An Extensive Quality Control and Quality Assurance (QC/QA) Program Significantly Improves Inter-Laboratory Concordance Rates of Flow-Cytometric Minimal Residual Disease Assessment in Acute Lymphoblastic Leukemia: An I-BFM-FLOW-Network Report

Monitoring of minimal residual disease (MRD) by flow cytometry (FCM) is a powerful prognostic tool for predicting outcomes in acute lymphoblastic leukemia (ALL). To apply FCM-MRD in large, collaborative trials, dedicated laboratory staff must be educated to concordantly high levels of expertise and their performance quality should be continuously monitored. We sought to install a unique and comprehensive training and quality control (QC) program involving a large number of reference laboratories within the international Berlin-Frankfurt-Münster (I-BFM) consortium, in order to complement the standardization of the methodology with an educational component and persistent quality control measures. Our QC and quality assurance (QA) program is based on four major cornerstones: (i) a twinning maturation program, (ii) obligatory participation in external QA programs (spiked sample send around, United Kingdom National External Quality Assessment Service (UK NEQAS)), (iii) regular participation in list-mode-data (LMD) file ring trials (FCM data file send arounds), and (iv) surveys of independent data derived from trial results. We demonstrate that the training of laboratories using experienced twinning partners, along with continuous educational feedback significantly improves the performance of laboratories in detecting and quantifying MRD in pediatric ALL patients. Overall, our extensive education and quality control program improved inter-laboratory concordance rates of FCM-MRD assessments and ultimately led to a very high conformity of risk estimates in independent patient cohorts

Visualization and Evaluation of Changes after Rapid Maxillary Expansion

Objectives: The aim of the study was to develop a mathematical model for the visualization and evaluation of transversal palatal soft tissue changes; and to carry out a statistical evaluation of the changes in vertical and sagittal dimensions after rapid maxillary expansion treatment. Material and Methods: 33 Caucasian children with posterior crossbite, 10 boys and 23 girls, aged 7 to 10 years (median 8 years 8 months) were treated with tooth-borne Haas type expander. Dental casts were digitalized by scanner and on the basis of quantitative mesh shape CPD-DCA analysis, coloured morphometrical maps were created. The statistical significance of individual vertex displacements was calculated by performing Hotelling’s T2 paired test. To determine the significance of the vertical and sagittal profile changes, the paired t-test and Wilcoxon signed rank test were carried out in 20 patients Results: Visualization of the palatal soft tissue widening showed it to be greatest in the areas of the second deciduous and first permanent molars with maximum of 0.75 mm for each palatal side. Hotelling’s T2 paired test showed significant differences of p<0.01 in transversal width dimension. Cephalometric measurements of the changes to vertical and sagittal dimensions were statistically evaluated using the Wilcoxon and paired t-tests, and were shown to have insignificant values of p>0.05. Conclusion: The expansion appliance in children resolved the crossbite and led to palatal widening, which was clearly visualized by creating mathematical morphometric models. The cephalometric measurements carried out did not reveal statistically significant relevance in changes to facial vertical or sagittal dimensions

Study of Biological Activities and ADMET-Related Properties of Novel Chlorinated <i>N</i>-arylcinnamamides

A series of eighteen 4-chlorocinnamanilides and eighteen 3,4-dichlorocinnamanilides were designed, prepared and characterized. All compounds were evaluated for their activity against gram-positive bacteria and against two mycobacterial strains. Viability on both cancer and primary mammalian cell lines was also assessed. The lipophilicity of the compounds was experimentally determined and correlated together with other physicochemical properties of the prepared derivatives with biological activity. 3,4-Dichlorocinnamanilides showed a broader spectrum of action and higher antibacterial efficacy than 4-chlorocinnamanilides; however, all compounds were more effective or comparable to clinically used drugs (ampicillin, isoniazid, rifampicin). Of the thirty-six compounds, six derivatives showed submicromolar activity against Staphylococcus aureus and clinical isolates of methicillin-resistant S. aureus (MRSA). (2E)-N-[3,5-bis(trifluoromethyl)phenyl]- 3-(4-chlorophenyl)prop-2-enamide was the most potent in series 1. (2E)-N-[3,5-bis(Trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-enamide, (2E)-3-(3,4-dichlorophenyl)-N-[3-(trifluoromethyl)phenyl]prop-2-enamide, (2E)-3-(3,4-dichloro- phenyl)-N-[4-(trifluoromethyl)phenyl]prop-2-enamide and (2E)-3-(3,4-dichlorophenyl)- N-[4-(trifluoromethoxy)phenyl]prop-2-enamide were the most active in series 2 and in addition to activity against S. aureus and MRSA were highly active against Enterococcus faecalis and vancomycin-resistant E. faecalis isolates and against fast-growing Mycobacterium smegmatis and against slow-growing M. marinum, M. tuberculosis non-hazardous test models. In addition, the last three compounds of the above-mentioned showed insignificant cytotoxicity to primary porcine monocyte-derived macrophages