Doxorubicin-loaded and Fe-SDFO-loaded TSLs displayed favorable release and stability characteristics in vitro. An in vivo proof-of-concept study showed the feasibility of monitoring drug release using the newly designed iron(III)-based CA loaded TSLs. The measured R1-contrast change correlated with the amount of doxorubicin delivered to the tumor. Moreover, the pattern of R1 change could elucidate the pattern of drug release across the tumor. This new iron(III)-based liposomal MR CA is a promising alternative to comparable Gd-based systems.

Context The genetic bases of osteoporosis (OP), a disorder with high heritability, are poorly understood at an individual level. Cases of idiopathic or familial OP have long puzzled clinicians as to whether an actionable genetic cause could be identified. Objective Genetic analysis of 28 cases of idiopathic, severe or familial osteoporosis, using targeted massively parallel sequencing (MPS). Design Targeted sequencing of 128 candidate genes using Illumina NextSeq. Variants of interest were confirmed by Sanger sequencing or SNP Array. Setting An academic tertiary hospital. Patients Thirty-seven patients (54% male, median 44 years old, 86% with fractures), corresponding to 28 sporadic or familial cases. Main Outcome Measure: Rare stop-gain, indel, splice site, copy-number or nonsynonymous variants altering protein function. Results Altogether, we identified 28 variants of interest, but only 3 were classified as pathogenic or likely pathogenic variants: COL1A2 p.(Arg708Gln), WNT1 p.(Gly169Asp) and IDUA p.(His82Gln). An association of variants in different genes was found in 21% of cases, including a young woman with severe OP bearing WNT1, PLS3 and NOTCH2 variants. Among genes of uncertain significance analyzed, a potential additional line of evidence has arisen for GWAS candidates GPR68 and NBR1, warranting further studies. Conclusions While we hope that continuing efforts to identify genetic predisposition to OP will lead to improved and personalized care in the future, the likelihood of identifying actionable pathogenic variants in intriguing cases of idiopathic or familial osteoporosis is seemingly low.

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Rev Med (São Paulo

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