Prevalence and renal prognosis of left ventricular diastolic dysfunction in non-dialysis chronic kidney disease patients with preserved systolic function.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is common in non-dialysis chronic kidney disease (ND-CKD) patients; however, the prevalence estimated according to the new diagnostic criteria as well as the prognostic role of diastolic dysfunction on CKD progression remain unknown. METHOD: We longitudinally evaluated consecutive ND-CKD patients and preserved systolic function (LV ejection fraction > 50%). According to the recently updated guidelines, LV diastolic dysfunction was assessed by four echocardiographic variables (annular e' velocity, average mitral valve E-wave/e' ratio, left atrial volume index and tricuspid regurgitation). Patients were classified as diastolic dysfunction, indeterminate and normal. Time-dependent estimated glomerular filtration rate (eGFR) change was assessed by mixed-effects regression model. Cumulative incidence of composite renal outcome (eGFR decline > 50% or chronic dialysis) was also estimated. RESULTS: Among 140 patients (age 66.2 ±â€Š14.5 years; 61% males; eGFR 39.8 ±â€Š21.8 ml/min per 1.73m2; 43.6% diabetics), diastolic dysfunction occurred in 22.9%, indeterminate in 45.7% and normal in 31.4%. Prevalence of diastolic dysfunction was much lower than that estimated with older criteria (62.7%). Logistic regression (odds ratio, 95% confidence interval [CI]) showed that diastolic dysfunction was associated with lower eGFR (0.97, 0.94-0.99), older age (1.04, 1.01-1.06) and night-time systolic blood pressure (1.04, 1.00-1.07). Across 1702 eGFR measurements collected during a median follow-up of 4.6 years, eGFR decline (ml/min per 1.73m2; per year) was faster in patients with diastolic dysfunction (-2.12, 95% CI from -2.68 to -1.56) and in the indeterminate (11.2/100 pts per year) as compared to normal (-1.14, 95% CI from -1.64 to -0.63). Incidence of composite renal outcome was significantly higher in diastolic dysfunction (13.8/100 pts/year) than in normal group (3.5/100 pts per year)'. CONCLUSION: In ND-CKD population, LV diastolic dysfunction is less frequent than previously described and acts as independent predictor of CKD progression.

Just add sugar for carbohydrate induced self-assembly of curcumin.

In nature, self-assembly processes based on amphiphilic molecules play an integral part in the design of structures of higher order such as cells. Among them, amphiphilic glycoproteins or glycolipids take on a pivotal role due to their bioactivity. Here we show that sugars, in particular, fructose, are capable of directing the self-assembly of highly insoluble curcumin resulting in the formation of well-defined capsules based on non-covalent forces. Simply by mixing an aqueous solution of fructose and curcumin in an open vessel leads to the generation of capsules with sizes ranging between 100 and 150 nm independent of the initial concentrations used. Our results demonstrate that hydrogen bonding displayed by fructose can induce the self-assembly of hydrophobic molecules such as curcumin into well-ordered structures, and serving as a simple and virtually instantaneous way of making nanoparticles from curcumin in water with the potential for template polymerization and nanocarriers.

High-flow arteriovenous fistula and heart failure: could the indexation of blood flow rate and echocardiography have a role in the identification of patients at higher risk?

BACKGROUND: Although only high-flow arteriovenous fistulas (AVFs) are postulated to cause high-output cardiac failure (HOCF), there are currently no universally accepted criteria defining a high-flow fistula. METHODS: To verify if vascular access blood flow (Qa) ≥ 2000 ml/min provides an accurate definition of high-flow fistula, we selected 29 consecutive patients with Qa ≥ 2000 ml/min at color-duplex ultrasound examination and assessed them for the presence of cardiac failure symptoms; transthoracic echocardiography was also performed. RESULTS: Nineteen patients (65%) had heart failure symptoms and were classified with HOCF. At receiver operating characteristic (ROC) curve analysis, Qa ml/min values did not identify patients with heart failure symptoms but when AVF blood flow was indexed for height2.7, Qa ≥ 603 ml/min/m2.7 detected the occurrence of HOCF with good accuracy (sensitivity 100%, specificity 60%, efficiency 86%, positive predictive value 83%, negative predictive value 100%, area under curve 0.75). At echocardiographic evaluation, patients with Qa ≥ 603 ml/min/m2.7 had a more severe increase of left ventricular mass (63 ± 18 vs. 47 ± 7 g/m2.7, p < 0.003), left ventricular diastolic volume (140 ± 42 vs. 109 ± 14 ml, p < 0.007), left atrial volume (53 ± 23 vs. 39 ± 5 ml/m2, p < 0.015), a higher incidence of diastolic dysfunction (70 vs. 17%, p < 0.019) and higher CO reduction after AVF manual compression (2151 ± 875 vs. 1292 ± 527 ml/min, p < 0.009) than patients with Qa < 603 ml/min/m2.7. CONCLUSIONS: Indexation of AVF blood flow should be considered in defining high-flow fistula because the effect of Qa may differ in individuals of different sizes. A Qa value ≥ 603 ml/min/m2.7 and its association with some echocardiographic alterations could identify patients at higher risk for HOCF.

