Hemodynamic impact of VASQ device in vascular access creation.

BACKGROUND: Native arteriovenous fistula is the preferred vascular access in term of functionality, efficiency and complication rate. Nevertheless, research continues to seek strategies to reduce the risk of neointimal hyperplasia and hemodynamic modification. The aim of the study was to evaluate the impact on hemodynamic of the VasQ device in arteriovenous fistulae creation. METHODS: The analysis included patients who underwent to fistula creation with or without implantation of the VasQ device between May and September 2019. The hemodynamic parameters were evaluated pre-operatively and at a follow-up of 1, 3, 6 months. The patency and complication rate were evaluated. RESULTS: Fifteen VasQ devices were implanted during 30 arteriovenous fistula surgery. The baseline patients features were similar between groups (VasQ treated/control). At baseline, preoperative arterial flow was similar; radial artery diameter at surgical site was 3.4 ± 0.8 mm in treated and 2.8 ± 0.5 mm in the control group. The mean arterial flow at 1 month was 480 ± 210 mL/min in treated and 561 ± 27 mL/min in the control group. At 3 months the mean arterial flow in treated was 645 ± 143 mL/min versus 824 ± 211 mL/min (p = 0.02) in the control group; at 6 months the arterial flow was 714 ± 146 mL/min versus 810 ± 194 mL/min (p = 0.05) in control group. The cardiac output flow at 6 months in the treated group was 4458 ± 928 mL/min versus 5599 ± 1355 mL/min (p = 0.05) in the control group. At 6 months the primary patency was 73% and 80% and the secondary patency 80% and 86% in treated compared to the control group, respectively. No VASQ device complications were recorded. CONCLUSION: The analysis of these data suggested that using VasQ device could be protective against the hemodynamic modification that occur during arteriovenous fistulae creation.

The Bacteriostatic Activity of 2-Phenylethanol Derivatives Correlates with Membrane Binding Affinity.

The hydrophobic tails of aliphatic primary alcohols do insert into the hydrophobic core of a lipid bilayer. Thereby, they disrupt hydrophobic interactions between the lipid molecules, resulting in a decreased lipid order, i.e., an increased membrane fluidity. While aromatic alcohols, such as 2-phenylethanol, also insert into lipid bilayers and disturb the membrane organization, the impact of aromatic alcohols on the structure of biological membranes, as well as the potential physiological implication of membrane incorporation has only been studied to a limited extent. Although diverse targets are discussed to be causing the bacteriostatic and bactericidal activity of 2-phenylethanol, it is clear that 2-phenylethanol severely affects the structure of biomembranes, which has been linked to its bacteriostatic activity. Yet, in fungi some 2-phenylethanol derivatives are also produced, some of which appear to also have bacteriostatic activities. We showed that the 2-phenylethanol derivatives phenylacetic acid, phenyllactic acid, and methyl phenylacetate, but not Tyrosol, were fully incorporated into model membranes and affected the membrane organization. Furthermore, we observed that the propensity of the herein-analyzed molecules to partition into biomembranes positively correlated with their respective bacteriostatic activity, which clearly linked the bacteriotoxic activity of the substances to biomembranes.

Inserting Small Molecules across Membrane Mixtures: Insight from the Potential of Mean Force.

Small solutes have been shown to alter the lateral organization of cell membranes and reconstituted phospholipid bilayers; however, the mechanisms by which these changes happen are still largely unknown. Traditionally, both experiment and simulation studies have been restricted to testing only a few compounds at a time, failing to identify general molecular descriptors or chemical properties that would allow extrapolating beyond the subset of considered solutes. In this work, we probe the competing energetics of inserting a solute in different membrane environments by means of the potential of mean force. We show that these calculations can be used as a computationally efficient proxy to establish whether a solute will stabilize or destabilize domain phase separation. Combined with umbrella-sampling simulations and coarse-grained molecular dynamics simulations, we are able to screen solutes across a wide range of chemistries and polarities. Our results indicate that for the system under consideration, preferential partitioning and therefore effectiveness in altering membrane phase separation are strictly linked to the location of insertion in the bilayer (i.e., midplane or interface). Our approach represents a fast and simple tool for obtaining structural and thermodynamic insight into the partitioning of small molecules between lipid domains and its relation to phase separation, ultimately providing a platform for identifying the key determinants of this process.

Molecular dynamics trajectories for 630 coarse-grained drug-membrane permeations.

The permeation of small-molecule drugs across a phospholipid membrane bears much interest both in the pharmaceutical sciences and in physical chemistry. Connecting the chemistry of the drug and the lipids to the resulting thermodynamic properties remains of immediate importance. Here we report molecular dynamics (MD) simulation trajectories using the coarse-grained (CG) Martini force field. A wide, representative coverage of chemistry is provided: across solutes-exhaustively enumerating all 105 CG dimers-and across six phospholipids. For each combination, umbrella-sampling simulations provide detailed structural information of the solute at all depths from the bilayer midplane to bulk water, allowing a precise reconstruction of the potential of mean force. Overall, the present database contains trajectories from 15,120 MD simulations. This database may serve the further identification of structure-property relationships between compound chemistry and drug permeability.

[Steroid-resistant focal segmental glomerulosclerosis treated with cascade plasmafiltration and rituximab].

