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Background/objectives: Patients with relapsed/refractory (R/R) AML with FLT3 mutation ( FLT3 mut ) have a dismal prognosis. FLT3 mut offers a target for therapy in these patients. Gilteritinib (gilter) and quizartinib (quizar) have demonstrated efficacy as single agents in two phase 3 clinical trials., Methods: We retrospectively analyzed the characteristics, treatments, and outcomes of 50 patients with R/R FLT3 mut AML who received gilter or quizar as monotherapy in 27 Spanish centers before their commercial availability. Forty-four patients were treated with gilter and six with quizar., Results: The median age was 62.5 years, and 52% were women. Most patients presented with FLT3 -ITD mutations (80%); 46% had refractory disease and 54% had relapsed disease at treatment initiation. First-line treatment was chemotherapy in 80% of patients, with 40% of these also receiving midostaurin. Twenty-five patients (50%) had previously received FLT3 inhibitor, and twenty-eight (56%) had received more than one line treatment before starting gilter/quizar. The rates of complete remission (CR), CR without hematological recovery (CRi), and partial remission were 22%, 18%, and 16%, respectively. The median overall survival (OS) and disease-free survival were 4.74 months and 2.99 months, respectively. We observed a significant improvement in OS in patients who had received only one prior line of therapy compared to those who had received two or more therapies (10.77 months vs. 4.24 months, p = 0.016). Multivariate analysis identified failure to achieve CR/CRi, receiving more than one prior line of therapy, age, and white blood cells count as independent prognostic factors for OS. The most common toxicities were febrile neutropenia, liver function abnormalities, and QT interval prolongation., Conclusions: Gilter/quizar monotherapy are effective and tolerable options for patients with R/R FLT3 mut AML in a real-world setting. Response and toxicity rates are similar to those reported in the phase 3 trials, despite the more heterogeneous nature of the study population.

In the industrial corridor of Boyacá, Colombia, population growth is accompanied by anthropogenic activities such as industrial operations, vehicle exhaust fumes, mining, smelting, atmospheric deposition, and excessive use of chemical products to promote crop growth. These activities are known to have a significant impact on urban and rural soils, contributing significantly to elevated concentrations of potentially hazardous elements in the environment. This industrial corridor is an area of economic and social development that needs to provide reference information that will allow us to know the state of soil quality to preserve and manage the public and geoenvironmental health of this region. Anthropogenic activities have contributed to the accumulation of potentially hazardous elements in the environment, affecting various levels of life and creating risks with economic and social implications. However, igneous activity or detrital deposition also enriches soils and creates geochemical anomalies in specific locations. In these cases, the identification of potentially hazardous elements involves the determination of likely sources of contamination and their relationship to the geological setting. In this study, the concentrations of As, Cd, Pb, Mn, Fe, Zn, Hg, Cu and Ni were determined in eighty-one soil samples from the Boyacá industrial corridor (Colombia). The sequential trend of the concentrations of potentially hazardous elements was as follows: Fe > Mn > Zn > Ni > Cu> Pb > As > Cd > Hg. Furthermore, the application of spatial analysis criteria in GIS software with multivariate statistical tools and geochemical indices allowed the identification of anthropogenic and geogenic sources. Most of the potentially hazardous elements were found in soils exposed to industrial and agricultural activities, except for iron. This element showed low variability in all samples, regardless of the geological formations. Due to the lack of reference values for potentially hazardous elements in Colombia, the concentrations were compared with the environmental standards of the Environmental Protection Agency (EPA) and the Ecuadorian Ministry of Environment, Water and Ecological Transition (MAE). The results demonstrate the complexity of the soil and represent the first exploratory study of potentially hazardous elements in this industrial corridor. These results are the starting point for the establishment of geochemical background lines in Colombia and for inspection policies for areas where productive activities converge., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The presence of >94% classical monocytes (MO1, CD14++/CD16-) in peripheral blood (PB) has an excellent performance for the diagnosis of chronic myelomonocytic leukemia (CMML). However, the monocyte gating strategy is not well defined. The objective of the study was to compare monocyte gating strategies and propose an optimal one., Methods: This is a prospective, single center study assessing monocyte subsets in PB. First, we compared monocyte subsets using 13 monocyte gating strategies in 10 samples. Then we developed our own 10 color tube and tested it on 124 patients (normal white blood cell counts, reactive monocytosis, CMML and a spectrum of other myeloid malignancies). Both conventional and computational (FlowSOM) analyses were used., Results: Comparing different monocyte gating strategies, small but significant differences in %MO1 and percentually large differences in %MO3 (nonclassical monocytes) were found, suggesting that the monocyte gating strategy can impact monocyte subset quantification. Then, we designed a 10-color tube for this purpose (CD45/CD33/CD14/CD16/CD64/CD86/CD300/CD2/CD66c/CD56) and applied it to 124 patients. This tube allowed proper monocyte gating even in highly abnormal PB. Computational analysis found a higher %MO1 and lower %MO3 compared to conventional analysis. However, differences between conventional and computational analysis in both MO1 and MO3 were globally consistent and only minimal differences were observed when comparing the ranking of patients according to %MO1 or %MO3 obtained with the conventional versus the computational approach., Conclusions: The choice of monocyte gating strategy appears relevant for the monocyte subset distribution test. Our 10-color proposal allowed satisfactory monocyte gating even in highly abnormal PB. Computational analysis seems promising to increase reproducibility in monocyte subset quantification., (© 2022 International Clinical Cytometry Society.)

