Cost-effective patient-specific intraoperative molded cranioplasty

Intraoperative molding of polymethyl-methacrylate into complex three-dimensional shapes with correct thickness is often a time-consuming process and may lead to unsatisfying cosmetical results. This article describes an intraoperative technique to assemble a polymethyl-methacrylate implant as a replica of the patient's bone flap. This approach provides a fast and inexpensive alternative technique with good cosmetic outcome. The technique is feasible and can be applied in early and delayed cranioplasty procedures. In selected patients, immediate single-stage reconstruction avoids a second operation.

Assessment of flow in perforating arteries during intracranial aneurysm surgery using intraoperative near-infrared indocyanine green videoangiography

OBJECTIVE: Perforating arteries are commonly involved during the surgical dissection and clipping of intracranial aneurysms. Occlusion of perforating arteries is responsible for ischemic infarction and poor outcome. The goal of this study is to describe the usefulness of near-infrared indocyanine green videoangiography (ICGA) for the intraoperative assessment of blood flow in perforating arteries that are visible in the surgical field during clipping of intracranial aneurysms. In addition, we analyzed the incidence of perforating vessels involved during the aneurysm surgery and the incidence of ischemic infarct caused by compromised small arteries. METHODS: Sixty patients with 64 aneurysms were surgically treated and prospectively included in this study. Intraoperative ICGA was performed using a surgical microscope (Carl Zeiss Co., Oberkochen, Germany) with integrated ICGA technology. The presence and involvement of perforating arteries were analyzed in the microsurgical field during surgical dissection and clip application. Assessment of vascular patency after clipping was also investigated. Only those small arteries that were not visible on preoperative digital subtraction angiography were considered for analysis. RESULTS: The ICGA was able to visualize flow in all patients in whom perforating vessels were found in the microscope field. Among 36 patients whose perforating vessels were visible on ICGA, 11 (30%) presented a close relation between the aneurysm and perforating arteries. In one (9%) of these 11 patients, ICGA showed occlusion of a P1 perforating artery after clip application, which led to immediate correction of the clip confirmed by immediate reestablishment of flow visible with ICGA without clinical consequences. Four patients (6.7%) presented with postoperative perforating artery infarct, three of whom had perforating arteries that were not visible or distant from the aneurysm. CONCLUSION: The involvement of perforating arteries during clip application for aneurysm occlusion is a usual finding. Intraoperative ICGA may provide visual information with regard to the patency of these small vessels.

Extended retinacular soft-tissue flap for intra-articular hip surgery: surgical technique, indications, and results of application

Osteotomies of the proximal femur for hip joint conditions are normally done at the intertrochanteric or subtrochanteric level. Intra-articular osteotomies would be more direct and therefore allow a more powerful correction with no or very little undesired side correction. However, concerns about the risk of vascular damage and osteonecrosis of the femoral head have so far basically excluded this technique from practical use. Based on detailed knowledge of the vascular anatomy of the proximal femur, an approach to safely dislocate the femoral head has been described and successfully performed. Experience as well as further studies of femoral head perfusion allowed a substantial extension of this approach, with subperiosteal exposure of the circumference of the femoral neck with constant intraoperative control of the blood supply to the head. Using the extended retinacular soft-tissue flap, four surgical techniques (relative neck lengthening, subcapital realignment in slipped capital femoral epiphysis, true femoral neck osteotomy, and femoral head reduction osteotomy) evolved or became safer with respect to perfusion of the femoral head. The extended retinacular soft-tissue flap offers the technical and biologic possibility for a new class of intra articular procedures. Although meticulous execution of the surgical steps is important, the procedures have a high level of safety for femoral head perfusion.