Binding and Release between Polymeric Carrier and Protein Drug: pH-Mediated Interplay of Coulomb Forces, Hydrogen Bonding, van der Waals Interactions, and Entropy.

The accelerating search for new types of drugs and delivery strategies poses challenge to understanding the mechanism of delivery. To this end, a detailed atomistic picture of binding between the drug and carrier is quintessential. Although many studies focus on the electrostatics of drug-vector interactions, it has also been pointed out that entropic factors relating to water and counterions can play an important role. By carrying out extensive molecular dynamics simulations and subsequently validating with experiments, we shed light herein on the binding in aqueous solution between a protein drug and polymeric carrier. We examined the complexation between the polymer poly(ethylene glycol) methyl ether acrylate-b-poly(carboxyethyl acrylate (PEGMEA-b-PCEA) and the protein egg white lysozyme, a system that acts as a model for polymer-vector/protein-drug delivery systems. The complexation has been visualized and characterized using contact maps and hydrogen bonding analyses for five independent simulations of the complex, each running over 100 ns. Binding at physiological pH is, as expected, mediated by Coulombic attraction between the positively charged protein and negatively charged carboxylate groups on the polymer. However, we find that consideration of electrostatics alone is insufficient to explain the complexation behavior at low pH. Intracomplex hydrogen bonds, van der Waals interactions, as well as water-water interactions dictate that the polymer does not release the protein at pH 4.8 or indeed at pH 3.2 even though the Coulombic attractions are largely removed as carboxylate groups on the polymer become titrated. Experiments in aqueous solution carried out at pH 7.0, 4.5, and 3.0 confirm the veracity of the computed binding behavior. Overall, these combined simulation and experimental results illustrate that coulomb interactions need to be complemented with consideration of other entropic forces, mediated by van der Waals interactions and hydrogen bonding, to search for adequate descriptors to predict binding and release properties of polymer-protein complexes. Advances in computational power over the past decade make atomistic molecular dynamics simulations such as implemented here one of the few avenues currently available to elucidate the complexity of these interactions and provide insights toward finding adequate descriptors. Thus, there remains much room for improvement of design principles for efficient capture and release delivery systems.

Dynamical Interactions of 5-Fluorouracil Drug with Dendritic Peptide Vectors: The Impact of Dendrimer Generation, Charge, Counterions, and Structured Water.

Molecular dynamics simulations are utilized to investigate the interactions between the skin cancer drug 5-fluorouracil (5FU) and peptide-based dendritic carrier systems. We find that these drug-carrier interactions do not conform to the traditional picture of long-time retention of the drug within a hydrophobic core of the dendrimer carrier. Rather, 5FU, which is moderately soluble in its own right, experiences weak, transient chattering interactions all over the dendrimer, mediated through multiple short-lived hydrogen bonding and close contact events. We find that charge on the periphery of the dendrimer actually has a negative effect on the frequency of drug-carrier interactions due to a counterion screening effect that has not previously been observed. However, charge is nevertheless an important feature since neutral dendrimers are shown to have a significant mutual attraction that can lead to clustering or agglomeration. This clustering is prevented due to charge repulsion for the titrated dendrimers, such that they remain independent in solution.

Effects of Confinement on the Dielectric Response of Water Extends up to Mesoscale Dimensions.

