The quantum dynamics of H2 on Cu(111) at a surface temperature of 925 K: Comparing state-of-the-art theory to state-of-the-art experiments 2.

State-of-the-art 6D quantum dynamics simulations for the dissociative chemisorption of H2 on a thermally distorted Cu(111) surface, using the static corrugation model, were analyzed to produce several (experimentally available) observables. The expected error, especially important for lower reaction probabilities, was quantified using wavepackets on several different grids as well as two different analysis approaches to obtain more accurate results in the region where a slow reaction channel was experimentally shown to be dominant. The lowest reaction barrier sites for different thermally distorted surface slabs are shown to not just be energetically, but also geometrically, different between surface configurations, which can be used to explain several dynamical effects found when including surface temperature effects. Direct comparison of simulated time-of-flight spectra to those obtained from state-of-the-art desorption experiments showed much improved agreement compared to the perfect lattice BOSS approach. Agreement with experimental rotational and vibrational efficacies also somewhat improved when thermally excited surfaces were included in the theoretical model. Finally, we present clear quantum effects in the rotational quadrupole alignment parameters found for the lower rotationally excited states, which underlines the importance of careful quantum dynamical analyses of this system.

The quantum dynamics of H2 on Cu(111) at a surface temperature of 925 K: Comparing state-of-the-art theory to state-of-the-art experiments.

We present results of our recently expanded static corrugation model (SCM) approach that included the relevant surface temperature effects, applied to the dissociative chemisorption reaction of H2 on a Cu(111) surface. The reaction and rovibrationally elastic scattering probabilities that we obtain at a quantum dynamical (QD) level, as an average of many statically distorted surface configurations, show great agreement with those of a dynamic surface model, which reinforces the validity of the sudden approximation inherent to the SCM. We further investigate several simple methods of binning the final rovibrational state of quasi-classical dynamics simulations, to find those best suited to reproduce the QD results for our system. Finally, we show that the SCM obtained results reproduce experimental dissociation curves very well, when the uncertainty in experimental saturation values is taken into account. Some indication of a slow channel, so far only observed in experiment, can also be found at low incidence energies, although more rigorous QD simulations are required to reduce the noise inherent to our propagation methods.

Accurate description of the quantum dynamical surface temperature effects on the dissociative chemisorption of H2 from Cu(111).

Accurately describing surface temperature effects for the dissociative scattering of H2 on a metal surface on a quantum dynamical (QD) level is currently one of the open challenges for theoretical surface scientists. We present the first QD simulations of hydrogen dissociating on a Cu(111) surface, which accurately describe all relevant surface temperature effects, using the static corrugation model. The reaction probabilities we obtain show very good agreement with those found using quasi-classical dynamics (QCD), both for individual surface slabs and for an averaged, thus Monte Carlo sampled, set of thermally distorted surface configurations. Rovibrationally elastic scattering probabilities show a much clearer difference between the QCD and QD results, which appears to be traceable back toward thermally distorted surface configurations with very low dissociation probabilities and underlines the importance of investigating more observables than just dissociation. By reducing the number of distorted surface atoms included in the dynamical model, we also show that only including one surface atom, or even three surface atoms, is generally not enough to accurately describe the effects of the surface temperature on dissociation and elastic scattering. These results are a major step forward in accurately describing hydrogen scattering from a thermally excited Cu(111) surface and open up a pathway to better describe reaction and scattering from other relevant crystal facets, such as stepped surfaces, at moderately elevated surface temperatures where quantum effects are expected to play a more important role in the dissociation of H2 on Cu.

Beyond the static corrugation model: Dynamic surfaces with the embedded atom method.

The D2 on Cu(111) system has for many years been one of the major benchmark systems for surface scientists. Generating surface configurations using the embedded atom method (EAM), we investigate the quality of the chemically accurate static corrugation model (SCM) for including surface temperature effects, with a focus on the random displacement approach to its distorted surface generation. With this EAM potential, we also treat the Cu(111) surface of our system fully dynamically and shine a further light on not only the quality of the SCM sudden approach but also the limited effect of energy exchange with the surface. Reaction and (in)elastic scattering probability curves, as well as simulated time-of-flight spectra, show good agreement with both earlier works and experimental results, with surface reactions showing a preference for surface atoms displaced away from the incoming molecule. The good agreement with the non-static surface model also further establishes the limited effect of energy exchange on not only the reaction but also on the elastic and inelastic scattering probabilities, even though some molecular translational energy is deposited into the surface.

