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Plant extracts are in the focus of the pharmaceutical industry as potential antimicrobials for oral care due to their high antimicrobial activity coupled with low production costs and safety for eukaryotic cells. Here, we show that the extract from Hop (Humulus lupulus L.) exhibits antimicrobial activity against Staphylococcus aureus and Streptococci in both planktonic and biofilm-embedded forms. An extract was prepared by acetone extraction from hop infructescences, followed by purification and solubilization of the remaining fraction in ethanol. The effect of the extract on S. aureus (MSSA and MRSA) was comparable with the reference antibiotics (amikacin, ciprofloxacin, and ceftriaxone) and did not depend on the bacterial resistance to methicillin. The extract also demonstrated synergy with amikacin on six S. aureus clinical isolates, on four of six isolates with ciprofloxacin, and on three of six isolates with ceftriaxone. On various Streptococci, while demonstrating lower antimicrobial activity, an extract exhibited a considerable synergistic effect in combination with two of three of these antibiotics, decreasing their MIC up to 512-fold. Moreover, the extract was able to penetrate S. aureus and S. mutans biofilms, leading to almost complete bacterial death within them. The thin-layer chromatography and LC-MS of the extract revealed the presence of prenylated flavonoids (2′,4′,6′,4-tetrahydroxy-3′-geranylchalcone) and acylphloroglucides (cohumulone, colupulone, humulone, and lupulone), apparently responsible for the observed antimicrobial activity and ability to increase the efficiency of antibiotics. Taken together, these data suggest an extract from H. lupulus as a promising antimicrobial agent for use both as a solely antiseptic and to potentiate conventional antimicrobials. [ABSTRACT FROM AUTHOR]

Modern information and telecommunication, transportation and logistic, economic and financial systems are represented by complex networks exhibiting traffic flows with spatio-temporal long-term persistence. Conventional queuing theory relies largely upon stationary models where traffic flows are assumed independent and are typically characterized by the first two moments of inter-arrival and service time distributions, leading to drastic underestimations of traffic flow delays. Here we extend a recent superstatistical approach focusing on traffic models with variable arrival rates by accounting for interdependent activity patterns on multiple network nodes. We suggest an analytical correction to the conventional stationary queue model given by the Kingman's formula based on the calculation of aggregated inter-arrival times variability from the variabilities of arrival rates at individual nodes and cross-correlations between them. We confirm our analytical approximations by comparing with computer simulation results and large-batch empirical traffic analysis from the backbone of a major academic network. We believe that our results, in combination with recent data on the effects of long-term temporal persistence in network traffic flow, are applicable to various complex networks not limited to information and telecommunication, transportation, and logistics but also to economics and finance, rainfall and river flow dynamics, water accumulation in reservoirs, and many other research domains exhibiting spatio-temporal interdependence patterns. • Abrupt bursts in traffic dynamics are governed by simultaneous multiple nodes access. • Inter-arrival times distribution is derived from cross-correlations between nodes. • Analytical correction for an approximate evaluation of waiting times is proposed. • Results are supported by computer simulations and large-batch traffic data analysis. • Corrections are applicable to complex networks governed by autonomous agents dynamics. [ABSTRACT FROM AUTHOR]

Candida albicans and Staphylococcus aureus are human pathogens that are able to form mixed biofilms on the surface of mucous membranes, implants and catheters. In biofilms, these pathogens have increased resistance to antimicrobials, leading to extreme difficulties in the treatment of mixed infections. The growing frequency of mixed infections caused by S. aureus and C. albicans requires either the development of new antimicrobials or the proposal of alternative approaches to increase the efficiency of conventional ones. Here, we show the antimicrobial, biofilm-preventing and biofilm-eradicating activity of 2(5H)-furanone derivative F131, containing an l-borneol fragment against S. aureus–C. albicans mixed biofilms. Furanone F131 is also capable of inhibiting the formation of monospecies and mixed biofilms by S. aureus and C. albicans. The minimal biofilm-prevention concentration (MBPC) of this compound was 8–16 μg/mL for S. aureus and C. albicans mono- and two-species biofilms. While the compound demonstrates slightly lower activity compared to conventional antimicrobials (gentamicin, amikacin, fluconazole, terbinafine and benzalkonium chloride), F131 also increases the antimicrobial activity of fluconazole–gentamicin and benzalkonium chloride against mixed biofilms of S. aureus–C. albicans, thus reducing MBPC of fluconazole–gentamicin by 4–16 times and benzalkonium chloride twofold. F131 does not affect the transcription of the MDR1, CDR1 and CDR2 genes, thus suggesting a low risk of micromycete resistance to this compound. Altogether, combined use of antibiotics with a F131 could be a promising option to reduce the concentration of fluconazole used in antiseptic compositions and reduce the toxic effect of benzalkonium chloride and gentamicin. This makes them an attractive starting point for the development of alternative antimicrobials for the treatment of skin infections caused by S. aureus–C. albicans mixed biofilms. [ABSTRACT FROM AUTHOR]

