A prognostic model for the preoperative identification of patients at risk for receiving transfusion of packed red blood cells in cardiac surgery.

BACKGROUND: Patients undergoing cardiothoracic surgery are at substantial risk for blood transfusion. Increased awareness and patient blood management have resulted in a significant reduction over the past years. The next step is preoperative treatment of patients at high risk for packed red blood cells (RBC) transfusion, with the ultimate goal to eventually prevent RBC transfusion. A prediction model was developed to select patients at high risk for RBC transfusion. MATERIALS AND METHODS: Data of all patients that underwent cardiac surgery in our center between 2008 and 2013 (n = 2951) were used for model development, and between 2014 and 2016 for validation (n = 1136). Only preoperative characteristics were included in a multinomial regression model with three outcome categories (no, RBC, other transfusion). The accuracy of the estimated risks and discriminative ability of the model were assessed. Clinical usefulness was explored. RESULTS: Risk factors included are sex, type of surgery, redo surgery, age, height, body mass index, preoperative hemoglobin level, and preoperative platelet count. The model has excellent discriminative ability for predicting RBC transfusion versus no transfusion (area under the curve [AUC] = 94%) and good discriminative ability for RBC transfusion versus other transfusion (AUC = 84%). With a cut-off value of RBC risk of 16.8% and higher, the model is well able to identify a high proportion of patients at risk for RBC transfusion (sensitivity = 87.1%, specificity = 82.3%). CONCLUSION: In the current study, a prediction tool was developed to be used for risk stratification of patients undergoing elective cardiac surgery at risk for blood transfusions.

Everolimus- vs. novolimus-eluting bioresorbable scaffolds in patients with acute coronary syndrome.

BACKGROUND: Limited data exist on bioresorbable scaffolds (BRS) in patients with acute coronary syndrome (ACS). The aim of the present study was to evaluate novolimus-eluting BRS (DESolve) as interventional treatment for patients with ACS, and to compare its 12-month outcomes with the everolimus-eluting bioresorbable scaffolds (Absorb). METHODS: In this retrospective study, patients with ACS (including unstable angina pectoris, ST-segment elevation myocardial infarction, or non-ST-segment elevation myocardial infarction) treated with either the Absorb or the DESolve BRS were evaluated in a 1:1 matched-pair analysis. Major adverse cardiac events (MACE), including death, myocardial infarction, and target lesion revascularization, were evaluated as a major endpoint. The occurrence of scaffold thrombosis was also assessed. RESULTS: A total of 102 patients were eligible for this analysis. The rate of MACE at 12 months was comparable between the Absorb and the DESolve group (8.3% vs. 6.8%, p = 0.738). The occurrence of target lesion revascularization (6.2% vs. 4.7%; p = 0.700) and scaffold thrombosis (4.1% vs. 2.1%; p = 0.580) was comparable as well. All instances of scaffold thrombosis occurred within 30 days of the index procedure. CONCLUSION: In this study, similar 12-month event rates were observed for both BRS types after implantation for the treatment of ACS.

Influence of an Anomalous Temperature Dependence of the Phase Coherence Length on the Conductivity of Magnetic Topological Insulators.

Magnetotransport constitutes a useful probe to understand the interplay between electronic band topology and magnetism in spintronic devices. A recent theory of Lu and Shen [Phys. Rev. Lett. 112, 146601 (2014)PRLTAO0031-900710.1103/PhysRevLett.112.146601] on magnetically doped topological insulators predicts that quantum corrections Δκ to the temperature dependence of conductivity can change sign across the Curie transition. This phenomenon has been attributed to a suppression of the Berry phase of the topological surface states at the Fermi level, caused by a magnetic energy gap. Here, we demonstrate experimentally that Δκ can reverse its sign even when the Berry phase at the Fermi level remains unchanged. The contradictory behavior to theory predictions is resolved by extending the model by Lu and Shen to a nonmonotonic temperature scaling of the inelastic scattering length showing a turning point at the Curie transition.

Spin-Resolved Spectroscopy of the Yu-Shiba-Rusinov States of Individual Atoms.

A magnetic atom in a superconducting host induces so-called Yu-Shiba-Rusinov (YSR) bound states inside the superconducting energy gap. By combining spin-resolved scanning tunneling spectroscopy with simulations we demonstrate that the pair of peaks associated with the YSR states of an individual Fe atom coupled to an oxygen-reconstructed Ta surface gets spin polarized in an external magnetic field. As theoretically predicted, the electron and hole parts of the YSR states have opposite signs of spin polarizations which keep their spin character when crossing the Fermi level through the quantum phase transition. The simulation of a YSR state right at the Fermi level reveals zero spin polarization which can be used to distinguish such states from Majorana zero modes in chains of YSR atoms.