The extent of confinement effects on water is not clear in the literature. While some properties are affected only within a few nanometers from the wall surface, others are affected over long length scales, but the range is not clear. In this work, we have examined the dielectric response of confined water under the influence of external electric fields along with the dipolar fluctuations at equilibrium. The confinement induces a strong anisotropic effect which is evident up to 100 nm channel width, and may extend to macroscopic dimensions. The root-mean-square fluctuations of the total orientational dipole moment in the direction perpendicular to the surfaces is 1 order of magnitude smaller than the value attained in the parallel direction and is independent of the channel width. Consequently, the isotropic condition is unlikely to be recovered until the channel width reaches macroscopic dimensions. Consistent with dipole moment fluctuations, the effect of confinement on the dielectric response also persists up to channel widths considerably beyond 100 nm. When an electric field is applied in the perpendicular direction, the orientational relaxation is 3 orders of magnitude faster than the dipolar relaxation in the parallel direction and independent of temperature.

Associations of Left Ventricular Hypertrophy and Geometry with Adverse Outcomes in Patients with CKD and Hypertension.

BACKGROUND AND OBJECTIVES: Left ventricular hypertrophy (LVH) and abnormal left ventricular (LV) geometry predict adverse outcomes in the general and hypertensive populations, but findings in CKD are still inconclusive. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We enrolled 445 patients with hypertension and CKD stages 2-5 in two academic nephrology clinics in 1999-2003 who underwent both echocardiography and ambulatory BP monitoring. LVH (LV mass >100 g/m(2) [women] and >131 g/m(2) [men]) and relative wall thickness (RWT) were used to define LV geometry: no LVH and RWT≤0.45 (normal), no LVH and RWT>0.45 (remodeling), LVH and RWT≤0.45 (eccentric), and LVH and RWT>0.45 (concentric). We evaluated the prognostic role of LVH and LV geometry on cardiovascular (CV; composite of fatal and nonfatal events) and renal outcomes (composite of ESRD and all-cause death). RESULTS: Age was 64.1±13.8 years old; 19% had diabetes, and 22% had CV disease. eGFR was 39.9±20.2 ml/min per 1.73 m(2). LVH was detected in 249 patients (56.0%); of these, 125 had concentric LVH, and 124 had eccentric pattern, whereas 71 patients had concentric remodeling. Age, women, anemia, and nocturnal hypertension were independently associated with both concentric and eccentric LVH, whereas diabetes and history of CV disease associated with eccentric LVH only, and CKD stages 4 and 5 associated with concentric LVH only. During follow-up (median, 5.9 years; range, 0.04-15.3), 188 renal deaths (112 ESRD) and 103 CV events (61 fatal) occurred. Using multivariable Cox analysis, concentric and eccentric LVH was associated with higher risk of CV outcomes (hazard ratio [HR], 2.59; 95% confidence interval [95% CI], 1.39 to 4.84 and HR, 2.79; 95% CI, 1.47 to 5.26, respectively). Similarly, greater risk of renal end point was detected in concentric (HR, 2.33; 95% CI, 1.44 to 3.80) and eccentric (HR, 2.30; 95% CI, 1.42 to 3.74) LVH. Sensitivity analysis using LVH and RWT separately showed that LVH but not RWT was associated with higher cardiorenal risk. CONCLUSIONS: In patients with CKD, LVH is a strong predictor of the risk of poor CV and renal outcomes independent from LV geometry.

Molecular dynamics study of nanoconfined water flow driven by rotating electric fields under realistic experimental conditions.

In our recent work, J. Chem. Phys. 2013, 138, 154712, we demonstrated the feasibility of unidirectional pumping of water, exploiting translational-rotational momentum coupling using nonequilibrium molecular dynamics simulations. Flow can be sustained when the fluid is driven out of equilibrium by an external spatially uniform rotating electric field and confined between two planar surfaces exposing different degrees of hydrophobicity. The permanent dipole moment of water follows the rotating field, thus inducing the molecules to spin, and the torque exerted by the field is continuously injected into the fluid, enabling a steady conversion of spin angular momentum into linear momentum. The translational-rotational coupling is a sensitive function of the rotating electric field parameters. In this work, we have found that there exists a small energy dissipation region attainable when the frequency of the rotating electric field matches the inverse of the dielectric relaxation time of water and when its amplitude lies in a range just before dielectric saturation effects take place. In this region, that is, when the frequency lies in a small window of the microwave region around ∼20 GHz and amplitude ∼0.03 V Å(-1), the translational-rotational coupling is most effective, yielding fluid velocities of magnitudes of ∼2 ms(-1) with only moderate fluid heating. In this work, we also confine water to a realistic nanochannel made of graphene giving a hydrophobic surface on one side and ß-cristobalite giving a hydrophilic surface on the other, reproducing slip-and-stick velocity boundary conditions, respectively. This enables us to demonstrate that in a realistic environment, the coupling can be effectively exploited to achieve noncontact pumping of water at the nanoscale. A quantitative comparison between nonequilibrium molecular dynamics and analytical solutions of the extended Navier-Stokes equations, including an external rotating electric field has been performed, showing excellent agreement when the electric field parameters match the aforementioned small energy dissipation region.