An improved static corrugation model.

Accurately describing surface temperature effects for the dissociation of H2 on Cu(111) remains challenging. While Ab initio Molecular Dynamics (AIMD), the current state-of-the-art method for modelling such systems, can produce accurate results, it is computationally very expensive to use for extensive testing of, for example, density functionals. A chemically accurate static corrugation model for H2 and D2 on Cu(111) dissociation was made by introducing effective three-body interactions as well as an H2-bond dependence and fitting the model to density functional theory energies for 15 113 different configurations. Reaction probabilities and rovibrational (in)elastic scattering probabilities were computed and compared to experiments and other calculations. Theoretical and experimental results are in good agreement, except for the reaction of (v = 0, J = 0) H2 where both AIMD and the newly developed static corrugation model, both based on the same underlying density functional, predict a similar deviation from the experiment.

[Is psychiatry ready to let patients review their own files? Inventory of initial experiences]. / Is de psychiatrie klaar voor de meelezende patiënt? Inventarisatie van eerste ervaringen.

BACKGROUND: Dutch patients will be granted the right to digitally access their own medical records, an option already available to the patients at the University Medical Center Utrecht since 2015. AIM: To start a conversation about the development of readily accessible online patient records. METHODS Describe the experiences of a University department of psychiatry with an online patient portal, obtained through discussions and questionnaires. RESULTS: During the next few years three legal developments will enable patients to acquire direct, remote, digital access to their medical files. Immediate online review of medical records improves accessibility and empowers the patient. Some therapists experienced a change in patient interaction. Furthermore, during documentation psychiatrists took into account that patients could review the contents at a later point. CONCLUSION: Patients' accessibility of online records will influence the patient-therapist dynamic. More research on the patient perspective and a discussion among professionals are necessary to further streamline broad implementation of online patient portals.

Exploring surface landscapes with molecules: rotationally induced diffraction of H2 on LiF(001) under fast grazing incidence conditions.

Atomic diffraction by surfaces under fast grazing incidence conditions has been used for almost a decade to characterize surface properties with more accuracy than with more traditional atomic diffraction methods. From six-dimensional solutions of the time-dependent Schrödinger equation, we show that diffraction of H2 molecules under fast grazing incidence conditions could be even more informative for the characterization of ionic surfaces, due to the large anisotropic electrostatic interaction between the quadrupole moment of the molecule and the electric field created by the ionic crystal. Using the LiF(001) surface as a benchmark, we show that fast grazing incidence diffraction of H2 strongly depends on the initial rotational state of the molecule, while rotationally inelastic processes are irrelevant. We demonstrate that, as a result of the anisotropy of the impinging projectile, initial rotational excitation leads to an increase in intensity of high-order diffraction peaks at incidence directions that satisfy precise symmetry constraints, thus providing a more detailed information on the surface characteristics than that obtained from low-order atomic diffraction peaks under fast grazing incidence conditions. As quadrupole-ion surface potentials are expected to accurately represent the interaction between H2 and any surface with a marked ionic character, our analysis should be of general applicability to any of such surfaces. Finally, we show that a density functional theory description of the molecule-ion surface potential catches the main features observed experimentally.

Towards a specific reaction parameter density functional for reactive scattering of H2 from Pd(111).

