On the thermodynamics of hydrogen adsorption over Pt(111) in 0.05M NaOH.

The reasons for the sluggish kinetics of the hydrogen adsorption reaction in alkaline media remain a question still to be solved. This information is important to achieve a complete understanding of the mechanistic details that could lead to the production of key catalytic materials necessary for the development of a future hydrogen economy. For a better understanding of this reaction, it is important to acquire information about the thermodynamic parameters characteristic of the different steps in the reaction. Among these, the hydrogen adsorption is a key step in the process of hydrogen evolution. Although some debate still remains about the difference between adsorbed hydrogen in the underpotential deposition (UPD) region and at the overpotential deposition region, there is no doubt that understanding the former can help in the understanding of the latter. Making use of charge density measurements, we report on this paper a thermodynamic study of the hydrogen UPD process on Pt(111) in 0.05M NaOH over the range of temperatures from 283 ≤ T/K ≤ 313. The coulometric features corresponding to HUPD allow for the calculation of the hydrogen coverage and a fit to a Generalized Frumkin isotherm. From these values, different thermodynamic functions for the UPD reaction have been calculated: ΔGads, ΔSads, ΔHads, and the Pt-H bond energy. From extrapolation, a value of ΔSads ◦=-7.5±4Jmol-1K-1 was found, which is very close to 0, much lower than previously reported measurements both in acid and in alkaline solutions. Such value has an effect on the enthalpy and bond energy calculations, the latter having a decreasing tendency with pH and coverage. This tendency is completely different from the acidic systems and implies that the change in the thermodynamic functions due to the formation of the double layer and the reorganization of interfacial water has a strong influence on the process in high pH solutions.

Semi-mechanistic PK/PD modelling of combined polymyxin B and minocycline against a polymyxin-resistant strain of Acinetobacter baumannii.

OBJECTIVES: To expand on previous reports of synergy between polymyxin B (PMB) and minocycline (MIN) against Acinetobacter baumannii; and to gain insight into the qualitative and quantitative determinants of their synergy. METHODS: A semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model was developed on the basis of data from in vitro time-kill experiments with determination of resistant bacterial count to describe the effects of PMB and MIN alone and in combination. The model was enriched by complementary experiments providing information on the characteristics of the resistant subpopulation. RESULTS: The model successfully described the data and made possible quantification of the strength of interaction between the two drugs and formulation of hypotheses about the mechanisms of the observed interaction. The effect of the combination was driven by MIN, with PMB acting as an helper drug; simulations at clinically achievable concentrations showed that 1.5 mg/L MIN +0.2 mg/L PMB is expected to produce sustained killing over 30 hours, while 0.3 mg/L MIN +1 mg/L PMB is met by bacterial regrowth. Interaction equations showed that maximal synergy is reached for PMB concentrations ≥0.1 mg/L and MIN concentrations ≥1 mg/L. CONCLUSIONS: Semi-mechanistic PK/PD modelling was used to investigate the quantitative determinants of synergy between PMB and MIN on a PMB-resistant A. baumannii strain. The developed model, improving on usual study techniques, showed asymmetry in the drug interaction, as PMB acted mostly as a helper to MIN, and provided simulations as a tool for future studies.

Imaging the optical properties of turbid media with single-pixel detection based on the Kubelka-Munk model.

We present a diffuse optical imaging system with structured illumination and integrated detection based on the Kubelka-Munk light propagation model for the spatial characterization of scattering and absorption properties of turbid media. The proposed system is based on the application of single-pixel imaging techniques. Our strategy allows us to retrieve images of the absorption and scattering properties of a turbid media slab by using integrating spheres with photodiodes as bucket detectors. We validate our idea by imaging the absorption and scattering coefficients of a spatially heterogeneous phantom.

Involvement of the -420C>G RETN polymorphism in myocardial fibrosis in patients with hypertrophic cardiomyopathy.

