Increase In Lag Time Research Articles

Molecular density regulating electron transfer efficiency of S. oneidensis MR-1 mediated roxarsone biotransformation

Efficient extracellular electron transport is a key for sufficient bioremediation of organoarsenic pollutants such as 4-hydroxy-3-nitrobenzenearsonic acid (roxarsone). The related apparent kinetics characteristics are essential for engineering practice of bioremediation activities and for full understanding the environmental fate of roxarsone, yet remains poorly understood. We report, to our knowledge, the first study of the electron transfer characteristics between roxarsone and participating S. oneidensis MR-1. The electron transfer rate during roxarsone biotransformation was estimated up to 3.1 × 106 electrons/cell/s, with its value being clearly associated with the apparent roxarsone concentration. Lowing roxarsone concentration extended the average separation distance between cells and neighboring roxarsone molecules and thereby augmented electric resistance as well as extended cell movement for foraging, thus reduced electron transfer rate. In addition, the presence of roxarsone significantly stimulated population growth of S. oneidensis MR-1 with nearly doubled maximum specific growth rate, albeit with clearly increased lag time, as compared with that of none-roxarsone scenario. These findings provide, at the first time, basic biostoichiometry of S. oneidensis MR-1 induced roxarsone biotransformation, which may shed lights for full understanding of roxarsone transformation process in waste treatment systems that are necessary for engineering practice and/or environmental risks assessment.

Sequence Duplication Within pmrB Gene Contribute to High-Level Colistin Resistance in Avian Pathogenic Escherichia coli.

Beyond the emergence of plasmid-encoded mechanisms, mutation within the pmrAB genes remains one of the primary colistin resistance mechanisms in Escherichia coli. However, the mechanisms of high-level colistin resistance (HLCR) have not been elucidated. In this study, we evaluated the HLCR mechanisms in five colistin-susceptible Avian pathogenic Escherichia coli (APEC) isolates after colistin exposure. Three PmrB substitutions (G19R, L167P, V88E) and two PmrB sequence duplication (PmrB-sd) mutations (68-77dup and 94-156dup) were detected. Chromosomal replacement and deletion mutagenesis revealed the two PmrB-sd mutations contribute to, but are not fully responsible for, HLCR in APEC strains. Quantitative reverse transcription/polymerase chain reaction (qRT-PCR) revealed that the PmrB-sd induction mutants showed an increased pmrAB transcript level and the PmrB-sd reversion mutants exhibited a reduction of pmrAB expression. All five induction mutants exhibited decreased minimum inhibitory concentrations to florfenicol and tetracycline. In addition, four mutants (G19R, L167P, V88E, and 94-156dup) and two mutants (68-77dup and 94-156dup) also displayed increased sensitivity to ceftiofur and gentamicin, respectively. Zeta potential measurement of the induction mutants showed that there was less negative charge on the cell surface compared with its parental strains in the absence of colistin. The induction mutants also showed an increase of lag time and decrease of fitness. In summary, the identification of novel PmrB-sd mutations contributing to HLCR is helpful to broaden the knowledge of colistin resistance. Attention should be paid to the use of colistin for the treatment of infections caused by APEC strains.

Decreased Thrombin Generation Potential in Lymphoma Patients Is Associated with Increased D-Dimer, CRP, Vwf and TNF-α. Interrelationship between Thrombogenesis and Inflammation

