Stabilization of subcritical bypass transition in the leading-edge boundary layer by suction

This work investigates the subcritical spatial transition in the swept Hiemenz boundary layer by means of direct numerical simulations (DNS). A pair of steady co-rotating vortices located at the attachment line is enforced as a primary disturbance leading to streaks which are stable. A small secondary, time-dependent disturbance interacts with these streaks such that instability and breakdown to turbulence may occur. The instability only occurs for a certain band of secondary disturbance frequencies. Positive secondary instability growth rates could be observed for Reynolds numbers as low as , whereas the linear critical Reynolds number is. Uniform wall suction is shown to stabilise this transition mechanism, analogously to results from linear stability theory. The effects of suction on the formation of primary streaks and on the secondary growth rate are decoupled. For streaks of different suction whose amplitude is held constant by adjusting the Reynolds number, the suction is shown to increase the growth rate of the secondary instability. The stabilising influence of wall suction consists in decreasing the streak amplitude only. Depending on the Reynolds number and the suction strength, breakdown may either occur locally and may be convected along the far-field streamlines, or occur globally and cover broad regions in the downstream direction.

Prediction of Post-Weaning Fibrinogen Status during Cardiopulmonary Bypass: An Observational Study in 110 Patients.

BACKGROUND After cardiac surgery with cardiopulmonary bypass (CPB), acquired coagulopathy often leads to post-CPB bleeding. Though multifactorial in origin, this coagulopathy is often aggravated by deficient fibrinogen levels. OBJECTIVE To assess whether laboratory and thrombelastometric testing on CPB can predict plasma fibrinogen immediately after CPB weaning. PATIENTS / METHODS This prospective study in 110 patients undergoing major cardiovascular surgery at risk of post-CPB bleeding compares fibrinogen level (Clauss method) and function (fibrin-specific thrombelastometry) in order to study the predictability of their course early after termination of CPB. Linear regression analysis and receiver operating characteristics were used to determine correlations and predictive accuracy. RESULTS Quantitative estimation of post-CPB Clauss fibrinogen from on-CPB fibrinogen was feasible with small bias (+0.19 g/l), but with poor precision and a percentage of error >30%. A clinically useful alternative approach was developed by using on-CPB A10 to predict a Clauss fibrinogen range of interest instead of a discrete level. An on-CPB A10 ≤10 mm identified patients with a post-CPB Clauss fibrinogen of ≤1.5 g/l with a sensitivity of 0.99 and a positive predictive value of 0.60; it also identified those without a post-CPB Clauss fibrinogen <2.0 g/l with a specificity of 0.83. CONCLUSIONS When measured on CPB prior to weaning, a FIBTEM A10 ≤10 mm is an early alert for post-CPB fibrinogen levels below or within the substitution range (1.5-2.0 g/l) recommended in case of post-CPB coagulopathic bleeding. This helps to minimize the delay to data-based hemostatic management after weaning from CPB.

Cardiopulmonary Bypass has No Significant Impact on Survival in Patients Undergoing Nephrectomy and Level III-IV Inferior Vena Cava Thrombectomy. A Multi-Institutional Analysis.

PURPOSE The impact of cardiopulmonary bypass in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We determine the impact of cardiopulmonary bypass on overall and cancer specific survival, as well as surgical complication rates and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without cardiopulmonary bypass. MATERIALS AND METHODS We retrospectively analyzed 362 patients with renal cell cancer and with level III or IV tumor thrombus from 1992 to 2012 at 22 U.S. and European centers. Cox proportional hazards models were used to compare overall and cancer specific survival between patients with and without cardiopulmonary bypass. Perioperative mortality and complication rates were assessed using logistic regression analyses. RESULTS Median overall survival was 24.6 months in noncardiopulmonary bypass cases and 26.6 months in cardiopulmonary bypass cases. Overall survival and cancer specific survival did not differ significantly in both groups on univariate analysis or when adjusting for known risk factors. On multivariate analysis no significant differences were seen in hospital length of stay, Clavien 1-4 complication rate, intraoperative or 30-day mortality and cancer specific survival. Limitations include the retrospective nature of the study. CONCLUSIONS In our multi-institutional analysis the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality on multivariate analysis. Greater surgical complications were not independently associated with the use of cardiopulmonary bypass.

