Orodispersible films (ODFs) possess potential to facilitate oral drug delivery to children; however, documentation of their acceptability in this age group is lacking. This study is the first to explore the initial perceptions, acceptability and ease of use of ODFs for infants and preschool children, and their caregivers through observed administration of the type of dosage form. Placebo ODFs were administered to children stratified into aged 6 to 12 months, 1 year, 2 years, 3 years, 4 years and 5 years old and into those with an acute illness or long-term stable condition in hospital setting. Acceptability of the dosage form and end-user views were assessed by (a) direct observation of administration, (b) questionnaires to caregivers and nurses, and (c) age-adapted questionnaires for children aged 3 years and over. The majority of children (78%) aged 3 years and over gave the ODF a positive rating both on verbal and non-verbal scales. Despite little prior experience, 78% of caregivers expressed positive opinion about ODFs before administration. After the ODFs were taken, 79% of infant caregivers and 86% caregivers of preschool children positively rated their child’s acceptance of the ODF. The intraclass correlation coefficient value was 0.92 showing good agreement between ratings of caregivers and nurses. ODFs showed a high degree of acceptability among young children and their caregivers. If drug loading permits, pharmaceutical companies should consider developing pediatric medicines in this format. The methodology described here is useful in assessing the acceptability of active ODF preparations and other dosage forms to children.
Performance of both monitors improves as age increases. Our results suggest a need for the development of new monitor algorithms or calibration to better account for the age-specific EEG dynamics of younger patients.
Actin-related protein 2/3 complex (ARPC2) is an actin-binding component involved in the regulation of actin polymerization. It mediates the formation of branched actin networks and contacts the mother actin filament. Migration and invasion are key processes which enable tumor cells to infiltrate blood vessels or lymphatic vessels, and the actin pathway plays a very important role. Given that ARPC2 is critical to this progression, the present study focused on ARPC2 activity in breast cancer (BrCa) cell invasion and migration. Limited data are available on the expression and role of ARPC2 proteins in breast carcinomas. We screened the Oncomine database for messenger RNAs (mRNAs) that are upregulated in BrCa and found that ARPC2 was one of the most consistently involved mRNAs in BrCa. The analysis of immunohistochemical data revealed that ARPC2 expression was higher in breast cancerous tissues than in adjacent non-cancerous tissues. In addition, ARPC2 was highly associated with the tumor stage, nodal metastasis, and overall survival of patients with BrCa. We performed siRNA-ARPC2 transfection to investigate the effect of ARPC2 on the proliferation, migration, invasion and arrest of BrCa cells. It was revealed that ectopic ARPC2 expression significantly upregulated N-cadherin, vimentin, ZEB1, MMP-9 and MMP-3 expression and also activated the TGF-β pathway to contribute to epithelial-mesenchymal transition (EMT). These results collectively indicated that ARPC2 promoted the tumorigenesis of breast carcinoma and the initiation of EMT. Therefore, ARPC2 was revealed to be a potential therapeutic target in patients with BrCa.
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