...both scoring systems were developed in the mid ‘90 s by Miranda et al. Nowadays, the smart technologies available at bedside relieve nurses from many of these tasks. ...the enhancement of ...multimodal monitoring systems plus the management of intravenous (vasoactive drugs) infusions represent two clear examples of this evolution. ...we are taking into account that the solely isolation precautions do not directly affect the increasing of nursing workloads in ICU, according to Elli et al.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Two years since the outbreak of the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, there remain few clinically effective drugs to complement ...vaccines. One is the anticoagulant, heparin, which in 2004 was found able to inhibit invasion of SARS-CoV (CoV-1) and which has been employed during the current pandemic to prevent thromboembolic complications and moderate potentially damaging inflammation. Heparin has also been shown experimentally to inhibit SARS-CoV-2 attachment and infection in susceptible cells. At high therapeutic doses however, heparin increases the risk of bleeding and prolonged use can cause heparin-induced thrombocytopenia, a serious side effect. One alternative, with structural similarities to heparin, is the plant-derived, semi-synthetic polysaccharide, pentosan polysulfate (PPS). PPS is an established drug for the oral treatment of interstitial cystitis, is well-tolerated, and exhibits weaker anticoagulant effects than heparin. In an established Vero cell model, PPS and its fractions of varying molecular weights inhibited invasion by SARS-CoV-2. Intact PPS and its size-defined fractions were characterized by molecular weight distribution and chemical structure using nuclear magnetic resonance spectroscopy and liquid chromatography–mass spectrometry, then employed to explore the structural basis of interactions with SARS-CoV-2 spike protein receptor-binding domain (S1 RBD) and the inhibition of Vero cell invasion. PPS was as effective as unfractionated heparin, but more effective in inhibiting cell infection than low-molecular-weight heparin (on a weight/volume basis). Isothermal titration calorimetry and viral plaque-forming assays demonstrated size-dependent binding to S1 RBD and inhibition of Vero cell invasion, suggesting the potential application of PPS as a novel inhibitor of SARS-CoV-2 infection.
Bacterial infections are a growing public health threat with carbapenem-resistant Pseudomonas aeruginosa being classified as a Priority 1 critical threat by the World Health Organization. ...Antibody-based therapeutics can serve as an alternative and in some cases supplement antibiotics for the treatment of bacterial infections. The glycans covering the bacterial cell surface have been proposed as intriguing targets for binding by antibodies; however, antibodies that can engage with high affinity and specificity with glycans are much less common compared to antibodies that engage with protein antigens. In this study, we sought to characterize an antibody that targets a conserved glycan epitope on the surface of Pseudomonas. First, we characterized the breadth of binding of VSX, demonstrating that the VSX is specific to Pseudomonas but can bind across multiple serotypes of the organism. Next, we provide insight into how VSX engages with its target epitope, using a combination of biolayer interferometry and nuclear magnetic resonance, and verify our results using site-directed mutagenesis experiments. We demonstrate that the antibody, with limited somatic hypermutation of the complementarity-determining regions (CDRs) and with a characteristic set of arginines within the CDRs, specifically targets the conserved inner core of Pseudomonas lipopolysaccharides. Our results provide important additional context to antibody–glycan contacts and provide insight useful for the construction of vaccines and therapeutics against Pseudomonas aeruginosa, an important human pathogen.
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IJS, KILJ, NUK, PNG, UL, UM
The heparan sulfate mimetic PI-88 is a complex mixture of sulfated oligosaccharides with anti-metastatic and anti-angiogenic activity due to its potent inhibition of heparanase and heparan ...sulfate-dependent angiogenic growth factors. It was recently in Phase III clinical trials for postresection hepatocellular carcinoma. The major oligosaccharide constituents of PI-88 were prepared for the first time by sulfonation of individually purified phosphorylated oligosaccharides isolated from the PI-88 precursor. PI-88 and its components were subjected to detailed 1D and 2D NMR spectroscopic analysis. The spectra of the individual components greatly assisted the assignment of minor resonances in the 1H NMR spectrum of PI-88. The data also showed that the majority of the oligosaccharides in PI-88 are fully sulfated and that undersulfated species present are largely due to anomeric desulfation. The solution conformation of the phosphomannopentaose sulfate (major component) of PI-88 was then determined by a combination of molecular dynamics simulations and NOE measurements which may provide insights into its binding interactions with target proteins.
