Caustic soda ingestion in children under-5 years presenting for fluoroscopic examinations in an Academic Hospital in Ghana

BACKGROUND: Disastrous effects and lifelong complications, ranging from respiratory and gastrointestinal burns to death can result from caustic soda ingestion. Accidental and non-accidental ingestions occur in different age groups. However, it is very troubling to find ingestion of caustic soda a very common occurrence among children below 5 years since they do not have the developmental level required to independently weigh up risks and are also under parental and societal protections. This study was therefore planned to investigate the ingestions of caustic soda by these children for purposes of proposing measures to curb the problem. METHODS: Descriptive survey was employed for this study. A 14-item, semi-structure questionnaire was purposively issued to 57 parents/guardians whose wards had ingested caustic soda. Data was analysed with SPSS V.20. RESULTS: Twenty-seven (47.4 %) children got access to the soda at storage, 1 (1.86 %) was administered accidentally by a sibling while 29 (50.9 %) ingested during soap preparation. In respect of the former, the majority got access because it was stored in soft drink and water bottles in their parents/guardians rooms or kitchen. For the later, the children got access to the left-over soda because the soap-makers failed to adhere to good storage and disposal practices. CONCLUSION: Storage of caustic soda in soft drink and water bottles in accessible places, and training of children to drink directly from bottles influence caustic soda ingestion in children under five. Non-compliance to good practices of storage and disposal of caustic soda during soap preparation increases exposure and access of children to caustic soda ingestion

Proteasome inhibitor-adapted myeloma cells are largely independent from proteasome activity and show complex proteomic changes, in particular in redox and energy metabolism

Adaptive resistance of myeloma to proteasome inhibition represents a clinical challenge, whose biology is poorly understood. Proteasome mutations were implicated as underlying mechanism, while an alternative hypothesis based on low activation status of the unfolded protein response was recently suggested (IRE1/XBP1-low model). We generated bortezomib- and carfilzomib-adapted, highly resistant multiple myeloma cell clones (AMO-BTZ, AMO-CFZ), which we analyzed in a combined quantitative and functional proteomic approach. We demonstrate that proteasome inhibitor-adapted myeloma cells tolerate subtotal proteasome inhibition, irrespective of a proteasome mutation, and uniformly show an 'IRE1/XBP1-low' signature. Adaptation of myeloma cells to proteasome inhibitors involved quantitative changes in >600 protein species with similar patterns in AMO-BTZ and AMO-CFZ cells: proteins involved in metabolic regulation, redox homeostasis, and protein folding and destruction were upregulated, while apoptosis and transcription/translation were downregulated. The quantitatively most upregulated protein in AMO-CFZ cells was the multidrug resistance protein (MDR1) protein ABCB1, and carfilzomib resistance could be overcome by MDR1 inhibition. We propose a model where proteasome inhibitor-adapted myeloma cells tolerate subtotal proteasome inhibition owing to metabolic adaptations that favor the generation of reducing equivalents, such as NADPH, which is supported by oxidative glycolysis. Proteasome inhibitor resistance may thus be targeted by manipulating the energy and redox metabolism