AIMS: Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and fibrosis. HCM is an autosomal-dominant disease caused by more than 400 mutations in sarcomeric genes. Changes in nonsarcomeric genes contribute to its phenotypic heterogeneity. Cardiac fibrosis can be studied using late gadolinium enhancement (LGE) cardiac magnetic resonance imaging. We evaluated the potential role of two polymorphisms in nonsarcomeric genes on interstitial fibrosis in HCM. MATERIALS AND METHODS: Two polymorphisms in nonsarcomeric genes [ACE (deletion of 287 bp in the 16th intron) and RETN (-420C>G)] were analysed in 146 HCM patients. Cardiac fibrosis was assessed using LGE to determine the number of affected segments. RESULTS: Allelic frequencies in ACE and RETN polymorphisms were consistent with the Hardy-Weinberg equilibrium (both P > 0.05). We found that the presence of the polymorphic allele in the -420C>G RETN polymorphism was independently associated with the number of affected segments of LGE (P = 0.038). Increased circulating resistin concentration, measured by enzyme-linked immunosorbent assay, was associated with a higher degree of cardiac fibrosis. Myocardial fibrosis, assessed by Masson's trichrome staining, was associated with the -420C>G RETN polymorphism in 46 tissue samples obtained by septal myectomy (P = 0.044). CONCLUSIONS: The -420C>G RETN polymorphism was independently associated with the degree of cardiac fibrosis, assessed by LGE, in patients with HCM. In addition, there was an association between the polymorphism and the circulating resistin levels as well as with myocardial fibrosis in tissues obtained by myectomy. Investigating the physiological implication of the RETN polymorphism in HCM in combination with the use of imaging technologies might help to establish the severity of disease in patients with HCM.

Prognostic value of two polymorphisms in non-sarcomeric genes for the development of atrial fibrillation in patients with hypertrophic cardiomyopathy.

BACKGROUND: Several non-sarcomeric genes have been postulated to act as modifiers in the phenotypic manifestations of hypertrophic cardiomyopathy (HCM). The development of atrial fibrillation (AF) in HCM has adverse prognostic implications with increased thromboembolism and functional class impairment. AIM: We tested the hypothesis that 2 non-sarcomeric genes [CYP11B2 (-344T>C) and COL1A1 (2046G>T)] are associated with the development of AF. DESIGN: Prospective study. METHODS: Two polymorphisms in non-sarcomeric genes [CYP11B2 (-344T>C) and COL1A1 (2046G>T)] were analysed in 159 HCM patients (49.3 ± 14.9 years, 70.6% male) and 136 controls. All subjects were clinically stable and in sinus rhythm at entry in the study, without ischemic heart disease or other significant co-morbidities that could mask the effect of the analysed polymorphisms (i.e. previous AF). Thirty-nine patients (24.4%) developed AF during a median follow-up of 49.5 months. RESULTS: Patients with the -344T>C polymorphism in CYP11B2 gene had a higher risk for AF development [HR: 3.31 (95% CI 1.29-8.50); P = 0.008]. In a multivariate analysis, the presence of the C allele in CYP11B2 gene [HR: 3.02 (1.01-8.99); P = 0.047], previous AF [HR: 2.81 (1.09-7.23); P = 0.033] and a left atrial diameter of ≥42 mm [HR: 2.69 (1.01-7.18); P = 0.048] were independent predictors of AF development. The presence of the polymorphic allele was associated with higher aldosterone serum levels. CONCLUSION: We have shown for the first time that the CYP11B2 polymorphism is an independent predictor for AF development in HCM patients. This highlights the importance of non-sarcomeric genes in the phenotypic heterogeneity of HCM. The association with higher aldosterone serum levels could relate to greater fibrosis and cardiac remodelling.

Influence of intestinal resections on biliary composition and liver ultrastructure.

BACKGROUND & AIMS: Among the multiple factors that can influence bile acid (BA) metabolism and biliary poles, intestinal resections could do so directly (through absorption alterations) and/or indirectly (bacterial translocation, alterations of the hepato-intestinal hormonal axis). Our aim was to study the influence of partial intestinal resections on bile metabolism and biliary structure in an animal model. METHODS: Dunkin Hartley guinea pigs were used: Group A with only jejunum resection, Group B with only ileum resection, and Group CtrG, the control group. They were monitored for 21 days, with oral nutrition. At the end of this period, samples of the bile were taken from the hepatic duct and vena cava. After liver perfusion, samples of hepatic tissue were taken for optical and electron microscopy. RESULTS: There was a significant decrease in serum cholesterol in both GA & GB. The levels of biliary phospholipids (Ph) and cholic acid decreased only in Group B, but not ketolithocholic acid nor total conjugated BA. Slight liver macrosteatosis was observed in GB, but there were no changes in the biliary poles or canaliculi in the electron microscopy samples. CONCLUSIONS: Ileum resections affect the biliary Ph and BA composition, which could increase bile lithogenicity but do not seem to affect biliary duct anatomy.

