Differential Solvent DEEP-STD NMR and MD Simulations Enable the Determinants of the Molecular Recognition of Heparin Oligosaccharides by Antithrombin to Be Disentangled.

The interaction of heparin with antithrombin (AT) involves a specific sequence corresponding to the pentasaccharide GlcNAc/NS6S-GlcA-GlcNS3S6S-IdoA2S-GlcNS6S (AGA*IA). Recent studies have revealed that two AGA*IA-containing hexasaccharides, which differ in the sulfation degree of the iduronic acid unit, exhibit similar binding to AT, albeit with different affinities. However, the lack of experimental data concerning the molecular contacts between these ligands and the amino acids within the protein-binding site prevents a detailed description of the complexes. Differential epitope mapping (DEEP)-STD NMR, in combination with MD simulations, enables the experimental observation and comparison of two heparin pentasaccharides interacting with AT, revealing slightly different bound orientations and distinct affinities of both glycans for AT. We demonstrate the effectiveness of the differential solvent DEEP-STD NMR approach in determining the presence of polar residues in the recognition sites of glycosaminoglycan-binding proteins.

PICC insertion and veins of the arm size variation during dialysis treatment: A prospective observational study.

BACKGROUND: Peripherally Inserted Central Catheters play an increasingly important role in Central Venous Access Devices. However, the use of these devices should be carefully considered in specific situations such as central catheterisation in patients with chronic kidney disease. When evaluating the feasibility of placement for a patient undergoing dialysis, the relationship between changes in circulating volume before and after dialysis treatment, and potential variations in the size of deep veins in the upper limbs, should be considered. MATERIALS: Upper limb veins, specifically the basilic or brachial veins, were identified and measured before and after dialysis treatment. Patient data and weight loss data during dialysis treatment were also collected. Linear regression analysis was performed to assess the correlation between the variables. RESULTS: The average variation in vein size for the entire sample was +0.17 ± 0.43 mm. The mean volume removed was 2.2 ± 0.8 l. In subgroup 1 (fluid volume loss <2000 ml), the population experienced a decrease in the measured vein size after dialysis. In subgroup 2 (fluid volume loss ⩾2000 ml), the population experienced an increase in the measured vein size after dialysis. CONCLUSIONS: Upper arm vascular access placement in dialysed patients with fluid removal of less than 2000 ml should be performed after the dialysis session. Conversely, in dialysed patients with fluid removal of more than 2000 ml, where a significant increase in vein size was observed, vascular access placement should be performed before the dialysis session when the veins are smaller. Additionally, it should be noted that in patients with chronic kidney disease, the venous system of the upper limbs should be preserved as much as possible to prevent thrombosis and stenosis in potential arteriovenous fistula creation.

Brachial Tunneled Peripherally Inserted Central Catheters and the Risk of Catheter Complications: A Systematic Review and Meta-Analysis.

INTRODUCTION: Situations involving increased workloads and stress (i.e., the COVID-19 pandemic) underline the need for healthcare professionals to minimize patient complications. In the field of vascular access, tunneling techniques are a possible solution. This systematic review and meta-analysis aimed to compare the effectiveness of tunneled Peripherally Inserted Central Catheters (tPICCs) to conventional Peripherally Inserted Central Catheters (cPICCs) in terms of bleeding, overall success, procedural time, and late complications. METHODS: Randomized controlled trials without language restrictions were searched using PUBMED®, EMBASE®, EBSCO®, CINAHL®, and the Cochrane Controlled Clinical Trials Register from August 2022 to August 2023. Five relevant papers (1238 patients) were included. RESULTS: There were no significant differences in overall success and nerve or artery injuries between the two groups (p = 0.62 and p = 0.62, respectively), although cPICCs caused slightly less bleeding (0.23 mL) and had shorter procedural times (2.95 min). On the other hand, tPICCs had a significantly reduced risk of overall complications (p < 0.001; RR0.41 [0.31-0.54] CI 95%), catheter-related thrombosis (p < 0.001; RR0.35 [0.20-0.59] IC 95%), infection-triggering catheter removal (p < 0.001; RR0.33 [0.18-0.61] IC 95%), wound oozing (p < 0.001; RR0.49 [0.37-0.64] IC 95%), and dislodgement (p < 0.001; RR0.4 [0.31-0.54] CI 95%). CONCLUSIONS: The tunneling technique for brachial access appears to be safe concerning intra-procedural bleeding, overall success, and procedural time, and it is effective in reducing the risk of late complications associated with catheterization.

