Solid Tumors and Kinase Inhibition: Management and Therapy Efficacy Evolution

The increasing numbers of cancer cases worldwide and the exceedingly high mortality rates of some tumor subtypes raise the question about if the current protocols for cancer management are effective and what has been done to improve upon oncologic patients’ prognoses. The traditional chemo-immunotherapy options for cancer treatment focus on the use of cytotoxic agents that are able to overcome neoplastic clones’ survival mechanisms and induce apoptosis, as well as on the ability to capacitate the host’s immune system to hinder the continuous growth of malignant cells. The need to avert the highly toxic profiles of conventional chemo-immunotherapy and to overcome the emerging cases of tumor multidrug resistance has fueled a growing interest in the field of precision medicine and targeted molecular therapies in the last couple of decades, although relatively new alternatives in oncologic practices, the increased specificity, and the positive clinical outcomes achieved through targeted molecular therapies have already consolidated them as promising prospects for the future of cancer management. In recent years, the development and application of targeted drugs as tyrosine kinase inhibitors have enabled cancer treatment to enter the era of specificity. In addition, the combined use of targeted therapy, immunotherapy, and traditional chemotherapy has innovated the standard treatment for many malignancies, bringing new light to patients with recurrent tumors. This article comprises a series of clinical trials that, in the past 5 years, utilized kinase inhibitors (KIs) as a monotherapy or in combination with other cytotoxic agents to treat patients afflicted with solid tumors. The results, with varying degrees of efficacy, are reported.     

Inactivation of Enterobacter sakazakii by pulsed electric field in buffered peptone water and infant formula milk

The effect of high-intensity pulsed electric field (PEF) treatment on the survival of Enterobacter sakazakii suspended in buffered peptone water (BPW) and powdered infant formula milk (IFM) was evaluated. Reference medium and IFM samples were treated with PEF. Electric field intensity and treatment time were varied from 10 to 40 kV cm⁻¹ and from 60 to 3895 μs, respectively. Samples of buffered peptone water (3 g L⁻¹) and IFM were inoculated with E. sakazakii (CECT 858) (10⁹ cfu mL⁻¹) and then treated with PEF. The inactivation data were adjusted to the Weibull frequency distribution function and Bigelow model, and constants were calculated for both substrates. A maximum 2.7 log (cfu mL⁻¹) reduction was achieved in BPW after exposure of E. sakazakii to PEF for 360 μs (2.5 μs pulse width) at 40 kV cm⁻¹. In IFM, exposure of E. sakazakii to PEF, with the same conditions, led to a 1.2 log (cfu mL⁻¹) reduction. The greater the field strength and treatment time, the greater the inactivation achieved in both substrates. Even though further research will be necessary, according to the results, there are good prospects for the use of PEF in hospitals to achieve safe reconstituted infant formula before storage at refrigerated temperatures.     

Applications of Plasma-Activated Water in Dentistry: A Review

The activation of water by non-thermal plasma creates a liquid with active constituents referred to as plasma-activated water (PAW). Due to its active constituents, PAW may play an important role in different fields, such as agriculture, the food industry and healthcare. Plasma liquid technology has received attention in recent years due to its versatility and good potential, mainly focused on different health care purposes. This interest has extended to dentistry, since the use of a plasma–liquid technology could bring clinical advantages, compared to direct application of non-thermal atmospheric pressure plasmas (NTAPPs). The aim of this paper is to discuss the applicability of PAW in different areas of dentistry, according to the published literature about NTAPPs and plasma–liquid technology. The direct and indirect application of NTAPPs are presented in the introduction. Posteriorly, the main reactors for generating PAW and its active constituents with a role in biomedical applications are specified, followed by a section that discusses, in detail, the use of PAW as a tool for different oral diseases.     

Pressure inactivation kinetics of Enterobacter sakazakii in infant formula milk

Survival curves of Enterobacter sakazakii inactivated by high hydrostatic pressure were obtained at four pressure levels (250, 300, 350, and 400 MPa), at temperatures below 30 degrees C, in buffered peptone water (BPW; 0.3%, wt/vol) and infant formula milk (IFM; 16%, wt/vol). A linear model and four nonlinear models (Weibull, log-logistic, modified Gompertz, and Baranyi) were fitted to the data, and the performances of the models were compared. The linear regression model for the survival curves in BPW and IFM at 250 MPa has fitted regression coefficient (R2) values of 0.940 to 0.700, respectively, and root mean square errors (RMSEs) of 0.770 to 0.370. For the other pressure levels, the linear regression function was not appropriate, as there was a strong curvature in the plotted data. The nonlinear regression models with the log-logistic and modified Gompertz equations had R2 values of 0.960 to 0.992 and RMSE values of 0.020 to 0.130 within pressure levels of 250 to 400 MPa, respectively. These results indicate that they are both better models for describing the pressure inactivation kinetics of E. sakazakii in IFM and BPW than the Weibull distribution function, which has an R2 minimum value of 0.832 and an RMSE maximum value of 0.650 at 400 MPa. On the other hand, the parameters for the Weibull distribution function, log-logistic model, and modified Gompertz equation did not have a clear dependence on pressure. The Baranyi model was also analyzed, and it was concluded that this model provided a reasonably good fit and could be used to develop predictions of survival data at pressures other than the experimental pressure levels in the range studied. The results provide accurate predictions of survival curves at different pressure levels and will be beneficial to the food industry in selecting optimum combinations of pressure and time to obtain desired target levels of E. sakazakii inactivation in IFM.     