Wavelength tuning of femtosecond pulses generated in nonlinear crystals by using diffractive lenses.

We demonstrate that diffractive lenses (DLs) can be used as a simple method to tune the central wavelength of femtosecond pulses generated from second-order nonlinear optical processes in birefringent crystals. The wavelength tunability is achieved by changing the relative distance between the nonlinear crystal and the DL, which acts in a focusing configuration. Besides the many practical applications of the so-generated pulses, the proposed method might be extended to other wavelength ranges by demonstrated similar effects on other nonlinear processes, such as high-order harmonic generation.

Enzyme replacement therapy in Fabry disease: influence on cardiac manifestations.

Fabry disease (FD) is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide (Gb3) in the lysosomes of different cells and tissues, causing principally ventricular hypertrophy, renal failure and cerebrovascular accidents, reducing lifespan both in hemizygous males and heterozygous females. Residual enzyme activity might lead to slow progression of the disease and result in the so-called cardiac or renal variants with delayed presentation. Two different forms of alpha-galactosidase A enzyme replacement therapies (ERT) are available for the treatment of FD, one genetically engineered in human cell line (agalsidase alfa, Replagal, Shire) and the other produced in a Chinese hamster ovary cell line (agalsidase beta, Fabrazyme, Genzyme). Although both proteins are structurally and functionally very similar, with the same amino acid sequence as the native human enzyme, they differ in the pattern of glycosilation of the protein depending on the originating cell line. Studies with both preparations have described a reduction in plasma, urinary sediment and tissue levels of Gb3, a decrease in the frequency of pain crisis and a reduction in left ventricular mass and improvement or stabilization of renal function. Studies have generally shown the greatest benefit when treatment is started at an early stage of the disease before extensive fibrosis or other irreversible tissue damage takes place. However, more data are needed to document long-term treatment outcomes. The aim of the present review is to provide an update overview of the two different forms of ERT for FD, their clinical effects in cardiac manifestations and their possible differences in terms of efficacy, side effects and safety profiles.

Left atrial remodelling in hypertrophic cardiomyopathy: relation with exercise capacity and biochemical markers of tissue strain and remodelling.

BACKGROUND: Left atrial remodelling, assessed as left atrial volume (LAV), has been proposed as a good marker of left ventricular diastolic dysfunction. The aim of this study was to analyse the influence of LAV on exercise performance in hypertrophic cardiomyopathy (HCM), and in a subset of subjects, assess the relation of LAV and exercise performance to four biomarkers of disease pathophysiology: matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) (as indices of tissue remodelling), N-terminal portion of pro B-type natriuretic peptide (NT-pro-BNP) (associated with ventricular dysfunction) and C-reactive protein (CRP, an index of inflammation). METHODS: We studied 75 consecutive HCM patients (aged 46 +/- 14 years, 56 men) where LAV was calculated assuming the ellipsoid model with two orthogonal planes. LAV was indexed to body surface area. Exercise capacity was evaluated by treadmill exercise test (symptom limited) and assessed with metabolic equivalent units (MET). Basal NT-pro-BNP and CRP levels were measured in 70 patients, whereas MMP-2 and TIMP-1 in 43 patients. RESULTS: Enlarged LAV was observed in those patients with previous atrial fibrillation (p = 0.016). Mean LAV was greater in patients with impaired functional New York Heart Association (NYHA) class (p < 0.001). LAV correlated with age (Spearman, r: 0.28), higher maximal left ventricular wall thickness (r: 0.32) and raised E/A ratio (r: 0.37) (all p < 0.01). LAV was significantly correlated with NT-pro-BNP values (r: 0.34; p = 0.04), MMP-2 (r: 0.32; p = 0.034), CRP (r: 0.33; p = 0.005) and correlated inversely with MET units (r: -0.39; p < 0.01). In multivariate analysis, MET units were only associated with NT-pro-BNP (p = 0.002) and LAV (p = 0.010). CONCLUSIONS: Enlarged LAV is associated with impaired functional NYHA class and inversely with treadmill exercise capacity. Enlarged LAV is also associated with NT-pro-BNP, MMP-2 and CRP, perhaps as markers of disease severity and tissue remodelling. Age, LAV and NT-pro-BNP are independent predictors of exercise performance.