Introduction: The prevalence of thrombosis in lymphoma patients is reportedly high and ranges from 3 - 10%, and further increased at advanced stages of the disease especially in hgNHL. Inflammation and other vascular factors contribute to the pathogenesis of these thrombotic complications. Biomarkers of hemostatic activation, vascular dysfunction and inflammation are elevated in lymphoma. We have previously reported that thrombin generation biomarkers such as D-Dimer, thrombin anti-thrombin complex (TAT) and prothrombin fragment (F1.2) along with inflammatory biomarkers are increased in cancer patients. Interestingly, despite an increase in thrombin generation markers, thrombin generation potential in these patients is decreased. This study was designed to compare the thrombin generation potential and its relevance to the generation of various biomarkers of hemostatic activation process and inflammatory responses. Methods: Citrated blood samples from 90 patients with confirmed diagnosis of non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) and Chronic lymphocytic leukemia/Small lymphocytic lymphoma (CLL/SLL) were collected from the Clinic of Hematology Unit, University of Belgrade, Belgrade, Serbia. 50 samples of normal human plasma (NHP) was obtained from George King Biomedical (Overland park, KS). NHP was prepared for referencing purposes. Thrombin generation studies were carried out using a commercially available a kinetic fluorogenic substrate method (calibrated automated thrombogram; CAT). Thrombin generation parameters such as peak thrombin (PT), lag time (LT) and area under the curve (AUC) were compiled. Plasma levels of D-Dimer, CRP, vWF and TNF- α were measured by using commercially available Sandwich ELISA assays. Results were compiled in terms of mean ± SD. Correlation analysis carried out by using Prism, Graphpad. Results: On a cumulative basis, lymphoma patients showed an increase in lag time (2.9 1.17) in comparison to the NHP (2.7). The peak thrombin levels was decreased (119.0 46.2) in the lymphoma patients in comparison to NHP (159.7 31.1). The AUC was decreased (670.2 290.01) in the lymphoma patients in comparison to NHP (700.9 ). When the lymphoma patients were sub grouped, peak thrombin levels were similar in HL (129.9), NHL (114.7) and CLL (127.4) and were decreased compared to NHP (159.7). However the AUC was increased in the HL (769), decreased in NHL (642.4) and was comparable for CLL (715.4) compared to NHP (700.9). Variations in lag time were noted in the three groups. The lymphoma patients also exhibited elevated levels of D-Dimer (878 1205 ng/ml) in comparison to NHP (280 ng/ml), CRP (15.2 26.6 ug/ml) in comparison to NHP (0.9 ug/ml), vWF (271.8 189.7 %) in comparison to NHP (122%) and TNF-α (16.4 20.64 pg/ml) in comparison to NHP (4.2 pg/ml). Interestingly, when the lymphoma group were subdivided into various groups, the D-Dimer level was highest in HL following the order HL>NHL>CLL. CRP and vWF levels were highest in HL and comparable in both NHL and CLL. Wide scatter in TNF-α data was noted with CLL exhibiting highest levels with the ranked order CLL>NHL>HL. The composite data on thrombin generation parameters and biomarkers is shown on the table 1A. In the HL group D-Dimer and CRP correlated well with AUC and PT, in this group vWF also showed a good correlation with PT. In the NHL group, CRP correlated well with LT. In the CLL group none of the biomarkers correlated well with the thrombin generation parameters. On a cumulative basis, D-Dimer, CRP, vWF and TNF-α had no significant relevance to thrombin generation parameters. The composite regression coefficience data is shown on table 1B. Conclusion: Lymphoma patients represent a heterogenous group in which both the hypercoagulable state and inflammatory responses simultaneously occur as evident by increase in D-Dimer and inflammatory biomarkers. While the overall thrombin generation potential in the plasma of these patients is decreased, thrombin is constantly generated in some of these patient leading to the formation of fibrin. The observed decrease in thrombin generation potential in these patients may be due to the consumption of prothrombin and other coagulation factors. Wide variations among these lymphoma groups are noted. Profiling of thrombin generation and inflammatory biomarkers may be helpful in thrombotic risk stratification of lymphoma patients and their anti-thrombotic management. Disclosures No relevant conflicts of interest to declare.

GIS-Based Site Selection for Check Dams in Watersheds: Considering Geomorphometric and Topo-Hydrological Factors

Check dams are widely used watershed management measures for reducing flood peak discharge and sediment transport, and increasing lag time and groundwater recharge throughout the world. However, identifying the best suitable sites for check dams within the stream networks of various watersheds remains challenging. This study aimed to develop an open-source software with user-friendly interface for screening the stream network possibilities and identifying and guiding the selection of suitable sites for check dams within watersheds. In this developed site selection software (SSS), multi-criteria decision analysis (MCDA) was integrated into geographic information systems (GIS), which allowed for numerous spatial data of the multiple criteria to be relatively simply and visually processed. Different geomorphometric and topo-hydrological factors were considered and accounted for to enhance the SSS identification of the best locations for check dams. The factors included topographic wetness index (TWI), terrain ruggedness index (TRI), topographic position index (TPI), sediment transport index (STI), stream power index (SPI), slope, drainage density (DD), and stream order (SO). The site identification performance of the SSS was assessed using the receiver operating characteristic (ROC) curve method, with results for the case study example of the Poldokhtar watershed in Iran showing excellent performance and identifying 327 potential sites for efficient check dam construction in this watershed. The SSS tool is not site-specific but is rather general, adaptive, and comprehensive, such that it can and should be further applied and tested across different watersheds and parts of the world.

