Triticum aestivum L. cv. Chamran) seedlings were planted in growth chambers filled with moist sand (at a matric suction of 20 hPa). Slight, moderate and severe mechanical stresses (i.e., penetration resistance, Q p , of 1.17, 4.17 and 5.96 MPa, respectively) were produced by a dead-load technique (i.e., placing a weight on the sand surface) in the root medium. Slight, moderate and severe drought stresses were induced using PEG 6000 solutions with osmotic potentials of 0, -0.3 and -0.5 MPa, respectively. After 30 days, plant physiological characteristics and root morphology were measured. An increase in Q p from 1.17 to 5.96 MPa led to greater leaf proline concentration and root diameter, and lower relative water content (RWC), leaf water potential (LWP), chlorophyll contents and root volume. Moreover, severe drought stress decreased root and shoot fresh weights, root volume, leaf area, RWC, LWP and chlorophyll content compared to control. Catalase (CAT) and ascorbate peroxidase (APX) activities under severe drought stress were about 1.5 and 2.9 times greater than control. Interaction of the stresses showed that mechanical stress primarily controls plant water status and physiological responses. However, endophyte presence mitigated the adverse effects of individual and combined stresses on plant growth. Colonized plants were better adapted and had greater root length and volume, RWC, LWP and chlorophyll contents under stressful conditions due to higher absorption sites for water and nutrients. Compared with uncolonized plants, colonized plants showed lower CAT activity implying that wheat inoculated with P. indica was more tolerant and experienced less oxidative damage induced by drought and/or mechanical stress. Copyright �

Combination Drug Therapy for Pain following Chronic Spinal Cord Injury

PubMed Central

Hama, Aldric; Sagen, Jacqueline

2012-01-01

A number of mechanisms have been elucidated that maintain neuropathic pain due to spinal cord injury (SCI). While target-based therapeutics are being developed based on elucidation of these mechanisms, treatment for neuropathic SCI pain has not been entirely satisfactory due in part to the significant convergence of neurological and inflammatory processes that maintain the neuropathic pain state. Thus, a combination drug treatment strategy, wherein several pain-related mechanism are simultaneously engaged, could be more efficacious than treatment against individual mechanisms alone. Also, by engaging several targets at once, it may be possible to reduce the doses of the individual drugs, thereby minimizing the potential for adverse side effects. Positive preclinical and clinical studies have demonstrated improved efficacy of combination drug treatment over single drug treatment in neuropathic pain of peripheral origin, and perhaps such combinations could be utilized for neuropathic SCI pain. At the same time, there are mechanisms that distinguish SCI from peripheral neuropathic pain, so novel combination therapies will be needed. PMID:22550581

Chloride Ion Transport by the E. coli CLC Cl-/H+ Antiporter: A Combined Quantum-Mechanical and Molecular-Mechanical Study.

PubMed

Wang, Chun-Hung; Duster, Adam W; Aydintug, Baris O; Zarecki, MacKenzie G; Lin, Hai

2018-01-01

We performed steered molecular dynamics (SMD) and umbrella sampling simulations of Cl - ion migration through the transmembrane domain of a prototypical E. coli CLC Cl - /H + antiporter by employing combined quantum-mechanical (QM) and molecular-mechanical (MM) calculations. The SMD simulations revealed interesting conformational changes of the protein. While no large-amplitude motions of the protein were observed during pore opening, the side chain rotation of the protonated external gating residue Glu148 was found to be critical for full access of the channel entrance by Cl - . Moving the anion into the external binding site (S ext ) induced small-amplitude shifting of the protein backbone at the N-terminal end of helix F. As Cl - traveled through the pore, rigid-body swinging motions of helix R separated it from helix D. Helix R returned to its original position once Cl - exited the channel. Population analysis based on polarized wavefunction from QM/MM calculations discovered significant (up to 20%) charge loss for Cl - along the ion translocation pathway inside the pore. The delocalized charge was redistributed onto the pore residues, especially the functional groups containing π bonds (e.g., the Tyr445 side chain), while the charges of the H atoms coordinating Cl - changed almost negligibly. Potentials of mean force computed from umbrella sampling at the QM/MM and MM levels both displayed barriers at the same locations near the pore entrance and exit. However, the QM/MM PMF showed higher barriers (~10 kcal/mol) than the MM PMF (~2 kcal/mol). Binding energy calculations indicated that the interactions between Cl - and certain pore residues were overestimated by the semi-empirical PM3 Hamiltonian and underestimated by the CHARMM36 force fields, both of which were employed in the umbrella sampling simulations. In particular, CHARMM36 underestimated binding interactions for the functional groups containing π bonds, missing the stabilizations of the Cl - ion due

Chloride Ion Transport by the E. coli CLC Cl−/H+ Antiporter: A Combined Quantum-Mechanical and Molecular-Mechanical Study

PubMed Central

Wang, Chun-Hung; Duster, Adam W.; Aydintug, Baris O.; Zarecki, MacKenzie G.; Lin, Hai

2018-01-01

We performed steered molecular dynamics (SMD) and umbrella sampling simulations of Cl− ion migration through the transmembrane domain of a prototypical E. coli CLC Cl−/H+ antiporter by employing combined quantum-mechanical (QM) and molecular-mechanical (MM) calculations. The SMD simulations revealed interesting conformational changes of the protein. While no large-amplitude motions of the protein were observed during pore opening, the side chain rotation of the protonated external gating residue Glu148 was found to be critical for full access of the channel entrance by Cl−. Moving the anion into the external binding site (Sext) induced small-amplitude shifting of the protein backbone at the N-terminal end of helix F. As Cl− traveled through the pore, rigid-body swinging motions of helix R separated it from helix D. Helix R returned to its original position once Cl− exited the channel. Population analysis based on polarized wavefunction from QM/MM calculations discovered significant (up to 20%) charge loss for Cl− along the ion translocation pathway inside the pore. The delocalized charge was redistributed onto the pore residues, especially the functional groups containing π bonds (e.g., the Tyr445 side chain), while the charges of the H atoms coordinating Cl− changed almost negligibly. Potentials of mean force computed from umbrella sampling at the QM/MM and MM levels both displayed barriers at the same locations near the pore entrance and exit. However, the QM/MM PMF showed higher barriers (~10 kcal/mol) than the MM PMF (~2 kcal/mol). Binding energy calculations indicated that the interactions between Cl− and certain pore residues were overestimated by the semi-empirical PM3 Hamiltonian and underestimated by the CHARMM36 force fields, both of which were employed in the umbrella sampling simulations. In particular, CHARMM36 underestimated binding interactions for the functional groups containing π bonds, missing the stabilizations of the Cl− ion

Chloride Ion Transport by the E. coli CLC Cl–/H+ Antiporter: A Combined Quantum-Mechanical and Molecular-Mechanical Study

NASA Astrophysics Data System (ADS)

Wang, Chun-Hung; Duster, Adam W.; Aydintug, Baris O.; Zarecki, MacKenzie G.; Lin, Hai

2018-03-01

We performed steered molecular dynamics (SMD) and umbrella sampling simulations of Cl– ion migration through the transmembrane domain of a prototypical E. coli CLC Cl–/H+ antiporter employing combined quantum-mechanical (QM) and molecular-mechanical (MM) calculations. The SMD simulations revealed interesting conformational changes of the protein. While no large-amplitude motions of the protein were observed during pore opening, the side chain rotation of the protonated external gating residue Glu148 was found critical to full access of the channel entrance by Cl–. Moving the anion into the external binding site (Sext) induced small-amplitude shifting of the protein backbone at the N-terminal end of helix F. As Cl– travelled through the pore, rigid-body swinging motions of helix R separated it from helix D. Helix R returned to its original position once Cl– exited the channel. Population analysis based on polarized wavefunction from QM/MM calculations discovered significant (up to 20%) charge loss for Cl– along the ion translocation pathway inside the pore. The delocalized charge was redistributed onto the pore residues, especially the functional groups containing pi bonds (e.g. the Tyr445 side chain), while the charges of the H atoms coordinating Cl– changed almost negligibly. Potentials of mean force computed from umbrella sampling at the QM/MM and MM levels both displayed barriers at the same locations near the pore entrance and exit. However, the QM/MM PMF showed higher barriers ( 10 kcal/mol) than the MM PMF ( 2 kcal/mol). Binding energy calculations indicated that the interactions between Cl– and certain pore residues were overestimated by the semi-empirical PM3 Hamiltonian and underestimated by the CHARMM36 force fields, both of which were employed in the umbrella sampling simulations. In particular, CHARMM36 underestimated binding interactions for the functional groups containing pi bonds, missing the stabilizations of the Cl– ion due to

High-reliability release mechanism

NASA Technical Reports Server (NTRS)

Paradise, J. J.

1971-01-01

Release mechanism employing simple clevis fitting in combination with two pin-pullers achieves high reliability degree through active mechanical redundancy. Mechanism releases solar arrays. It is simple and inexpensive and performs effectively. It adapts to other release-system applications with variety of pin-puller devices.

[THE ENVIRONMENTAL BASES AND MECHANISM FOR NATURAL OPISTHORCHIASIS FOCUS PULSATION IN THE COMBINED FOCUS OF OPISTHORCHIASIS AND TULAREMIA].

PubMed

Ushakov, A V

2015-01-01

A cyclic change in the epizootic activity of a tularemia activity underlies the mechanism of natural opisthorchiasis focus pulsation in the combined focus of opisthorchiasis and tularemia in the ecosystem of the Konda River. This is due to mass breeding and depression in the water vole (Arvicola terrestris) population. The mass breeding is predetermined by high population reproduction constants. The rodents' potential fecundity occurs with the high capacity of lands, which is caused by the hydrological regime of rivers. The size depression is predetermined by the epizootics of tularemia. The water vole is a host of the pathogens of opisthorchiasis and tularemia. So the mass rodent breeding in the combined infection and invasion focus causes an increase in the number of real invasion sources. The epizootic of tularemia is responsible for elimination of these invasion sources and for decreases in the flow of invasion material, the infection rate of Codiella and hence the amount of their produced cercarae, the extensive and intensive indicators of fish contamination, and the intensity of an epizootic process in the opisthorchiasis focus.

Combination of Functional Nanoengineering and Nanosecond Laser Texturing for Design of Superhydrophobic Aluminum Alloy with Exceptional Mechanical and Chemical Properties.

PubMed

Boinovich, Ludmila B; Modin, Evgeny B; Sayfutdinova, Adeliya R; Emelyanenko, Kirill A; Vasiliev, Alexander L; Emelyanenko, Alexandre M

2017-10-24

Industrial application of metallic materials is hindered by several shortcomings, such as proneness to corrosion, erosion under abrasive loads, damage due to poor cold resistance, or weak resistance to thermal shock stresses, etc. In this study, using the aluminum-magnesium alloy as an example of widely spread metallic materials, we show that a combination of functional nanoengineering and nanosecond laser texturing with the appropriate treatment regimes can be successfully used to transform a metal into a superhydrophobic material with exceptional mechanical and chemical properties. It is demonstrated that laser chemical processing of the surface may be simultaneously used to impart multimodal roughness and to modify the composition and physicochemical properties of a thick surface layer of the substrate itself. Such integration of topographical and physicochemical modification leads to specific surface nanostructures such as nanocavities filled with hydrophobic agent and hard oxynitride nanoinclusions. The combination of superhydrophobic state, nano- and micro features of the hierarchical surface, and the appropriate composition of the surface textured layer allowed us to provide the surface with the outstanding level of resistance of superhydrophobic coatings to external chemical and mechanical impacts. In particular, experimental data presented in this study indicate high resistance of the fabricated coatings to pitting corrosion, superheated water vapor, sand abrasive wear, and rapid temperature cycling from liquid nitrogen to room temperatures, without notable degradation of superhydrophobic performance.

MECHANISMS IN ENDOCRINOLOGY: An update in the genetic aetiologies of combined pituitary hormone deficiency.

PubMed

Castinetti, Frederic; Reynaud, Rachel; Saveanu, Alexandru; Jullien, Nicolas; Quentien, Marie Helene; Rochette, Claire; Barlier, Anne; Enjalbert, Alain; Brue, Thierry

2016-06-01

Over the last 5 years, new actors involved in the pathogenesis of combined pituitary hormone deficiency in humans have been reported: they included a member of the immunoglobulin superfamily glycoprotein and ciliary G protein-coupled receptors, as well as new transcription factors and signalling molecules. New modes of inheritance for alterations of genes encoding transcription factors have also been described. Finally, actors known to be involved in a very specific phenotype (hypogonadotroph hypogonadism for instance) have been identified in a wider range of phenotypes. These data thus suggest that new mechanisms could explain the low rate of aetiological identification in this heterogeneous group of diseases. Taking into account the fact that several reviews have been published in recent years on classical aetiologies of CPHD such as mutations of POU1F1 or PROP1, we focused the present overview on the data published in the last 5 years, to provide the reader with an updated review on this rapidly evolving field of knowledge. © 2016 European Society of Endocrinology.

Effect of Stretching Combined With Ultrashort Wave Diathermy on Joint Function and Its Possible Mechanism in a Rabbit Knee Contracture Model.

PubMed

Zhang, Quan Bing; Zhou, Yun; Zhong, Hua Zhang; Liu, Yi

2018-05-01

The aim of this study was to investigate the therapeutic effect of stretching combined with ultrashort wave on joint contracture and explore its possible mechanism. Thirty-two rabbits underwent unilateral immobilization of a knee joint at full extension to cause joint contracture. At 6 wks after immobilization, the rabbits were randomly divided into the following four groups: natural recovery group, stretching treatment group, ultrashort wave treatment group, and combined treatment group. For comparison, eight control group animals of corresponding age were also examined. The effect of stretching and ultrashort wave treatment on joint contracture was assessed by measuring the joint range of motion, evaluating the collagen deposition of joint capsule and assessing the mRNA and protein levels for transforming growth factor β1 in the joint capsule. The combined treatment group led to the best recovery of joint function. The combined treatment with stretching and ultrashort wave was more effective than stretching or ultrashort wave treatment alone against the synovial thickening of suprapatellar joint capsule, the collagen deposition of anterior joint capsule, and the elevated expression of transforming growth factor β1 in the joint capsule. Stretching combined with ultrashort wave treatment was effective in improving joint range of motion, reducing the biomechanical, histological, and molecular manifestations of joint capsule fibrosis in a rabbit model of extending joint contracture.

Velcro mechanics in wood

Treesearch

David Kretschmann

2003-12-01

The remarkable deformability of wood in a moist environment resembles that of ductile metals. A combination of traditional mechanical tests and cutting-edge diffraction experiments reveal the molecular mechanism that determines such behaviour.

Combined effects of scaffold stiffening and mechanical preconditioning cycles on construct biomechanics, gene expression, and tendon repair biomechanics.

PubMed

Nirmalanandhan, Victor Sanjit; Juncosa-Melvin, Natalia; Shearn, Jason T; Boivin, Gregory P; Galloway, Marc T; Gooch, Cynthia; Bradica, Gino; Butler, David L

2009-08-01

Our group has previously reported that in vitro mechanical stimulation of tissue-engineered tendon constructs significantly increases both construct stiffness and the biomechanical properties of the repair tissue after surgery. When optimized using response surface methodology, our results indicate that a mechanical stimulus with three components (2.4% strain, 3000 cycles/day, and one cycle repetition) produced the highest in vitro linear stiffness. Such positive correlations between construct and repair stiffness after surgery suggest that enhancing structural stiffness before surgery could not only accelerate repair stiffness but also prevent premature failures in culture due to poor mechanical integrity. In this study, we examined the combined effects of scaffold crosslinking and subsequent mechanical stimulation on construct mechanics and biology. Autologous tissue-engineered constructs were created by seeding mesenchymal stem cells (MSCs) from 15 New Zealand white rabbits on type I collagen sponges that had undergone additional dehydrothermal crosslinking (termed ADHT in this manuscript). Both constructs from each rabbit were mechanically stimulated for 8h/day for 12 consecutive days with half receiving 100 cycles/day and the other half receiving 3000 cycles/day. These paired MSC-collagen autologous constructs were then implanted in bilateral full-thickness, full-length defects in the central third of rabbit patellar tendons. Increasing the number of in vitro cycles/day delivered to the ADHT constructs in culture produced no differences in stiffness or gene expression and no changes in biomechanical properties or histology 12 weeks after surgery. Compared to MSC-based repairs from a previous study that received no additional treatment in culture, ADHT crosslinking of the scaffolds actually lowered the 12-week repair stiffness. Thus, while ADHT crosslinking may initially stiffen a construct in culture, this specific treatment also appears to mask any benefits

Combined Effects of Scaffold Stiffening and Mechanical Preconditioning Cycles on Construct Biomechanics, Gene Expression, and Tendon Repair Biomechanics

PubMed Central

Juncosa-Melvin, Natalia; Shearn, Jason T.; Boivin, Gregory P.; Galloway, Marc T.; Gooch, Cynthia; Bradica, Gino; Butler, David L.

2009-01-01

Our group has previously reported that in vitro mechanical stimulation of tissue-engineered tendon constructs significantly increases both construct stiffness and the biomechanical properties of the repair tissue after surgery. When optimized using response surface methodology, our results indicate that a mechanical stimulus with three components (2.4% strain, 3000 cycles/day, and one cycle repetition) produced the highest in vitro linear stiffness. Such positive correlations between construct and repair stiffness after surgery suggest that enhancing structural stiffness before surgery could not only accelerate repair stiffness but also prevent premature failures in culture due to poor mechanical integrity. In this study, we examined the combined effects of scaffold crosslinking and subsequent mechanical stimulation on construct mechanics and biology. Autologous tissue-engineered constructs were created by seeding mesenchymal stem cells (MSCs) from 15 New Zealand white rabbits on type I collagen sponges that had undergone additional dehydrothermal crosslinking (termed ADHT in this manuscript). Both constructs from each rabbit were mechanically stimulated for 8 h/day for 12 consecutive days with half receiving 100 cycles/day and the other half receiving 3000 cycles/day. These paired MSC–collagen autologous constructs were then implanted in bilateral full-thickness, full-length defects in the central third of rabbit patellar tendons. Increasing the number of in vitro cycles/day delivered to the ADHT constructs in culture produced no differences in stiffness or gene expression and no changes in biomechanical properties or histology 12 weeks after surgery. Compared to MSC-based repairs from a previous study that received no additional treatment in culture, ADHT crosslinking of the scaffolds actually lowered the 12-week repair stiffness. Thus, while ADHT crosslinking may initially stiffen a construct in culture, this specific treatment also appears to mask any

[Mechanisms of nitroxide-ergic dysregulation in tissues of parodontium in rats under combined excessive sodium nitrate and fluoride intake].

PubMed

Богданов, Алексей В; Гришко, Юлия М; Костенко, Виталий А

2016-01-01

intake of inorganic nitrates is typically accompanied by production of excessive amount of nitric oxide (NO), which level is maintained by the mechanism of autoregulation known as the NO cycle. Hypothetically, this process may be disrupted with fluorides that are able to suppress arginase pathway of L-arginine metabolism, which competes with NO-synthase pathway. to study mechanisms of disregulation of oxidative (NO-synthase) and non-oxidative (arginase) metabolic pathways of L-arginine in the tissues of periodontium under combined excessive sodium nitrate and fluoride intake. these investigations were carried out on 90 white Wistar rats. Homogenates of parodontium soft tissues were used to assess spectrophotometrically the total activities of NO-synthase (NOS), arginase, ornithine decarboxylase as well as the peroxynitrite concentration. typical for the isolated sodium nitrate administration inhibition of total NOS activity varies under combined administration of nitrate and sodium fluoride and is usually manifested by its hyperactivation that is accompanied by an increase in peroxynitrite concentration. At this time arginase and ornithine decarboxylase activity is observed to be substantially reduced. The administration of aminoguanidine, an iNOS inhibitor, (20 mg/kg, twice a week during the experiment) increases arginase and ornithine decarboxylase activities, and the administration of L-arginine (500 mg/kg, twice a week) results in the increase of arginase activity. The administration of L-selenomethionine, a peroxynitrite scavenger (3 mg/kg, twice a week), and JSH-23 (4-methyl-N-(3-phenylpropyl) benzene-1,2-diamine, an inhibitor of NF-κB activation (1 mg/kg, twice a week) for modeling binary nitrate and fluoride intoxication reduces the total concentration of NOS activity and peroxynitrite concentration, and increases ornithine decarboxylase activity. the combined effect of nitrate and sodium fluoride for 30 days leads to disregulatory increased activity of NO

[Mechanisms of nitroxide-ergic dysregulation in tissues of parodontium in rats under combined excessive sodium nitrate and fluoride intake].

