Simultaneous Combinations Research Articles

Gemcitabine Plus Nab-Paclitaxel Induces PD-L1 mRNA Expression in Plasma-Derived Microvesicles in Pancreatic Cancer.

Simple SummaryThere is an urgent need to improve the therapeutic options in pancreatic cancer. In this study, we assessed the ability of two standard-of-care chemotherapeutic regimens to modulate the levels of PD-L1 mRNA isolated from plasma-derived microvesicles (MVs) of patients with pancreatic cancer. Our findings demonstrate for the first time a statistically significant difference in MV-derived PD-L1 mRNA levels at 3 months vs. baseline in patients treated with GEMnPAC, compared to those receiving FOLFIRINOX. Although these findings need to be confirmed in larger prospective cohorts, they can represent a rational basis for testing the hypothesis that the GEMnPAC schedule may be used as an immunotherapy-modulating regimen in PDAC patients due to its capability of increasing PD-L1 mRNA expression.Pancreatic ductal adenocarcinoma (PDAC) is a non-immunogenic tumor poorly responsive to immune checkpoint inhibitors. This study investigates the effect of 5-fluorouracil (5-FU), irinotecan, and oxaliplatin (FOLFIRINOX), and gemcitabine plus nab-paclitaxel (GEMnPAC) regimens on PD-L1 mRNA expression in plasma-derived microvesicles (MVs) in 50 PDAC patients. Plasma was collected before starting chemotherapy and after 3 months of treatment. mRNA was extracted from MVs, and PD-L1 expression was measured by digital droplet PCR. Twenty-eight patients were PD-L1 positive in MVs at baseline, of which 18 were in the GEMnPAC cohort and 10 in the FOLFIRINOX one. The amount of PD-L1 expression in MVs increased from baseline to 3 months of treatment in patients receiving GEMnPAC (median value 0.002 vs. 0.005; p = 0.01) compared to those treated with FOLFIRINOX (median 0.003 vs. 0.004; p = 0.97). The increase in PD-L1 mRNA expression in MVs was not related to tumor response (PR + SD: p = 0.08; PD: p = 0.28). Our findings demonstrate that GEMnPAC can increase PD-L1 mRNA expression in patient-derived circulating MVs, providing a rationale for testing the efficacy of this regimen in sequential or simultaneous combinations with immunotherapy in PDAC patients.

Synergistic Growth Inhibition of HT-29 Colon and MCF-7 Breast Cancer Cells with Simultaneous and Sequential Combinations of Antineoplastics and CNS Drugs.

Several central nervous system (CNS) drugs exhibit potent anti-cancer activities. This study aimed to design a novel model of combination that combines different CNS agents and antineoplastic drugs (5-fluorouracil (5-FU) and paclitaxel (PTX)) for colorectal and breast cancer therapy, respectively. Cytotoxic effects of 5-FU and PTX alone and in combination with different CNS agents were evaluated on HT-29 colon and MCF-7 breast cancer cells, respectively. Three antimalarials alone and in combination with 5-FU were also evaluated in HT-29 cells. Different schedules and concentrations in a fixed ratio were added to the cultured cells and incubated for 48 h. Cell viability was evaluated using MTT and SRB assays. Synergism was evaluated using the Chou-Talalay, Bliss Independence and HSA methods. Our results demonstrate that fluphenazine, fluoxetine and benztropine have enhanced anticancer activity when used alone as compared to being used in combination, making them ideal candidates for drug repurposing in colorectal cancer (CRC). Regarding MCF-7 cells, sertraline was the most promising candidate alone for drug repurposing, with the lowest IC50 value. For HT-29 cells, the CNS drugs sertraline and thioridazine in simultaneous combination with 5-FU demonstrated the strongest synergism among all combinations. In MCF-7 breast cancer cells, the combination of fluoxetine, fluphenazine and benztropine with PTX resulted in synergism for all concentrations below IC50. We also found that the antimalarial artesunate administration prior to 5-FU produces better results in reducing HT-29 cell viability than the inverse drug schedule or the simultaneous combination. These results demonstrate that CNS drugs activity differs between the two selected cell lines, both alone and in combination, and support that some CNS agents may be promising candidates for drug repurposing in these types of cancers. Additionally, these results demonstrate that 5-FU or a combination of PTX with CNS drugs should be further evaluated. These results also demonstrate that antimalarial drugs may also be used as antitumor agents in colorectal cancer, besides breast cancer.

