In this work, a new approach towards virus reduction is taken, where modified membranes with large pore sizes (>450 nm) can reach high log10-unit virus reductions. Polyelectrolyte coatings were used ...to modify microfiltration (MF) membranes to impart antiviral properties. A stable covalent layer-by-layer (LBL) approach was used to create multilayers from a single polyelectrolyte, polyethyleneimine (PEI). Here terephthalaldehyde (TA) crosslinking was used to create crosslinked multilayers, both on model surfaces and on commercial polyether sulfone, (PES) MF membranes. The substrates were further coated with antiviral silver, and copper nanoparticles (Ag and CuNPs) stabilised with PEI. The specific fabrication during the LBL assembly was stepwise characterised using multi-surface analysis including Fourier transform infrared spectroscopy (FTIR), Atomic Force Microscope (AFM), ellipsometry, zeta potential and contact angle measurements. Model surfaces demonstrated a 4 log10-units reduction of MS2 viral titre, independent of the crosslinked PEI layer thickness. The crosslinked PEI and Ag/CuNPs-modified membranes efficiently reduced 4.5–5 log10-units of infectious MS2 bacteriophages by both adsorption and inactivation of viral particles. This was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR), which showed a stable performance over time. Pure water flux measurements on modified-membranes showed good long-term stability. Thus, 5000 L/m2 of virus-free water was produced in approximately 2 h, using gravity-based filtration. Furthermore, there was no observable leaching of nanoparticles from the membranes during filtration.
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•Crosslinked PEI layers on model surfaces lead to significant 4 log10 MS2 reductions.•These layers were successfully applied to MF membranes, with only a small decrease in permeability.•The coatings were found to be stable and performed well under gravity filtration.•Coated MF membranes showed a >3 log10 MS2 reduction.•Coated MF membranes optimised with Cu and Ag NPs showed >5 log10 MS2 reductions.
The target 2-aminopyridine-(
I), and 2-chloropyridine-3,5-dicarbonitriles (
II).
The synthesis, molecular modeling, and pharmacological analysis of new multipotent simple, and readily available ...2-aminopyridine-3,5-dicarbonitriles (
3–
20), and 2-chloropyridine-3,5-dicarbonitriles (
21–
28), prepared from 2-amino-6-chloropyridine-3,5-dicarbonitrile (
1) and 2-amino-6-chloro-4-phenylpyridine-3,5-dicarbonitrile (
2) is described. The biological evaluation showed that some of these molecules were modest inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), in the micromolar range. The 2-amino (
3,
4), and 2-chloro derivatives
21–
23,
25,
26 were AChE selective inhibitors, whereas 2-amino derivatives
5,
14 proved to be selective for BuChE. Only inhibitor
24 was equipotent for both cholinesterases. Kinetic studies on compound
23 showed that this compound is a mixed-type inhibitor of AChE showing a
K
i of 6.33
μM. No clear SAR can be obtained form these data, but apparently, compounds bearing small groups such as the
N,
N′-dimethylamino or the pyrrolidino, regardless of the presence of a 2-amino, or 6-chloro substituent in the pyridine ring, preferentially inhibit AChE. Molecular modeling on inhibitors
4,
5,
22, and
23 has been carried out to give a better insight into the binding mode on the catalytic active site (CAS), and peripheral anionic site (PAS) of AChE. The most important differences in the observed binding relay on the modifications of the group at C2, as the amino group forms two hydrogen bonds that direct the binding mode, while in the case of compounds with a chlorine atom, this is not possible. The neuroprotective profile of these molecules has been investigated. In the LDH test, only compounds
26,
3,
22, and
24 showed neuroprotection with values in the range 37.8–31.6% in SH-SY5Y neuroblastoma cells stressed with a mixture of oligomycin-A/rotenone, but in the MTT test only compound
17 (32.9%) showed a similar profile. Consequently, these compounds can be considered as attractive multipotent therapeutic molecules on two key pharmacological receptors playing key roles in the progress of Alzheimer, that is, cholinergic dysfunction and oxidative stress, and neuronal vascular diseases.
Exposure to contaminated aerosols and water originating from water features may pose public health risks. Endotoxins in air and water and fecal bacteria in water of water features were measured as ...markers for exposure to microbial cell debris and enteric pathogens, respectively. Information was collected about wind direction, wind force, distance to the water feature, the height of the water feature and the tangibility of water spray. The mean concentration of endotoxins in air nearby and in water of 31 water features was 10 endotoxin units (EU)/m3 (Geometric Mean (GM), range 0–85.5 EU/m3 air) and 773 EU/mL (GM, range 9–18,170 EU/mL water), respectively. Such mean concentrations may be associated with respiratory health effects. The water quality of 26 of 88 water features was poor when compared to requirements for recreational water in the Bathing Water Directive 2006/7/EC. Concentrations greater than 1000 colony forming units (cfu) Escherichia coli per 100 mL and greater than 400 cfu intestinal enterococci per 100 mL increase the probability of acquiring gastrointestinal health complaints. Regression analyses showed that the endotoxin concentration in air was significantly influenced by the concentration of endotoxin in water, the distance to the water feature and the tangibility of water spray. Exposure to air and water near water features was shown to lead to exposure to endotoxins and fecal bacteria. The potential health risks resulting from such exposure to water features may be estimated by a quantitative microbial risk assessment (QMRA), however, such QMRA would require quantitative data on pathogen concentrations, exposure volumes and dose–response relationships. The present study provides estimates for aerosolisation ratios that can be used as input for QMRA to quantify exposure and to determine infection risks from exposure to water features.
