Stent-assisted coiling of bifurcation aneurysms may improve endovascular treatment: a critical evaluation in an experimental model.

BACKGROUND AND PURPOSE: Endovascular treatment of wide-neck bifurcation aneurysms often results in incomplete occlusion or aneurysm recurrence. The goals of this study were to compare results of coil embolization with or without the assistance of self-expandable stents and to examine how stents may influence neointima formation. MATERIALS AND METHODS: Wide-neck bifurcation aneurysms were constructed in 24 animals and, after 4-6 weeks, were randomly allocated to 1 of 5 groups: 1) coil embolization using the assistance of 1 braided stent (n = 5); 2) coil embolization using the assistance of 2 braided stents in a Y configuration (n = 5); 3) coil embolization without stent assistance (n = 6); 4) Y-stenting alone (n = 4); and 5) untreated controls (n = 4). Angiographic results were compared at baseline and at 12 weeks, by using an ordinal scale. Neointima formation at the neck at 12 weeks was compared among groups by using a semiquantitative grading scale. Bench studies were performed to assess stent porosities. RESULTS: Initial angiographic results were improved with single stent-assisted coiling compared with simple coiling (P = .013). Angiographic results at 12 weeks were improved with any stent assistance (P = .014). Neointimal closure of the aneurysm neck was similar with or without stent assistance (P = .908), with neointima covering coil loops but rarely stent struts. Y-stent placement alone had no therapeutic effect. Bench studies showed that porosities can be decreased with stent compaction, but a relatively stable porous transition zone was a limiting factor. CONCLUSIONS: Stent-assisted coiling may improve results of embolization by allowing more complete initial coiling, but these high-porosity stents did not provide a scaffold for more complete neointimal closure of aneurysms.

Flow structures at an idealized bifurcation : a numerical experiment

River bifurcations are key nodes within braided river systems controlling the flow and sediment partitioning and therefore the dynamics of the river braiding process. Recent research has shown that certain geometrical configurations induce instabilities that lead to downstream mid-channel bar formation and the formation of bifurcations. However, we currently have a poor understanding of the flow division process within bifurcations and the flow dynamics in the downstream bifurcates, both of which are needed to understand bifurcation stability. This paper presents results of a numerical sensitivity experiment undertaken using computational fluid dynamics (CFD) with the purpose of understanding the flow dynamics of a series of idealized bifurcations. A geometric sensitivity analysis is undertaken for a range of channel slopes (0.005 to 0.03), bifurcation angles (22 degrees to 42 degrees) and a restricted set of inflow conditions based upon simulating flow through meander bends with different curvature on the flow field dynamics through the bifurcation. The results demonstrate that the overall slope of the bifurcation affects the velocity of flow through the bifurcation and when slope asymmetry is introduced, the flow structures in the bifurcation are modified. In terms of bifurcation evolution the most important observation appears to be that once slope asymmetry is greater than 0.2 the flow within the steep bifurcate shows potential instability and the potential for alternate channel bar formation. Bifurcation angle also defines the flow structures within the bifurcation with an increase in bifurcation angle increasing the flow velocity down both bifurcates. However, redistributive effects of secondary circulation caused by upstream curvature can very easily counter the effects of local bifurcation characteristics. Copyright (C) 2011 John Wiley & Sons, Ltd.

Clinical results of autologous infrainguinal revascularization using grafts originating distal to the femoral bifurcation in patients with mild inflow disease.