PubMed

Богданов, Алексей В; Гришко, Юлия М; Костенко, Виталий А

intake of inorganic nitrates is typically accompanied by production of excessive amount of nitric oxide (NO), which level is maintained by the mechanism of autoregulation known as the NO cycle. Hypothetically, this process may be disrupted with fluorides that are able to suppress arginase pathway of L-arginine metabolism, which competes with NO-synthase pathway. to study mechanisms of disregulation of oxidative (NO-synthase) and non-oxidative (arginase) metabolic pathways of L-arginine in the tissues of periodontium under combined excessive sodium nitrate and fluoride intake. these investigations were carried out on 90 white Wistar rats. Homogenates of parodontium soft tissues were used to assess spectrophotometrically the total activities of NO-synthase (NOS), arginase, ornithine decarboxylase as well as the peroxynitrite concentration. typical for the isolated sodium nitrate administration inhibition of total NOS activity varies under combined administration of nitrate and sodium fluoride and is usually manifested by its hyperactivation that is accompanied by an increase in peroxynitrite concentration. At this time arginase and ornithine decarboxylase activity is observed to be substantially reduced. The administration of aminoguanidine, an iNOS inhibitor, (20 mg/kg, twice a week during the experiment) increases arginase and ornithine decarboxylase activities, and the administration of L-arginine (500 mg/kg, twice a week) results in the increase of arginase activity. The administration of L-selenomethionine, a peroxynitrite scavenger (3 mg/kg, twice a week), and JSH-23 (4-methyl-N-(3-phenylpropyl) benzene-1,2-diamine, an inhibitor of NF-κB activation (1 mg/kg, twice a week) for modeling binary nitrate and fluoride intoxication reduces the total concentration of NOS activity and peroxynitrite concentration, and increases ornithine decarboxylase activity. the combined effect of nitrate and sodium fluoride for 30 days leads to disregulatory increased activity of NO

A simple combined floating and anchored collagen gel for enhancing mechanical strength of culture system.

PubMed

Harada, Ichiro; Kim, Sung-Gon; Cho, Chong Su; Kurosawa, Hisashi; Akaike, Toshihiro

2007-01-01

In this study, a simple combined method consisting of floating and anchored collagen gel in a ligament or tendon equivalent culture system was used to produce the oriented fibrils in fibroblast-populated collagen matrices (FPCMs) during the remodeling and contraction of the collagen gel. Orientation of the collagen fibrils along single axis occurred over the whole area of the floating section and most of the fibroblasts were elongated and aligned along the oriented collagen fibrils, whereas no significant orientation of fibrils was observed in normally contracted FPCMs by the floating method. Higher elasticity and enhanced mechanical strength were obtained using our simple method compared with normally contracted floating FPCMs. The Young's modulus and the breaking point of the FPCMs were dependent on the initial cell densities. This simple method will be applied as a convenient bioreactor to study cellular processes of the fibroblasts in the tissues with highly oriented fibrils such as ligaments or tendons. (c) 2006 Wiley Periodicals, Inc.

Right ventricular outflow tract aneurysm with thrombus

PubMed Central

Peer, Syed Murfad; Bhat, P.S. Seetharama; Furtado, Arul Dominic; Chikkatur, Raghavendra

2012-01-01

Right ventricular outflow tract (RVOT) aneurysm is a known complication of tetralogy of Fallot repair when a ventriculotomy is done. It leads to RV dysfunction and may require re-operation. We describe a rare instance of a patient who developed an RVOT aneurysm after trans-ventricular repair of tetralogy of Fallot, which was complicated with the formation of a thrombus in the aneurysm sac. The patient underwent re-operation with thrombectomy, excision of the RVOT aneurysm and pulmonary valve replacement. To the best of our knowledge, the occurrence of this combination and its implications have not been reported. PMID:22232231

Combined chemical and mechanical effects on free radicals in UHMWPE joints during implantation.

PubMed

Jahan, M S; Wang, C; Schwartz, G; Davidson, J A

1991-08-01

An electron spin resonance (ESR) technique is employed to determine the free radical distribution in the articulating surfaces of retrieved acetabular cups and knee-joint plateaus (retrieved after more than 6 years of implantation). Similar measurements made on samples prepared from cyclically stressed and unstressed cups, and on samples following oxidations in nitric acid and intralipid solutions provided sufficient data to gain more knowledge about the combined chemical and mechanical effects on PE free radicals during implantation. In UHMWPE free radicals are primarily initiated by gamma-ray sterilization; however, during implantation, peroxy (scission type) free radicals are formed and reach a maximum concentration level (equilibrium state) due to oxidation by chemical (hemoglobin and/or synovial fluids) environment of the joints. Subsequently, due to frictional heating and stress in the loading zones, free radical reaction is accelerated and their number is reduced only in those areas. This is consistent with the observations of a temperature rise in acetabular cups during in vitro frictional wear stress tests and in vivo telemetry observations, as reported by others. Compared with the previously reported SEM micrographs the low-free-radical regions are correlated with high-wear areas and the high-free-radical regions with the low-wear areas.

GaN-on-diamond electronic device reliability: Mechanical and thermo-mechanical integrity

NASA Astrophysics Data System (ADS)

Liu, Dong; Sun, Huarui; Pomeroy, James W.; Francis, Daniel; Faili, Firooz; Twitchen, Daniel J.; Kuball, Martin

2015-12-01

The mechanical and thermo-mechanical integrity of GaN-on-diamond wafers used for ultra-high power microwave electronic devices was studied using a micro-pillar based in situ mechanical testing approach combined with an optical investigation of the stress and heat transfer across interfaces. We find the GaN/diamond interface to be thermo-mechanically stable, illustrating the potential for this material for reliable GaN electronic devices.

Effect of the Combined Addition of Y and Ti on the Second Phase and Mechanical Properties of China Low-Activation Martensitic Steel

NASA Astrophysics Data System (ADS)

Zhang, Yangpeng; Zhan, Dongping; Qi, Xiwei; Jiang, Zhouhua; Zhang, Huishu

2018-05-01

In this study, approximately 0.35% Ti and two different Y contents were added to China low-activation martensitic (CLAM) steel during melting in a vacuum induction melting furnace. Scanning electron microscopy, transmission electron microscopy, x-ray diffraction, tensile tests, and Charpy impact tests were used to investigate the effects of the combined addition of Y and Ti on the second phase and mechanical properties. The results indicated that Y and Fe formed the large intermetallic compound Fe-Y; the compound easily aggregated in the grain boundaries and exhibited the strength of CLAM steel. Ti did not combine with Y to form the Y-Ti-O phase; however, it could combine with Ta and W to form MC precipitates, which were generally in the 20-50 nm size range. The CLAM steel with a higher Y content exhibited lower yield and tensile strengths at room temperature, with both steels yielding almost identical strengths at 600 °C.

Synergistic effects and related bioactive mechanisms of Potentilla fruticosa Linn. leaves combined with green tea polyphenols studied with microbial test system (MTS).

PubMed

Liu, Ze-Hua; Luo, Zi-Wen; Li, Deng-Wu; Wang, Dong-Mei; Ji, Xia

2018-06-01

Previous research found Potentilla fruticosa leaf extracts (PFE) combined with green tea polyphenols (GTP) showed obvious synergistic effects based on chemical mechanisms. This study further confirmed the synergy of PFE + GTP viewed from bioactivities using the microbial test system (MTS). The MTS antioxidant activity results showed the combination of PFE + GTP exhibited synergistic effect and the ratio 3:1 showed the strongest synergy, which were in accordance with the results in H 2 O 2 production rate. The combination of PFE + GTP promoted CAT and SOD enzyme activity and their gene expression especially at the ratio 3:1. Therefore, the synergism of PFE + GTP may be due to the promotion of CAT and SOD genes expression which enhanced the CAT and SOD enzyme activities. These results confirmed the synergy of PFE + GTP and could provide theoretical basis to produce a compounded tea made of a mixture of leaves from Potentilla species.

Effect of the Combined Addition of Y and Ti on the Second Phase and Mechanical Properties of China Low-Activation Martensitic Steel

NASA Astrophysics Data System (ADS)

Zhang, Yangpeng; Zhan, Dongping; Qi, Xiwei; Jiang, Zhouhua; Zhang, Huishu

2018-04-01

In this study, approximately 0.35% Ti and two different Y contents were added to China low-activation martensitic (CLAM) steel during melting in a vacuum induction melting furnace. Scanning electron microscopy, transmission electron microscopy, x-ray diffraction, tensile tests, and Charpy impact tests were used to investigate the effects of the combined addition of Y and Ti on the second phase and mechanical properties. The results indicated that Y and Fe formed the large intermetallic compound Fe-Y; the compound easily aggregated in the grain boundaries and exhibited the strength of CLAM steel. Ti did not combine with Y to form the Y-Ti-O phase; however, it could combine with Ta and W to form MC precipitates, which were generally in the 20-50 nm size range. The CLAM steel with a higher Y content exhibited lower yield and tensile strengths at room temperature, with both steels yielding almost identical strengths at 600 °C.

Traits, properties, and performance: how woody plants combine hydraulic and mechanical functions in a cell, tissue, or whole plant.

PubMed

Lachenbruch, Barbara; McCulloh, Katherine A

2014-12-01

This review presents a framework for evaluating how cells, tissues, organs, and whole plants perform both hydraulic and mechanical functions. The morphological alterations that affect dual functionality are varied: individual cells can have altered morphology; tissues can have altered partitioning to functions or altered cell alignment; and organs and whole plants can differ in their allocation to different tissues, or in the geometric distribution of the tissues they have. A hierarchical model emphasizes that morphological traits influence the hydraulic or mechanical properties; the properties, combined with the plant unit's environment, then influence the performance of that plant unit. As a special case, we discuss the mechanisms by which the proxy property wood density has strong correlations to performance but without direct causality. Traits and properties influence multiple aspects of performance, and there can be mutual compensations such that similar performance occurs. This compensation emphasizes that natural selection acts on, and a plant's viability is determined by, its performance, rather than its contributing traits and properties. Continued research on the relationships among traits, and on their effects on multiple aspects of performance, will help us better predict, manage, and select plant material for success under multiple stresses in the future. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Anti-tumor effects of ONC201 in combination with VEGF-inhibitors significantly impacts colorectal cancer growth and survival in vivo through complementary non-overlapping mechanisms.

PubMed

Wagner, Jessica; Kline, C Leah; Zhou, Lanlan; Khazak, Vladimir; El-Deiry, Wafik S

2018-01-22

Small molecule ONC201 is an investigational anti-tumor agent that upregulates intra-tumoral TRAIL expression and the integrated stress response pathway. A Phase I clinical trial using ONC201 therapy in advanced cancer patients has been completed and the drug has progressed into Phase II trials in several cancer types. Colorectal cancer (CRC) remains one of the leading causes of cancer worldwide and metastatic disease has a poor prognosis. Clinical trials in CRC and other tumor types have demonstrated that therapeutics targeting the vascular endothelial growth factor (VEGF) pathway, such as bevacizumab, are effective in combination with certain chemotherapeutic agents. We investigated the potential combination of VEGF inhibitors such as bevacizumab and its murine-counterpart; along with other anti-angiogenic agents and ONC201 in both CRC xenograft and patient-derived xenograft (PDX) models. We utilized non-invasive imaging and immunohistochemistry to determine potential mechanisms of action. Our results demonstrate significant tumor regression or complete tumor ablation in human xenografts with the combination of ONC201 with bevacizumab, and in syngeneic MC38 colorectal cancer xenografts using a murine VEGF-A inhibitor. Imaging demonstrated the impact of this combination on decreasing tumor growth and tumor metastasis. Our results indicate that ONC201 and anti-angiogenic agents act through distinct mechanisms while increasing tumor cell death and inhibiting proliferation. With the use of both a murine VEGF inhibitor in syngeneic models, and bevacizumab in human cell line-derived xenografts, we demonstrate that ONC201 in combination with anti-angiogenic therapies such as bevacizumab represents a promising approach for further testing in the clinic for the treatment of CRC.

Use of a Trellis Device for Endovascular Treatment of Venous Thrombosis Involving a Duplicated Inferior Vena Cava

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saettele, Megan R., E-mail: SaetteleM@umkc.edu; Morelli, John N., E-mail: dr.john.morelli@gmail.com; Chesis, Paul

Congenital anomalies of the inferior vena cava (IVC) are increasingly recognized with CT and venography techniques. Although many patients with IVC anomalies are asymptomatic, recent studies have suggested an association with venous thromboembolism. We report the case of a 62-year-old woman with extensive venous clot involving the infrarenal segment of a duplicated left IVC who underwent pharmacomechanical thrombectomy and tissue plasminogen activator catheter-directed thrombolysis with complete deep venous thrombosis resolution. To our knowledge this is the first reported case in the English literature of the use of a Trellis thrombectomy catheter in the setting of duplicated IVC.

Use of Percutaneous Aspiration Thrombectomy vs. Anticoagulation Therapy to Treat Acute Iliofemoral Venous Thrombosis: 1-year Follow-up Results of a Randomised, Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cakir, Volkan, E-mail: drvolkancakir@gmail.com; Gulcu, Aytac, E-mail: aytac.gulcu@deu.edu.tr; Akay, Emrah, E-mail: emrahakay@hotmail.com

2014-08-15

PurposeThe purpose of this study was to compare the efficacy of percutaneous aspiration thrombectomy (PAT) followed by standard anticoagulant therapy, with anticoagulation therapy alone, for the treatment of acute proximal lower extremity deep vein thrombosis.MethodsIn this randomised, prospective study, 42 patients with acute proximal iliofemoral deep vein thrombosis documented via Doppler ultrasound examination, were separated into an interventional treatment group (16 males, 5 females, average age 51 years) and a medical treatment group (13 males, 8 females, average age 59 years). In the interventional group, PAT with large-lumen 9-F diameter catheterisation was applied, after initiation of standard anticoagulant therapy. Balloon angioplasty (nmore » 19) and stent implementation (n: 14) were used to treat patients with residual stenosis (>50 %) after PAT. Prophylactic IVC filters were placed in two patients. The thrombus clearance status of the venous system was evaluated by venography. In both the medical and interventional groups, venous patency rates and clinical symptom scores were evaluated at months 1, 3, and 12 after treatment.ResultsDeep venous systems became totally cleared of thrombi in 12 patients treated with PAT. The venous patency rates in month 12 were 57.1 and 4.76 % in the interventional and medical treatment groups, respectively. A statistically significant improvement was observed in clinical symptom scores of the interventional group (PAT) with or without stenting (4.23 ± 0.51 before treatment; 0.81 ± 0.92 at month 12) compared with the medical treatment group (4.00 ± 0.63 before treatment; 2.43 ± 0.67 at month 12). During follow-up, four patients in the medical treatment and one in the interventional group developed pulmonary embolisms.ConclusionsFor treatment of acute deep vein thrombosis, PAT with or without stenting is superior to anticoagulant therapy alone in terms of both ensuring venous patency and improving clinical

Quantum mechanics/coarse-grained molecular mechanics (QM/CG-MM)

NASA Astrophysics Data System (ADS)

Sinitskiy, Anton V.; Voth, Gregory A.

2018-01-01

Numerous molecular systems, including solutions, proteins, and composite materials, can be modeled using mixed-resolution representations, of which the quantum mechanics/molecular mechanics (QM/MM) approach has become the most widely used. However, the QM/MM approach often faces a number of challenges, including the high cost of repetitive QM computations, the slow sampling even for the MM part in those cases where a system under investigation has a complex dynamics, and a difficulty in providing a simple, qualitative interpretation of numerical results in terms of the influence of the molecular environment upon the active QM region. In this paper, we address these issues by combining QM/MM modeling with the methodology of "bottom-up" coarse-graining (CG) to provide the theoretical basis for a systematic quantum-mechanical/coarse-grained molecular mechanics (QM/CG-MM) mixed resolution approach. A derivation of the method is presented based on a combination of statistical mechanics and quantum mechanics, leading to an equation for the effective Hamiltonian of the QM part, a central concept in the QM/CG-MM theory. A detailed analysis of different contributions to the effective Hamiltonian from electrostatic, induction, dispersion, and exchange interactions between the QM part and the surroundings is provided, serving as a foundation for a potential hierarchy of QM/CG-MM methods varying in their accuracy and computational cost. A relationship of the QM/CG-MM methodology to other mixed resolution approaches is also discussed.

Quantum mechanics/coarse-grained molecular mechanics (QM/CG-MM).

PubMed

Sinitskiy, Anton V; Voth, Gregory A

2018-01-07

Numerous molecular systems, including solutions, proteins, and composite materials, can be modeled using mixed-resolution representations, of which the quantum mechanics/molecular mechanics (QM/MM) approach has become the most widely used. However, the QM/MM approach often faces a number of challenges, including the high cost of repetitive QM computations, the slow sampling even for the MM part in those cases where a system under investigation has a complex dynamics, and a difficulty in providing a simple, qualitative interpretation of numerical results in terms of the influence of the molecular environment upon the active QM region. In this paper, we address these issues by combining QM/MM modeling with the methodology of "bottom-up" coarse-graining (CG) to provide the theoretical basis for a systematic quantum-mechanical/coarse-grained molecular mechanics (QM/CG-MM) mixed resolution approach. A derivation of the method is presented based on a combination of statistical mechanics and quantum mechanics, leading to an equation for the effective Hamiltonian of the QM part, a central concept in the QM/CG-MM theory. A detailed analysis of different contributions to the effective Hamiltonian from electrostatic, induction, dispersion, and exchange interactions between the QM part and the surroundings is provided, serving as a foundation for a potential hierarchy of QM/CG-MM methods varying in their accuracy and computational cost. A relationship of the QM/CG-MM methodology to other mixed resolution approaches is also discussed.

A combined experimental atomic force microscopy-based nanoindentation and computational modeling approach to unravel the key contributors to the time-dependent mechanical behavior of single cells.

PubMed

Florea, Cristina; Tanska, Petri; Mononen, Mika E; Qu, Chengjuan; Lammi, Mikko J; Laasanen, Mikko S; Korhonen, Rami K

2017-02-01

Cellular responses to mechanical stimuli are influenced by the mechanical properties of cells and the surrounding tissue matrix. Cells exhibit viscoelastic behavior in response to an applied stress. This has been attributed to fluid flow-dependent and flow-independent mechanisms. However, the particular mechanism that controls the local time-dependent behavior of cells is unknown. Here, a combined approach of experimental AFM nanoindentation with computational modeling is proposed, taking into account complex material behavior. Three constitutive models (porohyperelastic, viscohyperelastic, poroviscohyperelastic) in tandem with optimization algorithms were employed to capture the experimental stress relaxation data of chondrocytes at 5 % strain. The poroviscohyperelastic models with and without fluid flow allowed through the cell membrane provided excellent description of the experimental time-dependent cell responses (normalized mean squared error (NMSE) of 0.003 between the model and experiments). The viscohyperelastic model without fluid could not follow the entire experimental data that well (NMSE = 0.005), while the porohyperelastic model could not capture it at all (NMSE = 0.383). We also show by parametric analysis that the fluid flow has a small, but essential effect on the loading phase and short-term cell relaxation response, while the solid viscoelasticity controls the longer-term responses. We suggest that the local time-dependent cell mechanical response is determined by the combined effects of intrinsic viscoelasticity of the cytoskeleton and fluid flow redistribution in the cells, although the contribution of fluid flow is smaller when using a nanosized probe and moderate indentation rate. The present approach provides new insights into viscoelastic responses of chondrocytes, important for further understanding cell mechanobiological mechanisms in health and disease.

