AIMS: This study reports on the inhibitory and bactericidal properties of a new synthetized flavonoid. METHODS AND RESULTS: Tricyclic flavonoid 1 has been synthesized through a two‐step reaction ...sequence. The antimicrobial effects were tested using the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Also DNA fragmentation assay, fluorescence microscopy and SEM were used to study the mechanism of action. Our tested flavonoid displayed a strong antimicrobial activity with MIC and MBC values as low as 0·24 μg ml⁻¹ against Staphylococcus aureus and 3·9 μg ml⁻¹ against Escherichia coli. Flavonoid 1 displayed antimicrobial properties, causing not only the inhibition of bacterial growth, but also killing bacterial cells. The mechanism of action is related to the impairment of the cell membrane integrity and to cell agglutination. CONCLUSIONS: Tricyclic flavonoid 1 was found to have a stronger antibacterial effect at lower concentrations than those described in the earlier reports. SIGNIFICANCE AND IMPACT OF THE STUDY: Based on the strong antimicrobial activity observed, this new tricyclic flavonoid has a good potential for the design of new antimicrobial agents.
Owing to its resistance to degradation, hair is an important bio‐sample with unique properties used to study post mortem decompositional changes. The present paper is a microscopical approach to ...preserved human scalp hair discovered at the 18th–19th‐century archaeological site of Iași, Romania. The hair fibre alterations were assessed using optical microscopy, scanning electron microscopy, image analysis and hair histological scores. External alterations showed a statistically significant heterogeneous degradation. Image analysis results of the internal degradation of hairs were correlated to external lesions. The results consider the implication of intrinsic biological factors in the post mortem degradation of human hair preserved in graves with comparable environmental conditions.
Viral infections are one of the major causes of death worldwide, with HIV infection alone resulting in over 1.2 million casualties per year. Antiviral drugs are now being administered for a variety ...of viral infections, including HIV, hepatitis B and C, and influenza. These therapies target a specific phase of the virus's life cycle, yet their ultimate success depends on a variety of factors, such as adherence to a prescribed regimen and the emergence of viral drug resistance. The epidemiology and evolution of drug resistance have been extensively characterized, and it is generally assumed that drug resistance arises from mutations that alter the virus's susceptibility to the direct action of the drug. In this paper, we consider the possibility that a virus population can evolve towards synchronizing its life cycle with the pattern of drug therapy. The periodicity of the drug treatment could then allow for a virus strain whose life cycle length is a multiple of the dosing interval to replicate only when the concentration of the drug is lowest. This process, referred to as "drug tolerance by synchronization", could allow the virus population to maximize its overall fitness without having to alter drug binding or complete its life cycle in the drug's presence. We use mathematical models and stochastic simulations to show that life cycle synchronization can indeed be a mechanism of viral drug tolerance. We show that this effect is more likely to occur when the variability in both viral life cycle and drug dose timing are low. More generally, we find that in the presence of periodic drug levels, time-averaged calculations of viral fitness do not accurately predict drug levels needed to eradicate infection, even if there is no synchronization. We derive an analytical expression for viral fitness that is sufficient to explain the drug-pattern-dependent survival of strains with any life cycle length. We discuss the implications of these findings for clinically relevant antiviral strategies.
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The current progress in pharmaceutical nanotechnology field has been exploited in the design of functionalized radiolabelled nanoparticles that are able to deliver radionuclides in a ...selective manner to improve the outcome of diagnosis and treatment. Silica nanoparticles (SNPs) have been widely developed for biomedical applications due to their high versatility, excellent functional properties and low cost production, with the possibility to control different topological parameters relevant for multidisciplinary applications.
The aim of the present study was to characterize and evaluate both in vitro, by microscopy techniques, and in vivo, by scintigraphic imaging, the biodistribution of silica nanostructures derivatives (Cy5.5 conjugated SNPs and 99mTc radiolabelled SNPs) to be applied as radiotracers in biomedicine.
SNPs were synthesized by hydrolysis and condensation of silicon alkoxides, followed by surface functionalization with amino groups available for fluorescent dye and radiolabelling possibility.
Our data showed the particles size distribution (200–350nm), the surface charge (negative for bare and fluorescent SNPs and positive for amino SNPs), polydispersity index (broad distribution), the qualitative composition and the toxicity assessments (safe material) that made the obtained SNPs candidates for in vitro/in vivo studies. A high uptake of fluorescent SNPs in all the investigated organs was evidenced by confocal microscopy. The 99mTc radiolabelled SNPs biodistribution was quantified in the range of 12–100% counts/g organ using the scintigraphic images.
The obtained results reveal improved properties, namely, reduced toxicity with a low level of side effects, an improved biodistribution, high labelling efficiency and stability of the radiolabelled SNPs with potential to be applied in biomedical science, particularly in nuclear medicine as a radiotracer.
The numerical model investigated in this paper was implemented with Finite Element Method (FEM) based Comsol Multiphysics software, starting from a real cross-flow micro heat exchanger manufactured ...from 50 stainless steel plates for cold and hot fluid transfer. Each plate (foil) had 34 microchannels with rectangular cross-section, at a depth of 100 μm and a width of 200 μm. The working fluids were water and Al2O3-water nanofluids with volumetric concentrations of 0.5%, 1% and 1.5% in the temperature domain of 293 - 333 K. The oxide-based nanofluids are widely investigated in thermal energy transfer applications due to an increased heat transfer performance by comparing with pure water as a cooling fluid. Analytical models for the physical properties of water and nanofluid, referring to density, viscosity, thermal conductivity and specific heat capacity were used here. Microchannel bulk temperature profiles for cold and hot plates of the model with 1% Al2O3-water nanofluid were presented here in order to examine the uniformity of temperature distribution in the channel flow field area. Simulation results indicated that the total heat flow rate in the heat exchanger models increased with the increase in volume concentration of the nanoparticles at mass flow rates of 41, 61, 81, 101 and 150 Kg/h, but with the expense of a bigger pressure drop (or Fanning friction factor) at an increased pumping power required to drive flow through the channels.
