Fasting Plasma Ketone Bodies Are Associated with NT-proBNP: A Potential Mechanism to Provide Fuel for the Failing Heart.

Background: Heart failure (HF) features a shift in metabolism towards enhanced utilization of ketone bodies. While elevations in plasma natriuretic peptides represent a biochemical hallmark of HF, natriuretic peptides may promote lipolysis, thereby contributing to fatty acid availability for ketogenesis. Methods: We cross-sectionally tested to what extent fasting plasma total ketone bodies (measured using nuclear magnetic resonance spectroscopy) are associated with N-terminal pro-BNP (NT-proBNP; electrochemiluminescent sandwich immunoassay) in individuals with and without HF. Results: Among 6217 participants from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study, 203 were identified with HF. NT-proBNP was four-fold and total ketone bodies were 25% higher in HF participants (each p < 0.001). In both participants with and without HF, total ketone body levels correlated with NT-proBNP (r = 0.116 and 0.185, respectively; p < 0.001). In multivariable linear regression analysis adjusted for relevant covariates, total ketone bodies remained associated with NT-proBNP in the whole cohort (std ß = 0.08, p < 0.001), without a difference in participants with and without HF (p interaction: 0.52). Conclusion: This general population-based study reveals an independent association of fasting total body ketone bodies with plasma NT-proBNP. Our findings suggest that a metabolic defense mechanism could be operative, providing the myocardium with ketone bodies to meet its energy demands.

Multiphysics analysis of chip and resonator designs for increased damage threshold of external cavity high-power laser diodes.

We present a detailed analysis of multiphysics simulation results to evaluate the threshold for catastrophic optical damage (COD) of high-power laser diodes under misaligned external optical feedback. Three different chip designs are investigated: the non-injecting mirror concept, the non-absorbing mirror concept and the introduction of an additional energy barrier within the waveguide near the front facet. Furthermore, a modification of the external resonator that promises a lower sensitivity towards misalignments is considered. The dependence of the COD threshold on the additional design parameters (bandgap change, modification length, focal length) and the impact of the different approaches on electro-optical efficiency as well as beam quality are analyzed. Compared to the initial design, the different chip design concepts promise an increase of the achievable output power by 8%, 27% and 27% respectively, whereas the modified resonator fully prevents feedback-induced failure.

Dynamic correction of optical aberrations for height-independent selective laser induced etching processing strategies.

Optical aberrations are a critical issue for tight focusing and high precision manufacturing with ultrashort pulsed laser radiation in transparent media. Controlling the wave front of ultrashort laser pulses enable the correction of low order phase front distortion and significantly enhances the simplification of laser-based manufacturing of 3D-parts in glass. The influence of system-inherent, dominating aberrations such as spherical and astigmatic aberrations affect the focal area, the beam caustic and therefore the focus intensity distribution. We correct these aberrations by means of a spatial light modulator (SLM) for various processing depths in glass thickness of up to 12 mm. This flexible aberration correction significantly simplifies the process control and scanning strategies for the selective laser induced etching process. The influence on the selectivity is investigated by comparing the three different focus conditions of the intrinsic microscope objective aberration corrected, the aberrated and the SLM aberration corrected beam profile. The previously necessary pulse energy adjustment for different z positions in the glass volume is compensated via SLM aberration correction in the end. Furthermore, the spatial extend of the modified and etched area is investigated. In consequence, a simplified scan strategy and depth-independent processing parameters can be achieved for the selective laser induced etching process.

Short-Chain Fatty Acids in the Metabolism of Heart Failure - Rethinking the Fat Stigma.