Combined Activity of Colloid Nanosilver and Zataria Multiflora Boiss Essential Oil-Mechanism of Action and Biofilm Removal Activity.

PubMed

Shirdel, Maryam; Tajik, Hossein; Moradi, Mehran

2017-12-01

Purpose: The aim of this study was to investigate antimicrobial and biofilm removal potential of Zataria multiflora essential oil (ZEO) and silver nanoparticle (SNP) alone and in combination on Staphylococcus aureus and Salmonella Typhimurium and evaluate the mechanism of action. Methods: The minimum inhibitory concentration (MIC), and optimal inhibitory combination (OIC) of ZEO and SNP were determined according to fractional inhibitory concentration (FIC) method. Biofilm removal potential and leakage pattern of 260-nm absorbing material from the bacterial cell during exposure to the compounds were also investigated. Results: MICs of SNP for both bacteria were the same as 25 μg/ mL. The MICs and MBCs values of ZEO were 2500 and 1250 μg/mL, respectively. The most effective OIC value for SNP and ZEO against Salm. Typhimurium and Staph. aureus were 12.5, 625 and 0.78, 1250 μg/ mL, respectively. ZEO and SNP at MIC and OIC concentrations represented a strong removal ability (>70%) on biofilm. Moreover, ZEO at MIC and OIC concentrations did a 6-log reduction of primary inoculated bacteria during 15 min contact time. The effect of ZEO on the loss of 260-nm material from the cell was faster than SNP during 15 and 60 min. Conclusion: Combination of ZEO and SNP had significant sanitizing activity on examined bacteria which may be suitable for disinfecting the surfaces.

Subchromoplast Sequestration of Carotenoids Affects Regulatory Mechanisms in Tomato Lines Expressing Different Carotenoid Gene Combinations[C][W

PubMed Central

Nogueira, Marilise; Mora, Leticia; Enfissi, Eugenia M.A.; Bramley, Peter M.; Fraser, Paul D.

2013-01-01

Metabolic engineering of the carotenoid pathway in recent years has successfully enhanced the carotenoid contents of crop plants. It is now clear that only increasing biosynthesis is restrictive, as mechanisms to sequestrate these increased levels in the cell or organelle should be exploited. In this study, biosynthetic pathway genes were overexpressed in tomato (Solanum lycopersicum) lines and the effects on carotenoid formation and sequestration revealed. The bacterial Crt carotenogenic genes, independently or in combination, and their zygosity affect the production of carotenoids. Transcription of the pathway genes was perturbed, whereby the tissue specificity of transcripts was altered. Changes in the steady state levels of metabolites in unrelated sectors of metabolism were found. Of particular interest was a concurrent increase of the plastid-localized lipid monogalactodiacylglycerol with carotenoids along with membranous subcellular structures. The carotenoids, proteins, and lipids in the subchromoplast fractions of the transgenic tomato fruit with increased carotenoid content suggest that cellular structures can adapt to facilitate the sequestration of the newly formed products. Moreover, phytoene, the precursor of the pathway, was identified in the plastoglobule, whereas the biosynthetic enzymes were in the membranes. The implications of these findings with respect to novel pathway regulation mechanisms are discussed. PMID:24249831

Effect of combination ultrasonic and ball milling techniques of commercial fillers dispersion on mechanical properties of natural rubber (NR) latex films

NASA Astrophysics Data System (ADS)

Hamran, Noramirah; Rashid, Azura A.

2017-07-01

Commercial fillers such as silica and carbon black generally impart the reinforcing effects in dry rubber compound, but have an adverse effect on Natural rubber (NR) latex compounds. The addition of commercial fillers in NR latex has reduced the mechanical properties of NR latex films due to the destabilization effect in the NR latex compounds which govern by the dispersion quality, particle size and also the pH of the dispersion itself. The ball milling process is the conventional meth od of preparation of dispersions and ultrasonic has successfully used in preparation of nano fillers such as carbon nanotube (CNT). In this study the combination between the conventional methods; ball milling together the ultrasonic method were used to prepare the silica and carbon black dispersions. The different duration of ball milling (24, 48 and 72 hours) was compared with the ultrasonic method (30, 60, 90 and 120 minutes). The combination of ball milling and ultrasonic from the optimum individual technique was used to investigate the reduction of particle size of the fillers. The particle size analyzer, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) test were carried out to investigate the obtained particle size and the tensile and tear test were carried out to investigate the mechanical properties of the NR latex films. The reduction of filler particle size is expected to impart the properties of NR latex films.

Angular approach combined to mechanical model for tool breakage detection by eddy current sensors

NASA Astrophysics Data System (ADS)

Ritou, M.; Garnier, S.; Furet, B.; Hascoet, J. Y.

2014-02-01

The paper presents a new complete approach for Tool Condition Monitoring (TCM) in milling. The aim is the early detection of small damages so that catastrophic tool failures are prevented. A versatile in-process monitoring system is introduced for reliability concerns. The tool condition is determined by estimates of the radial eccentricity of the teeth. An adequate criterion is proposed combining mechanical model of milling and angular approach.Then, a new solution is proposed for the estimate of cutting force using eddy current sensors implemented close to spindle nose. Signals are analysed in the angular domain, notably by synchronous averaging technique. Phase shifts induced by changes of machining direction are compensated. Results are compared with cutting forces measured with a dynamometer table.The proposed method is implemented in an industrial case of pocket machining operation. One of the cutting edges has been slightly damaged during the machining, as shown by a direct measurement of the tool. A control chart is established with the estimates of cutter eccentricity obtained during the machining from the eddy current sensors signals. Efficiency and reliability of the method is demonstrated by a successful detection of the damage.

Potential of combining mechanical and physicochemical municipal wastewater pre-treatment with direct membrane filtration.

PubMed

Hey, Tobias; Väänänen, Janne; Heinen, Nicolas; la Cour Jansen, Jes; Jönsson, Karin

2017-01-01

At a full-scale wastewater treatment plant, raw municipal wastewater from the sand trap outlet was mechanically and physicochemically pre-treated before microfiltration (MF) in a large pilot-scale study. MF was performed using a low transmembrane pressure (0.03 bar) without backflushing for up to 159 h (∼6.6 d). Pre-filtration ensured stable MF operation compared with the direct application of raw wastewater on the membrane. The combination of physicochemical pre-treatment, such as coagulation, flocculation, and microsieving, with MF meets the European and Swedish discharge limits for small- and medium-sized wastewater treatment plants (WWTPs). The specific electricity footprint was 0.3-0.4 kWh·m -3 , which is an improvement compared to the median footprint of 0.75 kWh·m -3 found in 105 traditional Swedish WWTPs with sizes of 1500-10,000 person equivalents. Furthermore, the biological treatment step can be omitted, and the risk of releasing greenhouse gases was eliminated. The investigated wastewater treatment process required less space than conventional wastewater treatment processes, and more carbon was made available for biogas production.

Atomic-scale and pit-free flattening of GaN by combination of plasma pretreatment and time-controlled chemical mechanical polishing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng, Hui; Endo, Katsuyoshi; Yamamura, Kazuya, E-mail: yamamura@upst.eng.osaka-u.ac.jp

2015-08-03

Chemical mechanical polishing (CMP) combined with atmospheric-pressure plasma pretreatment was applied to a GaN (0001) substrate. The irradiation of a CF{sub 4}-containing plasma was proven to be very useful for modifying the surface of GaN. When CMP was conducted on a plasma-irradiated surface, a modified layer of GaF{sub 3} acted as a protective layer on GaN by preventing the formation of etch pits. Within a short duration (8 min) of CMP using a commercially available CeO{sub 2} slurry, an atomically flat surface with a root mean square (rms) roughness of 0.11 nm was obtained. Moreover, etch pits, which are inevitably introduced inmore » conventional CMP, could not be observed at the dislocation sites on the polished GaN surface. It was revealed that CMP combined with the plasma pretreatment was very effective for obtaining a pit-free and atomically flat GaN surface.« less

Dislocation mechanisms and 3D twin architectures generate exceptional strength-ductility-toughness combination in CrCoNi medium-entropy alloy.

PubMed

Zhang, Zijiao; Sheng, Hongwei; Wang, Zhangjie; Gludovatz, Bernd; Zhang, Ze; George, Easo P; Yu, Qian; Mao, Scott X; Ritchie, Robert O

2017-02-20

Combinations of high strength and ductility are hard to attain in metals. Exceptions include materials exhibiting twinning-induced plasticity. To understand how the strength-ductility trade-off can be defeated, we apply in situ, and aberration-corrected scanning, transmission electron microscopy to examine deformation mechanisms in the medium-entropy alloy CrCoNi that exhibits one of the highest combinations of strength, ductility and toughness on record. Ab initio modelling suggests that it has negative stacking-fault energy at 0K and high propensity for twinning. With deformation we find that a three-dimensional (3D) hierarchical twin network forms from the activation of three twinning systems. This serves a dual function: conventional twin-boundary (TB) strengthening from blockage of dislocations impinging on TBs, coupled with the 3D twin network which offers pathways for dislocation glide along, and cross-slip between, intersecting TB-matrix interfaces. The stable twin architecture is not disrupted by interfacial dislocation glide, serving as a continuous source of strength, ductility and toughness.

Optimization of Synergistic Combination Regimens against Carbapenem- and Aminoglycoside-Resistant Clinical Pseudomonas aeruginosa Isolates via Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling

PubMed Central

Yadav, Rajbharan; Nation, Roger L.

2016-01-01

ABSTRACT Optimizing antibiotic combinations is promising to combat multidrug-resistant Pseudomonas aeruginosa. This study aimed to systematically evaluate synergistic bacterial killing and prevention of resistance by carbapenem and aminoglycoside combinations and to rationally optimize combination dosage regimens via a mechanism-based mathematical model (MBM). We studied monotherapies and combinations of imipenem with tobramycin or amikacin against three difficult-to-treat double-resistant clinical P. aeruginosa isolates. Viable-count profiles of total and resistant populations were quantified in 48-h static-concentration time-kill studies (inoculum, 107.5 CFU/ml). We rationally optimized combination dosage regimens via MBM and Monte Carlo simulations against isolate FADDI-PA088 (MIC of imipenem [MICimipenem] of 16 mg/liter and MICtobramycin of 32 mg/liter, i.e., both 98th percentiles according to the EUCAST database). Against this isolate, imipenem (1.5× MIC) combined with 1 to 2 mg/liter tobramycin (MIC, 32 mg/liter) or amikacin (MIC, 4 mg/liter) yielded ≥2-log10 more killing than the most active monotherapy at 48 h and prevented resistance. For all three strains, synergistic killing without resistance was achieved by ≥0.88× MICimipenem in combination with a median of 0.75× MICtobramycin (range, 0.032× to 2.0× MICtobramycin) or 0.50× MICamikacin (range, 0.25× to 0.50× MICamikacin). The MBM indicated that aminoglycosides significantly enhanced the imipenem target site concentration up to 3-fold; achieving 50% of this synergistic effect required aminoglycoside concentrations of 1.34 mg/liter (if the aminoglycoside MIC was 4 mg/liter) and 4.88 mg/liter (for MICs of 8 to 32 mg/liter). An optimized combination regimen (continuous infusion of imipenem at 5 g/day plus a 0.5-h infusion with 7 mg/kg of body weight tobramycin) was predicted to achieve >2.0-log10 killing and prevent regrowth at 48 h in 90.3% of patients (median bacterial killing, >4.0 log10 CFU

[Mechanisms for the increased fertilizer nitrogen use efficiency of rice in wheat-rice rotation system under combined application of inorganic and organic fertilizers].

PubMed

Liu, Yi-Ren; Li, Xiang; Yu, Jie; Shen, Qi-Rong; Xu, Yang-Chun

2012-01-01

A pot experiment was conducted to study the effects of combined application of organic and inorganic fertilizers on the nitrogen uptake by rice and the nitrogen supply by soil in a wheat-rice rotation system, and approach the mechanisms for the increased fertilizer nitrogen use efficiency of rice under the combined fertilization from the viewpoint of microbiology. Comparing with applying inorganic fertilizers, combined application of organic and inorganic fertilizers decreased the soil microbial biomass carbon and nitrogen and soil mineral nitrogen contents before tillering stage, but increased them significantly from heading to filling stage. Under the combined fertilization, the dynamics of soil nitrogen supply matched best the dynamics of rice nitrogen uptake and utilization, which promoted the nitrogen accumulation in rice plant and the increase of rice yield and biomass, and increased the fertilizer nitrogen use efficiency of rice significantly. Combined application of inorganic and organic fertilizers also promoted the propagation of soil microbes, and consequently, more mineral nitrogen in soil was immobilized by the microbes at rice early growth stage, and the immobilized nitrogen was gradually released at the mid and late growth stages of rice, being able to better satisfy the nitrogen demand of rice in its various growth and development stages.

Mechanisms that Trigger a Good Health-Care Response to Intimate Partner Violence in Spain. Combining Realist Evaluation and Qualitative Comparative Analysis Approaches.

PubMed

Goicolea, Isabel; Vives-Cases, Carmen; Hurtig, Anna-Karin; Marchal, Bruno; Briones-Vozmediano, Erica; Otero-García, Laura; García-Quinto, Marta; San Sebastian, Miguel

2015-01-01

Health care professionals, especially those working in primary health-care services, can play a key role in preventing and responding to intimate partner violence. However, there are huge variations in the way health care professionals and primary health care teams respond to intimate partner violence. In this study we tested a previously developed programme theory on 15 primary health care center teams located in four different Spanish regions: Murcia, C Valenciana, Castilla-León and Cantabria. The aim was to identify the key combinations of contextual factors and mechanisms that trigger a good primary health care center team response to intimate partner violence. A multiple case-study design was used. Qualitative and quantitative information was collected from each of the 15 centers (cases). In order to handle the large amount of information without losing familiarity with each case, qualitative comparative analysis was undertaken. Conditions (context and mechanisms) and outcomes, were identified and assessed for each of the 15 cases, and solution formulae were calculated using qualitative comparative analysis software. The emerging programme theory highlighted the importance of the combination of each team's self-efficacy, perceived preparation and women-centredness in generating a good team response to intimate partner violence. The use of the protocol and accumulated experience in primary health care were the most relevant contextual/intervention conditions to trigger a good response. However in order to achieve this, they must be combined with other conditions, such as an enabling team climate, having a champion social worker and having staff with training in intimate partner violence. Interventions to improve primary health care teams' response to intimate partner violence should focus on strengthening team's self-efficacy, perceived preparation and the implementation of a woman-centred approach. The use of the protocol combined with a large working

Alendronate (ALN) combined with Osteoprotegerin (OPG) significantly improves mechanical properties of long bone than the single use of ALN or OPG in the ovariectomized rats

PubMed Central

2011-01-01

Background Alendronate (ALN) is the most common form of bisphosphonates used for the treatment of osteoporosis. Osteoprotegerin (OPG) has also been shown to reduce osteoporotic changes in both humans and experimental animals after systemic administration. The aim of this current study was to test if the anti-resorption effects of ALN may be enhanced when used in combination with OPG. Objectives To investigate the effects of ALN, OPG or combined on bone mass and bone mechanical properties in ovariectomized (OVX) rats. Methods OVX rats were treated with ALN, OPG-Fc, or OPG-Fc and ALN. Biochemical markers, trabecular bone mass, biomechanics, histomorphometry and RANKL expression in the bone tissues were examined following the treatments. Results The treatment of ALN, OPG-Fc and ALN+OPG-Fc all prevented bone loss in the OVX-rats, there was no statistical difference among the three treatment groups in terms of vertebrae BMD, mineralizing surfaces, mineral apposition rate, BFR/BS. The ALN+OPG-Fc treatment group had significantly increased the mechanical strength of lumber vertebral bodies and femoral shafts when compared to the ALN and OPG-Fc treatment groups. The RANKL protein expression in the vertebral bones was significantly decreased in the ALN and ALN+OPG-Fc treatment groups, suggesting the combined use of OPG-Fc and ALN might have amplified inhibition of bone resorption through inhibiting RANKL-dependent osteoclastogenesis. Conclusion The combined use of OPG-Fc and ALN may be a new treatment strategy for reversing bone loss and restoring bone quality in osteoprotic disorders. PMID:21752290

[The effect of positive pressure ventilation combined with diaphragm pacing on respiratory mechanics in patients with respiratory failure].

PubMed

Deng, Yi-Jun; Ji, You-Lin; Chen, Lan-Ping; Jin, Qin

2011-04-01

To observe the effects of combining positive pressure ventilation with diaphragm pacing on respiratory mechanics in patients with respiratory failure. Twenty patients with central respiratory failure were studied with cohorts. The effects on respiratory mechanics were respectively observed in patients in control group, in whom ventilation by positive pressure only, and patients in experimental group in whom ventilation was instituted by combining positive pressure ventilation with diaphragm pacing. Compared with control group, mean airway pressure (Paw, cm H(2)O, 1 cm H(2)O= 0.098 kPa) and plateau pressure (Pplat, cm H(2)O) were significantly decreased in experimental group (Paw: 6.1±1.3 vs. 7.3±1.8; Pplat: 10.4±2.5 vs. 12.1±2.6, both P<0.05), while the negative value of peak esophageal pressure (P(PEAK ES) , cm H(2)O), the negative value of the difference between peak and basic esophageal pressure (dP(ES), cm H(2)O), transpulmonary pressure at end of inspiration hold (Ptp plat, cm H(2)O ), static compliance (Cst, ml/cm H(2)O) were significantly increased in experimental group (P(PEAK ES): -8.3± 1.9 vs. -3.2±1.4; dP(ES) : -11.2±2.6 vs. -8.2±2.2; Ptp plat: 23.6±3.8 vs. 15.6±3.1; Cst: 52.7±8.2 vs. 48.3±7.2, all P<0.05). No differences were found in airway resistance (Raw, cm H(2)O×L(-1) ×s(-1) ) and lung resistance (R(L), cm H(2)O×L(-1) ×s(-1) ) between experimental group and control group (Raw: 2.1±0.5 vs. 2.3±0.4; R(L): 2.9±0.6 vs. 3.1±0.5, both P>0.05). Work of breath by patient (WOBp, J/L) was significantly increased and work of breath by ventilator (WOBv, J/L) was significantly decreased in experimental group compared with control group (WOBp: 0.18±0.03 vs. 0; WOBv: 0.31±0.07 vs. 0.53±0.11, both P<0.05). Compared with positive pressure ventilation , positive pressure ventilation combined with diaphragm pacing can decrease the Paw, increase intrathoracic negative pressure, transpulmonary pressure, and Cst, and decrease WOBv, while there is

[Effect of joss stick moxibustion combined with pricking and cupping for acute herpes zoster and its mechanism of analgesia].

PubMed

Ye, Guoping; Su, Meiling; Zhu, Dingyu; Zhang, Linyun; Lin, Wang; Huang, Li; Wu, Mingxia

2017-12-12

To observe the effects of conventional western medication and joss stick moxibustion combined with pricking and cupping for herpes zoster in acute stage, and to explore its analgesic mechanism. Seventy patients with acute herpes zoster were randomized into an observation group (33 cases after 2 dropping) and a control group (34 cases after 1 dropping). Patients in the observation group were treated with joss stick moxibustion combined with pricking and cupping at local ashi points for 7 times, once every other day. Oral acyclovir, vitamin B 1 and mecobalamin tablets were applied in the control group for continuous 14 days, and interferon injection was used for continuous 6 days, etc. The herpes evaluation indexes of blister stopping time, scab time and decrustation time as well as pain intensity were observed before and after treatment. Peripheral serum substance P (SP) content of herpes local situation was detected. The comprehensive effects were evaluated. The blister stopping time, scab time and decrustation time in the observation group were shorter than those in the control group (all P <0.05). There was no statistical significance for pain relief degree between the two groups ( P >0.05). The pain beginning to ease time and duration time in the observation group were better than those in the control group (both P <0.05). The contents of SP in the two groups decreased after treatment (both P <0.01), and it was better in the observation group ( P <0.05). The total effective rate of the observation group after treatment was 87.9% (29/33), and that of the control group was 85.3% (29/34), which were not statistically significant ( P >0.05). The cured rate of the observation group was better than that of the control group [66.7% (22/33) vs 58.8% (20/34), P <0.05]. Joss stick moxibustion combined with pricking and cupping are effective for herpes zoster, which have quicker and good analgesic effects than conventional western medication. Its mechanism may be related

[Interpretation of 2018 guidelines for the early management of patients with acute ischemic stroke].