A new and effective method for thermostatting confined fluids.

We present a simple thermostatting method suitable for nanoconfined fluid systems. Two conventional strategies involve thermostatting the fluid directly or employing a thermal wall that couples only the wall atoms with the thermostat. When only a thermal wall is implemented, the temperature control of the fluid is true to the actual experiment and the heat is transferred from the fluid to the walls. However, for large or complex systems it can often be computationally prohibitive to employ thermal walls. To overcome this limitation many researchers choose to freeze wall atoms and instead apply a synthetic thermostat to the fluid directly through the equations of motion. This, however, can have serious consequences for the mechanical, thermodynamic, and dynamical properties of the fluid by introducing unphysical behaviour into the system [Bernardi et al., J. Chem. Phys. 132, 244706 (2010)]. In this paper, we propose a simple scheme which enables working with both frozen walls and naturally thermostatted liquids. This is done by superimposing the walls with oscillating particles, which vibrate on the edge of the fluid control volume. These particles exchange energy with the fluid molecules, but do not interact with wall atoms or each other, thus behaving as virtual particles. Their displacements violate the Lindemann criterion for melting, in such a way that the net effect would not amount to an additional confining surface. One advantage over standard techniques is the reduced computational cost, particularly for large walls, since they can be kept rigid. Another advantage over accepted strategies is the opportunity to freeze complex charged walls such as ß-cristobalite. The method furthermore overcomes the problem with polar fluids such as water, as thermalized charged surfaces require higher spring constants to preserve structural stability, due to the effects of strong Coulomb interactions, thus inevitably degrading the thermostatting efficiency.

Electropumping of water with rotating electric fields.

Pumping of fluids confined to nanometer dimension spaces is a technically challenging yet vitally important technological application with far reaching consequences for lab-on-a-chip devices, biomimetic nanoscale reactors, nanoscale filtration devices and the like. All current pumping mechanisms require some sort of direct intrusion into the nanofluidic system, and involve mechanical or electronic components. In this paper, we present the first nonequilibrium molecular dynamics results to demonstrate that non-intrusive electropumping of liquid water on the nanoscale can be performed by subtly exploiting the coupling of spin angular momentum to linear streaming momentum. A spatially uniform rotating electric field is applied to water molecules, which couples to their permanent electric dipole moments. The resulting molecular rotational momentum is converted into linear streaming momentum of the fluid. By selectively tuning the degree of hydrophobicity of the solid walls one can generate a net unidirectional flow. Our results for the linear streaming and angular velocities of the confined water are in general agreement with the extended hydrodynamical theory for this process, though also suggest refinements to the theory are required. These numerical experiments confirm that this new concept for pumping of polar nanofluids can be employed under laboratory conditions, opening up significant new technological possibilities.

Oxidação de microcistinas-LR em águas pelo íon ferrato(VI) / Aqueous oxidation of microcystin-LR by ferrate(VI)

Toxinas de cianobactérias têm se tornado um grave problema na produção segura de água para consumo humano e animal. Técnicas convencionais de tratamento falham em atingir padrões de potabilidade. O ferrato(VI) de potássio, um composto oxidante e coagulante, mostra potencialidade no tratamento de águas contaminadas. Neste trabalho, são apresentados resultados da oxidação pelo ferrato(VI) de uma toxina gerada por cianobactérias, a microcistina-LR. Ensaios de cinética de oxidação e de teste de jarros mostram um valor médio de 0,012 min-1 para a constante de taxa de reação de pseudoprimeira ordem, para concentrações de MC-LR de 100 a 200 µg.L-1 na água bruta. Dosagens de 1,6 a 5,0 mg.L-1 de ferrato(VI) sugerem o atendimento ao padrão de potabilidade para microcistinas, mostrando que o oxidante poderá ser empregado como coadjuvante no tratamento de água.