Angiographic and clinical outcomes of patients treated with everolimus-eluting bioresorbable stents in routine clinical practice: Results of the ISAR-ABSORB registry.

OBJECTIVES: We aimed to analyze angiographic and clinical results of patients undergoing BRS implantation in a real-world setting. BACKGROUND: Angiographic and clinical outcome data from patients undergoing implantation of drug-eluting bioresorbable stents (BRS) in routine clinical practice is scant. METHODS: Consecutive patients undergoing implantation of everolimus-eluting BRS at two high-volume centers in Munich, Germany were enrolled. Data were collected prospectively. All patients were scheduled for angiographic surveillance 6-8 months after stent implantation. Quantitative coronary angiographic analysis was performed in a core laboratory. Clinical follow-up was performed to 12 months and events were adjudicated by independent assessors. RESULTS: A total of 419 patients were studied. Mean age was 66.6 ± 10.9 years, 31.5% had diabetes mellitus, 76.1% had multivessel disease, and 39.0% presented with acute coronary syndrome; 49.0% of lesions were AHA/ACC type B2/C, 13.1% had treatment of bifurcation lesions. Mean reference vessel diameter was 2.89 ± 0.46 mm. At angiographic follow-up in-stent late loss was 0.26 ± 0.51 mm, in-segment diameter stenosis was 27.5 ± 16.1, and binary angiographic restenosis was 7.5%. At 12 months, the rate of death, myocardial infarction, or target lesion revascularization was 13.1%. Definite stent thrombosis occurred in 2.6%. CONCLUSIONS: The use of everolimus-eluting BRS in routine clinical practice is associated with high antirestenotic efficacy in patients undergoing angiographic surveillance. Overall clinical outcomes at 12 months are satisfactory though stent thrombosis rates are not insignificant. Further study with longer term follow-up and larger numbers of treated patients is required before we can be sure of the role of these devices in clinical practice.

Preoperative hemoglobin level: the best predictor of transfusion of packed red cells.

Blood transfusions could have serious consequences for patients. A reduction in the transfusion rate could be accomplished by an optimized blood management. Clear guidelines and awareness among all employees at a single institution have resulted in a reduction in transfusion rates in recent years. Identification of the group of patients who still received a blood transfusion in recent years could result in a further reduction. This study enrolled 4022 patients undergoing cardiothoracic surgery between 2008 and 2013. Patients were divided into three groups: "no blood transfusion", "transfusion of packed red cells only" and "any other combinations of blood transfusion". In total, 16 variables were tested for their association with the administration of homologous blood. The variables associated with blood transfusion were included in a stepwise multinomial logistic regression analysis to find the variables with the strongest association. For the transfusion of packed red cells only and any other combinations of blood transfusion, the following predictors are found: gender, age, weight, type of surgery, reoperation, unstable angina pectoris, endocarditis, recent myocardial infarction, preoperative creatinine level, preoperative hemoglobin level and preoperative platelet count. The best predictor for the transfusion of packed red cells is preoperative hemoglobin level (4.1 to 7.8 mmol/l). For other blood products, the strongest association was found with type of surgery (aortic surgery, ventricular septal rupture and intracardiac tumour).

The effector SPRYSEC-19 of Globodera rostochiensis suppresses CC-NB-LRR-mediated disease resistance in plants.