A 39-year man with primary steroid resistant focal segmental glomerulosclerosis (FSGS) was treated with mycophenolate mofetil and ACE-inhibitors. After six months a different therapeutics approach was mandatory due to the worsening of renal function and the relapse of proteinuria at the nephrotic range. The combination of cascade plasmafiltration and single dose of rituximab (375 mg/m²) achieved clinical remission and improved renal function in six months follow up. Cascade plasmafiltration in association with rituximab can be considered as a salvage method for primary steroid-resistant FSGS. Clinical trials should be carried out for protocol approval.

An Eco-Friendly, Tunable and Scalable Method for Producing Porous Functional Nanomaterials Designed Using Molecular Interactions.

Despite significant improvements in the synthesis of templated silica materials, post-synthesis purification remains highly expensive and renders the materials industrially unviable. In this study this issue is addressed for porous bioinspired silica by developing a rapid room-temperature solution method for complete extraction of organic additives. Using elemental analysis and N2 and CO2 adsorption, the ability to both purify and controllably tailor the composition, porosity and surface chemistry of bioinspired silica in a single step is demonstrated. For the first time the extraction is modelled using molecular dynamics, revealing that the removal mechanism is dominated by surface-charge interactions. This is extended to other additive chemistry, leading to a wider applicability of the method to other materials. Finally the environmental benefits of the new method are estimated and compared with previous purification techniques, demonstrating significant improvements in sustainability.

Molecular Simulation Study of the Early Stages of Formation of Bioinspired Mesoporous Silica Materials.

The use of bioinspired templates, such as polyamines and polypeptides, could lead to significant improvements in the synthesis conditions under which mesoporous materials are traditionally produced, removing the need for strong pH as well as high temperature or pressure. In this work, we perform atomistic molecular dynamics simulations of 1,12-diaminododecane surfactants, in water and in the presence of silica monomers, to investigate the early stages of synthesis of one of the first examples of bioinspired silica materials. Different surfactant concentrations and pH were considered, clarifying the influence of the charge state of the molecules on the self-assembly process. We show that the amphiphilic amines form stable lamellar structures at equilibrium in the range from intermediate to high pH values. In a later stage, when silica species are added to the system, our results reveal that, in the same range of pH, silicates strongly adsorb around these aggregates at the interface with water. This causes a considerable modification of the curvature of the layer, which suggests a tendency for the system to evolve from a lamellar phase to the formation of vesicle structures. Furthermore, we show that silica monomers are able to penetrate the layer spontaneously when defects are created as a result of surfactants' head-to-head repulsion. These findings are in agreement with experimental observations and support the pillaring mechanism postulated for this class of materials. However, our simulations indicate that the aggregation process is driven by charge matching between surfactant heads and silica monomers rather than by hydrogen bond interactions between neutral species, as had been previously hypothesized.

[Quality of life assessment in patients on hemodialysis and peritoneal dialysis]. / Qualità di vita e aspetti psicologici dell'anziano uremico in trattamento dialitico: confronto tra emodialisi e dialisi peritoneale.

Assessment of the quality of life (QoL) of patients with end-stage renal disease undergoing replacement therapy is very important. The aim of our study was to assess the QoL of patients on hemodialysis (HD) and peritoneal dialysis (PD). To determine the state of health of the patients as well as psychological aspects we used two international questionnaires: the Health-Related Short Form (SF-36) and the Psychological General Well-being Index (PGWBI). The study included 48 patients (26 men, 22 women) with chronic kidney disease (KDOQI: 5). All patients were on dialysis treatment. Their mean age was 63 years (range 59-73) and the mean duration of dialysis was 18 months (range 12-34). Twenty-four patients (13 men, 11 women) were on DP and 24 (13 men, 11 women) on HD. The results demonstrate that the PD and HD groups diverged on almost all scales. The scales that measure both the mental and physical dimensions of QoL showed PD to be associated with a higher level of psychophysical well-being than HD. The SF-36 revealed that both the physical and mental dimensions were directly influenced by the type of treatment. On the depression scale of PGWBI we found that patients on HD were more prone to depression than patients on PD. In conclusion, PD appears to have clear advantages in terms of QoL, especially in elderly patients, thanks to the possibility to perform the treatment independently at the patient's home.

Extracorporeal photochemotherapy for the treatment of glomerulopathies with associated nephrotic syndrome.

INTRODUCTION: Patients with glomerulopathies associated with nephrotic syndrome have few effective treatment options. Here we report on the use of extracorporeal photochemotherapy (ECP) in 6 patients in whom glomerulopathy failed to respond to pharmacologic therapy. ECP is a promising immunomodulatory therapy associated with few side effects, that has been successfully used in the treatment of other immune-mediated conditions such as solid organ transplant rejection and graft-versus-host disease. METHODS: In this study, patients underwent 12 months of ECP. In all patients, progressive improvement in proteinuria was noted during the follow-up period, and total cholesterol and triglyceride levels also returned to near-normal values. RESULTS: In the 4 patients who had adequate renal function at study initiation, improvement of renal function was observed, as indicated by improved glomerular filtration rates (GFRs) and decreased proteinuria to creatininuria (Pru/Cru) ratios. In contrast, renal function progressively worsened in the 2 patients with inadequate renal function at study initiation. CONCLUSIONS: The results suggest that ECP is a feasible treatment for patients with glomerulopathies associated with nephrotic syndrome who have adequate baseline renal function. Additional clinical evaluation will have to be performed to better define the patient population in which ECP is most effective.