Heart failure (HF) remains a disease with immense global health burden. During the development of HF, the myocardium and therefore cardiac metabolism undergoes specific changes, with decreased long-chain fatty acid oxidation and increased anaerobic glycolysis, diminishing the overall energy yield. Based on the dogma that the failing heart is oxygen-deprived and on the fact that carbohydrates are more oxygen-efficient than FA, metabolic HF drugs have so far aimed to stimulate glucose oxidation or inhibit FA oxidation. Unfortunately, these treatments have failed to provide meaningful clinical benefits. We believe it is time to rethink the concept that fat is harmful to the failing heart. In this review we discuss accumulating evidence that short-chain fatty acids (SCFAs) may be an effective fuel for the failing heart. In contrast to long-chain fatty acids, SCFAs are readily taken up and oxidized by the heart and could serve as a nutraceutical treatment strategy. In addition, we discuss how SCFAs activate pathways that increase long chain fatty acid oxidation, which could help increase the overall energy availability. Another potential beneficial effect we discuss lies within the anti-inflammatory effect of SCFAs, which has shown to inhibit cardiac fibrosis - a key pathological process in the development of HF.

Laser vibrational excitation of radicals to prevent crystallinity degradation caused by boron doping in diamond.

Pursuing high-level doping without deteriorating crystallinity is prohibitively difficult but scientifically crucial to unleashing the hidden power of materials. This study demonstrates an effective route for maintaining lattice integrity during the combustion chemical vapor deposition of highly conductive boron-doped diamonds (BDDs) through laser vibrational excitation of a growth-critical radical, boron dihydride (BH2). The improved diamond crystallinity is attributed to a laser-enabled, thermal nonequilibrium suppression of the relative abundance of boron hydrides (BH), whose excessive presence induces boron segregation and disturbs the crystallization. The BDDs show a boron concentration of 4.3 × 1021 cm-3, a film resistivity of 28.1 milliohm·cm, and hole mobility of 55.6 cm2 V-1 s-1, outperforming a commercial BDD. The highly conductive and crystalline BDDs exhibit enhanced efficiency in sensing glucose, confirming the advantages of laser excitation in producing high-performance BDD sensors. Regaining crystallinity with laser excitation in doping process could remove the long-standing bottlenecks in semiconductor industry.

Wave Function and Density Functional Theory Studies of Dihydrogen Complexes.

We performed a benchmark study on a series of dihydrogen bond complexes and constructed a set of reference bond distances and interaction energies. The test set was employed to assess the performance of several wave function correlated and density functional theory methods. We found that second-order correlation methods describe relatively well the dihydrogen complexes. However, for high accuracy inclusion of triple contributions is important. On the other hand, none of the considered density functional methods can simultaneously yield accurate bond lengths and interaction energies. However, we found that improved results can be obtained by the inclusion of nonlocal exchange contributions.

Generalized Gradient Approximations of the Noninteracting Kinetic Energy from the Semiclassical Atom Theory: Rationalization of the Accuracy of the Frozen Density Embedding Theory for Nonbonded Interactions.

We present a new class of noninteracting kinetic energy (KE) functionals, derived from the semiclassical-atom theory. These functionals are constructed using the link between exchange and kinetic energies and employ a generalized gradient approximation (GGA) for the enhancement factor, namely, the Perdew-Burke-Ernzerhof (PBE) one. Two of them, named APBEK and revAPBEK, recover in the slowly varying density limit the modified second-order gradient (MGE2) expansion of the KE, which is valid for a neutral atom with a large number of electrons. APBEK contains no empirical parameters, while revAPBEK has one empirical parameter derived from exchange energies, which leads to a higher degree of nonlocality. The other two functionals, APBEKint and revAPBEKint, modify the APBEK and revAPBEK enhancement factors, respectively, to recover the second-order gradient expansion (GE2) of the homogeneous electron gas. We first benchmarked the total KE of atoms/ions and jellium spheres/surfaces: we found that functionals based on the MGE2 are as accurate as the current state-of-the-art KE functionals, containing several empirical parameters. Then, we verified the accuracy of these new functionals in the context of the frozen density embedding (FDE) theory. We benchmarked 20 systems with nonbonded interactions, and we considered embedding errors in the energy and density. We found that all of the PBE-like functionals give accurate and similar embedded densities, but the revAPBEK and revAPBEKint functionals have a significant superior accuracy for the embedded energy, outperforming the current state-of-the-art GGA approaches. While the revAPBEK functional is more accurate than revAPBEKint, APBEKint is better than APBEK. To rationalize this performance, we introduce the reduced-gradient decomposition of the nonadditive kinetic energy, and we discuss how systems with different interactions can be described with the same functional form.