The potato cyst nematode Globodera rostochiensis invades roots of host plants where it transforms cells near the vascular cylinder into a permanent feeding site. The host cell modifications are most likely induced by a complex mixture of proteins in the stylet secretions of the nematodes. Resistance to nematodes conferred by nucleotide-binding-leucine-rich repeat (NB-LRR) proteins usually results in a programmed cell death in and around the feeding site, and is most likely triggered by the recognition of effectors in stylet secretions. However, the actual role of these secretions in the activation and suppression of effector-triggered immunity is largely unknown. Here we demonstrate that the effector SPRYSEC-19 of G. rostochiensis physically associates in planta with the LRR domain of a member of the SW5 resistance gene cluster in tomato (Lycopersicon esculentum). Unexpectedly, this interaction did not trigger defense-related programmed cell death and resistance to G. rostochiensis. By contrast, agroinfiltration assays showed that the coexpression of SPRYSEC-19 in leaves of Nicotiana benthamiana suppresses programmed cell death mediated by several coiled-coil (CC)-NB-LRR immune receptors. Furthermore, SPRYSEC-19 abrogated resistance to Potato virus X mediated by the CC-NB-LRR resistance protein Rx1, and resistance to Verticillium dahliae mediated by an unidentified resistance in potato (Solanum tuberosum). The suppression of cell death and disease resistance did not require a physical association of SPRYSEC-19 and the LRR domains of the CC-NB-LRR resistance proteins. Altogether, our data demonstrated that potato cyst nematodes secrete effectors that enable the suppression of programmed cell death and disease resistance mediated by several CC-NB-LRR proteins in plants.

Spin excitations of individual Fe atoms on Pt(111): impact of the site-dependent giant substrate polarization.

We demonstrate using inelastic scanning tunneling spectroscopy and simulations based on density functional theory that the amplitude and sign of the magnetic anisotropy energy for a single Fe atom adsorbed onto the Pt(111) surface can be manipulated by modifying the adatom binding site. Since the magnitude of the measured anisotropy is remarkably small, up to an order of magnitude smaller than previously reported, electron-hole excitations are weak and thus the spin excitation exhibits long lived precessional lifetimes compared to the values found for the same adatom on noble metal surfaces.

Controllable magnetic doping of the surface state of a topological insulator.

A combined experimental and theoretical study of doping individual Fe atoms into Bi(2)Se(3) is presented. It is shown through a scanning tunneling microscopy study that single Fe atoms initially located at hollow sites on top of the surface (adatoms) can be incorporated into subsurface layers by thermally activated diffusion. Angle-resolved photoemission spectroscopy in combination with ab initio calculations suggest that the doping behavior changes from electron donation for the Fe adatom to neutral or electron acceptance for Fe incorporated into substitutional Bi sites. According to first principles calculations within density functional theory, these Fe substitutional impurities retain a large magnetic moment, thus presenting an alternative scheme for magnetically doping the topological surface state. For both types of Fe doping, we see no indication of a gap at the Dirac point.

Robust nodal structure of Landau level wave functions revealed by Fourier transform scanning tunneling spectroscopy.

Scanning tunneling spectroscopy is used to study the real-space local density of states of a two-dimensional electron system in a magnetic field, in particular within higher Landau levels. By Fourier transforming the local density of states, we find a set of n radial minima at fixed momenta for the nth Landau levels. The momenta of the minima depend only on the inverse magnetic length. By comparison with analytical theory and numerical simulations, we attribute the minima to the nodes of the quantum cyclotron orbits, which decouple in a Fourier representation from the random guiding center motion due to disorder. Adequate Fourier filtering reveals the nodal structure in real space in some areas of the sample with relatively smooth potential disorder.

In-plane magnetic anisotropy of Fe atoms on Bi2Se3(111).

The robustness of the gapless topological surface state hosted by a 3D topological insulator against perturbations of magnetic origin has been the focus of recent investigations. We present a comprehensive study of the magnetic properties of Fe impurities on the prototypical 3D topological insulator Bi(2)Se(3) using local low-temperature scanning tunneling spectroscopy and integral x-ray magnetic circular dichroism techniques. Single Fe adatoms on the Bi(2)Se(3) surface, in the coverage range ≈ 1% of a monolayer, are heavily relaxed into the surface and exhibit a magnetic easy axis within the surface plane, contrary to what was assumed in recent investigations on the supposed opening of a gap. Using ab initio approaches, we demonstrate that an in-plane easy axis arises from the combination of the crystal field and dynamic hybridization effects.

Itinerant nature of atom-magnetization excitation by tunneling electrons.

We have performed single-atom magnetization curve (SAMC) measurements and inelastic scanning tunneling spectroscopy (ISTS) on individual Fe atoms on a Cu(111) surface. The SAMCs show a broad distribution of magnetic moments with 3.5 µB being the mean value. ISTS reveals a magnetization excitation with a lifetime of 200 fsec which decreases by a factor of 2 upon application of a magnetic field of 12 T. The experimental observations are quantitatively explained by the decay of the magnetization excitation into Stoner modes of the itinerant electron system as shown by newly developed theoretical modeling.

Insulin resistance explains the relationship between novel cardiovascular risk factors and hypertension. The Telde Study.

