ResearchPad - original-manuscripts https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[A prospective study of hospital episodes of adults with intellectual disability]]> https://www.researchpad.co/article/elastic_article_6669 Previous research has shown poor hospital experiences and dire outcomes for people with intellectual disability. The main objective of this study was to prospectively track episodes for adults with intellectual disability (ID) in Australian hospitals, with a focus on indications of the quality of care provided.MethodsA prospective audit of hospital records over 35 months yielded quantitative data about patient characteristics, frequency and length of hospital episodes, diagnostic assessments and outcomes, post‐emergency department (ED) destinations and post‐discharge recommendations. Fifty participants were recruited largely by identification on hospital ED entry. An audit of patients' hospital records was conducted towards the end of hospital episodes, using a tool developed for the study.ResultsParticipants were mostly men (70%), aged 42.9 years on average, living mostly with family (46%) or in supported accommodation (44%). Of 157 recorded episodes, 96% started in ED,  85% required urgent or semi‐urgent care and 62% were in the first 3 months of study participation. Average time in ED exceeded the 4‐h national benchmark, met in 40% of episodes. One or more diagnostic assessments were conducted in 91% episodes and others in short stay units. Almost half (49%) resulted in a ward stay. With an extreme data point removed, <1–35 days were spent in wards. The most frequent diagnosis in 75% of episodes was for digestive problems, followed by nervous system problems then injuries. Median length of bed stays reflected data available for Australian refined diagnosis‐related groups. High hospital re‐presentations were found: for 67% of episodes in total, 26% (n = 12) of which were within 72 h and 59% (n = 23) within 30 days.ConclusionsAdults with ID presented frequently to ED and often had lengthy stays. We found no indication of poor care practices in terms of hospital staff willingness to keep patients in ED and conduct of diagnostic assessments. Frequent re‐presentations, however, indicated failed hospital care at some level. ]]> <![CDATA[IL‐6 promotes metastasis of non‐small‐cell lung cancer by up‐regulating TIM‐4 via NF‐κB]]> https://www.researchpad.co/article/Na83ed783-ac4d-45b3-869b-0b2bf9069a07

Abstract

Objectives

Interleukin‐6 (IL‐6) is critical for the development of non‐small‐cell lung cancer (NSCLC). Recently, we identified T‐cell immunoglobulin domain and mucin domain 4 (TIM‐4) as a new pro‐growth player in NSCLC progression. However, the role of TIM‐4 in IL‐6‐promoted NSCLC migration, invasion and epithelial‐to‐mesenchymal transition (EMT) remains unclear.

Materials and Methods

Expressions of TIM‐4 and IL‐6 were both evaluated by immunohistochemical staining in NSCLC tissues. Real‐time quantitative PCR (qPCR), Western blot, flow cytometry and RT‐PCR were performed to detect TIM‐4 expression in NSCLC cells with IL‐6 stimulation. The roles of TIM‐4 in IL‐6 promoting migration and invasion of NSCLC were detected by transwell assay. EMT‐related markers were analysed by qPCR and Western blot in vitro, and metastasis was evaluated in BALB/c nude mice using lung cancer metastasis mouse model in vivo.

Results

High IL‐6 expression was identified as an independent predictive factor for TIM‐4 expression in NSCLC tissues. NSCLC patients with TIM‐4 and IL‐6 double high expression showed the worst prognosis. IL‐6 promoted TIM‐4 expression in NSCLC cells depending on NF‐κB signal pathway. Both TIM‐4 and IL‐6 promoted migration, invasion and EMT of NSCLC cells. Interestingly, TIM‐4 knockdown reversed the role of IL‐6 in NSCLC and IL‐6 promoted metastasis of NSCLC by up‐regulating TIM‐4 via NF‐κB.

Conclusions

TIM‐4 involves in IL‐6 promoted migration, invasion and EMT of NSCLC.

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<![CDATA[Development of an in vitro PIG-A gene mutation assay in human cells]]> https://www.researchpad.co/article/5c02d34fd5eed0c48447640b

Abstract

Mutagens can be carcinogens, and traditionally, they have been identified in vitro using the Salmonella ‘Ames’ reverse mutation assay. However, prokaryotic DNA packaging, replication and repair systems are mechanistically very different to those in the humans we inevitably seek to protect. Therefore, for many years, mammalian cell line genotoxicity assays that can detect eukaryotic mutagens as well as clastogens and aneugens have been used. The apparent lack of specificity in these largely rodent systems, due partly to their mutant p53 status, has contributed to the use of animal studies to resolve data conflicts. Recently, silencing mutations at the PIG-A locus have been demonstrated to prevent glycophosphatidylinositol (GPI) anchor synthesis and consequentially result in loss of GPI-anchored proteins from the cell’s extracellular surface. The successful exploitation of this mutant phenotype in animal studies has triggered interest in the development of an analogous in vitro PIG-A mutation screening assay. This article describes the development of a robust assay design using metabolically active human cells. The assay includes viability and cell membrane integrity assessment and conforms to the future ideas of the 21st-century toxicology testing.

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