A quantitative MRI investigation of the association between iliotibial band syndrome and patellofemoral malalignment.

The iliotibial band (ITB) has a wide patellar insertion that provides lateral restraint to the patella and maintains the patellofemoral joint's stability. There has been limited investigation into the relationship between patellofemoral malalignment and iliotibial band syndrome (ITBS). We retrospectively analyzed 47 knees with ITBS by retrieving magnetic resonance imaging (MRI) data collected over an approximately 6-year period from our database. The Insall-Salvati ratio, lateral patellofemoral angle (LPA), lateral patellar tilt (LPT), lateral trochlear length (LTL), angle of the non-weight-bearing facet of the lateral femoral condyle (nwb-LFCA), and the ITB-lateral femoral condyle (IT-LFC) distance were measured on MR images. The knees of 47 age- and gender-matched subjects were enrolled as the normal group. In the ITBS group, over one third (34%, 16/47) of knees had abnormal patellofemoral measurements, including 8 (17%, 8/47) knees with patellar alta, 11 (23.4%, 11/47) knees with an abnormally decreased LPA, and 5 (10.6%, 5/47) knees with an abnormally increased LPT indicating lateral patellar tilt. Moreover, 8 knees had simultaneous combinations of two or three abnormality parameters, and 8 (17%, 8/47) knees presented with superolateral Hoffa's fat pad edema. The Insall-Salvati ratio, LPT, and nwb-LFCA in the ITBS group were significantly higher than those in the normal group (P=0.001, P<0.001, and P<0.001, respectively); the LPA and IT-LFC distances in the ITBS group were significantly lower (P=0.003, P<0.001, respectively) than those in the normal group. There were mild to moderate correlations between the MRI parameters and ITBS (P=0.006, P<0.001, respectively). This study confirmed that a higher position or lateral tilt of the patella and a steeper morphology of the anterior part of the lateral femoral condyle were associated with the development of ITBS, which is helpful in understanding and further exploring the mechanism of ITBS.

Comprehensive Genomic Characterization of Refractory Multiple Myeloma Reveals a Complex Mutational and Structural Landscape Associated with Drug Resistance

Comprehensive Genomic Characterization of Refractory Multiple Myeloma Reveals a Complex Mutational and Structural Landscape Associated with Drug Resistance

Harmonicity and Roughness in the Biology of Tonal Aesthetics.

Evidence supporting a link between harmoni-city and the attractiveness of simultaneous tone combinations has emerged from an experiment designed to mitigate effects of musical enculturation. I examine the analysis undertaken to produce this evidence and clarify its relation to an account of tonal aesthetics based on the biology of auditory-vocal communication.

Investigating the Effects of Bed Roughness on Incipient Motion in Rigid Boundary Channels with Developed Hybrid Geno-Fuzzy versus Neuro-Fuzzy Models

In present study, the comprehension of different types of bedforms generated by different bed roughness, in rectangular and circular cross-sectional rigid boundary channels and the resistance generated by the bed roughness against the flow are evaluated. Moreover, the critical condition of sediment motion under bed roughness influence is investigated. This study presents novel contributions in solving engineering problems that suffer from the lack of knowledge on the incipient motion of sediment particles in rigid boundary channels under bed roughness effects. Furthermore, soft computing and evolutionary computation methods have been combined to develop a new novel predictive model. The Evolutionary GENOFIS also aims at improving the ANFIS tool depends on Sugeno Fuzzy Inference System. The advantages of the proposed hybrid GENOFIS approach over the ANFIS tool is its novel ability to tackle the incipient prediction problem by using less fuzzy based rules and to represent the consequent part of the model as a constant, linear or non-linear function as well as with possible simultaneous combinations of them. For validation and comparison purposes, model performances of hybrid GENOFIS, ANFIS and data-based linear regression approaches are evaluated via experimental data partitioned for testing purposes. The model results are compared through corresponding RMSE and CE values. It is found that the hybrid GENOFIS model results outperformed the ANFIS and linear regression models. Consequently, novel experimental data-driven incipient motion formula and the hybrid GENOFIS approach are proposed to modeling complex incipient motion problems that are full of uncertainty and complication.

