Inter-laboratory study on standardized MPS libraries: evaluation of performance,concordance, and sensitivity using mixtures and degraded DNA

International Journal of Legal Medicine - We present results from an inter-laboratory massively parallel sequencing (MPS) study in the framework of the SeqForSTRs project to evaluate forensically...     

Conversion from twice- to once-daily tacrolimus in pediatric kidney recipients: a pharmacokinetic and bioequivalence study

Background

The objectives of this study were to investigate pharmacokinetic and pharmacogenetic parameters during the conversion on a 1:1 (mg:mg) basis from a twice-daily (Prograf) to once-daily (Advagraf) tacrolimus formulation in pediatric kidney transplant recipients.

Methods

Twenty-four-hour pharmacokinetic profiles were analyzed before and after conversion in 19 stable renal transplant recipients (age 7–19 years). Tacrolimus pharmacokinetic parameters [area under the concentration-time curve (AUC_0–24), minimum whole-blood concentration (C_min), maximum whole-blood concentration (C_max), and time to achieve maximum whole-blood concentration (t_max)] were compared between Tac formulations and between CYP3A5 and MDR1 genotypes after dose normalization.

Results

Both AUC_0–24 and C_min decreased after conversion (223.3 to 197.5 ng.h/ml and 6.5 to 5.6 ng/ml; p?=?0.03 and 0.01, respectively). However, the ratio of the least square means (LSM) for AUC_0–24 was 90.8 %, with 90 % CI limits of 85.3 to 96.7 %, falling within bioequivalence limits. The CYP3A5 genotype influences the dose-normalized C_min with the twice-daily formulation only.

Conclusions

Both tacrolimus formulations are bioequivalent in pediatric renal recipients. However, we observed a decrease in AUC_0–24 and C_min after the conversion, requiring close pharmacokinetic monitoring during the conversion period.     

Solvothermal synthesis and structural characterization of three polyoxotitanium-organic acid clusters

Three new titanium oxo-clusters Ti₄O₂(OⁱPr)₁₀(OOCPhMe)₂ (I), Ti₆O₄(OEt)₈(OOCPhMe)₈ (II) and Ti₆O₆(OEt)₆(OOCCHPh₂)₆ (III) were obtained by easy one-step solvothermal reactions of titanium(iv) isopropoxide, alcohols and carboxylic acids. The three compounds were characterized by single-crystal and powder X-ray diffraction, TGA/DSC, optical and electron microscopy, and FTIR and NMR spectroscopy. X-ray powder diffraction and spectroscopy confirmed the purity of the compounds. Structural analysis indicates that in all compounds the titanium(iv) ions are six-coordinated (distorted octahedra). (I) is a tetranuclear complex containing a Ti₄(μ₄-O)(μ₂-O) core, which is linked by two (μ₂-OOCPhMe), four (μ₂-OⁱPr) and six OⁱPr ligands. (II) and (III) are hexanuclear complexes with different cores, respectively Ti₆(μ₃-O)₂(μ₂-O)₂ and Ti₆(μ₃-O)₆. The coordination sphere of the Ti atoms is filled by eight (μ₂-OOCPhMe), two (μ₂-OEt) and six OEt in (II) and six (μ₂-OOCHPh₂) and six OEt in (III). Different steric hindrance of substituents attached to the carboxyl group or different concentrations lead to three main different cluster geometries with two ligands. The tetranuclear and the hexanuclear clusters were obtained with the OOCPhMe ligand, while the hexagonal prism cluster was obtained with the OOCCHPh₂ ligand. Hirshfeld surface calculations indicated that the packing is driven by C–O⋯H–C weak hydrogen bonds. The clusters can be used as molecular models of organic molecules bonded to titania surface, used in organic photovoltaic (dye sensitized solar cells) or other optoelectronic applications.

Crystal structures of three novel titanium oxo-clusters with different cores and ligands obtained by an easy and convenient solvothermal method.     

A preliminary observation: Male pattern hair loss among hospitalized COVID‐19 patients in Spain – A potential clue to the role of androgens in COVID‐19 severity

A preliminary observation of high frequency of male pattern hair loss among admitted COVID‐19 patients and suggest that androgen expression might be a clue to COVID‐19 severity.     

Standardization of Quality of Diagnoses,Interventions, and Outcomes (Q-DIO) Measurement Instrument for Use in Slovenia

PurposeTo describe the cross-cultural adaptation of the Quality of Diagnoses, Interventions and Outcomes (Q-DIO) Instrument into the Slovene language.MethodsBased on general international guidelines, a six-step process of localization to translate and adjust the instrument from English into the Slovene language was used. Content validity was quantified based on an agreement of eight experts. The instrument was tested using a sample of 140 nursing documentations from two Slovenian tertiary hospitals.Results26 of 29 items showed an excellent content validity index ranging from 0.857 to 1.000, and a modified kappa index above 0.856. The content validity indexes of the three remaining items adjusted based on experts’ comments were subsequently estimated at 1.000. Construct validity was significantly different between the two groups of documentations. The Cronbach coefficient for the whole questionnaire was 0.860. Cronbach’s alpha if item deleted reamins above 0.80 for all items. The criteria for the difficulty grades of items and discrimination validity were acceptably met for more than 75% of items.ConclusionBased on the results of the study, it may be concluded that Q-DIO is a reliable instrument for measuring the quality of nursing documentation. The deviations in the results of some items are due to poor nursing documentation quality, and indicate that nursing classifications have not yet been fully implemented into practice in the study setting. Additional testing of the instrument is recommended.