Use of polar decomposition of Mueller matrices for optimizing the phase response of a liquid-crystal-on-silicon display.

We provide experimental measurement of the Mueller matrices corresponding to an on-state liquid-crystal-on-silicon display as a function of the addressed voltage. The polar decomposition of the Mueller matrices determines the polarization properties of the device in terms of a diattenuation, a retardance and a depolarization effect. Although the diattenuation effect is shown to be negligible for the display, the behavior of the degree of polarization as a function of the input polarization state shows a maximum coupling of linearly polarized light into unpolarized light of about 10%. Concerning the retardation effect, we find that the display behaves as a retarder with a fast-axis orientation and a retardance angle that are voltage-dependent. The above decomposition provides a convenient framework to optimize the optical response of the display for achieving a phase-mostly modulation regime. To this end, the display is sandwiched between a polarization state generator and a polarization state analyzer. Laboratory results for a commercial panel show a phase modulation depth of 360 masculine at 633 nm with a residual intensity variation lower than 6 %.

Effect of deposited bismuth on the potential of maximum entropy of Pt(111) single-crystal electrodes.

The effect of bismuth adsorption on the entropy of formation of the double layer on Pt(111) electrodes has been studied with the laser-induced temperature jump method. The coulostatic response to the temperature change induced by pulsed laser illumination allows the estimation of the sign and magnitude of the thermal coefficient of the potential drop at the interphase. This is related to the entropy of formation of the double layer, and the particular potential where this thermal coefficient becomes zero can be identified with the potential of maximum entropy of double-layer formation (pme). The effect of bismuth adsorption on the pme depends on the adatom coverage. At high coverages, a marked decrease of the pme is observed. This trend follows the change of the potential of zero charge expected from work function measurements, and it is likely due to the change in the orientation of solvent molecules induced by surface dipoles originated between the adatom and the substrate. At low coverage, the pme increases with the bismuth coverage. The disruption of the water structure due to the presence of the bismuth adatoms is tentatively proposed as the most likely explanation for this behavior.

A new floating sensor array to detect electric near fields of beating heart preparations.

A new flexible sensor for in vitro experiments was developed to measure the surface potential, Phi, and its gradient, E (electric near field), at given sites of the heart. During depolarisation, E describes a vector loop from which direction and magnitude of local conduction velocity theta can be computed. Four recording silver electrodes (14 microm x 14 microm) separated by 50 microm, conducting leads, and solderable pads were patterned on a 50 microm thick polyimide film. The conductive structures, except the electrodes, were isolated with polyimide, and electrodes were chlorided. Spacer pillars mounted on the tip fulfil two functions: they keep the electrodes 70 microm from the tissue allowing non-contact recording of Phi and prevent lateral slipping. The low mass (9.1 mg) and flexibility (6.33 N/m) of the sensor let it easily follow the movement of the beating heart without notable displacement. We examined the electrodes on criteria like rms-noise of Phi, signal-to-noise ratio of Phi and E, maximum peak-slope recording dPhi/dt, and deviation of local activation time (LAT) from a common signal and obtained values of 24-28 microV, 46 and 41 dB, 497-561 V/s and no differences, respectively. With appropriate data acquisition (sampling rate 100 kHz, 24-bit), we were able to record Phi and to monitor E and theta on-line from beat-to-beat even at heart rates of 600 beats/min. Moreover, this technique can discriminate between uncoupled cardiac activations (as occur in fibrotic tissue) separated by less than 1 mm and 1 ms.

Taurine and cholestasis associated to TPN. Experimental study in rabbit model.