Introduction:
Midline catheters are widely used in clinical practice. Proper placement of midline catheter tip is usually assessed only by aspirating blood and flushing with normal saline without ...resistance.
Purpose:
To describe the ultrasound-guided tip location for midline catheters and its feasibility and to compare incidence of catheter-related venous thrombosis associated with or without ultrasound tip localization.
Methods:
The ultrasound-guided tip location is described step by step. Feasibility of the technique and incidence of catheter-related venous thrombosis were measured (study group) and compared with two historical groups: study group, 20-cm midline catheters inserted with ultrasound-guided tip location; group 1, 25-cm midline catheters inserted without ultrasound-guided tip location and group 2, 20-cm midline catheters inserted without ultrasound-guided tip location.
Results:
In the study group, ultrasound-guided tip location was easily feasible in 98.9% of patients. Incidence of catheter-related venous thrombosis was 2.42% in control group 1, 9% in control group 2 and 2.62% in the study group.
Discussion:
In the study group and control group 1, the tip was placed in the axillary vein, about 3 cm distal to the clavicle and in the subclavian vein. In control group 2, the tip was probably located at the transition between the axillary and the subclavian vein. It is possible that such position may have been associated with an increased incidence of catheter-related venous thrombosis.
Conclusion:
The ideal position of the tip of a midline catheter might be inside the axillary vein, about 3 cm distal to the axillary-subclavian transition or inside the subclavian vein. Ultrasound-guided tip location is safe, inexpensive, easy and potentially useful during midline catheters insertion.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
AIMThe aim of this study was to assess the noisiness levels produced by different gas source systems, breathing circuits setup, and gas flow rates during continuous positive airway pressure (CPAP) ...delivered through helmet.
METHODSThis was a crossover design study. Ten healthy subjects received helmet CPAP at 5 cm H2O in random order with different gas flow rates (60 and 80 L/min), 3 diverse gas source systems (AVenturi system, Boxygen and air flowmeters, Celectronic Venturi system), and 3 different breathing circuit configurations. During every step of this study, a heat and moisture exchanger (HME) was placed on the helmet inlet gas port to measure the effects on noise production. Noise intensity level was recorded through a sound-level meter. Participants scored their noisiness perception on a visual analog scale.
RESULTSThe noise level inside the helmet ranged between 76 ± 4 and 117 ± 1 Decibel A. The gas source and the gas flow rate always affected the noise level inside and outside the helmet (P < .001). The different “breathing circuit setup” did not change the noise levels inside the helmet (P = .244), but affected the noise level outside, especially when a Venturi system was used (P < .001). An HME filter placed at the junction between the inspiratory limb of the breathing circuit and the helmet significantly decreased the noise intensity inside the helmet (mean dBA without HME, 99.56 ± 13.30 vs 92.26 ± 10.72 with HME; P < .001) and outside (mean dBA without HME, 68.16 ± 12.05 vs 64.97 ± 12.17 with HME; P < .001). The perception of noise inside the helmet was lower when an HME filter was placed on the inspiratory inlet gas port (median, 6 interquartile range, 4–7 vs 7 5–8; P < .001).
CONCLUSIONSWhen helmet CPAP is delivered through gas flow rates up to 50 L/min, an HME placed on the helmet inlet gas port should be used to reduce noise inside the helmet and to improve patientsʼ comfort.