Docetaxel-dasatinib combination: A strategy to overcome unfavorable treatment outcomes due to dose reduction

Docetaxel is a highly potent chemotherapeutic agent used in the management of many cancers. Adverse effects associated with its use are the reasons clinicians usually resort to dose reduction and/or dose delays for patients. Dose reductions ≥15% are considered suboptimal doses and are reported to be associated with unfavorable treatment outcomes.The aim of this project was to redesign the delivery system of docetaxel and evaluate the dose-sparing effect of a cytostatic agent - dasatinib on docetaxel when used in combination. Using the nanoprecipitation method, docetaxel was entrapped in a polymer (Polycaprolactone) matrix as nanoparticles with poloxamer F-108 as the stabilizer. A triple negative breast cancer cell line (MDA-MB-231) was used as a model for cancer cells. The 50% inhibitory concentrations (IC50) were determined for each drug in solution and as nanoparticles using the Alamar blue proliferation assay. Simultaneous and sequential combinations of the two drug formulations were conducted and their effect on cell proliferation determined using the Alamar blue assay. The average size of nanoparticles ranged between 188.0 and 212.0 nm which is optimum for uptake and accumulation in the tumor microenvironment. The polycaprolactone matrix delayed the release the docetaxel, thus direct death of cells was avoided immediately after dosing until the drug was released. Simultaneous use of dasatinib with docetaxel yielded only mild synergy, however, pre-treating MDA-MB-231 cells with dasatinib for 2 hours prior to docetaxel administration resulted in about 10–14% more death of cells than in the group not given this regimen. Dasatinib has a dose-sparing effect on docetaxel. Further studies need to be conducted to confirm the use of dasatinib as premedication in docetaxel treatment regimen for breast cancer. Obtaining equivalent response using a lower dose of docetaxel will result in fewer adverse effects, prevent treatment delays and subsequently avoid treatment failures.

GS-PAT

Phased Arrays of Transducers (PATs) allow accurate control of ultrasound fields, with applications in haptics, levitation (i.e. displays) and parametric audio. However, algorithms for multi-point levitation or tactile feedback are usually limited to computing solutions in the order of hundreds of sound-fields per second, preventing the use of multiple high-speed points, a feature that can broaden the scope of applications of PATs. We present GS-PAT , a GPU multi-point phase retrieval algorithm, capable of computing 17K solutions per second for up to 32 simultaneous points in a mid-end consumer grade GPU (NVidia GTX 1660). We describe the algorithm and compare it to state of the art multi-point algorithms used for ultrasound haptics and levitation, showing similar quality of the generated sound-fields, and much higher computation rates. We then illustrate how the shift in paradigm enabled by GS-PAT (i.e. real-time control of several high-speed points) opens new applications for PAT technologies, such as in volumetric fully coloured displays, multi-point spatio-temporal tactile feedback, parametric audio and simultaneous combinations of these modalities.

Well-Formed Stimuli Lead to Perceptual Asymmetries in Discrimination: Evidence from Musical Chords and Rhythms

ABSTRACT In three experiments, listeners heard standard and comparison auditory sequences on each trial and judged whether they were the same or different. In Experiments 1 and 2, the sequences comprised chords (i.e., simultaneous combinations of pure tones) that were familiar (major), less familiar but with no sensory dissonance (diminished), or unfamiliar and dissonant. Performance was better in the major condition than in the other two conditions, but only when the major chord was the standard sequence. When it was the comparison, performance was poor. In Experiment 3, the stimuli were metrical or nonmetrical rhythms comprised of snare-drum beats. A discrimination advantage for metrical sequences was evident when the metrical sequence was the standard pattern but not when it was the comparison. In short, order of presentation determined whether well-formed stimuli facilitated discrimination. Well-formed auditory sequences led to advantages in discrimination when they were the standard (presented first), but this advantage was eliminated when the well-formed sequence was the comparison (presented second).