Evidence for chaotropicity/kosmotropicity offset in a yeast growth model.

Chaotropes are compounds which cause the disordering, unfolding and denaturation of biological macromolecules. It is the chaotropicity of fermentation products that often acts as the primary limiting factor in ethanol and butanol fermentations. Since ethanol is mildly chaotropic at low concentrations, it prevents the growth of the producing microbes via its impacts on a variety of macromolecular systems and their functions. Kosmotropes have the opposite effect to chaotropes and we hypothesised that it might be possible to use these to mitigate chaotrope-induced inhibition of Saccharomyces cerevisiae growth. We also postulated that kosmotrope-mediated mitigation of chaotropicity is not quantitatively predictable. The chaotropes ethanol and urea, and compatible solutes glycerol and betaine (kosmotrope), and the highly kosmotropic salt ammonium sulphate all inhibited the growth rate of Saccharomyces cerevisiae in the concentration range 5-15%. They resulted in increased lag times, decreased maximum specific growth rates, and decreased final optical densities. Surprisingly, neither the stress protectants nor ammonium sulphate reduced the inhibition of growth caused by ethanol. Whereas, in some cases, compatible solutes and kosmotropes mitigated against the inhibitory effects of urea. However, this effect was not mathematically additive from the quantification of chao-/kosmotropicity of each individual compound. The potential effects of glycerol, betaine and/or ammonium sulphate may have been reduced or masked by the metabolic production of compatible solutes. It may nevertheless be that the addition of kosmotropes to fermentations which produce chaotropic products can enhance metabolic activity, growth rate, and/or product formation.

Growth and Extracellular Enzyme Activity Responses of a Multi-enzymic Strain of Serratia sp. in a Simulated Diesel-contaminated System

Aim: The present study was aimed at elucidating the alternative metabolic preferences of Serratia sp. strain DW2 that permitted its survival in a diesel-contaminated environment.
 Study Design: We adopted a 4 x 4 x 3 completely randomized design of a full-factorial experiment for the study.
 Place and Duration of Study: The study was conducted at the Department of Microbiology, University of Calabar, Nigeria, during the months of March and June, 2019.
 Methodology: In this study, Serratia sp. strain DW2 was isolated from Douglas Creek water of the Qua Iboe Estuary, along the Qua Iboe terminal at Ibeno, Nigeria, as a significant biological contributor to the decontamination process through inherent ability to utilize diesel oil hydrocarbons. This paper elucidated the growth and responses of the bacterial lipase, caseinase and gelatinase activities to diesel-oil hydrocarbon contamination.
 Results: Range finding test results showed that the bacterium could grow in the presence of water soluble fraction of diesel (wsf-D) concentration between .0042 and .0335 µg/mL, albeit with increasing lag time and decreasing specific growth rate when compared with growth in glucose-Bushnell-Haas broth. Lag time changes were not significantly influenced by exposure time but changes in specific growth rate were. Gelatinase activity was most susceptible to toxicant onslaught but was least affected by exposure time. Conversely, lipase activity was the most affected by exposure time. Toxicant concentration/exposure time interaction of a two-way analysis of variance model for caseinase activity was not significant (P > .05) but those for lipase and gelatinase activities were.
 Conclusion: The bacterium survived diesel toxicity by exploiting its lipase and gelatinase activities for provision of alternative sources of carbon, energy and nitrogen to drive ecosystem decontamination in the event of refined petroleum contamination.

Time Lag and Accuracy of Continuous Glucose Monitoring During High Intensity Interval Training in Adults with Type 1 Diabetes.

