Gauging circadian variation in ketamine metabolism by real-time breath analysis

The time-of-day of drug application is an important factor in maximizing efficacy and minimizing toxicity. Real-time in vivo mass spectrometric breath analysis of mice was deployed to investigate time-of-day variation in ketamine metabolism. Different production rates of ketamine metabolites, including the recently described anti-depressant hydroxynorketamine, were found in opposite circadian phases. Thus, breath analysis has potential as a rapid and 3Rs (Replacement, Reduction and Refinement) conforming screening method to estimate the time-dependence of drug metabolism

Learning a Battery of COVID-19 Mortality Prediction Models by Multi-objective Optimization

The COVID-19 pandemic is continuously evolving with drastically changing epidemiological situations which are approached with different decisions: from the reduction of fatalities to even the selection of patients with the highest probability of survival in critical clinical situations. Motivated by this, a battery of mortality prediction models with different performances has been developed to assist physicians and hospital managers. Logistic regression, one of the most popular classifiers within the clinical field, has been chosen as the basis for the generation of our models. Whilst a standard logistic regression only learns a single model focusing on improving accuracy, we propose to extend the possibilities of logistic regression by focusing on sensitivity and specificity. Hence, the log-likelihood function, used to calculate the coefficients in the logistic model, is split into two objective functions: one representing the survivors and the other for the deceased class. A multi-objective optimization process is undertaken on both functions in order to find the Pareto set, composed of models not improved by another model in both objective functions simultaneously. The individual optimization of either sensitivity (deceased patients) or specificity (survivors) criteria may be conflicting objectives because the improvement of one can imply the worsening of the other. Nonetheless, this conflict guarantees the output of a battery of diverse prediction models. Furthermore, a specific methodology for the evaluation of the Pareto models is proposed. As a result, a battery of COVID-19 mortality prediction models is obtained to assist physicians in decision-making for specific epidemiological situations.This research is supported by the Basque Government (IT1504- 22, Elkartek) through the BERC 2022–2025 program and BMTF project, and by the Ministry of Science, Innovation and Universities: BCAM Severo Ochoa accreditation SEV-2017-0718 and PID2019-104966GB-I00. Furthermore, the work is also supported by the AXA Research Fund project “Early prognosis of COVID-19 infections via machine learning”

Solid and Aqueous Speciation of Yttrium in Passive Remediation Systems of Acid Mine Drainage

International audienceYttrium belongs to the rare earth elements (REEs) together with lanthanides and scandium. REEs are commonly used in modern technologies, and their limited supply has made it necessary to look for new alternative resources. Acid mine drainage (AMD) is a potential resource since it is moderately enriched in REEs. In fact, in passive remediation systems, which are implemented to minimize the environmental impacts of AMD, REEs are mainly retained in basaluminite, an aluminum hydroxysulfate precipitate. In this study, the solid and liquid speciation and the local structure of yttrium are studied in high-sulfate aqueous solutions, basaluminite standards, and samples from remediation columns using synchrotron-based techniques and molecular modeling. Pair distribution function (PDF) analyses and ab initio molecular dynamics density functional theory models of the yttrium sulfate solution show that the YSO4+ ion pair forms a monodentate inner-sphere complex. Extended X-ray absorption fine structure (EXAFS) and PDF analyses show that Y is retained by basaluminite, forming a monodentate inner-sphere surface complex on the aluminum hydroxide surface. EXAFS of the column samples shows that more than 72% of their signal is represented by the signal of basaluminite with which YSO4+ forms an inner-sphere complex. The atomic view of the REE configuration in AMD environments could facilitate a deeper research of REE recovery from waste generated in AMD remediation systems

Development of antimicrobial chitosan based nanofiber dressings for wound healing applications