Development of consonance preferences in Western listeners.

Many scholars consider preferences for consonance, as defined by Western music theorists, to be based primarily on biological factors, while others emphasize experiential factors, notably the nature of musical exposure. Cross-cultural experiments suggest that consonance preferences are shaped by musical experience, implying that preferences should emerge or become stronger over development for individuals in Western cultures. However, little is known about this developmental trajectory. We measured preferences for the consonance of simultaneous sounds and related acoustic properties in children and adults to characterize their developmental course and dependence on musical experience. In Study 1, adults and children 6 to 10 years of age rated their liking of simultaneous tone combinations (dyads) and affective vocalizations. Preferences for consonance increased with age and were predicted by changing preferences for harmonicity-the degree to which a sound's frequencies are multiples of a common fundamental frequency-but not by evaluations of beating-fluctuations in amplitude that occur when frequencies are close but not identical, producing the sensation of acoustic roughness. In Study 2, musically trained adults and 10-year-old children also rated the same stimuli. Age and musical training were associated with enhanced preference for consonance. Both measures of experience were associated with an enhanced preference for harmonicity, but were unrelated to evaluations of beating stimuli. The findings are consistent with cross-cultural evidence and the effects of musicianship in Western adults in linking Western musical experience to preferences for consonance and harmonicity. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Enhancement of Macarpine Production in Eschscholzia Californica Suspension Cultures under Salicylic Acid Elicitation and Precursor Supplementation

Macarpine is a minor benzophenanthridine alkaloid with interesting biological activities, which is produced in only a few species of the Papaveraceae family, including Eschscholzia californica. Our present study was focused on the enhancement of macarpine production in E. californica suspension cultures using three elicitation models: salicylic acid (SA) (4; 6; 8 mg/L) elicitation, and simultaneous or sequential combinations of SA and L-tyrosine (1 mmol/L). Sanguinarine production was assessed along with macarpine formation in elicited suspension cultures. Alkaloid production was evaluated after 24, 48 and 72 h of elicitation. Among the tested elicitation models, the SA (4 mg/L), supported by L-tyrosine, stimulated sanguinarine and macarpine production the most efficiently. While sequential treatment led to a peak accumulation of sanguinarine at 24 h and macarpine at 48 h, simultaneous treatment resulted in maximum sanguinarine accumulation at 48 h and macarpine at 72 h. The effect of SA elicitation and precursor supplementation was evaluated also based on the gene expression of 4′-OMT, CYP719A2, and CYP719A3. The gene expression of investigated enzymes was increased at all used elicitation models and their changes correlated with sanguinarine but not macarpine accumulation.

Effect of drug combinations on the kinetics of antibiotic resistance emergence in Escherichia coli CFT073 using an in vitro hollow-fibre infection model

Antibiotic resistance is one of the major threats to public health today. To address this problem requires an urgent comprehensive approach. Strategic and multitargeted combination therapy has been increasingly used clinically to treat bacterial infections. The hollow-fibre infection model (HFIM) is a well-controlled in vitro bioreactor system that is increasingly being used in the assessment of resistance emergence with monotherapies and combination antibiotic therapies. In this study, the HFIM was evaluated as a reliable in vitro method to quantitatively and reproducibly analyse the emergence of antibiotic resistance using ampicillin, fosfomycin and ciprofloxacin and their simultaneous combinations against Escherichia coli CFT073, a clinical uropathogenic strain. Bacteria were exposed to clinically relevant pharmacokinetic (PK) concentrations of the drugs for 10 days. Drug and bacterial samples were collected at different time points for PK analysis and to enumerate total and resistant bacterial populations, respectively. The results demonstrated that double or triple combinations significantly delayed the emergence of resistant E. coli CFT073 subpopulations. These findings suggest that strategic combinations of antimicrobials may play a role in controlling the emergence of resistance during treatment. Further animal and human trials will be needed to confirm this and to ensure that there is no adverse impact on the host microbiome or unexpected toxicity. The HFIM system could potentially be used to identify clinically relevant combination dosing regimens for use in a clinical trial evaluating the appearance of resistance to antibacterial drugs.