Background: This study investigated the accuracy of real-time continuous glucose monitoring (rtCGM) during high intensity interval training (HIIT) in patients with type 1 diabetes (T1D). Methods: Seventeen participants with T1D, using multiple daily injections (MDI) with basal insulin glargine 300 U/mL (Gla-300), completed four fasted HIIT sessions over 4 weeks while wearing a Dexcom rtCGM G4 Platinum system. Each exercise consisted of high intensity interval cycling and multimodal training over 25 min. Reference venous plasma glucose (PG) was measured at 60- and 10-min before exercise (Stage 1), every 10 min during exercise and then every 15 min until 180 min after the end of exercise (Stage 2: during exercise and 45-min early recovery; Stage 3: 45 min to 3 h after the end of exercise); and at 6-, 10-, and 13-h postexercise (Stage 4). Results: In the 64 HIIT sessions that resulted in hyperglycemia, PG increased 90.0 ± 32.4 mg/dL (mean ± standard deviation), peaking at 68.0 ± 18.4 min from the start of HIIT. Mean absolute relative difference was highest during exercise and early recovery (Stage 2) at 17.8%, versus Stage 1 (10.4%), Stage 3 (10.6%), and Stage 4 (11.5%) (P < 0.001). During Stage 2, rtCGM showed a significant negative bias of 35.3 mg/dL (P < 0.001) compared to reference glucose. Lag time to reach the half-maximal glucose rise was 35 min in rtCGM versus PG. The Surveillance Error Grid found that in Stage 2, only 65.5% of paired values were in the no-risk zone and the %15/15 was 50%, significantly lower than the other stages (P < 0.001). Conclusions: During HIIT and early recovery, there is an increase in lag time and a related decline in accuracy of Dexcom rtCGM G4, compared to pre-exercise and later recovery, in patients with T1D using MDI.

Effects of Formic and Levulinic Acids on Butyric Acid Synthesis by Clostridium tyrobutyricum in Xylose Media

Abstract. Weak acids released during hydrolysis of lignocellulosic biomass are potential inhibitors of microorganism fermentation. In this study, the effects of formic and levulinic acids on butyric acid synthesis by were investigated. With the addition of 1.2 to 4.8 g L-1 of formic acid, increased lag time, decreased cell density, and lower butyric acid productivity were observed. Up to 15% and 56% reduction in peak cell density and butyric acid productivity, respectively, were caused by formic acid addition, whereas there was no significant difference in butyric acid yield between the control and formic acid treated groups (except for the 2.4 g formic acid L-1 treatment). Levulinic acid did not show any notable effects on within the investigated concentration range (0 to 4.8 g L-1). Overall, showed strong tolerance of both formic and levulinic acids, but neither of these acids could be metabolized by the microbe.HighlightsFormic acid had dosage-dependent inhibitory effects on C. tyrobutyricum.Levulinic acid had no effects on cell growth or butyrate synthesis.Neither formic acid nor levulinic acid was metabolized by C. tyrobutyricum.C. tyrobutyricum showed strong tolerance to formic acid and levulinic acid. Keywords: Butyric acid, Clostridium tyrobutyricum, Formic acid, Levulinic acid, Lignocellulosic hydrolysate, Xylose.

Reduction and inhibition of Listeria monocytogenes in cold-smoked salmon by Verdad N6, a buffered vinegar fermentate, and UV-C treatments

Contamination, survival and growth of Listeria monocytogenes in cold-smoked salmon represent serious health hazards to consumers and major challenges for salmon processors. Verdad N6, a commercially available buffered vinegar, was evaluated as an ingredient in cold-smoked salmon with regard to anti-listerial effects under processing and storage, sensory quality and consumer preference, effects on background microbiota and yield during production. Cold-smoked salmon with Verdad N6 added in the dry-salting process was produced. Salmon fillets were surface contaminated with a mix of L. monocytogenes. Levels of L. monocytogenes were determined during vacuum pack refrigerated storage for 29 days. The use of Verdad N6 resulted in increased lag times and reduced growth rates of L. monocytogenes. The inhibitory effects were dependent on Verdad N6 levels (0–2%), storage time and temperature (4 or 8 °C), type of contamination (between slices or on non-sliced salmon) and degree of smoking. The presence of dextrose (1%) in the recipe had no significant effects on L. monocytogenes levels after storage. On sliced salmon, complete growth inhibition at 4 °C storage could be obtained using 1% Verdad N6 compared to a 3 log increase in L. monocytogenes counts in control salmon. At abuse temperatures (8 °C), corresponding L. monocytogenes levels increased <2 log and 5–6 log during 29 days storage. On non-sliced salmon, 1% Verdad N6 provided complete growth reductions at 4 and 8 °C storage while L. monocytogenes in control salmon increased 2.3 and 4.6 log, respectively, in the same period. The use of Verdad N6 in combination with bactericidal UV-C treatments (fluence 50 mJ/cm2) provided an initial 0.8 log reduction and complete L. monocytogenes growth inhibition on subsequent storage at 4 and 8 °C. Salmon with Verdad N6 showed reduced levels of total counts during storage and a shift in the dominating bacteria with reduced and increased relative levels of Photobacterium and lactic acid bacteria, respectively. A consumer test showed no consistent differences in liking of salmon with and without Verdad N6. In summary, Verdad N6 is an option for the production of high quality cold-smoked salmon with enhanced food safety through its robust listeriostatic effects. The application of Verdad N6 in combination with listericidal UV-C light treatment can further reduce the listeria-risks of this ready-to-eat food product category.