Microplastic (MP)-colonizing microorganisms are important links for the potential impacts on environmental, health, and biochemical circulation in various ecosystems but are not yet well understood. In addition, biofilms serve as bioindicators for the evaluation of pollutant effects on ecosystems. This study describes the ability of three polyethylene-type microplastics, white (W-), blue (B-), and fluorescent blue (FB-) MPs, to support microbial colonization of Pseudomonas aeruginosa, the effect of mixed organic contaminants (OCs: amoxicillin, ibuprofen, sertraline, and simazine) on plastic-associated biofilms, and the role of biofilms as transfer vectors of such emerging pollutants. Our results showed that P. aeruginosa had a strong ability to produce biofilms on MPs, although the protein amount of biomass formed on FB-MP was 1.6- and 2.4-fold higher than that on B- and W-MP, respectively. When OCs were present in the culture medium, a decrease in cell viability was observed in the W-MP biofilm (65.0%), although a general impairing effect of OCs on biofilm formation was ruled out. Microbial colonization influenced the ability of MPs to accumulate OCs, which was higher for FB-MP. In particular, the sorption of amoxicillin was lower for all bacterial-colonized MPs than for the bare MPs. Moreover, we analysed oxidative stress production to assess the impact of MPs or MPs/OCs on biofilm development. The exposure of biofilms to OCs induced an adaptive stress response reflected in the upregulation of the katB gene and ROS production, particularly on B- and FB-MP. This study improves our understanding of MP biofilm formation, which modifies the ability of MPs to interact with some organic pollutants. However, such pollutants could hinder microbial colonization through oxidative stress production, and thus, considering the key role of biofilms in biogeochemical cycles or plastic degradation, the co-occurrence of MPs/OCs should be considered to assess the potential risks of MPs in the environment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The globalization of the market, as well as the increasing world population, which require a higher demand for food products, pose a great challenge to ensure food safety and prevent food loss and waste. In this sense, active materials with antibacterial properties are an important alternative in the prolongation of shelf life and ensuring food safety. In this work, the ability of copper(II) hydroxy nitrate (CuHS) to obtain antibacterial films based on low density polyethylene (LDPE) and polylactic acid (PLA), was evaluated. The thermal properties of the composites, evaluated using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), showed that the concentrations of added CuHS do not particularly change these characteristics with respect to the neat polymer matrix films. The mechanical properties, determined using dynamic mechanical analysis (DMTA), indicate a small increase in the brittleness of the material in PLA-based composites. The antibacterial properties against Listeria monocytogenes and Salmonella enterica were evaluated using a surface contact test, and a bacterial reduction of at least 8 to 9 logarithmic units for the composites with 0.3% CuHS, both in LDPE and PLA and against both bacteria, were achieved. The reusability of the composite films after their first use demonstrated a higher stability against Listeria monocytogenes . The migration and cytotoxicity of the composites loaded with 0.3% CuHS was evaluated, demonstrating the safety of these materials, which reinforces their potential use in food packaging applications.

Enzyme immobilization on adequate carriers is a challenging strategy. Understanding the enzyme-carrier interactions and their effects on enzyme conformation and bioactivity is critical. In this study, a meso-macropores silica (MMS) was used to immobilize β-galactosidase from the yeast Kluyveromyces lactis (β-gal-KL) by physical adsorption. The bioactivity of the immobilized β-gal-KL was altered, evidenced by the increased K m , decreased V max and k cat , and increased activity at alkaline values. By performing infrared spectroscopy analysis and subsequent secondary structure assessment from the amide I band, the immobilized β-gal-KL suffered a β-sheet (∼31-35 %) to α-helix (∼15-19 %) transition with increased turns (∼21-22 %) with respect to the free β-gal-KL having ∼12 % α-helix, ∼42 % β-sheet, and ∼17 % turns. These findings led us to correlate the observed bioactivity performance to structural alterations to a non-native conformation. The presented line of thought can lead to a better understanding of the reasons causing bioactivity alterations upon enzyme immobilization., (© 2022 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)

