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MIC-A and MIC-B are the natural ligands for NKG2D, an activator receptor expressed in NK cells. Soluble isoforms of MIC-A and MIC-B (sMICA, sMICB) have been identified in different malignancies, affecting NK cells’ cytotoxicity. The study was performed to determine the levels of sMICA, sMICB, the expression of MIC-A, and MIC-B on tumor tissues, and lymphocyte subpopulations (CD4 + , CD8 + , NK, NKT, Tγδ cells, B cells, monocytes) in 94 patients with non-Hodgkin's lymphoma (NHL) and 72 healthy donors.The most frequent lymphoma was diffuse large B cell lymphoma (48%). Patients with NHL had decreased numbers of CD4 T cells, CD8 T cells, B cells, monocytes, NK cells, type 1 dendritic cells, γδ T cells, and increased iNKT cells. Patients showed higher levels of sMIC-A and similar serum levels of sMIC-B.Survival was poorer in patients having higher LDH values and lower numbers of CD4 T cells, type 1 dendritic cells, gamma-delta T cells, and high levels of sMIC-A.In conclusion, high levels of sMIC and decreased numbers in circulating lymphocyte subsets are related to poor outcomes in NHL.

Microbiologically influenced corrosion (MIC) is caused by microbial biofilms. In this work, an oilfield produced water sample was analyzed using a newly developed disposable electrochemical biofilm/MIC test kit consisting of two solid-state electrodes in a 10 mL standard serum vial for assessing biofilm growth, biocorrosivity and biocide treatment efficacy. The produced water sample was found to be low in microbial cell counts and nutrients. To simulate a possible worst-case scenario, the produced water sample was subcultured at 37 °C using enriched artificial seawater (EASW) for 3 rounds before being used as the seed culture for further MIC and biocide tests. The electrochemical test results from the 10 mL biofilm/MIC test kit including polarization resistance (Rp) from linear polarization resistance scans and corrosion current density (icorr) from Tafel scans indicated a corrosion rate sequence of no biocide treatment > 20 ppm (w/w) tetrakis hydroxymethyl phosphonium sulfate (THPS) > 50 ppm THPS. Rp was able to predict biofilm maturity time using the incubation time when Rp leveled off (i.e., time to reach maximum corrosivity). Two common electron transfer promotors were found to accelerate MIC in the test kit vial injection tests, pointing to extracellular electron transfer-MIC as the main mechanism. This observation was consistent with the 30% corrosive sulfate reducers among all microbes in the mixed culture sample found by metagenomics. In the coupon incubation tests in 125 mL anaerobic vials, the 7-d X60 carbon steel weight loss was 1.1 ± 0.2 mg/cm2 (2.9 mpy uniform corrosion rate) without biocide treatment. With 20 ppm THPS biocide in EASW, it dropped to 0.5 ± 0.2 mg/cm2 (1.3 mpy), and with 50 ppm THPS, it became negligible. The corresponding MIC pit depths were 10.5, 8.9 μm, and no well-defined pits, respectively for the three biocide treatment conditions. The weight loss data confirmed the corrosion rate sequence from the biofilm/MIC test kit. This work presents a new MIC monitoring and biocide treatment assessment system for oilfield applications using the new biofilm/MIC test kit.

In addition to the maximum plasma concentration (C ) to the minimum inhibitory concentration (MIC) ratio, the 24-hour area under the concentration-time curve (AUC ) to MIC has recently been suggested as pharmacokinetic/pharmacodynamic (PK/PD) targets for efficacy and safety in once-daily dosing of gentamicin (ODDG) in critically ill patients. This study aimed to predict the optimal effective dose and risk of nephrotoxicity for gentamicin in critically ill patients for two different PK/PD targets within the first 3 days of infection. The gathered pharmacokinetic and demographic data in critically ill patients from 21 previously published studies were used to build a one-compartment pharmacokinetic model. The Monte Carlo Simulation (MCS) method was conducted with the use of gentamicin once-daily dosing ranging from 5-10 mg/kg. The percentage target attainment (PTA) for efficacy, C /MIC ~8-10 and AUC /MIC ≥110 targets, were studied. The AUC >700 mg⋅h/L and C >2 mg/L were used to predict the risk of nephrotoxicity. Gentamicin 7 mg/kg/day could achieve both efficacy targets for more than 90% when the MIC was <0.5 mg/L. When the MIC increased to 1 mg/L, gentamicin 8 mg/kg/day could reach the PK/PD and safety targets. However, for pathogens with MIC ≥2 mg/L, no studied gentamicin doses were sufficient to reach the efficacy target. The risk of nephrotoxicity using AUC >700 mg⋅h/L was small, but the risk was greater when applying a C target >2 mg/L. Considering both targets of Cmax/MIC ~8-10 and AUC /MIC ≥110, an initial gentamicin dose of 8 mg/kg/day should be recommended in critically ill patients for pathogens with MIC of ≤1 mg/L. Clinical validation of our results is essential.