Design of Highly Water Resistant, Impermeable, and Flexible Thin-Film Encapsulation Based on Inorganic/Organic Hybrid Layers

The lack of a transparent, flexible, and reliable encapsulation layer for organic-based devices makes it difficult to commercialize wearable, transparent, flexible displays. The reliability of organic-based devices sensitive to water vapor and oxygen must be guaranteed through an additional encapsulation layer for the luminance efficiency and lifetime. Especially, one of the major difficulties in current and future OLED applications has been the absence of thin-film encapsulation with superior barrier performance, mechanical flexibility, and water-resistant properties. In this work, we fabricated highly water-resistant, impermeable, and flexible inorganic/organic multilayers with optimized Al2O3 and functional organic layers. The key properties of the fabricated multilayers were compared according to the thickness and functionality of the inorganic and organic layers. Improvement of the barrier performance is mainly attributed to the optimized thickness of the Al2O3 films, and is additionally due to the increased lag time and effective surface planarization effects caused by the use of micrometer-thick organic layers. As a result, the 3-dyad multilayer structure composed of 60 nm-thick Al2O3 layers deposited at 70 °C and 2-μm-thick silane-based inorganic/organic hybrid polymer (silamer) layers with layered silica exhibited the lowest WVTR value of 1.11 × 10-6 g/m2/day in storage conditions of 30 °C/90% relative humidity. In addition, the multibarrier exhibited good mechanical stability through the use of alternating stacks of brittle inorganic and soft organic layers, without showing a large increase in the WVTR after bending tests. In addition, silamer layers improved the environmental stability of the Al2O3 ALD film. The silamer layer coated on the Al2O3 film effectively worked as a protective layer against harsh environments. The effective contact at the interface of Al2O3/silamer makes the barrier structure more impermeable and corrosion-resistant. In this study, we not only demonstrated an optimized multilayer based on functional organic layers but also provided a methodology for designing a wearable encapsulation applicable to wearable organic electronics.

Effect of Manure Application Rate and Rainfall Timing on the Leaching of Antibiotic-Resistant Bacteria and Their Associated Genes

In this study, we investigate the effect of application rate and timing of liquid swine slurry on leaching of antibiotic-resistant bacteria (ARB) and their antibiotic resistance genes (ARGs) through soil columns. Swine slurry was added to laboratory soil columns at rates of 5000 or 30,000 gal ac−1. For both application rates, rainfall was applied at either 1, 7, or 21 days after slurry application. Column effluent and the top centimeter of soil in the columns were sampled post-rainfall for cultivable bacteria and quantitative PCR was used to quantify tetracycline, methicillin, β-lactam, and erythromycin resistance genetic determinants. We also conducted similar experiments using swine lagoon slurry spiked with antibiotic-resistant E. coli and Salmonella. We found that the concentration of ARB and ARG recovered in the column effluent following application of the swine lagoon slurry generally decreased with increasing lag time between slurry application and simulated rainfall, though most of these decreases were not statistically significant. Moreover, no statistically significant differences in CFU or GU concentration in the column leachate were observed between the low and high slurry application rates. In the experiments using swine slurry spiked with E. coli and Salmonella, concentrations of both microorganisms eluted from fine sand columns were affected by both slurry application rate and lag time; recovery of ARGs, however, was mostly unaffected, but some differences were observed. In columns packed with loamy sand, no recovery was detected in the column effluent for either organism and recovery of ARG was unaffected by manure application rate or rainfall lag time.

Physiological response of 10 phytoplankton species exposed to macondo oil and the dispersant, Corexit.