Background and Objectives: Candida albicans causes various diseases ranging from superficial mycoses to life-threatening systemic infections often associated with biofilm formation, including mixed fungal–bacterial consortia. The biofilm matrix protects cells, making Candida extremely resistant to treatment. Here, we show that the bovhyaluronidase azoximer (Longidaza®) in vitro destroys the biofilm formed by either C. albicans alone or mixed with bacteria, this way decreasing the concentrations of antimicrobials required for the pathogen's eradication. Materials and Methods: Bovhyaluronidase azoximer, Longidaza® was obtained from NPO Petrovax Pharm Ltd., Moscow, Russia as lyophilized powder. The antifungal activity was assessed by microdilution assay and CFUs counting. Antibiofilm activity was evaluated via biofilms staining and scanning electron microscopy. Results: Thus, treatment with Longidaza® reduced the biofilm biomass of nine C. albicans clinical isolates by 30–60%, while mixed biofilms of C. albicans with various bacteria were destroyed by 30–40%. Furthermore, the concentration of fluconazole required to achieve a similar reduction of the residual respiratory activity of detached cell clumps of four C. albicans isolates has been reduced four-fold when combined with Longidaza®. While in the biofilm, two of four isolates became significantly more susceptible to fluconazole in combination with Longidaza®. Conclusion: Taken together, our data indicate that Longidaza® is capable of suppression of tissues and artificial surfaces biofouling by C. albicans biofilms, as well as facilitating drug penetration into the cell clumps, this way decreasing the effective MIC of antifungals. [ABSTRACT FROM AUTHOR]

Anthropogenic interventions lead to various direct and indirect impacts on natural ecosystems that are often hindered by natural long-term variability, and thus their detection and evaluation remain challenging. Ecological systems are strongly affected by climate variations that typically exhibit long-term correlations capable of imitating or hindering external trends in finite-time observations, thus complicating their detection and correct attribution to either anthropogenic interventions or natural variability. Here we focus on the quantitative assessment of the alterations in the tree-ring width (TRW) of four tree species in response to the changes in the soil water regime following a drainage experiment in a dwarf-shrub type peatland forest. We consider the long-term effects of the intervention, focusing on two characteristic quantities: the durations of clusters when significant discrepancies with relevant controls could be observed in every single consecutive year, and relative trends in the data reflecting long-term, gradual changes in the ecosystem. By extrapolating pre-drainage TRW dynamics and adjusting for recent climate variations using a multivariate model, we simulate surrogate data series that act as additional controls for the post-drainage time period. By comparing the long-term dynamics of the observational TRW data series against both natural and surrogate controls over several decades following the drainage experiment, we evaluate long-term alterations and gradual trends in the tree growth dynamics and reassess the statistical significance of these effects, taking into account long-term correlations in the natural TRW variations. Our results also indicate pronounced alterations in the drought stress response characterized by significant negative trends in the tree growth dynamics following the 2010 heatwave and associated flash drought in the drained area, while no similar effect could be observed in the undrained area, indicating that the increased productivity of the forest ecosystem following the drainage likely comes at the cost of its reduced drought stress resilience. • Long-term correlations in tree-ring and climate records can imitate or hinder trends. • Extrapolated pre-experimental tree-ring data series can be used as surrogate control. • Significance of multi-year discrepancies can be re-evaluated from cluster durations. • Drainage increases productivity of forests at the cost of drought stress resilience. [ABSTRACT FROM AUTHOR]