Recently, an implementation of the specific reaction parameter (SRP) approach to density functional theory (DFT) was used to study several reactive scattering experiments of H2 on Cu(111). It was possible to obtain chemical accuracy (1 kcal/mol ≈ 4.2 kJ/mol), and therefore, accurately model this paradigmatic example of activated H2 dissociation on a metal surface. In this work, the SRP-DFT methodology is applied to the dissociation of hydrogen on a Pd(111) surface, in order to test whether the SRP-DFT approach is also applicable to non-activated H2-metal systems. In the calculations, the Born-Oppenheimer static surface approximations are used. A comparison to molecular beam sticking experiments, performed at incidence energies ≥125 meV, on H2 + Pd(111) suggested the PBE-vdW [where the Perdew, Burke, and Ernzerhof (PBE) correlation is replaced by van der Waals correlation] functional as a candidate SRP density functional describing the reactive scattering of H2 on Pd(111). Unfortunately, quantum dynamics calculations are not able to reproduce the molecular beam sticking results for incidence energies <125 meV. From a comparison to initial state-resolved (degeneracy averaged) sticking probabilities it seems clear that for H2 + Pd(111) dynamic trapping and steering effects are important, and that these effects are not yet well modeled with the potential energy surfaces considered here. Applying the SRP-DFT method to systems where H2 dissociation is non-activated remains difficult. It is suggested that a density functional that yields a broader barrier distribution and has more non-activated pathways than PBE-vdW (i.e., non-activated dissociation at some sites but similarly high barriers at the high energy end of the spectrum) should allow a more accurate description of the available experiments. Finally, it is suggested that new and better characterized molecular beam sticking experiments be done on H2 + Pd(111), to facilitate the development of a more accurate theoretical description of this system.

Reactive scattering of H2 from Cu(100): comparison of dynamics calculations based on the specific reaction parameter approach to density functional theory with experiment.

We present new experimental and theoretical results for reactive scattering of dihydrogen from Cu(100). In the new experiments, the associative desorption of H(2) is studied in a velocity resolved and final rovibrational state selected manner, using time-of-flight techniques in combination with resonance-enhanced multi-photon ionization laser detection. Average desorption energies and rotational quadrupole alignment parameters were obtained in this way for a number of (v = 0, 1) rotational states, v being the vibrational quantum number. Results of quantum dynamics calculations based on a potential energy surface computed with a specific reaction parameter (SRP) density functional, which was derived earlier for dihydrogen interacting with Cu(111), are compared with the results of the new experiments and with the results of previous molecular beam experiments on sticking of H(2) and on rovibrationally elastic and inelastic scattering of H(2) and D(2) from Cu(100). The calculations use the Born-Oppenheimer and static surface approximations. With the functional derived semi-empirically for dihydrogen + Cu(111), a chemically accurate description is obtained of the molecular beam experiments on sticking of H(2) on Cu(100), and a highly accurate description is obtained of rovibrationally elastic and inelastic scattering of D(2) from Cu(100) and of the orientational dependence of the reaction of (v = 1, j = 2 - 4) H(2) on Cu(100). This suggests that a SRP density functional derived for H(2) interacting with a specific low index face of a metal will yield accurate results for H(2) reactively scattering from another low index face of the same metal, and that it may also yield accurate results for H(2) interacting with a defected (e.g., stepped) surface of that same metal, in a system of catalytic interest. However, the description that was obtained of the average desorption energies, of rovibrationally elastic and inelastic scattering of H(2) from Cu(100), and of the orientational dependence of reaction of (v = 0, j = 3 - 5, 8) H(2) on Cu(100) compares less well with the available experiments. More research is needed to establish whether more accurate SRP-density functional theory dynamics results can be obtained for these observables if surface atom motion is added to the dynamical model. The experimentally and theoretically found dependence of the rotational quadrupole alignment parameter on the rotational quantum number provides evidence for rotational enhancement of reaction at low translational energies.

Static surface temperature effects on the dissociation of H2 and D2 on Cu(111).

A model for taking into account surface temperature effects in molecule-surface reactions is reported and applied to the dissociation of H(2) and D(2) on Cu(111). In contrast to many models developed before, the model constructed here takes into account the effects of static corrugation of the potential energy surface rather than energy exchange between the impinging hydrogen molecule and the surface. Such an approximation is a vibrational sudden approximation. The quality of the model is assessed by comparison to a recent density functional theory study. It is shown that the model gives a reasonable agreement with recently performed ab initio molecular dynamics calculations, in which the surface atoms were allowed to move. The observed broadening of the reaction probability curve with increasing surface temperature is attributed to the displacement of surface atoms, whereas the effect of thermal expansion is found to be primarily a shift of the curve to lower energies. It is also found that the rotational quadrupole alignment parameter is generally lowered at low energies, whereas it remains approximately constant at high energies. Finally, it is shown that the approximation of an ideal static surface works well for low surface temperatures, in particular for the molecular beams for this system (T(s) = 120 K). Nonetheless, for the state-resolved reaction probability at this surface temperature, some broadening is found.