PubMed

Wang, Gang; Fang, Bangjiang; Yu, Xuezhong; Li, Zhijun

2018-04-01

In 2018, the American Heart Association/American Stroke Association (AHA/ASA) has developed the latest 2018 guidelines for the early management of patients with acute ischemic stroke (AIS), based on the latest evidences. The 2018 guidelines including recommendations on pre-hospital and in-hospital management treatment, has revised and add new recommendations from 2013 guideline. The major changes in 2018 guideline involve applications of brain imaging in early stage, intravenous thrombolysis and mechanical thrombectomy, et al. This review interprets the 2018 guidelines for clinicians to improve the clinical diagnosis, treatment and outcome of patients with AIS.

Mechanism underlying the effect of combined therapy using glucosamine and low-dose cyclosporine A on the development of atopic dermatitis-like skin lesions in NC/Nga mice.

PubMed

Kim, Chang-Hyun; Choi, Yun-Seok; Cheong, Kyung Ah; Lee, Ai-Young

2013-02-01

Combination therapy is often used in the treatment of atopic dermatitis (AD) to improve clinical efficacy or to spare the dose of each drug. Cyclosporine A (CsA) is a calcineurin inhibitor that was developed for the treatment of AD. Glucosamine (Glu) is a potent immunosuppressant that inhibits Th2-mediated immunity. We previously reported that Glu has an ameliorative effect on the development of the pathology in NC/Nga mice. The aims of our study were to investigate the therapeutic efficacy of combination of Glu and low-dose CsA in dermatophagoides farina (Df)-induced AD-like skin lesions in NC/Nga mice and to determine the underlying therapeutic mechanisms. The Df-induced NC/Nga mice with a clinical score of 7 were used for treatment with Glu (500mg/kg) alone, low-dose CsA (2, 5, and 10mg/kg) or in combination. The clinical scores were reduced significantly by the combination treatment with Glu and low-dose CsA. The suppression of dermatitis by combined therapy was accompanied by decrease in the plasma level of IgE and in the splenic level of IL-4, IL-5, IL-13, TARC and eotaxin. Histological analysis of the skin also revealed that combination treatment significantly reduced the inflammatory cellular infiltrate, including mast cells and eosinophils. Particularly, immunological evaluation reveals an increase of CD4(+)CD25(+) Treg cells in the combined treatment. The induction of TSLP, which leads to systemic Th2 response, was reduced in the skin on combination treatment. The protein expression of filaggrin and involucrin was recovered by combination treatment in the skin lesions, whereas the protein expression of keratin-10 and keratin-14 decreased in the combination treatment. Collectively, our findings suggest that combination treatment of Glu and low-dose CsA leads to the therapeutic effects in Df-induced AD-like skin lesion in NC/Nga mice through inhibition of IgE, inflammatory cellular infiltrate, and recovery of skin barrier function via a mechanism that may

Ultrasound assisted extraction of food and natural products. Mechanisms, techniques, combinations, protocols and applications. A review.

PubMed

Chemat, Farid; Rombaut, Natacha; Sicaire, Anne-Gaëlle; Meullemiestre, Alice; Fabiano-Tixier, Anne-Sylvie; Abert-Vian, Maryline

2017-01-01

This review presents a complete picture of current knowledge on ultrasound-assisted extraction (UAE) in food ingredients and products, nutraceutics, cosmetic, pharmaceutical and bioenergy applications. It provides the necessary theoretical background and some details about extraction by ultrasound, the techniques and their combinations, the mechanisms (fragmentation, erosion, capillarity, detexturation, and sonoporation), applications from laboratory to industry, security, and environmental impacts. In addition, the ultrasound extraction procedures and the important parameters influencing its performance are also included, together with the advantages and the drawbacks of each UAE techniques. Ultrasound-assisted extraction is a research topic, which affects several fields of modern plant-based chemistry. All the reported applications have shown that ultrasound-assisted extraction is a green and economically viable alternative to conventional techniques for food and natural products. The main benefits are decrease of extraction and processing time, the amount of energy and solvents used, unit operations, and CO 2 emissions. Copyright © 2016 Elsevier B.V. All rights reserved.

[Mechanisms for the formation of a combination of the natural foci of trematodiases and tularemia in the floodplain-river ecosystem of the Konda River in different periods of epizootic activity of an infection focus].

PubMed

Ushakov, A V

2011-01-01

The basis of the mechanism responsible for the formation of a combination of the natural foci of trematodiases and tularemia in the infection foci in the interepizootic periods is their association with the morphological structure of the floodplain-river landscape of the Konda River. The landscape's facias and holes, which are common to the foci, are integrated, by predetermining the territorial combination. The formation of a closed trinomial Francisella tularensis parasite system integrating these foci serves as a basis for the mechanism of the formation of a combination of the natural foci of trematodiases and tularemia on transition of the latter from the interepizootic state to epizooty. The absence of host populations linking the foci of methorchiasis (M. xanthosomus), bilharziasis, and tularemia determines their combination both in the interepizootic periods and at the level of the landscape morphological structure. The basis for the mechanism of the formation of a combination of the natural foci of trematodiases and tularemia in the periods of diffuse epizooties in the infection foci is the formation of an open binomial F. tularensis parasite system and the infestation of the co-members of F. tularensis trematode parasite systems. By penetrating into them, the pathogen forces the F. tularensis parasite system to enter the trematode parasite systems, causing their complete (opisthorchiases, methorchiases) or partial (bilharziasis) coincidence. Thus, these foci are combined at the level of parasitocenoses of the parasite systems of infections and infestations, by giving rise to pseudosystem combined foci. The natural foci of B. polonica and F. tularensis are combined at the level of parasitocenosis of the coacting hemipopulation of trematode parthenitas, F. tularensis subpopulations and intermediate host population, by forming an autoecious population-combination bilharziasis-tularemia focus. The formation of territorial-combination, autoecious population-combination

Effects of Zoledronate and Mechanical Loading during Simulated Weightlessness on Bone Structure and Mechanical Properties

NASA Technical Reports Server (NTRS)

Scott, R. T.; Nalavadi, M. O.; Shirazi-Fard, Y.; Castillo, A. B.; Alwood, J. S.

2016-01-01

Space flight modulates bone remodeling to favor bone resorption. Current countermeasures include an anti-resorptive drug class, bisphosphonates (BP), and high-force loading regimens. Does the combination of anti-resorptives and high-force exercise during weightlessness have negative effects on the mechanical and structural properties of bone? In this study, we implemented an integrated model to mimic mechanical strain of exercise via cyclical loading (CL) in mice treated with the BP Zoledronate (ZOL) combined with hindlimb unloading (HU). Our working hypothesis is that CL combined with ZOL in the HU model induces additive structural and mechanical changes. Thirty-two C57BL6 mice (male,16 weeks old, n8group) were exposed to 3 weeks of either HU or normal ambulation (NA). Cohorts of mice received one subcutaneous injection of ZOL (45gkg), or saline vehicle, prior to experiment. The right tibia was axially loaded in vivo, 60xday to 9N in compression, repeated 3xweek during HU. During the application of compression, secant stiffness (SEC), a linear estimate of slope of the force displacement curve from rest (0.5N) to max load (9.0N), was calculated for each cycle once per week. Ex vivo CT was conducted on all subjects. For ex vivo mechanical properties, non-CL left femurs underwent 3-point bending. In the proximal tibial metaphysis, HU decreased, CL increased, and ZOL increased the cancellous bone volume to total volume ratio by -26, +21, and +33, respectively. Similar trends held for trabecular thickness and number. Ex vivo left femur mechanical properties revealed HU decreased stiffness (-37),and ZOL mitigated the HU stiffness losses (+78). Data on the ex vivo Ultimate Force followed similar trends. After 3 weeks, HU decreased in vivo SEC (-16). The combination of CL+HU appeared additive in bone structure and mechanical properties. However, when HU + CL + ZOL were combined, ZOL had no additional effect (p0.05) on in vivo SEC. Structural data followed this trend with

Combined binary collision and continuum mechanics model applied to focused ion beam milling of a silicon membrane

NASA Astrophysics Data System (ADS)

Hobler, Gerhard

2015-06-01

Many experiments indicate the importance of stress and stress relaxation upon ion implantation. In this paper, a model is proposed that is capable of describing ballistic effects as well as stress relaxation by viscous flow. It combines atomistic binary collision simulation with continuum mechanics. The only parameters that enter the continuum model are the bulk modulus and the radiation-induced viscosity. The shear modulus can also be considered but shows only minor effects. A boundary-fitted grid is proposed that is usable both during the binary collision simulation and for the spatial discretization of the force balance equations. As an application, the milling of a slit into an amorphous silicon membrane with a 30 keV focused Ga beam is studied, which demonstrates the relevance of the new model compared to a more heuristic approach used in previous work.

Functional innovation from changes in protein domains and their combinations.

PubMed

Lees, Jonathan G; Dawson, Natalie L; Sillitoe, Ian; Orengo, Christine A

2016-06-01

Domains are the functional building blocks of proteins. In this work we discuss how domains can contribute to the evolution of new functions. Domains themselves can evolve through various mechanisms, altering their intrinsic function. Domains can also facilitate functional innovations by combining with other domains to make novel proteins. We discuss the mechanisms by which domain and domain combinations support functional innovations. We highlight interesting examples where changes in domain combination promote changes at the domain level. Copyright © 2016 Elsevier Ltd. All rights reserved.

p-Aminophenol degradation by ozonation combined with sonolysis: operating conditions influence and mechanism.

PubMed

He, Zhiqiao; Song, Shuang; Ying, Haiping; Xu, Lejin; Chen, Jianmeng

2007-07-01

The degradation of p-aminophenol (PAP) in aqueous solution by sonolysis, by ozonation, and by a combination of both was investigated in laboratory-scale experiments. Operation parameters such as pH, temperature, ultrasonic energy density and ozone dose were optimized with regard to the efficiency of PAP removal. The concentration of PAP during the reaction was detected by high-pressure liquid chromatography. The concentrations of ammonium ions and nitrate ions were monitored during the degradation. Intermediate products such as 4-iminocyclohexa-2,5-dien-1-one, phenol, but-2-enedioic acid, and acetic acid were detected by gas chromatography coupled with mass spectrometry. The degradation rate of PAP was higher in the combined system than in the linear combination of separate experiments. The degradation efficiency was decreased rapidly when n-butanol was added to the combined reaction system, which showed that some radical reaction might proceed during the laboratory experiments.

Combined exposure to big endothelin-1 and mechanical loading in bovine sternal cores promotes osteogenesis

PubMed Central

Meyer, Luisa A.; Johnson, Michael G.; Cullen, Diane M.; Vivanco, Juan F.; Blank, Robert D.; Ploeg, Heidi-Lynn; Smith, Everett L.

2016-01-01

to the CC group on days 15, 19 and 23. The data suggest that combined exposure to big ET1 and mechanical loading results in increased osteogenesis as measured in biomechanical, histomorphometric and biochemical responses. PMID:26855374

Combined exposure to big endothelin-1 and mechanical loading in bovine sternal cores promotes osteogenesis.

PubMed

Meyer, Luisa A; Johnson, Michael G; Cullen, Diane M; Vivanco, Juan F; Blank, Robert D; Ploeg, Heidi-Lynn; Smith, Everett L

2016-04-01

, 19 and 23. The data suggest that combined exposure to big ET1 and mechanical loading results in increased osteogenesis as measured in biomechanical, histomorphometric and biochemical responses. Copyright © 2016 Elsevier Inc. All rights reserved.

Survival mechanism of Escherichia coli O157:H7 against combined treatment with acetic acid and sodium chloride.

PubMed

Lee, Sun-Young; Kang, Dong-Hyun

2016-05-01

The combination of salt and acid is commonly used in the production of many foods, including pickles and fermented foods. However, in our previous studies, the addition of salt significantly reduced the inhibitory effect of acetic acid on Escherichia coli O157:H7 in laboratory media and pickled cucumbers. Therefore, this study was conducted to determine the mechanism by which salt confers resistance against acetic acid in E. coli O157:H7. The addition of high concentrations (up to 9% or 15% [w/v]) of salt increased the resistance of E. coli O157:H7 to acetic acid treatment. Combined treatment with acetic acid and salt showed varying results among different bacterial strains (an antagonistic effect for E. coli O157:H7 and Shigella and a synergistic effect for Listeria monocytogenes and Staphylococcus aureus). The addition of salt increased the cytoplasmic pH of E. coli O157:H7, but decreased the cytoplasmic pH of L. monocytogenes and S. aureus on treatment with acetic acid. Therefore, the addition of salt increases the acid resistance of E. coli O157:H7 possibly by increasing its acid resistance response and consequently preventing the acidification of its cytoplasm by organic acids. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rescue therapeutic strategy combining ultra-protective mechanical ventilation with extracorporeal CO2 removal membrane in near-fatal asthma with severe pulmonary barotraumas: A case report.

PubMed

Pavot, Arthur; Mallat, Jihad; Vangrunderbeeck, Nicolas; Thevenin, Didier; Lemyze, Malcolm

2017-10-01

Mechanical ventilation of severe acute asthma is still considered a challenging issue, mainly because of the gas trapping phenomenon with the potential for life-threatening barotraumatic pulmonary complications. Herein, we describe 2 consecutive cases of near-fatal asthma for whom the recommended protective mechanical ventilation approach using low tidal volume of 6 mL/kg and small levels of PEEP was rapidly compromised by giant pneumomediastinum with extensive subcutaneousemphysema. Near fatal asthma. A rescue therapeutic strategy combining extracorporeal CO2 removal membrane with ultra-protective extremely low tidal volume (3 mL/kg) ventilation was applied. Both patients survived hospital discharge. These 2 cases indicate that ECCO2R associated with ultra-protective ventilation could be an alternative to surgery in case of life-threatening barotrauma occurring under mechanical ventilation.

Mechanical code comparator

DOEpatents

Peter, Frank J.; Dalton, Larry J.; Plummer, David W.

2002-01-01

A new class of mechanical code comparators is described which have broad potential for application in safety, surety, and security applications. These devices can be implemented as micro-scale electromechanical systems that isolate a secure or otherwise controlled device until an access code is entered. This access code is converted into a series of mechanical inputs to the mechanical code comparator, which compares the access code to a pre-input combination, entered previously into the mechanical code comparator by an operator at the system security control point. These devices provide extremely high levels of robust security. Being totally mechanical in operation, an access control system properly based on such devices cannot be circumvented by software attack alone.

Investigating the complex mechanism of B migration in a magnetic-tunnel-junction trilayer structure—a combined study using XPS and TOF-SIMS

NASA Astrophysics Data System (ADS)

Ying, Ji-Feng; Ji, Rong; Ter Lim, Sze; Tran, Michael N.; Wang, Chen Chen; Ernult, Franck

2016-02-01

The magnetic-tunnel-junction (MTJ) structure is the core of many important devices, such as magnetic recording head and STT-RAM. CoFeB/MgO/CoFeB tri-layer thin-film stack is a widely researched MTJ structure. In this tri-layer, the functional property of the MTJ, i.e. its TMR ratio, is critically dependent on the crystal orientation of the CoFe grains. In order for the desired (1 0 0) out of plane texture to develop in the CoFeB layers, B needs to be engineered to be expelled out of these CoFeB layers, and diffuse or migrate into the adjacent layers. Ta is usually used as a seed layer adjacent to the MTJ structure. In this work, we investigated the important B-migration mechanisms within this MTJ structure through a combined XPS/TOF-SIMS study. Specifically, we tried to elucidate the possible physical/chemical interactions between the B and Ta that could happen with different film stack designs. Previous works have shown that there might be two possible B-migration mechanisms. One mechanism is direct B diffusion into the adjacent Ta layer during annealing. The other B-migration mechanism is through the formation of TaBOx species, in which B could be carried out by the Ta diffusion. In particular, through studying a series of film stacks, we discussed the circumstances under which one of these B-migration mechanisms becomes dominant. Furthermore, we discussed how these B-migration mechanisms facilitated the B expulsion in a common MTJ structure.

Macro-mechanics controls quantum mechanics: mechanically controllable quantum conductance switching of an electrochemically fabricated atomic-scale point contact.

PubMed

Staiger, Torben; Wertz, Florian; Xie, Fangqing; Heinze, Marcel; Schmieder, Philipp; Lutzweiler, Christian; Schimmel, Thomas

2018-01-12

Here, we present a silver atomic-scale device fabricated and operated by a combined technique of electrochemical control (EC) and mechanically controllable break junction (MCBJ). With this EC-MCBJ technique, we can perform mechanically controllable bistable quantum conductance switching of a silver quantum point contact (QPC) in an electrochemical environment at room temperature. Furthermore, the silver QPC of the device can be controlled both mechanically and electrochemically, and the operating mode can be changed from 'electrochemical' to 'mechanical', which expands the operating mode for controlling QPCs. These experimental results offer the perspective that a silver QPC may be used as a contact for a nanoelectromechanical relay.

Dislocation mechanisms and 3D twin architectures generate exceptional strength-ductility-toughness combination in CrCoNi medium-entropy alloy

DOE PAGES

Zhang, Zijiao; Sheng, Hongwei; Wang, Zhangjie; ...

2017-02-20

Combinations of high strength and ductility are hard to attain in metals. Exceptions include materials exhibiting twinning-induced plasticity. To understand how the strength-ductility trade-off can be defeated, we apply in situ, and aberration-corrected scanning, transmission electron microscopy to examine deformation mechanisms in the medium-entropy alloy CrCoNi that exhibits one of the highest combinations of strength, ductility and toughness on record. Ab initio modelling suggests that it has negative stacking-fault energy at 0K and high propensity for twinning. With deformation we find that a three-dimensional (3D) hierarchical twin network forms from the activation of three twinning systems. This serves a dualmore » function: conventional twin-boundary (TB) strengthening from blockage of dislocations impinging on TBs, coupled with the 3D twin network which offers pathways for dislocation glide along, and cross-slip between, intersecting TB-matrix interfaces. The stable twin architecture is not disrupted by interfacial dislocation glide, serving as a continuous source of strength, ductility and toughness.« less

Dislocation mechanisms and 3D twin architectures generate exceptional strength-ductility-toughness combination in CrCoNi medium-entropy alloy

PubMed Central

Zhang, Zijiao; Sheng, Hongwei; Wang, Zhangjie; Gludovatz, Bernd; Zhang, Ze; George, Easo P.; Yu, Qian; Mao, Scott X.; Ritchie, Robert O.