Analysis of sensitization phenomenon in friction stir welded 304 stainless steel

This study evaluates the degree of sensitization (DOS) of 304 stainless steel joined by friction stir welding (FSW). Single-loop electrochemical potentiokinetic reactivation tests were performed using a 0.5 mol/L H₂SO₄ + 0.01 mol/L KSCN solution. Sensitization was promoted by exposition of the stainless steel at temperatures between 400°C and 850°C. The microstructure was characterized using optical microscopy to identify the weld zone and the base metal. The samples treated at 550°C showed the most severe intergranular corrosion. The DOS was lower in the weld zone than in the base metal after heat treatments. This reduction in the DOS for the weld zone indicates that FSW is a beneficial process in joining stainless steel.     

A multidimensional segmentation evaluation for medical image data

Evaluation of segmentation methods is a crucial aspect in image processing, especially in the medical imaging field, where small differences between segmented regions in the anatomy can be of paramount importance. Usually, segmentation evaluation is based on a measure that depends on the number of segmented voxels inside and outside of some reference regions that are called gold standards. Although some other measures have been also used, in this work we propose a set of new similarity measures, based on different features, such as the location and intensity values of the misclassified voxels, and the connectivity and the boundaries of the segmented data. Using the multidimensional information provided by these measures, we propose a new evaluation method whose results are visualized applying a Principal Component Analysis of the data, obtaining a simplified graphical method to compare different segmentation results. We have carried out an intensive study using several classic segmentation methods applied to a set of MRI simulated data of the brain with several noise and RF inhomogeneity levels, and also to real data, showing that the new measures proposed here and the results that we have obtained from the multidimensional evaluation, improve the robustness of the evaluation and provides better understanding about the difference between segmentation methods.     

A Weibull model to describe antimicrobial kinetics of oregano and lemongrass essential oils against Salmonella Enteritidis in ground beef during refrigerated storage

The antimicrobial effect of oregano (Origanum vulgare L.) and lemongrass (Cymbopogon citratus (DC.) Stapf.) essential oils (EOs) against Salmonella enterica serotype Enteritidis in in vitro experiments, and inoculated in ground bovine meat during refrigerated storage (4 ± 2 °C) for 6 days was evaluated. The Weibull model was tested to fit survival/inactivation bacterial curves (estimating of p and δ parameters). The minimum inhibitory concentration (MIC) value for both EOs on S. Enteritidis was 3.90 μl/ml. The EO concentrations applied in the ground beef were 3.90, 7.80 and 15.60 μl/g, based on MIC levels and possible activity reduction by food constituents. Both evaluated EOs in all tested levels, showed antimicrobial effects, with microbial populations reducing (p ≤ 0.05) along time storage. Evaluating fit-quality parameters (RSS and RSE) Weibull models are able to describe the inactivation curves of EOs against S. Enteritidis. The application of EOs in processed meats can be used to control pathogens during refrigerated shelf-life.     

Electrochemical regeneration of partially ethoxylated polyethylenimine used in the polymer-supported ultrafiltration of copper

This work is focussed on the application of an electrochemical technology to regenerate the bonding agent of a polymer-supported ultrafiltration process, technique commonly used to remove metal ions from wastewaters. To do this, a batch rotating-electrode electrochemical cell has been set up to recover the copper bind to partially ethoxylated polyethyleneimine by electrodeposition. The influence of the main parameters (current efficiency, stirring rate, pH, electrode material and nature of the counterion) on the performance of the process has been studied. Current efficiency is clearly enhanced with the stirring rate, reaching values as high as 0.93 for the optimum working conditions. Regarding pH, this variable has been observed to play an important role in process efficiency. Thus, it has been found that the reactor can operate at pH 4 without affecting process performance. This is a clear advantage with respect to other regeneration techniques and also to previous works of electrochemical regeneration. The electrode material seems to have a clear influence on process behaviour and especially on the appearance of a first transitory stage with lower current efficiency. Finally, the electrolyte salt also influences significantly on the results and the presence of sulphate as counterion leads to the best system performance.