Patients' recollections of helmet-CPAP treatment during COVID-19 pandemic: A qualitative study.

BACKGROUND: During the pandemic outbreak, helmet continuous positive airway pressure (CPAP) was widely used as respiratory support for COVID-19 patients, inside and outside of intensive care units. The available literature suggests specific interventions to improve the comfort of patients treated with helmet-CPAP. Few reports are available on the experiences of patients undergoing this treatment. AIM: This qualitative study aimed to explore the views and recollections of COVID-19 patients undergoing helmet-CPAP. STUDY DESIGN: We conducted semi-structured interviews with thematic analysis. Participants were recruited from the follow-up programme for COVID-19 patients discharged from an Italian general intensive care unit. Participants were interviewed by telephone. Data analysis followed the principles of thematic synthesis approach. FINDINGS: We conducted 29 phone calls in patients eligible for the study. Five participants declared that they did not remember the time spent in hospital on helmet-CPAP. Twenty-four patients were then included. Two themes and six subthemes were generated from their interview data: (1) The helmet-CPAP as a life-saving treatment (subthemes: recognition of the usefulness of treatment and resilience); (2) the negative feelings related to helmet-CPAP application (subthemes: communication problems, entrapment, mental confusion, fear of dying). Each patient's experience was unique, but some discomfort elements such as noise, gas flow turbulence, choking sensation and thirst were found to be very common. CONCLUSIONS: The application of helmet-CPAP treatment generated positive and negative memories and feelings in COVID-19 patients during the pandemic. The patients' experience has provided an overview of the main factors of discomfort. This can be a starting point for taking corrective measures to promote greater helmet tolerance and subsequent treatment success. RELEVANCE TO CLINICAL PRACTICE: This study has provided an insight into the patient's recollections about helmet-CPAP treatment during a worldwide pandemic. The findings suggested strict applications of interventions aimed to reduce some issues that participants reported, to improve their compliance to treatment. Results from this study could help nurses in understanding the needs of patients treated with helmet-CPAP and may foster a care focused on patient-centred outcomes.

Can the length of a catheter change the time to bubble at the tip performing the "Bubble Test"? A bench study.

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.

Femoral venous access: State of the art and future perspectives.

In the past 5 years, non-dialysis femoral venous access has changed in terms of indications, techniques of insertion, and expected incidence of complications. To the traditional non-emergency indication for femoral catheters-obstruction of the superior vena cava-many other indications have been added, both in intensive and non-intensive care. The insertion technique has evolved, thanks to ultrasound guided venipuncture, tunneling, and ultrasound based intraprocedural tip location. Insertion of femorally inserted central catheters may be today regarded as a procedure with an extremely low intraprocedural and post-procedural risk. The risk of infection is reduced by the possibility of the exit site at mid-thigh, by the use of cyanoacrylate glue for sealing the exit site, and by appropriate intraprocedural strategies of infection prevention. The risk of catheter-related thrombosis is low, due to several concomitant strategies: a proper match between vein diameter and catheter caliber; an accurate intraprocedural assessment of tip location by ultrasound and/or intracavitary ECG; the consistent use of ultrasound guided venipuncture and micro-introducer kits; an adequate stabilization of the catheter at the exit site. The risk of mechanical complications and the risk of lumen occlusion are minimized when using polyurethane, power injectable catheters. All these novelties have brought a revolution in the field of femoral venous access, so that this route may be considered as safe and effective as other approaches to central venous catheterization.

Molecular Recognition of Aromatics in Spherical Nanocages.

In general, due to the lack of efficient specific molecular interactions, achieving host-guest molecular recognition inside large and neutral metal-organic cages (MOCs) is challenging. Preferential molecular recognition of aromatics using the internal binding sites of interlocked icosahedral (i. e., spherical) M12 L8 MOCs within poly-[n]-catenane (1) is reported. The guest absorption was monitored directly in the solid-state by consecutive single-crystal-to-single-crystal (SCSC) reactions in a gas-solid environment, in single-crystal X-ray diffraction (SC-XRD) experiments. The preferential guest uptake was corroborated by density functional theory (DFT) calculations by determining the host-guest interaction energy (Ehost-guest ) with a nitrobenzene (NB)≫p-xylene (p-xy)≫o-dichlorobenzene (o-DCB) trend (i. e., from 44 to 25 kcal mol-1 ), assessing the XRD outcomes. Combining SC-XRD, DFT and solid-state 13 C NMR, the exceptional stability of the M12 L8 cages, together with the guest exchange/release properties were rationalized by considering the presence of mechanical bonds (efficient π-π interactions) and by the pyridine's rotor-like behaviour (with 3 kcal mol-1 rotational energy barrier). The structure-function properties of M12 L8 makes 1 a potential candidate in the field of molecular sensors.