2017-01-01

Combinations of high strength and ductility are hard to attain in metals. Exceptions include materials exhibiting twinning-induced plasticity. To understand how the strength-ductility trade-off can be defeated, we apply in situ, and aberration-corrected scanning, transmission electron microscopy to examine deformation mechanisms in the medium-entropy alloy CrCoNi that exhibits one of the highest combinations of strength, ductility and toughness on record. Ab initio modelling suggests that it has negative stacking-fault energy at 0K and high propensity for twinning. With deformation we find that a three-dimensional (3D) hierarchical twin network forms from the activation of three twinning systems. This serves a dual function: conventional twin-boundary (TB) strengthening from blockage of dislocations impinging on TBs, coupled with the 3D twin network which offers pathways for dislocation glide along, and cross-slip between, intersecting TB-matrix interfaces. The stable twin architecture is not disrupted by interfacial dislocation glide, serving as a continuous source of strength, ductility and toughness. PMID:28218267

The effect of combination of sugar palm fruit, carrageenan, and citric acid on mechanical properties of biodegradable film

NASA Astrophysics Data System (ADS)

Rinanda, S. A.; Nastabiq, M.; Raharjo, S. H.; Hayati, S. K.; Yaqin, M. A.; Ratnawati

2017-11-01

Biodegradable film is a type of plastic material that can be degraded naturally and is usually made of organic material. The material commonly used is polysaccharides. The purpose of this study is to observe the effect of the combination of sugar palm fruit, carrageenan, and citric acid (CA) on the mechanical properties of the biodegradable films, such as tensile strength, elongation and film thickness. The experiment begins with dissolving the sugar palm fruit porridge and carrageenan with ratios of 1:0, 3:1, 2:1, 1:1 in water. The mixture was heated using a heater and magnetic stirrer at 80° C for 10 minutes. Glycerol and citric acid (CA) were added to the solution and stirred for 5 minutes. Each film solution was printed on a modified acrylic and, dried for 18 hours in an oven at 55° C. The formed film layer was then removed from the acrylic mold and inserted in a desiccatorsat 23° C for 1 hour. Then the film analyzed for its tensile strength, elongation using Dynamic Mechanical Thermal Analysis (DMTA), and thickness. The optimum result shown by sugar palm fruit and carrageenan ratio of 1:1 with 1% citric acid (CA).

Bio-Inspired Metallo-Supramolecular Polymers for Combined Mechanical Properties

DTIC Science & Technology

2010-01-01

3 4 5 6 0 50 100 150 200 Temp (°C) H ea t F lo w (m W ) Figure 8. DSC trace of polymer 7. 1H NMR analysis indicated complete reaction of the...static and dynamic mechanical analysis methods. 11 5. References 1. Guan, Z. Polymer International 2007, 56, 467. 2. Oberhauser, A. F ...Hansma, P. K.; Carrion-Vazques, M.; Fernandez, J. M. Proc. Natl. Acad. Sci. USA 2001, 98, 468. 3. Reif, M. Gautel, M.; Oesterhelt, F .; Fernandez, J

Combined Mechanical and Electrical Study of Polymers of Biological Origin

NASA Astrophysics Data System (ADS)

Zsoldos, G.; Szoda, K.; Marossy, K.

2017-02-01

Thermally Simulated Depolarization Current measurement is an excellent but not widely used method for identifying relaxation processes in polymers. The DMA method is used here to analyze the mechanical changes depend on temperature in biopolymers. The two techniques take advantage of the energy changes involved in the various phase transitions of certain polymer molecules. This allows for several properties of the material to be ascertained; melting points, enthalpies of melting, crystallization temperatures, glass transition temperatures and degradation temperatures. The examined biopolymer films are made from biological materials such as proteins and polysaccharides. These materials have gained wide usage in pharmaceutical, medical and food areas. The uses of biopolymer films depend on their structure and mechanical properties. This work is based on pectin and gelatin films. The films were prepared by casting. The casting technique used aqueous solutions in each case of sample preparation. The manufacturing process of the pectin and gelatin films was a single stage solving process.

Does mechanism of drug action matter to inform rational polytherapy in epilepsy?

PubMed

Giussani, Giorgia; Beghi, Ettore

2013-05-01

When monotherapy for epilepsy fails, add-on therapy is an alternative option. There are several possible antiepileptic drug combinations based on their different and multiple mechanisms of action and pharmacokinetic interactions. However, only when benefits of drug combinations outweigh the harms, polytherapy can be defined as "rational". In the past 20 years, second generation AEDs have been marketed, some of which have better defined mechanisms of action and better pharmacokinetic profile. The mechanisms of action of AEDs involve, among others, blockade of voltage-gated sodium channels, blockade of voltage-gated calcium channel, activation of the ionotropic GABAA receptor and increase of GABA levels at the synaptic cleft, blockade of glutamate receptors, binding to synaptic vesicle protein 2A, and opening of KCNQ (Kv7) potassium channels. Aim of this review was to examine published reports on AEDs combinations in animal models and humans focusing on mechanisms of action and pharmacokinetic interactions. Studies in animals have shown that AED combinations are more effective when using drugs with different mechanisms of action. The most effective combination was found using a drug with a single mechanism of action and another with multiple mechanisms of action. In humans some combinations between a blocker of voltage-gated sodium channels and a drug with multiple mechanisms of action may be synergistic. Future studies are necessary to better define rational combinations and complementary mechanisms of action, considering also pharmacokinetic interactions and measures of toxicity and not only drug efficacy.

Water Assisted Reaction Mechanism of OH- with CCl4 in Aqueous Solution - Hybrid Quantum Mechanical and Molecular Mechanics Investigation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Jie; Yin, Hongyun; Wang, Dunyou

2013-02-20

The OH- (H2O) + CCl4 reaction in aqueous solution was investigated using the combined quantum mechanical and molecular mechanics approach. The reaction mechanism of OH- (H2O) + CCl4 consists of two concerted steps - formation of OH- in the favorable attack conformation via the proton transfer process, and the nucleophilic substitution process in which the newly formed OH- attacks the CCl4. The free energy activation barrier is 38.2 kcal/mol at CCSD(T)/MM level of theory for this reaction, which is about 10.3 kcal/mol higher than that of the direct nucleophilic substitution mechanism of the OH- + CCl4 reaction in aqueous solution.

Managing iliofemoral deep venous thrombosis of pregnancy with a strategy of thrombus removal is safe and avoids post-thrombotic morbidity.

PubMed

Herrera, Santiago; Comerota, Anthony J; Thakur, Subhash; Sunderji, Shiraz; DiSalle, Robert; Kazanjian, Sahira N; Assi, Zakaria

2014-02-01

Extensive deep venous thrombosis (DVT) during pregnancy is usually treated with anticoagulation alone, risking significant post-thrombotic syndrome (PTS) in young patients. Catheter-directed thrombolysis (CDT) and operative venous thrombectomy have been safely and effectively used in nonpregnant patients, demonstrating significant reduction in post-thrombotic morbidity. This report reviews short- and long-term outcomes of 13 patients with extensive DVT of pregnancy treated with a strategy of thrombus removal. From 1999 to 2013, 13 patients with iliofemoral DVT during pregnancy were offered CDT, pharmacomechanical thrombolysis (PMT), and/or venous thrombectomy. Gestational age ranged from 8 to 34 weeks. Fetal monitoring was performed throughout hospitalization. Radiation exposure was minimized with pelvic lead shields, focal fluoroscopy, and limited angiographic runs. Follow-up included objective vein evaluation using venous duplex and PTS assessment using the Villalta scale. CDT and/or PMT were used in 11 patients. Two patients underwent venous thrombectomy alone, and one patient had operative thrombectomy as an adjunct to CDT and PMT. Each patient had complete or near-complete thrombus resolution and rapid improvement in clinical symptoms. Eight of 11 having CDT or PMT underwent venoplasty and stenting of the involved iliac veins. Twelve of the 13 delivered healthy infants at term. One patient opted for termination of her pregnancy. Mean patient and gestational ages were 26 years and 26 weeks, respectively. Mean follow-up was 1.3 years, with only one recurrence. Duplex ultrasonography demonstrated patent veins in all but one patient and normal valve function in 10 patients. Eleven patients had Villalta scores <5 (considered normal), with a mean score of 0.7. Extensive DVT of pregnancy can be effectively and safely treated with a strategy of thrombus removal, resulting in a patent venous system, normal valve function in many, prevention of PTS, and reduction in

Effectiveness of Mechanical Debridement Combined With Adjunctive Therapies for Nonsurgical Treatment of Periimplantitis: A Systematic Review.

PubMed

de Almeida, Juliano Milanezi; Matheus, Henrique Rinaldi; Rodrigues Gusman, David Jonathan; Faleiros, Paula Lazilha; Januário de Araújo, Nathália; Noronha Novaes, Vivian Cristina

2017-02-01

This study aimed to perform a systematic review of the effectiveness of nonsurgical treatment associated with different adjuvant therapies on periimplantitis. Different individuals, following a research process, performed a network research of controlled and randomized controlled clinical trials on PubMed, Embase/MEDLINE, with 20 years' time constraint and the last search in January 2016. From 108 articles found by the first search, they analyzed 10 full texts, and in none did they find a standard control group. When compared, mechanical therapies combined with adjuvant therapy decreased prevalence of periimplant ratios; however, some groups showed unsatisfactory results, mainly related to the probing depth and bleeding index. When comparing debridement with other nonsurgical therapies (Er:YAG, Vector, air abrasive with amino acid glycine powder), increased periimplant levels were noticed in the test and control groups, although in different periods. Despite the improvement in the periimplant indices, there is no sufficient evidence to score the best results or even to choose the best association for nonsurgical treatment of periimplantitis; hence, more trials are necessary to answer this question.

Cerebral mechanism of puncturing at He-Mu point combination for functional dyspepsia: study protocol for a randomized controlled parallel trial.

PubMed

Yin, Shuai; Chen, Yuan; Lei, Du; Sun, Rui-Rui; Ma, Ting-Ting; Feng, Pei-Min; He, Zhao-Xuan; Suo, Xue-Ling; Ma, Pei-Hong; Qu, Yu-Zhu; Qiu, Ke; Jing, Miao-Miao; Gong, Qi-Yong; Liang, Fan-Rong; Chen, Jiao; Zeng, Fang

2017-05-01

Acupuncture is widely used to treat functional dyspepsia with satisfactory outcomes. Combination of the He and Mu acupoints is commonly used and has a synergistic effect on functional dyspepsia; however, its underlying mechanisms remain unclear. Therefore, a randomized controlled parallel clinical trial is currently underway at Chengdu University of Traditional Chinese Medicine, China. This trial is designed to explore the efficacy of and central responses to the He-Mu point combination in patients with functional dyspepsia using functional magnetic resonance imaging. A total of 105 patients with functional dyspepsia will be allocated into 3 groups: the low-He point group (puncturing at Zusanli (ST36)), Mu point group (puncturing at Zhongwan (CV12)), and He-Mu point combination group (puncturing at ST36 and CV12). Every participant will receive 20 sessions of manual acupuncture for 4 weeks. The needles will be inserted perpendicularly to a depth of 1 to 2 cun. The angle of rotation and twisting will range from 90 to 180 degrees, while lifting and thrusting will range from 0.3 to 0.5 cm. The various manipulations will be performed 60 to 90 times per minute. The needles will remain in place for 30 minutes, during which manipulation will be applied every 10 minutes. Magnetic resonance imaging will be performed before and after 20 sessions of acupuncture. The primary outcome is symptom improvement according to the Chinese version of the Nepean Dyspepsia Index. Secondary outcomes include the Leeds dyspepsia questionnaire, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Beck Anxiety Inventory, Beck Depression Inventory, and visual analogue scale scores before and after 10 and 20 sessions of acupuncture. Needle sensation and adverse events will be used to assess the therapeutic effects. This study will promote more widespread awareness of the benefits of acupoint combination in the clinical setting and provide a further explanation of the neuromechanism by which

Patient Adherence to Olmesartan/Amlodipine Combinations: Fixed Versus Extemporaneous Combinations.

PubMed

Levi, Miriam; Pasqua, Alessandro; Cricelli, Iacopo; Cricelli, Claudio; Piccinni, Carlo; Parretti, Damiano; Lapi, Francesco

2016-03-01

Lack of adherence to prescribed therapies is often a cause of suboptimal blood pressure control in patients with hypertension. To enhance patients' adherence to treatment, fixed-dose combinations of active substances with complementary mechanisms of action have been developed. An angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker (ARB) is often combined with a calcium channel blocker. Olmesartan is the most used ARB in combination therapy. In Italy, in September 2011, a fixed-dose combination of olmesartan/amlodipine (olmesartan/amlodipine 20/5 mg, 40/5 mg, or 40/10 mg) was introduced to treat patients with hypertension for whom control of blood pressure is not reached with either olmesartan or amlodipine alone. Prior research on adherence to olmesartan/amlodipine combinations was carried out in local contexts (e.g., claims databases of Italian regions or local health authorities), and/or it was limited by the fact that adherence was assessed against monotherapies already known for their low compliance profile, such as diuretics. To compare adherence with olmesartan/amlodipine fixed-dose combination (FDC) and extemporaneous combination in primary care in Italy. A nationwide, population-based study was conducted by using the Health Search IMS Health Longitudinal Patient Database. Patients aged > 17 years, affected by hypertension and treated with the FDC or extemporaneous combination of olmesartan/amlodipine, were identified. Adherence to these 2 therapeutic regimens was estimated by calculating the proportion of days covered (PDC). Patients were classified into 3 levels of adherence: high (PDC ≥ 80%), intermediate (PDC = 40%-79%), or low (PDC < 40%). In the 6-month follow-up, FDC showed higher adherence compared with an extemporaneous combination (55.1% vs. 15.9%, P < 0.001). This difference was confirmed in a multivariable logistic regression model clustered on patient identifier (odds ratio = 6.65; 95% CI = 3.10-14.26; P < 0.001). The

Blood-brain barrier permeability assessed by perfusion computed tomography predicts hemorrhagic transformation in acute reperfusion therapy.

PubMed

Kim, Taewon; Koo, Jaseong; Kim, Seong-Hoon; Song, In-Uk; Chung, Sung-Woo; Lee, Kwang-Soo

2018-06-16

Hemorrhagic transformation (HT) is one of the most feared complications of acute recanalization therapies. The aim of this study was to evaluate whether blood-brain barrier permeability (BBBP) imaging can predict HT in the setting of acute recanalization therapy and to determine the sensitivity and specificity of BBBP for the prediction of HT according to the type of reperfusion therapy. We assessed a total of 46 patients who received recanalization therapy (intravenous (IV) recombinant tissue plasminogen activator (tPA), mechanical thrombectomy with a stent retriever or both) for acute ischemic stroke within the internal carotid artery or middle cerebral artery. BBBP above the threshold was significantly associated with HT after adjustment for confounding factors in all patients (OR 45.4, 95% CI 2.9~711.2, p = 0.007), patients who received IV tPA (OR 20.1, 95% CI 1.2-336.7, p = 0.037), and patients who received endovascular therapy (OR 47.2, 95% CI 1.9-1252.5, p = 0.022). The sensitivity and specificity of the initial BBBP measurement as a predictor of HT in the overall 46 patients were 80 and 71%, respectively. These values were 75 and 64% in only IV tPA group, 100 and 80% in only endovascular group, 77 and 67% in IV tPA with or without endovascular therapy group, and 86 and 76% in endovascular therapy with or without bridging IV tPA therapy group. Increased pretreatment BBBP values were significantly associated with HT after acute recanalization therapy. This correlation with HT was stronger in patients receiving endovascular mechanical thrombectomy than in patients receiving IV rtPA.

Development of a 3D parallel mechanism robot arm with three vertical-axial pneumatic actuators combined with a stereo vision system.

PubMed

Chiang, Mao-Hsiung; Lin, Hao-Ting

2011-01-01

This study aimed to develop a novel 3D parallel mechanism robot driven by three vertical-axial pneumatic actuators with a stereo vision system for path tracking control. The mechanical system and the control system are the primary novel parts for developing a 3D parallel mechanism robot. In the mechanical system, a 3D parallel mechanism robot contains three serial chains, a fixed base, a movable platform and a pneumatic servo system. The parallel mechanism are designed and analyzed first for realizing a 3D motion in the X-Y-Z coordinate system of the robot's end-effector. The inverse kinematics and the forward kinematics of the parallel mechanism robot are investigated by using the Denavit-Hartenberg notation (D-H notation) coordinate system. The pneumatic actuators in the three vertical motion axes are modeled. In the control system, the Fourier series-based adaptive sliding-mode controller with H(∞) tracking performance is used to design the path tracking controllers of the three vertical servo pneumatic actuators for realizing 3D path tracking control of the end-effector. Three optical linear scales are used to measure the position of the three pneumatic actuators. The 3D position of the end-effector is then calculated from the measuring position of the three pneumatic actuators by means of the kinematics. However, the calculated 3D position of the end-effector cannot consider the manufacturing and assembly tolerance of the joints and the parallel mechanism so that errors between the actual position and the calculated 3D position of the end-effector exist. In order to improve this situation, sensor collaboration is developed in this paper. A stereo vision system is used to collaborate with the three position sensors of the pneumatic actuators. The stereo vision system combining two CCD serves to measure the actual 3D position of the end-effector and calibrate the error between the actual and the calculated 3D position of the end-effector. Furthermore, to

Development of a 3D Parallel Mechanism Robot Arm with Three Vertical-Axial Pneumatic Actuators Combined with a Stereo Vision System

PubMed Central

Chiang, Mao-Hsiung; Lin, Hao-Ting

2011-01-01

This study aimed to develop a novel 3D parallel mechanism robot driven by three vertical-axial pneumatic actuators with a stereo vision system for path tracking control. The mechanical system and the control system are the primary novel parts for developing a 3D parallel mechanism robot. In the mechanical system, a 3D parallel mechanism robot contains three serial chains, a fixed base, a movable platform and a pneumatic servo system. The parallel mechanism are designed and analyzed first for realizing a 3D motion in the X-Y-Z coordinate system of the robot’s end-effector. The inverse kinematics and the forward kinematics of the parallel mechanism robot are investigated by using the Denavit-Hartenberg notation (D-H notation) coordinate system. The pneumatic actuators in the three vertical motion axes are modeled. In the control system, the Fourier series-based adaptive sliding-mode controller with H∞ tracking performance is used to design the path tracking controllers of the three vertical servo pneumatic actuators for realizing 3D path tracking control of the end-effector. Three optical linear scales are used to measure the position of the three pneumatic actuators. The 3D position of the end-effector is then calculated from the measuring position of the three pneumatic actuators by means of the kinematics. However, the calculated 3D position of the end-effector cannot consider the manufacturing and assembly tolerance of the joints and the parallel mechanism so that errors between the actual position and the calculated 3D position of the end-effector exist. In order to improve this situation, sensor collaboration is developed in this paper. A stereo vision system is used to collaborate with the three position sensors of the pneumatic actuators. The stereo vision system combining two CCD serves to measure the actual 3D position of the end-effector and calibrate the error between the actual and the calculated 3D position of the end-effector. Furthermore, to

Management of Cavoatrial Deep Venous Thrombosis: Incorporating New Strategies

PubMed Central

Zayed, Mohamed A.; De Silva, Gayan S.; Ramaswamy, Raja S.; Sanchez, Luis A.

2017-01-01

Cavoatrial deep venous thrombosis (DVT) is diagnosed with increasing prevalence. It can be managed medically with anticoagulation or with directed interventions aimed to efficiently reduce the thrombus burden within the target venous segment. The type of management chosen depends greatly on the etiology and chronicity of the thrombosis, existing patient comorbidities, and the patient's tolerance to anticoagulants and thrombolytic agents. In addition to traditional percutaneous catheter-based pharmacomechanical thrombolysis, other catheter-based suction thrombectomy techniques have emerged in recent years. Each therapeutic modality requires operator expertise and a coordinated care paradigm to facilitate successful outcomes. Open surgical thrombectomy is alternatively reserved for specific patient conditions, including intolerance of anticoagulation, failed catheter-based interventions, or acute emergencies. PMID:28265127

Introductory Education for Mechanical Engineering by Exercise in Mechanical Disassembly

NASA Astrophysics Data System (ADS)

Matsui, Yoshio; Asakawa, Naoki; Iwamori, Satoru

An introductory program “Exercise for engineers in mechanical disassembly” is an exercise that ten students of every team disassemble a motor scooter to the components and then assemble again to the initial form in 15 weeks. The purpose of this program is to introduce mechanical engineering by touching the real machine and learning how it is composed from various mechanical parts to the students at the early period after the entrance into the university. Additional short lectures by young teachers and a special lecture by a top engineer in the industry encourage the students to combine the actual machine and the mechanical engineering subjects. Furthermore, various educations such as group leader system, hazard prediction training, parts filing are included in this program. As a result, students recognize the importance of the mechanical engineering study and the way of group working.