AIM: Chronic critical limb ischemia (CLI) often requires venous bypass grafting to distal arterial segments. However, graft patency is influenced by the length and quality of the graft and occasionally patients may have limited suitable veins. We investigated short distal bypass grafting from the superficial femoral or popliteal artery to the infrapopliteal, ankle or foot arteries, despite angiographic alterations of inflow vessels, providing that invasive pressure measurement at the site of the planned proximal anastomosis revealed an inflow-brachial pressure difference of <or=10 mmHg. METHODS: Four hundred and twenty-three consecutive infrainguinal bypass grafts were performed for CLI between June, 1999 and November, 2002 at our institution. All patients underwent preoperative clinical examination, arteriography and assessment of the veins by duplex ultrasound. The study group are patients in whom the proximal and distal anastomoses of the bypass are below the femoral bifurcation and the popliteal artery, respectively. Invasive arterial pressure measurements were recorded at the level of the planned proximal anastomosis which was performed at that level if the difference of the inflow-brachial pressure was <or=10 mmHg, irrespective of angiographic alterations of the inflow vessels proximal to the planned anastomosis. All patients had a clinical follow-up included a duplex examination of their graft, at 1 week, 3, 9 and 12 months and, thereafter, annually. No patient was lost to follow-up. RESULTS: Sixty-seven patients underwent 71 short distal bypass grafts in 71 limbs with reversed saphenous vein grafts in 52, in situ saphenous veins in 11, reversed cephalic vein in 1 and composite veins in 7, respectively. Surgical or endovascular interventions to improve inflow were required in 4 limbs (5.6%). The mean follow-up time was 22.5 months and the two-year survival was 92.5%. Primary and secondary patency rates at 2 years were 73% and 93%, respectively, and the limb salvage rate was 98.5%. CONCLUSION: In appropriately selected patients, short distal venous bypass grafts can be performed with satisfactory patency and limb salvage rates even in the presence of morphologic alterations of the inflow vessels providing that these are not hemodynamically significant, or can be corrected intraoperatively.

Coordination pattern adaptability: energy cost of degenerate behaviors.

This study investigated behavioral adaptability, which could be defined as a blend between stability and flexibility of the limbs movement and their inter-limb coordination, when individuals received informational constraints. Seven expert breaststroke swimmers performed three 200-m in breaststroke at constant submaximal intensity. Each trial was performed randomly in a different coordination pattern: 'freely-chosen', 'maximal glide' and 'minimal glide'. Two underwater and four aerial cameras enabled 3D movement analysis in order to assess elbow and knee angles, elbow-knee pair coordination, intra-cyclic velocity variations of the center of mass, stroke rate and stroke length and inter-limb coordination. The energy cost of locomotion was calculated from gas exchanges and blood lactate concentration. The results showed significantly higher glide, intra-cyclic velocity variations and energy cost under 'maximal glide' compared to 'freely-chosen' instructional conditions, as well as higher reorganization of limb movement and inter-limb coordination (p<0.05). In the 'minimal glide' condition, the swimmers did not show significantly shorter glide and lower energy cost, but they exhibited significantly lower deceleration of the center of mass, as well as modified limb movement and inter-limb coordination (p<0.05). These results highlight that a variety of structural adaptations can functionally satisfy the task-goal.

Death caused by cardioinhibitory reflex cardiac arrest--a systematic review of cases.

Forensic pathologists often refer to the cardioinhibitory reflex cardiac arrest (CiRCA) following short neck trauma as a mechanism of death. We sought via a systematic review of the literature to identify circumstances under which carotid bifurcation stimulation could lead to death. Two independent reviewers selected case studies or reports from Medline, ISI Web of Knowledge, and Embase. Circumstances and contributory factors were extracted for each case. From the available data, authors independently assessed whether CiRCA was highly probable (no alternative explanation possible), probable (alternative explanation possible), or unlikely (alternative explanation highly probable). A narrative approach was used to define circumstances in which CiRCA remained possible. From the 48 published cases evoking CiRCA as a possible cause of death between 1881 and 2009, 28 were most likely to result of other mechanism of death (i.e., cerebral hypoxia due to carotid compression, mechanical asphyxia, myocardial infarction). CiRCA remained possible for 20 cases (including five based on anecdotal evidence only) with only one case with no alternative explanation other than CiRCA. Our findings support the presumption that reflex cardiac arrhythmia due to carotid bifurcation stimulation cannot provoke death alone. Actual state of knowledge suggests CiRCA might be contributory to death in the presence of drug abuse and/or cardiac pathology, often associated with physical and/or mental excitation.

Evaluation of cumulative PCB exposure estimated by a job exposure matrix versus PCB serum concentrations.