Kinetic trapping of 2,4,6-tris(4-pyridyl)benzene and ZnI2 into M12L8 poly-[n]-catenanes using solution and solid-state processes.

Here, we show that in a supramolecular system with more than 20 building blocks forming large icosahedral M12L8 metal-organic cages (MOCs), using the instant synthesis method, it is possible to kinetically trap and control the formation of interlocking M12L8 nanocages, giving rare M12L8 TPB-ZnI2 poly-[n]-catenane. The catenanes are obtained in a one-pot reaction, selectively as amorphous (a1) or crystalline states, as demonstrated by powder X-ray diffraction (powder XRD), thermogravimetric (TG) analysis and 1H NMR. The 300 K M12L8 poly-[n]-catenane single crystal X-ray diffraction (SC-XRD) structure including nitrobenzene (1) indicates strong guest binding with the large M12L8 cage (i.e., internal volume ca. 2600 Å3), allowing its structural resolution. Conversely, slow self-assembly (5 days) leads to a mixture of the M12L8 poly-[n]-catenane and a new TPB-ZnI2 (2) coordination polymer (i.e., thermodynamic product), as revealed by SC-XRD. The neat grinding solid-state synthesis also yields amorphous M12L8 poly-[n]-catenane (a1'), but not coordination polymers, selectively in 15 min. The dynamic behavior of the M12L8 poly-[n]-catenanes demonstrated by the amorphous-to-crystalline transformation upon the uptake of ortho-, meta- and para-xylenes shows the potential of M12L8 poly-[n]-catenanes as functional materials in molecular separation. Finally, combining SC-XRD of 1 and DFT calculations specific for the solid-state, the role of the guests in the stability of the 1D chains of M12L8 nanocages is reported. Energy interactions such as interaction energies (E), lattice energies (E*), host-guest energies (Ehost-guest) and guest-guest energies (Eguest-guest) were analysed considering the X-ray structure with and without the nitrobenzene guest. Not only the synthetic control achieved in the synthesis of the M12L8 MOCs but also their dynamic behavior either in the crystalline or amorphous phase are sufficient to raise scientific interest in areas ranging from fundamental to applied sides of chemistry and material sciences.

Midline catheters for blood gas and acid/base monitoring in critical patients: A prospective observational study.

BACKGROUND: Arterial lines and central venous catheter (CVC) allow to monitor patients' acid-base status and gas exchange. Their placement and maintenance may however be burdened by severe complications. Midline Catheters (MC) are peripheral venous accesses that are less invasive and easier to insert compared to CVC and arterial lines. METHODS: A prospective observational study was performed including stabilized critical patients with clinical indication to midline positioning before intensive care unit (ICU) discharge. The primary aim was to assess if venous sampling from MCs can be a reliable alternative to CVC for pH and CO2 monitoring. The secondary aim was to evaluate the correlation between samplings from MC, CVC and arterial line with regards to pH, carbon dioxide tension (pCO2), lactates and electrolytes. Three samples from CVC, arterial line and MC were collected simultaneously. Agreement and correlation of the studied parameters between different sampling sites were explored. RESULTS: 40 patients were included in the analysis. A good agreement for pH and pCO2 was recorded between MC and CVC: mean differences were 0.001 (95% CI -0.006 to 0.007) and 0.7 (-0.1 to 1.5), percentage error 0.4% and 11.2%, respectively. Correlation between MC and both central venous and arterial samples for pH, pCO2, lactates and electrolytes was found to be moderate-to-strong (Pearson's R coefficient range 0.59-0.99, p < 0.001 for all these parameters). CONCLUSIONS: In stabilized critical patients, midline catheters represent a reliable alternative to CVC and arterial lines to monitor acid-base disturbances, CO2 levels and electrolytes. The present findings add to the known advantages of MC, which might be considered a first-line vascular access for non-critical or stabilized patients who do not require infusion of vesicant or irritant drugs.