Culture experiments were conducted on ten phytoplankton species to examine their biological and physiological responses during exposure to oil and a combination of oil and dispersant. The species tested included a range of taxa typically found in the Gulf of Mexico such as cyanobacteria, chlorophytes, and diatoms. Cultures were exposed to Macondo surrogate oil using the water accommodated fraction (WAF), and dispersed oil using a chemically enhanced WAF (CEWAF) and diluted CEWAF, to replicate conditions following the Deepwater Horizon spill in the Gulf of Mexico. A range of responses were observed, that could broadly class the algae as either "robust" or "sensitive" to oil and/or dispersant exposure. Robust algae were identified as Synechococcus elongatus, Dunaliella tertiolecta, two pennate diatoms Phaeodactylum tricornutum and Navicula sp., and Skeletonema grethae CCMP775, and were largely unaffected by any of the treatments (no changes to growth rate or time spent in lag phase relative to controls). The rest of the phytoplankton, all centric diatoms, exhibited at least some combination of reduced growth rates or increased lag time in response to oil and/or dispersant exposure. Photophysiology did not have a strong treatment effect, with significant inhibition of photosynthetic efficiency (Fv /Fm ) only observed in the CEWAF, if at all. We found that the effects of oil and dispersants on phytoplankton physiology were species-dependent, and not always detrimental. This has significant implications on how oil spills might impact phytoplankton community structure and bloom dynamics in the Gulf of Mexico, which in turn impacts higher trophic levels.

Thrombin generation estimates the anticoagulation effect of direct oral anticoagulants with significant interindividual variability observed.

: Direct oral anticoagulants (DOACs) are increasingly being used, primarily due to their drug stability and patient convenience. Although these drugs have been evaluated to be well tolerated in numerous clinical trials, their impact on in-vivo anticoagulation effect, variability and therapeutic drug level remains unknown. Hence, we aim to study the effect and variability of DOACs on thrombin generation via the calibrated automated thrombogram. Anonymized coagulation specimens from outpatients on warfarin were collected. Pooled normal plasma samples were spiked with increasing concentrations of dabigatran, rivaroxaban and apixaban. Similarly, plasma samples with normal coagulation profiles were spiked with two concentrations each of dabigatran, rivaroxaban and apixaban. Thrombin generation via calibrated automated thrombogram was run using the above samples and compared with a dataset of normal controls. Increasing international normalized ratio was associated with a reduction of endogenous thrombin potential (ETP) and thrombin peak and increasing lag time. Factor Xa inhibitors produced a flattened thrombin generation curve with a reduction of thrombin peak and relative preservation of ETP. Direct thrombin inhibitors produced a reduction of both ETP and thrombin peak and increasing lag time. Seventy-one citrated plasma samples (26 dabigatran, 21 rivaroxaban and 24 apixaban) were evaluated. The two concentrations produced a reduction of thrombin generation parameters with significant interindividual variability compared with neat plasma of 35-93, 13-31 and 18-71% and for dabigatran, rivaroxaban and apixaban, respectively. Thrombin generation can measure the anticoagulation effect of commonly used DOACs, with each drug having a unique thrombin generation profile. The variability noted using the same concentration suggests significant interindividual pharmacodynamic differences, which maybe relevant with respect to efficacy as well as bleeding side effects. Further delineation of the modifiers of interindividual differences is required in the in-vivo setting.

Fructose-Enhanced Antimicrobial Activity of Silver Nanoparticle-Embedded Polymersome Nanocarriers.