Does point of care prothrombin time measurement reduce the transfusion of fresh frozen plasma in patients undergoing major surgery? The POC-OP randomized-controlled trial

BACKGROUND: Bleeding is a frequent complication during surgery. The intraoperative administration of blood products, including packed red blood cells, platelets and fresh frozen plasma (FFP), is often live saving. Complications of blood transfusions contribute considerably to perioperative costs and blood product resources are limited. Consequently, strategies to optimize the decision to transfuse are needed. Bleeding during surgery is a dynamic process and may result in major blood loss and coagulopathy due to dilution and consumption. The indication for transfusion should be based on reliable coagulation studies. While hemoglobin levels and platelet counts are available within 15 minutes, standard coagulation studies require one hour. Therefore, the decision to administer FFP has to be made in the absence of any data. Point of care testing of prothrombin time ensures that one major parameter of coagulation is available in the operation theatre within minutes. It is fast, easy to perform, inexpensive and may enable physicians to rationally determine the need for FFP. METHODS/DESIGN: The objective of the POC-OP trial is to determine the effectiveness of point of care prothrombin time testing to reduce the administration of FFP. It is a patient and assessor blind, single center randomized controlled parallel group trial in 220 patients aged between 18 and 90 years undergoing major surgery (any type, except cardiac surgery and liver transplantation) with an estimated blood loss during surgery exceeding 20% of the calculated total blood volume or a requirement of FFP according to the judgment of the physicians in charge. Patients are randomized to usual care plus point of care prothrombin time testing or usual care alone without point of care testing. The primary outcome is the relative risk to receive any FFP perioperatively. The inclusion of 110 patients per group will yield more than 80% power to detect a clinically relevant relative risk of 0.60 to receive FFP of the experimental as compared with the control group. DISCUSSION: Point of care prothrombin time testing in the operation theatre may reduce the administration of FFP considerably, which in turn may decrease costs and complications usually associated with the administration of blood products. TRIAL REGISTRATION: NCT00656396.

A dose-controlled system for air-liquid interface cell exposure and application to zinc oxide nanoparticles

BACKGROUND: Engineered nanoparticles are becoming increasingly ubiquitous and their toxicological effects on human health, as well as on the ecosystem, have become a concern. Since initial contact with nanoparticles occurs at the epithelium in the lungs (or skin, or eyes), in vitro cell studies with nanoparticles require dose-controlled systems for delivery of nanoparticles to epithelial cells cultured at the air-liquid interface. RESULTS: A novel air-liquid interface cell exposure system (ALICE) for nanoparticles in liquids is presented and validated. The ALICE generates a dense cloud of droplets with a vibrating membrane nebulizer and utilizes combined cloud settling and single particle sedimentation for fast (~10 min; entire exposure), repeatable (<12%), low-stress and efficient delivery of nanoparticles, or dissolved substances, to cells cultured at the air-liquid interface. Validation with various types of nanoparticles (Au, ZnO and carbon black nanoparticles) and solutes (such as NaCl) showed that the ALICE provided spatially uniform deposition (<1.6% variability) and had no adverse effect on the viability of a widely used alveolar human epithelial-like cell line (A549). The cell deposited dose can be controlled with a quartz crystal microbalance (QCM) over a dynamic range of at least 0.02-200 mug/cm(2). The cell-specific deposition efficiency is currently limited to 0.072 (7.2% for two commercially available 6-er transwell plates), but a deposition efficiency of up to 0.57 (57%) is possible for better cell coverage of the exposure chamber. Dose-response measurements with ZnO nanoparticles (0.3-8.5 mug/cm(2)) showed significant differences in mRNA expression of pro-inflammatory (IL-8) and oxidative stress (HO-1) markers when comparing submerged and air-liquid interface exposures. Both exposure methods showed no cellular response below 1 mug/cm(2 )ZnO, which indicates that ZnO nanoparticles are not toxic at occupationally allowed exposure levels. CONCLUSION: The ALICE is a useful tool for dose-controlled nanoparticle (or solute) exposure of cells at the air-liquid interface. Significant differences between cellular response after ZnO nanoparticle exposure under submerged and air-liquid interface conditions suggest that pharmaceutical and toxicological studies with inhaled (nano-)particles should be performed under the more realistic air-liquid interface, rather than submerged cell conditions.