A review of antithrombotic therapy and the rationale and design of the randomized edoxaban in patients with peripheral artery disease (ePAD) trial adding edoxaban or clopidogrel to aspirin after femoropopliteal endovascular intervention.

Compared with the coronary setting, knowledge about antithrombotic therapies after endovascular treatment (EVT) is inadequate in patients with peripheral artery disease (PAD). Based on a review of trials and guidelines, which is summarized in this article, there is scant evidence that antithrombotic drugs improve outcome after peripheral EVT. To address this knowledge gap, the randomized, open-label, multinational edoxaban in patients with Peripheral Artery Disease (ePAD) study (ClinicalTrials.gov identifier NCT01802775) was designed to explore the safety and efficacy of a combined regimen of antiplatelet therapy with clopidogrel and anticoagulation with edoxaban, a selective and direct factor Xa inhibitor, both combined with aspirin. As of July 2014, 203 patients (144 men; mean age 67 years) from 7 countries have been enrolled. These patients have been allocated to once-daily edoxaban [60 mg for 3 months (or 30 mg in the presence of factors associated with increased exposure)] or clopidogrel (75 mg/d for 3 months). All patients received aspirin (100 mg/d) for the 6-month duration of the study. The primary safety endpoint is major or clinically relevant nonmajor bleeding; the primary efficacy endpoint is restenosis or reocclusion at the treated segment(s) measured at 1, 3, and 6 months using duplex ultrasound scanning. All outcomes will be assessed and adjudicated centrally in a masked fashion. The ePAD study is the first of its kind to investigate a combined regimen of antiplatelet therapy and anticoagulation through factor Xa inhibition with edoxaban.

Synchronous carotid and coronary bypass surgery using minimal extracorporeal circulation does not increase the risk of in-hospital stroke compared to isolated carotid endarterectomy under general anaesthesia

Gebiet: Chirurgie Abstract: Introduction: Carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) could be approached in a combined or a staged fashion. Some crucial studies have shown no significant difference in peri-operative stroke and death rate in combined versus staged CEA/CABG. At present conventional extracorporeal circulation (CECC) is regarded as the gold standard for performing on-pump coronary artery bypass grafting. On contrary, the use of minimized extracorporeal circulation (MECC) for CABG diminishes hemodilution, blood-air contact, foreign surface contact and inflammatory response. At the same time, general anaesthesia (GA) is a potential risk factor for higher perioperative stroke rate after isolated CEA, not only for the ipsilateral but also for the contralateral side especially in case of contralateral high-grade stenosis or occlusion. The aim of the study was to analyze if synchronous CEA/CABG using MECC (CEA/CABG group) allows reducing the perioperative stroke risk to the level of isolated CEA performed under GA (CEA-GA group). – Methods: A retrospective analysis of all patients who underwent CEA at our institution between January 2005 and December 2012 was performed. We compared outcomes between all patients undergoing CEA/CABG to all isolated CEA-GA during the same time period. The CEA/CABG group was additionally compared to a reference group consisting of patients undergoing isolated CEA in local anaesthesia. Primary outcome was in-hospital stroke. – Results: A total of 367 CEAs were performed, from which 46 patients were excluded having either off-pump CABG or other cardiac surgery procedures than CABG combined with CEA. Out of 321 patients, 74 were in the CEA/CABG and 64 in the CEA-GA group. There was a significantly higher rate of symptomatic stenoses among patients in the CEA-GA group (p<0.002). Three (4.1%) strokes in the CEA/CABG group were registered, two ipsilateral (2.7%) and one contralateral (1.4%) to the operated side. In the CEA-GA group 2 ipsilateral strokes (3.1%) occurred. No difference was noticed between the groups (p=1.000). One patient with stroke in each group had a symptomatic stenosis preoperatively. – Conclusions: Outcome with regard to mortality and neurologic injury is very good in both -patients undergoing CEA alone as well as patients undergoing synchronous CEA and CABG using the MECC system. Although the CEA/CABG group showed slightly increased risk of stroke, it can be considered as combined treatment in particular clinical situations.