Helmet CPAP bundle: A narrative review of practical aspects and nursing interventions to improve patient's comfort.

BACKGROUND: The application of Continuous Positive Airway Pressure (CPAP) with a helmet is increasing around the world, both inside and outside of the intensive care unit. Current published literature focus's on indications, contraindications and efficiency of Helmet CPAP in differing clinical scenarios. Few reports, summarising the available knowledge concerning technical characteristics and nursing interventions to improve patient's comfort, are available. AIM: To identify the crucial technical aspects in managing patients undergoing Helmet-CPAP, and what nursing interventions may increase comfort. METHODS: A narrative literature review of primary research published 2002 onwards. The search strategy comprised an electronic search of three bibliographic databases (Pubmed, Embase, CINAHL). RESULTS: Twenty-three studies met the inclusion criteria and were included in the review. Research primarily originated from Italy. Nine key themes emerged from the review: gas flow management, noise reduction, impact of gas flow and HME filters on delivered FiO2, filtration of exhaled gas / environmental protection, PEEP monitoring, airway pressure monitoring, active humidification of gas flow, helmet fixation and tips to implement awake prone position during Helmet-CPAP. CONCLUSIONS: A Helmet-CPAP check-list has been made of nine key interventions based on the available evidence regarding system set up, monitoring and management. Implementation of this check-list may help nurses and physicians to increase the comfort of patients treated with Helmet CPAP and enhance their compliance with long-term treatment.

Sound and Light Levels in a General Intensive Care Unit Without Windows to Provide Natural Light.

BACKGROUND: Appropriate levels and patterns of sound and light in an intensive care room help to maintain the patient's normal physiological functions. High sound levels can disrupt the patient's normal sleep architecture, cause hearing deficits, and induce the onset of delirium. Intensive care unit patients frequently report poor sleep, partly due to the environment. OBJECTIVES: An observational pilot prospective study was designed to record sound pressure and light pollution levels in an Italian intensive care unit, without windows to provide natural light. METHOD: Sound levels were measured in decibel A (dBA) every 10 seconds. Sound data were analyzed for sound peak, defined as the number of times sound levels exceeded 45, 50, 60, 65, 70, 75, 80, and 85 dBA. Light measures were taken every 10 seconds on a continuous basis. Light data were analyzed for light "peaks," defined as the number of times light levels exceeded 100, 200, 300, 400, and 500 lux. RESULTS: The overall median sound level during the study period was equal to 54.60 (interquartile range [IQR], 51.70-57.70) dBA. The daytime median sound level was 56.00 (IQR, 53.00-59.50) dBA, and the nighttime median was 53.00 (IQR, 49.50-55.20) dBA (P < .001). The overall median light level was equal to 114 (IQR, 0-225) lux. The daytime median light level was 184 (IQR, 114-293) lux, and the nighttime median was 0 (IQR, 0-50) lux (P < .001). With respect to room lighting, rooms were observed to have "no lights on" 12.6% of daytime and 41% of nighttime. DISCUSSION: The sound levels recorded in our sample demonstrated that peaks >45 dBA during daytime and nighttime are, respectively, equal to 99.9% and 98.6% of all readings. The Environmental Protection Agency/World Health Organization recommended thresholds for both day (45 dBA) and night (35 dBA). Sound levels reached "toxic levels" when sound-generating activities were performed by nurses and physicians.

Management of vascular access for extracorporeal life support: A cohort study.

Extracorporeal membrane oxygenation (ECMO) is required for patients with refractory cardiac or respiratory failure. Inadequate securement of ECMO cannulae may lead to adverse events, ranging from line kinking to catastrophic accidents, such as air entrainment into the circuit or massive bleeding. Furthermore, the micro-motion of the cannulae at the entry site might increase the risk of local infections. Since 2015, we implemented a written protocol for management of ECMO cannulae and tubing, which specifically includes the securement of each cannula with three sutureless devices. The aim of the present study was to retrospectively assess cannulae micro-motion and the rate of bleeding events at the insertion site. Secondarily we aimed to evaluate the impact of prone positioning maneuvers during ECMO on these events. We performed a single-centre retrospective analysis of prospectively collected data on nursing care of ECMO cannulae. We included adult patients treated with veno-venous (V-V) or veno-arterial (V-A) ECMO between 2015 and 2018 in our general intensive care unit. The distance between the insertion site and the end of the wire-wound part of the cannula was recorded daily. Variations of this distance (defined as "cannula micro-motion") were recorded. Forty-five ECMO consecutive adult patients (40 V-V and 5 V-A) were included. No accidental cannula dislodgement was recorded. Median daily "cannula micro-motion" was 0.0 (-0.5 to 0.2) cm, without any significant difference between ECMO configuration, cannula type, and insertion site. Twelve patients (26%) presented at least one bleeding episode at cannula insertion site, none of which required surgical intervention. In the subgroup of patients who underwent prone positioning, no difference in cannulae micro-motion was recorded. An ECMO nursing protocol for cannulae management providing sutureless devices for cannula and tubing securement allows safe line stabilization, with the potential to reduce complications related to ECMO vascular access.