Although polychlorinated biphenyls (PCBs) have been banned in many countries for more than three decades, exposures to PCBs continue to be of concern due to their long half-lives and carcinogenic effects. In National Institute for Occupational Safety and Health studies, we are using semiquantitative plant-specific job exposure matrices (JEMs) to estimate historical PCB exposures for workers (n = 24,865) exposed to PCBs from 1938 to 1978 at three capacitor manufacturing plants. A subcohort of these workers (n = 410) employed in two of these plants had serum PCB concentrations measured at up to four times between 1976 and 1989. Our objectives were to evaluate the strength of association between an individual worker's measured serum PCB levels and the same worker's cumulative exposure estimated through 1977 with the (1) JEM and (2) duration of employment, and to calculate the explained variance the JEM provides for serum PCB levels using (3) simple linear regression. Consistent strong and statistically significant associations were observed between the cumulative exposures estimated with the JEM and serum PCB concentrations for all years. The strength of association between duration of employment and serum PCBs was good for highly chlorinated (Aroclor 1254/HPCB) but not less chlorinated (Aroclor 1242/LPCB) PCBs. In the simple regression models, cumulative occupational exposure estimated using the JEMs explained 14-24% of the variance of the Aroclor 1242/LPCB and 22-39% for Aroclor 1254/HPCB serum concentrations. We regard the cumulative exposure estimated with the JEM as a better estimate of PCB body burdens than serum concentrations quantified as Aroclor 1242/LPCB and Aroclor 1254/HPCB.

Amino acid coevolution reveals three-dimensional structure and functional domains of insect odorant receptors.

Insect odorant receptors (ORs) comprise an enormous protein family that translates environmental chemical signals into neuronal electrical activity. These heptahelical receptors are proposed to function as ligand-gated ion channels and/or to act metabotropically as G protein-coupled receptors (GPCRs). Resolving their signalling mechanism has been hampered by the lack of tertiary structural information and primary sequence similarity to other proteins. We use amino acid evolutionary covariation across these ORs to define restraints on structural proximity of residue pairs, which permit de novo generation of three-dimensional models. The validity of our analysis is supported by the location of functionally important residues in highly constrained regions of the protein. Importantly, insect OR models exhibit a distinct transmembrane domain packing arrangement to that of canonical GPCRs, establishing the structural unrelatedness of these receptor families. The evolutionary couplings and models predict odour binding and ion conduction domains, and provide a template for rationale structure-activity dissection.

Is there a common factor for vision?

In cognition, common factors play a crucial role. For example, different types of intelligence are highly correlated, pointing to a common factor, which is often called g. One might expect that a similar common factor would also exist for vision. Surprisingly, no one in the field has addressed this issue. Here, we provide the first evidence that there is no common factor for vision. We tested 40 healthy students' performance in six basic visual paradigms: visual acuity, vernier discrimination, two visual backward masking paradigms, Gabor detection, and bisection discrimination. One might expect that performance levels on these tasks would be highly correlated because some individuals generally have better vision than others due to superior optics, better retinal or cortical processing, or enriched visual experience. However, only four out of 15 correlations were significant, two of which were nontrivial. These results cannot be explained by high intraobserver variability or ceiling effects because test-retest reliability was high and the variance in our student population is commensurate with that from other studies with well-sighted populations. Using a variety of tests (e.g., principal components analysis, Bayes theorem, test-retest reliability), we show the robustness of our null results. We suggest that neuroplasticity operates during everyday experience to generate marked individual differences. Our results apply only to the normally sighted population (i.e., restricted range sampling). For the entire population, including those with degenerate vision, we expect different results.

Superinfection with drug-resistant HIV is rare and does not contribute substantially to therapy failure in a large European cohort.