[Role of retroperitoneal laparoscopic nephroureterectomy in the current treatment of upper urinary tract urothelial carcinoma]. / Locul nefroureterectomiei laparoscopice retroperitoneale in tratamentul actual al carcinomului urotelial de cai urinare superioare.

INTRODUCTION: Nowadays, the standard treatment for upper tract transitional cell carcinoma is open nephroureterectomy, by double lumbar and iliac approach, with peri-meat bladder cuff excision. Since the first laparoscopic nephroureterectomy was performed, several surgical teams were interested by this approach for the treatment of the upper tract transitional cell carcinoma. OBJECTIVE: To plead for retro-peritoneoscopic nephroureterectomy and to assess the surgical indications. MATERIAL AND METHOD: Were analyzed the results of the recent published series on nephroureterectomy for upper urinary tract transitional cell carcinoma. Were included studies on conventional, laparoscopic and retro-peritoneoscopic nephroureterectomy, with at least 10 cases, published after 2000. RESULTS: The advantages of retro-peritoneoscopic nephroureterectomy are: minimum blood loss, reduced analgesic intake, a shorter hospital stay and a faster return to previous activities, lower rate of intra- or postoperative complications compared with trans-peritoneal laparoscopy or conventional surgery. With a proper case selection the oncologic safety of the retro-peritoneoscopy is equivalent with open surgery. CONCLUSIONS: On short term, retro-peritoneoscopic approach shows similar oncological outcome with other techniques. Retroperitoneal laparoscopic nephroureterectomy is a viable alternative to conventional or trans-peritoneoscopic procedure, with clear cut benefits for the patient. Retro-peritoneoscopy is associated with a low morbidity.

Application of oscillating potentials to the Shaker potassium channel.

Nonequilibrium response spectroscopy (NRS) has been proposed recently to complement standard electrophysiological techniques used to investigate ion channels. It involves application of rapidly oscillating potentials that drive the ion channel ensemble far from equilibrium. It is argued that new, so far undiscovered features of ion channel gating kinetics may become apparent under such nonequilibrium conditions. In this paper we explore the possibility of using regular, sinusoidal voltages with the NRS protocols to facilitate Markov model selection for ion channels. As a test case we consider the Shaker potassium channel for which various Markov models have been proposed recently. We concentrate on certain classes of such models and show that while some models might be virtually indistinguishable using standard methods, they show marked differences when driven with an oscillating voltage. Model currents are compared to experimental data obtained for the Shaker K+ channel expressed in mammalian cells (tsA 201).

Slow molecule detection or Ramsey fringes in two-photon spectroscopy: which is better for high resolution spectroscopy and metrology ?

The CO2 laser locked onto a saturated absorption resonance of OsO4 provides a secondary frequency standard in the 10 mm region, with an accuracy of 50 Hz to 1 kHz. For averaging times less than 100 s its stability performance is better than the Hydrogen maser. This paper deals with the present attempt to increase this performance by using a two-photon molecular resonance as a reference. We begin with some preliminary and promising results on a two-photon line of SF6 leading to characteristics similar to those obtained with a saturation line of OsO4 . Then two alternative methods to increase the resolution are presented : optical detection of slow molecules and a new development of the well-known Ramsey fringes. Metrological features are analyzed for both methods.

[Effectiveness of a water iodination system for preventing iodine deficiency diseases in Central Africa]. / Efficacité d'un système d'iodation de l'eau dans la lutte contre les troubles dus à la carence iodée en Afrique centrale.