Taurine seems to be essential in the newborn for bile acid (BA) tauroconjugation, and its deficiency has been implicated in total parenteral nutrition-associated cholestasis (TPN-AC). Our purpose was to study the relationship between taurine (Ta) and TPN-AC in rabbits, which have a similar biliary metabolism to that of humans. We used 40 young rabbits, fed for 10 days according to the following four groups: GA [10] given TPN, with amino acid solution (AA) but without taurine (Ta) or its AA-precursors (methionine, cysteine, and serine); GB [10] the same but only without taurine; GC [10] the same but with taurine and its precursors; and GD [10] the control group with oral nutrition and saline infusion. Complete blood and bile analytical data were obtained and analyzed, including plasma AA and BA. Liver samples were studied under optical and electron microscopy. Serum: In GC there was a 20% increase in the AA-precursors, but paradoxically it was greater in GA. Bile: In GC there was 30% more excretion of total and free BA compared with less than 20% in GA and GB. Regarding toxic BA, there was a 15% decline in GLC3S excretion, but more than 20% in LCA excretion, than in GA and GB. Moreover, in GC the glyco-/tauro-conjugate ratio was worse than in the other groups. Histomorphology: While in GA and GB liver steatosis was diffuse (microsteatohepatitis type), in GC there was macrosteatosis with mitochondria-surrounded lipid droplets. In GA and GB, the canaliculi appeared dilated, with abundant bile plugs and loss of microvilli. There are signs that taurine may protect against TPN-AC. The mechanism does not seem to be BA tauroconjugation, but probably taurine's antioxidant, membrane stabilization (with Ca2+ and HCO3-), and/or osmotic effects.

Sinus node revisited in the era of electroanatomical mapping and catheter ablation.

OBJECTIVE: To study the architecture of the human sinus node to facilitate understanding of mapping and ablative procedures in its vicinity. METHODS: The sinoatrial region was examined in 47 randomly selected adult human hearts by histological analysis and scanning electron microscopy. RESULTS: The sinus node, crescent-like in shape, and 13.5 (2.5) mm long, was not insulated by a sheath of fibrous tissue. Its margins were irregular, with multiple radiations interdigitating with ordinary atrial myocardium. The distances from the node to endocardium and epicardium were variable. In 72% of the hearts, the whole nodal body was subepicardial and in 13 specimens (28%) the inner aspect of the nodal body was subendocardial. The nodal body cranial to the sinus nodal artery was more subendocardial than the remaining nodal portion, which was separated from the endocardium by the terminal crest. In 50% of hearts, the most caudal boundaries of the body of the node were at least 3.5 mm from the endocardium. When the terminal crest was > 7 mm thick (13 hearts, 28%), the tail was subepicardial or intramyocardial and at least 3 mm from the endocardium. CONCLUSIONS: The length of the node, the absence of an insulating sheath, the presence of nodal radiations, and caudal fragments offer a potential for multiple breakthroughs of the nodal wavefront. The very extensive location of the nodal tissue, the cooling effect of the nodal artery, and the interposing thick terminal crest caudal to this artery have implications for nodal ablation or modification with endocardial catheter techniques.

Plasma von Willebrand factor, soluble thrombomodulin, and fibrin D-dimer concentrations in acute onset non-rheumatic atrial fibrillation.

OBJECTIVE: To investigate whether new onset acute atrial fibrillation (AF) of < 48 hours' duration creates a prothrombotic state in the absence of anticoagulation and to assess the evolution in research indices after spontaneous or pharmacological cardioversion. METHODS: 24 patients were recruited with first onset acute non-rheumatic AF, in whom sinus rhythm was restored within 48 hours of arrhythmia onset, without anticoagulant treatment. Atrial mechanical function was assessed by transmitral inflow. Soluble thrombomodulin and von Willebrand factor concentrations (both as indices of endothelial damage or dysfunction) and fibrin D-dimer concentrations (as an index of thrombogenesis) were measured. Blood samples were drawn and echocardiographic studies were performed at days 1, 3, 7, and 30 after cardioversion. Research indices were compared with those of 24 healthy participants, 24 patients with chronic AF, and 24 patients with ischaemic heart disease in sinus rhythm. RESULTS: Patients with AF had higher concentrations of soluble thrombomodulin (acute AF 12.1 (4.1) ng/ml; chronic AF 11.8 (4.6) ng/ml), von Willebrand factor (acute AF 137.2 (36.9) ng/ml; chronic AF 133.1 (25.0) ng/ml), and fibrin D-dimer concentrations (acute AF 2.35 (2.68) microg/ml; chronic AF 1.12 (0.65) microg/ml) than did healthy controls (5.9 (2.7) ng/ml, 86.7 (33.2) ng/ml, and 0.39 (0.28) microg/ml, respectively) and patients with ischaemic heart disease (7.4 (3.7) ng/ml, 110.0 (29.0) ng/ml, and 0.99 (0.73) microg/ml, respectively) (all p < 0.05). Day 30 concentrations of fibrin D-dimer were higher in patients with acute AF than in patients with chronic AF (p = 0.038) but sTM and von Willebrand factor concentrations were not different (both not significant). There were no significant changes in research indices or echocardiographic parameters after cardioversion (all p > 0.05). CONCLUSIONS: There was evidence among patients with acute onset AF of endothelial damage or dysfunction and increased thrombogenesis, which persisted up to 30 days after cardioversion.

