Development and Testing of a New Simplified Endoscopic Mucosal Assessment for Crohn's Disease: The SEMA-CD.

OBJECTIVES: Endoscopic mucosal improvement is the gold standard for assessing treatment efficacy in clinical trials of Crohn's disease. Current endoscopic indices are not routinely used in clinical practice. The lack of endoscopic information in large clinical registries limits their use for research. A quick, easy, and accurate method is needed for assessing mucosal improvement for clinicians in real-world practice. We developed and tested a novel simplified endoscopic mucosal assessment for Crohn's disease (SEMA-CD). METHODS: We developed a 5-point scale for ranking endoscopic severity of ileum and colon based on Simple Endoscopic Score for Crohn's disease (SES-CD). Central readers were trained to perform SES-CD and SEMA-CD. Pediatric patients with Crohn's disease undergoing colonoscopy were enrolled. Video recordings of colonoscopies were de-identified and randomly assigned to blinded central readers. The SES-CD and SEMA-CD were scored for each video. The SES-CD was considered the validated standard for comparison. Correlation was assessed with Spearman rho, inter- and intrarater reliability with kappa statistics. RESULTS: Fifty-seven colonoscopies were read a total of 212 times. Correlation between SEMA-CD and SES-CD was strong (rho = 0.98, P < 0.0001). Inter-rater reliability for SEMA-CD was 0.80, and intrarater reliability was 0.83. Central readers rated SEMA-CD as easier than SES-CD. CONCLUSION: The SEMA-CD accurately and reproducibly correlates with the standard SES-CD. Central readers viewed SEMA-CD as easier than SES-CD. Use of SEMA-CD in practice should enable collecting mucosal improvement information in large populations of patients. This will improve the quality of research that can be conducted in clinical registries. External validation is needed.

Self-Assembled Au@Fe Core/Satellite Magnetic Nanoparticles for Versatile Biomolecule Functionalization.

Although the functionalization of magnetic nanoparticles (MNPs) with biomolecules has been widely explored for various biological applications, achieving efficient bioconjugations with a wide range of biomolecules through a single, universal, and versatile platform remains a challenge, which may significantly impact their applications' outcomes. Here, we report a novel MNP platform composed of Au@Fe core/satellite nanoparticles (CSNPs) for versatile and efficient bioconjugations. The engineering of the CSNPs is facilely formed through the self-assembly of ultrasmall gold nanoparticles (AuNPs, 2-3 nm in diameter) around MNPs with a polysiloxane-containing polymer coating. The formation of the hybrid magnetic nanostructure is revealed by absorption spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), element analysis using atomic absorption spectroscopy, and vibrating sample magnetometer. The versatility of biomolecule loading to the CSNP is revealed through the bioconjugation of a wide range of relevant biomolecules, including streptavidin, antibodies, peptides, and oligonucleotides. Characterizations including DLS, TEM, lateral flow strip assay, fluorescence assay, giant magnetoresistive nanosensor array, high-performance liquid chromatography, and absorption spectrum are performed to further confirm the efficiency of various bioconjugations to the CSNP. In conclusion, this study demonstrates that the CSNP is a novel MNP-based platform that offers versatile and efficient surface functionalization with various biomolecules.

Pharmacokinetics and Pharmacogenomics of Bupropion in Three Different Formulations with Different Release Kinetics in Healthy Human Volunteers.

The purpose of this pharmacokinetics (PK) study was to investigate whether different release kinetics from bupropion hydrochloride (HCl) immediate release (IR), sustained release (SR), and extended release (ER) formulations alter its metabolism and to test the hypothesis that the unsuccessful bioequivalence (BE) study of the higher strength (300 mg) of bupropion HCl ER tablets based on the successful BE study of the lower strength (150 mg) was due to metabolic saturation in the gastrointestinal (GI) lumen. A randomized six-way crossover study was conducted in healthy volunteers. During each period, subjects took a single dose of IR (75/100 mg), SR (100/150 mg), or ER (150/300 mg) formulations of bupropion HCl; plasma samples for PK analysis were collected from 0-96 h for all formulations. In addition, each subject's whole blood was collected for the genotyping of various single-nucleotide polymorphisms (SNPs) of bupropion's major metabolic enzymes. The data indicates that the relative bioavailability of the ER formulations was 72.3-78.8% compared with IR 75 mg. No differences were observed for ratio of the area under the curve (AUC) of metabolite to AUC of parent for the three major metabolites. The pharmacogenomics analysis suggested no statistically significant correlation between polymorphisms and PK parameters of the various formulations. Altogether, these data suggested that the different release kinetics of the formulations did not change metabolites-to-parent ratio. Therefore, the differing BE result between the 150 and 300 mg bupropion HCl ER tablets was unlikely due to the metabolic saturation in the GI lumen caused by different release patterns.