[Acute limb ischemia from the general surgeon's point of view. How much knowledge of vascular surgery is necessary?].

PubMed

Kopp, R; Weidenhagen, R; Hornung, H; Jauch, K W; Lauterjung, L

2003-12-01

The diagnosis of acute peripheral ischemia can be obtained based on clinical presentation, inspection, and palpation of the affected extremity. Unfractionated heparin as a single shot is immediately given followed by continuous infusion when diagnosis is clinically evident and contraindications are excluded. Thromboembolectomy using a Fogarty catheter is immediately performed in patients with evidence of arterial embolization and signs of advanced ischemia (TASC IIb/III) followed by intraoperative angiography. Patients with evidence of arterial thrombosis require urgent angiography followed by thrombectomy and probably subsequent endovascular or surgical interventions and vascular reconstruction. For patients with moderate ischemia (TASC IIa), initial diagnostic angiography is recommended followed by primary thrombectomy with subsequent intraoperative angiography and immediate endovascular or operative treatment of remaining vascular problems. As an alternative therapeutic option initial catheter-guided local thrombolysis can be performed in selected patients with the intention of subsequent limb revascularization or unmasking relevant vessel alterations leading to specific endovascular or surgically performed vascular reconstruction. Possible development of muscle ischemia because of increased compartment pressure should be considered and fasciotomy performed when indicated. Primary amputation of the severely ischemic limb after initial thrombectomy might be recommended in patients with life-threatening organ failure related to muscle necrosis.

Insights into the mechanism and inhibition of fatty acid amide hydrolase from quantum mechanics/molecular mechanics (QM/MM) modelling.

PubMed

Lodola, Alessio; Mor, Marco; Sirirak, Jitnapa; Mulholland, Adrian J

2009-04-01

FAAH (fatty acid amide hydrolase) is a promising target for the treatment of several central nervous system and peripheral disorders. Combined QM/MM (quantum mechanics/molecular mechanics) calculations have elucidated the role of its unusual catalytic triad in the hydrolysis of oleamide and oleoylmethyl ester substrates, and have identified the productive inhibitor-binding orientation for the carbamoylating compound URB524. These are potentially crucial insights for designing new covalent inhibitors of this drug target.

Iceberg calving of Thwaites Glacier, West Antarctica: full-Stokes modeling combined with linear elastic fracture mechanics

NASA Astrophysics Data System (ADS)

Yu, Hongju; Rignot, Eric; Morlighem, Mathieu; Seroussi, Helene

2017-05-01

Thwaites Glacier (TG), West Antarctica, has been losing mass and retreating rapidly in the past few decades. Here, we present a study of its calving dynamics combining a two-dimensional flow-band full-Stokes (FS) model of its viscous flow with linear elastic fracture mechanics (LEFM) theory to model crevasse propagation and ice fracturing. We compare the results with those obtained with the higher-order (HO) and the shallow-shelf approximation (SSA) models coupled with LEFM. We find that FS/LEFM produces surface and bottom crevasses that are consistent with the distribution of depth and width of surface and bottom crevasses observed by NASA's Operation IceBridge radar depth sounder and laser altimeter, whereas HO/LEFM and SSA/LEFM do not generate crevasses that are consistent with observations. We attribute the difference to the nonhydrostatic condition of ice near the grounding line, which facilitates crevasse formation and is accounted for by the FS model but not by the HO or SSA models. We find that calving is enhanced when pre-existing surface crevasses are present, when the ice shelf is shortened or when the ice shelf front is undercut. The role of undercutting depends on the timescale of calving events. It is more prominent for glaciers with rapid calving rates than for glaciers with slow calving rates. Glaciers extending into a shorter ice shelf are more vulnerable to calving than glaciers developing a long ice shelf, especially as the ice front retreats close to the grounding line region, which leads to a positive feedback to calving events. We conclude that the FS/LEFM combination yields substantial improvements in capturing the stress field near the grounding line of a glacier for constraining crevasse formation and iceberg calving.

Comparison between effectiveness of Mechanical and Manual Traction combined with mobilization and exercise therapy in Patients with Cervical Radiculopathy.

PubMed

Bukhari, Syed Rehan Iftikhar; Shakil-Ur-Rehman, Syed; Ahmad, Shakeel; Naeem, Aamer

2016-01-01

Cervical radiculopathy is a common neuro-musculo-skeletal disorder causing pain and disability. Traction is part of the evidence based manual physical therapy management due to its mechanical nature, type of traction and parameters related to its applicability and are still to be explored more through research. Our objective was to determine the Effects of Mechanical versus Manual Traction in Manual Physical Therapy combined with segmental mobilization and exercise therapy in the physical therapy management of Patients with Cervical Radiculopathy. This randomized control trial was conducted at department of physical therapy and rehabilitation, Rathore Hospital Faisalabad, from February to July 2015. Inclusion criteria were both male and female patients with evident symptoms of cervical spine radiculopathy and age ranged between 20-70 years. The exclusion criteria were Patients with history of trauma, neck pain without radiculopathy, aged less than 20 and more than 70. A total of 72 patients with cervical radiculopathy were screened out as per the inclusion criteria, 42 patients were randomly selected and placed into two groups by toss and trial method, and only 36 patients completed the study, while 6 dropped out. The mechanical traction was applied in group A and manual traction in group B along with common intervention of segmental mobilization and exercise therapy in both groups for 6 weeks. The patient's outcomes were assessed by self reported NPRS and NDI at the baseline and after completion of 06 weeks exercise program at 3 days per week. The data was analyzed through SPSS version-21, and paired T test was applied at 95% level significance to determine the statistical deference between two groups. Clinically the group of patients treated with mechanical traction managed pain (mean pre 6.26, mean post 1.43), and disability (mean pre 24.43 and mean post 7.26) more effectively as compared with the group of patients treated with manual traction (Pain mean pre 6

Self-Pierce Riveting Through 3 Sheet Metal Combinations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersson, Roger; Jonason, Paul; Pettersson, Tommy

2011-05-04

One way to reduce the CO{sub 2} emissions in automotives is to reduce the weight of the Body-In-White. One easy to achieve the weight reduction is to replace steel sheet materials with Al alloys, which is 3 times lighter. One issue is the joining process, especially with combinations between steel grades and AL alloys. Example of combination of mixed material combinations (Al-steel) might be found in the door structure. The reason is because of the AL alloys worthier crash performance so the automotive manufacturer might want to use crash impact beams made by high strength steels in a AL intensivemore » door structure. The joining process between aluminum and steel are problematic due it's not possible to use traditional spot-welding technologies due to the materials total difference in microstructure characteristics as well thermal properties. To overcome this issue then mechanical as well adhesion joining are frequently used. This paper describes a development process and subsequently analysis of a self-pierce rivet (SPR) process between 3 sheet metal combinations. The multi-material combinations in this study were a combination of ultra high strength steels sheets (DP1000) and a Al-alloy (AA 6014). The analysis of the SPR process, in sense of mechanical strengths, has been done by peel- and shear tests. To reduce the amount of future physical tests a virtual FE-model has been developed for the process. This FE model of the process has been subsequently used to analyze the mechanical strength during plastic deformation. By using inverse analysis a correct contact algorithm has been evaluated that would predict the binding force between the rivet and sheet under a deformation process. With this new virtual model it will not only possible to analyze and develop the SPR process but also to achieve the final strength of the joint.« less

Macro-mechanics controls quantum mechanics: mechanically controllable quantum conductance switching of an electrochemically fabricated atomic-scale point contact

NASA Astrophysics Data System (ADS)

Staiger, Torben; Wertz, Florian; Xie, Fangqing; Heinze, Marcel; Schmieder, Philipp; Lutzweiler, Christian; Schimmel, Thomas

2018-01-01

Here, we present a silver atomic-scale device fabricated and operated by a combined technique of electrochemical control (EC) and mechanically controllable break junction (MCBJ). With this EC-MCBJ technique, we can perform mechanically controllable bistable quantum conductance switching of a silver quantum point contact (QPC) in an electrochemical environment at room temperature. Furthermore, the silver QPC of the device can be controlled both mechanically and electrochemically, and the operating mode can be changed from ‘electrochemical’ to ‘mechanical’, which expands the operating mode for controlling QPCs. These experimental results offer the perspective that a silver QPC may be used as a contact for a nanoelectromechanical relay.

[Study on intersection and regulation mechanism of "efficacy-toxicity network" of aconite in combination environment of Sini decoction].

PubMed

Li, Zhi-yong; Bao, Hong-juan; Zhang, Shuo-feng; Ye, Tian-yuan; Yang, Ce; Li, Yan-wen

2015-02-01

To explore the intersection and regulation mechanism of "efficacy-toxicity network" of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata's action gene in the combination environment of Sini decoction with the network pharmacological method. The gene interaction network of Aconiti Lateralis Radix Praeparata, Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma were mined and established with Cytoscape software and Agilent literature search plug-in. The "efficiency-toxicity network" intersection of Aconiti Lateralis Radix Praeparata was formed according to its effects in anti-heart failure, neurotoxicity and cardiotoxicity. The target genes were clustered with Clusterviz plug-in. And the possible pathways of the "efficacy-tox- icity network" intersection of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata were forecasted in DAVID database. There were five genes related to neurotoxicity, cardiotoxicity and anti-heart failure function of Aconiti Lateralis Radix Praeparata, namely AKT1, BAX, HCC, IL6 and IL8, which formed 47 nodes genes in the "efficiency-toxicity network" intersection of Aconiti Lateralis Radix Praeparata. There were 29 and 27 coincident genes in the "efficiency-toxicity network" of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata. There were 23 and 17 possible regulatory pathways. In the combination environment of Sini decoction, Glycyrrhizae Radix et Rhizoma and Zingiberis Rhizoma may regulate the efficiency-toxicity network of Aconiti Lateralis Radix Praeparata by influencing immune-inflammatory signaling pathway, apoptosis-autophagy signaling pathway, nerve cell and myocardial ischemia and hypoxia protection signaling pathways.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeromel, Miran, E-mail: miran.jeromel@gmail.com; Milosevic, Z. V., E-mail: zoran.milosevic@guest.arnes.si; Kocijancic, I. J., E-mail: igor.kocijancic@gmail.com

BackgroundEndovascular mechanical revascularization (thrombectomy) is an increasingly used method for intracranial large vessel recanalization in acute stroke. The purpose of the study was to analyze the recanalization rate, clinical outcome, and complication rate in our stroke patients treated with mechanical revascularization. A total of 57 patients with large vessel stroke (within 3 h for anterior and 12 h for posterior circulation) were treated with mechanical revascularization at a single center during 24 months. The primary goal of endovascular treatment using different mechanical devices was recanalization of the occluded vessel. Recanalization rate (reported as thrombolysis in cerebral infarction [TICI] score), clinicalmore » outcome (reported as National Institutes of Health Stroke Scale [NIHSS] score and modified Rankin scale [mRS] score), as well as periprocedural complications were analyzed. The mean age of the patients was 63.1 {+-} 12.9 years, with baseline median NIHSS score of 14 (interquartile range, 9.5-19). Successful recanalization (TICI 2b or 3) was achieved in 41 (72 %) patients. Twenty patients (35 %) presented with favorable outcome (mRS {<=}2) 30 days after stroke. Overall, significant neurological improvement ({>=}4 NIHSS point reduction) occurred in 36 (63 %) patients. A clinically significant procedure-related adverse events (vessel disruption, peri/postprocedural intracranial bleeding) defined with decline in NIHSS of {>=}4 or death occurred in three (5 %) patients. The study showed a high recanalization rate with improved clinical outcome and a low rate of periprocedural complications in our stroke patients treated with mechanical revascularization. Therefore, we could conclude that endovascular revascularization (primary or in combination with a bridging thrombolysis) was an effective and safe procedure for intracranial large vessel recanalization in acute stroke.« less

Combined valence bond-molecular mechanics potential-energy surface and direct dynamics study of rate constants and kinetic isotope effects for the H + C2H6 reaction.

PubMed

Chakraborty, Arindam; Zhao, Yan; Lin, Hai; Truhlar, Donald G

2006-01-28

This article presents a multifaceted study of the reaction H+C(2)H(6)-->H(2)+C(2)H(5) and three of its deuterium-substituted isotopologs. First we present high-level electronic structure calculations by the W1, G3SX, MCG3-MPWB, CBS-APNO, and MC-QCISD/3 methods that lead to a best estimate of the barrier height of 11.8+/-0.5 kcal/mol. Then we obtain a specific reaction parameter for the MPW density functional in order that it reproduces the best estimate of the barrier height; this yields the MPW54 functional. The MPW54 functional, as well as the MPW60 functional that was previously parametrized for the H+CH(4) reaction, is used with canonical variational theory with small-curvature tunneling to calculate the rate constants for all four ethane reactions from 200 to 2000 K. The final MPW54 calculations are based on curvilinear-coordinate generalized-normal-mode analysis along the reaction path, and they include scaled frequencies and an anharmonic C-C bond torsion. They agree with experiment within 31% for 467-826 K except for a 38% deviation at 748 K; the results for the isotopologs are predictions since these rate constants have never been measured. The kinetic isotope effects (KIEs) are analyzed to reveal the contributions from subsets of vibrational partition functions and from tunneling, which conspire to yield a nonmonotonic temperature dependence for one of the KIEs. The stationary points and reaction-path potential of the MPW54 potential-energy surface are then used to parametrize a new kind of analytical potential-energy surface that combines a semiempirical valence bond formalism for the reactive part of the molecule with a standard molecular mechanics force field for the rest; this may be considered to be either an extension of molecular mechanics to treat a reactive potential-energy surface or a new kind of combined quantum-mechanical/molecular mechanical (QM/MM) method in which the QM part is semiempirical valence bond theory; that is, the new potential

Incidence and mechanisms of resistance to the combination of amoxicillin and clavulanic acid in Escherichia coli.

PubMed Central

Stapleton, P; Wu, P J; King, A; Shannon, K; French, G; Phillips, I

1995-01-01

Among Escherichia coli organisms isolated at St. Thomas's Hospital during the years 1990 to 1994, the frequency of resistance to amoxicillin-clavulanic acid (tested by disk diffusion in a ratio of 2:1) remained constant at about 5% of patient isolates (10 to 15% of the 41 to 45% that were amoxicillin resistant). Mechanisms of increased resistance were determined for 72 consecutively collected such amoxicillin-clavulanic acid-resistant isolates. MICs of the combination were 16-8 micrograms/ml for 51 (71%) of these and > or = 32-16 micrograms/ml for the remainder. The predominant mechanism was hyperproduction of enzymes isoelectrically cofocusing with TEM-1 (beta-lactamase activities, > 200 nmol of nitrocefin hydrolyzed per min per mg of protein) which was found in 44 isolates (61%); two isolates produced smaller amounts (approximately 150 nmol/min/mg) of such enzymes, and two isolates hyperproduced enzymes cofocusing with TEM-2. Eleven isolates produced enzymes cofocusing with OXA-1 beta-lactamase, which has previously been associated with resistance to amoxicillin-clavulanic acid. Ten isolates produced increased amounts of chromosomal beta-lactamase, and four of these additionally produced TEM-1 or TEM-2. Three isolates produced inhibitor-resistant TEM-group enzymes. In one of the enzymes (pI, 5.4), the amino acid sequence change was Met-67-->Val, and thus the enzyme is identical to TEM-34. Another (pI, 5.4) had the substitution Met-67-->Ile and is identical to IRT-I67, which we propose now be given the designation TEM-40. The third (pI, 5.2) had the substitution Arg-241-->Thr; this enzyme has not been reported previously and should be called TEM-41. The rarity and diversity of inhibitor-resistant TEM-group enzymes suggest that they are the result of spontaneous mutations that have not yet spread. PMID:8585729

Ruxolitinib and Polycation Combination Treatment Overcomes Multiple Mechanisms of Resistance of Pancreatic Cancer Cells to Oncolytic Vesicular Stomatitis Virus

PubMed Central

Felt, Sébastien A.; Droby, Gaith N.

2017-01-01

ABSTRACT Vesicular stomatitis virus (VSV) is a promising oncolytic virus (OV). Although VSV is effective against a majority of pancreatic ductal adenocarcinoma cell (PDAC) cell lines, some PDAC cell lines are highly resistant to VSV, and the mechanisms of resistance are still unclear. JAK1/2 inhibitors (such as ruxolitinib and JAK inhibitor I) strongly stimulate VSV replication and oncolysis in all resistant cell lines but only partially improve the susceptibility of resistant PDACs to VSV. VSV tumor tropism is generally dependent on the permissiveness of malignant cells to viral replication rather than on receptor specificity, with several ubiquitously expressed cell surface molecules playing a role in VSV attachment to host cells. However, as VSV attachment to PDAC cells has never been tested before, here we examined if it was possibly inhibited in resistant PDAC cells. Our data show a dramatically weaker attachment of VSV to HPAF-II cells, the most resistant human PDAC cell line. Although sequence analysis of low-density lipoprotein (LDL) receptor (LDLR) mRNA did not reveal any amino acid substitutions in this cell line, HPAF-II cells displayed the lowest level of LDLR expression and dramatically lower LDL uptake. Treatment of cells with various statins strongly increased LDLR expression levels but did not improve VSV attachment or LDL uptake in HPAF-II cells. However, LDLR-independent attachment of VSV to HPAF-II cells was dramatically improved by treating cells with Polybrene or DEAE-dextran. Moreover, combining VSV with ruxolitinib and Polybrene or DEAE-dextran successfully broke the resistance of HPAF-II cells to VSV by simultaneously improving VSV attachment and replication. IMPORTANCE Oncolytic virus (OV) therapy is an anticancer approach that uses viruses that selectively infect and kill cancer cells. This study focuses on oncolytic vesicular stomatitis virus (VSV) against pancreatic ductal adenocarcinoma (PDAC) cells. Although VSV is effective against

Current perspectives on the mechanism of action of artemisinins.

PubMed

Golenser, Jacob; Waknine, Judith H; Krugliak, Miriam; Hunt, Nicholas H; Grau, Georges E

2006-12-01

Artemisinin derivatives are the most recent single drugs approved and introduced for public antimalarial treatment. Although their recommended use is for treatment of Plasmodium falciparum infection, these drugs also act against other parasites, as well as against tumor cells. The mechanisms of action attributed to artemisinin include interference with parasite transport proteins, disruption of parasite mitochondrial function, modulation of host immune function and inhibition of angiogenesis. Artemisinin combination therapies are currently the preferred treatment for malaria. These combinations may prevent the induction of parasite drug resistance. However, in view of the multiple mechanisms involved, especially when additional drugs are used, the combined therapy should be carefully examined for antagonistic effects. It is now a general theory that the crucial mechanism is interference with plasmodial SERCA. Therefore, future development of resistance may be associated with overproduction or mutations of this transporter. However, a general mechanism, such as alterations in general drug transport pathways, is feasible. In this article, we review the evidence for each mechanism of action suggested.

High-performance reactionless scan mechanism

NASA Technical Reports Server (NTRS)

Williams, Ellen I.; Summers, Richard T.; Ostaszewski, Miroslaw A.

1995-01-01

A high-performance reactionless scan mirror mechanism was developed for space applications to provide thermal images of the Earth. The design incorporates a unique mechanical means of providing reactionless operation that also minimizes weight, mechanical resonance operation to minimize power, combined use of a single optical encoder to sense coarse and fine angular position, and a new kinematic mount of the mirror. A flex pivot hardware failure and current project status are discussed.

Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate.

