PROTEIN BOUND IODINE LEVEL IN CHILDREN WITH OBESITY

No abstrac

SERUM GLYCOPROTEINS IN RHEUMATIC CHILDREN

No abstract

Multicenter evaluation of a new electrochemiluminescence immunoassay for everolimus concentrations in whole blood

Background: The precise monitoring of everolimus, an immunosuppressant drug, is vital for transplant recipients due to its narrow therapeutic range. This study evaluated the analytical performance of a new electrochemiluminescence immunoassay (ECLIA) for everolimus concentrations in whole blood. Methods: Accuracy, imprecision, and sensitivity studies for the Roche Elecsys everolimus ECLIA were performed at 5 European laboratories. The ECLIA was compared with liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods, as well as the Quantitative Microsphere System everolimus assay. Results: Everolimus ECLIA accuracies were within the range 100% +/- 9%. Coefficients of variation (CVs) across the target range were <= 4.8% for repeatability and <= 8.4% for intermediate imprecision, whereas multisite reproducibility at lower (2.71 mcg/L) and higher everolimus concentrations (3.0-30.0 mcg/L) resulted in CVs of <= 13.7% and <= 12.4%, respectively. The CV at the assay's lower limit of quantification without considering bias was excellent, estimated as <= 9.3% at 0.5 mcg/L. The weighted Deming regression analysis, used for comparison of the results obtained by everolimus ECLIA and by LC-MS/MS methods, yielded a slope of 1.21 [95% confidence interval (CI): 1.15-1.26], intercept of 0.478 mcg/L (95% CI: 0.241-0.716), and a Pearson correlation coefficient (r) of 0.91. A single-site comparison between the ECLIA and the Quantitative Microsphere System assay revealed a slope of 1.05 (95% CI: 0.917-1.17), intercept of 1.03 mcg/L (95% CI: 0.351-1.70), and r of 0.91. Conclusions: Based on these results, the Roche Elecsys everolimus ECLIA can be considered suitable for routine therapeutic drug monitoring. A positive bias was observed with respect to LC-MS/MS methods, suggesting that it may be necessary to rebaseline individual patients when switching from LC-MS/MS to the ECLIA; however, this must also be considered for any change of method for everolimus measurement

Distance learning as a means of forming subjective attitude in physically challenged children

The article analyzes the results of a research aimed at identification of the pedagogical technology promoting the formation of a subjective attitude in children with disabilities / physically challenged children studying remotely. Key words: physically challenged children, e-learning, informational and educational environment, subjective attitude

Noninvasive assessment of an engineered bioactive graft in myocardial infarction: impact on cardiac function and scar healing

Cardiac tissue engineering, which combines cells and biomaterials, is promising for limiting the sequelae of myocardial infarction (MI). We assessed myocardial function and scar evolution after implanting an engineered bioactive impedance graft (EBIG) in a swine MI model. The EBIG comprises a scaffold of decellularized human pericardium, green fluorescent protein-labeled porcine adipose tissue-derived progenitor cells (pATPCs), and a customized-design electrical impedance spectroscopy (EIS) monitoring system. Cardiac function was evaluated noninvasively by using magnetic resonance imaging (MRI). Scar healing was evaluated by using the EIS system within the implanted graft. Additionally, infarct size, fibrosis, and inflammation were explored by histopathology. Upon sacrifice 1 month after the intervention, MRI detected a significant improvement in left ventricular ejection fraction (7.5%64.9% vs. 1.4%63.7%; p = .038) and stroke volume (11.565.9 ml vs. 364.5 ml; p = .019) in EBIG-treated animals. Noninvasive EIS data analysis showed differences in both impedance magnitude ratio (20.02 6 0.04 per day vs. 20.48 6 0.07 per day; p = .002) and phase angle slope (20.18°60.24° per day vs.23.52°60.84° per day; p = .004) in EBIG compared with control animals. Moreover, in EBIG-treated animals, the infarct size was 48% smaller (3.4%60.6% vs. 6.5%61%; p = .015), less inflammation was found by means of CD25+ lymphocytes (0.65 6 0.12 vs. 1.26 6 0.2; p = .006), and a lower collagen I/III ratio was detected (0.4960.06 vs. 1.6660.5; p = .019). An EBIG composed of acellular pericardium refilled with pATPCs significantly reduced infarct size and improved cardiac function in a preclinical model of MI. Noninvasive EIS monitoring was useful for tracking differential scar healing in EBIG-treated animals, which was confirmed by less inflammation and altered collagen deposit.Peer ReviewedPostprint (published version