Prior physicochemical stress exposures and subsequent UV-C resistance of E. coli O157:H7 in coconut liquid endosperm

This study determined the effects of prior exposures to individual acid, desiccation, and heat stress, and all their possible simultaneous combinations, on the subsequent ultraviolet-C (UV-C) inactivation kinetics of E. coli O157:H7 in a coconut liquid endosperm suspending medium. Sublethal injury rates determined in the cells after stress exposure and acclimation in the suspending medium ranged from 0.00% (acid stressed) to 84.24% (desiccation+heat stressed). Regardless of the previous stress to which cells were exposed, a logarithmic linear inactivation behavior was observed in the cells. The decimal reduction energy (DUV-C) of the stressed cells ranged from 152.17mJ/cm2 (acid+desiccation+heat stressed) to 209.81mJ/cm2 (acid+heat stressed). No apparent relationship was observed between % injury and DUV-C values possibly because the nature of the injury the cells incurred after exposures to the stresses was not determined. Cells previously exposed to the combined acid and heat stress exhibited the highest D ratio (DUV-C stressed/ DUV-C control), indicative of heterologous adaptation that resulted in cells 30% more resistant towards UV-C. The results established in this study contribute in further understanding the utility and limitations of UV-C radiation as an alternative nonthermal processing technique for fruit juices.

Synergistic Action of Phage and Antibiotics: Parameters to Enhance the Killing Efficacy Against Mono and Dual-Species Biofilms.

Pseudomonas aeruginosa and Staphylococcus aureus are opportunistic pathogens and are commonly found in polymicrobial biofilm-associated diseases, namely chronic wounds. Their co-existence in a biofilm contributes to an increased tolerance of the biofilm to antibiotics. Combined treatments of bacteriophages and antibiotics have shown a promising antibiofilm activity, due to the profound differences in their mechanisms of action. In this study, 48 h old mono and dual-species biofilms were treated with a newly isolated P. aeruginosa infecting phage (EPA1) and seven different antibiotics (gentamicin, kanamycin, tetracycline, chloramphenicol, erythromycin, ciprofloxacin, and meropenem), alone and in simultaneous or sequential combinations. The therapeutic efficacy of the tested antimicrobials was determined. Phage or antibiotics alone had a modest effect in reducing biofilm bacteria. However, when applied simultaneously, a profound improvement in the killing effect was observed. Moreover, an impressive biofilm reduction (below the detection limit) was observed when gentamicin or ciprofloxacin were added sequentially after 6 h of phage treatment. The effect observed does not depend on the type of antibiotic but is influenced by its concentration. Moreover, in dual-species biofilms it was necessary to increase gentamicin concentration to obtain a similar killing effect as occurs in mono-species. Overall, combining phages with antibiotics can be synergistic in reducing the bacterial density in biofilms. However, the concentration of antibiotic and the time of antibiotic application are essential factors that need to be considered in the combined treatments.

Interaction between somatostatin analogues and targeted therapies in neuroendocrine tumor cells.

Somatostatin analogues (SSA) represent the standard of care for symptom control in patients with functional gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In addition, SSA exert significant anti-proliferative effects in mid-gut and pancreatic NET (PanNET). In parallel, molecularly targeted therapies (MTT) have been shown to improve progression free survival (PFS) in patients with PanNET. However, due to either primary or acquired resistance to MTT, their impact on overall survival (OS) remains unclear. To date, various hypotheses exist to explain differences in patient responsiveness to SSA and MTT. However, data addressing one of the most pivotal questions, whether combining SSA with novel MTT will result in synergistic or additive efficacy compared to monotherapy, are lacking. The aim of this study is to characterize the interaction, optimal sequence and dosing of SSA-based and molecularly targeted therapies in PanNET. Somatostatin receptor subtypes 1–5 (SSTR) were evaluated in the neuroendocrine cell lines Bon1, QGP1 and Ins-1 via immunoblot and qRT-PCR. The impact of the SSA-analogue lanreotide alone or in combination with the MTT sunitinib, everolimus and regorafenib on intracellular signalling, hormone secretion and cell proliferation was determined in cell lysates and supernatants. In addition, synergistic effects of SSA and MTT in various sequential therapeutic approaches were investigated. SSTR were differently expressed in the examined neuroendocrine tumor cell lines. SSTR modulation via lanreotide moderately influenced proliferation, mainly via modulating AKT and ERK signalling, which was paralleled by decreased chromogranin A (CgA) expression and secretion. Interestingly, MTT treatment with regorafenib upregulated the expression of SSTR-2 and -5, while sunitinib and everolimus did not significantly alter SSTR expression. Cell viability was significantly reduced by all MTT, with regorafenib exerting the most significant effects. However, compared to the marked effects of MTT alone, synergistic effects of combined MTT and lanreotide treatment were only modest and time- and dose-dependent. SSTR are differentially expressed in various NEN cell lines. Their expression is influenced by MTT treatment. Various sequential or simultaneous combinations of lanreotide and MTT did not lead to significant synergistic effects.

