Population Pharmacokinetic Modelling of the Complex Release Kinetics of Octreotide LAR: Defining Sub-Populations by Cluster Analysis

The aim of the study is to develop a population pharmacokinetic (PPK) model, of Octreotide long acting repeatable (LAR) formulation in healthy volunteers, which describes the highly variable, multiple peak absorption pattern of the pharmacokinetics of the drug, in individual and population levels. An empirical absorption model, coupled with a one-compartment distribution model with linear elimination was found to describe the data well. Absorption was modelled as a weighted sum of a first order and three transit compartment absorption processes, with delays and appropriately constrained model parameters. Identifiability analysis verified that all twelve parameters of the structural model are identifiable. A machine learning method, i.e., cluster analysis, was performed as pre-processing of the PK profiles, to define subpopulations, before PPK modelling. It revealed that 13% of the patients deviated considerably from the typical absorption pattern and allowed better characterization of the observed heterogeneity and variability of the study, while the approach may have wider applicability in building PPK models. The final model was evaluated by goodness of fit plots, Visual Predictive Check plots and bootstrap. The present model is the first to describe the multiple-peak absorption pattern observed after octreotide LAR administration and may be useful to provide insights and validate hypotheses regarding release from PLGA-based formulations.

Microhardness homogeneity of RBCs light-cured with a multiple-peak LED and surface characterization after wear

This in vitro study evaluated the effect of the beam homogeneity of a multiple-peak light-curing unit on the surface microhardness and the effect of toothbrushing wear on the microhardness, surface roughness, roughness profile, volume loss, and gloss retention of incremental and bulk-fill resin-based composites (RBCs). A LED light-curing unit (VALO) with four LEDs at the tip end (405, 445, 465A, and 465B nm emission peak) was used according to each manufacturer-recommended time to obtain disks (n=10) of six RBCs: Estelite Sigma Quick, Charisma Classic, Tetric EvoCeram Bulk Fill, Filtek Z250, Filtek Supreme Ultra, and Filtek Bulk Fill. Microhardness values were obtained according to each LED positioning of the light-curing unit on the top surface of the RBCs and were analyzed before and after toothbrushing regarding microhardness, surface roughness, roughness profile, volume loss, and gloss retention. Microhardness was considered homogeneous on the top surface regardless of the type of RBC or wavelength tested (p>0.05). Overall, toothbrushing did not reduce the microhardness of the RBCs but influenced the gloss values for most RBCs (p<0.001). Charisma Classic presented the greatest surface roughness and roughness profile after toothbrushing (p<0.05). Volume loss did not differ among RBCs (p>0.05). In conclusion, different wavelengths of the LED did not affect the top surface microhardness, regardless of the RBCs tested; and bulk-fill composites presented similar surface changes (microhardness, surface roughness, roughness profile, volume loss, and gloss retention) when compared to conventional composites after toothbrushing.

ChIP-AP – An Integrated ChIP-Seq Analysis Pipeline

ChIP-Seq is a technique used to analyse protein-DNA interactions. The protein-DNA complex is pulled down using a protein antibody, after which sequencing and analysis of the bound DNA fragments is performed. A key bioinformatics analysis step is “peak” calling - identifying regions of enrichment. Benchmarking studies have consistently shown that no optimal peak caller exists. Peak callers have distinct selectivity and specificity characteristics which are often not additive and seldom completely overlap in many scenarios. In the absence of a universal peak caller, we rationalized one ought to utilize multiple peak-callers to 1) gauge peak confidence as determined through detection by multiple algorithms, and 2) more thoroughly survey the protein-bound landscape by capturing peaks not detected by individual peak callers owing to algorithmic limitations and biases. We therefore developed an integrated ChIP-Seq Analysis Pipeline (ChIP-AP) which performs all analysis steps from raw fastq files to final result, and utilizes four commonly used peak callers to more thoroughly and comprehensively analyse datasets. Results are integrated and presented in a single file enabling users to apply selectivity and sensitivity thresholds to select the consensus peak set, the union peak set, or any sub-set in-between to more confidently and comprehensively explore the protein-bound landscape. (https://github.com/JSuryatenggara/ChIP-AP).

Extrinsic nature of double broadband photoluminescence from BaTiO3 perovskite: generation of white light emitters

The electronic properties of BaTiO3 perovskite oxides are not completely understood, despite its excellent electro-optical performance and potential for light generation. Particularly, when there is a multiple peak formation in...

Effect of Curing Light and Exposure Time on the Polymerization of Bulk-Fill Resin-Based Composites in Molar Teeth

SUMMARY Objectives: This study examined the influence of different light-curing units (LCUs) and exposure times on the microhardness across bulk-fill resin-based composite (RBC) restorations in a molar tooth. Methods and Materials: Tip diameter, radiant power, radiant exitance, emission spectra, and light beam profile were measured on two single-emission-peak LCUs (Celalux 3 and DeepCure-S) and two multiple-peak LCUs (Bluephase 20i and Valo Grand). A mold was made using a human molar that had a 12-mm mesial-distal length, a 2.5-mm deep occlusal box, and two 4.5-mm deep proximal boxes. Two bulk-fill RBCs (Filtek Bulk Fill Posterior and Tetric EvoCeram Bulk Fill) were photoactivated for 10 seconds and for 20 seconds, with the light guide positioned at the center of the occlusal surface. Microhardness was then measured across the transverse surface of the restorations. The light that reached the bottom of the proximal boxes was examined. Data were statistically analyzed with the Student t-test, two-way analysis of variance, and the Tukey post hoc test (α=0.05). Results: The four LCUs were different regarding all the tested characteristics. Even when using LCUs with wide tips and a homogeneous beam profile, there were significant differences in the microhardness results obtained at the central and proximal regions of the RBCs (p&lt;0.05). LCUs with wider tips used for 20 seconds produced higher microhardness values (p&lt;0.05). The multiple-peak LCUs produced greater hardness values in Tetric EvoCeram Bulk Fill than did the single-emission-peak LCUs (Celalux 3 and DeepCure-S). Results for the light measured at the bottom of proximal boxes showed that little light reached these regions when the light tip was positioned at the center of restorations. Conclusions: Curing lights with wide tips, homogeneous light beam profiles, and longer exposure times are preferred when light-curing large MOD restorations. Light curing from more than one position may be required for adequate photopolymerization.