Minimized Extracorporeal Circulation does not impair cognitive brain function after coronary artery bypass grafting

Gebiet: Chirurgie Abstract: Minimized Extracorporeal Circulation does not impair cognitive brain function after coronary artery bypass grafting – – Objectives – Objective evaluation of the impact of minimized extracorporeal circulation (MECC) on perioperative cognitive brain function in coronary bypass grafting (CABG) by Electroencephalogram (EEG) P 300 wave event related potentials (ERP) and number connection test ( NCT) as metrics of cognitive function. – – Methods – Cognitive brain function was assessed in 31 patients with a mean age of 65y (Standard Deviation/SD 10) undergoing coronary artery bypass grafting (CABG) by the use of MECC with P300 auditory evoked potentials (peak latencies in milliseconds [ms]) directly prior to intervention, 7 days after and 3 month later. Number connection test (NCT), serving as method of control, was performed simultaneously in all patients. – – Results – Seven days following CABG, cognitive P300 evoked potentials were comparable to preoperative baseline values (vertex [Cz] 376 (SD 11) ms vs. 378 (18) ms, p=0.39, frontal [Fz] 377 (11) vs. 379 (21) ms, p=0.53). Cognitive brain function showed at 3 months compared to baseline values ([Cz] 376 (11) ms vs. 371 (14 ms) p=0.09, [Fz] 377 (11) ms vs. 371 (15) ms, p=0.04. Between the first postoperative measurement and 3 months later, significant improvement was observed ([Cz] 378 (18) ms vs. 371 (14) ms, p=0.03, [Fz] 379 (21) vs. 371 (15) ms, p=0.02). Similar clearly corresponding patterns could be obtained via number connection test. Results could be confirmed in repeated measures analysis of variance for Cz (p = 0.05) and (Fz) results (p = 0.04). – – Conclusions

ADAPTATION OF INTESTINAL MUSCLE IN THE RAT AFTER INTESTINAL BYPASS

After intestinal bypass, the mucosa of the in-continuity segment (ICS) of intestine undergoes adaptive hyperplasia which results in increased absorptive function per length of intestine. In the present study, 70% of the small intestine was bypassed in rats to determine if intestinal muscle also adapts after bypass. To determine the effect of bypass on intestinal transit, a poorly absorbed marker substance was introduced into the orad portion of the ICS or bypassed loop (BL). Significantly less marker (P < 0.05) was passed from the ICS into the colon in 50 minutes in fed rats at 14 days compared to at 3 days after bypass. In 150 minutes there was more marker in the colon of fed rats at 3 and 14 days but not at 35 days after bypass than in control. In the BL, transit was slowed significantly in fed rats at 3 and 35 days and in fasted rats at 3 days but not 35 days after bypass compared to control. The circular muscle from the BL and the distal but not proximal portion of the ICS developed significantly more carbachol-stimulated force in vitro at 35 but not 3 days after bypass compared to unoperated but not sham-operated controls. At 35 days after bypass, the muscle layers had a greater muscle wet weight and protein content compared to both unoperated and sham-operated control in both the proximal and distal portions of the ICS. Similarly, there was more muscle in histological sections of the BL and distal portion of the ICS at 35 days after bypass compared to either control. Nonetheless, at 35 days after bypass actomyosin content as a fraction of muscle weight or total protein content was not different from control. The results support the hypothesis that there was a functional adaptation, i.e. slowed transit in fed rats that allowed more time for absorption. Feeding caused slowed transit in the BL as well as the ICS. Other results suggest that an increased amount of functional muscle formed in the distal portion of the ICS after bypass. ^

Multiple pathways to bypass the enhancer requirement of sigma 54 RNA polymerase: Roles for DNA and protein determinants

Sigma 54 is a required factor for bacterial RNA polymerase to respond to enhancers and directs a mechanism that is a hybrid between bacterial and eukaryotic transcription. Three pathways were found that bypass the enhancer requirement in vitro. These rely on either deletion of the sigma 54 N terminus or destruction of the DNA consensus −12 promoter recognition element or altering solution conditions to favor transient DNA melting. Each of these allows unstable heparin-sensitive pre-initiation complexes to form that can be driven to transcribe in the absence of both enhancer protein and ATP β–γ hydrolysis. These disparate pathways are proposed to have a common basis in that multiple N-terminal contacts may mediate the interactions between the polymerase and the DNA region where melting originates. The results raise possibilities for common features of open complex formation by different RNA polymerases.