Pharmacological effects of the simultaneous and sequential combinations of trifluridine/tipiracil (TAS-102) and 5-fluorouracil in fluoropyrimidine-sensitive colon cancer cells.

The aim of this study was to investigate possible synergistic effects in vitro of trifluridine/tipiracil (TAS-102) and 5-fluoruracil (5-FU) on fluoropyrimidine-sensitive colon cancer cell lines of different mutational status in order to build a rational basis for the future use of this combination therapy in adjuvant settings or as a first-line treatment for metastatic disease. Proliferation assays were performed on HT-29 (B-raf mutated), SW-620 (ras mutated), and Caco-2 (wild type) colon cancer cell lines exposed to 120-h treatments of 5-FU, TAS-102 and their different combination schedules (simultaneous, sequential and reverse) at equimolar and non-equimolar ratios. The synergistic, additive and antagonistic effects of 5-FU and TAS-102 were determined by the combination index (CI) and dose reduction index (DRI). Our preclinical in vitro results may suggest an apparently counterintuitive but strongly synergistic combination of 5-FU and TAS-102 in fluoropyrimidine-sensitive colon cancer cells allowing a marked theoretical reduction in the administered doses of both drugs. In particular, this association seems to be highly effective in wild-type colon cancer cells, both in sequential and simultaneous schedules. Together, these data may build a rational basis for the future use of TAS-102 combined with 5-FU in adjuvant settings, or as a first-line treatment for metastatic disease.

MUSIC THEORY

It is only on the higher level of abstraction and generalization that the two human branches of acoustic communication, speech and music are separated from each other. Speech is primarily adjusted to the conceptual-verbal symbols and representation of an objectified, static world. In the linguistic communication the main role is played by the elements of noise, the consonants. It has never been doubted that music is a kind of communication, the mediator of human relationships, but it has been a question what music wants to express. Since the Pythagoreans, some believe to find the key to interpreting its message in the common quantifiable nature of the musical medium and the cosmos. Another historical tradition considered music as the direct expression of human emotions. Representants of the doctrine of imitation derived music from the intonation of speech and the text seems for many to be a support to “understand” music. Music separated from the primary source of sound phenomena and their direct sensual effect constructed a specific communication system. It possesses an inestimable potential richness of discrete pitches and times, colours and sound intensity. The infinite potentials of successive and simultaneous combinations are suitable for erecting the audible, dynamic models of human relations and types of behavior, internal events and interactions, different situations. European polyphony established a strictly regulated, closed syntax of musical communication which comes close to conceptual precision.

Influence of simultaneous application of copper oxide nanoparticles and Satureja Khuzestanica essential oil on properties of kefiran–carboxymethyl cellulose films