Iodine deficiency disorders are major problems in most developing countries. According to WHO more than one billion people worldwide are at risk for iodine deficiency. However, prophylaxis programs based on the distribution of iodized salt have been unsuccessful in developing countries for socioeconomic reasons. We tested the efficacy of iodination of water with sodium iodide incorporated into silicone matrices (Rhône-Poulenc-Rorer-Doma). Nine such matrices were placed into each of the 198 wells supplying more than 90% of the 85,037 inhabitants of the Nana-Grebizi prefecture (figure 1). Efficacy was evaluated by following classical markers of iodine deficiency in representative samples of the population (figure 2): goiter size was measured immediately before (T = 0, n = 3,090) and twelve months after (T = 12, n = 2,645) installation of the matrices; and urinary iodine concentrations were assayed at T = 0 (n = 319), 6 (n = 304) and 12 (n = 261). The prevalence of goiter was 60.9% (visible goiter 10.7%, cretinism 0.7%) and the median urinary iodine concentration was 2.1 (95% confidence interval 2.0-2.3) micrograms/dl. Thus the population suffered from severe iodine deficiency. All villages were severely affected, despite inter-village variations (tables 1 and 2, figure 4). Twelve months after iodination of wells, the overall prevalence of goiter fell to 44.5% (p < 0.0001, table 1 and figure 3) and that of visible goiter to 2.5% (p < 0.0001). With the exception of one village (Bokanzi) the prevalence of goiter decreased by 18.6 to 56.3% (table 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of direct, reflex and exercise-provoked increases in sympathetic tone on idiopathic ventricular tachycardia.

Exercise treadmill testing and direct enhancement of sympathetic influence with agents such as isoproterenol are often used to reproduce ventricular tachycardia (VT). The cardiac effects of, and arrhythmia responses to, graded exercise, isoproterenol infusion and lower body negative pressure (the latter 2 with and without atrial and ventricular stimulation) were studied in 11 patients with idiopathic VT. During maximal exercise, substantial increases in heart rate and blood pressure occurred, but only 2 of 9 exercised patients had VT (during recovery in both). During programmed stimulation alone, VT was initiated in 6 patients. During maximum levels of lower body negative pressure (-60 cm of water in most), mean systolic blood pressure decreased by 10 mm Hg, heart rate increased by 15 beats/min, and ventricular refractory period decreased by 10 ms. In 4 patients VT occurred spontaneously during lower body negative pressure; in 2, lower body negative pressure was the only intervention producing VT. During isoproterenol infusion VT occurred spontaneously in 2 patients; both had VT initiated during other interventions. Lower body negative pressure and isoproterenol increased VT rate, but did not prolong it. It is concluded that there is significant variability in arrhythmia responses to sympathetic augmentation, suggesting that additional covariables such as parasympathetic input and ventricular volume may also have a role in arrhythmia occurrence.

Bradycardia and syncope as manifestations of partial epilepsy.

Although transient increases in heart rate typically occur, bradycardia has infrequently been noted in association with partial seizures. Five patients with temporal lobe epilepsy are described in whom sinus bradyarrhythmias and syncope were prominent manifestations of seizure activity. Partial improvement occurred in one of two patients in whom a permanent pacemaker was implanted before a diagnosis of epilepsy was established. Treatment with phenytoin or carbamazepine resulted in nearly complete resolution of symptoms in all five patients. Because pacemaker implantation does not prevent recurrent symptoms, but anticonvulsant therapy does, this experience underscores the importance of considering the diagnosis of partial epilepsy in selected patients with sinus bradyarrhythmias and syncope.

Induced sustained ventricular tachycardia in nonischemic dilated cardiomyopathy: dependence on clinical presentation and response to antiarrhythmic agents.

Thirty-one patients with nonischemic dilated cardiomyopathy either idiopathic or due to regurgitant valvular disease were studied in the cardiac electrophysiology lab. The indications for study were sustained ventricular tachycardia (VT) in 16, ventricular fibrillation (VF) in 11, and syncope of unknown etiology in 4. Sustained VT was reproducibly induced in 17 patients, including 12 with a history of sustained VT, 2 with VF and 3 with syncope. Of 15 patients undergoing serial antiarrhythmic drug studies, sustained VT was rendered noninducible or nonsustained in 13. Three had recurrent arrhythmic events while on therapy predicted to be effective. One of 2 patients discharged on a regimen predicted to be ineffective had a recurrence of sustained VT that resulted in cardiac arrest. Of 14 patients in whom sustained VT could not be reproducibly induced, 2 subsequently had spontaneous occurrences of sustained VT, and 2 experienced aborted sudden death. These results suggest the following: (1) the induction of sustained VT in the setting of nonischemic dilated cardiomyopathy is dependent on the clinical presentation; (2) antiarrhythmic drugs frequently render sustained VT noninducible or nonsustained; (3) antiarrhythmic drug suppression of inducible sustained VT predicts long-term prevention of spontaneous recurrences; and (4) noninducibility of sustained VT in the baseline state does not predict freedom from subsequent episodes of VT or sudden death.

