Search

Background Regular blood tests for monitoring metabolic side effects are often unable to be collected for people with an intellectual/developmental disability (ID/DD) and challenging behaviours (CBs) using usual pathways. We aimed to develop a model of care to facilitate venipuncture for children and young adults with ID/DD and CBs.Methods A systematic tiered model of care was developed for venipuncture to suit the individual needs of children and young adults with ID/DD and CBs. A partnership was formed by the disability health team with a community pathology service provider. An observational retrospective study of the baseline demographic data, severity of disability and diagnosis, oral sedation requirement, and outcome data on the success/failure of venipuncture was done.Results 14 children (mean (SD), 12.8 (3.1) years) had 17 attempted venipuncture with ‘reasonable adjustments’ such as preparation with social stories, distraction, low sensory strategies and oral sedation at school clinics. 14 (82%) attempts were successful. After the success of the pilot programme at school, venipuncture was replicated in settings such as home, day programmes, pathology centres and a respite facility. 16 people with ID/DD and CBs (mean (SD)17.3 (3.7) years), had 14 successful venipuncture performed out of 18 attempts (success rate, 77.7%). Overall, 11 attempts (31.4%) succeeded without requiring oral sedation using only reasonable adjustments. 16 attempts (45.7%) succeeded with conscious oral sedation along with reasonable adjustments. Of those 16, 10 required olanzapine (5 mg), 1 required olanzapine (10 mg), 1 required combination of risperidone (1 mg) and diazepam (5 mg), 1 required clonazepam (2.5 mg) and olanzapine (5 mg), 1 required combination of olanzapine (10 mg) and diazepam (10 mg), 1 required combination of olanzapine (10 mg) and diazepam (5 mg) while 1 required only diazepam (5 mg). One had to be switched to the tier-3 pathway.Conclusion A model of care was developed to ensure compassionate and non-stressful venipuncture for children and young adults with disabilities. We demonstrated that a significant proportion of carefully selected children and young adults with ID/DD and CBs, considered ‘challenging for blood collection’ can have venipuncture performed successfully in non-hospital settings using ‘reasonable adjustments’ and oral sedation.

Here the authors identify distinct mechanisms by which domain-specific p53 mutations activate cancer cell growth via the epidermal growth factor receptor (EGFR). These mechanisms affect sensitivity to EGFR inhibitors, opening avenues for targeted therapy.

Plant respiratory burst oxidase homologs (RBOHs) are plasma membrane-localized NADPH oxidases that generate superoxide anion radicals, which then dismutate to H2O2, into the apoplast using cytoplasmic NADPH as an electron donor. PaRBOH1 is the most highly expressed RBOH gene in developing xylem as well as in a lignin-forming cell culture of Norway spruce (Picea abies L. Karst.). Since no previous information about regulation of gymnosperm RBOHs exist, our aim was to resolve how PaRBOH1 is regulated with a focus on phosphorylation. The N-terminal part of PaRBOH1 was found to contain several putative phosphorylation sites and a four-times repeated motif with similarities to the Botrytis-induced kinase 1 target site in Arabidopsis AtRBOHD. Phosphorylation was indicated for six of the sites in in vitro kinase assays using 15 amino-acid-long peptides for each of the predicted phosphotarget site in the presence of protein extracts of developing xylem. Serine and threonine residues showing positive response in the peptide assays were individually mutated to alanine (kinase-inactive) or to aspartate (phosphomimic), and the wild type PaRBOH1 and the mutated constructs transfected to human kidney embryogenic (HEK293T) cells with a low endogenous level of extracellular ROS production. ROS-producing assays with HEK cells showed that Ca2+ and phosphorylation synergistically activate the enzyme and identified several serine and threonine residues that are likely to be phosphorylated including a novel phosphorylation site not characterized in other plant species. These were further investigated with a phosphoproteomic study. Results of Norway spruce, the first gymnosperm species studied in relation to RBOH regulation, show that regulation of RBOH activity is conserved among seed plants.