Diffractive and reactive scattering of H2 from Ru(0001): experimental and theoretical study.

We present a combined experimental and theoretical study of the diffraction of H(2) from Ru(0001) in the incident energy range 78-150 meV, and a theoretical study of dissociative chemisorption of H(2) in the same system. Pronounced out-of-plane diffraction was observed in the whole energy range studied. The energy dependence of the elastic diffraction intensities was measured along the two main symmetry directions for a fixed parallel translational energy. The data were compared with quantum dynamics calculations performed by using DFT-based, six-dimensional potential energy surfaces calculated with both the PW91 and RPBE functionals, as well as with a functional obtained from a weighted average of both (the MIX functional, which was earlier shown to perform quite well for H(2) + Cu(111)). Our results show that the PW91 functional describes the H(2) diffraction intensities more accurately than the RPBE and the MIX functionals, although the absolute values of these intensities are overestimated in the calculations. For the reaction probabilities a preference for one or the other functional cannot be given over the entire energy range probed by the sticking experiments. The PW91 functional yields too high reaction probabilities over the entire investigated energy range, but is better than RPBE at low collision energies (<0.1 eV). The RPBE functional gives too low reaction probabilities at low energy and somewhat too high reaction probabilities at high energy, but agrees better with experiment than PW91 for energies >0.1 eV. The results suggest that, in order to get a better description of both H(2) diffraction and dissociative chemisorption for this system, a specific reaction parameter functional for H(2) + Ru(0001) is needed that is a weighted average of functionals other than PW91 and RPBE. We speculate that differences between the H(2) + Ru(0001) system (early and low reaction barrier) and H(2) + Cu(111) (late and high reaction barrier) may well lead to fundamentally different specific reaction parameter functionals, and that including a reasonable accurate description of the van der Waals interaction might be important for H(2) + Ru(0001) which has barriers localised far away from the surface. Based on our results we advocate new, systematic combined theoretical and experimental studies of H(2) interacting with transition metals in early and late barrier systems, with the aim of determining whether specific reaction parameter functionals for these systems might differ in a systematic way.

Belgian consensus guideline on the management of hemorrhoidal disease.

Introduction: Hemorrhoidal disease is a common problem that arises when hemorrhoidal structures become engorged and/or prolapse through the anal canal. Both conservative and invasive treatment options are diverse and guidance to their implementation is lacking. Methods: A Delphi consensus process was used to review current literature and draft relevant statements. These were reconciliated until sufficient agreement was reached. The grade of evidence was determined. These guidelines were based on the published literature up to June 2020. Results: Hemorrhoids are normal structures within the anorectal region. When they become engorged or slide down the anal canal, symptoms can arise. Every treatment for symptomatic hemorrhoids should be tailored to patient profile and expectations. For low-grade hemorrhoids, conservative treatment should consist of fiber supplements and can include a short course of venotropics. Instrumental treatment can be added case by case : infrared coagulation or rubber band ligation when prolapse is more prominent. For prolapsing hemorrhoids, surgery can be indicated for refractory cases. Conventional hemorrhoidectomy is the most efficacious intervention for all grades of hemorrhoids and is the only choice for non-reducible prolapsing hemorrhoids. Conclusions: The current guidelines for the management of hemorrhoidal disease include recommendations for the clinical evaluation of hemorrhoidal disorders, and their conservative, instrumental and surgical management.

Hand-preference and population schizotypy: a meta-analysis.