•Chronic kidney disease is a major cause of mortality in cats, but sensitive and specific biomarkers are currently lacking.•This study aimed to apply proteomic techniques to map the cat urine ...proteome and compare it with that in cats with CKD.•Our work produced a reference map of the normal cat urine proteome containing 20 proteins identified by mass spectrometry.•We identified 13 proteins differentially represented in CKD.•Most of these proteins are indicative of tubulointerstitial damage when not reabsorbed or not secreted.
Chronic kidney disease (CKD) is a major cause of mortality in cats, but sensitive and specific biomarkers for early prediction and monitoring of CKD are currently lacking. The present study aimed to apply proteomic techniques to map the urine proteome of the healthy cat and compare it with the proteome of cats with CKD. Urine samples were collected by cystocentesis from 23 healthy young cats and 17 cats with CKD. One-dimensional sodium-dodecyl-sulfate polyacrylamide gel electrophoresis (1D-SDS-PAGE) was conducted on 4–12% gels. Two-dimensional electrophoresis (2DE) was applied to pooled urine samples from healthy cats (n = 4) and cats with CKD (n = 4), respectively. Sixteen protein bands and 36 spots were cut, trypsin-digested and identified by mass spectrometry.
1D-SDS-PAGE yielded an overall view of the protein profile and the separation of 32 ± 6 protein bands in the urine of healthy cats, while CKD cats showed significantly fewer bands (P < 0.01). 2-DE was essential in fractionation of the complex urine proteome, producing a reference map that included 20 proteins. Cauxin was the most abundant protein in urine of healthy cats. Several protease inhibitors and transport proteins that derive from plasma were also identified, including alpha-2-macroglobulin, albumin, transferrin, haemopexin and haptoglobin. There was differential expression of 27 spots between healthy and CKD samples (P < 0.05) and 13 proteins were unambiguously identified. In particular, increased expression of retinol-binding protein, cystatin M and apolipoprotein-H associated with decreased expression of uromodulin and cauxin confirmed tubular damage in CKD cats suggesting that these proteins are candidate biomarkers.
Neonatal hearing screening in France involves confirmation by a childhood hearing expert centre in case of suspected hearing loss. Although click-evoked air-conduction auditory brainstem responses ...(AC-ABR) are the gold standard in France, there are no guidelines for bone-conduction ABRs (BC-ABR). The present study assessed the interest of associating click-evoked BC- and AC-ABRs for diagnostic confirmation in neonatal hearing screening.
A retrospective study included 59 infant ears with conductive hearing loss referred to the centre of Lyon, France. Objective hearing thresholds were compared between click-evoked BC- and AC-ABRs on a method previously validated in a normal-hearing population.
There was a significant difference in mean threshold between AC-ABR (53.27±1.189 dBnHL) and BC-ABR (28.1±0.935 dBnHL) (P<0.001). AC thresholds ranged from 40 to 60 dBnHL while BC thresholds exceeded 40 dBnHL in only 9 ears.
Using BC-ABRs could reduce the false-positive rate in neonatal bilateral permanent hearing loss screening, in complement to AC-ABRs using the same stimulus. Click-evoked BC-ABR could be contributive whenever conductive hearing loss is suspected, in complement to AC-ABR, without unreasonably increasing examination time.
Abstract
A possible strategy for reducing energy consumption and carbon dioxide emissions in order to protect the environment is the recovery of heat from wastewater. This study aims to achieve an ...improvement in the effectiveness of heat transfer by changing the flow parameters by using a double heat exchanger to recover the heat from greywater. The results, the thermal energy from wastewater can be recovered, the effectiveness ranged between (25 % — 45 %) with the discharge of (0.15-0.51m3/h) lower to higher, respectively. The cold water flow has a clear effect on the heat transfer efficiency, the decrease in cold water velocity led to the increase in heat transfer performance. This technique is simple to implement and inexpensive. It can be designed and built on the basement of the multi-storey building. The dual heat exchanger splits the flow into two-pipe, decreasing the flow rate velocity and thus, increasing the heat transfer efficiency.
A new design of a detector plane of sub-millimetre thickness for an electromagnetic sampling calorimeter is presented. It is intended to be used in the luminometers LumiCal and BeamCal in future ...linear e
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collider experiments. The detector planes were produced utilising novel connectivity scheme technologies. They were installed in a compact prototype of the calorimeter and tested at DESY with an electron beam of energy 1–5 GeV. The performance of a prototype of a compact LumiCal comprising eight detector planes was studied. The effective Molière radius at 5 GeV was determined to be (8.1 ± 0.1 (stat) ± 0.3 (syst)) mm, a value well reproduced by the Monte Carlo (MC) simulation (8.4 ± 0.1) mm. The dependence of the effective Molière radius on the electron energy in the range 1–5 GeV was also studied. Good agreement was obtained between data and MC simulation.
Status and prospects of nuclear clustering studies by dissociation of relativistic nuclei in nuclear track emulsion are presented. The unstable 8Be and 9B nuclei are identified in dissociation of the ...isotopes 9Be, 10B, 10C and nC, and the Hoyle state in the cases 12C and 16O. On this ground searching for the Hoyle state and more complex α-particle states in the dissociation of the heavier nuclei is suggested. A detailed study of a low-density baryonic matter arising in dissociation of the heaviest nuclei is forthcoming long-term problem. An analysis of nuclear fragmentation induced by relativistic muons is proposed to examine the mechanism dissociation.
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