Evidence for Multiple Binding Modes in the Initial Contact Between SARS-CoV-2 Spike S1 Protein and Cell Surface Glycans.

Infection of host cells by SARS-CoV-2 begins with recognition by the virus S (spike) protein of cell surface heparan sulfate (HS), tethering the virus to the extracellular matrix environment, and causing the subunit S1-RBD to undergo a conformational change into the 'open' conformation. These two events promote the binding of S1-RBD to the angiotensin converting enzyme 2 (ACE2) receptor, a preliminary step toward viral-cell membrane fusion. Combining ligand-based NMR spectroscopy with molecular dynamics, oligosaccharide analogues were used to explore the interactions between S1-RBD of SARS CoV-2 and HS, revealing several low-specificity binding modes and previously unidentified potential sites for the binding of extended HS polysaccharide chains. The evidence for multiple binding modes also suggest that highly specific inhibitors will not be optimal against protein S but, rather, diverse HS-based structures, characterized by high affinity and including multi-valent compounds, may be required.

Molecular modeling and phylogenetic analyses highlight the role of amino acid 347 of the N1 subtype neuraminidase in influenza virus host range and interspecies adaptation.

The N1 neuraminidases (NAs) of avian and pandemic human influenza viruses contain tyrosine and asparagine, respectively, at position 347 on the rim of the catalytic site; the biological significance of this difference is not clear. Here, we used molecular dynamics simulation to model the effects of amino acid 347 on N1 NA interactions with sialyllacto-N-tetraoses 6'SLN-LC and 3'SLN-LC, which represent NA substrates in humans and birds, respectively. Our analysis predicted that Y347 plays an important role in the NA preference for the avian-type substrates. The Y347N substitution facilitates hydrolysis of human-type substrates by resolving steric conflicts of the Neu5Ac2-6Gal moiety with the bulky side chain of Y347, decreasing the free energy of substrate binding, and increasing the solvation of the Neu5Ac2-6Gal bond. Y347 was conserved in all N1 NA sequences of avian influenza viruses in the GISAID EpiFlu database with two exceptions. First, the Y347F substitution was present in the NA of a specific H6N1 poultry virus lineage and was associated with the substitutions G228S and/or E190V/L in the receptor-binding site (RBS) of the hemagglutinin (HA). Second, the highly pathogenic avian H5N1 viruses of the Gs/Gd lineage contained sporadic variants with the NA substitutions Y347H/D, which were frequently associated with substitutions in the HA RBS. The Y347N substitution occurred following the introductions of avian precursors into humans and pigs with N/D347 conserved during virus circulation in these hosts. Comparative evolutionary analysis of site 347 revealed episodic positive selection across the entire tree and negative selection within most host-specific groups of viruses, suggesting that substitutions at NA position 347 occurred during host switches and remained under pervasive purifying selection thereafter. Our results elucidate the role of amino acid 347 in NA recognition of sialoglycan substrates and emphasize the significance of substitutions at position 347 as a marker of host range and adaptive evolution of influenza viruses.

Femorally inserted central catheters with exit site at mid-thigh: A low risk alternative for central venous catheterization.