Decreased factor XIII availability for thrombin and early loss of clot firmness in patients with unexplained intraoperative bleeding

To explore relevant changes in unexplained intraoperative bleeding, we evaluated elements of the final steps of the coagulation cascade in 226 consecutive patients undergoing elective surgery. Patients were stratified for the occurrence of unexplained intraoperative bleeding according to predefined criteria. Twenty patients (8.8%) developed unexplained bleeding. The median intraoperative blood loss was 1350 mL (bleeders) and 400 mL (nonbleeders) (P < 0.001). Fibrinogen and Factor XIII (F. XIII) were more rapidly consumed in bleeders (P < 0.001). Soluble fibrin formation (fibrin monomer) was increased in bleeders throughout surgery (P < or = 0.014). However, F. XIII availability per unit thrombin generated was significantly decreased in bleeders before, during, and after surgery (P < or = 0.051). Computerized thrombelastography showed a parallel, significant reduction in clot firmness. We suggest that mild preexisting coagulopathy is not rare in surgical patients and probably can result in clinically relevant intraoperative bleeding. This hemostatic disorder shows impaired clot firmness, probably secondary to decreased cross-linking (due to a loss of F. XIII, both in absolute measures and per unit thrombin generated). We suggest that the application of F. XIII might be worthwhile to test in a prospective clinical trial to increase clot firmness in patients at risk for this intraoperative coagulopathy.

Ctp1 and the MRN-complex are required for endonucleolytic Rec12 removal with release of a single class of oligonucleotides in fission yeast

DNA double-strand breaks (DSBs) are formed during meiosis by the action of the topoisomerase-like Spo11/Rec12 protein, which remains covalently bound to the 5' ends of the broken DNA. Spo11/Rec12 removal is required for resection and initiation of strand invasion for DSB repair. It was previously shown that budding yeast Spo11, the homolog of fission yeast Rec12, is removed from DNA by endonucleolytic cleavage. The release of two Spo11 bound oligonucleotide classes, heterogeneous in length, led to the conjecture of asymmetric cleavage. In fission yeast, we found only one class of oligonucleotides bound to Rec12 ranging in length from 17 to 27 nucleotides. Ctp1, Rad50, and the nuclease activity of Rad32, the fission yeast homolog of Mre11, are required for endonucleolytic Rec12 removal. Further, we detected no Rec12 removal in a rad50S mutant. However, strains with additional loss of components localizing to the linear elements, Hop1 or Mek1, showed some Rec12 removal, a restoration depending on Ctp1 and Rad32 nuclease activity. But, deletion of hop1 or mek1 did not suppress the phenotypes of ctp1Delta and the nuclease dead mutant (rad32-D65N). We discuss what consequences for subsequent repair a single class of Rec12-oligonucleotides may have during meiotic recombination in fission yeast in comparison to two classes of Spo11-oligonucleotides in budding yeast. Furthermore, we hypothesize on the participation of Hop1 and Mek1 in Rec12 removal.

The performance of single- and multi-proxy transfer functions (testate amoebae, bryophytes, vascular plants) for reconstructing mire surface wetness and pH

Peatlands are widely exploited archives of paleoenvironmental change. We developed and compared multiple transfer functions to infer peatland depth to the water table (DWT) and pH based on testate amoeba (percentages, or presence/absence), bryophyte presence/absence, and vascular plant presence/absence data from sub-alpine peatlands in the SE Swiss Alps in order to 1) compare the performance of single-proxy vs. multi-proxy models and 2) assess the performance of presence/absence models. Bootstrapping cross-validation showing the best performing single-proxy transfer functions for both DWT and pH were those based on bryophytes. The best performing transfer functions overall for DWT were those based on combined testate amoebae percentages, bryophytes and vascular plants; and, for pH, those based on testate amoebae and bryophytes. The comparison of DWT and pH inferred from testate amoeba percentages and presence/absence data showed similar general patterns but differences in the magnitude and timing of some shifts. These results show new directions for paleoenvironmental research, 1) suggesting that it is possible to build good-performing transfer functions using presence/absence data, although with some loss of accuracy, and 2) supporting the idea that multi-proxy inference models may improve paleoecological reconstruction. The performance of multi-proxy and single-proxy transfer functions should be further compared in paleoecological data.

