Modelling,Analysis, and Optimization of the Effects of Pulsed Electrophoretic Deposition Parameters on TiO2 Films Properties Using Desirability Optimization Methodology

Titanium dioxide thin films immobilized over treated stainless steel were prepared using the pulsed electrophoretic deposition technique. The effects of process parameters (deposition time, applied voltage, initial concentration, and duty cycle) on photocatalytic efficiency and adhesion properties were investigated. To optimize the multiple properties of the thin film, a response surface methodology was combined with a desirability optimization methodology. Additionally, a quadratic model was established based on response surface analysis. The precision of the models was defined based on the analysis of variance (ANOVA), R², and the normal plot of residuals. Then, a desirability function was used to optimize the multiple responses of the TiO₂ thin film. The optimum values of applied voltage, catalyst concentration, duty cycle, and deposition time were 4 V, 16.34 g/L, 90% DC, and 150 s, respectively. Under these conditions, the decolorization efficiency of tested dye solution reached 82.75%. The values of critical charges L_C1, L_C2, and L_C3 were 5.9 N, 12.5 N, and 16.7 N, respectively.     

Extended infusion of beta-lactam antibiotics: optimizing therapy in critically-ill patients in the era of antimicrobial resistance

Introduction: Beta-lactams are at the cornerstone of therapy in critical care settings, but their clinical efficacy is challenged by the rise in bacterial resistance. Infections with multi-drug resistant organisms are frequent in intensive care units, posing significant therapeutic challenges. The problem is compounded by a dearth in the development of new antibiotics. In addition, critically-ill patients have unique physiologic characteristics that alter the drugs pharmacokinetics and pharmacodynamics.

Areas covered: The prolonged infusion of antibiotics (extended infusion [EI] and continuous infusion [CI]) has been the focus of research in the last decade. As beta-lactams have time-dependent killing characteristics that are altered in critically-ill patients, prolonged infusion is an attractive approach to maximize their drug delivery and efficacy. Several studies have compared traditional dosing to EI/CI of beta-lactams with regard to clinical efficacy. Clinical data are primarily composed of retrospective studies and some randomized controlled trials. Several reports show promising results.

Expert commentary: Reviewing the currently available evidence, we conclude that EI/CI is probably beneficial in the treatment of critically-ill patients in whom an organism has been identified, particularly those with respiratory infections. Further studies are needed to evaluate the efficacy of EI/CI in the management of infections with resistant organisms.     

Hypoxia promotes the phenotypic change of aldehyde dehydrogenase activity of breast cancer stem cells

Stable breast cancer cell (BCC) lines are valuable tools for the identification of breast cancer stem cell (BCSC) phenotypes that develop in response to several stimuli as well as for studying the basic mechanisms associated with the initiation and maintenance of BCSCs. However, the characteristics of individual, BCC‐derived BCSCs varies and these cells show distinct phenotypes depending on the different BCSC markers used for their isolation. Aldehyde dehydrogenase (ALDH) activity is just such a recognized biomarker of BCSCs with a CD44⁺/CD24^? phenotype. We isolated BCSCs with high ALDH activity (CD44⁺/CD24^?/Aldefluor^pos) from a primary culture of human breast cancer tissue and observed that the cells had stem cell properties compared to BCSCs with no ALDH activity (CD44⁺/CD24^?/Aldefluor^neg). Moreover, we found Aldefluor^pos BCSCs had a greater hypoxic response and subsequent induction of HIF‐1α expression compared to the Aldefluor^neg BCSCs. We also found that knocking down HIF‐1α, but not HIF‐2α, in Aldefluor^pos BCSCs led to a significant reduction of the stem cell properties through a decrease in the mRNA levels of genes associated with the epithelial‐mesenchymal transition. Indeed, HIF‐1α overexpression in Aldefluor^neg BCSCs led to Slug and Snail mRNA increase and the associated repression of E‐cadherin and increase in Vimentin. Of note, prolonged hypoxic stimulation promoted the phenotypic changes of Aldefluor^neg BCSCs including ALDH activity, tumorigenesis and metastasis, suggesting that hypoxia in the tumor environment may influence BCSC fate and breast cancer clinical outcomes.