Improved delivery of voriconazole to Aspergillus fumigatus through solid lipid nanoparticles as an effective carrier

Novel voriconazole-loaded solid lipid nanoparticles (VRC-SLNs) were prepared via probe-ultrasonication method, and the resultant nanoparticles were tested on A. fumigatus. Voriconazole-loaded solid lipid nanoparticles were prepared using the probe ultrasonication technique. Photon correlation spectroscopy (PCS) was used to determine the average particle size and zeta potential of SLN formulations. Transmission electron microscopy was also used to determine the morphology of solid lipid nanoparticles. To determine MIC for all SLN formulations against strains of Aspergillus the Clinical and Laboratory Standards Institute guidelines was followed. The results showed that SLNs containing voriconazole exhibited almost spherical shape with a diameter and zeta potential of 286.6 ± 4.7 nm and −15 ± 4.1 mV respectively. This novel formulation of VRC led to a significant reduction in MICs for all Aspergillus either VRC-susceptible or VRC-resistant isolates (P < 0.05). The MIC50 drug concentration was obtained as 0.015 μg/ml for both VRC-susceptible strains of A. fumigates while it was 0.25 μg/ml against VRC (p < 0.05). VRC-resistant strains showed a MIC50 of 0.015 μg/ml as well. These novel drug formulations may increase the bioavailability through an increase in the dissolution rate of voriconazole. This study showed, for the first time, VRC-SLNs can be employed as an effective delivery systems for VRC on A. fumigatus isolates

Caspian Sea Mycosands: The Variety and Abundance of Medically Important Fungi in Beach Sand and Water

Samples from a total of 67 stations, distributed amongst 32 cities along the Caspian Sea coastline, were collected during the summer of 2021 on sunny days. The samples were collected from each station, including both dry/wet sand and shoreline water. The grown samples were primarily analyzed for the macro/microscopic morphologic features of the fungi. Moreover, identification by PCR-RFLP was performed for yeasts, dermatophytes, and Aspergillus sp. strains. Antifungal susceptibility tests were performed for probable-isolated Aspergillus and Candida sp. A total of 268 samples were collected, from which 181 (67.54%) isolates were recovered. Yeast-like fungi and potential pathogenic black fungi were detected in 12 (6.6%) and 20 (11%) of the sand (dry/wet) samples. Potential pathogenic hyaline fungi were identified in 136 (75.1%) samples, in which Aspergillus sp. was the predominant genus and was detected in 76/136 (47.8%) samples as follows: A. section Flavi n = 44/76 (57.9%), A. section Nigri n = 19/76 (25%), A. section Nidulantes n = 9/76 (11.8%), and A. section Fumigati n = 4/76 (5.3%). The most effective azole antifungal agent was different per section: in A. section Fumigati, PSZ; in Aspergillus section Nigri, ITZ and ISZ; in A. section Flavi, EFZ; and in A. section Nidulantes, ISZ. Candida isolates were susceptible to the antifungals tested.Authors wish to thank Mazandaran University of Medical Sciences for the financial support.info:eu-repo/semantics/publishedVersio

Improved yeast delivery of fluconazole with a nanostructured lipid carrier system

Despite the growing trends in the number of patients at risk for invasive fungal infections, management with current antifungal agents results in complications due to changes in the epidemiology and drug susceptibility of invasive fungal infections. In the present research fluconazole-loaded nanostructured lipid carriers were prepared using probe ultrasonication techniques and investigated the efficacy of the optimal formulation on a large number of Candida species. The morphology of the obtained nanostructured lipid carriers was characterized by transmission-electron microscopy. The minimum inhibitory concentrations (MIC) for the new formulations against strains of Candida were investigated using the Clinical and Laboratory Standards Institute document M27-A3 and M27-S4 as a guideline. The fluconazole-loaded nanostructured lipid carriers presented a spherical shape with a mean diameter, zeta potential and entrapment efficiency of 126.4 ± 15.2 nm, −35.1 ± 3.0 mV, and 93.6 ± 3.5%, respectively. The drug release from fluconazole-loaded nanostructured lipid carriers exhibited burst-release behavior at the initial stage followed by sustained release over 24 h. Using a new formulation of fluconazole led to a significant decrease in MICs for all Candida groups (P < 0.05). Furthermore, C. albicans isolates showed more susceptibility to fluconazole-loaded nanostructured lipid carriers than C. glabrata and C. parapsilosis (P < 0.05). The MIC50 drug concentration was obtained as 0.0625, 0.031 and 0.25 μg/ml for fluconazole-resistant strains of C. albicans, C. glabrata, and C. parapsilosis, respectively. In conclusion, a novel delivery system which can be used as part of a strategy to improve the antifungal activity of fluconazole against various Candida strains with different susceptibilities to conventional formulations of fluconazole was evaluated

Evaluation of Candida colonization index, molecular identification, and antifungal susceptibility pattern of Candida species isolated from critically ill pediatric patients: A singlecenter study in Iran

Background and Purpose: Given the high mortality rate of invasive candidiasis inhospitalized pediatric patients, it is crucial to establish a predictive system to achieveearly diagnosis and treatment of patients who are likely to benefit from early antifungal treatment. This study aimed to assess the Candida colonization index, species distribution, and antifungal susceptibility pattern of Candida strains isolated frompediatric patients with high Candida colonization index (CI)Materials and Methods: This study was carried out at the Children’s Medical Center inTehran-Iran. In total, 661 samples were collected from 83 patients. The Candida CI wascalculated according to the descriptions of previous studies. The isolates were identified using polymerase chain reaction-based techniques. The Clinical and Laboratory Standard Institute protocol M60 was used to conduct the antifungal susceptibility test.Results: A colonization index greater than 0.5 was confirmed in 29 cases (58% ofpositive samples) with two children developing candidemia. Candida albicans (n=53,49.5%) was the most common Candida species in patients with CI > 0.5. Except foracute lymphoblastic leukemia, no risk factors were linked to a high index in colonizedchildren (P > 0.05). Twelve isolates (7.01%) were multi-azole resistant with high MICsagainst both isavuconazole and ravuconazole and seven strains (4.09%) wereechinocandins resistant.Conclusion: In pediatric intensive care units, patients are at risk of fungal infection,particularly candidemia. In this study, more than half of the children with positive yeastcultures had CI > 0.5, and 6.8% developed candidemia

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| &lt; 0.03 at 95% confidence level. [Figure not available: see fulltext.

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe

An embedding technique to determine ττ backgrounds in proton-proton collision data

An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Measurement of prompt open-charm production cross sections in proton-proton collisions at root s=13 TeV

The production cross sections for prompt open-charm mesons in proton-proton collisions at a center-of-mass energy of 13TeV are reported. The measurement is performed using a data sample collected by the CMS experiment corresponding to an integrated luminosity of 29 nb(-1). The differential production cross sections of the D*(+/-), D-+/-, and D-0 ((D) over bar (0)) mesons are presented in ranges of transverse momentum and pseudorapidity 4 < p(T) < 100 GeV and vertical bar eta vertical bar < 2.1, respectively. The results are compared to several theoretical calculations and to previous measurements.Peer reviewe