Color and Scent: How Single Genes Influence Pollinator Attraction

A major function of angiosperm flowers is the recruitment of animal pollinators that serve to transfer pollen among conspecific plants. Distinct sets of floral characteristics, called pollination syndromes, are correlated with visitation by specific groups of pollinators. Switches among pollination syndromes have occurred in many plant families. Such switches must have involved coordinated changes in multiple traits and multiple genes. Two well-studied floral traits affecting pollinator attraction are petal color and scent production. We review current knowledge about the biosynthetic pathways for floral color and scent production and their interaction at the genetic and biochemical levels. A key question in the field concerns the genes that underlie natural variation in color and scent and how such genes affect pollinator preference, reproductive isolation, and ultimately speciation.

Is characterization of a single isolate sufficient for valid publication of a new genus or species? Proposal to modify recommendation 30b of the Bacteriological Code (1990 Revision)

From 1990 to 2000, the number of published named taxa based upon new isolates at species and genus levels in International Journal of Systematic and Evolutionary Microbiology, formerly International Journal of Systematic Bacteriology, have increased by approximately four- and sevenfold, respectively. New taxa based upon characterization of only a single isolate remained at around 40% for both categories. The Bacteriological Code (1990 Revision) has no recommendations on the number of strains required for definition of new taxa. For a few groups, a minimum number of 5-10 strains has been suggested in minimal standards. Since an exponential increase in new taxa can be expected in the future, the authors discuss problems related to naming new species and genera based upon descriptions of a single isolate and suggest that this practice is re-evaluated. It is proposed that the following should be added to Recommendation 30b of the Bacteriological Code: 'Descriptions should be based on as many strains as possible (minimum five), representing different sources with respect to geography and ecology in order to be well characterized both phenotypically and genotypically, to establish the centre (from which the type strain could be chosen) and the extent of the cluster to be named. In addition, comparative studies should be performed, including reference strains that represent neighbouring species and/or genera, in order to give descriptions that are sufficiently detailed to allow differentiation from these neighbours.'

Single-dose piracetam effects on global complexity measures of human spontaneous multichannel EEG

Global complexity of 47-channel resting electroencephalogram (EEG) of healthy young volunteers was studied after intake of a single dose of a nootropic drug (piracetam, Nootropil® UCB Pharma) in 12 healthy volunteers. Four treatment levels were used: 2.4, 4.8, 9.6 g piracetam and placebo. Brain electric activity was assessed through Global Dimensional Complexity and Global Omega-Complexity as quantitative measures of the complexity of the trajectory of multichannel EEG in state space. After oral ingestion (1–1.5 h), both measures showed significant decreases from placebo to 2.4 g piracetam. In addition, Global Dimensional Complexity showed a significant return to placebo values at 9.6 g piracetam. The results indicate that a single dose of piracetam dose-dependently affects the spontaneous EEG in normal volunteers, showing effects at the lowest treatment level. The decreased EEG complexity is interpreted as increased cooperativity of brain functional processes.

Electrochemical characterization of self-assembled Ferrocene-terminated alkanethiol monolayers on low-index gold single crystal electrodes

We present a voltammetric and in situ STM study of 11-ferrocenyl-1-undecanethiol (FcC11) assembled on low-index single crystal and polycrystalline gold electrodes. The influence of electrode surface structure as well as of structure defects in the self-assembled FcC11 monolayers on the electrochemical response during the oxidation and reduction of the terminal ferrocene group is explored. The nature of the redox peaks is discussed in detail. We identified the coexistence of disordered FcC11 regions with 2D patches of “locally ordered” FcC11 species. We demonstrate that close-packed domains are preferentially formed at atomically flat terraces. Increasing the defect density of the substrate surface leads to a decreasing amount of locally ordered FcC11 molecules.