Propranolol blocks ventricular refractory period changes with orthostatic stress in humans.

The purpose of this study was to test the hypothesis that orthostatic stress shortens the right ventricular effective refractory period by reflex activation of beta-adrenergic receptors. Twelve patients undergoing electrophysiologic testing for standard clinical indications were studied. After a full electrophysiologic study, patients underwent graded lower body negative pressure before and after administration of either propranolol (0.2 mg/kg intravenously) in Group I or atropine (0.035 mg/kg intravenously) in Group II. Before the addition of drugs, lower body negative pressure produced decreases in systolic blood pressure and significant increases in sinus rate. The effective refractory period shortened from 214 +/- 8 (mean +/- SEM) to 206 +/- 7 ms at -40 cm H2O and to 197 +/- 4 ms at -60 cm H2O lower body negative pressure. After propranolol, Group I patients had no change in right ventricular effective refractory period despite similar changes in sinus rate and systolic blood pressure. In group II patients, atropine did not alter effective refractory period responses to lower body negative pressure. Thus, reflex adjustments to orthostatic stress result in shortening of right ventricular effective refractory period mediated by way of beta-adrenergic mechanisms. These findings constitute the first evidence that sympathetic influences mobilized by the body can directly modulate ventricular electrophysiologic changes.

Possible proarrhythmic effects of tocainide in dilated cardiomyopathy.

A patient with a dilated cardiomyopathy experienced a cardiac arrest when taking tocainide for asymptomatic nonsustained ventricular tachycardia. After successful resuscitation from ventricular fibrillation and exclusion of a myocardial infarction, an electrophysiological evaluation was performed. Drug-free study #1 revealed no induction of ventricular tachycardia. A tocainide study revealed induction of sustained monomorphic ventricular tachycardia. Drug-free study #2 revealed induction of nonsustained ventricular tachycardia. This report illustrates a possible proarrhythmic effect of tocainide.

Enhanced efficacy of oral sotalol for sustained ventricular tachycardia refractory to type I antiarrhythmic drugs.

Sotalol is a nonselective beta-adrenergic blocking agent with Vaughn-Williams class III activity. Its efficacy was tested in 9 patients with sustained ventricular tachycardia (VT) that had previously remained inducible during electrophysiologic testing of type I drugs (procainamide or quinidine). Eight patients had coronary artery disease with remote myocardial infarction and 1 had cardiomyopathy (ejection fraction 0.34 +/- 0.08, mean +/- standard deviation). Type I drugs prolonged the effective refractory period of the right ventricle 12 +/- 14% and prolonged the VT cycle length 41 +/- 24%. In contrast, despite an equivalent effect on the effective refractory period, a sustained VT could no longer be initiated in any of the 8 patients ultimately tested while taking oral sotalol. Daily doses averaged 600 +/- 103 mg and blood levels associated with VT suppression in electrophysiologic studies were generally greater than 3,000 ng/ml. In addition, sotalol was moderately effective at reducing ventricular ectopic activity measured by ambulatory electrocardiography. Over a mean follow-up of 23 months (range 1 to 37), mild heart failure (3 patients), symptomatic brady-cardia requiring pacemaker (1) and drug-related polymorphous VT (1) have occurred. Sudden death occurred in 1 patient and nonfatal VT recurrence was noted in 2. Five of 8 chronically treated patients currently are successfully treated with minimal side effects. Sotalol appears to be a promising antiarrhythmic drug in the treatment of serious ventricular arrhythmias, even in patients refractory to type I antiarrhythmic agents.