Objective(s): Chitosan based composite fine fibers were successfully produced via a centrifugal spinning technology. This study evaluates the ability of the composites to function as scaffolds for cell growth while maintaining an antibacterial activity. Materials and Methods: Two sets of chitosan fiber composites were prepared, one filled with anti-microbial silver nanoparticles and another one with cinnamaldeyhde. Chitosan powder was dissolved in trifluoroacetic acid and dichloromethane followed by addition of the fillers. The fiber output was optimized by configuring the polymer weight concentration (7, 8, and 9 w/w% chitosan) and applied angular velocity (6000-9000 RPM) within the spinning process. Results: Scanning electron microscopy revealed fiber diameters ranging from 800-1500 nm. Cinnamaldehyde and silver nanoparticles helped to improve and control the anti-bacterial activity. Through a verified cell counting method and disk diffusion method, it was proven that the chitosan based composite fibers possess an enhanced anti-bacterial/microbial activity against gram-positive Staphylococcus aureus. Both composite systems showed anti-bacterial activity, inhibition zones fluctuating between 5 to 10 mm were observed depending on the size of the fiber mat and no bacteria was found within the mats. The developed fiber scaffolds were found to be noncytotoxic serving as effective three-dimensional substrates for cell adhesion and viability. Conclusion: These results provide potential to use these scaffolds in wound healing and tissue regeneration applications

The Mediterranean diet protects against waist circumference enlargement in 12Ala carriers for the PPARgamma gene: 2 years' follow-up of 774 subjects at high cardiovascular risk.

The PPARgamma gene regulates insulin sensitivity and adipogenesis. The Pro12Ala polymorphism of this gene has been related to fat accumulation. Our aim was to analyse the effects of a 2-year nutritional intervention with Mediterranean-style diets on adiposity in high-cardiovascular risk patients depending on the Pro12Ala polymorphism of the PPARgamma gene. The population consisted of a substudy (774 high-risk subjects aged 55-80 years) of the Prevención con Dieta Mediterránea (PREDIMED) randomised trial aimed at assessing the effect of the Mediterranean diet for CVD prevention. There were three nutritional intervention groups: two of them of a Mediterranean-style diet and the third was a control group advised to follow a conventional low-fat diet. All the participants were genotyped by PCR-restriction fragment length polymorphism (RFLP). The results showed that carriers of the 12Ala allele allocated to the control group had a statistically significant higher change in waist circumference (adjusted difference coefficient = 2.37 cm; P = 0.014) compared with wild-type subjects after 2 years of nutritional intervention. This adverse effect was not observed among 12Ala carriers allocated to both Mediterranean diet groups. In diabetic patients a statistically significant interaction between Mediterranean diet and the 12Ala allele regarding waist circumference change was observed ( - 5.85 cm; P = 0.003). In conclusion, the Mediterranean diet seems to be able to reduce waist circumference in a high-cardiovascular risk population, reversing the negative effect that the 12Ala allele carriers of the PPARgamma gene appeared to have. The beneficial effect of this dietary pattern seems to be higher among type 2 diabetic subjects

Phase imaging with intermodulation atomic force microscopy

Intermodulation atomic force microscopy (IMAFM) is a dynamic mode of atomic force microscopy (AFM) with two-tone excitation. The oscillating AFM cantilever in close proximity to a surface experiences the nonlinear tip-sample force which mixes the drive tones and generates new frequency components in the cantilever response known as intermodulation products (IMPs). We present a procedure for extracting the phase at each IMP and demonstrate phase images made by recording this phase while scanning. Amplitude and phase images at intermodulation frequencies exhibit enhanced topographic and material contrast.Comment: 6 pages, 6 page

Compressive Review about Taxol: History and Future Challenges

© 2020. The authors. This document is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by /4.0/ This document is the Published version of a Published Work that appeared in final form in Molecules. To access the final edited and published work see DOI: 10.3390/molecules25245986Taxol®, which is also known as paclitaxel, is a chemotherapeutic agent widely used to treat different cancers. Since the discovery of its antitumoral activity, Taxol® has been used to treat over one million patients, making it one of the most widely employed antitumoral drugs. Taxol® was the first microtubule targeting agent described in the literature, with its main mechanism of action consisting of the disruption of microtubule dynamics, thus inducing mitotic arrest and cell death. However, secondary mechanisms for achieving apoptosis have also been demonstrated. Despite its wide use, Taxol® has certain disadvantages. The main challenges facing Taxol® are the need to find an environmentally sustainable production method based on the use of microorganisms, increase its bioavailability without exerting adverse effects on the health of patients and minimize the resistance presented by a high percentage of cells treated with paclitaxel. This review details, in a succinct manner, the main aspects of this important drug, from its discovery to the present day. We highlight the main challenges that must be faced in the coming years, in order to increase the effectiveness of Taxol® as an anticancer agent