PubMed

Saldanha, Sabita N; Kala, Rishabh; Tollefsbol, Trygve O

2014-05-15

Bioactive compounds are considered safe and have been shown to alter genetic and epigenetic profiles of tumor cells. However, many of these changes have been reported at molecular concentrations higher than physiologically achievable levels. We investigated the role of the combinatorial effects of epigallocatechin gallate (EGCG), a predominant polyphenol in green tea, and sodium butyrate (NaB), a dietary microbial fermentation product of fiber, in the regulation of survivin, which is an overexpressed anti-apoptotic protein in colon cancer cells. For the first time, our study showed that the combination treatment induced apoptosis and cell cycle arrest in RKO, HCT-116 and HT-29 colorectal cancer cells. This was found to be regulated by the decrease in HDAC1, DNMT1, survivin and HDAC activity in all three cell lines. A G2/M arrest was observed for RKO and HCT-116 cells, and G1 arrest for HT-29 colorectal cancer cells for combinatorial treatment. Further experimentation of the molecular mechanisms in RKO colorectal cancer (CRC) cells revealed a p53-dependent induction of p21 and an increase in nuclear factor kappa B (NF-κB)-p65. An increase in double strand breaks as determined by gamma-H2A histone family member X (γ-H2AX) protein levels and induction of histone H3 hyperacetylation was also observed with the combination treatment. Further, we observed a decrease in global CpG methylation. Taken together, these findings suggest that at low and physiologically achievable concentrations, combinatorial EGCG and NaB are effective in promoting apoptosis, inducing cell cycle arrest and DNA-damage in CRC cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Combined Enzymatic and Mechanical Cell Disruption and Lipid Extraction of Green Alga Neochloris oleoabundans

PubMed Central

Wang, Dongqin; Li, Yanqun; Hu, Xueqiong; Su, Weimin; Zhong, Min

2015-01-01

Microalgal biodiesel is one of the most promising renewable fuels. The wet technique for lipids extraction has advantages over the dry method, such as energy-saving and shorter procedure. The cell disruption is a key factor in wet oil extraction to facilitate the intracellular oil release. Ultrasonication, high-pressure homogenization, enzymatic hydrolysis and the combination of enzymatic hydrolysis with high-pressure homogenization and ultrasonication were employed in this study to disrupt the cells of the microalga Neochloris oleoabundans. The cell disruption degree was investigated. The cell morphology before and after disruption was assessed with scanning and transmission electron microscopy. The energy requirements and the operation cost for wet cell disruption were also estimated. The highest disruption degree, up to 95.41%, assessed by accounting method was achieved by the combination of enzymatic hydrolysis and high-pressure homogenization. A lipid recovery of 92.6% was also obtained by the combined process. The combined process was found to be more efficient and economical compared with the individual process. PMID:25853267

The force-dependent mechanism of DnaK-mediated mechanical folding

PubMed Central

Perales-Calvo, Judit; Giganti, David; Stirnemann, Guillaume; Garcia-Manyes, Sergi

2018-01-01

It is well established that chaperones modulate the protein folding free-energy landscape. However, the molecular determinants underlying chaperone-mediated mechanical folding remain largely elusive, primarily because the force-extended unfolded conformation fundamentally differs from that characterized in biochemistry experiments. We use single-molecule force-clamp spectroscopy, combined with molecular dynamics simulations, to study the effect that the Hsp70 system has on the mechanical folding of three mechanically stiff model proteins. Our results demonstrate that, when working independently, DnaJ (Hsp40) and DnaK (Hsp70) work as holdases, blocking refolding by binding to distinct substrate conformations. Whereas DnaK binds to molten globule–like forms, DnaJ recognizes a cryptic sequence in the extended state in an unanticipated force-dependent manner. By contrast, the synergetic coupling of the Hsp70 system exhibits a marked foldase behavior. Our results offer unprecedented molecular and kinetic insights into the mechanisms by which mechanical force finely regulates chaperone binding, directly affecting protein elasticity. PMID:29487911

Escherichia coli Free Radical-Based Killing Mechanism Driven by a Unique Combination of Iron Restriction and Certain Antibiotics

PubMed Central

Ma, Li; Gao, Yongjun

2015-01-01

ABSTRACT Bacterial resistance to antibiotics is precipitating a medical crisis, and new antibacterial strategies are being sought. Hypothesizing that a growth-restricting strategy could be used to enhance the efficacy of antibiotics, we determined the effect of FDA-approved iron chelators and various antibiotic combinations on invasive and multidrug-resistant extraintestinal pathogenic Escherichia coli (ExPEC), the Gram-negative bacterium most frequently isolated from the bloodstreams of hospitalized patients. We report that certain antibiotics used at sublethal concentrations display enhanced growth inhibition and/or killing when combined with the iron chelator deferiprone (DFP). Inductively coupled plasma optical emission spectrometry reveals abnormally high levels of cell-associated iron under these conditions, a response that correlates with an iron starvation response and supraphysiologic levels of reactive oxygen species (ROS). The high ROS level is reversed upon the addition of antioxidants, which restores bacterial growth, suggesting that the cells are inhibited or killed by excessive free radicals. A model is proposed in which peptidoglycan-targeting antibiotics facilitate the entry of lethal levels of iron-complexed DFP into the bacterial cytoplasm, a process that drives the generation of ROS. This new finding suggests that, in addition to restriction of access to iron as a general growth-restricting strategy, targeting of cellular pathways or networks that selectively disrupt normal iron homeostasis can have potent bactericidal outcomes. IMPORTANCE The prospect that common bacteria will become resistant to all antibiotics is challenging the medical community. In addition to the development of next-generation antibiotics, new bacterial targets that display cytotoxic properties when altered need to be identified. Data presented here demonstrate that combining subinhibitory levels of both iron chelators and certain antibiotics kills pathogenic Escherichia

Mechanism of the protective effects of the combined treatment with rhynchophylla total alkaloids and sinapine thiocyanate against a prothrombotic state caused by vascular endothelial cell inflammatory damage

PubMed Central

Li, Yunlun; Zhang, Xinya; Yang, Wenqing; Li, Chao; Chu, Yanjun; Jiang, Haiqiang; Shen, Zhenzhen

2017-01-01

The aim of the present study was to investigate the effect and the underlying mechanism of the combined treatment of rhynchophylla total alkaloids (RTA) and sinapine thiocyanate for protection against a prothrombotic state (PTS) associated with the tumor necrosis factor-alpha (TNF-α)-induced inflammatory injury of vascular endothelial cells (VECs). A TNF-α-induced VEC inflammatory injury model was established, and cell morphology of VECs was evaluated using scanning electron microscopy. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein expression of coagulation-related factors, including nuclear factor-κB (NF-κB), transforming growth factor-β1 (TGF-β1), tissue factor (TF), plasminogen activator inhibitor (PAI-1), protease-activation receptors (PAR-1) and protein kinase C (PKC-α) in VECs. Combined treatment with RTA and sinapine thiocyanate was demonstrated to reduce, to a varying extent, the mRNA and protein expression of NF-κB, TGF-β1, TF, PAR-1, PKC-α and PAI-1. Furthermore, combined treatment with RTA and sinapine thiocyanate was able to downregulate the expression of coagulation-related factors in injured VECs, thereby inhibiting the PTS induced by vascular endothelial injury. The underlying mechanism is partially associated with the TF-mediated activation of the thrombin-receptor signaling pathway that suppresses coagulation during inflammation and balances fibrinolysis in order to inhibit fibrin generation and deposition. PMID:28587383

Mechanism of the protective effects of the combined treatment with rhynchophylla total alkaloids and sinapine thiocyanate against a prothrombotic state caused by vascular endothelial cell inflammatory damage.

PubMed

Li, Yunlun; Zhang, Xinya; Yang, Wenqing; Li, Chao; Chu, Yanjun; Jiang, Haiqiang; Shen, Zhenzhen

2017-06-01

The aim of the present study was to investigate the effect and the underlying mechanism of the combined treatment of rhynchophylla total alkaloids (RTA) and sinapine thiocyanate for protection against a prothrombotic state (PTS) associated with the tumor necrosis factor-alpha (TNF-α)-induced inflammatory injury of vascular endothelial cells (VECs). A TNF-α-induced VEC inflammatory injury model was established, and cell morphology of VECs was evaluated using scanning electron microscopy. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein expression of coagulation-related factors, including nuclear factor-κB (NF-κB), transforming growth factor-β1 (TGF-β1), tissue factor (TF), plasminogen activator inhibitor (PAI-1), protease-activation receptors (PAR-1) and protein kinase C (PKC-α) in VECs. Combined treatment with RTA and sinapine thiocyanate was demonstrated to reduce, to a varying extent, the mRNA and protein expression of NF-κB, TGF-β1, TF, PAR-1, PKC-α and PAI-1. Furthermore, combined treatment with RTA and sinapine thiocyanate was able to downregulate the expression of coagulation-related factors in injured VECs, thereby inhibiting the PTS induced by vascular endothelial injury. The underlying mechanism is partially associated with the TF-mediated activation of the thrombin-receptor signaling pathway that suppresses coagulation during inflammation and balances fibrinolysis in order to inhibit fibrin generation and deposition.

Nasal inhalation of butorphanol in combination with ketamine quickly elevates the mechanical pain threshold in the model of chronic constriction injury to the sciatic nerve of rat.

PubMed

Chen, Feng; Wang, LiQin; Chen, ShuJun; Li, ZhiGao; Chen, ZhouLin; Zhou, XinHua; Zhai, Dong

2014-01-01

The aim of the present study is to explore the impact of butorphanol in combination with ketamine via nasal inhalation (NI) on neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve in a rat model. CCI rats (n = 12) were equally randomized to four groups based on the treatments received as follows: 100 μL of 0.9% normal saline via NI (NS/NI group); 100 μg of butorphanol plus 1 mg of ketamine via NI (B + K/NI group); 100 μg of butorphanol alone via NI (B/NI group); and 100 μg of butorphanol plus 1 mg of ketamine via subcutaneous injection (B + K/SC group). Mechanical pain threshold was measured at 10 min, 30 min, 2 h, 4 h, and 6 h after drug administration. The mechanical pain threshold in the B + K/NI group was improved significantly 4 h after drug administration as compared with that in the B/NI or B + K/SC group (P < 0.05). The onset and intensity of drug action in the B + K/NI group were better than those of the other two groups, but the duration of drug action was not prolonged. NI of butorphanol in combination with ketamine quickly elevates the mechanical pain threshold in a rat neuropathic pain model induced by CCI to the sciatic nerve. Copyright © 2014 Elsevier Inc. All rights reserved.

Carotid artery stenting versus no stenting assisting thrombectomy for acute ischaemic stroke: protocol for a systematic review of randomised clinical trials with meta-analyses and trial sequential analyses.

PubMed

Steglich-Arnholm, Henrik; Holtmannspötter, Markus; Gluud, Christian; Krieger, Derk Wolfgang

2016-12-01

In patients with intracranial large vessel arterial occlusion, ipsilateral extracranial carotid artery occlusions or near-occlusions pose a significant hurdle in endovascular management of acute ischaemic stroke. Stenting of the carotid lesion may be beneficial in this situation to provide a stable access for introducing catheters through the carotid lesion into the intracranial vasculature and the target occlusion. Furthermore, carotid stenting may ensure ample blood flow for wash-out of clot material and reperfusion of the ischaemic penumbral tissue. However, antiplatelet therapy administered to prevent stent thrombosis and sudden increase in blood flow after reopening of the carotid lesion may increase the risk for intracranial haemorrhagic complications. This review aims to assess the benefits and harms of carotid stenting vs. no stenting assisting thrombectomy for acute ischaemic stroke. International and regional electronic databases will be searched to identify eligible randomised clinical trials. To identify further published, unpublished, or on-going and planned trials searches of Google Scholar, Worldwide Food and Drug Administrations, Worldwide Medicines Agencies, company homepages, reference lists, conference proceedings, and the Science Citation Index cited reference search index will be conducted. Manufacturers of relevant interventional equipment, authors, colleagues, and researchers active in the field will be contacted. No language restrictions will be applied to these searches. Randomised clinical trials will be included for assessing benefits and harms and quasi-randomised studies, and observational studies will be included for assessing harms of the intervention. Meta-analyses will be performed according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, and Trial Sequential Analyses will be conducted to control the risk of random errors and prevent premature statements of superiority of the experimental or

COMBINE genetics study: the pharmacogenetics of alcoholism treatment response: genes and mechanisms.

PubMed

Goldman, David; Oroszi, Gabor; O'Malley, Stephanie; Anton, Raymond

2005-07-01

Partial efficacy of treatment and differences in adverse events across individuals are a challenge and an opportunity in the treatment of alcoholism. Individuation of therapy and understanding origins of differential treatment response may require identification of inherited functional variants of genes. The neurobiology of reward, executive cognitive function, anxiety and dysphoria have been identified as critical domains that may have a genetic basis that could predict treatment response. The COMBINE Study presents a unique opportunity to evaluate specific genetic loci (markers) that affect neurobiology central to addiction and extended withdrawal. The study also addresses variation in drug metabolism and action. Candidate genetic markers are selected for study based on functionality and abundance. COMT Vall58Met is a common (minor allele frequency 0.42), functional, catecholamine-metabolizing enzyme polymorphism with threefold relevance. Vall58Met alters executive cognitive function, stress and anxiety responses and brain endogenous opioid function. OPRM1 Asn40Asp is a common (minor allele frequency 0.10), functional polymorphism of the mu-opioid receptor, which may serve as a gatekeeper molecule in naltrexone's actions and was recently reported to affect naltrexone response. HTTLPR (minor allele frequency 0.40) alters serotonin transporter function to affect anxiety, dysphoria and obsessional behavior, which are assessed in COMBINE and may be related to relapse and addictive behavior. All genetic testing is consented through a separate human research protocol, and the testing is conducted nonclinically, confidentially and apart from the clinical record to protect human research participants who have volunteered for this aspect of COMBINE.

Diffusion-weighted imaging score of the brain stem: A predictor of outcome in acute basilar artery occlusion treated with the Solitaire FR device.

PubMed

Mourand, I; Machi, P; Nogué, E; Arquizan, C; Costalat, V; Picot, M-C; Bonafé, A; Milhaud, D

2014-06-01

The prognosis for ischemic stroke due to acute basilar artery occlusion is very poor: Early recanalization remains the main factor that can improve outcomes. The baseline extent of brain stem ischemic damage can also influence outcomes. We evaluated the validity of an easy-to-use DWI score to predict clinical outcome in patients with acute basilar artery occlusion treated by mechanical thrombectomy. We analyzed the baseline clinical and DWI parameters of 31 patients with acute basilar artery occlusion, treated within 24 hours of symptom onset by using a Solitaire FR device. The DWI score of the brain stem was assessed with a 12-point semiquantitative score that separately considered each side of the medulla, pons, and midbrain. Clinical outcome was assessed at 180 days by using the mRS. According to receiver operating characteristic analyses, the cutoff score determined the optimal positive predictive value for outcome. The Spearman rank correlation coefficient assessed the correlation between the DWI brain stem score and baseline characteristics. Successful recanalization (Thrombolysis in Cerebral Infarction 3-2b) was achieved in 23 patients (74%). A favorable outcome (mRS ≤ 2) was observed in 11 patients (35%). An optimal DWI brain stem score of <3 predicted a favorable outcome. The probability of a very poor outcome (mRS ≥ 5) if the DWI brain stem score was ≥5 reached 80% (positive predictive value) and 100% if this score was ≥6. Interobserver reliability of the DWI brain stem score was excellent, with an intraclass correlation coefficient of 0.97 (95% CI, 0.96-0.99). The DWI brain stem score was significantly associated with baseline tetraplegia (P = .001) and coma (P = .005). In patients with acute basilar artery occlusion treated by mechanical thrombectomy, the baseline DWI brain lesion score seems to predict clinical outcome. © 2014 by American Journal of Neuroradiology.

Electronic door locking mechanism

DOEpatents

Williams, Gary Lin; Kirby, Patrick Gerald

1997-01-01

The invention is a motorized linkage for engaging a thumb piece in a door mechanism. The device has an exterior lock assembly with a small battery cell and combination lock. Proper entry by a user of a security code allows the battery to operate a small motor within the exterior lock assembly. The small motor manipulates a cam-plunger which moves an actuator pin into a thumb piece. The user applies a force on to the thumb piece. This force is transmitted by the thumb piece to a latch engagement mechanism by the actuator pin. The latch engagement mechanism operates the door latch.

Bidirectional Drive-And-Brake Mechanism

NASA Technical Reports Server (NTRS)

Swan, Scott A.

1991-01-01

Vehicle that crawls along monorail combines features of both bicycle and railroad handcar. Bidirectional drive-and-brake mechanism includes selectable-pawl-and-ratchet overrunning clutch (drive mechanism) and mating stationary and rotating conical surfaces pressing against each other (brake mechanism). Operates similarly to bicycle drive-and-brake mechanism except limits rotation of sprocket in both directions and brakes at both limits. Conceived for use by astronaut traveling along structure in outer space, concept also applied on Earth to make very small railraod handcars or crawling vehicles for use on large structures, in pipelines under construction, or underwater.

Fracture Mechanics Analyses of Subsurface Defects in Reinforced Carbon-Carbon Joggles Subjected to Thermo-Mechanical Loads

NASA Technical Reports Server (NTRS)

Knight, Norman F., Jr.; Raju, Ivatury S.; Song, Kyongchan

2011-01-01

Coating spallation events have been observed along the slip-side joggle region of the Space Shuttle Orbiter wing-leading-edge panels. One potential contributor to the spallation event is a pressure build up within subsurface voids or defects due to volatiles or water vapor entrapped during fabrication, refurbishment, or normal operational use. The influence of entrapped pressure on the thermo-mechanical fracture-mechanics response of reinforced carbon-carbon with subsurface defects is studied. Plane-strain simulations with embedded subsurface defects are performed to characterize the fracture mechanics response for a given defect length when subjected to combined elevated-temperature and subsurface-defect pressure loadings to simulate the unvented defect condition. Various subsurface defect locations of a fixed-length substrate defect are examined for elevated temperature conditions. Fracture mechanics results suggest that entrapped pressure combined with local elevated temperatures have the potential to cause subsurface defect growth and possibly contribute to further material separation or even spallation. For this anomaly to occur, several unusual circumstances would be required making such an outcome unlikely but plausible.

Thermal and mechanical high-intensity focused ultrasound: perspectives on tumor ablation, immune effects and combination strategies.

PubMed

van den Bijgaart, Renske J E; Eikelenboom, Dylan C; Hoogenboom, Martijn; Fütterer, Jurgen J; den Brok, Martijn H; Adema, Gosse J

2017-02-01

Tumor ablation technologies, such as radiofrequency-, cryo- or high-intensity focused ultrasound (HIFU) ablation will destroy tumor tissue in a minimally invasive manner. Ablation generates large volumes of tumor debris in situ, releasing multiple bio-molecules like tumor antigens and damage-associated molecular patterns. To initiate an adaptive antitumor immune response, antigen-presenting cells need to take up tumor antigens and, following activation, present them to immune effector cells. The impact of the type of tumor ablation on the precise nature, availability and suitability of the tumor debris for immune response induction, however, is poorly understood. In this review, we focus on immune effects after HIFU-mediated ablation and compare these to findings using other ablation technologies. HIFU can be used both for thermal and mechanical destruction of tissue, inducing coagulative necrosis or subcellular fragmentation, respectively. Preclinical and clinical results of HIFU tumor ablation show increased infiltration and activation of CD4 + and CD8 + T cells. As previously observed for other types of tumor ablation technologies, however, this ablation-induced enhanced infiltration alone appears insufficient to generate consistent protective antitumor immunity. Therapies combining ablation with immune stimulation are therefore expected to be key to boost HIFU-induced immune effects and to achieve systemic, long-lasting, antitumor immunity.

Cell mechanics: a dialogue.