BACKGROUND: Superinfection with drug resistant HIV strains could potentially contribute to compromised therapy in patients initially infected with drug-sensitive virus and receiving antiretroviral therapy. To investigate the importance of this potential route to drug resistance, we developed a bioinformatics pipeline to detect superinfection from routinely collected genotyping data, and assessed whether superinfection contributed to increased drug resistance in a large European cohort of viremic, drug treated patients. METHODS: We used sequence data from routine genotypic tests spanning the protease and partial reverse transcriptase regions in the Virolab and EuResist databases that collated data from five European countries. Superinfection was indicated when sequences of a patient failed to cluster together in phylogenetic trees constructed with selected sets of control sequences. A subset of the indicated cases was validated by re-sequencing pol and env regions from the original samples. RESULTS: 4425 patients had at least two sequences in the database, with a total of 13816 distinct sequence entries (of which 86% belonged to subtype B). We identified 107 patients with phylogenetic evidence for superinfection. In 14 of these cases, we analyzed newly amplified sequences from the original samples for validation purposes: only 2 cases were verified as superinfections in the repeated analyses, the other 12 cases turned out to involve sample or sequence misidentification. Resistance to drugs used at the time of strain replacement did not change in these two patients. A third case could not be validated by re-sequencing, but was supported as superinfection by an intermediate sequence with high degenerate base pair count within the time frame of strain switching. Drug resistance increased in this single patient. CONCLUSIONS: Routine genotyping data are informative for the detection of HIV superinfection; however, most cases of non-monophyletic clustering in patient phylogenies arise from sample or sequence mix-up rather than from superinfection, which emphasizes the importance of validation. Non-transient superinfection was rare in our mainly treatment experienced cohort, and we found a single case of possible transmitted drug resistance by this route. We therefore conclude that in our large cohort, superinfection with drug resistant HIV did not compromise the efficiency of antiretroviral treatment.

Widespread occurrence of non-canonical transcription termination by human RNA polymerase III.

Human RNA polymerase (Pol) III-transcribed genes are thought to share a simple termination signal constituted by four or more consecutive thymidine residues in the coding DNA strand, just downstream of the RNA 3'-end sequence. We found that a large set of human tRNA genes (tDNAs) do not display any T(≥4) stretch within 50 bp of 3'-flanking region. In vitro analysis of tDNAs with a distanced T(≥4) revealed the existence of non-canonical terminators resembling degenerate T(≥5) elements, which ensure significant termination but at the same time allow for the production of Pol III read-through pre-tRNAs with unusually long 3' trailers. A panel of such non-canonical signals was found to direct transcription termination of unusual Pol III-synthesized viral pre-miRNA transcripts in gammaherpesvirus 68-infected cells. Genome-wide location analysis revealed that human Pol III tends to trespass into the 3'-flanking regions of tDNAs, as expected from extensive terminator read-through. The widespread occurrence of partial termination suggests that the Pol III primary transcriptome in mammals is unexpectedly enriched in 3'-trailer sequences with the potential to contribute novel functional ncRNAs.

Temporary caval stenting improves venous drainage during cardiopulmonary bypass

OBJECTIVES: Assess the benefit of temporary caval stenting for remote venous drainage during cardiopulmonary bypass (CPB). METHODS: Temporary caval stenting was realized in bovine experiments (65+/-6 kg) by the means of self-expanding (18F for insertion, 36F in situ) venous cannulas (Smartcanula LLC, Lausanne, Switzerland) with various lengths: 43 cm, 53 cm, 63 cm vs. a standard 28F wire armed cannula in trans-jugular fashion. Maximal blood flows were assessed for 20, 25 and 30 mmHg of driving pressure with a motorized table height adjustment system. In addition, the inferior caval diameters (just above its bifurcation) were measured in real time with intra-vascular ultrasound (IVUS). RESULTS: Venous drainage (flow in l/min) at 20 mmHg, 25 mmHg, and 30 mmHg drainage load was 3.5+/-0.5, 3.7+/-0.7 and 4.0+/-0.6 for the 28F standard vs. 4.1+/-0.7, 4.0+/-1.3 and 3.9+/-1.1 for the 36F smart 43 cm, vs. 5.0+/-0.7, 5.3+/-1.3 and 5.4+/-1.4 for the 36F smart 53 cm, vs. 5.2+/-0.5*, 5.6+/-1.1* and 5.8+/-1.0* for the 36F smart 63 cm. The inferior vena caval diameters at 30 mmHg were 13.5+/-4.8 mm for 28F standard, 11.1+/-3.6 for 36F smart 43 cm, 11.3+/-3.2 for 36F 53 cm, and 17.0+/-0.1* for 36F 63 cm (*P<0.05 for 28F standard vs. 36F smart 63 cm long) CONCLUSIONS: The 43 cm self-expanding 36F smartcanula outperforms the 28F standard wire armed cannula at low drainage pressures and without augmentation. Temporary caval stenting with long self-expanding venous cannulas provides even better drainage (+51%).

Skin permeation and metabolism of di(2-ethylhexyl) phthalate (DEHP).