Synthesis of migrastatin analogues as inhibitors of tumour cell migration: exploring structural change in and on the macrocyclic ring

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Migrastatin and isomigrastatin analogues have been synthesised in order to contribute to structure-activity studies on tumour cell migration inhibitors. These include macrocycles varying in ring size, functionality and alkene stereochemistry, as well as glucuronides. The synthesis work included application of the Saegusa-Ito reaction for regio- and stereoselective unsaturated macroketone formation, diastereoselective Brown allylation to generate 9-methylmigrastatin analogues and chelation-induced anomerisation to vary glucuronide configuration. Compounds were tested in vitro against both breast and pancreatic cancer cell lines and inhibition of tumour cell migration was observed in both wound-healing (scratch) and Boyden chamber assays. One unsaturated macroketone showed low affinity for a range of secondary drug targets, indicating it is at low risk of displaying adverse side effects.This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) and is co‐funded under the European Regional Development Fund under Grant Number 14/SP/2710. The research leading to these results has also received funding in part from the People Programme (Marie Curie Actions) of the European Union′s Seventh Framework Programme FP7/2007‐2013/ under REA grant agreement No. PIEF‐GA‐2011‐299042 and the Poland National Science Council.Published versio

СТРУКТУРА И ФАЗОВЫЙ СОСТАВ МНОГОСЛОЙНЫХ РЕНТГЕНОВСКИХ ЗЕРКАЛ W-Si

Методами рентгеновской дифрактометрии в жесткой области (l~0,154 нм) исследована фазовая структура, состав и строение многослойных рентгеновских зеркал (МРЗ) W/Si с толщиной слоев вольфрама tW2,7 нм слои вольфрама имеют поликристаллическую (ОЦК) структуру, а при tW<1,9 нм они аморфны. При помощи sin2Y-метода установлено, что в тонких кристаллических слоях вольфрама (tW<10 нм) может содержаться более 3 ат.% Si. Растягивающие напряжения в слоях кристаллического вольфрама не превышают 1,1 ГПа. Построение функций радиального распределения атомов позволило установить, что аморфные слои вольфрама имеют расположение атомов, близкое к b-W. Во всех образцах за счет взаимодействия на межфазных границах наблюдается формирование силицидных прослоек, в результате чего реальная толщина слоев вольфрама меньше номинальной. Аморфные силицидные прослойки, обязательно формирующиеся на стадии изготовления МРЗ, содержат дисилицид вольфрама. В зависимости от скорости осаждения дисилицид может иметь расположение атомов, близкое либо к тетрагональной фазе, t-WSi2 (~0,6 нм/с.), либо к гексагональной фазе, h-WSi2 (~0,15 нм/с.). Представлена уточненная модель строения аморфных МРЗ W/Si. Предложены механизмы формирования силицидных прослоек, согласно которым нижние силицидные прослойки (W-на-Si) формируются преимущественно за счет баллистического перемешивания атомов вольфрама и кремния, а верхние – вследствие диффузионного перемешивания. Сделана оценка коэффициентов взаимной диффузии, которые позволили установить, что осаждаемая поверхность слоев может быть разогрета, по меньшей мере, на 250° выше температуры подложки. Предложены пути снижения межфазного взаимодействия

Personalized therapy for mycophenolate:Consensus report by the international association of therapeutic drug monitoring and clinical toxicology

When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted.</p