Language functions in schizophrenia patients are represented more bilateral, i.e. less lateralized than in healthy subjects. This decreased lateralization is also observed in individuals at increased risk for schizophrenia. Language lateralization is related to handedness; in that left- and mixed-handed individuals more frequently have decreased lateralization in comparison to right-handed subjects. Population schizotypy can be considered part of the schizophrenia spectrum disorders. In line with this, population schizotypy has repeatedly, though inconsistently, been associated with left-handedness. In order to define the exact association between handedness and schizotypy, we performed meta-analyses on the available literature. We found that non-right-handed subjects, but not strong left-handers, had higher scores on schizotypy questionnaires than right-handed subjects. Mixed-handers showed a trend towards higher schizotypy in comparison to strong left-handers. It is argued that the higher schizotypy in non-right-handed individuals reflects the higher incidence of bilateral language lateralization in this group. Bilateral language organisation may underlie loosening of association, possibly leading to higher schizotypy scores.

The fate of nitrite and nitrate during anaerobic digestion.

Anaerobic digestion is widely used to produce renewable energy. However, the main drawback is the limited conversion efficiency of organic matter. Applying an advanced oxidation process as a digestate post-treatment is able to increase this conversion efficiency but will also lead to the oxidation of ammonium to nitrite or nitrate. In this lab-scale study, the fate of the latter in the digester was investigated. Nitrite and nitrate were therefore added in concentrations that could arise from rate-limiting ammonium concentrations (1.25-5 g L-1 N). The study clearly demonstrated that nitrite and nitrate were denitrified during the subsequent digestion process resulting in the formation of nitrogen gas. After a concentration-dependent adaptation period, in which some biogas was produced, the added nitrite was denitrified in amounts proportional to the amounts of electron donor present. This denitrification, however, strongly reduces the possibility that Anammox bacteria can develop. Nitrate was also denitrified in amounts proportional to the amounts of electron donor, but biogas production was not completely blocked in this case. Moreover, high concentrations of nitrite and nitrate inhibited their own denitrification. The methane formed was used as electron donor for the further denitrification of nitrate and nitrite when no other readily available electron donor was present. After addition of either nitrite or nitrate and their denitrification, the biogas production did not recover properly.

The effect of vascular access location and size on circuit survival in pediatric continuous renal replacement therapy: a report from the PPCRRT registry.

PURPOSE: Well-functioning vascular access is essential for the provision of adequate CRRT. However, few data exist to describe the effect of catheter size or location on CRRT performance in the pediatric population. METHODS: Data for vascular access site, size, and location, as well as type of anticoagulant used and patient demographic data were gathered from the ppCRRT registry. Kaplan-Meier curves were generated and then analyzed by log-rank test or Cox Proportional Hazards model. RESULTS: Access diameter was found to significantly affect circuit survival. None of the 5 French catheters lasted longer than 20 hours. Seven and 9 French, but not 8 French, catheters fared worse than larger diameter catheters (p=0.002). Circuits associated with internal jugular access survived longer than subclavian or femoral access associated circuits (p<0.05). Circuit survival was also found to be favorably associated with the CVVHD modality (p<0.001). CONCLUSIONS: Functional CRRT circuit survival in children is favored by larger catheter diameter, internal jugular vein insertion site and CVVHD. For patients requiring catheter diameters less than 10 French, CRRT circuit survival might be optimized if internal jugular vein insertion is feasible. Conversely, when a vascular access site other than the internal jugular vein is most prudent, consideration should be given to using the largest diameter catheter appropriate for the size of the child. The CVVHD modality was associated with longer circuit survival, but the mechanism by which this occurs is unclear.

Manometric and ultrasonographic characteristics of patients with coexisting fecal incontinence and constipation.