BACKGROUND: Femorally inserted central catheters are increasingly used, especially after the COVID-19 pandemic, also thanks to widespread of tunneling techniques that allow the exit site to be moved away from the groin. METHODS: In this retrospective observational study, femorally inserted catheters, with exit site at mid-thigh and the tip in Inferior vena cava or in Inferior vena cava at the junction with right atrium, have been observed and complications have been analyzed. All catheters were inserted by trained Nurses of a tertiary hospital Vascular Access Team. RESULTS: In 142 catheters (126 inserted via common femoral vein and 16 inserted via superficial femoral vein) and 3060 catheter days, we observed an infection rate of 1.3 events/1000 catheter days (all of them in oncologic patients and up to 30 days of catheterization), 2 cases of thrombotic events (1.41%) and 17 cases of accidental removal (11.97%). Other rare complications, as primary malposition, tip migration, arterial pseudoaneurysm, have been recorded. The average length of catheters inserted, from the exit site to the tip, was 47.6 ± 2.4 cm. CONCLUSION: The attention to the correct position of the tip, the exit site at mid-thigh and the new techniques during insertion make these femoral catheters as safe as other central vascular access devices. For this kind of central access device, a catheter at least 50 cm long is needed.

Pentosan Polysulfate Inhibits Attachment and Infection by SARS-CoV-2 In Vitro: Insights into Structural Requirements for Binding.

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.

Retrospective survey from vascular access team Lombardy net in COVID-19 era.

BACKGROUND: Venous Access Devices (VADs) are the most used devices in COVID-19 patients. OBJECTIVE: Identify VADs implanted, catheter related thrombosis (CRT), catheter-related bloodstream infection (CRBSI), and accidental remove of VADs in both COVID-19 positive and COVID-19 free patients. Successive analysis was conducted comparing COVID-19 positive patients with COVID-19 free with inverse probability propensity score weights using simple regression to account for these two confounders (peripheral tip as central/peripheral and hospitalization as no/yes). METHODS: This multicenter, retrospective cohort study collected data from seven hospitals in Lombardy during the pandemic period from February 21st to May 31st 2020. RESULTS: A total of 2206 VADs were evaluated, 1107 (50.2%) of which were inserted in COVID-19 patients. In COVID-19 cohort the first choice was Long Peripheral Cannula in 388 patients (35.1%) followed by Midline Catheter in 385 (34.8%). The number of "central tip" VADs inserted in COVID-free inpatients and COVID-19 positive were similar (307 vs 334). We recorded 42 (1.9%) CRT; 32 (79.2%) were observed in COVID-19 patients. A total of 19 CRBSI were diagnosed; 15 (78.95%) were observed in COVID-19. Accidental removals were the more represented complication with 123 cases, 85 (69.1%) of them were in COVID-19. COVID-19 significantly predicted occurrence of CRT (OR = 2.00(1.85-5.03); p < 0.001), CRSB (OR = 3.82(1.82-8.97); p < 0.001), and Accidental Removal (OR = 2.39(1.80-3.20); p < 0.001) in our propensity score weighted models. CONCLUSIONS: CRT, CRBSI, and accidental removal are significantly more frequent in COVID-19 patients. Accidental removals are the principal complication, for this reason, the use of subcutaneously anchored securement is recommended for a shorter period than usual.

Mechanochemical synthesis of mechanical bonds in M12L8 poly-[n]-catenanes.

Using mechanochemistry by grinding TPB and ZnBr2, an amorphous poly-[n]-catenane of interlocked M12L8 nanocages is obtained in good yields (∼80%) and within 15 minutes. The mechanical bond among the icosahedral M12L8 cages in the amorphous phase has been demonstrated by single crystal XRD, powder XRD and FT-IR spectroscopy following an amorphous-to-crystalline transformation by guest uptake of the amorphous phase. High-resolution solid-state 13C NMR spectroscopy gives insights into the local structure of the amorphous catenane focusing on TPB aromatic-aromatic interactions.

Enisamium Inhibits SARS-CoV-2 RNA Synthesis.

Pandemic SARS-CoV-2 causes a mild to severe respiratory disease called coronavirus disease 2019 (COVID-19). While control of the SARS-CoV-2 spread partly depends on vaccine-induced or naturally acquired protective herd immunity, antiviral strategies are still needed to manage COVID-19. Enisamium is an inhibitor of influenza A and B viruses in cell culture and clinically approved in countries of the Commonwealth of Independent States. In vitro, enisamium acts through metabolite VR17-04 and inhibits the activity of the influenza A virus RNA polymerase. Here we show that enisamium can inhibit coronavirus infections in NHBE and Caco-2 cells, and the activity of the SARS-CoV-2 RNA polymerase in vitro. Docking and molecular dynamics simulations provide insight into the mechanism of action and indicate that enisamium metabolite VR17-04 prevents GTP and UTP incorporation. Overall, these results suggest that enisamium is an inhibitor of SARS-CoV-2 RNA synthesis in vitro.