High concentrations of non-essential heavy metals/metalloids (arsenic, cadmium, and lead) in soils and irrigation water represent a threat to the environment, food safety, and human and animal health. Microbial bioremediation has emerged as a promising strategy to reduce the concentration of heavy metals in the environment due to the demonstrated ability of microorganisms, especially bacteria, to sequester and transform these compounds. Although several bacterial strains have been reported to be capable of remediation of soils affected by heavy metals, published information has not been comprehensively analyzed to date to recommend the most efficient microbial resources for application in bioremediation or bacterial-assisted phytoremediation strategies that may help improve plant growth and yield in contaminated soils. In this study, we critically analyzed eighty-five research articles published over the past 15 years, focusing on bacteria-assisted remediation strategies for the non-essential heavy metals, arsenic, cadmium, and lead, and selected based on four criteria: i) The bacterial species studied are part of a plant microbiome, i.e., they interact closely with a plant species ii) these same bacterial species exhibit plant growth-promoting characteristics, iii) bacterial resistance to the metal(s) is expressed in terms of the Minimum Inhibitory Concentration (MIC), and iv) metal resistance is related to biochemical or molecular mechanisms. A total of sixty-two bacterial genera, comprising 424 bacterial species/strains associated with fifty plant species were included in our analysis. Our results showed a close relationship between the tolerance level exhibited by the bacteria and metal identity, with lower MIC values found for cadmium and lead, while resistance to arsenic was widespread and significantly higher. In-depth analysis of the most commonly evaluated genera, Agrobacterium, Bacillus, Klebsiella, Enterobacter, Microbacterium, Pseudomonas, Rhodococcus, and Mesorhizobium showed significantly different tolerance levels among them and highlighted the deployment of different biochemical and molecular mechanisms associated with plant growth promotion or with the presence of resistance genes located in the cad and ars operons. In particular, the genera Klebsiella and Enterobacter exhibited the highest levels of cadmium and lead tolerance, clearly supported by molecular and biochemical mechanisms; they were also able to mitigate plant growth inhibition under phytotoxic metal concentrations. These results position Klebsiella and Enterobacter as the best potential candidates for bioremediation and bacteria-assisted phytoremediation strategies in soils contaminated with arsenic, cadmium, and lead.

Inefficiency of medical therapies used in order to cure patients with bacterial infections requires not only to actively look for new therapeutic strategies but also to carefully select antibiotics based on variety of parameters, including microbiological. Minimal inhibitory concentration (MIC) defines in vitro levels of susceptibility or resistance of specific bacterial strains to applied antibiotic. Reliable assessment of MIC has a significant impact on the choice of a therapeutic strategy, which affects efficiency of an infection therapy. In order to obtain credible MIC, many elements must be considered, such as proper method choice, adherence to labeling rules, and competent interpretation of the results. In this paper, two methods have been discussed: dilution and gradient used for MIC estimation. Factors which affect MIC results along with the interpretation guidelines have been described. Furthermore, opportunities to utilize MIC in clinical practice, with pharmacokinetic /pharmacodynamic parameters taken into consideration, have been investigated. Due to problems related to PK determination in individual patients, statistical estimation of the possibility of achievement of the PK/PD index, based on the Monte Carlo, was discussed. In order to provide comprehensive insights, the possible limitations of MIC, which scientists are aware of, have been outlined.

Acquired resistance is an important driver of multidrug-resistant tuberculosis (TB), even with good treatment adherence. However, exactly what initiates the resistance and how it arises remain poorly understood. To identify the relationship between drug concentrations and drug susceptibility readouts (minimum inhibitory concentrations [MICs]) in the TB cavity. We recruited patients with medically incurable TB who were undergoing therapeutic lung resection while on treatment with a cocktail of second-line anti-TB drugs. On the day of surgery, antibiotic concentrations were measured in the blood and at seven prespecified biopsy sites within each cavity. Mycobacterium tuberculosis was grown from each biopsy site, MICs of each drug identified, and whole-genome sequencing performed. Spearman correlation coefficients between drug concentration and MIC were calculated. Fourteen patients treated for a median of 13 months (range, 5-31 mo) were recruited. MICs and drug resistance-associated single-nucleotide variants differed between the different geospatial locations within each cavity, and with pretreatment and serial sputum isolates, consistent with ongoing acquisition of resistance. However, pretreatment sputum MIC had an accuracy of only 49.48% in predicting cavitary MICs. There were large concentration-distance gradients for each antibiotic. The location-specific concentrations inversely correlated with MICs (P < 0.05) and therefore acquired resistance. Moreover, pharmacokinetic/pharmacodynamic exposures known to amplify drug-resistant subpopulations were encountered in all positions. These data inform interventional strategies relevant to drug delivery, dosing, and diagnostics to prevent the development of acquired resistance. The role of high intracavitary penetration as a biomarker of antibiotic efficacy, when assessing new regimens, requires clarification.