BACKGROUND: Most studies describing an association between hypertension and an inflammatory/pro-thrombotic state do not assess insulin resistance. AIM: To examine the association between hypertension and new cardiovascular risk factors when considering both classical risk factors and insulin resistance. METHODS: In a population-based sample of 1030 subjects, clinical information and blood samples were obtained. Subjects were classified according to the presence or absence of hypertension, and insulin resistance was estimated using the homeostasis model of assessment (HOMA). To identify variables independently associated with hypertension, a four-model multiple logistic regression was performed: model 1 included novel risk factors (Plasminogen Activator Inhibitor- 1 [PAI-1], fibrinogen, von Willebrand Factor [vWF], lipoprotein(a), homocysteine and C-reactive Protein [CRP]); model 2, novel risk factors plus HOMA; model 3 included both classical (smoking, triglycerides, HDL cholesterol, total cholesterol, waist circumference and diabetes) and novel risk factors and model 4, model 3 plus HOMA. All were adjusted for age, BMI and gender and compared using Akaike's Information Criterion (AIC). RESULTS: In model 1, only PAI-1, age and BMI showed association with hypertension.When HOMA and classical risk factors were also included, PAI-1 was replaced by triglyceride, smoking and diabetes. The lowest AIC value (best adjustment) was displayed by model 4, comprising all of the variables. Only age, BMI, HOMA and smoking remained significantly associated with hypertension. CONCLUSIONS: The novel cardiovascular risk factors assessed do not add information as markers of hypertension when classical risk factors or insulin resistance are included in the evaluation.

Mechanism of gonadotropin action in amphibia: involvement of mitochondria.

Luteinizing hormone (a pituitary gonadotropic hormone) stimulates Delta(5)-3beta- hydroxysteroid dehydrogenase activity in the microsomal fraction of frog testes when incubated together with the mitochondria; incubation together with the nuclei instead of the mitochondria does not result in increased, Delta(5)-3beta-hydroxysteroid dehydrogenase activity. The increase is not, induced by adenosine triphosphate, it appears to be hormone-specific, and it is sensitive to puromycin and actinomycin D. These data suggest that the mitochondrial DNA may be involved in mediating the action of luteinizing hormone in amphibian steroidogenesis.

Tongue-lip adhesion in the treatment of Pierre Robin sequence.

OBJECTIVE: Pierre Robin sequence (PRS) is a congenital malformation in which micrognathia causes retroposition of the tongue. This results in feeding and breathing difficulties that can lead to severe complications. If conservative treatment is not sufficient, a surgical procedure such as a tongue-lip adhesion can be performed. The objective of this study was to evaluate our benefits and complications with this operation. SETTING: All patients under the care of the Department of Plastic and Reconstructive Surgery of the VU University Medical Center, Amsterdam, The Netherlands, in the period 1993 to 2002. PATIENTS: A consecutive series of 22 patients who needed operative intervention for PRS. All underwent a tongue-lip adhesion. METHODS: Retrospective analysis of the patient charts. Follow-up has been performed for a minimum of 1 year. RESULTS: In 16 (73%) of the patients operated on, feeding and breathing have improved. In 6 children, the results were limited because of concomitant congenital anomalies. Complications, all without lasting effect, were observed in 12 (55%) of the patients: 4 of 5 children with dehiscence of the adhesion needed reoperation, 6 developed small chin abscess that resolved after removal of the supporting suture, and 1 patient was reintubated for bronchospasm. CONCLUSIONS: Tongue-lip adhesion is a good surgical treatment for most children with PRS who have an isolated tongue-base airway obstruction. More invasive procedures such as mandibular distraction can be reserved for patients where a tongue-lip adhesion has not been successful.

Chemical composition of industrially and laboratory processed Cyperus esculentus rhizomes.

We report here the results of the study of the chemical composition of Cyperus esculentus rhizomes. Ethanolic extracts have been separated by column chromatography and analyzed by magnetic resonance spectroscopy and mass spectrometry. Quercetin, stigmasterol, and linoleic and oleic acid glycerol esters, together with 4-chlorobutyl oleate, oleamide, myricetin, tyramine and N-feruloyltyramine, found for the first time in Cyperus esculentus rhizomes, have been isolated and quantified in the extracts. Alkaloids have not been detected, and the presence of flavonoids and sterols is moderate.

Engineering the spin couplings in atomically crafted spin chains on an elemental superconductor.