Algae toxins are becoming a severe problem in the water treatment industry, especially for human and animal consumption. Traditional treatment processes have failed in complying with water supply standards. Potassium ferrate(VI) is a powerful oxidant, disinfectant and, also, a coagulant. In this paper, the results of microcystin-LR oxidation by ferrate(VI) ion are presented. Kinetic and jar tests showed a average value of 0,012 min-1 for the pseudo first order reaction rate constant, for 100 and 200 µg.L-1 concentration of MC-LR. Ferrate(VI) dosages between 1.6 and 5.0 mg.L-1 suggest that water supply standards for MC-LR can be reached, which means that the oxidant may be employed as coadjuvant in water treatment.

A novel non-protein-coding infection-specific gene family is clustered throughout the genome of Phytophthora infestans.

Phytophthora infestans is the cause of late blight, a devastating and re-emerging disease of potato. Significant advances have been made in understanding the biology of P. infestans, and in the development of molecular tools to study this oomycete. Nevertheless, little is known about the molecular bases of the establishment or development of disease in this hemibiotrophic pathogen. Suppression subtractive hybridization (SSH) was used to generate cDNA enriched for sequences upregulated during potato infection. To identify pathogen-derived cDNAs, and eliminate host sequences from further study, SSH cDNA was hybridized to a P. infestans bacterial artificial chromosome library. A new gene family was identified called Pinci1, comprising more than 400 members arranged in clusters of up to nine copies throughout the P. infestans draft genome sequence. Real-time RT-PCR was used to quantify the expression of five classes of transcript within the family, relative to the constitutively expressed PiactA gene, and it revealed them to be significantly upregulated from 12 to 33 h post-inoculation, a period defining the biotrophic phase of infection. Computational analysis of sequences suggested that transcripts were non-protein coding, and this was confirmed by transient expression of FLAG-tagged ORFs in P. infestans.

Sodium ferrate (IV) and sodium hypochlorite in disinfection of biologically treated effluents. Ammonium nitrogen protection against THMs and HAAs.

The work described in this paper presents an evaluation of disinfection by-products generation in four different biological treatment plant effluents, making use of sodium hypochlorite and sodium ferrate (IV) at varying concentration and reaction time. Correlations between pH, chemical oxygen demand, total organic carbon, ammonium nitrogen, combined chlorine and trihalomethanes (THMs) and haloacetic acids (HAAs) were carried out. Disinfection by-products generation presented a direct relation with concentration and sodium hypochlorite reaction time. For the highest hypochlorite concentration employed (20 mg L(-1)) and highest reaction time (168 h), the THMs total did not exceed 312.96 microg L(-1), a value that lies below the Brazilian emission standard for treated effluents (1 mg L(-1) of chloroform). The THMs presented an inverse correlation with ammonium nitrogen, when inverse (R(2) = 0.646; P < 0.001) and exponential (R(2) = 0.707; P < 0.001) function were used. As per HAAs this same relation was observed for logarithmic (R(2) = 0.0397 P < 0.001) and exponential (R(2) = 0.508; P < 0.001) functions. The more nitrified the effluent, the bigger the chlorinated disinfection by-product generation. The disinfectant sodium ferrate (IV) does not lead to halogenated by-product formation.

Indice de impacto dos resíduos sólidos urbanos na saúde pública (IIRSP): metodologia e aplicação / Impact index of solid wastes management systems on public health (IIRSP): methodology and application

A redução do número de enfermidades produzidas, direta ou indiretamente, pelos resíduos sólidos depende de uma coleta eficiente e de uma adequada disposição final. Com as informações obtidas da aplicação de um questionário enviado aos municípios sul rio-grandenses divididos em sete regiões homogêneas, foram desenvolvidos indicadores e, por meio de procedimentos estatísticos não paramétricos, estruturados oito índices (índices específicos) que formaram um índice geral de controle de qualidade dos serviços de limpeza urbana. O artigo apresenta um sumário e um exemplo da metodologia utilizada para a criação do índice de Impacto dos Resíduos Sólidos Urbanos na Saúde Pública (IIRSP), o qual mais diretamente espelha a relação Resíduos sólidos-homem-saúde pública.