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These results suggest that highly HAL-resistant cancer cells can be sensitized with cyclosporine A or elacridar, specific P-gp inhibitors that exert their effects at a low dose. These findings provide important information regarding the sensitization of highly HAL-resistant cells with selective P-gp inhibitors and indicate that elacridar may be used to treat such highly HAL-resistant cancer cells.

This study analyzed the role of financial literacy as a mediator between financial education and sound personal finance to assess how financial education affects the soundness of personal finance. In particular, this study conducted three sets of mediation analyses using data from the 2014 Consumer Empowerment Index survey of the Korea Consumer Agency to verify whether the mediating relationship is valid across different income classes of the Korean population. The results suggest that financial literacy works as a mediator between financial education and sound personal finance in the high‐income class and the middle‐income classes. Therefore, policymakers should consider the limitations of financial education and financial literacy when addressing low‐income consumers.

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The nuclear retinoic acid receptors (RARs) play key roles in skeletal development and endochondral ossification. Previously, we showed that RARγ regulates chondrogenesis and that pharmacological activation of RARγ blocked heterotopic ossification (HO), pathology in which endochondral bone forms in soft tissues. Thus, we reasoned that pharmacological inhibition of RARγ should enhance endochondral ossification, leading to a potential therapeutic strategy for bone deficiencies. We created surgical bone defects in wild type and RARγ-null mice and monitored bone healing. Fibrous, cartilaginous, and osseous tissues formed in both groups by day 7, but more cartilaginous tissue formed in mutants within and around the defects compared to controls. Next, we implanted a mixture of Matrigel and rhBMP2 subdermally to induce ectopic endochondral ossification. Administration of RARγ antagonists significantly stimulated ectopic bone formation in wild type but not in RARγ-null mice. The antagonist-induced increases in bone formation were preceded by increases in cartilage formation and were accompanied by higher levels of phosphorylated Smad1/5/8 (pSmad1/5/8) compared to vehicle-treated control. Higher pSmad1/5/8 levels were also observed in cartilaginous tissues forming in healing bone defects in RARγ-null mice, and increases in pSmad1/5/8 levels and Id1-luc activity were observed in RARγ antagonist-treated chondrogenic cells in culture. Our data show that genetic or pharmacological interference with RARγ stimulates endochondral bone formation and does so at least in part by stimulating canonical BMP signaling. This pharmacologic strategy could represent a new tool to enhance endochondral bone formation in the setting of various orthopedic surgical interventions and other skeletal deficiencies. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1096-1105, 2017.

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ImportanceThe COVID-19 pandemic has been associated with an increase in mental health diagnoses among adolescents, though the extent of the increase, particularly for severe cases requiring hospitalization, has not been well characterized. Large-scale federated informatics approaches provide the ability to efficiently and securely query health care data sets to assess and monitor hospitalization patterns for mental health conditions among adolescents.ObjectiveTo estimate changes in the proportion of hospitalizations associated with mental health conditions among adolescents following onset of the COVID-19 pandemic.Design, Setting, and ParticipantsThis retrospective, multisite cohort study of adolescents 11 to 17 years of age who were hospitalized with at least 1 mental health condition diagnosis between February 1, 2019, and April 30, 2021, used patient-level data from electronic health records of 8 children’s hospitals in the US and France.Main Outcomes and MeasuresChange in the monthly proportion of mental health condition–associated hospitalizations between the prepandemic (February 1, 2019, to March 31, 2020) and pandemic (April 1, 2020, to April 30, 2021) periods using interrupted time series analysis.ResultsThere were 9696 adolescents hospitalized with a mental health condition during the prepandemic period (5966 [61.5%] female) and 11 101 during the pandemic period (7603 [68.5%] female). The mean (SD) age in the prepandemic cohort was 14.6 (1.9) years and in the pandemic cohort, 14.7 (1.8) years. The most prevalent diagnoses during the pandemic were anxiety (6066 [57.4%]), depression (5065 [48.0%]), and suicidality or self-injury (4673 [44.2%]). There was an increase in the proportions of monthly hospitalizations during the pandemic for anxiety (0.55%; 95% CI, 0.26%-0.84%), depression (0.50%; 95% CI, 0.19%-0.79%), and suicidality or self-injury (0.38%; 95% CI, 0.08%-0.68%). There was an estimated 0.60% increase (95% CI, 0.31%-0.89%) overall in the monthly proportion of mental health–associated hospitalizations following onset of the pandemic compared with the prepandemic period.Conclusions and RelevanceIn this cohort study, onset of the COVID-19 pandemic was associated with increased hospitalizations with mental health diagnoses among adolescents. These findings support the need for greater resources within children’s hospitals to care for adolescents with mental health conditions during the pandemic and beyond.