Curcumin, a principal bioactive substance of turmeric (Curcuma longa L.), is reported as a strong antioxidant, anti-inflammatory, antibacterial, antifungal, and antiviral agent. However, its antimicrobial properties require further detailed investigations into clinical and multidrug-resistant (MDR) isolates. In this work, we tested curcumin’s efficacy against over 100 strains of pathogens belonging to 19 species. This activity was determined by the broth microdilution method and by calculating the minimum inhibitory concentration (MIC). Our findings confirmed a much greater sensitivity of Gram-positive than Gram-negative bacteria. This study exhibited a significantly larger variation in the curcumin activity than previous works and suggested that numerous clinical strains of widespread pathogens have a poor sensitivity to curcumin. Similarly, the MICs of the MDR types of Staphylococcus aureus, S. haemolyticus, Escherichia coli, and Proteus mirabilis were high (≥2000 µg/mL). However, curcumin was effective against some species and strains: Streptococcus pyogenes (median MIC = 31.25 µg/mL), methicillin-sensitive S. aureus (250 µg/mL), Acinetobacter lwoffii (250 µg/mL), and individual strains of Enterococcus faecalis and Pseudomonas aeruginosa (62.5 µg/mL). The sensitivity of species was not associated with its affiliation to the genus, and it could differ a lot (e.g., S. pyogenes, S. agalactiae and A. lwoffii, A. baumannii). Hence, curcumin can be considered as a promising antibacterial agent, but with a very selective activity.

Polymeric hydrogels are common dosage forms designed for the topical administration of antimicrobial drugs to treat vaginal infections. One of the major advantages of using chitosan in these formulations is related to the intrinsic and broad antimicrobial activity exerted on bacteria and fungi by this natural polymer. Most vaginal yeast infections are caused by the pathogenic fungus Candida albicans. However, despite the anti-Candida activity towards and strains susceptibility to low molecular weight chitosan being documented, no information is available regarding the antimicrobial efficacy of mixed hydrogels in which chitosan is dispersed in a polymeric matrix. Therefore, the aim of the study is to evaluate the anti-Candida activity against eight different albicans and non-albicans strains of a mixed hydroxypropyl methylcellulose (HPMC)/chitosan hydrogel. Importantly, chitosan was dispersed in HPMC matrix either assembled in nanoparticles or in a monomolecular state to eventually correlate any variation in terms of rheological and mucoadhesive properties, as well as anti-Candida activity, with the chitosan form. Hydrogels containing 1% w/w chitosan, either as free polymer chain or assembled in nanoparticles, showed an improved mucoadhesiveness and an anti-Candida effect against all tested albicans and non-albicans strains. Overall, the results demonstrate the feasibility of preparing HPMC/CS mixed hydrogels intended for the prevention and treatment of Candida infections after vaginal administration.

Uropathogenic Escherichia coli (UPEC) is a primary cause of urinary tract infections (UTIs), with recurrent cases often linked to its ability to form biofilms. This study investigated the effects of various antibiotics on UPEC biofilm formation and the subsequent interaction of these biofilms/their supernatants with human neutrophils. We determined the minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC), and biofilm eradication concentrations (MBEC) for ampicillin, gentamicin, chloramphenicol, ciprofloxacin, and levofloxacin. Our results showed an increase in MBEC compared to MBC for all tested antibiotics, confirming the enhanced antibiotic resistance of bacteria in biofilm. We found that sub-MICs of ciprofloxacin, which moderately inhibited planktonic growth, actually stimulated an increase in biofilm biomass. This antibiotic-induced biofilm growth was accompanied by changes in bacterial morphology, including the formation of elongated, filamentous cells, an adaptive stress response. Biofilm-embedded bacteria, but not their supernatants, significantly reduced neutrophil viability, primarily by inducing neutrophil necrosis. The presence of ciprofloxacin during biofilm formation did not fundamentally alter interactions with neutrophils. These findings highlight the importance of studying effects of antibiotic pressure on biofilm formation, underscoring the challenges in antibiotic treatment of UTIs.

Staphylococcus aureus (S. aureus) is a Gram-positive bacteria considered one of the leading causes of community and hospital-acquired illnesses or public health concerns. Antibiotic resistance in this microorganism is one of the greatest issues in global health care. The use of metal nanoparticles and their oxides is one of the potential approaches to combating bacteria resistance to antibiotics. The antibacterial properties of ZnO NPs against enterotoxigenic S. aureus were studied. ZnO NPs were tested in vitro by agar diffusion test. They resulted in 26 and 22 mm zones of inhibition for a size of 20 nm and a concentration of 20 mM against 105 and 107 CFU/mL S. aureus, respectively. The MIC of ZnO NPs of various sizes, 20 and 50 nm, with 105 CFU/mL was 2.5 and 5 mM, respectively. MIC with 107 CFU/mL was five mM for 20 and 50 nm ZnO NPs. Further, the highest growth reduction percentage, 98.99% in the counts of S. aureus was achieved by ZnO NPs of size 20 nm and concentration of 10 mM. Moreover, the obtained ELISA results indicated a significantly decreased concentration of enterotoxin A with all concentrations and sizes of ZnO NPs. PCR analysis showed a significant effect on sea gene in response to ZnO NPs treatments leading to loss of the gene, unlike the unaffected nuc gene. Moreover, morphological changes and cell shape distortion were detected by scanning electron microscope for bacterial cells treated with ZnO NPs.