Phthalates are suspected to be endocrine disruptors. Di(2-ethylhexyl) phthalate (DEHP) is assumed to have low dermal absorption; however, previous in vitro skin permeation studies have shown large permeation differences. Our aims were to determine DEHP permeation parameters and assess extent of skin DEHP metabolism among workers highly exposed to these lipophilic, low volatile substances. Surgically removed skin from patients undergoing abdominoplasty was immediately dermatomed (800 μm) and mounted on flow-through diffusion cells (1.77 cm(2)) operating at 32°C with cell culture media (aqueous solution) as the reservoir liquid. The cells were dosed either with neat DEHP or emulsified in aqueous solution (166 μg/ml). Samples were analysed by HPLC-MS/MS. DEHP permeated human viable skin only as the metabolite MEHP (100%) after 8h of exposure. Human skin was able to further oxidize MEHP to 5-oxo-MEHP. Neat DEHP applied to the skin hardly permeated skin while the aqueous solution readily permeated skin measured in both cases as concentration of MEHP in the receptor liquid. DEHP pass through human skin, detected as MEHP only when emulsified in aqueous solution, and to a far lesser degree when applied neat to the skin. Using results from older in vitro skin permeation studies with non-viable skin may underestimate skin exposures. Our results are in overall agreement with newer phthalate skin permeation studies.

Evaluation of exposure biomarkers in offshore workers exposed to low benzene and toluene concentrations.

Characterize ethylbenzene and xylene air concentrations, and explore the biological exposure markers (urinary t,t-muconic acid (t,t-MA) and unmetabolized toluene) among petroleum workers offshore. Offshore workers have increased health risks due to simultaneous exposures to several hydrocarbons present in crude oil. We discuss the pooled benzene exposure results from our previous and current studies and possible co-exposure interactions. BTEX air concentrations were measured during three consecutive 12-h work shifts among 10 tank workers, 15 process operators, and 18 controls. Biological samples were collected pre-shift on the first day of study and post-shift on the third day of the study. The geometric mean exposure over the three work shifts were 0.02 ppm benzene, 0.05 ppm toluene, 0.03 ppm ethylbenzene, and 0.06 ppm xylene. Benzene in air was significantly correlated with unmetabolized benzene in blood (r = 0.69, p < 0.001) and urine (r = 0.64, p < 0.001), but not with urinary t,t-MA (r = 0.27, p = 0.20). Toluene in air was highly correlated with the internal dose of toluene in both blood (r = 0.70, p < 0.001) and urine (r = 0.73, p < 0.001). Co-exposures were present; however, an interaction of metabolism was not likely at these low benzene and toluene exposures. Urinary benzene, but not t,t-MA, was a reliable biomarker for benzene at low exposure levels. Urinary toluene was a useful biomarker for toluene exposure. Xylene and ethylbenzene air levels were low. Dermal exposure assessment needs to be performed in future studies among these workers.

Generation of polycyclic aromatic hydrocarbons (PAHs) during woodworking operations.

Occupational exposures to wood dust have been associated with an elevated risk of sinonasal cancer (SNC). Wood dust is recognized as a human carcinogen but the specific cancer causative agent remains unknown. One possible explanation is a co-exposure to; wood dust and polycyclic aromatic hydrocarbons (PAHs). PAHs could be generated during incomplete combustion of wood due to heat created by use of power tools. To determine if PAHs are generated from wood during common wood working operations, PAH concentrations in wood dust samples collected in an experimental chamber operated under controlled conditions were analyzed. In addition, personal air samples from workers exposed to wood dust (n = 30) were collected. Wood dust was generated using three different power tools: vibrating sander, belt sander, and saw; and six wood materials: fir, Medium Density Fiberboard (MDF), beech, mahogany, oak and wood melamine. Monitoring of wood workers was carried out by means of personal sampler device during wood working operations. We measured 21 PAH concentrations in wood dust samples by capillary gas chromatography-ion trap mass spectrometry (GC-MS). Total PAH concentrations in wood dust varied greatly (0.24-7.95 ppm) with the lowest being in MDF dust and the highest in wood melamine dust. Personal PAH exposures were between 37.5-119.8 ng m(-3) during wood working operations. Our results suggest that PAH exposures are present during woodworking operations and hence could play a role in the mechanism of cancer induction related to wood dust exposure.