In Situ SHINERS at Electrochemical Single-Crystal Electrode/Electrolyte Interfaces: Tuning Preparation Strategies and Selected Applications

We have studied Au(55 nm)@SiO2 nanoparticles (NPs) on two low-index phases of gold and platinum single crystal electrodes in ClO4– and SO42– ion-containing electrolytes by both electrochemical methods and in-situ shell-isolated nanoparticle enhanced Raman spectroscopy (SHINERS). We showed the blocking of the electrode with surfactants originating from the synthesis of as-prepared SHINERS NPs. We introduce an efficient procedure to overcome this problem, which provides a fundamental platform for the application of SHINERS in surface electrochemistry and beyond. Our method is based on a hydrogen evolution treatment of the SHINERS-NP-modified single-crystal surfaces. The reliability of our preparation strategy is demonstrated in electrochemical SHINERS experiments on the potential-controlled adsorption and phase formation of pyridine on Au(hkl) and Pt(hkl). We obtained high-quality Raman spectra on these well-defined and structurally carefully characterized single-crystal surfaces. The analysis of the characteristic A1 vibrational modes revealed perfect agreement with the interpretation of single-crystal voltammetric and chronoamperometric experiments. Our study demonstrates that the SHINERS protocol developed in this work qualifies this Raman method as a pioneering approach with unique opportunities for in situ structure and reactivity studies at well-defined electrochemical solid/liquid interfaces.

Charge Transport in Photoswitchable Dimethyldihydropyrene-Type Single-Molecule Junctions

The conductance properties of a photoswitchable dimethyldihydropyrene (DHP) derivative have been investigated for the first time in single-molecule junctions using the mechanically controllable break junction technique. We demonstrate that the reversible structure changes induced by isomerization of a single bispyridine-substituted DHP molecule are correlated with a large drop of the conductance value. We found a very high ON/OFF ratio (>104) and an excellent reversibility of conductance switching.

Single-Molecule Conductance of Functionalized Oligoynes: Length Dependence and Junction Evolution

We report a combined experimental and theoretical investigation of the length dependence and anchor group dependence of the electrical conductance of a series of oligoyne molecular wires in single-molecule junctions with gold contacts. Experimentally, we focus on the synthesis and properties of diaryloligoynes with n = 1, 2, and 4 triple bonds and the anchor dihydrobenzo[b]thiophene (BT). For comparison, we also explored the aurophilic anchor group cyano (CN), amino (NH2), thiol (SH), and 4-pyridyl (PY). Scanning tunneling microscopy break junction (STM-BJ) and mechanically controllable break junction (MCBJ) techniques are employed to investigate single-molecule conductance characteristics. The BT moiety is superior as compared to traditional anchoring groups investigated so far. BT-terminated oligoynes display a 100% probability of junction formation and possess conductance values which are the highest of the oligoynes studied and, moreover, are higher than other conjugated molecular wires of similar length. Density functional theory (DFT)-based calculations are reported for oligoynes with n = 1−4 triple bonds. Complete conductance traces and conductance distributions are computed for each family of molecules. The sliding of the anchor groups leads to oscillations in both the electrical conductance and the binding energies of the studied molecular wires. In agreement with experimental results, BT-terminated oligoynes are predicted to have a high electrical conductance. The experimental attenuation constants βH range between 1.7 nm−1 (CN) and 3.2 nm−1 (SH) and show the following trend: βH(CN) < βH(NH2) < βH(BT) < βH(PY) ≈ βH(SH). DFT-based calculations yield lower values, which range between 0.4 nm−1 (CN) and 2.2 nm−1 (PY).