Magnetic atoms on a superconductor give rise to Yu-Shiba-Rusinov (YSR) states within the superconducting energy gap. A spin chain of magnetic adatoms on an s-wave superconductor may lead to topological superconductivity accompanied by the emergence of Majorana modes at the chain ends. For their usage in quantum computation, it is a prerequisite to artificially assemble the chains and control the exchange couplings between the spins in the chain and in the substrate. Here, using a scanning tunneling microscope tip, we demonstrate engineering of the energy levels of the YSR states by placing interstitial Fe atoms in close proximity to adsorbed Fe atoms on an oxidized Ta surface. Based on this prototype platform, we show that the interaction within a long chain can be strengthened by linking the adsorbed Fe atoms with the interstitial ones. Our work adds an important step towards the controlled design and manipulation of Majorana end states.

Toxicological assessment of Xanthigen® nutraceutical extract combination: Mutagenicity, genotoxicity and oral toxicity.

Xanthigen® is a nutraceutical combination for weight management capable of increasing energy expenditure via uncoupling protein 1 (UCP-1) in white adipose tissue. It consists of brown seaweed Undaria pinnatifida extract, rich in the carotenoid fucoxanthin (FX) and pomegranate seed oil (PSO), rich in punicic acid. Xanthigen was screened to determine its genotoxicity and 90-days repeated oral toxicity. Genotoxicity was assessed with the Ames test (TA89, TA100, TA1535, TA1537, WP2), chromosomal aberration assay (Chinese hamster ovary cells) and mammalian micronucleus test (in mice). Xanthigen did not exhibit genotoxicity in any tested strain. Sub-chronic toxicity was evaluated with daily oral administration of 250, 500 and 1000 mg/kg/day doses of Xanthigen® to Sprague-Dawley rats over 90 days. No deaths and no deleterious effects were observed during the 90-day treatment, indicating an absence of sub-chronic toxicity and a no observed adverse effect level greater than 1000 mg/kg/day. A statistically significant decrease in bodyweight and food intake in Xanthigen® treated groups was attributed to the weight loss property of Xanthigen®. Overall, Xanthigen® shows no significant mutagenic or toxic effects.

Regulation of estrogen receptor (ER) levels in MCF-7 cells by progesterone metabolites.

Estradiol-17beta (E2) may participate in carcinoma of mammary cells containing estradiol receptors (ER) at sufficient levels. Hence, the regulation of ER levels may be important for the progression of estrogen-dependent mammary carcinomas. Our previous findings that the progesterone metabolite, 5alpha-pregnane-3,20-dione (5alphaP), exhibits marked mitogenic and metastatic properties, whereas the progesterone metabolites, 4-pregnen-3alpha-ol-20-one (3alphaHP) and 4-pregnen-20alpha-ol-3-one (20alphaHP), oppose these actions, prompted examination of the possible effects of these progesterone metabolites on ER concentration in MCF-7 breast cancer cells. Cells were exposed for 24h to 0 (control) or 10(-10) to 10(-6)M E2, 5alphaP, 3alphaHP, 20alphaHP or combinations of these steroids, and ER concentrations were determined for intracellular estrogen receptors by specific binding of [(3)H]E2. The total ER number (nuclear plus cytosolic) in control samples was 2551+/-164 per cell. E2 and 5alphaP resulted in significant dose-dependent increases in total ER numbers ( approximately 1.6-fold and approximately 2.2-fold at 10(-6)M, respectively). In combination, E2+5alphaP resulted in additive increases in ER numbers. Individually, 3alphaHP and 20alphaHP each resulted in dose-dependent decreases (43% and 54% at 10(-6)M, respectively) in total ER numbers and inhibited the E2- or 5alphaP-induced increases in ER levels. In combination, 3alphaHP+20alphaHP resulted in dose-dependent additive suppression of ER levels. Treatment with cycloheximide or actinomycin D indicated that both transcription and translation are involved in 5alphaP and 3alphaHP action on ER numbers. Real time RT-PCR showed increases in expression of ERalpha transcripts due to 5alphaP and increases in expression of ERbeta due to 3alphaHP; expression levels of either ERalpha or ERbeta were not significantly altered when cells were treated with 5alphaP+3alphaHP. The results are the first to show that the pro- and anti-cancer progesterone metabolites also have marked selective (up or down) regulatory effects on ER levels in MCF-7 breast cancer cells.