Heparanase is the only known endoglycosidase able to cleave heparan sulfate. Roneparstat and necuparanib, heparanase inhibitors obtained from heparin and currently being tested in man as a potential ...drugs against cancer, contain in their structure glycol-split uronic acid moieties probably responsible for their strong inhibitory activity. We describe here the total chemical synthesis of the trisaccharide GlcNS6S-GlcA-1,6anGlcNS (
) and its glycol-split (gs) counterpart GlcNS6S-gsGlcA-1,6anGlcNS (
) from glucose. As expected, in a heparanase inhibition assay, compound
is one order of magnitude more potent than
. Using molecular modeling techniques we have created a 3D model of
and
that has been validated by NOESY NMR experiments. The pure synthetic oligosaccharides have allowed the first in depth study of the conformation of a glycol-split glucuronic acid. Introducing a glycol-split unit in the structure of
increases the conformational flexibility and shortens the distance between the two glucosamine motives, thus promoting interaction with heparanase. However, comparing the relative activities of
and roneparstat, we can conclude that the glycol-split motive is not the only determinant of the strong inhibitory effect of roneparstat.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Introduction:
Intraprocedural tip control techniques are critical during central venous catheter placement. According to international guidelines (INS 2021), intracavitary electrocardiography is the ...first method of choice to verify it; when this technique is not feasible, it is considered acceptable to use a contrast-enhanced ultrasound-based tip location method, commonly known as “bubble-test” as an effective alternative.
Objective:
To assess whether the length of the vascular catheter can alter the time between the injection of the contrast media and its appearance at the catheter tip and the injection duration. Differences between operators stratified according to experience were evaluated as secondary endpoints.
Methods:
A bench study was conducted using an extracorporeal circuit. For each catheter length (60, 40, and 20 cm), three injections were obtained by each of the five operators with different levels of experience for a total of 45 measurements. Differences among operators were evaluated using ANOVA, and the impact of catheter length and operator expertise on times was assessed using repeated measurement models.
Results:
Hub-to-tip times of 247.33 ms (SD 168.82), 166 ms (SD 95.46), 138 ms (SD 54.48), and injection duration of 1620 ms (SD 748.58), 1614 ms (SD 570.95), 1566 ms (SD 302.83) were observed for 60, 40, 20 cm catheter length, respectively. A significant time variability between operators was observed. Moreover, moving from 60 to 20 cm, hub-to-tip time was significantly longer for 60 cm devices ( p = 0.0124), while little differences were observed for injection duration.
Conclusions:
Catheter length can change both the time between the injection of the contrast media and its appearance at the catheter tip and the injection duration. Hub-to-tip times obtained with 20 and 40 cm and overall injection duration did not differ significantly; skilled personnel could substantially reduce both values analyzed in this study.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Heparin is a highly sulfated glycosaminoglycan (GAG) of natural origin used as an anticoagulant and antithrombotic drug. These properties are principally based on the binding and activation of ...antithrombin (AT) through the pentasaccharide sequence GlcNAc/NS,6S‐GlcA‐GlcNS,3,6S‐IdoA2S‐GlcNS,6S (AGA*IA). Literature data show that the population of the 2S0 ring conformation of the 2‐O‐sulfo‐α‐l‐iduronic acid (IdoA2S) motif correlates with the affinity and activation of AT. It was recently demonstrated that two synthetic AGA*IA‐containing hexasaccharides (one G unit added at the reducing end), differing in the degree of sulfation of the IdoA unit, show comparable affinity and ability to activate AT, despite a different conformation of the IdoA residue. In this paper, the binding of these two glycans to AT was studied by isothermal titration microcalorimetry (ITC), transferred (tr‐) NOESY, saturation transfer difference (STD) NMR spectroscopy and molecular dynamics (MD) simulations. Results indicated that both the IdoA2S and the IdoA units assume a 2S0 conformation when bound with AT, and so present a common binding epitope for the two glycans, centred on the AGA*IA sequence.
Oligosaccharide anticoagulants: The conformation of the IdoA subunit in a pair of synthetic hexasaccharides is changed from 1C4 to 2S0 upon binding to antithrombin (AT), with the contact network between the AT heparin‐binding site (HBS) and residues surrounding the trisaccharide sequences GlcNS3S6S‐IdoA2S/IdoA‐GlcNS6S′′ playing a significant role, independently of the 2‐O‐sulfation state of IdoA.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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