In recent years, an increasing body of research has indicated that the antimicrobial activity of certain antibiotic drugs can be enhanced by the addition of specific metabolites. This study aimed to incorporate these findings into polymersomes (novel polymer-based nanoscale drug delivery vehicles) which can be loaded with various therapeutic molecules and nanoparticles. Polymersome technology has shown promising results in treating antibiotic-resistant infections by co-encapsulating the antibiotic methicillin with silver nanoparticles. Here, silver nanoparticle-embedded polymersomes (AgPs) were synthesized in a similar fashion with gentamicin replacing methicillin as the antibiotic agent and supplemented with fructose to promote efficacy. Two clinically-isolated strains of methicillin-resistant Staphylococcus aureus (MRSA) (ATCC #43300 and ATCC #25923) were cultured and treated with the new AgP formulations, with the former strain being susceptible to gentamicin and the latter strain being resistant to gentamicin. The treatment of the non-resistant strain yielded promising results with the polymersomes without fructose supplementation inducing a maximal growth rate reduction of up to 40% and an increase in lag time of up to 141% relative to the untreated control. Impressively, the fructose-loaded polymersomes completely eliminated the bacterial growth over the observed time period at the higher doses and outperformed the no-fructose treatment at all concentrations. However, despite significantly reducing bacterial growth, the treatment of the gentamicin-resistant strain did not seem to be enhanced by the addition of fructose. Lastly, the present study demonstrated that the presence of fructose in the polymersomes seemed to slightly ameliorate the cytotoxic effect of the treatment on human dermal fibroblasts (a model mammalian cell). In addition to developing and testing a new polymersome formulation with fructose resulting in increased efficacy, the results of this study also demonstrated the variability inherent to developing novel antimicrobial treatments for different bacterial strains.

The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease.

The protein α-synuclein (αSN) aggregates to form fibrils in neuronal cells of Parkinson's patients. Here we report on the effect of neutral (zwitterionic) nanoliposomes (NLPs), supplemented with cholesterol (NLP-Chol) and decorated with PEG (NLP-Chol-PEG), on αSN aggregation and neurotoxicity. Both NLPs retard αSN fibrillization in a concentration-independent fashion. They do so largely by increasing lag time (formation of fibrillization nuclei) rather than elongation (extension of existing nuclei). Interactions between neutral NLPs and αSN may locate to the N-terminus of the protein. This interaction can even perturb the interaction of αSN with negatively charged NLPs which induces an α-helical structure in αSN. This interaction was found to occur throughout the fibrillization process. Both NLP-Chol and NLP-Chol-PEG were shown to be biocompatible in vitro, and to reduce αSN neurotoxicity and reactive oxygen species (ROS) levels with no influence on intracellular calcium in neuronal cells, emphasizing a prospective role for NLPs in reducing αSN pathogenicity in vivo as well as utility as a vehicle for drug delivery.

Formulation of Modified Release Pellets of Montelukast Sodium

The present study was carried out with an aim of preparing modified release pellets of the antiasthma drug montelukast sodium. The patients suffering from chronic asthma many a times suffer from exacerbations during the early morning hours i.e. around 4am to 6 am. Thus the need to take an immediate release medication arises during early morning hours which is not quiet feasible for the patients. The delivery of the drug at this time can be made possible by the use of modified release formulation of montelukast sodium which when taken at the bed time would release the drug as a pulsed delivery without the need of the patient to wake up. The montelukast sodium pellets prepared by extrusion-spheronization were coated with release retarding polymer ethyl cellulose using the Wurster method. The ethyl cellulose coating helped in lag time increase due to prolonged water uptake time. The increase in the coating level increased the lag time sufficiently that might release the drug during the early morning hours. Thus a modified release pellets dosage form to prevent the early morning asthma attacks and exacerbations was developed successfully.

Ion-crosslinked wood-derived nanocellulose hydrogels with tunable antibacterial properties: Candidate materials for advanced wound care applications

Development of advanced dressings with antimicrobial properties for the treatment of infected wounds is an important approach in the fight against evolution of antibiotic resistant bacterial strains. Herein, the effects of ion-crosslinked nanocellulose hydrogels on bacteria commonly found in infected wounds were investigated in vitro. By using divalent calcium or copper ions as crosslinking agents, different antibacterial properties against the bacterial strains Staphylococcus epidermidis and Pseudomonas aeruginosa were obtained. Calcium crosslinked hydrogels were found to retard S. epidermidis growth (up to 266% increase in lag time, 36% increase in doubling time) and inhibited P. aeruginosa biofilm formation, while copper crosslinked hydrogels prevented S. epidermidis growth and were bacteriostatic towards P. aeruginosa (49% increase in lag time, 78% increase in doubling time). The wound dressing candidates furthermore displayed barrier properties towards both S. epidermidis and P. aeruginosa, hence making them interesting for further development of advanced wound dressings with tunable antibacterial properties.