•Endotoxins in air and water were measured at water features.•Determinants of endotoxin content of air were explored using regression analyses.•Endotoxin concentration in air depends on endotoxin concentration of source waters.•Risk assessment may quantify the risks of infection from exposure to water features.
Numerous outbreaks have been attributed to the consumption of raw or minimally processed leafy green vegetables contaminated with enteric viral pathogens. The aim of the present study was an ...integrated virological monitoring of the salad vegetables supply chain in Europe, from production, processing and point-of-sale. Samples were collected and analysed in Greece, Serbia and Poland, from ‘general’ and ‘ad hoc’ sampling points, which were perceived as critical points for virus contamination. General sampling points were identified through the analysis of background information questionnaires based on HACCP audit principles, and they were sampled during each sampling occasion where as-ad hoc sampling points were identified during food safety fact-finding visits and samples were only collected during the fact-finding visits. Human (hAdV) and porcine (pAdV) adenovirus, hepatitis A (HAV) and E (HEV) virus, norovirus GI and GII (NoV) and bovine polyomavirus (bPyV) were detected by means of real-time (RT-) PCR-based protocols. General samples were positive for hAdV, pAdV, HAV, HEV, NoV GI, NoV GII and bPyV at 20.09 % (134/667), 5.53 % (13/235), 1.32 % (4/304), 3.42 % (5/146), 2 % (6/299), 2.95 % (8/271) and 0.82 % (2/245), respectively. Ad hoc samples were positive for hAdV, pAdV, bPyV and NoV GI at 9 % (3/33), 9 % (2/22), 4.54 % (1/22) and 7.14 % (1/14), respectively. These results demonstrate the existence of viral contamination routes from human and animal sources to the salad vegetable supply chain and more specifically indicate the potential for public health risks due to the virus contamination of leafy green vegetables at primary production.
Highlights • Protection by synthetic sulfated disaccharides of hyaluronan in brain ischemia-related models. • The disaccharide di4,6S, given post-stroke, reduces infarct volume and improves ...neurological decline. • Protection involves activation of PI3K/Akt, reduction of oxidative stress and inhibition of NFκB.
In the current report, we have examined the ability of natural killer (NK) cells to produce T cell-recruiting chemokines following dual stimulation with interleukin (IL)-2 or IL-12 and human breast ...cancer cells coated with an antitumor antibody (trastuzumab). NK cells stimulated in this manner secreted an array of T cell-recruiting chemotactic factors, including IL-8, macrophage-derived chemokine, macrophage inflammatory protein 1alpha (MIP-1alpha), monocyte chemoattractant protein 1, and regulated on activation, normal T-cell expressed and secreted (RANTES), whereas stimulation of NK cells with either agent alone had minimal effect. Furthermore, these factors were functional for T-cell chemotaxis as culture supernatants derived from costimulated NK cells induced migration of both naïve and activated T cells in an in vitro chemotaxis assay. T-cell migration was significantly reduced when neutralizing antibodies to IL-8, MIP-1alpha, or RANTES were added to culture supernatants before their use in the chemotaxis assay. In addition, coadministration of trastuzumab-coated tumor cells and IL-12 to mice led to enhanced serum MIP-1alpha. As a clinical correlate, we examined the chemokine content of serum samples from breast cancer patients enrolled on a phase I trial of trastuzumab and IL-12, and found elevated levels of IL-8, RANTES, IFN-gamma inducible protein 10, monokine induced by IFN-gamma, and MIP-1alpha, specifically in those patients that experienced a clinical benefit. Sera from these patients exhibited the ability to direct T-cell migration in a chemotaxis assay, and neutralization of chemokines abrogated this effect. These data are the first to show chemokine production by NK cells, specifically in response to stimulation with antibody-coated tumor cells, and suggest a potential role for NK cell-derived chemokines in patients receiving therapeutic monoclonal antibodies.
Highlights • Legionella pneumophila ST47 is frequently isolated from patients, but not from environmental sources. • The sources currently targeted in source investigations are probably not the right ...sources. • We have isolated ST47 from soil in a garden. • Possibly, natural soil is an alternate, yet overlooked source for Legionella.
This retrospective study analyzes the clinical, neuroradiological, pathological and surgical characteristics of well-described intraventricular craniopharyngiomas with the aims of: (i) critically to ...review the criteria used to affirm the diagnosis of an intraventricular location (ii) defining more accurately this topographical diagnosis preoperatively, and (iii) to investigate factors influencing the surgical outcome.
Clinical, neuroradiological, pathological and surgical objective data of 104 well-described intraventricular craniopharyngiomas (IVC) reported in the literature, in addition to a new case, were analyzed. On the basis of the proofs provided for third ventricle intactness, a new topographical classification for IVC was developed, distinguishing between: (i) strict IVC, with a proved third ventricle floor integrity and (ii) non-strict IVC, without any reliable proof confirming the intactness of the third ventricle floor. Following this classification, clinical features, pathology and surgical outcome for strictly and non-strictly IVC were compared.
For 105 IVC compiled, 36 belonged to the strictly group and 69 to the non-strictly group. Two pathological features were associated with the non-strictly IVC group: a preferentially adamantinomatous pattern (p=0.106) and wider and tighter adherences to third ventricle margins (p=0.01). The non-strict topography was also associated with a worse postoperative outcome (p=0.046). There was a significant relationship between the surgical approach and the final outcome (p=0.05), being the translamina terminalis approach associated with the best outcome.
Two different topographies might be considered among IVC: strict and non-strict intraventricular location. Non-strictly IVC have wider and tighter adhesions to third ventricle boundaries and this subtype is associated with a worse outcome.
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