The globalization of the market and the increase of the global population that requires a higher demand of food products superimposes a big challenge to ensure food safety. In this sense, a common strategy to extend the shelf life and save life of food products is by avoiding bacterial contamination. For this, the development of antibacterial contact surfaces is an urgent need to fulfil the above-mentioned strategy. In this work, the role of MXene (Ti 3 C 2 T x ) in providing antibacterial contact surfaces was studied through the creation of composite films from polylactic acid (PLA), as the chosen polymeric matrix. The developed PLA/MXene films maintained the thermal and mechanical properties of PLA and also presented the attractive antibacterial properties of MXene. The composites' behaviour against two representative foodborne bacteria was studied: Listeria mono-cytogenes and Salmonella enterica (representing Gram-positive and Gram-negative bacteria , respectively). The composites prevented bacterial growth, and in the case of Listeria only 0.5 wt.% of MXene was necessary to reach 99.9999% bactericidal activity (six log reductions), while against Salmonella , 5 wt.% was necessary to achieve 99.999% bactericidal activity (five log reductions). Cy-totoxicity tests with fHDF/TER166 cell line showed that none of the obtained materials were cytotoxic. These results make MXene particles promising candidates for their use as additives into a polymeric matrix, useful to fabricate antibacterial contact surfaces that could prove useful for the food packaging industry., Competing Interests: The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Decoration of matrices such as silicates, graphene, etc. is an efficient technique in order to develop multifunctional materials with enhanced properties, which are of use for microbial control. Consequently, it leads to an increased search for alternative matrices and synthesis methods for decoration. Herein, decoration of a fumed silica is proposed, with structures that consisted of silver (Ag@FS), copper hydroxy salt (CuHS@FS), and copper (Cu@FS), for antibacterial applications. With the simple combination of the metal precursor salt, the appropriate solvent, and the fumed silica, the composites were obtained by one-pot solvothermal (200 °C for 1 h), rapid (2 min) microwave assisted precipitation, and by ascorbic acid chemical reduction, respectively. Characterization by powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), and field emission scanning electron microscopy (FE-SEM) proved the successful decoration of the fumed silica with layered copper hydroxy salt (90 width x 970 length nm) and round-like metallic Ag (210 nm) and Cu (370 nm) particles. Fourier transformed infrared (FTIR) and Raman spectroscopy evidenced the presence of SiOMetal interactions. The antibacterial activity was evaluated against the Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, giving inhibition and bactericidal values between 3-12 mg/ mL and 12-24 mg/ mL, respectively, with a maximum ion liberation ratio of 1.4 %. The application of the fumed silica presented here, is an attractive alternative to existing matrices, in order to fabricate multifunctional materials, as it is ready-to-use and feasible for large-scale production. Moreover, the applied synthesis routes provide rapid approaches for decoration, creating composites useful for antibacterial applications., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Palbociclib is a specific inhibitor of cyclin-dependent kinases 4 and 6 that is approved for the treatment of advanced or metastatic breast cancer patients. Despite a good toxicity profile in pivotal trials, where asymptomatic neutropenia was the main adverse effect, its wider use in clinical practice may show less prevalent but serious toxicities., Case Presentation: Here, we describe a case of pneumonitis due to palbocicblib. A 57-year-old female with breast cancer with bone metastasis presented dyspnea at rest 3 months after beginning treatment with palbociclib and letrozole. Palbociclib-induced pneumonitis was considered the most probable cause after ruling out all alternatives, and the patient was successfully treated with steroids and showed complete remission., Conclusions: In summary, we present a well-documented case report of pneumonitis related to palbociclib. However, the mechanism of toxicity is still unknown, and there are as yet no reliable biomarkers to predict toxicity with cyclin-dependent kinase 4/6 inhibitors. In this case report, we alert physicians about new drugs that can provoke old toxicities., Competing Interests: E.F.: travel grant: Pfizer, Roche, Lilly, and Novartis. M.M.: travel grant: Celgene and Kern; consultant or advisory role: Novartis, Pfizer, Roche, and Kern; speakers bureau: Novartis. B.C.: travel grant: Roche, BMS, Eisai, Merck, and Pierre-Fabre; consultant or advisory role: BMS, Roche, Merck, and Eisai. V.Q.: travel grant: BMS, Roche, Novartis, and Pfizer; consultant or advisory role: Kern; speakers bureau: Roche and Eisai. M.R.: travel grant: Pfizer, MSD; consultant or advisory role: Tesaro, AstraZeneca, and Roche. L.L., C.P.-M., D.Q., I.T., I.G., C.C., and E.B. have no conflicts of interest to disclose., (Copyright © 2019 by S. Karger AG, Basel.)

The present work is dedicated to the analysis of dry heat exchanges as measured by a thermal manikin placed in still air. We believe that the understanding of some fundamental aspects governing fluid flow and heat transfer around three-dimensional bodies such as human beings deserves appropriate attention. This should be of great significance for improving physiological models concerned with thermal exposures. The potential interest of such work can be directed towards quite distinct targets such as working conditions, sports, the military, or healthcare personnel and patients. In the present study, we made use of a climate chamber and an articulated thermal manikin of the Pernille type, with 16 body parts. The most common occidental postures (standing, sitting and lying) were studied. In order to separate heat losses due to radiation and convection, the radiative heat losses of the manikin were significantly reduced by means of a shiny aluminium coating, which was carefully applied to the artificial skin. The air temperature within the test chamber was varied between 13 degrees C and 29 degrees C. The corresponding mean differences between the skin and the operative temperatures changed from 3.8 degrees C up to 15.8 degrees C. The whole-body heat transfer coefficients by radiation and convection for both standing and sitting postures are in good agreement with those in the published literature. The lying posture appears to be more efficient for losing heat by convection. This is confirmed when the heat losses of each individual part are considered. The proposed correlations for the whole body suggest that natural convection is mainly laminar.