BACKGROUND: The treatment of fecal incontinence (FI) depends upon the dominant pathophysiology: impaired sphincter contractility or overflow due to pelvic floor dyssynergia and insufficient rectal emptying. In this study, we aimed to define the manometric and anorectal ultrasound characteristics in FI patients with and without constipation. METHODS: We did a retrospective study of 365 anal manometries, performed between October 2012 and July 2015, in patients with FI. Clinical information was obtained from questionnaires. In 220 of these patients an anorectal ultrasound was also available. Key results : A high prevalence of self-reported constipation was seen in the total population of FI patients (66%). This number was lower (31%) when Rome IV criteria were applied. A very high percentage of manometric pelvic floor dyssynergia was seen in the total population with FI (81%). However, patients with FI and constipation did not show pelvic floor dyssynergia more often than patients without constipation. Anal resting pressure, squeeze pressure and anorectal pressure sensitivity were not different when comparing patients without and with constipation. The prevalence of a functional defecation disorder (FDD) in our study population of FI patients was 20%. Wexner score in this subgroup was lower compared with patients without FDD. Anal sphincter defects were more prevalent in women than men, and were associated with diminished sphincter contractility. CONCLUSION AND INFERENCES: A very high percentage of FI patients showed manometric pelvic floor dyssynergia. The coexistence of fecal incontinence and constipation did not increase this percentage. KEY MESSAGES: Constipation is a frequent and underestimated cause of FI. A correct diagnosis has a major impact on treatment. We aimed to characterize the manometric and transrectal ultrasound profile of FI patients with and without signs of coexisting constipation. - A very high percentage of incontinent patients showed pelvic floor dyssynergia, however no significant difference between the group with and the group without constipation was seen. Anal resting pressure, squeeze pressure and anorectal pressure sensitivity did not differ significantly either.

Dynamic platelet function on von Willebrand factor is different in preterm neonates and full-term neonates: changes in neonatal platelet function.

Essentials It is unclear if platelet function differs between preterm and full-term neonates. Platelet behavior was characterized using a flow-based assay on von Willebrand Factor (VWF). Preterms had increased platelet interaction with VWF and glycoprotein Ibα expression. Platelets from preterm neonates behave differently on VWF compared to full-term neonates. SUMMARY: Background Very low birth weight (VLBW) preterm neonates have an increased risk of hemorrhage-related morbidity and mortality as compared with their full-term counterparts. It is unclear whether platelet function differs between preterm and full-term neonates. This is partly because of the large volumes of blood required to perform standard platelet function tests, and the difficulty in obtaining such samples in neonates. Objectives This study was designed to characterize platelet behavior in neonates with a physiologic flow-based assay that quantifies platelet function in microliter volumes of blood under arterial shear. Methods Blood from VLBW preterm neonates of ≤ 32 weeks' gestation (n = 15) and full-term neonates (n = 13) was perfused under arterial shear over surface-immobilized von Willebrand factor (VWF). Platelet behavior was recorded by digital-image microscopy and analyzed. Surface expression of platelet glycoprotein (GP) Ibα and GPIIIa of VLBW preterm and full-term neonates was also measured. Results VLBW preterm neonates had increased numbers of platelets interacting with VWF, and increased GPIbα expression on the platelet surface. Despite the increased numbers of VWF interactions as reflected by flow-driven platelet translocation along the protein surface, no significant differences were observed in the numbers of platelets that adhered in a stationary fashion to VWF. Platelets from VLBW preterm neonates and those from full-term neonates behaved differently on VWF. Conclusions These differences in platelet function may contribute to the higher incidence of bleeding observed in VLBW preterm neonatal populations, or may represent a compensatory mechanism to counteract this risk of bleeding.

Vascular superoxide production and vasomotor function in hypertension induced by deoxycorticosterone acetate-salt.

BACKGROUND: Angiotensin II-induced hypertension is associated with increased vascular superoxide production, which contributes to hypertension caused by the octapeptide. In cell culture, stretch increases endothelial and vascular smooth muscle production of reactive oxygen species (ROS). In perfused isolated vessels, elevations of pressure can increase vessel angiotensin II production. The effects of low-renin hypertension on vascular ROS production remain unclear. Furthermore, the role of ROS in vascular function and hypertension in low-renin hypertension is undefined. METHODS AND RESULTS: Rats were treated with DOCA and saline drinking water for 3 weeks. Both systolic blood pressure (189+/-4 versus 126+/-2 mm Hg) and aortic superoxide production (3972+/-257 versus 852+/-287, P<0. 05) were increased compared with controls. Relaxations of vascular segments to acetylcholine (ACh, 100+/-2% versus 75+/-2%, P<0.05) and the calcium ionophore A23187 (92+/-2% versus 72+/-3%, P<0.05) were also impaired in DOCA-salt. Heparin-binding superoxide dismutase (1200 U/d IV for 3 days) had no effect on blood pressure but significantly improved relaxations to ACh and A23187. Losartan (25 mg x kg(-1) x d(-1) PO) for 7 days did not correct the hypertension or endothelium-dependent vessel relaxation in DOCA-salt rats, excluding a role of a local renin/angiotensin II system. CONCLUSIONS: These findings indicate that increased vascular superoxide production occurs not only in angiotensin II-induced hypertension but also in hypertension known to be associated with low-renin states. Increased superoxide production alters large-vessel endothelium-dependent vascular relaxation but does not modulate blood pressure in low-renin hypertension.

Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin.

BACKGROUND: Altered endothelial cell nitric oxide (NO(*)) production in atherosclerosis may be due to a reduction of intracellular tetrahydrobiopterin, which is a critical cofactor for NO synthase (NOS). In addition, previous literature suggests that inactivation of NO(*) by increased vascular production superoxide (O(2)(*-)) also reduces NO(*) bioactivity in several disease states. We sought to determine whether these 2 seemingly disparate mechanisms were related. METHODS AND RESULTS: Endothelium-dependent vasodilation was abnormal in aortas of apoE-deficient (apoE(-/-)) mice, whereas vascular superoxide production (assessed by 5 micromol/L lucigenin) was markedly increased. Treatment with either liposome-entrapped superoxide dismutase or sepiapterin, a precursor to tetrahydrobiopterin, improved endothelium-dependent vasodilation in aortas from apoE(-/-) mice. Hydrogen peroxide had no effect on the decay of tetrahydrobiopterin, as monitored spectrophotometrically. In contrast, superoxide modestly and peroxynitrite strikingly increased the decay of tetrahydrobiopterin over 500 seconds. Luminol chemiluminescence, inhibitable by the peroxynitrite scavengers ebselen and uric acid, was markedly increased in apoE(-/-) aortic rings. In vessels from apoE(-/-) mice, uric acid improved endothelium-dependent relaxation while having no effect in vessels from control mice. Treatment of normal aortas with exogenous peroxynitrite dramatically increased vascular O(2)(*-) production, seemingly from eNOS, because this effect was absent in vessels lacking endothelium, was blocked by NOS inhibition, and did not occur in vessels from mice lacking eNOS. CONCLUSIONS: Reactive oxygen species may alter endothelium-dependent vascular relaxation not only by the interaction of O(2)(*-) with NO(*) but also through interactions between peroxynitrite and tetrahydrobiopterin. Peroxynitrite oxidation of tetrahydrobiopterin may represent a pathogenic cause of "uncoupling" of NO synthase.

Amniotic fluid insulin at 14-20 weeks' gestation: association with later maternal glucose intolerance and birth macrosomia.

OBJECTIVE: To examine the hypothesis that early second trimester amniotic fluid (AF) insulin concentration is elevated and later fetal growth is augmented in gravidas demonstrating later oral glucose intolerance. RESEARCH DESIGN AND METHODS: In this prospective observational cohort study, AF was sampled at 14-20 weeks' gestation in 247 subjects, and 1-h 50-g oral glucose challenge tests (GCTs) were performed at > or = 24 weeks. AF insulin was assayed by an automated immuno-chemiluminometric assay (8). Macrosomia was defined as birth weight above the 90th centile. RESULTS: AF insulin concentration (range 1.4-44.5 pmol/l) correlated positively with gestational age and maternal weight. A logistic regression analysis, adjusted for maternal age and midpregnancy weight, showed increased AF insulin multiples of gestational age-specific medians to be associated with subsequently diagnosed gestational diabetes mellitus (GDM) (OR 1.9, CI 1.3-2.4, P = 0.029). Among 60 subjects with GCT values > 7.2 mmol/l, each unit increase in AF insulin multiple of median (MOM) was associated with a threefold increase in fetal macrosomia incidence (3.1, 1.3-4.9, P = 0.048). CONCLUSIONS: An elevated AF insulin concentration at 14-20 weeks' gestation is associated with subsequently documented maternal glucose intolerance. Among gravidas with GCT values > 7.2 mmol/l, elevated early AF insulin concentration is associated with fetal macrosomia. Maternal glucose intolerance may affect fetal insulin production before 20 weeks' gestation.