Pleiotropic Alterations in Lipid Metabolism in Yeast sac1 Mutants: Relationship to “Bypass Sec14p” and Inositol Auxotrophy

SacIp dysfunction results in bypass of the requirement for phosphatidylinositol transfer protein (Sec14p) function in yeast Golgi processes. This effect is accompanied by alterations in inositol phospholipid metabolism and inositol auxotrophy. Elucidation of how sac1 mutants effect “bypass Sec14p” will provide insights into Sec14p function in vivo. We now report that, in addition to a dramatic accumulation of phosphatidylinositol-4-phosphate, sac1 mutants also exhibit a specific acceleration of phosphatidylcholine biosynthesis via the CDP-choline pathway. This phosphatidylcholine metabolic phenotype is sensitive to the two physiological challenges that abolish bypass Sec14p in sac1 strains; i.e. phospholipase D inactivation and expression of bacterial diacylglycerol (DAG) kinase. Moreover, we demonstrate that accumulation of phosphatidylinositol-4-phosphate in sac1 mutants is insufficient to effect bypass Sec14p. These data support a model in which phospholipase D activity contributes to generation of DAG that, in turn, effects bypass Sec14p. A significant fate for this DAG is consumption by the CDP-choline pathway. Finally, we determine that CDP-choline pathway activity contributes to the inositol auxotrophy of sac1 strains in a novel manner that does not involve obvious defects in transcriptional expression of the INO1 gene.

Two modes of transvection: Enhancer action in trans and bypass of a chromatin insulator in cis

Ed Lewis introduced the term “transvection” in 1954 to describe mechanisms that can cause the expression of a gene to be sensitive to the proximity of its homologue. Transvection since has been reported at an increasing number of loci in Drosophila, where homologous chromosomes are paired in somatic tissues, as well as at loci in other organisms. At the Drosophila yellow gene, transvection can explain intragenic complementation involving the yellow2 allele (y2). Here, transvection was proposed to occur by enhancers of one allele acting in trans on the promoter of a paired homologue. In this report, we describe two yellow alleles that strengthen this model and reveal an unexpected, second mechanism for transvection. Data suggest that, in addition to enhancer action in trans, transvection can occur by enhancer bypass of a chromatin insulator in cis. We propose that bypass results from the topology of paired genes. Finally, transvection at yellow can occur in genotypes not involving y2, implying that it is a feature of yellow itself and not an attribute of one particular allele.

Mechanism of stimulation of the DNA glycosylase activity of hOGG1 by the major human AP endonuclease: bypass of the AP lyase activity step

The generation of reactive oxygen species in the cell provokes, among other lesions, the formation of 8-oxo-7,8-dihydroguanine (8-oxoG) in DNA. Due to mispairing with adenine during replication, 8-oxoG is highly mutagenic. To minimise the mutagenic potential of this oxidised purine, human cells have a specific 8-oxoG DNA glycosylase/AP lyase (hOGG1) that initiates the base excision repair (BER) of 8-oxoG. We show here that in vitro this first enzyme of the BER pathway is relatively inefficient because of a high affinity for the product of the reaction it catalyses (half-life of the complex is >2 h), leading to a lack of hOGG1 turnover. However, the glycosylase activity of hOGG1 is stimulated by the major human AP endonuclease, HAP1 (APE1), the enzyme that performs the subsequent step in BER, as well as by a catalytically inactive mutant (HAP1-D210N). In the presence of HAP1, the AP sites generated by the hOGG1 DNA glycosylase can be occupied by the endonuclease, avoiding the re-association of hOGG1. Moreover, the glycosylase has a higher affinity for a non-cleaved AP site than for the cleaved DNA product generated by HAP1. This would shift the equilibrium towards the free glycosylase, making it available to initiate new catalytic cycles. In contrast, HAP1 does not affect the AP lyase activity of hOGG1. This stimulation of only the hOGG1 glycosylase reaction accentuates the uncoupling of its glycosylase and AP lyase activities. These data indicate that, in the presence of HAP1, the BER of 8-oxoG residues can be highly efficient by bypassing the AP lyase activity of hOGG1 and thus excluding a potentially rate limiting step.