Impacts of varying durations of passive oxygen exposure on freshwater denitrifier community structure and function

Fertilizer use has dramatically increased the availability of nitrate (NO3 −) in aquatic systems. Microbe-mediated denitrification is one of the predominant means of NO3 − removal from freshwaters, yet oxygenation (O2)-induced disruptions—e.g., extreme precipitation events—can occur, resulting in a disproportional increase in nitrous oxide (N2O) production and efflux as facultative anaerobic bacterial populations use of O2 as a terminal electron acceptor increases. We examined the effects of 12- and 24-h passive O2 exposure on previously anaerobic bacterial communities focusing on denitrification enzyme activity (DEA), N2O production, and bacterial community 16S rRNA and nitrous oxide reductase gene (nosZ) profiles after 12, 24, and 48 h of anaerobic recovery. Treatments experiencing 24-h O2 exposure had significantly higher DEA 12 h into anaerobic recovery than treatments undergoing 12-h O2 exposure. Initial N2O emissions were significantly lower in the 24-h O2 exposure treatments although by 24 h a dramatic spike (tenfold relative to the 12-h O2 exposure treatments) in N2O concentrations was observed. However, within 6 h (30-h anaerobic recovery) these differences were gone. Community nosZ profiles experiencing 24-h O2 exposure exhibited reduced diversity after 24-h recovery, which corresponded with an increase in N2O emissions. However, after 48 h of anaerobic recovery, nosZ diversity had recovered. These observations highlight the effects of short-term aerobic disruption on denitrification, as well as the effects on the denitrifier community profile. Together, these data suggest that recovery to ambient N cycling is exacerbated by disturbance length due to increased lag time and subsequent loss of denitrifier community diversity.

Delayed sample arrival at the laboratory does not lead to more false negatives in the Danish population screening for colorectal cancer

In Denmark, biennial population screening for colorectal cancer was introduced in 2014 for all aged 50–74 years. Five laboratories representative for the regional division of Denmark perform the immunochemical testing of faecal occult blood in the screening samples (iFOBT, OC-Sensor (Eiken Chemical, cut-off 100 µg/L)). In July 2016, a new agreement on the public post-delivery entailed an increased lag time (five days) from the screening participant drops the screening sample into a mail-box until sample arrival at the laboratories. Previous work had reported that a lag time above five days led to more false negative iFOBT tests. We investigated if this was true also under Danish conditions. We performed two stability tests; one with sample storage at 30 °C for 14 days (N = 60), and another with sample storage at room temperature for 13 days (N = 10). We extracted data from our laboratory information system (LABKA) on all iFOBT tests performed in the entire Central Denmark Region (N = 104,328 patients) during the last six months for each calendar year 2014–16. For each year, we computed the distribution of iFOBT tests below and above cut-off. Our stability tests showed no positive samples switching to false negative after storage; however, some negative samples turned false positive, especially at 30 °C. The data showed no change in the distribution of iFOBT tests below and above cut-off after July 2016. We found no evidence that an enhanced lag time increased the number of false negative iFOBT tests in the Danish screening program for colorectal cancer.

ENSO-induced drought hazards and wet spells and related agricultural losses across Anhui province, China

Using daily precipitation data from 25 meteorological stations for a period of 1961–2014, spatiotemporal features of wet spells and droughts and related impacts on agricultural production across Anhui province, China, were investigated with a linear regressive technique, the Standardized Precipitation Evapotranspiration Index (SPEI) and the modified Mann–Kendall trend test method. Results indicated that: (1) ENSO-induced wet spells and droughts accounted for 83 and 68% of the total wet spells and droughts and droughts were closely related to La Nina events of the same and subsequent years. Wet spells, however, were closely related to El Nino events; (2) a larger variability was found in the SPEI, showing larger flood and drought risks during spring and autumn than those during summer and winter seasons. Generally, wet spells in winter were relatively high and the drying tendency was identified in winter during recent years; (3) relations between SPEI and SSTA were shifting during warm and cold phases of ENSO. The warm phase of ENSO tended to have larger impacts on SPEI in southern Anhui province, and the cold phase of ENSO had a greater impact on the SPEI variation in northern Anhui province. Comparatively, SSTA had an increasing impact on wet spells and droughts with increasing lag time; and (4) the reduction of rice and maize production in southern Anhui province was found mainly during 1 year earlier to the ENSO events. The amount of reduction of maize was larger in northern Anhui province and Jianghuai region, years with maize reduction were more often in southern Anhui province. Irrigation in central Anhui province can mitigate the negative effects of wet spells and droughts.