A factorial experiment was designed to analyze nanobiocomposite films based on kefiran–carboxymethyl cellulose carbohydrates with copper oxide nanoparticles (CuONPs) (0, 1, 1.5 and 2%) and Satureja khuzestanica essential oil (SEO) (0, 1, 1.5 and 2%) as well as their combination in order to investigate their physical, mechanical, antioxidant, antimicrobial, optical, color, dynamic mechanical thermal, and morphological properties. It was generally found that the separate addition of CuONPs and SEO to the film improved its properties. In addition, results showed that the simultaneous application of CuONPs and SEO had substantially improved the physical and mechanical properties of the films. Besides the nature of CuONPs and SEO, this effect was due to the formation of hydrogen interactions between them and the biopolymer matrix, as supported by Fourier transform infrared spectroscopy (FTIR). The simultaneous application of CuONPs and SEO had a synergistic effect on antimicrobial properties against Staphylococcus aureus and Escherichia coli bacteria and further made a significant change in color parameters and percentage of light transmission within the visible and ultraviolet light spectral ranges. The results of the dynamic mechanical thermal analysis (DMTA) showed that the films containing simultaneous combinations of CuONPs and SEO had the highest storage modulus and glass transition temperature. Results of electron microscopy images indicated that the simultaneous presence of CuONPs and SEO in films was consistent with the biopolymer matrix and distributed properly in the medium. In summary, the results of this study showed that nanobiocomposite films containing the simultaneous combination of CuONPs and SEO may be useful in food packaging.

Effects of suboptimal growth conditions on the subsequent UV-C resistance of Listeria monocytogenes in coconut liquid endosperm and apple juice

This study determined the ultraviolet-C (UVC) resistance of Listeria monocytogenes in coconut liquid endosperm and apple juice after previous exposures to suboptimal growth conditions. L. monocytogenes 1/2c and 4b strains were individually exposed to gradual acidification (final pH 4.5), desiccation (aw 0.96), heating (40 °C), and all their simultaneous combinations. Results showed that regardless of prior growth conditions and fruit beverage suspending medium, L. monocytogenes exhibited log-linear inactivation behavior. The UV-C energy dose necessary to reduce microbial population by 1 log cycle (DUV-C) varied across growth conditions and between fruit beverages. Regardless of growth condition, L. monocytogenes exhibited greater resistance in apple juice. In coconut liquid endosperm, the greatest UV-C resistance was observed in cells previously exposed to acidification and heat (A+H) (DUV-C 37.32 mJ/cm2), while cells previously exposed to acidification and desiccation (A+D) exhibited the greatest resistance to UV-C in apple juice (DUV-C 726.76 mJ/cm2). L. monocytogenes exhibited least UV-C resistance in coconut when previously exposed to heating (DUV-C 25.40 mJ/cm2), while exposure to A+H resulted in least UV-C resistance when suspended in apple juice (DUV-C 298.81 mJ/cm2). These results suggest that in addition to intrinsic suspending medium properties, implicit microbial physiology also affect the efficacy of UV-C treatment.

Experimental Warming Differentially Influences the Vulnerability of Phototrophic and Heterotrophic Periphytic Communities to Copper Toxicity.

Aquatic ecosystems are generally subjected to multiple perturbations due to simultaneous or successive combinations of various natural and anthropogenic environmental pressures. To better assess and predict the resulting ecological consequences, increasing attention should be given to the accumulation of stresses on freshwater ecosystems and its effects on the vulnerability of aquatic organisms, including microbial communities, which play crucial functional roles. Here we used a microcosm study to assess the influence of an experimental warming on the vulnerability of phototrophic and heterotrophic periphytic communities to acute and chronic copper (Cu) toxicity. Natural periphytic communities were submitted for 4 weeks to three different temperatures (18, 23, and 28°C) in microcosms contaminated (at about 15 μg L-1) or not with Cu. The vulnerability of both phototrophic and heterotrophic microbial communities to subsequent acute Cu stress was then assessed by measuring their levels of sensitivity to Cu from bioassays targeting phototrophic (photosynthetic activity) and heterotrophic (β-glucosidase and leucine aminopeptidase extracellular enzymatic activities) microbial functions. We postulated that both the increase in temperature and the chronic Cu exposure would modify microbial community structure, thus leading to changes in the capacity of phototrophic and heterotrophic communities to tolerate subsequent acute exposure to Cu. Our results demonstrated that the influence of temperature on the vulnerability of phototrophic and heterotrophic microbial communities to Cu toxicity can vary greatly according to function studied. These findings emphasize the importance of considering different functional compartments and different functional descriptors to better assess the vulnerability of periphyton to multiple stresses and predict the risks induced by multiple stressors for ecosystem balance and functioning.