PubMed

Tao, Jiaxiang; Li, Yizeng; Vig, Dhruv K; Sun, Sean X

2017-03-01

Under the microscope, eukaryotic animal cells can adopt a variety of different shapes and sizes. These cells also move and deform, and the physical mechanisms driving these movements and shape changes are important in fundamental cell biology, tissue mechanics, as well as disease biology. This article reviews some of the basic mechanical concepts in cells, emphasizing continuum mechanics description of cytoskeletal networks and hydrodynamic flows across the cell membrane. We discuss how cells can generate movement and shape changes by controlling mass fluxes at the cell boundary. These mass fluxes can come from polymerization/depolymerization of actin cytoskeleton, as well as osmotic and hydraulic pressure-driven flow of water across the cell membrane. By combining hydraulic pressure control with force balance conditions at the cell surface, we discuss a quantitative mechanism of cell shape and volume control. The broad consequences of this model on cell mechanosensation and tissue mechanics are outlined.

Cell mechanics: a dialogue

NASA Astrophysics Data System (ADS)

Tao, Jiaxiang; Li, Yizeng; Vig, Dhruv K.; Sun, Sean X.

2017-03-01

Under the microscope, eukaryotic animal cells can adopt a variety of different shapes and sizes. These cells also move and deform, and the physical mechanisms driving these movements and shape changes are important in fundamental cell biology, tissue mechanics, as well as disease biology. This article reviews some of the basic mechanical concepts in cells, emphasizing continuum mechanics description of cytoskeletal networks and hydrodynamic flows across the cell membrane. We discuss how cells can generate movement and shape changes by controlling mass fluxes at the cell boundary. These mass fluxes can come from polymerization/depolymerization of actin cytoskeleton, as well as osmotic and hydraulic pressure-driven flow of water across the cell membrane. By combining hydraulic pressure control with force balance conditions at the cell surface, we discuss a quantitative mechanism of cell shape and volume control. The broad consequences of this model on cell mechanosensation and tissue mechanics are outlined.

Cardiopulmonary effects of administration of a combination solution of xylazine, guaifenesin, and ketamine or inhaled isoflurane in mechanically ventilated calves.

PubMed

Kerr, Carolyn L; Windeyer, Claire; Bouré, Ludovic P; Mirakhur, Kuldip K; McDonell, Wayne

2007-12-01

To compare the cardiopulmonary effects of administration of a solution of xylazine, guaifenesin, and ketamine (XGK) or inhaled isoflurane in mechanically ventilated calves undergoing surgery. 13 male calves 2 to 26 days of age. Procedures-In calves in the XGK group, anesthesia was induced (0.5 mL/kg) and maintained (2.5 mL/kg/h) with a combination solution of xylazine (0.1 mg/mL), guaifenesin (50 mg/mL), and ketamine (1.0 mg/mL). For calves in the isoflurane group, anesthesia was induced and maintained with isoflurane in oxygen. The rates of XGK infusion and isoflurane administration were adjusted to achieve suitable anesthetic depth. All calves received 100% oxygen and were mechanically ventilated to maintain end-tidal carbon dioxide concentrations from 35 to 40 mm Hg and underwent laparoscopic bladder surgery through an abdominal approach. Cardiopulmonary variables were measured before induction and at intervals up to 90 minutes after anesthetic induction. The quality of induction was excellent in all calves. The XGK requirements were 0.57 +/- 0.18 mL/kg and 2.70 +/- 0.40 mL/kg/h to induce and maintain anesthesia, respectively. Heart rate was significantly lower than baseline throughout the anesthetic period in the XGK group. Systolic arterial blood pressure was significantly higher in the XGK group, compared with the isoflurane group, from 5 to 90 minutes. Cardiac index was lower than baseline in both groups. Differences between groups in cardiac index and arterial blood gas values were not significant. Administration of XGK resulted in excellent anesthetic induction and maintenance with cardiopulmonary alterations similar to those associated with isoflurane in mechanically ventilated calves.

Evolution of endovascular stroke therapies and devices.

PubMed

Wallace, Adam N; Kansagra, Akash P; McEachern, James; Moran, Christopher J; Cross, Dewitte T; Derdeyn, Colin P

2016-01-01

Acute ischemic stroke is caused by occlusion of a cerebral artery, resulting in loss of brain tissue and neurologic deficits. However, a portion of the ischemic brain can be salvaged if blood flow is restored within an appropriate time frame. The past year has seen the publication of five positive randomized controlled trials demonstrating substantial benefit of mechanical thrombectomy in select patients with large vessel cerebrovascular occlusion. This progress is related to several factors, but most importantly, dramatic improvements in speed and rates of recanalization with the latest generation devices. In this article, we review the evolution of endovascular acute ischemic stroke therapies and key design features of the most widely used devices.

Preparation for Testing a Multi-Bay Box Subjected to Combined Loads

NASA Technical Reports Server (NTRS)

Rouse, Marshall; Jegley, Dawn

2015-01-01

The COmbined Loads Test System (COLTS) facility at NASA Langley Research Center provides a test capability to help develop validated structures technologies. The test machine was design to accommodate a range of fuselage structures and wing sections and subject them to both quasistatic and cyclic loading conditions. The COLTS facility is capable of testing fuselage barrels up to 4.6 m in diameter and 13.7 m long with combined mechanical, internal pressure, and thermal loads. The COLTS facility is currently being prepared to conduct a combined mechanical and pressure loading for a multi-bay pressure box to experimentally verify the structural performance of a composite structure which is 9.1 meters long and representative of a section of a hybrid wing body fuselage section in support of the Environmentally Responsible Aviation Project at NASA. This paper describes development of the multi-bay pressure box test using the COLTS facility. The multi-bay test article will be subjected to mechanical loads and internal pressure loads up to design ultimate load. Mechanical and pressure loads will be applied independently in some tests and simultaneously in others.

Radiation Combined Injury: DNA Damage, Apoptosis, and Autophagy

DTIC Science & Technology

2010-01-01

combined injured-mice, Bacillus and Lactobacillus were isolated within the first 8 d after radiation combined injury. The data imply that mice...Gy followed immediately by 15% total body surface skin-wound trauma. Ileal lysates were prepared 7 d after sham-treatment (Sham), wound- ing (Wound...secretion and increased risk of infection; and ( d ) delayed wound healing—often double the healing time of wounding alone. Since the mechanisms of

Electronic door locking mechanism

DOEpatents

Williams, G.L.; Kirby, P.G.

1997-10-21

The invention is a motorized linkage for engaging a thumb piece in a door mechanism. The device has an exterior lock assembly with a small battery cell and combination lock. Proper entry by a user of a security code allows the battery to operate a small motor within the exterior lock assembly. The small motor manipulates a cam-plunger which moves an actuator pin into a thumb piece. The user applies a force on to the thumb piece. This force is transmitted by the thumb piece to a latch engagement mechanism by the actuator pin. The latch engagement mechanism operates the door latch. 6 figs.

Enhancing anaerobic digestion of waste activated sludge by the combined use of NaOH and Mg(OH)2: Performance evaluation and mechanism study.

PubMed

Huang, Cheng; Lai, Jia; Sun, Xiuyun; Li, Jiansheng; Shen, Jinyou; Han, Weiqing; Wang, Lianjun

2016-11-01

In this study, the combination treatment of NaOH and Mg(OH)2 was applied to anaerobic digestion of waste activated sludge (WAS) for simultaneously enhancement of volatile fatty acids (VFAs) production, nutrients removal and sludge dewaterability. The maximum VFAs production (461mg COD/g VSS) was obtained at the NaOH/Mg(OH)2 ratio of 75:25, which was much higher than that of the blank or sole NaOH. Moreover, nutrients removal and sludge dewaterability were improved by the combined using of NaOH and Mg(OH)2. Mechanism investigations revealed that the presence of Mg(OH)2 could maintain alkaline environment, which contributed to inhibit the activity of methanogens. Also, the bridging between Mg(2+) and extracellular polymeric substances (EPS) plays an important role in the solubilization and dewatering of sludge. High-throughput sequencing analysis demonstrated that the abundance of bacteria involved in sludge hydrolysis and VFAs accumulation was greatly enriched with the mixtures of NaOH and Mg(OH)2. Copyright © 2016 Elsevier Ltd. All rights reserved.

Computational Biochemistry-Enzyme Mechanisms Explored.

PubMed

Culka, Martin; Gisdon, Florian J; Ullmann, G Matthias

2017-01-01

Understanding enzyme mechanisms is a major task to achieve in order to comprehend how living cells work. Recent advances in biomolecular research provide huge amount of data on enzyme kinetics and structure. The analysis of diverse experimental results and their combination into an overall picture is, however, often challenging. Microscopic details of the enzymatic processes are often anticipated based on several hints from macroscopic experimental data. Computational biochemistry aims at creation of a computational model of an enzyme in order to explain microscopic details of the catalytic process and reproduce or predict macroscopic experimental findings. Results of such computations are in part complementary to experimental data and provide an explanation of a biochemical process at the microscopic level. In order to evaluate the mechanism of an enzyme, a structural model is constructed which can be analyzed by several theoretical approaches. Several simulation methods can and should be combined to get a reliable picture of the process of interest. Furthermore, abstract models of biological systems can be constructed combining computational and experimental data. In this review, we discuss structural computational models of enzymatic systems. We first discuss various models to simulate enzyme catalysis. Furthermore, we review various approaches how to characterize the enzyme mechanism both qualitatively and quantitatively using different modeling approaches. © 2017 Elsevier Inc. All rights reserved.

Cell mechanics: a dialogue

PubMed Central

Tao, Jiaxiang; Li, Yizeng; Vig, Dhruv K; Sun, Sean X

2017-01-01

Under the microscope, eukaryotic animal cells can adopt a variety of different shapes and sizes. These cells also move and deform, and the physical mechanisms driving these movements and shape changes are important in fundamental cell biology, tissue mechanics, as well as disease biology. This article reviews some of the basic mechanical concepts in cells, emphasizing continuum mechanics description of cytoskeletal networks and hydrodynamic flows across the cell membrane. We discuss how cells can generate movement and shape changes by controlling mass fluxes at the cell boundary. These mass fluxes can come from polymerization/depolymerization of actin cytoskeleton, as well as osmotic and hydraulic pressure-driven flow of water across the cell membrane. By combining hydraulic pressure control with force balance conditions at the cell surface, we discuss a quantitative mechanism of cell shape and volume control. The broad consequences of this model on cell mechanosensation and tissue mechanics are outlined. PMID:28129208

Cerebral Venous Congestion as Indication for Thrombolytic Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsai, Fong Y., E-mail: ftsai@uci.edu; Kostanian, Varoujan; Rivera, Monica

Purpose. To carry out a retrospective analysis of patients with acute dural sinus thrombosis, and the role of cerebral venous congestion in patient management. Methods. Twenty-five patients were identified with the clinical and imaging diagnosis of acute dural sinus thrombosis. The imaging diagnosis was by magnetic resonance (MR) and/or computed tomography (CT) venography. There was a female predominance with a female to male ratio of 1.5 to 1 (16 women, 9 men). The age range was from 19 to 64 years old with an average age of 37 years. The first 10 patients, who ranged in age from 21 tomore » 64 years old (average 37 years), received only anticoagulation therapy with heparin and warfarin for periods ranging from 5 days to 2 months. The remaining 15 patients ranged in age from 19 to 57 years old (average 38 years). They either underwent subsequent thrombectomy after a trial of anticoagulation therapy, or went straight to thrombectomy. These latter 15 patients had initial evidence of cerebral venous congestion, either clinically by severe or worsening symptoms despite anticoagulation therapy, or on initial or subsequent CT or MR imaging. In our experience, the cerebral venous congestion imaging findings included intracranial hemorrhage, a hematoma, or edema. The thrombolytic treatment technique consisted of the advancement of a 6 Fr guiding catheter to the jugular bulb or sigmoid sinus from a transfemoral approach. A microcatheter was then advanced to the proximal portion of the thrombus and then either tissue plasminogen activator (tPA) or urokinase was injected to prevent clot propagation. A balloon catheter was used to perform thrombectomy since the thrombolytic agents can be injected via the inner lumen with an inflated balloon. The inflated balloon helped to keep the venous flow from washing out the thrombolytic agent, thus facilitating the agent's effect. Results. The first 10 patients received only anticoagulation therapy with heparin and warfarin for

Combined in vivo and ex vivo analysis of mesh mechanics in a porcine hernia model.

PubMed

Kahan, Lindsey G; Lake, Spencer P; McAllister, Jared M; Tan, Wen Hui; Yu, Jennifer; Thompson, Dominic; Brunt, L Michael; Blatnik, Jeffrey A

2018-02-01

Hernia meshes exhibit variability in mechanical properties, and their mechanical match to tissue has not been comprehensively studied. We used an innovative imaging model of in vivo strain tracking and ex vivo mechanical analysis to assess effects of mesh properties on repaired abdominal walls in a porcine model. We hypothesized that meshes with dissimilar mechanical properties compared to native tissue would alter abdominal wall mechanics more than better-matched meshes. Seven mini-pigs underwent ventral hernia creation and subsequent open repair with one of two heavyweight polypropylene meshes. Following mesh implantation with attached radio-opaque beads, fluoroscopic images were taken at insufflation pressures from 5 to 30 mmHg on postoperative days 0, 7, and 28. At 28 days, animals were euthanized and ex vivo mechanical testing performed on full-thickness samples across repaired abdominal walls. Testing was conducted on 13 mini-pig controls, and on meshes separately. Stiffness and anisotropy (the ratio of stiffness in the transverse versus craniocaudal directions) were assessed. 3D reconstructions of repaired abdominal walls showed stretch patterns. As pressure increased, both meshes expanded, with no differences between groups. Over time, meshes contracted 17.65% (Mesh A) and 0.12% (Mesh B; p = 0.06). Mesh mechanics showed that Mesh A deviated from anisotropic native tissue more than Mesh B. Compared to native tissue, Mesh A was stiffer both transversely and craniocaudally. Explanted repaired abdominal walls of both treatment groups were stiffer than native tissue. Repaired tissue became less anisotropic over time, as mesh properties prevailed over native abdominal wall properties. This technique assessed 3D stretch at the mesh level in vivo in a porcine model. While the abdominal wall expanded, mesh-ingrown areas contracted, potentially indicating stresses at mesh edges. Ex vivo mechanics demonstrate that repaired tissue adopts mesh properties, suggesting

4. INTERIOR OF DRAFT REGULATOR & MIXING DAMPER COMBINATION. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. INTERIOR OF DRAFT REGULATOR & MIXING DAMPER COMBINATION. - Hot Springs National Park, Bathhouse Row, Lamar Bathhouse: Mechanical & Piping Systems, State Highway 7, 1 mile north of U.S. Highway 70, Hot Springs, Garland County, AR

Factors Influencing the Learning of Classical Mechanics.

ERIC Educational Resources Information Center

Champagne, Audrey B.; And Others

1980-01-01

Describes a study investigating the combined effect of certain variables on student achievement in classical mechanics. The purpose was to (1) describe preinstructional knowledge and skills; (2) correlate these variables with the student's success in learning classical mechanics; and (3) develop hypothesis about relationships between these…

Mechanical stability of heat-treated nanoporous anodic alumina subjected to repetitive mechanical deformation

NASA Astrophysics Data System (ADS)

Bankova, A.; Videkov, V.; Tzaneva, B.; Mitov, M.

2018-03-01

We report studies on the mechanical response and deformation behavior of heat-treated nanoporous anodic alumina using a micro-balance test and experimental test equipment especially designed for this purpose. AAO samples were characterized mechanically by a three-point bending test using a micro-analytical balance. The deformation behavior was studied by repetitive mechanical bending of the AAO membranes using an electronically controlled system. The nanoporous AAO structures were prepared electrochemically from Al sheet substrates using a two-step anodizing technique in oxalic acid followed by heat treatment at 700 °C in air. The morphological study of the aluminum oxide layer after the mechanical tests and mechanical deformation was conducted using scanning electron and optical microscopy, respectively. The experimental results showed that the techniques proposed are simple and accurate; they could, therefore, be combined to constitute a method for mechanical stability assessment of nanostructured AAO films, which are important structural components in the design of MEMS devices and sensors.

Alpha-lipoic acid alone and combined with clozapine reverses schizophrenia-like symptoms induced by ketamine in mice: Participation of antioxidant, nitrergic and neurotrophic mechanisms.

PubMed

Vasconcelos, Germana Silva; Ximenes, Naiara Coelho; de Sousa, Caren Nádia Soares; Oliveira, Tatiana de Queiroz; Lima, Laio Ladislau Lopes; de Lucena, David Freitas; Gama, Clarissa Severino; Macêdo, Danielle; Vasconcelos, Silvânia Maria Mendes

2015-07-01

Oxidative stress has important implications in schizophrenia. Alpha-lipoic acid (ALA) is a natural antioxidant synthesized in human tissues with clinical uses. We studied the effect of ALA or clozapine (CLZ) alone or in combination in the reversal of schizophrenia-like alterations induced by ketamine (KET). Adult male mice received saline or KET for 14 days. From 8th to 14th days mice were additionally administered saline, ALA (100 mg/kg), CLZ 2.5 or 5 mg/kg or the combinations ALA+CLZ2.5 or ALA+CLZ5. Schizophrenia-like symptoms were evaluated by prepulse inhibition of the startle (PPI) and locomotor activity (positive-like), social preference (negative-like) and Y maze (cognitive-like). Oxidative alterations (reduced glutathione - GSH and lipid peroxidation - LP) and nitrite in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) and BDNF in the PFC were also determined. KET caused deficits in PPI, working memory, social interaction and hyperlocomotion. Decreased levels of GSH, nitrite (HC) and BDNF and increased LP were also observed in KET-treated mice. ALA and CLZ alone reversed KET-induced behavioral alterations. These drugs also reversed the decreases in GSH (HC) and BDNF and increase in LP (PFC, HC and ST). The combination ALA+CLZ2.5 reversed behavioral and some neurochemical parameters. However, ALA+CLZ5 caused motor impairment. Therefore, ALA presented an antipsychotic-like profile reversing KET-induced positive- and negative-like symptoms. The mechanism partially involves antioxidant, neurotrophic and nitrergic pathways. The combination of ALA+CLZ2.5 improved most of the parameters evaluated in this study without causing motor impairment demonstrating, thus, that possibly when combined with ALA a lower dose of CLZ is required. Copyright © 2015 Elsevier B.V. All rights reserved.

Analysis of the new code stroke protocol in Asturias after one year. Experience at one hospital.

PubMed

García-Cabo, C; Benavente, L; Martínez-Ramos, J; Pérez-Álvarez, Á; Trigo, A; Calleja, S

2018-03-01

Prehospital code stroke (CS) systems have been proved effective for improving access to specialised medical care in acute stroke cases. They also improve the prognosis of this disease, which is one of the leading causes of death and disability in our setting. The aim of this study is to analyse results one year after implementation of the new code stroke protocol at one hospital in Asturias. We prospectively included patients who were admitted to our tertiary care centre as per the code stroke protocol for the period of one year. We analysed 363 patients. Mean age was 69 years and 54% of the cases were men. During the same period in the previous year, there were 236 non-hospital CS activations. One hundred forty-seven recanalisation treatments were performed (66 fibrinolysis and 81 mechanical thrombectomies or combined treatments), representing a 25% increase with regard to the previous year. Recent advances in the management of acute stroke call for coordinated code stroke protocols that are adapted to the needs of each specific region. This may result in an increased number of patients receiving early care, as well as revascularisation treatments. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

ELECTROMAGNETIC RELEASE MECHANISM

DOEpatents

Michelson, C.

1960-09-13

An electromagnetic release mechanism is offered that may be used, for example, for supporting a safety rod for a nuclear reactor. The release mechanism is designed to have a large excess holding force and a rapid, uniform, and dependable release. The fast release is accomplished by providing the electromagnet with slotttd polts separated by an insulating potting resin, and by constructing the poles with a ferro-nickel alloy. The combination of these two features materially reduces the eddy current power density whenever the magnetic field changes during a release operation. In addition to these features, the design of the armature is such as to provide ready entrance of fluid into any void that might tend to form during release of the armature. This also improves the release time for the mechanism. The large holding force for the mechanism is accomplished by providing a small, selected, uniform air gap between the inner pole piece and the armature.