High-contrast white-light Lau fringes.

We present a new optical assembly with which to achieve Lau fringes with totally incoherent illumination. Gratinglike codification of the spatially incoherent source combined with an achromatic Fresnel diffraction setup allows us to achieve Lau fringe-pattern visibility of almost 100% with broadband light. The white-light character to our proposed setup is in stark contrast to previous monochromatic implementations. Potential implications of this fact are identified.

The terminal crest: morphological features relevant to electrophysiology.

OBJECTIVE: To investigate the detailed anatomy of the terminal crest (crista terminalis) and its junctional regions with the pectinate muscles and intercaval area to provide the yardstick for structural normality. DESIGN: 97 human necropsy hearts were studied from patients who were not known to have medical histories of atrial arrhythmias. The dimensions of the terminal crest were measured in width and thickness from epicardium to endocardium, at the four points known to be chosen as sites of ablation. RESULTS: The pectinate muscles originating from the crest and extending along the wall of the appendage towards the vestibule of the tricuspid valve had a non-uniform trabecular pattern in 80% of hearts. Fine structure of the terminal crest studied using light and scanning electron microscopy consisted of much thicker and more numerous fibrous sheaths of endomysium with increasing age of the patient. 36 specimens of 45 (80%) specimens studied by electron microscopy had a predominantly uniform longitudinal arrangement of myocardial fibres within the terminal crest. In contrast, in all specimens, the junctional areas of the terminal crest with the pectinate muscles and with the intercaval area had crossing and non-uniform architecture of myofibres. CONCLUSIONS: The normal anatomy of the muscle fibres and connective tissue in the junctional area of the terminal crest/pectinate muscles and terminal crest/intercaval bundle favours non-uniform anisotropic properties.

Wavelength-compensated Fourier and Fresnel transformers: a unified approach.

We recognize that one can adapt any dispersion-compensated broadband optical Fourier transformer to achieve wavelength compensation in the Fresnel diffraction region just by inserting a diffractive lens at the input plane and vice versa. This unification procedure is employed in a second stage in the design of a novel hybrid (diffractive-refractive) optical setup that provides, in a sequential way, nearly wavelength-independent Fresnel diffraction patterns in the irradiance of the object transmittance.

Broadband space-variant Fresnel processor.

We present a radically new class of optical setup working with white-light illumination, namely, a chromatically compensated processor operating in the Fresnel domain. The optical configuration is a hybrid (diffractive-refractive) three-lens system that exhibits an intermediate achromatic Fresnel plane and an output image plane without chromatic distortion. As a first application of this optical arrangement we develop a parallel space-variant color pattern-recognition experiment with white light.

[A case of Carney syndrome]. / Un caso de síndrome de Carney.

The Carney complex is an autosomal dominant syndrome characterised by multiple neoplasies, including myxomas at various sites (cardiac, cutaneous, mammary), spotty pigmentation, endocrine overactivity (Cushing's syndrome, acromegalia), testicular tumours and schwannomas. This report describes the case of a 43-year-old woman with an acute inferior myocardial infarction, probably due to coronary embolization from a large left atrial myxoma and who presented this association. A brief review of the Carney complex is provided after discussion of this rare case that required an screening of family members.